# Probiotic Bacteria and IBS



## eric (Jul 8, 1999)

FYIwith permission from the uncProbiotic Bacteria and IBSY. Ringel, MDAssistant Professor of MedicineDivision of Gastroenterology and HepatologyThe University of North Carolina at Chapel HillMember, UNC Center for Functional GI and Motility DisordersWe are often asked if there is a clinical use for probiotic bacteria in patients with IrritableBowel Syndrome (IBS). Probiotics are live micro-organisms (bacteria) which, uponingestion, benefit the host beyond their inherent general nutrition. Probiotics areconsidered ï¿½diet supplements,ï¿½ and are available as capsules, tablets, gel caps, or liquids.They fall under the US Food and Drug Administration (FDA) special category of dietarysupplements and are, therefore, subject to FDA jurisdiction regarding their safety,labeling and health statements.The most studied organisms in the treatment of human intestinal diseases are thelactobacilli (L. GG, L. plantarum, and L. acidophilus) and bifidobacteria (B. infantis).The apparent success of the use of probiotics in several intestinal disorders ï¿½ includingchronic inflammatory bowel disease (IBD), childhood diarrhea (rotavirus infection), andtravelers diarrhea ï¿½ has led to increased interest in their use in patients with IBS. The dataon the use of probiotics in IBS are still very limited and the results, so far, are notconsistent. But, some studies show encouraging results and suggest a clinicalsymptomatic response and parallel improvement in quality of life. For example, onestudy reported a decrease in abdominal pain and bloating in patients with IBS that weretreated with lactobacillus plantarum. Another study showed a decrease in bloating ï¿½ butno effect on pain or gut transit ï¿½ in IBS patients with diarrhea that were treated with aprobiotic composite containing multiple bacterial strains.Growing interest in the potential health benefits of certain cretin diets and nutritionalfood supplements has led to a significant increase in the availability and marketing ofthese products to the average consumer. However, despite some of the preliminaryencouraging results described above, current data do not allow a definitive conclusion orrecommendation regarding the use of probiotics for the treatment of IBS. Only a fewclinical trials on probiotics and IBS have been performed to date, most of them haveinvolved only a small number of treated subjects, and they have used different bacterialstrains and doses. Larger double-blind, placebo-controlled studies are still needed. Untilsuch studies are performed and completed, the use of probiotics in the treatment of IBSshould be considered speculative and experimental.Dr. Ringel is researching the role of bacteria in the pathogenesis of functionalgastrointestinal (GI) disorders and the possible benefit of probiotic treatment for thesedisorders.www.med.unc.edu/medicine/...nd_ibs.pdfThis doesn't mean they should not be tried really, they may actually help some people, but its good to know where they are at with them and IBS and that it is still trial and error with them and knowing its up to the individual to try them and what ones to try.Some people have had good results with them though and some are known benefical.


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## Talissa (Apr 10, 2004)

Here's more(for new people who haven't yet seen this)~04/09/2004 MEDSCAPE"Probiotics and Prebiotics in Gastrointestinal Disorders""Summary: The use of probiotics and prebiotics as therapeutic agents for gastrointestinal disorders is rapidly moving into the mainstream.Mechanisms of action explain the therapeutic effects and randomized; controlled trials provide the necessary evidence for their incorporation into the therapeutic armamentarium....Two papers in the past year have demonstrated that some strains of probiotic bacteria can enhance barrier function through distinctly different mechanisms. Resta-Lenert and Barrett[16] showed that live Streptococcus thermophilus and Lactobacillus acidophilus could inhibit the adhesion and invasion of enteroinvasive Escherichia coli into human intestinal cell lines. ...It has been well documented that probiotic bacteria can interact with epithelial and immune cells and alter signal transduction pathways in the presence or absence of pathogenic bacteria and cytokines. ...In addition to their direct role in H. pylori, probiotics have been suggested to increase efficacy of eradication therapy by preventing antibiotic-associated side effects and thus increasing compliance. Cremonini et al.[35] randomized 85 patients with H. pylori undergoing eradication with triple therapy to one of four groups:Lactobacillus casei subspecies rhamnosus, Saccharomyces boulardii, L. acidophilus plus Bifidobacterium lactis, or placebo. In all probiotic-supplemented groups, there was a significantly lower incidence of antibiotic-associated diarrhea and taste disturbance relative to placebo....The mechanism of action of probiotics in IBS is poorly understood and has been thought to be attributable to changes in fermentation products...Once again, these discordant results support the concept of specific probiotic strains being more effective than others across varied disease states....In a novel study, Sambol et al.[76] colonized hamsters with nontoxigenic C. difficile strains and found that these nontoxigenic strains were able to prevent diarrheal disease in 87% to 97% of hamsters subsequently challenged with toxigenic C. difficile. This novel probiotic strategy needs to be explored for C. difficile-associated disease in humans.[76]...Two studies examined the mechanism of the probiotic effect and antibiotic-associated diarrhea. Sullivan et al. demonstrated that the probiotics (administered as yogurt) prevented antibiotic-induced changes in Bacteroides fragilis microflora cultured from human feces.[82] Using an anaerobic culture system, Payne et al.[83] demonstrated that L. plantarum 299v diminished antibiotic-induced overgrowth of Candida albicans....CONCLUSION: Level II evidence is emerging in support of the use of probiotics in other gastrointestinal infections, in the prevention of postoperative bacterial translocation, in IBS, and in both ulcerative colitis and Crohn disease. Nevertheless, one consistent feature has emerged over the past year: Not all probiotic bacteria have similar therapeutic effects. Future clinical trials will need to incorporate this fact into trial planning and design. The use of probiotics and prebiotics as therapeutic agents for gastrointestinal disorders is rapidly moving into the mainstream." http://www.medscape.com/viewarticle/470571?src=mp


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## Talissa (Apr 10, 2004)

Here's more(for new people who haven't yet seen this)~04/09/2004 MEDSCAPE"Probiotics and Prebiotics in Gastrointestinal Disorders""Summary: The use of probiotics and prebiotics as therapeutic agents for gastrointestinal disorders is rapidly moving into the mainstream.Mechanisms of action explain the therapeutic effects and randomized; controlled trials provide the necessary evidence for their incorporation into the therapeutic armamentarium....Two papers in the past year have demonstrated that some strains of probiotic bacteria can enhance barrier function through distinctly different mechanisms. Resta-Lenert and Barrett[16] showed that live Streptococcus thermophilus and Lactobacillus acidophilus could inhibit the adhesion and invasion of enteroinvasive Escherichia coli into human intestinal cell lines. ...It has been well documented that probiotic bacteria can interact with epithelial and immune cells and alter signal transduction pathways in the presence or absence of pathogenic bacteria and cytokines. ...In addition to their direct role in H. pylori, probiotics have been suggested to increase efficacy of eradication therapy by preventing antibiotic-associated side effects and thus increasing compliance. Cremonini et al.[35] randomized 85 patients with H. pylori undergoing eradication with triple therapy to one of four groups:Lactobacillus casei subspecies rhamnosus, Saccharomyces boulardii, L. acidophilus plus Bifidobacterium lactis, or placebo. In all probiotic-supplemented groups, there was a significantly lower incidence of antibiotic-associated diarrhea and taste disturbance relative to placebo....The mechanism of action of probiotics in IBS is poorly understood and has been thought to be attributable to changes in fermentation products...Once again, these discordant results support the concept of specific probiotic strains being more effective than others across varied disease states....In a novel study, Sambol et al.[76] colonized hamsters with nontoxigenic C. difficile strains and found that these nontoxigenic strains were able to prevent diarrheal disease in 87% to 97% of hamsters subsequently challenged with toxigenic C. difficile. This novel probiotic strategy needs to be explored for C. difficile-associated disease in humans.[76]...Two studies examined the mechanism of the probiotic effect and antibiotic-associated diarrhea. Sullivan et al. demonstrated that the probiotics (administered as yogurt) prevented antibiotic-induced changes in Bacteroides fragilis microflora cultured from human feces.[82] Using an anaerobic culture system, Payne et al.[83] demonstrated that L. plantarum 299v diminished antibiotic-induced overgrowth of Candida albicans....CONCLUSION: Level II evidence is emerging in support of the use of probiotics in other gastrointestinal infections, in the prevention of postoperative bacterial translocation, in IBS, and in both ulcerative colitis and Crohn disease. Nevertheless, one consistent feature has emerged over the past year: Not all probiotic bacteria have similar therapeutic effects. Future clinical trials will need to incorporate this fact into trial planning and design. The use of probiotics and prebiotics as therapeutic agents for gastrointestinal disorders is rapidly moving into the mainstream." http://www.medscape.com/viewarticle/470571?src=mp


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## Nath (Jan 5, 1999)

> quote:It has been well documented that probiotic bacteria can interact with epithelial and immune cells and alter signal transduction pathways in the presence or absence of pathogenic bacteria and cytokines.


Interesting stuff, might be a little critter out there that can effect serotonin signaling in the gut.


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## Nath (Jan 5, 1999)

> quote:It has been well documented that probiotic bacteria can interact with epithelial and immune cells and alter signal transduction pathways in the presence or absence of pathogenic bacteria and cytokines.


Interesting stuff, might be a little critter out there that can effect serotonin signaling in the gut.


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## Talissa (Apr 10, 2004)

Hey Nath, might be indeed. Because serotonin is normally released as an immune response to pathogens, and IBSr's have low beneficial bacteria(dysbiosis), and in some, the low grade inflammation is chronic, it all makes you wonder.This info is interesting in the same vein~Gut 2004ï¿½ï¿½The idea that events such as acute infection may trigger IBS and that low grade inflammation or immune activation may be responsible for prolonged gut dysfunction, akin to asthma, is now being given greater credence. ï¿½There is increasing interest in the role of bacteria in IBS and the influence, if any, of manipulating the gastrointestinal flora. Bacteria can interact with intestinal epithelial cells and generate mediators, including cytokines( & serotonin), that can influence sensory nerve endings, and they can also influence intestinal permeability." http://gut.bmjjournals.com/cgi/content/full/53/suppl_2/ii22 Gut 2004ï¿½ï¿½There is increasing recognition of the importance of infection in the pathogenesis of IBS, and the study of Wang and colleagues16 places this relationship in a broad global context. With emerging evidence supporting a role for inflammation and immune activation in IBS, studies are encouraged to address the influence of the microbial environment on the epidemiology and clinical expression of IBS across the globe. ï¿½ http://gut.bmjjournals.com/cgi/content/full/53/8/1068 World Journal of Gasteroenterology JULY 2003ï¿½Results of recent experimental studies on irritable bowel syndrome speculated that low grade inflammation of colonic mucosa, induced by changes in bacterial microflora, could affect the enteric nervous system, which is crucial for normal gut function, thus favouring symptom development.ï¿½ http://www.wjgnet.com/1007-9327/9/1385.asp Gut 2000ï¿½The implications of persistent immune, inflammatory, and EC changes in colorectal mucosa following Campylobacter infection and in acute onset IBS are numerousï¿½ï¿½ http://gut.bmjjournals.com/cgi/content/full/47/6/804 >>>>>>>>>>>>>>>>>>Things that make you say "Hmmm"...


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## Talissa (Apr 10, 2004)

Hey Nath, might be indeed. Because serotonin is normally released as an immune response to pathogens, and IBSr's have low beneficial bacteria(dysbiosis), and in some, the low grade inflammation is chronic, it all makes you wonder.This info is interesting in the same vein~Gut 2004ï¿½ï¿½The idea that events such as acute infection may trigger IBS and that low grade inflammation or immune activation may be responsible for prolonged gut dysfunction, akin to asthma, is now being given greater credence. ï¿½There is increasing interest in the role of bacteria in IBS and the influence, if any, of manipulating the gastrointestinal flora. Bacteria can interact with intestinal epithelial cells and generate mediators, including cytokines( & serotonin), that can influence sensory nerve endings, and they can also influence intestinal permeability." http://gut.bmjjournals.com/cgi/content/full/53/suppl_2/ii22 Gut 2004ï¿½ï¿½There is increasing recognition of the importance of infection in the pathogenesis of IBS, and the study of Wang and colleagues16 places this relationship in a broad global context. With emerging evidence supporting a role for inflammation and immune activation in IBS, studies are encouraged to address the influence of the microbial environment on the epidemiology and clinical expression of IBS across the globe. ï¿½ http://gut.bmjjournals.com/cgi/content/full/53/8/1068 World Journal of Gasteroenterology JULY 2003ï¿½Results of recent experimental studies on irritable bowel syndrome speculated that low grade inflammation of colonic mucosa, induced by changes in bacterial microflora, could affect the enteric nervous system, which is crucial for normal gut function, thus favouring symptom development.ï¿½ http://www.wjgnet.com/1007-9327/9/1385.asp Gut 2000ï¿½The implications of persistent immune, inflammatory, and EC changes in colorectal mucosa following Campylobacter infection and in acute onset IBS are numerousï¿½ï¿½ http://gut.bmjjournals.com/cgi/content/full/47/6/804 >>>>>>>>>>>>>>>>>>Things that make you say "Hmmm"...


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## eric (Jul 8, 1999)

RomeIrritable Bowel Syndrome: How far do you go in the Workup?"There is evidence that IBS is a heterogeneous disorder where different physiological subgroups contribute to the clinical expression of the syndrome. For example, there is a subgroup of patients, called "post-infectious IBS" who appear to respond to an enteric infection such as campylobactor jejuni with an increased inflammatory cell response (22). This is associated with activating enterochromaffin cells to produce 5HT, and CD3 cells to produce cytokines, which in turn leads to enhanced motility and lowered visceral sensation thresholds (22;23). *But microscopic inflammation cannot be a diagnostic marker for IBS because it does not typically produce pain in those who have it. All patients with active celiac disease have microscopic inflammation, but a large proportion do not have abdominal pain, and patients with ulcerative colitis who also have microscopic inflammation when compared to patients with IBS appear to have higher pain thresholds * (24). In individuals with these disorders, there may be *central nervous system counter-regulatory measures responding to the peripheral pain/inflammatory processes that increase pain thresholds. * *With regard to IBS, the gut-related effects of microscopic inflammation may be only one component of a dysfunctional brain-gut system."* http://www.romecriteria.org/reading1.html


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## eric (Jul 8, 1999)

RomeIrritable Bowel Syndrome: How far do you go in the Workup?"There is evidence that IBS is a heterogeneous disorder where different physiological subgroups contribute to the clinical expression of the syndrome. For example, there is a subgroup of patients, called "post-infectious IBS" who appear to respond to an enteric infection such as campylobactor jejuni with an increased inflammatory cell response (22). This is associated with activating enterochromaffin cells to produce 5HT, and CD3 cells to produce cytokines, which in turn leads to enhanced motility and lowered visceral sensation thresholds (22;23). *But microscopic inflammation cannot be a diagnostic marker for IBS because it does not typically produce pain in those who have it. All patients with active celiac disease have microscopic inflammation, but a large proportion do not have abdominal pain, and patients with ulcerative colitis who also have microscopic inflammation when compared to patients with IBS appear to have higher pain thresholds * (24). In individuals with these disorders, there may be *central nervous system counter-regulatory measures responding to the peripheral pain/inflammatory processes that increase pain thresholds. * *With regard to IBS, the gut-related effects of microscopic inflammation may be only one component of a dysfunctional brain-gut system."* http://www.romecriteria.org/reading1.html


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## Talissa (Apr 10, 2004)

The above article by Drossman, Er, has references which date only up to 2001(one reference).The emergence of mast cells being an integral part of the intestinal immune response in humans(which causes inflammation) had not yet been well established by 2001.I've got about 10 references to this.Thus, it would seem, the above article is dated already.


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## Talissa (Apr 10, 2004)

The above article by Drossman, Er, has references which date only up to 2001(one reference).The emergence of mast cells being an integral part of the intestinal immune response in humans(which causes inflammation) had not yet been well established by 2001.I've got about 10 references to this.Thus, it would seem, the above article is dated already.


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## eric (Jul 8, 1999)

The information itself is not dated. Inflammation cannot be a diagnotic marker for IBS!Funny this is on their site also and has been for a while, not to mention the fact that they have been looking at mast cells for quite sometime know and have already figured a bunch of things out, like chronic stressors can inflame the mast cells without a pathogen. A ton of research has gone into this, your just not reading it.You also don't realize how many research scientists are working and conmbining the information through the UNC and other centers."An increase in inflammatory mediators alone is insufficient to explain the pathogenesis of IBS. From post-infective IBS, we know that the most people who have gastroenteritis and accompanying inflammation do not develop IBS. As discussed earlier, several factors may be important in interacting with the gut insult and in predicting those who develop symptoms - one interesting factor here is the role of stress. Psychological stress is known to affect gut function in normal healthy humans, and in people with IBS stress may trigger or exacerbate symptoms. More recently there is evidence of a link between stress and inflammatory responses. Exposure to stress in both animals and humans has been shown to result in the release of mast cell mediators in the colon (18,19) and in a recent study stress was capable reactivating previous inflammation in rats (15). An important challenge for future work will be to clarify the interaction between inflammation, stress and IBS symptoms." http://www.med.unc.edu/medicine/fgidc/infl...rymediators.htm also what does this mean to you Tal and do you really understand what they are saying here?"Neurologic correlates: in most people, stimuli from intestine registered in anterior cingulate gyrus and easily ignored; in patients with IBS, stimuli from intestine registered in prefrontal cortex and difficult to ignore Pain gate: filtration system in spinal column; IBS patients have dysfunctional pain gate, causing them to feel every little stimulus from gut; pain can be managed using SSEX (ie, Stress, Sleep, Endorphins or eXercise); stressï¿½pain gets worse when patients under stress; stress management using cognitive therapy and self-guided imagery works extremely well; sleepï¿½patients have poor sleep patterns and often feel fatigue because they do not sleep well and wake up with pain; exerciseï¿½induces endorphins that can block receptors in pain gate; unusual to see athlete with IBS " http://www.audio-digest.org/cgi-bin/htmlos...43888964/GE1706


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## eric (Jul 8, 1999)

The information itself is not dated. Inflammation cannot be a diagnotic marker for IBS!Funny this is on their site also and has been for a while, not to mention the fact that they have been looking at mast cells for quite sometime know and have already figured a bunch of things out, like chronic stressors can inflame the mast cells without a pathogen. A ton of research has gone into this, your just not reading it.You also don't realize how many research scientists are working and conmbining the information through the UNC and other centers."An increase in inflammatory mediators alone is insufficient to explain the pathogenesis of IBS. From post-infective IBS, we know that the most people who have gastroenteritis and accompanying inflammation do not develop IBS. As discussed earlier, several factors may be important in interacting with the gut insult and in predicting those who develop symptoms - one interesting factor here is the role of stress. Psychological stress is known to affect gut function in normal healthy humans, and in people with IBS stress may trigger or exacerbate symptoms. More recently there is evidence of a link between stress and inflammatory responses. Exposure to stress in both animals and humans has been shown to result in the release of mast cell mediators in the colon (18,19) and in a recent study stress was capable reactivating previous inflammation in rats (15). An important challenge for future work will be to clarify the interaction between inflammation, stress and IBS symptoms." http://www.med.unc.edu/medicine/fgidc/infl...rymediators.htm also what does this mean to you Tal and do you really understand what they are saying here?"Neurologic correlates: in most people, stimuli from intestine registered in anterior cingulate gyrus and easily ignored; in patients with IBS, stimuli from intestine registered in prefrontal cortex and difficult to ignore Pain gate: filtration system in spinal column; IBS patients have dysfunctional pain gate, causing them to feel every little stimulus from gut; pain can be managed using SSEX (ie, Stress, Sleep, Endorphins or eXercise); stressï¿½pain gets worse when patients under stress; stress management using cognitive therapy and self-guided imagery works extremely well; sleepï¿½patients have poor sleep patterns and often feel fatigue because they do not sleep well and wake up with pain; exerciseï¿½induces endorphins that can block receptors in pain gate; unusual to see athlete with IBS " http://www.audio-digest.org/cgi-bin/htmlos...43888964/GE1706


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## eric (Jul 8, 1999)

There is also more then one bacterial pathogen, that can cause celluralr changes in the gut that can then lead to IBS.But not everyone who gets a pathogen like dysentary come down with IBS. The people who do are those that are stressed at the time of infection. The stress system also fights infection and both are connected to mast cells in the gut.There is also now some evidence that a virus play lead to IBS also.The Pathogen can inflame the gut and cause macroscopic cell changes, specifically serotonin cells and mast cells, when the pathogen is resolved, the changes still produce IBS symptoms. A lot is known about all this already.They can induce IBS in mice this way also, infect them with a pathogen, then stress them, then reslove the pathogen and infection and when the infection is resloved the mice basically have IBS.


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## eric (Jul 8, 1999)

There is also more then one bacterial pathogen, that can cause celluralr changes in the gut that can then lead to IBS.But not everyone who gets a pathogen like dysentary come down with IBS. The people who do are those that are stressed at the time of infection. The stress system also fights infection and both are connected to mast cells in the gut.There is also now some evidence that a virus play lead to IBS also.The Pathogen can inflame the gut and cause macroscopic cell changes, specifically serotonin cells and mast cells, when the pathogen is resolved, the changes still produce IBS symptoms. A lot is known about all this already.They can induce IBS in mice this way also, infect them with a pathogen, then stress them, then reslove the pathogen and infection and when the infection is resloved the mice basically have IBS.


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## Talissa (Apr 10, 2004)

Your last post, Er, I agree with. Stress can also cause mast cell degranulation & inflammation. Here, they suggest probiotics for stress-induced inflammation as well:"Altered stress responses are a hallmark of these kinds of disorders(like IBS). In particular, the hypothalamic-pituitary-adrenal axis (HPA), the core neuroendocrine (nerve+hormone) stress system in man which maintains the bodyï¿½s internal balance, and plays a key role in response to stress, has been shown to be altered in IBS. Chronic stress acting through the HPA may affect the immune system, resulting in the subtle low-grade inflammation seen in IBS. Probiotics may prove to be useful in the prevention or treatment of IBS." http://apc.ucc.ie/content/phys.html ***Just because I'm new to this board, doesn't mean I just fell off the turnip truck, Er. And I don't smoke pot, so my thinking generally runs clearly. I'm also a certified nutritionist, since becoming an IBS statistic.__________________________________RE: MAST CELLS~2000, not quite there yet, but onto something..."Thus, mast cells do have a role in innate immunity in defined animal models of bacterial infection. Whether mast cells participate in innate immune responses in the protection of the human host against bacteria remains to be determined." http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=10719674 2001, getting closer..."However, although it has been demonstrated that mast cells may have a role in innate immunity in defined in vitro and animal models, it remains to be determined whether mast cells are protective in innate immune responses in humans. http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=11424870 2002, Eureka!, we're there..."Mast cells (MCs) play a prominent role in the early immune response to invading pathogenic bacteria. This newly discovered role for MCs involves the release of chemoattractants that recruit neutrophils and the direct phagocytosis and killing of opsonized bacteria." http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=11864844 2003, it's now "firmly established"!"Moreover, the role of mast cells in innate immunity is now firmly established, and the capacity for numerous microbial pathogens to initiate their activation in vitro and in vivo suggest mechanisms by which microbes could initiate disease exacerbations." http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=12895603 2003, but wait, there's more!"Mast cells play a critical role in host defense against bacterial infection." http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=12574323 2004, a little more specific..."On the one hand, mast cells are endowed with unique effector capabilities and activation responses that initiate innate immunity to bacteria and are essential to host defense against helminthic parasites. On the other hand, they are the major effector of type I hypersensitivity and an important participant in a number of disease processes." http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=15055558 2004, bringing nerves into the picture..."Signals from the mast cells are interpreted by the ENS as a labeled code for the presence of a threat in the intestinal lumen." http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=15300595 ___________________The moral of the story is, in my mind, the need to address stress(meditation is best in my opinion) AS WELL AS address flora imbalances in the gut.The ongoing low grade inflammatory response? In my opinion, needs to be addressed. Just not sure how. Staying away from inflammatory foods for one. Ibsacol maybe? Chinese medicines? There's a product for allergies with histidine in it that I may try...I'll get to 100% normal, so close, like others, & no one called "Eric", "Shawn", or "Drossman" can convince me that 100% isn't possible just to sell tapes or drugs.Have a good wkd!Tal


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## Talissa (Apr 10, 2004)

Your last post, Er, I agree with. Stress can also cause mast cell degranulation & inflammation. Here, they suggest probiotics for stress-induced inflammation as well:"Altered stress responses are a hallmark of these kinds of disorders(like IBS). In particular, the hypothalamic-pituitary-adrenal axis (HPA), the core neuroendocrine (nerve+hormone) stress system in man which maintains the bodyï¿½s internal balance, and plays a key role in response to stress, has been shown to be altered in IBS. Chronic stress acting through the HPA may affect the immune system, resulting in the subtle low-grade inflammation seen in IBS. Probiotics may prove to be useful in the prevention or treatment of IBS." http://apc.ucc.ie/content/phys.html ***Just because I'm new to this board, doesn't mean I just fell off the turnip truck, Er. And I don't smoke pot, so my thinking generally runs clearly. I'm also a certified nutritionist, since becoming an IBS statistic.__________________________________RE: MAST CELLS~2000, not quite there yet, but onto something..."Thus, mast cells do have a role in innate immunity in defined animal models of bacterial infection. Whether mast cells participate in innate immune responses in the protection of the human host against bacteria remains to be determined." http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=10719674 2001, getting closer..."However, although it has been demonstrated that mast cells may have a role in innate immunity in defined in vitro and animal models, it remains to be determined whether mast cells are protective in innate immune responses in humans. http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=11424870 2002, Eureka!, we're there..."Mast cells (MCs) play a prominent role in the early immune response to invading pathogenic bacteria. This newly discovered role for MCs involves the release of chemoattractants that recruit neutrophils and the direct phagocytosis and killing of opsonized bacteria." http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=11864844 2003, it's now "firmly established"!"Moreover, the role of mast cells in innate immunity is now firmly established, and the capacity for numerous microbial pathogens to initiate their activation in vitro and in vivo suggest mechanisms by which microbes could initiate disease exacerbations." http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=12895603 2003, but wait, there's more!"Mast cells play a critical role in host defense against bacterial infection." http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=12574323 2004, a little more specific..."On the one hand, mast cells are endowed with unique effector capabilities and activation responses that initiate innate immunity to bacteria and are essential to host defense against helminthic parasites. On the other hand, they are the major effector of type I hypersensitivity and an important participant in a number of disease processes." http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=15055558 2004, bringing nerves into the picture..."Signals from the mast cells are interpreted by the ENS as a labeled code for the presence of a threat in the intestinal lumen." http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=15300595 ___________________The moral of the story is, in my mind, the need to address stress(meditation is best in my opinion) AS WELL AS address flora imbalances in the gut.The ongoing low grade inflammatory response? In my opinion, needs to be addressed. Just not sure how. Staying away from inflammatory foods for one. Ibsacol maybe? Chinese medicines? There's a product for allergies with histidine in it that I may try...I'll get to 100% normal, so close, like others, & no one called "Eric", "Shawn", or "Drossman" can convince me that 100% isn't possible just to sell tapes or drugs.Have a good wkd!Tal


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## Talissa (Apr 10, 2004)

One more thing, on stress.Stress alters micro-flora balance in the gut.It's true, and probablly why the folks I first posted abt above suggested probiotics as possible treatment~2002"CONCLUSIONS: These findings suggest that chronic psychological stress can be an initiating factor in intestinal inflammation by impairing mucosal defenses against luminal bacteria and highlight the importance of mast cells in this process." http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=12360472 2002"Elucidation of the gut-brain-immune axis has provided insight into the mechanisms by which stress may result in gut inflammation...Stress also results in increased bacterial adherence and decreased luminal lactobacilli.>(the good bugs)As a result of all these changes luminal antigens may gain access to the epithelium, causing inflammation." http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=12452934 2004"These results show that the barrier function of follicle associated epithelium can be modulated, and that chronic stress enhances the uptake of luminal antigens and bacteria via the follicle associated epithelium. This can increase antigen exposure in Peyer's patches thereby having implications in the initiation of proinflammatory immune responses within the intestinal mucosa." http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=15016742 "...when stress is chronic, immune function is compromised, and bacteria, viruses, and other biological baddies can get the upper hand. " http://www.moaa.org/TodaysOfficer/HealthLi...alth_Stress.asp ______________________Cortisol, it seems, when under stress is the villain in lowering beneficial bacteria, which normally don't allow pathogen bacteria adherence to the gut wall:"Stress causes the adrenal glands to release cortisol into circulation...These effects persist well beyond the actual cessation of the stressful event resulting in lowered levels of natural killer cell activity, secretory IgA activity, lowered healthy gut bacteria and elevations of unhealthy gut bacteria. " http://www.island.net/~ipincott/article53.htm


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## Talissa (Apr 10, 2004)

One more thing, on stress.Stress alters micro-flora balance in the gut.It's true, and probablly why the folks I first posted abt above suggested probiotics as possible treatment~2002"CONCLUSIONS: These findings suggest that chronic psychological stress can be an initiating factor in intestinal inflammation by impairing mucosal defenses against luminal bacteria and highlight the importance of mast cells in this process." http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=12360472 2002"Elucidation of the gut-brain-immune axis has provided insight into the mechanisms by which stress may result in gut inflammation...Stress also results in increased bacterial adherence and decreased luminal lactobacilli.>(the good bugs)As a result of all these changes luminal antigens may gain access to the epithelium, causing inflammation." http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=12452934 2004"These results show that the barrier function of follicle associated epithelium can be modulated, and that chronic stress enhances the uptake of luminal antigens and bacteria via the follicle associated epithelium. This can increase antigen exposure in Peyer's patches thereby having implications in the initiation of proinflammatory immune responses within the intestinal mucosa." http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=15016742 "...when stress is chronic, immune function is compromised, and bacteria, viruses, and other biological baddies can get the upper hand. " http://www.moaa.org/TodaysOfficer/HealthLi...alth_Stress.asp ______________________Cortisol, it seems, when under stress is the villain in lowering beneficial bacteria, which normally don't allow pathogen bacteria adherence to the gut wall:"Stress causes the adrenal glands to release cortisol into circulation...These effects persist well beyond the actual cessation of the stressful event resulting in lowered levels of natural killer cell activity, secretory IgA activity, lowered healthy gut bacteria and elevations of unhealthy gut bacteria. " http://www.island.net/~ipincott/article53.htm


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## eric (Jul 8, 1999)

Your telling me things I have been trying to tell you for months now, which you did not understand. Its also funny these were things I posted before you disregarded as irrelevent.Your not totally there yet, but getting there.The stress CAN CAUSE the bacterial imbalance, but so can abnormal gut transit?Nor is bacterial imbalance the only abnormalities they have found, there are quite a few actually. You need a bigger picture still. Its just your main focus, you need to have bacteria in there?This was from 2000 and they were already figuring this out and the connections to the brain gut axis."Jack Wood, PhDProfessor of Physiology and Internal MedicineChairman Emeritus, Department of PhysiologyThe Ohio State University College of Medicine Dr. Wood was the first to use microelectrodes to record the electrical and synaptic behavior of neurons in the enteric nervous system. He coined the term "brain-in-the-gut" in view of emerging evidence that the enteric nervous system had neurophysiological properties like the brain and spinal cord. In recent years he has focused on signaling interactions between the enteric immune system and the brain-in-the-gut during infectious enteritis and food allergy. In this lecture he shows how the central nervous system, enteric nervous system and intestinal immune system are integrated during physical and emotional stress to produce irritable bowel symptoms of diarrhea and abdominal pain and discomfort. ""Nigel Bunnett, PhDUniversity of California School of MedicineDepartment of Surgery and PhysiologyAccumulating evidence indicates that sensory nerves play a major role in inflammation of multiple tissues, and that communication between the nervous system and mast cells is of particular importance. Dr. Bunnettï¿½s lecture will highlight recent experimental evidence that mast cell proteases signal to sensory nerves through novel receptors that couple to the release of proinflammatory peptides, and that defects in this mechanism result in uncontrolled inflammation and disease. Dr. Bunnett will present evidence that therapies designed to block signaling by neuropeptides and proteases are attractive treatments for inflammation.""The Effect of Mucosal Inflammation on Enteric Neuromotor Function: Implications for the Development of IBS post-infectious gastroenteritis " http://www.conference-cast.com/ibs/Lecture...dRegLecture.cfm For the last four years since 2000 and before they have been confirming the role of mast cells and stress hormones in IBS and the mechanisms via brain gut pathways. Do you think you can post without all the nasty comments? How about a rational discussion with out the anger and jabs?You didn't comment on the neuro issues I posted?Also why do more women then men have IBS?Serotonin is still majorally important in all this and IBS and the EC cells as important as the mast cells.


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## eric (Jul 8, 1999)

Your telling me things I have been trying to tell you for months now, which you did not understand. Its also funny these were things I posted before you disregarded as irrelevent.Your not totally there yet, but getting there.The stress CAN CAUSE the bacterial imbalance, but so can abnormal gut transit?Nor is bacterial imbalance the only abnormalities they have found, there are quite a few actually. You need a bigger picture still. Its just your main focus, you need to have bacteria in there?This was from 2000 and they were already figuring this out and the connections to the brain gut axis."Jack Wood, PhDProfessor of Physiology and Internal MedicineChairman Emeritus, Department of PhysiologyThe Ohio State University College of Medicine Dr. Wood was the first to use microelectrodes to record the electrical and synaptic behavior of neurons in the enteric nervous system. He coined the term "brain-in-the-gut" in view of emerging evidence that the enteric nervous system had neurophysiological properties like the brain and spinal cord. In recent years he has focused on signaling interactions between the enteric immune system and the brain-in-the-gut during infectious enteritis and food allergy. In this lecture he shows how the central nervous system, enteric nervous system and intestinal immune system are integrated during physical and emotional stress to produce irritable bowel symptoms of diarrhea and abdominal pain and discomfort. ""Nigel Bunnett, PhDUniversity of California School of MedicineDepartment of Surgery and PhysiologyAccumulating evidence indicates that sensory nerves play a major role in inflammation of multiple tissues, and that communication between the nervous system and mast cells is of particular importance. Dr. Bunnettï¿½s lecture will highlight recent experimental evidence that mast cell proteases signal to sensory nerves through novel receptors that couple to the release of proinflammatory peptides, and that defects in this mechanism result in uncontrolled inflammation and disease. Dr. Bunnett will present evidence that therapies designed to block signaling by neuropeptides and proteases are attractive treatments for inflammation.""The Effect of Mucosal Inflammation on Enteric Neuromotor Function: Implications for the Development of IBS post-infectious gastroenteritis " http://www.conference-cast.com/ibs/Lecture...dRegLecture.cfm For the last four years since 2000 and before they have been confirming the role of mast cells and stress hormones in IBS and the mechanisms via brain gut pathways. Do you think you can post without all the nasty comments? How about a rational discussion with out the anger and jabs?You didn't comment on the neuro issues I posted?Also why do more women then men have IBS?Serotonin is still majorally important in all this and IBS and the EC cells as important as the mast cells.


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## Talissa (Apr 10, 2004)

I'm not angry at all. Truly.What did I say above that was nasty?Your filter through which you see the world is cloudy Eric.Stop making it a competition.Less stress


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## Talissa (Apr 10, 2004)

I'm not angry at all. Truly.What did I say above that was nasty?Your filter through which you see the world is cloudy Eric.Stop making it a competition.Less stress


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## peardrops (Jan 3, 2004)

Before I got Campylobacter I was "normal". That was 20 years ago! How I wish I could turn the clock back - I'd never have eaten that chicken takeaway....


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## peardrops (Jan 3, 2004)

Before I got Campylobacter I was "normal". That was 20 years ago! How I wish I could turn the clock back - I'd never have eaten that chicken takeaway....


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## eric (Jul 8, 1999)

what's up with these comments?they have nothing to do with the research or the conversation!!!"Er. And I don't smoke pot, so my thinking generally runs clearly."or this which is 100 percent inaccurate"I'll get to 100% normal, so close, like others, & no one called "Eric", "Shawn", or "Drossman" can convince me that 100% isn't possible just to sell tapes or drugs."That is not the reason IBS is considered a chronic condition. 100 percent maybe possible for you, but IBS is still considered a chronic conditon of which the cause is not fully understood and which there is no cure for every IBSer at this time. That is a fact, you need to understand."Stop making it a competition."Its no competition to me, I already know these things and a whole lot more that has not been discussed and that you have not grasped yet. Like I said I have been studying this way longer then you have had IBS. I also know why a lot of things can help these problems, inculding medications, diet and otcs and stress reduction.


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## eric (Jul 8, 1999)

what's up with these comments?they have nothing to do with the research or the conversation!!!"Er. And I don't smoke pot, so my thinking generally runs clearly."or this which is 100 percent inaccurate"I'll get to 100% normal, so close, like others, & no one called "Eric", "Shawn", or "Drossman" can convince me that 100% isn't possible just to sell tapes or drugs."That is not the reason IBS is considered a chronic condition. 100 percent maybe possible for you, but IBS is still considered a chronic conditon of which the cause is not fully understood and which there is no cure for every IBSer at this time. That is a fact, you need to understand."Stop making it a competition."Its no competition to me, I already know these things and a whole lot more that has not been discussed and that you have not grasped yet. Like I said I have been studying this way longer then you have had IBS. I also know why a lot of things can help these problems, inculding medications, diet and otcs and stress reduction.


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## Talissa (Apr 10, 2004)

Well, maybe the dark side of my type "A" personality enjoys the competition. Hmmm, will think about that later...







In my defense, however, not too long ago, you were saying:"Bacteria has nothing to do with IBS!!!""There is no inflammation in IBS!!!""Mast cells in IBS have nothing to do with the immune system!!!""Okay, well, EC cells have nothing to do the immune system!!!"wrong, wrong, wrong, wrong.One day, I sincerely hope, I'll be able to say "wrong" again, when they find IBS to be organic and treatable into full remission.


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## Talissa (Apr 10, 2004)

Well, maybe the dark side of my type "A" personality enjoys the competition. Hmmm, will think about that later...







In my defense, however, not too long ago, you were saying:"Bacteria has nothing to do with IBS!!!""There is no inflammation in IBS!!!""Mast cells in IBS have nothing to do with the immune system!!!""Okay, well, EC cells have nothing to do the immune system!!!"wrong, wrong, wrong, wrong.One day, I sincerely hope, I'll be able to say "wrong" again, when they find IBS to be organic and treatable into full remission.


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## eric (Jul 8, 1999)

You really make these things up as you go don't you?""Bacteria has nothing to do with IBS!!!"No, I said to date they have not found one specific bacteria that causes IBS. In fact they have found more then one bacteria and maybe even a virus that can lead to IBS, because of what the infection process does to the digestive system after it has FULLY recovered from the intial pathogen and infection. It is well known stress can contribute to IBS when people have an enteric infection. That is one reason why not all people get IBS after an infection of the digestive system.also it is believed that the altered motility can alter the gut flora, in one part because it can sit longer to ferment or move to quickly, as well as chronic stressors in IBS.At this time, there is no eveidence IBS is gennerated by altered gut flora. It is however something being looked into and a ton of work has been done on IBS and bacteria over the years, even though there is more to do still. ""There is no inflammation in IBS!!!"No again, I said there is no OVERT INFLAMATION in IBS, IBS is not an inflamatory bowel disease.One should not imply to people with IBS there is major inflammation going on!!! I have known about the macroscopic inflammation for years now. I was reading and watching those IBS lecture series before you had IBS in 2000.Once again wrong."Mast cells in IBS have nothing to do with the immune system!!!"Give me a break, the fact really is I have been trying to point out all the parts of the immune system they are connected too! Again, something I have known about for years.What is not part of the immune system, is food intolerences."Okay, well, EC cells have nothing to do the immune system!!!""wrong againThey are connected but not directly, because the release of serotonin from the ec cells also helps fight infections as well as there very important role in controling bowel functions via serotonin.Maybe the problem is more in how you interpret or listen to what I have said again and again before you dismiss and tell me I am wrong or while the information was ignored? But the path is taking you in the same direction as you start learning more, because that is part of the path of IBS research. I give you that, at least your reading and learning, even though bacteria is a major focus if not your only focus, which I have said before, there is more to it all and you should watchout for tunnel vision. You also don't seem to be answering the questions I am asking you about? Why is that?Someday they will find organic reasons, they already have found some, but not a biological marker in all IBSers yet. But they have found many abnormalities and problems already that are treatable when you understand them better and how to treat them effectively. And later so this is not misunderstood, I am not in any way agaisnt probiotics at all. I also want to say this to about your sig."Canadian study finds that imbalanced gut flora can affect motility, absorption and secretion, and intestinal permeability"Its effect not cause, wording is really important in the research studies, they are very careful about what they say in them.does it lead to the impairment of the anterior cinculate cortex?Does it over activate the prefrontal cortex?Does it cause rectal hypersensitivity? 80 percent of IBSers have rectal sensitvity.Why would more women then men be effected with altered gut flora?There is a lot more but things for you to ponder.


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## eric (Jul 8, 1999)

You really make these things up as you go don't you?""Bacteria has nothing to do with IBS!!!"No, I said to date they have not found one specific bacteria that causes IBS. In fact they have found more then one bacteria and maybe even a virus that can lead to IBS, because of what the infection process does to the digestive system after it has FULLY recovered from the intial pathogen and infection. It is well known stress can contribute to IBS when people have an enteric infection. That is one reason why not all people get IBS after an infection of the digestive system.also it is believed that the altered motility can alter the gut flora, in one part because it can sit longer to ferment or move to quickly, as well as chronic stressors in IBS.At this time, there is no eveidence IBS is gennerated by altered gut flora. It is however something being looked into and a ton of work has been done on IBS and bacteria over the years, even though there is more to do still. ""There is no inflammation in IBS!!!"No again, I said there is no OVERT INFLAMATION in IBS, IBS is not an inflamatory bowel disease.One should not imply to people with IBS there is major inflammation going on!!! I have known about the macroscopic inflammation for years now. I was reading and watching those IBS lecture series before you had IBS in 2000.Once again wrong."Mast cells in IBS have nothing to do with the immune system!!!"Give me a break, the fact really is I have been trying to point out all the parts of the immune system they are connected too! Again, something I have known about for years.What is not part of the immune system, is food intolerences."Okay, well, EC cells have nothing to do the immune system!!!""wrong againThey are connected but not directly, because the release of serotonin from the ec cells also helps fight infections as well as there very important role in controling bowel functions via serotonin.Maybe the problem is more in how you interpret or listen to what I have said again and again before you dismiss and tell me I am wrong or while the information was ignored? But the path is taking you in the same direction as you start learning more, because that is part of the path of IBS research. I give you that, at least your reading and learning, even though bacteria is a major focus if not your only focus, which I have said before, there is more to it all and you should watchout for tunnel vision. You also don't seem to be answering the questions I am asking you about? Why is that?Someday they will find organic reasons, they already have found some, but not a biological marker in all IBSers yet. But they have found many abnormalities and problems already that are treatable when you understand them better and how to treat them effectively. And later so this is not misunderstood, I am not in any way agaisnt probiotics at all. I also want to say this to about your sig."Canadian study finds that imbalanced gut flora can affect motility, absorption and secretion, and intestinal permeability"Its effect not cause, wording is really important in the research studies, they are very careful about what they say in them.does it lead to the impairment of the anterior cinculate cortex?Does it over activate the prefrontal cortex?Does it cause rectal hypersensitivity? 80 percent of IBSers have rectal sensitvity.Why would more women then men be effected with altered gut flora?There is a lot more but things for you to ponder.


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## SpAsMaN* (May 11, 2002)

Probiotics dosen't seems to overcome IBS.OR even helping.Where are the testimonials?The roots of the condition seems too agressive to be effective with an oral consummation of probiotics.


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## SpAsMaN* (May 11, 2002)

Probiotics dosen't seems to overcome IBS.OR even helping.Where are the testimonials?The roots of the condition seems too agressive to be effective with an oral consummation of probiotics.


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## Nath (Jan 5, 1999)

Spasman all the studies into probiotics seem to used different strains of bacteria, which is one of the resaons they are having problems evaluating the data. If you are interested trying probiotics, then it might be wise to give a couple of different formulations a try.


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## Nath (Jan 5, 1999)

Spasman all the studies into probiotics seem to used different strains of bacteria, which is one of the resaons they are having problems evaluating the data. If you are interested trying probiotics, then it might be wise to give a couple of different formulations a try.


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## Talissa (Apr 10, 2004)

Ericï¿½s inconsistenciesBLOOPERS, if you will~7/26ï¿½There is NO inflammation of the colon wall in IBS!!!!ï¿½ http://www.ibsgroup.org/cgi-local/ubbcgi/u...ic;f=1;t=038726 8/14ï¿½No again, I said there is no OVERT INFLAMATION in IBSï¿½>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>4/?ï¿½Serotonin is released from EC cells in the gut to intiate digestion in all humans and this process has nothing to do with bacteria. IN IBS this process is abnormal.The release of serotonin from mast cells has to do with fighting bacteria.ï¿½(from my post in April, ï¿½IBSgas, etc caused by bacteriaï¿½, which is now mysteriously deleted)8/14"Mast cells in IBS have nothing to do with the immune system!!!"Give me a break, the fact really is I have been trying to point out all the parts of the immune system they are connected too! Again, something I have known about for years.What is not part of the immune system, is food intolerences."Okay, well, EC cells have nothing to do the immune system!!!"wrong againï¿½>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>(fighting bacteria, viuses, perceived threats, etc is what the imm sys does)7/26ï¿½Some IBSers have alter gut flora, but it is not believed to be the cause of IBS.ï¿½ http://www.ibsgroup.org/cgi-local/ubbcgi/u...ic;f=1;t=038726 7/24 or 25From Ericï¿½s post of a study in news & abstracts, couldnï¿½t find it there now? Capt Colon posted it again, & we know what happened next. Anywaysï¿½.ï¿½CONCLUSION: There are intestinal flora disorders in IBS patients, which may be involved in triggering the IBS-like symptoms.ï¿½ http://www.ibsgroup.org/ubb/ultimatebb.php...=5;t=000529;p=1 (Not some, patients with IBS have intestinal flora disordersï¿½.)Above was from the abstract, the same study in full also said in its discussionï¿½ï¿½These effects may contribute to the occurrence of diarrhea. Microecological modulators could prominently relieve IBS-like enteric symptoms, suggesting the close relationship between gut flora and IBSï¿½.However, there was dysbacteriosis in IBS patients. Whether it is the effect or just cause of IBS remains unclear.ï¿½(It has not been proven the the dysbiosis in IBS patients is the cause or the result of IBS. To say unequivocally that IBS isnï¿½t caused by dysbiosis is premature. It is unknown & being studied. It is suspected to be a cause.)Btw~ï¿½Colonic bacteria modify the contents such that biogenic amines like histamine or serotonin may be formedï¿½ï¿½ http://www.e-gastrointestinal.com/ Iï¿½d post more bloopers, but Iï¿½m too disgusted that my thread got deleted right now, am thinking theyï¿½ve been cleaned upï¿½HOWEVER, I will say Iï¿½m fairly ctn when Eric said the hypnotherapy tapes were available for free from his website, he was not being truthful. He may not be ï¿½sellingï¿½ the tapes from his house, but he does get monetary gain from sales from his site. He(you) should just be honest about it


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## Talissa (Apr 10, 2004)

Ericï¿½s inconsistenciesBLOOPERS, if you will~7/26ï¿½There is NO inflammation of the colon wall in IBS!!!!ï¿½ http://www.ibsgroup.org/cgi-local/ubbcgi/u...ic;f=1;t=038726 8/14ï¿½No again, I said there is no OVERT INFLAMATION in IBSï¿½>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>4/?ï¿½Serotonin is released from EC cells in the gut to intiate digestion in all humans and this process has nothing to do with bacteria. IN IBS this process is abnormal.The release of serotonin from mast cells has to do with fighting bacteria.ï¿½(from my post in April, ï¿½IBSgas, etc caused by bacteriaï¿½, which is now mysteriously deleted)8/14"Mast cells in IBS have nothing to do with the immune system!!!"Give me a break, the fact really is I have been trying to point out all the parts of the immune system they are connected too! Again, something I have known about for years.What is not part of the immune system, is food intolerences."Okay, well, EC cells have nothing to do the immune system!!!"wrong againï¿½>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>(fighting bacteria, viuses, perceived threats, etc is what the imm sys does)7/26ï¿½Some IBSers have alter gut flora, but it is not believed to be the cause of IBS.ï¿½ http://www.ibsgroup.org/cgi-local/ubbcgi/u...ic;f=1;t=038726 7/24 or 25From Ericï¿½s post of a study in news & abstracts, couldnï¿½t find it there now? Capt Colon posted it again, & we know what happened next. Anywaysï¿½.ï¿½CONCLUSION: There are intestinal flora disorders in IBS patients, which may be involved in triggering the IBS-like symptoms.ï¿½ http://www.ibsgroup.org/ubb/ultimatebb.php...=5;t=000529;p=1 (Not some, patients with IBS have intestinal flora disordersï¿½.)Above was from the abstract, the same study in full also said in its discussionï¿½ï¿½These effects may contribute to the occurrence of diarrhea. Microecological modulators could prominently relieve IBS-like enteric symptoms, suggesting the close relationship between gut flora and IBSï¿½.However, there was dysbacteriosis in IBS patients. Whether it is the effect or just cause of IBS remains unclear.ï¿½(It has not been proven the the dysbiosis in IBS patients is the cause or the result of IBS. To say unequivocally that IBS isnï¿½t caused by dysbiosis is premature. It is unknown & being studied. It is suspected to be a cause.)Btw~ï¿½Colonic bacteria modify the contents such that biogenic amines like histamine or serotonin may be formedï¿½ï¿½ http://www.e-gastrointestinal.com/ Iï¿½d post more bloopers, but Iï¿½m too disgusted that my thread got deleted right now, am thinking theyï¿½ve been cleaned upï¿½HOWEVER, I will say Iï¿½m fairly ctn when Eric said the hypnotherapy tapes were available for free from his website, he was not being truthful. He may not be ï¿½sellingï¿½ the tapes from his house, but he does get monetary gain from sales from his site. He(you) should just be honest about it


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## Talissa (Apr 10, 2004)

I never imply there is major inflammation in IBS, ever. Thatï¿½s IBD, which Iï¿½ve known for 6 six years.I try to always say ï¿½low grade inflammationï¿½ initially when I talk about the inflammation in IBS & it is VERY important, which theyï¿½re discovering now, and its probably why ROME III was pushed back. Itï¿½s being studied.To say the inflammation in IBS cannot be used as a diagnostic marker is ridiculous. It will be after ROME III comes out is my guess.But hereï¿½s some info available today on the importance of low grade inflammation in IBS~ï¿½Attention has been directed to the putative role of low grade mucosal inflammation in irritable bowel syndrome (IBS) on the basis of evidence showing that some patients with IBS have an increased number of inflammatory cells in the colonic and ileal mucosa. Previous episodes of infectious enteritis, genetic factors, undiagnosed food allergies, and changes in bacterial microflora may all play a role in promoting and perpetuating this low grade inflammatory process.ï¿½ http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=12077063 ï¿½There is increasing evidence suggesting the role of inflammation in the pathogenesis of IBSï¿½ http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=14669335 ï¿½ï¿½low grade inflammation is a predictable inducer of these states, and recent evidence suggests that a subpopulation of patients with IBS develop chronic symptoms after acute gastroenteritis. This and other inflammatory stimuli may induce a hyperalgesic state and alter motor function in patients with IBS. Substances that mediate these changes are not fully understood, but there is growing recognition of the role of serotonin as a sensitizing agent.ï¿½ http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=11694910 ï¿½As reflected by an increasing number of publications on the subject, considerable interest in the putative role of low-grade chronic inflammation in the pathogenesis of IBS has recently emerged.[3] ï¿½. Because a significant number of patients meeting the Rome criteria also met the histologic criteria for a diagnosis of lymphocytic colitis, the findings highlight a major problem with the way we currently diagnose IBS. By definition, the diagnosis of an organic disease such as lymphocytic colitis is inconsistent with a diagnosis of IBS.ï¿½ http://www.medscape.com/viewarticle/457728_print ï¿½Therefore, the microscopic inflammation and its physiologic effects on motility and sensation contribute to, but are not always sufficient for, the clinical explanation of IBS pain.24 ï¿½ http://www.clevelandclinicmeded.com/diseas...tro/ibs/ibs.htm ï¿½However, the triggering factor initiating the inflammatory response remains unclear. In IBS, an immune response to infection,[30] a disinhibition of the immune system during chronic sustained stress (Fig. 1), or a combination of both are plausible mechanisms that could result in the initial immune activation. The persistence of low-grade inflammation after pathogen clearance or after resolution of the psychosocial stressor, in a subset of individuals, may be related to an inability to efficiently downregulate the inflammatory response.ï¿½ http://www.medscape.com/viewarticle/457728_4 ï¿½Inflammation may play a role in the pathogenesis of irritable bowel syndrome in some individuals, such as in those who develop symptoms following a dysenteric illness. Persisting inflammation, resulting from an imbalance of cytokines regulating the inflammatory response, is one possible mechanism.ï¿½(GUT 2003)http://www.lef.org/Lefcms/Template/protoco...C-81D3-FE20C9FE 1A4E%7d&NRCACHEHINT=NoModifyGuest#11[/URL]Now, the question of the dayï¿½WILL THIS POST NOW BE DELETED LIKE MY PREVIOUS POST which I also put much time into & also quoted many impeccable sources?Will my thread get booted like Dr Dahlman's because they fly in the face of Rx drugs and hypnotherapy as the only viable treatment for IBS?Hmmm... time will tell.If so, I'm really, really gonna miss you guys, & for those of us who KNOW that natural treatments work to get out of IBS hell, pls keep up the good fight!







Talissa


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## Talissa (Apr 10, 2004)

I never imply there is major inflammation in IBS, ever. Thatï¿½s IBD, which Iï¿½ve known for 6 six years.I try to always say ï¿½low grade inflammationï¿½ initially when I talk about the inflammation in IBS & it is VERY important, which theyï¿½re discovering now, and its probably why ROME III was pushed back. Itï¿½s being studied.To say the inflammation in IBS cannot be used as a diagnostic marker is ridiculous. It will be after ROME III comes out is my guess.But hereï¿½s some info available today on the importance of low grade inflammation in IBS~ï¿½Attention has been directed to the putative role of low grade mucosal inflammation in irritable bowel syndrome (IBS) on the basis of evidence showing that some patients with IBS have an increased number of inflammatory cells in the colonic and ileal mucosa. Previous episodes of infectious enteritis, genetic factors, undiagnosed food allergies, and changes in bacterial microflora may all play a role in promoting and perpetuating this low grade inflammatory process.ï¿½ http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=12077063 ï¿½There is increasing evidence suggesting the role of inflammation in the pathogenesis of IBSï¿½ http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=14669335 ï¿½ï¿½low grade inflammation is a predictable inducer of these states, and recent evidence suggests that a subpopulation of patients with IBS develop chronic symptoms after acute gastroenteritis. This and other inflammatory stimuli may induce a hyperalgesic state and alter motor function in patients with IBS. Substances that mediate these changes are not fully understood, but there is growing recognition of the role of serotonin as a sensitizing agent.ï¿½ http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=11694910 ï¿½As reflected by an increasing number of publications on the subject, considerable interest in the putative role of low-grade chronic inflammation in the pathogenesis of IBS has recently emerged.[3] ï¿½. Because a significant number of patients meeting the Rome criteria also met the histologic criteria for a diagnosis of lymphocytic colitis, the findings highlight a major problem with the way we currently diagnose IBS. By definition, the diagnosis of an organic disease such as lymphocytic colitis is inconsistent with a diagnosis of IBS.ï¿½ http://www.medscape.com/viewarticle/457728_print ï¿½Therefore, the microscopic inflammation and its physiologic effects on motility and sensation contribute to, but are not always sufficient for, the clinical explanation of IBS pain.24 ï¿½ http://www.clevelandclinicmeded.com/diseas...tro/ibs/ibs.htm ï¿½However, the triggering factor initiating the inflammatory response remains unclear. In IBS, an immune response to infection,[30] a disinhibition of the immune system during chronic sustained stress (Fig. 1), or a combination of both are plausible mechanisms that could result in the initial immune activation. The persistence of low-grade inflammation after pathogen clearance or after resolution of the psychosocial stressor, in a subset of individuals, may be related to an inability to efficiently downregulate the inflammatory response.ï¿½ http://www.medscape.com/viewarticle/457728_4 ï¿½Inflammation may play a role in the pathogenesis of irritable bowel syndrome in some individuals, such as in those who develop symptoms following a dysenteric illness. Persisting inflammation, resulting from an imbalance of cytokines regulating the inflammatory response, is one possible mechanism.ï¿½(GUT 2003)http://www.lef.org/Lefcms/Template/protoco...C-81D3-FE20C9FE 1A4E%7d&NRCACHEHINT=NoModifyGuest#11[/URL]Now, the question of the dayï¿½WILL THIS POST NOW BE DELETED LIKE MY PREVIOUS POST which I also put much time into & also quoted many impeccable sources?Will my thread get booted like Dr Dahlman's because they fly in the face of Rx drugs and hypnotherapy as the only viable treatment for IBS?Hmmm... time will tell.If so, I'm really, really gonna miss you guys, & for those of us who KNOW that natural treatments work to get out of IBS hell, pls keep up the good fight!







Talissa


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## Talissa (Apr 10, 2004)

P.S.I NEVER SAID THERE'S A CURE FOR IBS. EVER.I THINK IT'S POSSIBLE TO GET TO 100% REMISSION.AND FROM THERE, YOU STILL HAVE TO TAKE PROBIOTICS, EAT WHOLE FOODS, NOT TAKE NSAIDS, ETC TO KEEP IBS FROM FROM RECURRING.THERE IS NO CURE FOR IBS.IT IS CHRONIC.BUT REMISSION IS POSSIBLE.TALK TO KEL OR GRET.THEY ARE 100% & MAY OR MAY NOT CALL IT CURED.I CALL IT REMISSION.BANDAID DRUGS & HYPNOTHERAPY WILL NOT BRING REMISSION.I AM 97%, NO DRUGS, NO HYPNO.(To anyone else reading this, sorry for shouting!)


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## Talissa (Apr 10, 2004)

P.S.I NEVER SAID THERE'S A CURE FOR IBS. EVER.I THINK IT'S POSSIBLE TO GET TO 100% REMISSION.AND FROM THERE, YOU STILL HAVE TO TAKE PROBIOTICS, EAT WHOLE FOODS, NOT TAKE NSAIDS, ETC TO KEEP IBS FROM FROM RECURRING.THERE IS NO CURE FOR IBS.IT IS CHRONIC.BUT REMISSION IS POSSIBLE.TALK TO KEL OR GRET.THEY ARE 100% & MAY OR MAY NOT CALL IT CURED.I CALL IT REMISSION.BANDAID DRUGS & HYPNOTHERAPY WILL NOT BRING REMISSION.I AM 97%, NO DRUGS, NO HYPNO.(To anyone else reading this, sorry for shouting!)


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## anmegrl (Jul 4, 2004)

You go Girl!!!!







Which thread of yours was deleted?


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## anmegrl (Jul 4, 2004)

You go Girl!!!!







Which thread of yours was deleted?


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## Kacebece3 (Apr 17, 2002)

Way to go Talissa, keep up the good work. It is a shame that Dr. Dahlam's info has been pigeon holed to the products and services site. His methods are spoken of a lot on all the sites, that are using probiotics and restoring health to the bowels. Note this is just not Dr.Dahlmans approach but the way to relief spoken of by many others. Your research shows this as does the posts from many.Ken


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## Kacebece3 (Apr 17, 2002)

Way to go Talissa, keep up the good work. It is a shame that Dr. Dahlam's info has been pigeon holed to the products and services site. His methods are spoken of a lot on all the sites, that are using probiotics and restoring health to the bowels. Note this is just not Dr.Dahlmans approach but the way to relief spoken of by many others. Your research shows this as does the posts from many.Ken


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## eric (Jul 8, 1999)

You really have a hard time with information don't you."ï¿½There is NO inflammation of the colon wall in IBS!!!!ï¿½"The inflammation is not seen lining the colon wall, it is for one mast cell embedded under the colon wall tissue. They do not see inflammation with a colonoscopy, they only see it when they peel back the layers and go deeper into the colon wall.Have you not looked at pictures of these cells?"ï¿½Serotonin is released from EC cells in the gut to intiate digestion in all humans and this process has nothing to do with bacteria. IN IBS this process is abnormal."The process of the release of serotonin from cells in the gut is abnormal in IBS and that process has nothing to do with bacteria, not that serotonin has nothing to do with bacteria. Serotonin released from mast cells helps fight infections.There is a molecular defect its believed. This already in part explains the c and d and d/c symptoms. "There are intestinal flora disorders in IBS patients, which may be involved in triggering the IBS-like symptoms."The gut will react to ALL stimulis, including any bacteria that may irritiate the colon, every day we are subjected to bacteria aroound our environment. But bacteria is not the only stimulis the gut will react to in IBS. They are saying it may be involved in triggering the gut, not that it is involved for sure and certainly not that it is a cause, they know about PI IBS leading to IBS also, they have a lot of research on this and more being done.they also study bacteria and digestion in IBD conditions and uclers and many other diseases they are researching along with IBS.To date not one bacteria is found to be the cause of IBS. You also need to really understand what infection in the gut does and the symptoms it can cause, some of which are not IBS symptoms.Not to mention infections in the gut, mainly cause D, not d/c or c.I had nothing to do with the deletion of your posts whatsoever. I could not do that even if I wanted to. Your paranoid.another HT bash."I don't work with Mike and the tapes anymore, they are on my website for free. I never really sold them in the first place, I did Mike's websites, and I was introduced to him here and yes there are studies on tapes although not many and in the future ones on Mike's will be done. They have already been shown to work here and other places and through Mike's own clinical trials. But they were not controlled.I don't think you will find one post of mine where I ever pushed them on anyone either, or that I ever said they were a cure to anyone either. I have once in a great while recommended them to a specific person who I thought personally may majorally benefit from them, but even that is rare, they grew on this bb, because of the success rate they have on their own. other wise they would not have lasted the four years on this bb!!!This is a way for people who are housebound or don't have anexpert nearby them or to save a good chunck of money or to use a very specific gut directed form of HT for IBS.The reason for this is the attack on HT from certain people here just trying to attack me and information, but instead of sticking to the topic and information and research at hand they try to puch my buttons through HT and my association with Mike, which went back years on this bb when we were a small family of sufferers trying to help each other out and posting accurate info and watching waht we did and said so as not to hurt people. Mike was a member then, and he no longer posts because he wants to help people, but will not argue with them, like most good healthcare providers in the world. Every time someone bashes HT they do a major disservice to IBS and an effective treatment for IBS and global symptoms. Its a done deal that it can help and your not screwing me with these attacks but your fellow sufferers who might majorally benefit from it. Mike trains HT and IBS in the UK and has been doing it for years and years where it is much more popular in the UK and the US, but that is majorally changing, he is one of the best in the world and I know, because I know the researchers who all do this and research it and have seen his results over the three years. You have to also understand when you see someone in person, they still use the scripts and its standardized HT with gut focus. They even do group seesions. It is not crucial you see a therapist in person.But you don't really care about HT really do you. You would rather not understand it and bash a treatment that is already proven in IBS treatments. I am more then thrilled in reality to have worked with him on the tapes and the people we have really helped in the hundreds and the nice comments we have receieved over the years, using a technique, that is safe and effective and recommend by the experts. It does not work for everyone and ocassionally you will see it did not work for a person, and there maybe a lot of reasons for this, but then they might say they suck, but they are not thinking about all the others that have been heklped and are doing very well. They are thinking it didn't help me personally so all HT sucks. That' not how it works.For the vast majority it does work and it coninues to work after you stop for most people. It has the highest success rate to date statistically.You will also being hearing much more about it in the future. In the UK they have opened an HT unit for IBS in hospital where it all got started twenty years ago, there is twenty years of research on it to back it up.Again, if you want to know about HT and IBS research it. But when you bash it, you are really hurting others from using and established and effective treatment. Which a lot of people have trouble in making the connection to HT and IBS in the first place and the psycophysiological ways it is SO effective in IBS.Not to mention the stigma to the name itself and to tv HT, which is not what clinical medical HT is all about at all.I have no fincial ties to the bb at all anymore. period.On my website advertisers pay flat year rates. I also make sure there is research behind anything I put on my site.I am an IBS sufferer of over thirty three years and am in remission.But I don't pull the wool over any IBSers eyes ever. What IBS has done to me from childhood some people will never know or fully understand, some might and some will have their own feelings about what its done to them. When people Like DR D call me a failure in curing a chronic condition or call others names and liars, I can only personally think how unprofessional is this guy.Tal, you may want to attack me when you can, but I have done my homework on IBS for sure, before you ever got PI IBS. I have also worked with education and support groups on IBS at hospitals to help give back to IBSers. As a volunteer, although one later decided to pay me for it.The difference between me and DR D, is I know IBSers need as much accurate information as possible, I don't say there is a cure for IBS for a MAJOR REASON! But that is only the tip of the iceberg with him I feel personally.I have IBS and for over 29 years until remission through Mike's tapes, which were the only thing that ever really worked and worked well for me, and it was majorally severe pain for one, that crippled me and my life. So I set of to learn all I could and now have help from many xperts in the field who have also become my friends. I know for a fact also that they REALLY CARE, regarless of the bull**** the experts are only in drug money and their research doesn't count, nothing could be farther from the truth to some of the experts I know and listen too. They do care and not only do they care, the complexties of IBS are like puzzles to them they need to learn about and some have a major interest in figuring ut these complexities. Yes, there maybe a few out for money, but in the real world reality they are very few and far between in the research deptment on IBS.People bash this also and they are our hope, maybe our only hope and they are the ones from many fields that will solve the problems in the future. People need to think sometimes more then just about themselves and the games they can play on the bb here without any reprocussions to their actions, this is no game with IBS or other health problems." http://www.ibsgroup.org/ubb/ultimatebb.php...=5;t=000529;p=5 "To say the inflammation in IBS cannot be used as a diagnostic marker is ridiculous. It will be after ROME III comes out is my guess."There is not inflammation in every IBSers, so it can't be used as a diagnostic marker.The inflammation is mainly seen in PI IBS leading to the full clinical expression of IBS.Rome 111 was not pushed back, they are sending out questionaires right now. the release date is for the end of the year. But it is a complex process. "WILL THIS POST NOW BE DELETED LIKE MY PREVIOUS POST which I also put much time into & also quoted many impeccable sources?"Most of your sources are good, you just need more time to fully understand them.You even posted as I have many times, inflammation "ï¿½Therefore, the microscopic inflammation and its physiologic effects on motility and sensation contribute to, but are not always sufficient for, the clinical explanation of IBS pain.24 ï¿½Inflammation cannot be a diagnostic marker for IBS. It does not produce pain in all people who have it, pain is a hallmark of IBS.You don't understand this yet."Will my thread get booted like Dr Dahlman's because they fly in the face of Rx drugs and hypnotherapy as the only viable treatment for IBS?"Ask Jeff why he moved the threads. It had nothing to do with HT or medications for IBS."Will my thread get booted like Dr Dahlman's because they fly in the face of Rx drugs and hypnotherapy as the only viable treatment for IBS?""I THINK IT'S POSSIBLE TO GET TO 100% REMISSION."Gald to hear you think that way its very postitive. Of course yelling doesn't help and shows more of your a type personality."AND FROM THERE, YOU STILL HAVE TO TAKE PROBIOTICS, EAT WHOLE FOODS, NOT TAKE NSAIDS, ETC TO KEEP IBS FROM FROM RECURRING."there is way more to managing IBS then the above, but it might be a good start."TALK TO KEL OR GRET"are they cured?kel has been cured twice now it two years. Gret has mentioned she gets symptoms still from eating a type of sugar?Even if you have no symptoms, does that mean for sure the underlying pathology is CURED?"BANDAID DRUGS & HYPNOTHERAPY WILL NOT BRING REMISSION"Are you sure about that? Not what the 20 years of research on HT has shown. But you don't study it or understand it, so your comments are void. Not to mention its a totally safe and natural effective treatment.Some people also do go into remission with some of the new meds. It is not up to you either to bash those people who use researched methods to treat their IBS either.Also if you really knew, the experts recommend a more holistic approach to treatment then you have picked up on. In fact the experts reserve drugs for last.How come its HT and drugs you bash? Why not relaxatrion tecniques, like yoga or music therapy that you use, they are natural and safe treatments for IBS like HT Or why not bash CBT or other pyscological treatments while your at it? Again you have ignore my questions why is that you think?"Canadian study finds that imbalanced gut flora can affect motility, absorption and secretion, and intestinal permeability"Its effect not cause, wording is really important in the research studies, they are very careful about what they say in them.does it lead to the impairment of the anterior cinculate cortex?Does it over activate the prefrontal cortex?Does it cause rectal hypersensitivity? 80 percent of IBSers have rectal sensitvity.Why would more women then men be effected with altered gut flora?One more thing you keep missing.In IBS, the brain and the gut are operational to cause the symptoms, this is a done deal.


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## eric (Jul 8, 1999)

You really have a hard time with information don't you."ï¿½There is NO inflammation of the colon wall in IBS!!!!ï¿½"The inflammation is not seen lining the colon wall, it is for one mast cell embedded under the colon wall tissue. They do not see inflammation with a colonoscopy, they only see it when they peel back the layers and go deeper into the colon wall.Have you not looked at pictures of these cells?"ï¿½Serotonin is released from EC cells in the gut to intiate digestion in all humans and this process has nothing to do with bacteria. IN IBS this process is abnormal."The process of the release of serotonin from cells in the gut is abnormal in IBS and that process has nothing to do with bacteria, not that serotonin has nothing to do with bacteria. Serotonin released from mast cells helps fight infections.There is a molecular defect its believed. This already in part explains the c and d and d/c symptoms. "There are intestinal flora disorders in IBS patients, which may be involved in triggering the IBS-like symptoms."The gut will react to ALL stimulis, including any bacteria that may irritiate the colon, every day we are subjected to bacteria aroound our environment. But bacteria is not the only stimulis the gut will react to in IBS. They are saying it may be involved in triggering the gut, not that it is involved for sure and certainly not that it is a cause, they know about PI IBS leading to IBS also, they have a lot of research on this and more being done.they also study bacteria and digestion in IBD conditions and uclers and many other diseases they are researching along with IBS.To date not one bacteria is found to be the cause of IBS. You also need to really understand what infection in the gut does and the symptoms it can cause, some of which are not IBS symptoms.Not to mention infections in the gut, mainly cause D, not d/c or c.I had nothing to do with the deletion of your posts whatsoever. I could not do that even if I wanted to. Your paranoid.another HT bash."I don't work with Mike and the tapes anymore, they are on my website for free. I never really sold them in the first place, I did Mike's websites, and I was introduced to him here and yes there are studies on tapes although not many and in the future ones on Mike's will be done. They have already been shown to work here and other places and through Mike's own clinical trials. But they were not controlled.I don't think you will find one post of mine where I ever pushed them on anyone either, or that I ever said they were a cure to anyone either. I have once in a great while recommended them to a specific person who I thought personally may majorally benefit from them, but even that is rare, they grew on this bb, because of the success rate they have on their own. other wise they would not have lasted the four years on this bb!!!This is a way for people who are housebound or don't have anexpert nearby them or to save a good chunck of money or to use a very specific gut directed form of HT for IBS.The reason for this is the attack on HT from certain people here just trying to attack me and information, but instead of sticking to the topic and information and research at hand they try to puch my buttons through HT and my association with Mike, which went back years on this bb when we were a small family of sufferers trying to help each other out and posting accurate info and watching waht we did and said so as not to hurt people. Mike was a member then, and he no longer posts because he wants to help people, but will not argue with them, like most good healthcare providers in the world. Every time someone bashes HT they do a major disservice to IBS and an effective treatment for IBS and global symptoms. Its a done deal that it can help and your not screwing me with these attacks but your fellow sufferers who might majorally benefit from it. Mike trains HT and IBS in the UK and has been doing it for years and years where it is much more popular in the UK and the US, but that is majorally changing, he is one of the best in the world and I know, because I know the researchers who all do this and research it and have seen his results over the three years. You have to also understand when you see someone in person, they still use the scripts and its standardized HT with gut focus. They even do group seesions. It is not crucial you see a therapist in person.But you don't really care about HT really do you. You would rather not understand it and bash a treatment that is already proven in IBS treatments. I am more then thrilled in reality to have worked with him on the tapes and the people we have really helped in the hundreds and the nice comments we have receieved over the years, using a technique, that is safe and effective and recommend by the experts. It does not work for everyone and ocassionally you will see it did not work for a person, and there maybe a lot of reasons for this, but then they might say they suck, but they are not thinking about all the others that have been heklped and are doing very well. They are thinking it didn't help me personally so all HT sucks. That' not how it works.For the vast majority it does work and it coninues to work after you stop for most people. It has the highest success rate to date statistically.You will also being hearing much more about it in the future. In the UK they have opened an HT unit for IBS in hospital where it all got started twenty years ago, there is twenty years of research on it to back it up.Again, if you want to know about HT and IBS research it. But when you bash it, you are really hurting others from using and established and effective treatment. Which a lot of people have trouble in making the connection to HT and IBS in the first place and the psycophysiological ways it is SO effective in IBS.Not to mention the stigma to the name itself and to tv HT, which is not what clinical medical HT is all about at all.I have no fincial ties to the bb at all anymore. period.On my website advertisers pay flat year rates. I also make sure there is research behind anything I put on my site.I am an IBS sufferer of over thirty three years and am in remission.But I don't pull the wool over any IBSers eyes ever. What IBS has done to me from childhood some people will never know or fully understand, some might and some will have their own feelings about what its done to them. When people Like DR D call me a failure in curing a chronic condition or call others names and liars, I can only personally think how unprofessional is this guy.Tal, you may want to attack me when you can, but I have done my homework on IBS for sure, before you ever got PI IBS. I have also worked with education and support groups on IBS at hospitals to help give back to IBSers. As a volunteer, although one later decided to pay me for it.The difference between me and DR D, is I know IBSers need as much accurate information as possible, I don't say there is a cure for IBS for a MAJOR REASON! But that is only the tip of the iceberg with him I feel personally.I have IBS and for over 29 years until remission through Mike's tapes, which were the only thing that ever really worked and worked well for me, and it was majorally severe pain for one, that crippled me and my life. So I set of to learn all I could and now have help from many xperts in the field who have also become my friends. I know for a fact also that they REALLY CARE, regarless of the bull**** the experts are only in drug money and their research doesn't count, nothing could be farther from the truth to some of the experts I know and listen too. They do care and not only do they care, the complexties of IBS are like puzzles to them they need to learn about and some have a major interest in figuring ut these complexities. Yes, there maybe a few out for money, but in the real world reality they are very few and far between in the research deptment on IBS.People bash this also and they are our hope, maybe our only hope and they are the ones from many fields that will solve the problems in the future. People need to think sometimes more then just about themselves and the games they can play on the bb here without any reprocussions to their actions, this is no game with IBS or other health problems." http://www.ibsgroup.org/ubb/ultimatebb.php...=5;t=000529;p=5 "To say the inflammation in IBS cannot be used as a diagnostic marker is ridiculous. It will be after ROME III comes out is my guess."There is not inflammation in every IBSers, so it can't be used as a diagnostic marker.The inflammation is mainly seen in PI IBS leading to the full clinical expression of IBS.Rome 111 was not pushed back, they are sending out questionaires right now. the release date is for the end of the year. But it is a complex process. "WILL THIS POST NOW BE DELETED LIKE MY PREVIOUS POST which I also put much time into & also quoted many impeccable sources?"Most of your sources are good, you just need more time to fully understand them.You even posted as I have many times, inflammation "ï¿½Therefore, the microscopic inflammation and its physiologic effects on motility and sensation contribute to, but are not always sufficient for, the clinical explanation of IBS pain.24 ï¿½Inflammation cannot be a diagnostic marker for IBS. It does not produce pain in all people who have it, pain is a hallmark of IBS.You don't understand this yet."Will my thread get booted like Dr Dahlman's because they fly in the face of Rx drugs and hypnotherapy as the only viable treatment for IBS?"Ask Jeff why he moved the threads. It had nothing to do with HT or medications for IBS."Will my thread get booted like Dr Dahlman's because they fly in the face of Rx drugs and hypnotherapy as the only viable treatment for IBS?""I THINK IT'S POSSIBLE TO GET TO 100% REMISSION."Gald to hear you think that way its very postitive. Of course yelling doesn't help and shows more of your a type personality."AND FROM THERE, YOU STILL HAVE TO TAKE PROBIOTICS, EAT WHOLE FOODS, NOT TAKE NSAIDS, ETC TO KEEP IBS FROM FROM RECURRING."there is way more to managing IBS then the above, but it might be a good start."TALK TO KEL OR GRET"are they cured?kel has been cured twice now it two years. Gret has mentioned she gets symptoms still from eating a type of sugar?Even if you have no symptoms, does that mean for sure the underlying pathology is CURED?"BANDAID DRUGS & HYPNOTHERAPY WILL NOT BRING REMISSION"Are you sure about that? Not what the 20 years of research on HT has shown. But you don't study it or understand it, so your comments are void. Not to mention its a totally safe and natural effective treatment.Some people also do go into remission with some of the new meds. It is not up to you either to bash those people who use researched methods to treat their IBS either.Also if you really knew, the experts recommend a more holistic approach to treatment then you have picked up on. In fact the experts reserve drugs for last.How come its HT and drugs you bash? Why not relaxatrion tecniques, like yoga or music therapy that you use, they are natural and safe treatments for IBS like HT Or why not bash CBT or other pyscological treatments while your at it? Again you have ignore my questions why is that you think?"Canadian study finds that imbalanced gut flora can affect motility, absorption and secretion, and intestinal permeability"Its effect not cause, wording is really important in the research studies, they are very careful about what they say in them.does it lead to the impairment of the anterior cinculate cortex?Does it over activate the prefrontal cortex?Does it cause rectal hypersensitivity? 80 percent of IBSers have rectal sensitvity.Why would more women then men be effected with altered gut flora?One more thing you keep missing.In IBS, the brain and the gut are operational to cause the symptoms, this is a done deal.


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## eric (Jul 8, 1999)

regarless of the cause of IBS and directly addressing IBS and HT."Hypnosis is one of the oldest remedies against physical diseases and mental disorders of mankind. The term hypnosis is used for the description of a technique as well as for the description of an altered state of consciousness which is induced by this technique. Hypnosis is a scientific tool in psychophysiological studies of gastrointestinal functions secretion, motility, visceral sensitivity and their processing in the central nervous system. Hypnosis is an empirically validated treatment of the irritable bowel syndrome even refractory to medical treatment which is recommended by international expert groups Rome II and the British Society of Gastroenterology."BBC"'Imagine your gut as a river...' By Caroline Ryan BBC News Online health staff Patients undergo 12 sessions of hypnotherapy Visualising your digestive system as a river may not seem the most obvious way of treating an illness. But that is exactly how hypnotherapists at a unique centre in Withington Hospital, Manchester, have been helping people with Irritable Bowel Syndrome (IBS). The condition can leave people in constant discomfort and can cause severe pain. And it can prevent them from working or socialising normally. Dr Peter Whorwell, the gastroenterologist who founded the centre, devised the "river" concept. The aim is to make the river flow smoothly. If there is a blockage or a flood, they are asked to visualise a way the problem can be solved. 'Just let go and relax' 'Hypnotherapy changed my life' Sessions with a therapist, interspersed with home practice using a CD, are aimed at "retraining" a patient's gut and eradicating their problems. Since IBS affects everyone differently, the therapy is tailored to each patient. So someone with constipation may visualise rocks which are blocking the river and have to be removed, while someone with diarrhoea may want to shore up the banks to prevent the river running so swiftly. The therapy has proved highly effective, with a recent study showing it had helped 71% of patients for up to five years after their course of treatment. Vivien Miller, one of the team of hypnotherapists at the centre, said: "We are helping people control what's going on in their bodies, and telling them they can control their symptoms." Constant worry The centre is the only one of its kind in the UK and treats around 160 patients from across the country each year. IBS affects between 10 to 15% of the UK's population. Most will only have minor symptoms - but a fifth of them will suffer from faecal incontinence. We had to stay in the closet to begin with and doctors can still be a bit sniffy about it Dr Peter Whorwell 'Your mind and your body can work together' Patients are referred to the centre if they are experiencing severe IBS - where their lives are constantly affected by feelings of bloating, discomfort or constipation, or diarrhoea which can strike at any time. Dr Whorwell became interested in the potential of hypnotherapy for IBS patients over 20 years ago. He kept his new interest under wraps from sceptical colleagues until research proved it was effective. "We had to stay in the closet to begin with and doctors can still be a bit sniffy about it." 'No stage-show' He stresses the hypnotherapy he and his team use is nothing like the TV or stage hypnotists who make people dance like chickens or take their clothes off. Dr Peter Whorwell devised the idea of using hypnotherapy to treat IBS And he says it is no cure-all. "I give a lot of lectures to sceptical doctors. A lot of hypnotists take things very seriously and say they can cure anything. I don't. "But IBS is a nuisance to treat. There are no treatments that are effective, so I thought we should try hypnotherapy." He added: "People are suspicious because they have seen stage hypnotists. "But you cannot be hypnotised against your will. And you won't act out of character while you're hypnotised." Dr Whorwell is trying to spread the word to other doctors around the country. But he says many are still reluctant to use the technique. There are two theories for why hypnotherapy works for IBS. One is that by making people less anxious, it in some way makes the bowel less sensitive, thereby reducing symptoms. Another suggests hypnotherapy may have an impact on a part of the brain which processes pain called the anterior cingulate cortex (ACC). One study showed patients could put their hands into boiling hot water without registering pain after being hypnotised, when they had earlier experienced intense pain. The hypnotherapy reduced the amount of activity in the ACC. Choice While many doctors may still be a little suspicious of using hypnotherapy, Dr Whorwell says patients have no such qualms. "They are falling over themselves to have the therapy, particularly the younger ones. "Many are on antidepressants, because they have the effect of lessening pain sensations at low doses. "But if you're 25 and you had the option of a long-term course of antidepressants or having hypnotherapy that will put you right, which would you choose?" http://news.bbc.co.uk/2/hi/health/3341093.stm "Pioneer PressPosted on Sun, Oct. 12, 2003 HEALTH: Hypnosis gaining respectability among doctors, patientsBY MICHAEL WALDHOLZWall Street JournalHypnosis, often misunderstood and almost always controversial, is increasingly being employed in mainstream medicine.Numerous scientific studies have emerged in recent years showing that the hypnotized mind can exert a real and powerful effect on the body. The new findings are leading major hospitals to try hypnosis to help relieve pain and speed recovery in a variety of illnesses.At the University of North Carolina, hypnosis is transforming the treatment of irritable bowel syndrome, an often-intractable gastro-intestinal disorder, by helping patients to use their mind to quiet an unruly gut.Doctors at the University of Washington's regional burn center in Seattle regularly use it to help patients alleviate excruciating pain.Several hospitals affiliated with Harvard Medical School are employing hypnosis to speed up postsurgical recovery time. In one of the most persuasive studies yet, a Harvard researcher reports that hypnosis quickened the typical healing time of bone fractures by several weeks."Hypnosis may sound like magic, but we are now producing evidence showing it can be significantly therapeutic," says David Spiegel, a Stanford University psychologist. "We know it works, but we don't exactly know how, though there is some science beginning to figure that out, too."Hypnosis can't help everyone, many practitioners say, and some physicians reject it entirely. Even those who are convinced of its effect say some people are more hypnotizable than others, perhaps based on an individual's willingness to suspend logic or to simply be open to the potential effectiveness of the process.GOING MAINSTREAMThese days, legitimate hypnosis is often performed by psychiatrists and psychologists though people in other medical specialties are becoming licensed in it, too. It can involve just one session, but often it takes several ï¿½ or listening to a tape in which a therapist guides an individual into a trancelike state.Whatever the form, it is increasingly being used to help women give birth without drugs, for muting dental pain, treating phobias and severe anxieties, for helping people lose weight, stop smoking or even perform better in thletics or academic tests. Many health-insurance plans, even some HMOs, now will pay for hypnosis when part of an accepted medical treatment.Until the past decade, many traditional science journals regularly declined to publish hypnosis studies, and research funding was scarce. That's changing. Spiegel, for instance, is co-author of a widely referenced randomized trial involving 241 patients at several prestigious medical centers. Published several years ago in the Lancet, a respected medical journal, it found that patients hypnotized before surgery required less pain medication, sustained fewer complications and left the hospital faster than a similar group not given hypnosis.Using new imaging and brain-wave measuring tools, Helen Crawford, an experimental psychologist at Virginia Polytechnic Institute in Blacksburg, Va., has shown that hypnosis alters brain function, activating specific regions that control a person's ability to focus attention."The biological impact is very real and it can be quantified," Crawford says.STAYING LEGITIMATEStill, proponents say they typically spend a great deal of time dispelling commonly held myths and answering skeptics. Hypnosis, they say, cannot make people do or say something against their will.Credible hypnotists don't wave a watch in front of their clients, as portrayed in many old movies. People who enter into a so-called hypnotic trance are not, generally, put to sleep. On the contrary, practitioners say, they refocus their concentration to gain greater control.Even so, the field continues to be hurt by quacks, says Marc Oster, president of the American Society of Clinical Hypnosis. His group, along with the Society for Clinical and Experimental Hypnosis, publishes research studies, conducts educational seminars for health providers and certifies those who complete course work and meet other standards.Oster suggests that people interested in hypnosis see a health provider licensed in a medical discipline who is also certified by one of the hypnosis societies ï¿½ someone who "uses hypnosis as an adjunct" to a principal medical practice.Researchers say that most people unwittingly enter into hypnosislike trances on their own in everyday life. When reading a riveting novel or watching a film or TV, many people are experiencing a trancelike state when they are so focused they become only vaguely aware of nearby noise, conversation or activity.In a dream, when someone imagines falling off a cliff and is startled awake by the sensation of falling, they are triggering the same mental machinery that in hypnosis allows the mind to influence the body, says Dabney Ewin, a psychiatrist at Tulane University Medical School.Katie Miley used self-hypnosis, taught to her by a Chicago-area psychologist, to help her give birth "without being so anxious and without pain medication." For weeks preceding the delivery, Miley, herself a psychologist, used tapes provided by the therapist to practiced slipping into a hypnotic state. During the birth, and as suggested by the therapist, she muted the pain by imagining the contractions "as a warm blanket enveloping me," she says."It was weird," she says. "I was aware of everyone in the room and I was interacting, but mentally my focus was elsewhere, and I just allowed the process to unfold."Some of the clearest clinically measured results come from using hypnosis to mute severe and chronic pain ï¿½ as the University of Washington's regional burn-treatment center in Seattle is doing with burn patients.Patients sent there must undergo frequent therapy to sterilize their damaged skin and get new grafts. They must be awake and alert during the treatment, and even the most powerful narcotics rarely diminish the intense pain.CHANGING FOCUSDavid Patterson, a psychologist at the center, induces a hypnotic trance with a typical and relatively quick technique. Patients are told to close their eyes, breath deeply and imagine they are floating. Through a variety of verbal suggestions, Patterson then helps the patient imagine themselves elsewhere, away from the treatment."The pain is still there, of course, but patients simply don't experience it as before," he says.While relieving physical pain is one of the more common uses of hypnotism, it is also the hardest to explain. Patterson and others report that hypnosis doesn't appear to act on the body's natural pain-killing chemicals, the way drugs do. Instead, scientists believe, through hypnosis a person can be trained to focus away from the pain, not on it as most people usually do.Many athletes often unconsciously use such a technique to play through severe pain, concentrating their attention on the game or task ahead, instead of on their injury.Hypnosis, in some form or another, has been used for more than 200 years. It began gaining credibility as a medical tool in the early decades of the past century as psychiatry and psychoanalysis began to show how the unconscious mind often rules daily life. Its usefulness was cemented when combat physicians reported using it during World War II for the wounded.By 1958, as more doctors described their experiences in the war, the American Medical Association certified hypnosis as a legitimate treatment tool. Few doctors employed it.But in 1996, a National Institutes of Health panel ruled hypnosis as an effective intervention for alleviating pain from cancer and other chronic conditions. These days, as many people accept that stress can exacerbate illness, the potential curative power of hypnosis is becoming more acceptable, too.--------------------------------------------------------------------------------ï¿½ 2003 Pioneer Press and wire service sources. All Rights Reserved. http://www.twincities.com http://www.ibsgroup.org/cgi-local/ubbcgi/u...c;f=11;t=001693 FYI"Hypnotherapeutic options. Hypnotherapy has been shown in randomized studies to improve IBS symptoms.37 Simren and associates38 evaluated 26 patients with refractory IBS; 13 were randomized to receive gut-directed hypnotherapy and 13 to receive supportive therapy. Colonic sensory thresholds were evaluated before and after lipid infusion. The study authors found that there were higher colonic baseline tones present in the hypnotherapy group compared with the control group at 3 months. Phasic motor events were similar in both groups, but hypnotherapy appeared to reduce colonic hypersensitivity to lipid infusion. Presumably, hypnotherapy alters colonic function via central mechanisms, but this remains to be ascertained. Gonsalkorale and colleagues39 followed up with 239 patients who had undergone gut-directed hypnotherapy between 1 and 5 years previously. They found that 83% of patients reported that their symptoms had remained controlled since the end of hypnotherapy, and that only 17% had suffered some deterioration. Quality of life also remained improved, but these observations were uncontrolled. Therefore, gut-directed hypnotherapy should be considered an option for patients who have persistent symptoms despite standard therapy and who do not have significant psychologic comorbidity." http://www.medscape.com/viewarticle/434526 Why Consider Hypnosis Treatment for IBS?by Olafur S. Palsson, Psy.D.Hypnosis is only one of several approaches to treating irritable bowel syndrome and may not be the most suitable option for all patients (click here for discussion of treatment options for IBS). However, hypnosis treatment has some advantages which makes it an attractive option for many IBS sufferers with chronic and severe symptoms:- It is one of the most successful treatment approaches for chronic IBS. The response rate to treatment is 80% and better in most published studies to date. - The treatment often helps individuals who have failed to get improvements with other methods (see for example: Whorwell et al., 1984, 1987; Palsson et al., 1997, 2000).- It is a uniquely comfortable form of treatment; relaxing, easy and generally enjoyable.- It utilizes the healing power of the person's own mind, and is generally completely without negative side effects. - The treatment sometimes results in improvement in other symptoms or problems such as migraine or tension headaches, along with the improvement in IBS symptoms.- The beneficial effects of the treatment last long after the end of the course of treatment. According to research, individuals who improve from hypnosis treatment for IBS can generally look forward to years of reduced bowel symptoms. http://www.ibshypnosis.com/whyhypnosis.html gastroenterologyThe growing case for hypnosis as adjunctive therapy for functional gastrointestinal disorders http://www2.us.elsevierhealth.com/scripts/...16508502004821& The Effects of Hypnosison Gastrointestinal Problems http://www.med.unc.edu/medicine/fgidc/hypnosis.htm Hypnosis Treatment of Irritable Bowel Syndrome By: Olafur S. Palsson, Psy.D., Research Associate, Department of Medicine, University of North Carolina at Chapel Hill "Hypnosis for IBS The results of the first formal research study(4) on hypnosis treatment for IBS were published in the Lancet in 1984. The investigators, Dr. Peter Whorwell and his group in Manchester in England, reported remarkable success from a seven-session hypnosis treatment of 15 patients with severe IBS problems who had not responded to any other treatment. All 15 patients treated with seven sessions of hypnotherapy improved, with dramatic improvement seen in all the central symptoms of IBS. The researchers furthermore showed that this therapeutic impact was not merely due to belief or expectancy of improvement, because a comparison group of 15 IBS patients who were instead treated with the same number of psychotherapy sessions and also received placebo pills (pills with no medication) showed only slight improvement. This was a powerful demonstration of the impact hypnotherapy could have on IBS, and led to considerable subsequent interest in this approach to IBS treatment. Since this first report, more than a dozen other published research reports have confirmed that hypnosis treatment is effective in treating IBS. Generally, the treatment procedures reported in the literature consists of 4 to 12 sessions (shorter treatment than 7 sessions may be a bit less effective). Hypnosis sessions are typically conducted weekly or once every other week, last 30-40 minutes and consist of induction of hypnosis followed by deep relaxation and the use of gut-directed imagery and suggestions. Patients are commonly given short audiotape hypnosis home exercises to use during the course of treatment in addition to the sessions with the clinicians. The experience to date may be outlined as follows: Reported success rates range from approximately 70-95% in all studies with any significant number of patients [for example, in the work of the Manchester group in England(4,5,13) and our studies(6,7)]. The improvement enjoyed from this treatment often lasts at least two years after the end of treatment(5). All major IBS symptoms improve from this kind of treatment (abdominal pain, diarrhea/constipation, and bloating). There are some indications that individuals with certain characteristics are somewhat less likely to benefit from this kind of treatment(5,7,13): People with very little hypnotizability (perhaps 15-25 % of all people), persons with psychiatric disorders, and maybe (according to one report) males with diarrhea-predominant type of IBS. This treatment can be effective also when people are treated in groups(14). In addition to effects on physical symptoms, the treatment commonly improves psychological well-being and life functioning substantially(6,7,13,15) and can have long-term positive effects in reducing disability and health care costs and improving the quality of life of IBS patients(15). How hypnosis treatment improves IBS symptoms Although it is by now well established that hypnosis treatment often improves the symptoms of IBS, it remains a mystery exactly how hypnosis influences IBS in such a beneficial way. Our research team has conducted two studies to try to shed some light on this issue, using completely standardized seven-session protocol with written hypnosis scripts where all treated patients receive the same exact hypnosis treatment word for word. Our first study(6), which was the first hypnosis group trial for IBS in the U.S., was conducted in Dr. Whitehead's research laboratory at the University of North Carolina at Chapel Hill in 1995-1996. In this study, we sought to understand how the treatment influenced the intestinal tract, by measuring changes in rectal pain sensitivity and gut muscle tone with a computerized balloon inflation test. We found no significant changes in pain sensitivity or muscle tone in the gut after hypnosis treatment. However, 17 of the 18 treated patients, all of whom had unsuccessfully tried conventional treatment methods, rated their IBS symptoms significantly improved after treatment. It should be noted that the Manchester group has also conducted two studies to examine the changes in the gut after hypnosis treatment. They similarly found no overall changes in gut pain sensitivity (although in one study(16) a subgroup of the most pain-sensitive individuals showed reduced sensitivity) nor muscle tone changes after treatment, even though the clinical symptoms of their patients improved. We conducted our second study(7) at Eastern Virginia Medical School in Norfolk, Virginia, to examine whether the effects of the hypnotherapy on IBS could be explained by treatment changes in nervous system activity, and also to test further our standardized treatment protocol. Twenty-four people with severe IBS were treated with our standard protocol, and we measured the activity of the autonomic nervous system (the part of the nervous system that automatically controls the body's inner functions) in various ways before and after treatment. We measured sweat gland activity, heart rate, blood pressure, skeletal muscle tension, and skin temperature in the participants, both at rest and in response to a standard mental stress task (problem-solving under time pressure). Twenty-one of the 24 patients (87.5%) treated in the study improved substantially and maintained their improvement at 10-month follow-up. The only change we saw after hypnosis treatment in the nervous system data, however, was a small reduction in sweat gland activity, suggesting somewhat lessened physical stress. This seemed to be unrelated to the much larger improvement in clinical symptoms from the treatment, and could not account for the mechanism of improvement. In contrast, we did find that patients had greatly reduced experience of general (non-IBS) bodily symptoms after treatment, and this was statistically related to their improvement of IBS symptoms. This suggests that changes in the mind's interpretation of, or attention to, signals from the body play some role in the improvement. The overall conclusion from our work and the studies of the Manchester group is that we still know relatively little about exactly what makes the hypnosis treatment so effective for IBS, in spite of four studies examining that to date. We plan to continue doing research to address that question. Efforts to make hypnosis treatment for IBS more widely available As IBS sufferers in the U.S. have become increasingly aware of hypnosis as a treatment option, we have received numerous inquiries about how people can get such therapy in their home area. Unfortunately, the demand for such treatment is largely unmet in the U.S. For that reason, we are making two types of effort to help make this treatment more generally available: A list of clinicians in the U.S. who use a treatment protocol standardized by Olafur S. Palsson, Psy.D et.al., from the Department of Medicine, University of North Carolina, Chapel Hill, may be found at this web site: http://www.ibshypnosis.com/IBSclinicians.html We started a couple of years ago to give qualified clinicians, nationwide, permission (at no cost) to use the treatment protocol we have tested and found successful in our research studies. The protocol package contains verbatim scripts and full instructions sufficient for experienced hypnotherapists to successfully conduct such treatment. In this way, more than eighty clinicians throughout the country have been able to begin using this treatment. To further facilitate this, we have established a Web page where individuals with IBS can get information about clinicians using hypnotherapy for IBS in different states, and where clinicians can request our treatment protocol package. The web address is www.ibshypnosis.com. Secondly, we are now conducting a pilot study at UNC-Chapel Hill, under the direction of Dr. Whitehead, of a home treatment version of our standardized treatment protocol. In this study, IBS patients receive the same treatment, word-for-word, as in our studies, but instead of working with a clinician in person, they use a set of audio CDs at home. It must be emphasized that at the present time, we do not know whether this home treatment format will be effective. However, we hope that at least some of the therapeutic effects of hypnosis treatment can be achieved that way, so that the benefits of this type of treatment can be made more widely available. " http://www.aboutibs.org/Publications/HypnosisPalsson.html Hypnotherapy for Functional Gastrointestinal Disorders By: Peter J. Whorwell, M.D., University Hospital of South Manchester, England "It seems likely that a variety of techniques such as relaxation, yoga, transcendental meditation, reflexology, aromatherapy, and others are different methods of achieving a similar state to that witnessed in hypnosis. Hypnosis probably only differs in that it concentrates more on the "trance" element and is usually targeted at a specific problem, which in the past has most often been identified as psychological. However, we have applied the use of hypnosis in a more physical way without, of course, forgetting its psychological benefits. Irritable bowel syndrome (IBS) would seem to be a disorder that might be amenable to treatment with hypnosis. There is no structural damage and the various possible underlying mechanisms such as disordered motility and visceral (internal) sensitivity might be susceptible to modulation by the mind. Thus, nearly 20 years ago, we undertook the first controlled trial of hypnotherapy in this disorder. The results were extremely encouraging and eventually led us to developing a hypnotherapy unit dedicated to the provision of this service. We recently published an audit of the first 250 patients treated and found that hypnosis not only helps the symptoms of IBS but also significantly improves quality of life.(1) Interestingly, it also relieves the additional symptoms from which so many patients with IBS suffer such as nausea, lethargy, backache, and urinary problems. This is in sharp contrast to the medications currently available for IBS, which often help one or two symptoms if at all. We have also undertaken some research in an attempt to ascertain how hypnosis might lead to benefit. There is no doubt that it can improve anxiety and coping capacities as might be expected. However, of far more interest, was the observation that motility and visceral sensitivity could also be modified in the desired direction. Thus, this approach to treatment appears to offer symptomatic, psychological, and physiological benefit and this presumably explains why it appears to be so effective. However, hypnosis should not be regarded as a panacea as up to 25% of patients fail to respond. Even when patients do improve, conventional approaches to treatment should not necessarily be ignored. Therefore it is still important that lifestyle factors such as diet are also taken into account. In addition, some patients may find that an occasional loperamide or laxative, depending on the bowel habit abnormality, maybe required. One concern over the use of hypnotherapy is the possibility that patients might relapse once a course of treatment has been completed. We have recently addressed this question with a study on the long-term follow up of patients attending the unit. This has shown that after a period of between one and five years, 83% of responders remained well with 59% requiring no further medication at all. Patients also took much less time off work and consulted the medical profession less often. Following the success in patients with IBS, we have recently looked at the use of hypnotherapy in functional dyspepsia, which is a closely related condition resulting in primarily upper gastrointestinal symptoms. Again, compared with controls, the hypnotherapy patients showed substantial improvements in both symptoms and quality of life. One of the most striking outcomes of this particular study was that, after a follow up of one year, not one patient in the hypnotherapy group required any further medication compared with 82% and 90% of subjects in the 2 control groups. Similar trends to those observed in the IBS studies were seen for a reduction in medical consultations and time off work. Unfortunately, most patients, especially those with severe symptoms, require multiple sessions of treatment. In our unit, we allow up to 12 sessions which therefore results in this being a time consuming and costly approach in the short term. However, as a result of the undoubted sustained benefits of treatment, it has been calculated that it becomes cost effective within 2 years when compared to conventional approaches. As new (and likely expensive) drugs now in development for IBS reach the market, hypnotherapy may become a more viable option from the financial point of view. Hypnotherapy therefore appears to be a realistic option in the treatment of conditions such as IBS. Our success has been reproduced by others, but the technique has, so far, not been generally adopted. This is probably because of the unfounded suspicion that surrounds the subject coupled with the fact it is not something with which most physicians or gastroenterologists are especially familiar. Hopefully these negative attributes will decline with time, especially if the success of the technique continues to be supported by a strong evidence base." http://www.aboutibs.org/Publications/hypnosis.html Its really to bad some people here continue to bash Hypnotherapy for IBS, without understanding it and totally ignoring how effective in IBS it has shown to be in managing IBS.Who does this really help? Does it help fellow IBS suffers from a treatment that may actually work for IBS and work well on global symptoms?People bash it because they don't understand it and somehow see it as a threat I guess?"Is It Possible to Reduce Non-gastrointestinal Symptoms in IBS?It is unknown to what degree standard medical treatment for IBS, when successful, also results in improvement in non-GI symptoms. The problem is that most IBS treatment research has not examined how non-IBS symptoms change. Non-IBS symptoms have also not been a focus of standard IBS treatment. An exception to this is psychological treatment trials for IBS, which sometimes have included general physical symptom questionnaires among the measures of treatment effects. We therefore know from our two studies of hypnosis treatment for IBS(22) as well as from research in England(23) that hypnosis treatment for IBS regularly improves non-GI symptoms substantially in addition to beneficial effects on bowel symptoms. " http://www.med.unc.edu/wrkunits/2depts/med...d_the_bowel.htm Not only has it been shown to really help IBS, but also non gi symptoms associated with IBS.


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## eric (Jul 8, 1999)

regarless of the cause of IBS and directly addressing IBS and HT."Hypnosis is one of the oldest remedies against physical diseases and mental disorders of mankind. The term hypnosis is used for the description of a technique as well as for the description of an altered state of consciousness which is induced by this technique. Hypnosis is a scientific tool in psychophysiological studies of gastrointestinal functions secretion, motility, visceral sensitivity and their processing in the central nervous system. Hypnosis is an empirically validated treatment of the irritable bowel syndrome even refractory to medical treatment which is recommended by international expert groups Rome II and the British Society of Gastroenterology."BBC"'Imagine your gut as a river...' By Caroline Ryan BBC News Online health staff Patients undergo 12 sessions of hypnotherapy Visualising your digestive system as a river may not seem the most obvious way of treating an illness. But that is exactly how hypnotherapists at a unique centre in Withington Hospital, Manchester, have been helping people with Irritable Bowel Syndrome (IBS). The condition can leave people in constant discomfort and can cause severe pain. And it can prevent them from working or socialising normally. Dr Peter Whorwell, the gastroenterologist who founded the centre, devised the "river" concept. The aim is to make the river flow smoothly. If there is a blockage or a flood, they are asked to visualise a way the problem can be solved. 'Just let go and relax' 'Hypnotherapy changed my life' Sessions with a therapist, interspersed with home practice using a CD, are aimed at "retraining" a patient's gut and eradicating their problems. Since IBS affects everyone differently, the therapy is tailored to each patient. So someone with constipation may visualise rocks which are blocking the river and have to be removed, while someone with diarrhoea may want to shore up the banks to prevent the river running so swiftly. The therapy has proved highly effective, with a recent study showing it had helped 71% of patients for up to five years after their course of treatment. Vivien Miller, one of the team of hypnotherapists at the centre, said: "We are helping people control what's going on in their bodies, and telling them they can control their symptoms." Constant worry The centre is the only one of its kind in the UK and treats around 160 patients from across the country each year. IBS affects between 10 to 15% of the UK's population. Most will only have minor symptoms - but a fifth of them will suffer from faecal incontinence. We had to stay in the closet to begin with and doctors can still be a bit sniffy about it Dr Peter Whorwell 'Your mind and your body can work together' Patients are referred to the centre if they are experiencing severe IBS - where their lives are constantly affected by feelings of bloating, discomfort or constipation, or diarrhoea which can strike at any time. Dr Whorwell became interested in the potential of hypnotherapy for IBS patients over 20 years ago. He kept his new interest under wraps from sceptical colleagues until research proved it was effective. "We had to stay in the closet to begin with and doctors can still be a bit sniffy about it." 'No stage-show' He stresses the hypnotherapy he and his team use is nothing like the TV or stage hypnotists who make people dance like chickens or take their clothes off. Dr Peter Whorwell devised the idea of using hypnotherapy to treat IBS And he says it is no cure-all. "I give a lot of lectures to sceptical doctors. A lot of hypnotists take things very seriously and say they can cure anything. I don't. "But IBS is a nuisance to treat. There are no treatments that are effective, so I thought we should try hypnotherapy." He added: "People are suspicious because they have seen stage hypnotists. "But you cannot be hypnotised against your will. And you won't act out of character while you're hypnotised." Dr Whorwell is trying to spread the word to other doctors around the country. But he says many are still reluctant to use the technique. There are two theories for why hypnotherapy works for IBS. One is that by making people less anxious, it in some way makes the bowel less sensitive, thereby reducing symptoms. Another suggests hypnotherapy may have an impact on a part of the brain which processes pain called the anterior cingulate cortex (ACC). One study showed patients could put their hands into boiling hot water without registering pain after being hypnotised, when they had earlier experienced intense pain. The hypnotherapy reduced the amount of activity in the ACC. Choice While many doctors may still be a little suspicious of using hypnotherapy, Dr Whorwell says patients have no such qualms. "They are falling over themselves to have the therapy, particularly the younger ones. "Many are on antidepressants, because they have the effect of lessening pain sensations at low doses. "But if you're 25 and you had the option of a long-term course of antidepressants or having hypnotherapy that will put you right, which would you choose?" http://news.bbc.co.uk/2/hi/health/3341093.stm "Pioneer PressPosted on Sun, Oct. 12, 2003 HEALTH: Hypnosis gaining respectability among doctors, patientsBY MICHAEL WALDHOLZWall Street JournalHypnosis, often misunderstood and almost always controversial, is increasingly being employed in mainstream medicine.Numerous scientific studies have emerged in recent years showing that the hypnotized mind can exert a real and powerful effect on the body. The new findings are leading major hospitals to try hypnosis to help relieve pain and speed recovery in a variety of illnesses.At the University of North Carolina, hypnosis is transforming the treatment of irritable bowel syndrome, an often-intractable gastro-intestinal disorder, by helping patients to use their mind to quiet an unruly gut.Doctors at the University of Washington's regional burn center in Seattle regularly use it to help patients alleviate excruciating pain.Several hospitals affiliated with Harvard Medical School are employing hypnosis to speed up postsurgical recovery time. In one of the most persuasive studies yet, a Harvard researcher reports that hypnosis quickened the typical healing time of bone fractures by several weeks."Hypnosis may sound like magic, but we are now producing evidence showing it can be significantly therapeutic," says David Spiegel, a Stanford University psychologist. "We know it works, but we don't exactly know how, though there is some science beginning to figure that out, too."Hypnosis can't help everyone, many practitioners say, and some physicians reject it entirely. Even those who are convinced of its effect say some people are more hypnotizable than others, perhaps based on an individual's willingness to suspend logic or to simply be open to the potential effectiveness of the process.GOING MAINSTREAMThese days, legitimate hypnosis is often performed by psychiatrists and psychologists though people in other medical specialties are becoming licensed in it, too. It can involve just one session, but often it takes several ï¿½ or listening to a tape in which a therapist guides an individual into a trancelike state.Whatever the form, it is increasingly being used to help women give birth without drugs, for muting dental pain, treating phobias and severe anxieties, for helping people lose weight, stop smoking or even perform better in thletics or academic tests. Many health-insurance plans, even some HMOs, now will pay for hypnosis when part of an accepted medical treatment.Until the past decade, many traditional science journals regularly declined to publish hypnosis studies, and research funding was scarce. That's changing. Spiegel, for instance, is co-author of a widely referenced randomized trial involving 241 patients at several prestigious medical centers. Published several years ago in the Lancet, a respected medical journal, it found that patients hypnotized before surgery required less pain medication, sustained fewer complications and left the hospital faster than a similar group not given hypnosis.Using new imaging and brain-wave measuring tools, Helen Crawford, an experimental psychologist at Virginia Polytechnic Institute in Blacksburg, Va., has shown that hypnosis alters brain function, activating specific regions that control a person's ability to focus attention."The biological impact is very real and it can be quantified," Crawford says.STAYING LEGITIMATEStill, proponents say they typically spend a great deal of time dispelling commonly held myths and answering skeptics. Hypnosis, they say, cannot make people do or say something against their will.Credible hypnotists don't wave a watch in front of their clients, as portrayed in many old movies. People who enter into a so-called hypnotic trance are not, generally, put to sleep. On the contrary, practitioners say, they refocus their concentration to gain greater control.Even so, the field continues to be hurt by quacks, says Marc Oster, president of the American Society of Clinical Hypnosis. His group, along with the Society for Clinical and Experimental Hypnosis, publishes research studies, conducts educational seminars for health providers and certifies those who complete course work and meet other standards.Oster suggests that people interested in hypnosis see a health provider licensed in a medical discipline who is also certified by one of the hypnosis societies ï¿½ someone who "uses hypnosis as an adjunct" to a principal medical practice.Researchers say that most people unwittingly enter into hypnosislike trances on their own in everyday life. When reading a riveting novel or watching a film or TV, many people are experiencing a trancelike state when they are so focused they become only vaguely aware of nearby noise, conversation or activity.In a dream, when someone imagines falling off a cliff and is startled awake by the sensation of falling, they are triggering the same mental machinery that in hypnosis allows the mind to influence the body, says Dabney Ewin, a psychiatrist at Tulane University Medical School.Katie Miley used self-hypnosis, taught to her by a Chicago-area psychologist, to help her give birth "without being so anxious and without pain medication." For weeks preceding the delivery, Miley, herself a psychologist, used tapes provided by the therapist to practiced slipping into a hypnotic state. During the birth, and as suggested by the therapist, she muted the pain by imagining the contractions "as a warm blanket enveloping me," she says."It was weird," she says. "I was aware of everyone in the room and I was interacting, but mentally my focus was elsewhere, and I just allowed the process to unfold."Some of the clearest clinically measured results come from using hypnosis to mute severe and chronic pain ï¿½ as the University of Washington's regional burn-treatment center in Seattle is doing with burn patients.Patients sent there must undergo frequent therapy to sterilize their damaged skin and get new grafts. They must be awake and alert during the treatment, and even the most powerful narcotics rarely diminish the intense pain.CHANGING FOCUSDavid Patterson, a psychologist at the center, induces a hypnotic trance with a typical and relatively quick technique. Patients are told to close their eyes, breath deeply and imagine they are floating. Through a variety of verbal suggestions, Patterson then helps the patient imagine themselves elsewhere, away from the treatment."The pain is still there, of course, but patients simply don't experience it as before," he says.While relieving physical pain is one of the more common uses of hypnotism, it is also the hardest to explain. Patterson and others report that hypnosis doesn't appear to act on the body's natural pain-killing chemicals, the way drugs do. Instead, scientists believe, through hypnosis a person can be trained to focus away from the pain, not on it as most people usually do.Many athletes often unconsciously use such a technique to play through severe pain, concentrating their attention on the game or task ahead, instead of on their injury.Hypnosis, in some form or another, has been used for more than 200 years. It began gaining credibility as a medical tool in the early decades of the past century as psychiatry and psychoanalysis began to show how the unconscious mind often rules daily life. Its usefulness was cemented when combat physicians reported using it during World War II for the wounded.By 1958, as more doctors described their experiences in the war, the American Medical Association certified hypnosis as a legitimate treatment tool. Few doctors employed it.But in 1996, a National Institutes of Health panel ruled hypnosis as an effective intervention for alleviating pain from cancer and other chronic conditions. These days, as many people accept that stress can exacerbate illness, the potential curative power of hypnosis is becoming more acceptable, too.--------------------------------------------------------------------------------ï¿½ 2003 Pioneer Press and wire service sources. All Rights Reserved. http://www.twincities.com http://www.ibsgroup.org/cgi-local/ubbcgi/u...c;f=11;t=001693 FYI"Hypnotherapeutic options. Hypnotherapy has been shown in randomized studies to improve IBS symptoms.37 Simren and associates38 evaluated 26 patients with refractory IBS; 13 were randomized to receive gut-directed hypnotherapy and 13 to receive supportive therapy. Colonic sensory thresholds were evaluated before and after lipid infusion. The study authors found that there were higher colonic baseline tones present in the hypnotherapy group compared with the control group at 3 months. Phasic motor events were similar in both groups, but hypnotherapy appeared to reduce colonic hypersensitivity to lipid infusion. Presumably, hypnotherapy alters colonic function via central mechanisms, but this remains to be ascertained. Gonsalkorale and colleagues39 followed up with 239 patients who had undergone gut-directed hypnotherapy between 1 and 5 years previously. They found that 83% of patients reported that their symptoms had remained controlled since the end of hypnotherapy, and that only 17% had suffered some deterioration. Quality of life also remained improved, but these observations were uncontrolled. Therefore, gut-directed hypnotherapy should be considered an option for patients who have persistent symptoms despite standard therapy and who do not have significant psychologic comorbidity." http://www.medscape.com/viewarticle/434526 Why Consider Hypnosis Treatment for IBS?by Olafur S. Palsson, Psy.D.Hypnosis is only one of several approaches to treating irritable bowel syndrome and may not be the most suitable option for all patients (click here for discussion of treatment options for IBS). However, hypnosis treatment has some advantages which makes it an attractive option for many IBS sufferers with chronic and severe symptoms:- It is one of the most successful treatment approaches for chronic IBS. The response rate to treatment is 80% and better in most published studies to date. - The treatment often helps individuals who have failed to get improvements with other methods (see for example: Whorwell et al., 1984, 1987; Palsson et al., 1997, 2000).- It is a uniquely comfortable form of treatment; relaxing, easy and generally enjoyable.- It utilizes the healing power of the person's own mind, and is generally completely without negative side effects. - The treatment sometimes results in improvement in other symptoms or problems such as migraine or tension headaches, along with the improvement in IBS symptoms.- The beneficial effects of the treatment last long after the end of the course of treatment. According to research, individuals who improve from hypnosis treatment for IBS can generally look forward to years of reduced bowel symptoms. http://www.ibshypnosis.com/whyhypnosis.html gastroenterologyThe growing case for hypnosis as adjunctive therapy for functional gastrointestinal disorders http://www2.us.elsevierhealth.com/scripts/...16508502004821& The Effects of Hypnosison Gastrointestinal Problems http://www.med.unc.edu/medicine/fgidc/hypnosis.htm Hypnosis Treatment of Irritable Bowel Syndrome By: Olafur S. Palsson, Psy.D., Research Associate, Department of Medicine, University of North Carolina at Chapel Hill "Hypnosis for IBS The results of the first formal research study(4) on hypnosis treatment for IBS were published in the Lancet in 1984. The investigators, Dr. Peter Whorwell and his group in Manchester in England, reported remarkable success from a seven-session hypnosis treatment of 15 patients with severe IBS problems who had not responded to any other treatment. All 15 patients treated with seven sessions of hypnotherapy improved, with dramatic improvement seen in all the central symptoms of IBS. The researchers furthermore showed that this therapeutic impact was not merely due to belief or expectancy of improvement, because a comparison group of 15 IBS patients who were instead treated with the same number of psychotherapy sessions and also received placebo pills (pills with no medication) showed only slight improvement. This was a powerful demonstration of the impact hypnotherapy could have on IBS, and led to considerable subsequent interest in this approach to IBS treatment. Since this first report, more than a dozen other published research reports have confirmed that hypnosis treatment is effective in treating IBS. Generally, the treatment procedures reported in the literature consists of 4 to 12 sessions (shorter treatment than 7 sessions may be a bit less effective). Hypnosis sessions are typically conducted weekly or once every other week, last 30-40 minutes and consist of induction of hypnosis followed by deep relaxation and the use of gut-directed imagery and suggestions. Patients are commonly given short audiotape hypnosis home exercises to use during the course of treatment in addition to the sessions with the clinicians. The experience to date may be outlined as follows: Reported success rates range from approximately 70-95% in all studies with any significant number of patients [for example, in the work of the Manchester group in England(4,5,13) and our studies(6,7)]. The improvement enjoyed from this treatment often lasts at least two years after the end of treatment(5). All major IBS symptoms improve from this kind of treatment (abdominal pain, diarrhea/constipation, and bloating). There are some indications that individuals with certain characteristics are somewhat less likely to benefit from this kind of treatment(5,7,13): People with very little hypnotizability (perhaps 15-25 % of all people), persons with psychiatric disorders, and maybe (according to one report) males with diarrhea-predominant type of IBS. This treatment can be effective also when people are treated in groups(14). In addition to effects on physical symptoms, the treatment commonly improves psychological well-being and life functioning substantially(6,7,13,15) and can have long-term positive effects in reducing disability and health care costs and improving the quality of life of IBS patients(15). How hypnosis treatment improves IBS symptoms Although it is by now well established that hypnosis treatment often improves the symptoms of IBS, it remains a mystery exactly how hypnosis influences IBS in such a beneficial way. Our research team has conducted two studies to try to shed some light on this issue, using completely standardized seven-session protocol with written hypnosis scripts where all treated patients receive the same exact hypnosis treatment word for word. Our first study(6), which was the first hypnosis group trial for IBS in the U.S., was conducted in Dr. Whitehead's research laboratory at the University of North Carolina at Chapel Hill in 1995-1996. In this study, we sought to understand how the treatment influenced the intestinal tract, by measuring changes in rectal pain sensitivity and gut muscle tone with a computerized balloon inflation test. We found no significant changes in pain sensitivity or muscle tone in the gut after hypnosis treatment. However, 17 of the 18 treated patients, all of whom had unsuccessfully tried conventional treatment methods, rated their IBS symptoms significantly improved after treatment. It should be noted that the Manchester group has also conducted two studies to examine the changes in the gut after hypnosis treatment. They similarly found no overall changes in gut pain sensitivity (although in one study(16) a subgroup of the most pain-sensitive individuals showed reduced sensitivity) nor muscle tone changes after treatment, even though the clinical symptoms of their patients improved. We conducted our second study(7) at Eastern Virginia Medical School in Norfolk, Virginia, to examine whether the effects of the hypnotherapy on IBS could be explained by treatment changes in nervous system activity, and also to test further our standardized treatment protocol. Twenty-four people with severe IBS were treated with our standard protocol, and we measured the activity of the autonomic nervous system (the part of the nervous system that automatically controls the body's inner functions) in various ways before and after treatment. We measured sweat gland activity, heart rate, blood pressure, skeletal muscle tension, and skin temperature in the participants, both at rest and in response to a standard mental stress task (problem-solving under time pressure). Twenty-one of the 24 patients (87.5%) treated in the study improved substantially and maintained their improvement at 10-month follow-up. The only change we saw after hypnosis treatment in the nervous system data, however, was a small reduction in sweat gland activity, suggesting somewhat lessened physical stress. This seemed to be unrelated to the much larger improvement in clinical symptoms from the treatment, and could not account for the mechanism of improvement. In contrast, we did find that patients had greatly reduced experience of general (non-IBS) bodily symptoms after treatment, and this was statistically related to their improvement of IBS symptoms. This suggests that changes in the mind's interpretation of, or attention to, signals from the body play some role in the improvement. The overall conclusion from our work and the studies of the Manchester group is that we still know relatively little about exactly what makes the hypnosis treatment so effective for IBS, in spite of four studies examining that to date. We plan to continue doing research to address that question. Efforts to make hypnosis treatment for IBS more widely available As IBS sufferers in the U.S. have become increasingly aware of hypnosis as a treatment option, we have received numerous inquiries about how people can get such therapy in their home area. Unfortunately, the demand for such treatment is largely unmet in the U.S. For that reason, we are making two types of effort to help make this treatment more generally available: A list of clinicians in the U.S. who use a treatment protocol standardized by Olafur S. Palsson, Psy.D et.al., from the Department of Medicine, University of North Carolina, Chapel Hill, may be found at this web site: http://www.ibshypnosis.com/IBSclinicians.html We started a couple of years ago to give qualified clinicians, nationwide, permission (at no cost) to use the treatment protocol we have tested and found successful in our research studies. The protocol package contains verbatim scripts and full instructions sufficient for experienced hypnotherapists to successfully conduct such treatment. In this way, more than eighty clinicians throughout the country have been able to begin using this treatment. To further facilitate this, we have established a Web page where individuals with IBS can get information about clinicians using hypnotherapy for IBS in different states, and where clinicians can request our treatment protocol package. The web address is www.ibshypnosis.com. Secondly, we are now conducting a pilot study at UNC-Chapel Hill, under the direction of Dr. Whitehead, of a home treatment version of our standardized treatment protocol. In this study, IBS patients receive the same treatment, word-for-word, as in our studies, but instead of working with a clinician in person, they use a set of audio CDs at home. It must be emphasized that at the present time, we do not know whether this home treatment format will be effective. However, we hope that at least some of the therapeutic effects of hypnosis treatment can be achieved that way, so that the benefits of this type of treatment can be made more widely available. " http://www.aboutibs.org/Publications/HypnosisPalsson.html Hypnotherapy for Functional Gastrointestinal Disorders By: Peter J. Whorwell, M.D., University Hospital of South Manchester, England "It seems likely that a variety of techniques such as relaxation, yoga, transcendental meditation, reflexology, aromatherapy, and others are different methods of achieving a similar state to that witnessed in hypnosis. Hypnosis probably only differs in that it concentrates more on the "trance" element and is usually targeted at a specific problem, which in the past has most often been identified as psychological. However, we have applied the use of hypnosis in a more physical way without, of course, forgetting its psychological benefits. Irritable bowel syndrome (IBS) would seem to be a disorder that might be amenable to treatment with hypnosis. There is no structural damage and the various possible underlying mechanisms such as disordered motility and visceral (internal) sensitivity might be susceptible to modulation by the mind. Thus, nearly 20 years ago, we undertook the first controlled trial of hypnotherapy in this disorder. The results were extremely encouraging and eventually led us to developing a hypnotherapy unit dedicated to the provision of this service. We recently published an audit of the first 250 patients treated and found that hypnosis not only helps the symptoms of IBS but also significantly improves quality of life.(1) Interestingly, it also relieves the additional symptoms from which so many patients with IBS suffer such as nausea, lethargy, backache, and urinary problems. This is in sharp contrast to the medications currently available for IBS, which often help one or two symptoms if at all. We have also undertaken some research in an attempt to ascertain how hypnosis might lead to benefit. There is no doubt that it can improve anxiety and coping capacities as might be expected. However, of far more interest, was the observation that motility and visceral sensitivity could also be modified in the desired direction. Thus, this approach to treatment appears to offer symptomatic, psychological, and physiological benefit and this presumably explains why it appears to be so effective. However, hypnosis should not be regarded as a panacea as up to 25% of patients fail to respond. Even when patients do improve, conventional approaches to treatment should not necessarily be ignored. Therefore it is still important that lifestyle factors such as diet are also taken into account. In addition, some patients may find that an occasional loperamide or laxative, depending on the bowel habit abnormality, maybe required. One concern over the use of hypnotherapy is the possibility that patients might relapse once a course of treatment has been completed. We have recently addressed this question with a study on the long-term follow up of patients attending the unit. This has shown that after a period of between one and five years, 83% of responders remained well with 59% requiring no further medication at all. Patients also took much less time off work and consulted the medical profession less often. Following the success in patients with IBS, we have recently looked at the use of hypnotherapy in functional dyspepsia, which is a closely related condition resulting in primarily upper gastrointestinal symptoms. Again, compared with controls, the hypnotherapy patients showed substantial improvements in both symptoms and quality of life. One of the most striking outcomes of this particular study was that, after a follow up of one year, not one patient in the hypnotherapy group required any further medication compared with 82% and 90% of subjects in the 2 control groups. Similar trends to those observed in the IBS studies were seen for a reduction in medical consultations and time off work. Unfortunately, most patients, especially those with severe symptoms, require multiple sessions of treatment. In our unit, we allow up to 12 sessions which therefore results in this being a time consuming and costly approach in the short term. However, as a result of the undoubted sustained benefits of treatment, it has been calculated that it becomes cost effective within 2 years when compared to conventional approaches. As new (and likely expensive) drugs now in development for IBS reach the market, hypnotherapy may become a more viable option from the financial point of view. Hypnotherapy therefore appears to be a realistic option in the treatment of conditions such as IBS. Our success has been reproduced by others, but the technique has, so far, not been generally adopted. This is probably because of the unfounded suspicion that surrounds the subject coupled with the fact it is not something with which most physicians or gastroenterologists are especially familiar. Hopefully these negative attributes will decline with time, especially if the success of the technique continues to be supported by a strong evidence base." http://www.aboutibs.org/Publications/hypnosis.html Its really to bad some people here continue to bash Hypnotherapy for IBS, without understanding it and totally ignoring how effective in IBS it has shown to be in managing IBS.Who does this really help? Does it help fellow IBS suffers from a treatment that may actually work for IBS and work well on global symptoms?People bash it because they don't understand it and somehow see it as a threat I guess?"Is It Possible to Reduce Non-gastrointestinal Symptoms in IBS?It is unknown to what degree standard medical treatment for IBS, when successful, also results in improvement in non-GI symptoms. The problem is that most IBS treatment research has not examined how non-IBS symptoms change. Non-IBS symptoms have also not been a focus of standard IBS treatment. An exception to this is psychological treatment trials for IBS, which sometimes have included general physical symptom questionnaires among the measures of treatment effects. We therefore know from our two studies of hypnosis treatment for IBS(22) as well as from research in England(23) that hypnosis treatment for IBS regularly improves non-GI symptoms substantially in addition to beneficial effects on bowel symptoms. " http://www.med.unc.edu/wrkunits/2depts/med...d_the_bowel.htm Not only has it been shown to really help IBS, but also non gi symptoms associated with IBS.


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## Kacebece3 (Apr 17, 2002)

Well Eric I'm not going to wade thru your long post. I will simply tell you my gastro DR., his name is James P Lynch,said and I quote " I have run numerous tests on you, you do have low grade inflamation, the problems that you (meaning ME)descibe are consistent with people we put in a group we say suffer with IBS. So I guess all the education this man has, all the equipment he uses, and all the clinical experience he has was a waste of time because he diagnosed me with IBSKen


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## Kacebece3 (Apr 17, 2002)

Well Eric I'm not going to wade thru your long post. I will simply tell you my gastro DR., his name is James P Lynch,said and I quote " I have run numerous tests on you, you do have low grade inflamation, the problems that you (meaning ME)descibe are consistent with people we put in a group we say suffer with IBS. So I guess all the education this man has, all the equipment he uses, and all the clinical experience he has was a waste of time because he diagnosed me with IBSKen


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## eric (Jul 8, 1999)

Read or don't read that is up to you. Its your loss.If he saw inflammation on colonoscopy, I would be thinking about what is causing the inflammation and that needs to be investigated for sure. Did you ask him about it and what did he say?Do you have any of these alarm features?"Alarm SignsAs previously stated, typical symptoms point toward IBS, but certain co-existing alarm signs should alert the physician to the possibility of another disorder. These alarm signsï¿½which are not attributable to IBSï¿½include weight loss, frequent awakening by symptoms, fever, rectal bleeding, and anemia. These features can be a clue that another disorder besides IBS is responsible for the gastrointestinal symptoms and may call for further testing. However, a separate, benign problem is often found that explains the problem. For example, rectal bleeding with features typical of an anal origin that is reported by patients with an unchanged, chronic pattern of IBS symptoms is usually found to be caused by hemorrhoids. "The vast majority of IBSers have healthy looking colons upon colonoscopy. Some problems occur for some IBSers when they dig deeper into the colon wall.So he needs to be telling you why there is inflammation there and looking for the reason for it, if you external colon wall is inflammed.Current Approach to the Diagnosis of Irritable Bowel Syndrome"It is important to realize that in clinical practice the Rome II criteria and previous symptom criteria are reliable *only when there is no abnormal intestinal anatomy or metabolic process that would explain the symptoms; that is, negative results from a physical examination and additional diagnostic testing, as needed. * Furthermore, certain co-existing features ("alarm signs") call for special consideration of other disorders before a patient's symptoms can be attributed to IBS. Various symptom criteria have been used effectively in practice, and it is currently unclear whether the recent Rome II criteria are superior to previous ones. The important point is that typical symptoms in the absence of "alarm signs" or abnormalities from physical examination and limited investigation have high diagnostic accuracy. "Its also possible to have more then one thing going on. It might also depend on how you got it in the first place. Or if you polyps there.You know I am not sure why some of you want to argue with me and why that that is more important, then reading the information and learning more about IBS?FYI"Long disparaged as a "wastebasket disease," irritable bowel syndrome (IBS) appears to be gaining newfound respect among researchers, drug makers and gastroenterologists. The question now: Will other physicians begin to recognize IBS as a treatable condition, or will they continue to view it as a largely psychosomatic illness? *Researchers have made major strides in detecting the physiologic underpinnings of IBS as well as the nature of patients' "gut-brain" interactions. * At the same time, drug makers now offer treatments that specifically target a broad range of IBS symptoms. *And gastroenterologists have identified the signs of IBS that can lead to a definitive diagnosis, crafting guidelines to help physicians distinguish IBS from other conditions.* *But as many gastroenterologists are quick to point out, much of the progress being made on IBS has been lost on general practitioners. Rapid advances have created a "very big gap between primary care and gastroenterology," * said Douglas A. Drossman, FACP, co-director of the University of North Carolina Center for Functional Gastrointestinal and Motility Disorders at Chapel Hill. *"Primary care doctors are not up to speed."* To help close that gap, here is an overview of the latest developments in IBS research and treatment.""Help with the diagnosis *Until recently, physicians lacked a clear definition of what exactly constituted an IBS diagnosis. The condition required a diagnosis of exclusion, frustrating physicians and patients alikeï¿½and generally hampering treatment.* *Even worse, arriving at an IBS diagnosis made many physicians fear they had missed a more dangerous condition such as colon cancer. Without any real guidance, it was difficult to feel sure that an IBS diagnosis didn't mean you were overlooking something more serious.* *With the advent of new guidelines, known as the "Rome criteria," however, diagnosing irritable bowel syndrome has become more straightforward. The latest version of the criteriaï¿½Rome IIï¿½was developed by international experts and published in 2000. The criteria point to IBS as a genuine, treatable disorder.* The guidelines "give physicians something to hang a diagnosis on," said gastroenterologist Brian Lacy, MD, PhD, director of the Marvin M. Schuster Center for Digestive and Motility Disorders at Johns Hopkins Bayview Medical Center in Baltimore.According to the Rome II criteria, patients suffering from IBS have experienced several specific symptoms for at least 12 weeks during the previous year. The guidelines emphasize that IBS is a multifaceted condition that involves not only a faulty defecation pattern, but pain. (For more on the Rome criteria, see "The Rome II diagnostic criteria for irritable bowel syndrome," below.) "If they don't have pain, they don't have IBS," Dr. Lacy said, "even if they have diarrhea 15 times a day or go to the bathroom only once a month." *While the guidelines still require physicians to rule out other conditions such as functional diarrhea or pelvic floor disorders, both of which are similar to IBS, experts say the criteria reduce much of the diagnostic uncertainty by limiting the range of other possible conditions. You don't need to run most patients through an extensive battery of tests to reach a diagnosis.* Last year, both the American Gastroenterological Association and the American College of Gastroenterology (ACG) issued position statements that agree with that diagnostic approach. *The organizations identified key "alarm signals" that should alert you to other potential diagnoses when working with possible IBS patients.* While you may feel compelled to list several problems like pain, bloating and constipation when treating IBS patients, Dr. Lacy said that approach is unnecessary. *"These patients have one unifying diagnosisï¿½IBSï¿½that should make it easier to treat them," he explained. "You need to think about treating this whole constellation of symptoms."* *Performing fewer tests to make an IBS diagnosis benefits not only health plans, but patients themselves. Excessive testing can distress patients,* noted gastroenterologist George F. Longstreth, MD, chief of gastroenterology at Kaiser Permanente Medical Care Program in San Diego." *Too many tests sometimes create more anxiety," he said, a factor that can be a real liability when research suggests that IBS patients may have more pronounced intestinal reactions to stress than other patients.* (For more on the "gut-brain" connection, see "IBS: An anatomy of what goes wrong in the body," below.)  *And while internists instinctively worry about missing another disease, they need to guard against making the opposite mistake: confusing IBS symptoms for those of other medical conditions. * *Studies have shown, for example, that IBS patients are more likely to have their gallbladders removed or to have a hysterectomy. "IBS patients shouldn't automatically have their gallbladders taken out," Dr. Longstreth said. "Their pain may be due to IBS.""* *"While many patients may not yet be ready for cutting-edge treatments, IBS experts stress the importance of taking time to educate patients about IBS. One goal should be reassuring them that they don't have a more deadly condition such as ulcerative colitis or colon cancer.* "A lot of the improvement IBS patients experience probably comes as a result of them being reassured and having their symptoms explained to them," said Dr. Longstreth. "The doctor is functioning as the placebo." With that in mind, Dr. Lacy said, don't expect any quick cures when working with IBS patients. "Doctors really want to cure things,s but this is not something you can cure," he explained. "You need to take a nice deep breath, realize it's going to be a chronic problem, and don't get discouraged or let your patients get discouraged." http://www.acponline.org/journals/news/sep03/ibs.htm


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## eric (Jul 8, 1999)

Read or don't read that is up to you. Its your loss.If he saw inflammation on colonoscopy, I would be thinking about what is causing the inflammation and that needs to be investigated for sure. Did you ask him about it and what did he say?Do you have any of these alarm features?"Alarm SignsAs previously stated, typical symptoms point toward IBS, but certain co-existing alarm signs should alert the physician to the possibility of another disorder. These alarm signsï¿½which are not attributable to IBSï¿½include weight loss, frequent awakening by symptoms, fever, rectal bleeding, and anemia. These features can be a clue that another disorder besides IBS is responsible for the gastrointestinal symptoms and may call for further testing. However, a separate, benign problem is often found that explains the problem. For example, rectal bleeding with features typical of an anal origin that is reported by patients with an unchanged, chronic pattern of IBS symptoms is usually found to be caused by hemorrhoids. "The vast majority of IBSers have healthy looking colons upon colonoscopy. Some problems occur for some IBSers when they dig deeper into the colon wall.So he needs to be telling you why there is inflammation there and looking for the reason for it, if you external colon wall is inflammed.Current Approach to the Diagnosis of Irritable Bowel Syndrome"It is important to realize that in clinical practice the Rome II criteria and previous symptom criteria are reliable *only when there is no abnormal intestinal anatomy or metabolic process that would explain the symptoms; that is, negative results from a physical examination and additional diagnostic testing, as needed. * Furthermore, certain co-existing features ("alarm signs") call for special consideration of other disorders before a patient's symptoms can be attributed to IBS. Various symptom criteria have been used effectively in practice, and it is currently unclear whether the recent Rome II criteria are superior to previous ones. The important point is that typical symptoms in the absence of "alarm signs" or abnormalities from physical examination and limited investigation have high diagnostic accuracy. "Its also possible to have more then one thing going on. It might also depend on how you got it in the first place. Or if you polyps there.You know I am not sure why some of you want to argue with me and why that that is more important, then reading the information and learning more about IBS?FYI"Long disparaged as a "wastebasket disease," irritable bowel syndrome (IBS) appears to be gaining newfound respect among researchers, drug makers and gastroenterologists. The question now: Will other physicians begin to recognize IBS as a treatable condition, or will they continue to view it as a largely psychosomatic illness? *Researchers have made major strides in detecting the physiologic underpinnings of IBS as well as the nature of patients' "gut-brain" interactions. * At the same time, drug makers now offer treatments that specifically target a broad range of IBS symptoms. *And gastroenterologists have identified the signs of IBS that can lead to a definitive diagnosis, crafting guidelines to help physicians distinguish IBS from other conditions.* *But as many gastroenterologists are quick to point out, much of the progress being made on IBS has been lost on general practitioners. Rapid advances have created a "very big gap between primary care and gastroenterology," * said Douglas A. Drossman, FACP, co-director of the University of North Carolina Center for Functional Gastrointestinal and Motility Disorders at Chapel Hill. *"Primary care doctors are not up to speed."* To help close that gap, here is an overview of the latest developments in IBS research and treatment.""Help with the diagnosis *Until recently, physicians lacked a clear definition of what exactly constituted an IBS diagnosis. The condition required a diagnosis of exclusion, frustrating physicians and patients alikeï¿½and generally hampering treatment.* *Even worse, arriving at an IBS diagnosis made many physicians fear they had missed a more dangerous condition such as colon cancer. Without any real guidance, it was difficult to feel sure that an IBS diagnosis didn't mean you were overlooking something more serious.* *With the advent of new guidelines, known as the "Rome criteria," however, diagnosing irritable bowel syndrome has become more straightforward. The latest version of the criteriaï¿½Rome IIï¿½was developed by international experts and published in 2000. The criteria point to IBS as a genuine, treatable disorder.* The guidelines "give physicians something to hang a diagnosis on," said gastroenterologist Brian Lacy, MD, PhD, director of the Marvin M. Schuster Center for Digestive and Motility Disorders at Johns Hopkins Bayview Medical Center in Baltimore.According to the Rome II criteria, patients suffering from IBS have experienced several specific symptoms for at least 12 weeks during the previous year. The guidelines emphasize that IBS is a multifaceted condition that involves not only a faulty defecation pattern, but pain. (For more on the Rome criteria, see "The Rome II diagnostic criteria for irritable bowel syndrome," below.) "If they don't have pain, they don't have IBS," Dr. Lacy said, "even if they have diarrhea 15 times a day or go to the bathroom only once a month." *While the guidelines still require physicians to rule out other conditions such as functional diarrhea or pelvic floor disorders, both of which are similar to IBS, experts say the criteria reduce much of the diagnostic uncertainty by limiting the range of other possible conditions. You don't need to run most patients through an extensive battery of tests to reach a diagnosis.* Last year, both the American Gastroenterological Association and the American College of Gastroenterology (ACG) issued position statements that agree with that diagnostic approach. *The organizations identified key "alarm signals" that should alert you to other potential diagnoses when working with possible IBS patients.* While you may feel compelled to list several problems like pain, bloating and constipation when treating IBS patients, Dr. Lacy said that approach is unnecessary. *"These patients have one unifying diagnosisï¿½IBSï¿½that should make it easier to treat them," he explained. "You need to think about treating this whole constellation of symptoms."* *Performing fewer tests to make an IBS diagnosis benefits not only health plans, but patients themselves. Excessive testing can distress patients,* noted gastroenterologist George F. Longstreth, MD, chief of gastroenterology at Kaiser Permanente Medical Care Program in San Diego." *Too many tests sometimes create more anxiety," he said, a factor that can be a real liability when research suggests that IBS patients may have more pronounced intestinal reactions to stress than other patients.* (For more on the "gut-brain" connection, see "IBS: An anatomy of what goes wrong in the body," below.) *And while internists instinctively worry about missing another disease, they need to guard against making the opposite mistake: confusing IBS symptoms for those of other medical conditions. * *Studies have shown, for example, that IBS patients are more likely to have their gallbladders removed or to have a hysterectomy. "IBS patients shouldn't automatically have their gallbladders taken out," Dr. Longstreth said. "Their pain may be due to IBS.""* *"While many patients may not yet be ready for cutting-edge treatments, IBS experts stress the importance of taking time to educate patients about IBS. One goal should be reassuring them that they don't have a more deadly condition such as ulcerative colitis or colon cancer.* "A lot of the improvement IBS patients experience probably comes as a result of them being reassured and having their symptoms explained to them," said Dr. Longstreth. "The doctor is functioning as the placebo." With that in mind, Dr. Lacy said, don't expect any quick cures when working with IBS patients. "Doctors really want to cure things,s but this is not something you can cure," he explained. "You need to take a nice deep breath, realize it's going to be a chronic problem, and don't get discouraged or let your patients get discouraged." http://www.acponline.org/journals/news/sep03/ibs.htm


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## eric (Jul 8, 1999)

"J Neuroimmunol. 2004 Jan;146(1-2):1-12. Related Articles, Links Critical role of mast cells in inflammatory diseases and the effect of acute stress.Theoharides TC, Cochrane DE.Department of Pharmacology and Experimental Therapeutics, Tufts-New England Medical Center, Boston, MA, USA. theoharis.theoharides###tufts.eduMast cells are not only necessary for allergic reactions, but recent findings indicate that they are also involved in a variety of neuroinflammatory diseases, especially those worsened by stress. In these cases, mast cells appear to be activated through their Fc receptors by immunoglobulins other than IgE, as well as by anaphylatoxins, neuropeptides and cytokines to secrete mediators selectively without overt degranulation. These facts can help us better understand a variety of sterile inflammatory conditions, such as multiple sclerosis (MS), migraines, inflammatory arthritis, atopic dermatitis, coronary inflammation, interstitial cystitis and irritable bowel syndrome, *in which mast cells are activated without allergic degranulation.* Publication Types: Review Review, Tutorial PMID: 14698841The hpa axis and chronic stress in IBS can inflame and activate mast cells without an alllergic reaction. Chronic stressors can activate the pathways and degrangulate the cells without a pathogen. The mast cells then release toxins onto the smooth muscle and they believe this contributes to pain in IBS, a ton of research has already been done on this and a lot more being done."Readers' ExchangeDefining Stress in IBSFall 2003From Arizona -- Thank you so much for your efforts and support for those of us with GI disorders. Your first issue (Spring 2003) of Digestive Health Matters is both professional and informative. I would like to comment on one of the articles - "The CNS: Center for Neurovisceral Sciences and Women's Health at UCLA." I am encouraged to know that steps are being taken for funding research of IBS and interstitial cystitis. However, it is discouraging that researchers are still expending time and money to research "neurobiological mechanisms by which stress modulates brain-visceral interaction." I realize that stress is a popular theory in the discussion of IBS triggers, however, I believe this is completely backward and it is the chronic pain and totally unreliable bowel function of an IBS sufferer which causes the greatest stress. If research would focus on "fixing" the bowel, no doubt the panic and fear of IBS would be greatly alleviated. Comment from Emeran Mayer, M.D. -- In contrast to the common interpretation of the term "stress" as a psychological phenomenon, it should be understood as any real or perceived perturbation of an organism's homeostasis, or state of harmony or balance. For example, in this viewpoint a severe hemorrhage, starvation, extreme temperature, or worry about the unpredictable onset of abdominal pain all qualify as stressors -- some as "physical" stressors, others as "psychological" stressors. The fear to leave the house in the morning without knowing if one can make it to work without having to stop on the freeway because of an uncontrollable bowel movement, or the fear of experiencing uncontrollable abdominal discomfort during an important business meeting are sufficient stressors to activate the central stress system. The central stress system involves the release of chemical stress mediators in the brain (such as corticotropin releasing factor), which in turn orchestrate an integrated autonomic, behavioral, neuroendocrine, and pain modulatory response. This biological response in turn will alter the way the brain and the viscera interact, and this altered brain-gut interaction can result in worsening of IBS symptoms. Thus, pain and discomfort, fear of these symptoms, activation of the stress response, and modulation of the brain-gut interactions by stress mediators are part of a vicious cycle which need to be interrupted to produce symptom relief. The neurobiology of stress is not a theory, but a topic that can be studied in animal models, and one of the hottest topics in drug development for treatment of IBS (e.g., substance P antagonists, corticotropin releasing factor antagonists). http://www.aboutibs.org/Publications/StressDefined.html "What would be an example of new understanding?Well one example is that we're starting to understand how the brain is responding to the pain in IBS. There have been some studies done where they've artificially created a kind of an irritable bowel by placing a balloon to stretch the bowel, and that produces pain. Then they've compared people with IBS to non-IBS, or "normal" individuals. And what they've found is that when you stretch the bowel-and use PET scans to monitor the response-in normal individuals, certain areas of the brain that register pain respond and release chemicals called neurotransmitters that suppress and lower the pain. But it seems that doesn't happen as well in people with IBS. *In fact, in people with IBS another area of the brain responds that is associated with anxiety. So what we find is that people with IBS, aside from having a bowel problem, may have some difficulty in terms of the way their brain is regulating the pain."* http://www.aboutibs.org/Publications/clinicalIssues.html So what would the increase activation in the prefrontal cortex have to do with the HPA axis and stress and anxiety and mast cells in the gut?What neurotransmitter is involved in the signalling from the gut to the brain that activates the prefrontal cortex and the anterior cinculate cortex?All pain is registered in the brain. http://www.aboutibs.org/Publications/clinicalIssues.html I will also point this out again.History of Functional Disorders Douglas A. Drossman, MDCenter-Co-Director, UNC Center for Functional GI & Motility Disorders, UNC-Chapel Hill School of Medicine Melissa Swantkowski New York UniversityPrintable formatTHE PASTHISTORICAL PRECEDENTSHistorians and physicians have documented the presence of Functional GI disorders throughout recorded human history. However, until recently, limited attention has been granted to these disorders due to the lack of identifiable pathology and the absence of a conceptual framework to understand and categorize them. Systematic investigation of functional GI disorders did not begin until the middle of the 20th century. Prior to this time, only occasional reports of functional GI symptoms were published, the first appearing just 200 years ago. Over the past 25 years, scientific attention to understanding and properly caring for patients with functional GI disorders has grown progressively. With increased understanding comes the rationale for use of medications directed at intestinal receptors as well as psychopharmacological, behavioral, and psychological forms of treatment. There has also been an increase in the rate of scientific publications and greater media exposure to the public through television, radio and the Internet. To understand the historical classification of these disorders, two differing theories relating to the interaction between the mind and body should be considered.Holism: a theory built upon the foundation that the mind and body are integrated and utterly inseparable.Dualism: a theory that proposes a separation between the mind and the body.Greek philosophers Plato, Aristotle and Hippocrates first proposed the principle of holism about 3,000 years ago. Later in the 12th century, Jewish physician and philosopher Maimonides reexamined this philosophy. Based on holism, the study of medical disease must take into account the whole person rather than merely the diseased part. However, societal concepts of illness and disease drastically shifted when European philosopher Rene Descartes offered the divergent theory of dualism in the 17th century. Prior to the notion of dualism, the church discouraged human dissection on the premise that the spirit resided in the body. The acceptance of dualism paved the way for the emergence of scientific investigation and new medical discoveries by lifting the prohibition of human dissection. This shift in medical thought was congruent with the societal changes of the 17th century -- the shift towards a separation in church and state. IMPLICATIONS FOR FUNCTIONAL GI DISORDERSBased on the concept of dualism, disease was now understood in terms of structural abnormalities. Therefore, the validity of a disease rested with the observation of morphological abnormalities. Medical conditions occurring in the absence of such morphological abnormalities and symptoms were not considered legitimate, and were often viewed as psychiatric, consistent with the concept of dualism. The concept of dualism had other effects with regard to treatment. For example, this would include all the functional GI disorders and other somatic syndromes, such as fibromyalgia. Until the latter part of the 20th century, a medical illness was considered amenable to scientific inquiry and treatment. However, patients with psychiatric disorders were interred in insane asylums and considered to no longer be treatable by medical physicians. Unfortunately, this concept leads to a clinical dilemma. Specific diseases explain only about 10% of medical illnesses seen by physicians. Furthermore, people with a structural (i.e. organic) diagnosis, such as inflammatory bowel disease (IBD) or cancer, show considerable variation in their symptom presentation and clinical behavior. Gastroenterologists (as well as other health care practitioners) are all too familiar with the poor correlation between structural findings on endoscopy and their patient's symptoms. Although efforts to find morphological or even motility etiologies for functional GI disorders in the latter part of the 20th century were unsuccessful, the assumption that functional GI disorders must be psychiatric has developed and has permeated current thinking. However, in the face of current scientific research, this is being seriously challenged. Studies have shown that persons with irritable bowel syndrome who do not seek health care are psychologically much like healthy subjects. THE PRESENT CONCEPTUAL BASES FOR THE STUDY OF FUNCTIONAL GI DISORDERSThe recent acceptance of functional GI disorders as legitimate medical entities is based on the following three developments: the concept of the biopsychosocial model of illness and disease the development of new investigative methods for studying disease the development of the Rome Criteria Biopsychosocial ModelIn 1977, publication of the concept of the biopsychosocial model by George Engel, and its later demonstration specifically for gastrointestinal disorders, marked an important change in thinking. A biopsychosocial model of illness and disease provides the needed framework to understand, categorize and treat common GI symptoms. These symptoms are the integrated product of altered motility, enhanced visceral sensitivity, and brain-gut dysregulation and often are influenced by psychosocial factors. Early in life, genetics and environmental influences (family attitudes about bowel training or illness in general, major loss or abuse history, or exposure to infection) may affect one's psychosocial development (susceptibility to life stress, psychological state, coping skills, social support) or the development of gut dysfunction (abnormal motility or visceral hypersensitivity). The presence and nature of a functional GI disorder is also determined by the interaction of psychosocial factors and altered physiology via the brain-gut axis. In other words, an individual afflicted with a bowel disorder but with no psychosocial disturbances, good coping skills and adequate social support may have less severe symptoms and not seek medical care. By contrast, another individual having similar symptoms but with coexistent psychosocial disturbance, high life stress, or poor coping skills may frequent his physician's office and have generally poor outcome. Development of New Investigative Methods The second important development has been the expansion and refinement of investigative methods that allow the study of functional GI disorders in terms of biological, cultural and psychosocial (i.e. brain) influences. These developments include:the improvement of motility assessment the standardization of the barostat to measure visceral sensitivity the enhancement of psychometric instruments to determine psychosocial influences the introduction of brain imaging (PET, fMRI) to determine CNS contribution to symptoms the molecular investigation of brain-gut peptides, which provide insight into how these symptoms become manifest. In less than ten years, these methods have produced new knowledge of the underlying pathophysiological features that characterize the age-old symptoms we now define as functional GI disorders. Rome CriteriaThe Rome Criteria is an international effort to characterize and classify the functional GI disorders using a symptom-based classification system. This approach has its precedents with classification systems in psychiatry and rheumatology. The rationale for such a system is based on the premise that patients with functional GI complaints consistently report symptoms that breed true in their clinical features, yet cannot be classified by any existing structural, physiological or biochemical substrate. The Rome Criteria was built upon the Manning Criteria, which was developed from discriminate function analysis of GI patients. The decision to develop diagnostic criteria by international consensus was introduced as part of a larger effort to address issues within gastroenterology that are not easily resolved by usual scientific inquiry or literature review. By 1992, several committees had met to discuss the criteria, which ultimately resulted in the publishing of many articles in Gastroenterology International and a book detailing the criteria titled "The Functional Gastrointestinal Disorders (Rome I)". Elaboration of the Rome I criteria led to a second edition of the Rome criteria (titled Rome II) in 2000 as well as the publication of a supplement to the journal Gut in 1999. Recently, the Rome Coordinating Committee has met to begin Rome III, expected to be published in 2006. To learn more about the Rome Committees and to see a summary of the Rome II book: go to www.romecriteria.com.PATHOPHYSIOLOGICAL OBSERVATIONS Despite differences among the functional gastrointestinal disorders in location and symptom features, common characteristics are shared with regard to:motor and sensory physiology central nervous system relationships approach to patient care What follows are the general observations and guidelines. MotilityIn healthy subjects, stress can increase motility in the esophagus, stomach, small and large intestine, and colon. Abnormal motility can generate a variety of GI symptoms including vomiting, diarrhea, constipation, acute abdominal pain, and fecal incontinence. Functional GI patients have even greater increased motility in response to stressors in comparison to normal subjects. While abnormal motility plays a vital role in understanding many of the functional GI disorders and their symptoms, it is not sufficient to explain reports of chronic or recurrent abdominal pain.Visceral HypersensitivityVisceral hypersensitivity helps to account for disorders associated with chronic or recurrent pain, which are not well correlated with changes in gastrointestinal motility and, in some cases, where motility disturbances do not exist. Patients suffering from visceral hypersensitivity have a lower pain threshold with balloon distension of the bowel or have increased sensitivity to even normal intestinal function. Additionally, there may be an increased or unusual area of somatic referral of visceral pain. Recently, it has been concluded that visceral hypersensitivity may be induced in response to rectal or colonic distension in normal subjects and, to a greater degree, in persons with IBS. Therefore, it is possible that the pain of functional GI disorders may relate to sensitization resulting from chronic abnormal motor hyperactivity, GI infection, or trauma/injury to the viscera. Brain-Gut AxisThe concept of brain-gut interactions brings together observations relating to motility and visceral hypersensitivity and their modulation by psychosocial factors. By integrating intestinal and CNS (central nervous system) activity, the brain-gut axis explains the symptoms relating to functional GI disorders. In other words, senses such as vision and smell, as well as enteroceptive information (i.e. emotion and thought) have the ability to affect gastrointestinal sensation, motility, secretion, and inflammation. Conversely, viscerotopic effects reciprocally affect central pain perception, mood and behavior. For example, spontaneously induced contractions of the colon in rats lead to activation of the locus coeruleus in the pons, an area closely connected to pain and emotional centers in the brain. The increased arousal or anxiety is associated with a decrease in the frequency of MMC activity of the small bowel possibly mediated by stress hormones in the brain. Based on these observations, it is no longer rational to try to differentiate whether physiological or psychological factors produce pain or other bowel symptoms. Instead, the functional GI disorders are understood in terms of dysregulation of brain-gut function, and the task is to determine to what degree each is remediable. Therefore, a treatment approach consistent with the concept of brain-gut dysfunction may focus on the neuropeptides and receptors that are present in both enteric and central nervous systems. Role for Psychological FactorsAlthough psychological factors do not define these disorders and are not required for diagnosis, they are important modulators of the patient's experience and, ultimately, the clinical outcome. Research on the psychosocial aspects of patients with functional GI disorders has led to three general observations: Psychological stress exacerbates gastrointestinal symptoms in patients with functional GI disorders and can even produce symptoms in healthy patients (but to a lesser degree). Psychological disturbances modify the experience of illness and illness behaviors, such as health care seeking. For example, a history of major psychological trauma (e.g. sexual or physical abuse) is more common among patients seen in referral centers than in primary care and is associated with a more severe disorder and a poorer clinical outcome. Psychological trauma may increase pain-reporting tendency. Having a functional GI disorder has psychological consequences in terms of one's general well-being, daily functional status, concerns relating to control over symptoms, and future implications of the illness (e.g. functioning at work and home). APPROACH TO TREATMENTEffective treatment for all functional GI disorders is based on a therapeutic physician-patient relationship. The importance of a good physician-patient relationship is supported by evidence that patients with functional GI disorders have anywhere from a 30 to 80% placebo response rate regardless of treatment. Because functional GI disorders are chronic, it is important to determine the immediate reasons behind each visit, after which treatment decisions can be based on severity and nature of symptoms, physiological and psychosocial determinants of the patients illness behavior, and the degree of functional impairment. These factors can separate patients into mild, moderate, and severe categories.Patients with mild symptomsusually seen in primary care do not have major impairment in function or psychological disturbance can maintain normal activity These patients have concerns about their condition, but do not need to make many visits to their physician. Regarding treatment, these patients require education about their disorder and its symptoms as well as information regarding a proper diet and the kinds of medication that can have adverse effects. Patients with moderate symptomsseen in both primary and secondary care facilities experience intermittent disruptions in activity on account of their symptoms may identify a close relationship between symptoms and inciting events such as stress, travel, or dietary indiscretion For these patients, symptom monitoring to record time, severity and presence of associated factors can help to identify inciting factors and give the patient a sense of control over the disorder. Pharmacotherapy directed at specific symptoms, particularly those that impair daily function, can be helpful, as can psychological treatments (relaxation, hypnosis, cognitive-behavioral therapy, and combination treatments) in reducing anxiety and encouraging health promoting behaviors. Patients with severe symptomshave trouble functioning daily find their disorder to be disabling and debilitating in nearly every facet of life have a high frequency of associated psychological difficulties make frequent visits to their physicians may hope for a magical cure In these cases, a longer-term physician-patient relationship that sets realistic treatment goals (such as improved quality of life rather than elimination of all pain) is necessary. The focus for these patients needs to shift from treating a disease to coping with a chronic disorder, where much of the responsibility is placed on the patient. Furthermore, antidepressants have proven useful to control pain and alleviate associated depressive symptoms. THE FUTUREFuture studies will identify pathophysiological subgroups, each having their own set of determinants and treatment. Examples are as follows:Some patients will develop their disorders or exacerbate symptoms via sensitization of afferent transmission from infection, enhanced motility, or trauma to the gut. They may respond to the newly developing neurotransmitter blocking agents. Patients with more painful and severe symptoms may prove to have "abnormal perception of normal gut function" rather than abnormal function. This dysfunction in the central regulation of incoming visceral signs may be remedied with a psychopharmacological treatment approach. The symptoms of some patients could be attributed to genetic factors, which result in abnormalities in central reactivity to stress, in which case genetic manipulation strategies would prove beneficial. Early learning within the familial structure and socio-cultural influences have been shown to affect symptom perception and illness behavior. Future studies are also likely to identify psychological and behavioral interventions that are targeted for this subgroup. While it is likely that there are potent new treatments that will follow our growing pathphysiologic knowledge of these disorders, it is unlikely they will replace some of the fundamental clinical principles: active listening careful decision making an effective patient-physician relationship patient centered biopsychosocial plan of care. http://www.med.unc.edu/wrkunits/2depts/med...aldisorders.htm


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## eric (Jul 8, 1999)

"J Neuroimmunol. 2004 Jan;146(1-2):1-12. Related Articles, Links Critical role of mast cells in inflammatory diseases and the effect of acute stress.Theoharides TC, Cochrane DE.Department of Pharmacology and Experimental Therapeutics, Tufts-New England Medical Center, Boston, MA, USA. theoharis.theoharides###tufts.eduMast cells are not only necessary for allergic reactions, but recent findings indicate that they are also involved in a variety of neuroinflammatory diseases, especially those worsened by stress. In these cases, mast cells appear to be activated through their Fc receptors by immunoglobulins other than IgE, as well as by anaphylatoxins, neuropeptides and cytokines to secrete mediators selectively without overt degranulation. These facts can help us better understand a variety of sterile inflammatory conditions, such as multiple sclerosis (MS), migraines, inflammatory arthritis, atopic dermatitis, coronary inflammation, interstitial cystitis and irritable bowel syndrome, *in which mast cells are activated without allergic degranulation.* Publication Types: Review Review, Tutorial PMID: 14698841The hpa axis and chronic stress in IBS can inflame and activate mast cells without an alllergic reaction. Chronic stressors can activate the pathways and degrangulate the cells without a pathogen. The mast cells then release toxins onto the smooth muscle and they believe this contributes to pain in IBS, a ton of research has already been done on this and a lot more being done."Readers' ExchangeDefining Stress in IBSFall 2003From Arizona -- Thank you so much for your efforts and support for those of us with GI disorders. Your first issue (Spring 2003) of Digestive Health Matters is both professional and informative. I would like to comment on one of the articles - "The CNS: Center for Neurovisceral Sciences and Women's Health at UCLA." I am encouraged to know that steps are being taken for funding research of IBS and interstitial cystitis. However, it is discouraging that researchers are still expending time and money to research "neurobiological mechanisms by which stress modulates brain-visceral interaction." I realize that stress is a popular theory in the discussion of IBS triggers, however, I believe this is completely backward and it is the chronic pain and totally unreliable bowel function of an IBS sufferer which causes the greatest stress. If research would focus on "fixing" the bowel, no doubt the panic and fear of IBS would be greatly alleviated. Comment from Emeran Mayer, M.D. -- In contrast to the common interpretation of the term "stress" as a psychological phenomenon, it should be understood as any real or perceived perturbation of an organism's homeostasis, or state of harmony or balance. For example, in this viewpoint a severe hemorrhage, starvation, extreme temperature, or worry about the unpredictable onset of abdominal pain all qualify as stressors -- some as "physical" stressors, others as "psychological" stressors. The fear to leave the house in the morning without knowing if one can make it to work without having to stop on the freeway because of an uncontrollable bowel movement, or the fear of experiencing uncontrollable abdominal discomfort during an important business meeting are sufficient stressors to activate the central stress system. The central stress system involves the release of chemical stress mediators in the brain (such as corticotropin releasing factor), which in turn orchestrate an integrated autonomic, behavioral, neuroendocrine, and pain modulatory response. This biological response in turn will alter the way the brain and the viscera interact, and this altered brain-gut interaction can result in worsening of IBS symptoms. Thus, pain and discomfort, fear of these symptoms, activation of the stress response, and modulation of the brain-gut interactions by stress mediators are part of a vicious cycle which need to be interrupted to produce symptom relief. The neurobiology of stress is not a theory, but a topic that can be studied in animal models, and one of the hottest topics in drug development for treatment of IBS (e.g., substance P antagonists, corticotropin releasing factor antagonists). http://www.aboutibs.org/Publications/StressDefined.html "What would be an example of new understanding?Well one example is that we're starting to understand how the brain is responding to the pain in IBS. There have been some studies done where they've artificially created a kind of an irritable bowel by placing a balloon to stretch the bowel, and that produces pain. Then they've compared people with IBS to non-IBS, or "normal" individuals. And what they've found is that when you stretch the bowel-and use PET scans to monitor the response-in normal individuals, certain areas of the brain that register pain respond and release chemicals called neurotransmitters that suppress and lower the pain. But it seems that doesn't happen as well in people with IBS. *In fact, in people with IBS another area of the brain responds that is associated with anxiety. So what we find is that people with IBS, aside from having a bowel problem, may have some difficulty in terms of the way their brain is regulating the pain."* http://www.aboutibs.org/Publications/clinicalIssues.html So what would the increase activation in the prefrontal cortex have to do with the HPA axis and stress and anxiety and mast cells in the gut?What neurotransmitter is involved in the signalling from the gut to the brain that activates the prefrontal cortex and the anterior cinculate cortex?All pain is registered in the brain. http://www.aboutibs.org/Publications/clinicalIssues.html I will also point this out again.History of Functional Disorders Douglas A. Drossman, MDCenter-Co-Director, UNC Center for Functional GI & Motility Disorders, UNC-Chapel Hill School of Medicine Melissa Swantkowski New York UniversityPrintable formatTHE PASTHISTORICAL PRECEDENTSHistorians and physicians have documented the presence of Functional GI disorders throughout recorded human history. However, until recently, limited attention has been granted to these disorders due to the lack of identifiable pathology and the absence of a conceptual framework to understand and categorize them. Systematic investigation of functional GI disorders did not begin until the middle of the 20th century. Prior to this time, only occasional reports of functional GI symptoms were published, the first appearing just 200 years ago. Over the past 25 years, scientific attention to understanding and properly caring for patients with functional GI disorders has grown progressively. With increased understanding comes the rationale for use of medications directed at intestinal receptors as well as psychopharmacological, behavioral, and psychological forms of treatment. There has also been an increase in the rate of scientific publications and greater media exposure to the public through television, radio and the Internet. To understand the historical classification of these disorders, two differing theories relating to the interaction between the mind and body should be considered.Holism: a theory built upon the foundation that the mind and body are integrated and utterly inseparable.Dualism: a theory that proposes a separation between the mind and the body.Greek philosophers Plato, Aristotle and Hippocrates first proposed the principle of holism about 3,000 years ago. Later in the 12th century, Jewish physician and philosopher Maimonides reexamined this philosophy. Based on holism, the study of medical disease must take into account the whole person rather than merely the diseased part. However, societal concepts of illness and disease drastically shifted when European philosopher Rene Descartes offered the divergent theory of dualism in the 17th century. Prior to the notion of dualism, the church discouraged human dissection on the premise that the spirit resided in the body. The acceptance of dualism paved the way for the emergence of scientific investigation and new medical discoveries by lifting the prohibition of human dissection. This shift in medical thought was congruent with the societal changes of the 17th century -- the shift towards a separation in church and state. IMPLICATIONS FOR FUNCTIONAL GI DISORDERSBased on the concept of dualism, disease was now understood in terms of structural abnormalities. Therefore, the validity of a disease rested with the observation of morphological abnormalities. Medical conditions occurring in the absence of such morphological abnormalities and symptoms were not considered legitimate, and were often viewed as psychiatric, consistent with the concept of dualism. The concept of dualism had other effects with regard to treatment. For example, this would include all the functional GI disorders and other somatic syndromes, such as fibromyalgia. Until the latter part of the 20th century, a medical illness was considered amenable to scientific inquiry and treatment. However, patients with psychiatric disorders were interred in insane asylums and considered to no longer be treatable by medical physicians. Unfortunately, this concept leads to a clinical dilemma. Specific diseases explain only about 10% of medical illnesses seen by physicians. Furthermore, people with a structural (i.e. organic) diagnosis, such as inflammatory bowel disease (IBD) or cancer, show considerable variation in their symptom presentation and clinical behavior. Gastroenterologists (as well as other health care practitioners) are all too familiar with the poor correlation between structural findings on endoscopy and their patient's symptoms. Although efforts to find morphological or even motility etiologies for functional GI disorders in the latter part of the 20th century were unsuccessful, the assumption that functional GI disorders must be psychiatric has developed and has permeated current thinking. However, in the face of current scientific research, this is being seriously challenged. Studies have shown that persons with irritable bowel syndrome who do not seek health care are psychologically much like healthy subjects. THE PRESENT CONCEPTUAL BASES FOR THE STUDY OF FUNCTIONAL GI DISORDERSThe recent acceptance of functional GI disorders as legitimate medical entities is based on the following three developments: the concept of the biopsychosocial model of illness and disease the development of new investigative methods for studying disease the development of the Rome Criteria Biopsychosocial ModelIn 1977, publication of the concept of the biopsychosocial model by George Engel, and its later demonstration specifically for gastrointestinal disorders, marked an important change in thinking. A biopsychosocial model of illness and disease provides the needed framework to understand, categorize and treat common GI symptoms. These symptoms are the integrated product of altered motility, enhanced visceral sensitivity, and brain-gut dysregulation and often are influenced by psychosocial factors. Early in life, genetics and environmental influences (family attitudes about bowel training or illness in general, major loss or abuse history, or exposure to infection) may affect one's psychosocial development (susceptibility to life stress, psychological state, coping skills, social support) or the development of gut dysfunction (abnormal motility or visceral hypersensitivity). The presence and nature of a functional GI disorder is also determined by the interaction of psychosocial factors and altered physiology via the brain-gut axis. In other words, an individual afflicted with a bowel disorder but with no psychosocial disturbances, good coping skills and adequate social support may have less severe symptoms and not seek medical care. By contrast, another individual having similar symptoms but with coexistent psychosocial disturbance, high life stress, or poor coping skills may frequent his physician's office and have generally poor outcome. Development of New Investigative Methods The second important development has been the expansion and refinement of investigative methods that allow the study of functional GI disorders in terms of biological, cultural and psychosocial (i.e. brain) influences. These developments include:the improvement of motility assessment the standardization of the barostat to measure visceral sensitivity the enhancement of psychometric instruments to determine psychosocial influences the introduction of brain imaging (PET, fMRI) to determine CNS contribution to symptoms the molecular investigation of brain-gut peptides, which provide insight into how these symptoms become manifest. In less than ten years, these methods have produced new knowledge of the underlying pathophysiological features that characterize the age-old symptoms we now define as functional GI disorders. Rome CriteriaThe Rome Criteria is an international effort to characterize and classify the functional GI disorders using a symptom-based classification system. This approach has its precedents with classification systems in psychiatry and rheumatology. The rationale for such a system is based on the premise that patients with functional GI complaints consistently report symptoms that breed true in their clinical features, yet cannot be classified by any existing structural, physiological or biochemical substrate. The Rome Criteria was built upon the Manning Criteria, which was developed from discriminate function analysis of GI patients. The decision to develop diagnostic criteria by international consensus was introduced as part of a larger effort to address issues within gastroenterology that are not easily resolved by usual scientific inquiry or literature review. By 1992, several committees had met to discuss the criteria, which ultimately resulted in the publishing of many articles in Gastroenterology International and a book detailing the criteria titled "The Functional Gastrointestinal Disorders (Rome I)". Elaboration of the Rome I criteria led to a second edition of the Rome criteria (titled Rome II) in 2000 as well as the publication of a supplement to the journal Gut in 1999. Recently, the Rome Coordinating Committee has met to begin Rome III, expected to be published in 2006. To learn more about the Rome Committees and to see a summary of the Rome II book: go to www.romecriteria.com.PATHOPHYSIOLOGICAL OBSERVATIONS Despite differences among the functional gastrointestinal disorders in location and symptom features, common characteristics are shared with regard to:motor and sensory physiology central nervous system relationships approach to patient care What follows are the general observations and guidelines. MotilityIn healthy subjects, stress can increase motility in the esophagus, stomach, small and large intestine, and colon. Abnormal motility can generate a variety of GI symptoms including vomiting, diarrhea, constipation, acute abdominal pain, and fecal incontinence. Functional GI patients have even greater increased motility in response to stressors in comparison to normal subjects. While abnormal motility plays a vital role in understanding many of the functional GI disorders and their symptoms, it is not sufficient to explain reports of chronic or recurrent abdominal pain.Visceral HypersensitivityVisceral hypersensitivity helps to account for disorders associated with chronic or recurrent pain, which are not well correlated with changes in gastrointestinal motility and, in some cases, where motility disturbances do not exist. Patients suffering from visceral hypersensitivity have a lower pain threshold with balloon distension of the bowel or have increased sensitivity to even normal intestinal function. Additionally, there may be an increased or unusual area of somatic referral of visceral pain. Recently, it has been concluded that visceral hypersensitivity may be induced in response to rectal or colonic distension in normal subjects and, to a greater degree, in persons with IBS. Therefore, it is possible that the pain of functional GI disorders may relate to sensitization resulting from chronic abnormal motor hyperactivity, GI infection, or trauma/injury to the viscera. Brain-Gut AxisThe concept of brain-gut interactions brings together observations relating to motility and visceral hypersensitivity and their modulation by psychosocial factors. By integrating intestinal and CNS (central nervous system) activity, the brain-gut axis explains the symptoms relating to functional GI disorders. In other words, senses such as vision and smell, as well as enteroceptive information (i.e. emotion and thought) have the ability to affect gastrointestinal sensation, motility, secretion, and inflammation. Conversely, viscerotopic effects reciprocally affect central pain perception, mood and behavior. For example, spontaneously induced contractions of the colon in rats lead to activation of the locus coeruleus in the pons, an area closely connected to pain and emotional centers in the brain. The increased arousal or anxiety is associated with a decrease in the frequency of MMC activity of the small bowel possibly mediated by stress hormones in the brain. Based on these observations, it is no longer rational to try to differentiate whether physiological or psychological factors produce pain or other bowel symptoms. Instead, the functional GI disorders are understood in terms of dysregulation of brain-gut function, and the task is to determine to what degree each is remediable. Therefore, a treatment approach consistent with the concept of brain-gut dysfunction may focus on the neuropeptides and receptors that are present in both enteric and central nervous systems. Role for Psychological FactorsAlthough psychological factors do not define these disorders and are not required for diagnosis, they are important modulators of the patient's experience and, ultimately, the clinical outcome. Research on the psychosocial aspects of patients with functional GI disorders has led to three general observations: Psychological stress exacerbates gastrointestinal symptoms in patients with functional GI disorders and can even produce symptoms in healthy patients (but to a lesser degree). Psychological disturbances modify the experience of illness and illness behaviors, such as health care seeking. For example, a history of major psychological trauma (e.g. sexual or physical abuse) is more common among patients seen in referral centers than in primary care and is associated with a more severe disorder and a poorer clinical outcome. Psychological trauma may increase pain-reporting tendency. Having a functional GI disorder has psychological consequences in terms of one's general well-being, daily functional status, concerns relating to control over symptoms, and future implications of the illness (e.g. functioning at work and home). APPROACH TO TREATMENTEffective treatment for all functional GI disorders is based on a therapeutic physician-patient relationship. The importance of a good physician-patient relationship is supported by evidence that patients with functional GI disorders have anywhere from a 30 to 80% placebo response rate regardless of treatment. Because functional GI disorders are chronic, it is important to determine the immediate reasons behind each visit, after which treatment decisions can be based on severity and nature of symptoms, physiological and psychosocial determinants of the patients illness behavior, and the degree of functional impairment. These factors can separate patients into mild, moderate, and severe categories.Patients with mild symptomsusually seen in primary care do not have major impairment in function or psychological disturbance can maintain normal activity These patients have concerns about their condition, but do not need to make many visits to their physician. Regarding treatment, these patients require education about their disorder and its symptoms as well as information regarding a proper diet and the kinds of medication that can have adverse effects. Patients with moderate symptomsseen in both primary and secondary care facilities experience intermittent disruptions in activity on account of their symptoms may identify a close relationship between symptoms and inciting events such as stress, travel, or dietary indiscretion For these patients, symptom monitoring to record time, severity and presence of associated factors can help to identify inciting factors and give the patient a sense of control over the disorder. Pharmacotherapy directed at specific symptoms, particularly those that impair daily function, can be helpful, as can psychological treatments (relaxation, hypnosis, cognitive-behavioral therapy, and combination treatments) in reducing anxiety and encouraging health promoting behaviors. Patients with severe symptomshave trouble functioning daily find their disorder to be disabling and debilitating in nearly every facet of life have a high frequency of associated psychological difficulties make frequent visits to their physicians may hope for a magical cure In these cases, a longer-term physician-patient relationship that sets realistic treatment goals (such as improved quality of life rather than elimination of all pain) is necessary. The focus for these patients needs to shift from treating a disease to coping with a chronic disorder, where much of the responsibility is placed on the patient. Furthermore, antidepressants have proven useful to control pain and alleviate associated depressive symptoms. THE FUTUREFuture studies will identify pathophysiological subgroups, each having their own set of determinants and treatment. Examples are as follows:Some patients will develop their disorders or exacerbate symptoms via sensitization of afferent transmission from infection, enhanced motility, or trauma to the gut. They may respond to the newly developing neurotransmitter blocking agents. Patients with more painful and severe symptoms may prove to have "abnormal perception of normal gut function" rather than abnormal function. This dysfunction in the central regulation of incoming visceral signs may be remedied with a psychopharmacological treatment approach. The symptoms of some patients could be attributed to genetic factors, which result in abnormalities in central reactivity to stress, in which case genetic manipulation strategies would prove beneficial. Early learning within the familial structure and socio-cultural influences have been shown to affect symptom perception and illness behavior. Future studies are also likely to identify psychological and behavioral interventions that are targeted for this subgroup. While it is likely that there are potent new treatments that will follow our growing pathphysiologic knowledge of these disorders, it is unlikely they will replace some of the fundamental clinical principles: active listening careful decision making an effective patient-physician relationship patient centered biopsychosocial plan of care. http://www.med.unc.edu/wrkunits/2depts/med...aldisorders.htm


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## Talissa (Apr 10, 2004)

Amnegirl & Ken, thanks!Ken,Very interesting that you definitely have low grade inflammation & your doc says its consistent with IBS. Your MD is far above average & its encouraging, because maybe he's a sign of things to come!>>>>>>>>>>>>>>>>>>>>>>>I'm not going to answer your post, point by point Eric, no time, no desire right now.I will say that I shouted at you because for some reason, you keep saying I say IBS can be "cured."I do not.Shouting seemed to be the only way to get you to stop saying that.I also want to say that that while I don't believe hypnotherapy alone is a way to get to 100%, I don't mean to put it down.I think it could help alot(but so does meditation, music therapy, yoga).All of the answers, Eric, aren't in yet re: the low grade inflammation of IBS and if intestinal flora dysbiosis/imbalance is the cause or the effect of IBS, so I'm sorry if I get rattled when you think that this "syndrome" which has ongoing studies to figure it out, is something you have figured out. If you have this "syndrome" figured out & know all the answers, you should be bloody rich, my friend.All people with IBS have not been biopsied for the low grade inflammation with the special microscopic lenses necessary to detect it(Ken is lucky!), so they have to say, for now, its only the post infectious subgroup of IBS patients. They're the only group studied for it.Why can't we PI IBSr's down-regulate the microscopic inflammation?Autoimmunity? Problems with the HPA axis? This is what I want to know. It's being studied.But if you are 100% Eric, I'm incredibly happy for you.Just please, stop trying to stop others who've gotten well from helping people on this "self help" bb & acting like you know more than God regarding IBS & noone else can possibly grasp the intricacies of the condition.It incites.


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## Talissa (Apr 10, 2004)

Amnegirl & Ken, thanks!Ken,Very interesting that you definitely have low grade inflammation & your doc says its consistent with IBS. Your MD is far above average & its encouraging, because maybe he's a sign of things to come!>>>>>>>>>>>>>>>>>>>>>>>I'm not going to answer your post, point by point Eric, no time, no desire right now.I will say that I shouted at you because for some reason, you keep saying I say IBS can be "cured."I do not.Shouting seemed to be the only way to get you to stop saying that.I also want to say that that while I don't believe hypnotherapy alone is a way to get to 100%, I don't mean to put it down.I think it could help alot(but so does meditation, music therapy, yoga).All of the answers, Eric, aren't in yet re: the low grade inflammation of IBS and if intestinal flora dysbiosis/imbalance is the cause or the effect of IBS, so I'm sorry if I get rattled when you think that this "syndrome" which has ongoing studies to figure it out, is something you have figured out. If you have this "syndrome" figured out & know all the answers, you should be bloody rich, my friend.All people with IBS have not been biopsied for the low grade inflammation with the special microscopic lenses necessary to detect it(Ken is lucky!), so they have to say, for now, its only the post infectious subgroup of IBS patients. They're the only group studied for it.Why can't we PI IBSr's down-regulate the microscopic inflammation?Autoimmunity? Problems with the HPA axis? This is what I want to know. It's being studied.But if you are 100% Eric, I'm incredibly happy for you.Just please, stop trying to stop others who've gotten well from helping people on this "self help" bb & acting like you know more than God regarding IBS & noone else can possibly grasp the intricacies of the condition.It incites.


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## Jeffrey Roberts (Apr 15, 1987)

Talissa and Eric,You both make some very good points. Please for everyones sake, can you try and do this in a constructive respectable manner.Generally we tend to steer away from anecdotal remedies and discuss medically and clinically proven coping techniques and/or medicines here.I hope that provides some guidance for you going forward.Jeff


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## Jeffrey Roberts (Apr 15, 1987)

Talissa and Eric,You both make some very good points. Please for everyones sake, can you try and do this in a constructive respectable manner.Generally we tend to steer away from anecdotal remedies and discuss medically and clinically proven coping techniques and/or medicines here.I hope that provides some guidance for you going forward.Jeff


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## Talissa (Apr 10, 2004)

Jeffrey,Thanks for the interference. I'm sorry we clash as we do.The guidance you've given is interesting.But I have a question. It is sincere, I'd really like to know...Since hypnotherapy tapes, as opposed to hypnotherapy with a therapist, have NOT been clinically proven, does this mean discussing the tapes should be steered away from?Talissa


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## Talissa (Apr 10, 2004)

Jeffrey,Thanks for the interference. I'm sorry we clash as we do.The guidance you've given is interesting.But I have a question. It is sincere, I'd really like to know...Since hypnotherapy tapes, as opposed to hypnotherapy with a therapist, have NOT been clinically proven, does this mean discussing the tapes should be steered away from?Talissa


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## Jeffrey Roberts (Apr 15, 1987)

Talissa,I don't think I'm actually qualified to answer that ie: I don't know if there are any studies with tapes vs. a therapist. I have had numerous discussions with Olafur S. Palsson at UNC and he has never given me an indication otherwise that tapes did not show the same clinical results.In anycase, well established, clinically studied coping tools are best discussed in this forum if another forum doesn't already exist on the BB.I hope that helps.JeffP.S. I am a huge believer that gut flora has a lot to do with my own IBS. I have been using Digestive Advantage IBS for almost 4 months now with excellent results.


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## Jeffrey Roberts (Apr 15, 1987)

Talissa,I don't think I'm actually qualified to answer that ie: I don't know if there are any studies with tapes vs. a therapist. I have had numerous discussions with Olafur S. Palsson at UNC and he has never given me an indication otherwise that tapes did not show the same clinical results.In anycase, well established, clinically studied coping tools are best discussed in this forum if another forum doesn't already exist on the BB.I hope that helps.JeffP.S. I am a huge believer that gut flora has a lot to do with my own IBS. I have been using Digestive Advantage IBS for almost 4 months now with excellent results.


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## drdahlman (Nov 6, 2000)

Jeff, What would happen if you stopped taking Digestive Advantage-IBS? I want to thank you for filling us in on the success you're having. I find it interesting that the product contains lactobacillus cultures, an amino acid and fiber, as does my program. The exact ingredients from the package are: Cellulose, Lactobacillus Cultures, L-Lysine, Hydroxypropyl Methylcellulose, Maltodextrin, Magnesium Stearate, Flavor, FD&C Blue Lake, Red Sucrose Specs.None of my products contain artificial colors or sucrose, which breaks down to glucose and fructose and may cause some a problem.The reason that this product will not work for everyone or only to a limited degree is because there are patients that will need the bifidus cultures, other amino acids pertinent to the gut and the temporary, hopefully temporary, removal of certain foods that they have become intolerant of or allergic to. If you were to experiment and stop taking the product, I would suspect that you would lose any benefit that you have experienced. That would tell us that the lactobacillus cultures in the product are transient and not the specific strains that a human would need. Great way to build repeat business, similar to what Garden of Life is doing with Primal Defense.Thanks for confirming the basics of my program with the comments about your success with DA-IBS.Difference is that you are finished with my the product portion of my protocol in a few months, though dietary exclusions may need to be continued.I must say one more time, as I have said through private email to you, that I will be happy to provide for you all of my products and my time...at no charge to you whatsoever...and let's follow my exact program and see if it works for you the way I say it works for everyone. I will also pay for any necessary lab tests. It would also provide a possibility that you could report that it didn't work. I'm willing to take that chance, are you ready to eliminate all your symptoms?


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## drdahlman (Nov 6, 2000)

Jeff, What would happen if you stopped taking Digestive Advantage-IBS? I want to thank you for filling us in on the success you're having. I find it interesting that the product contains lactobacillus cultures, an amino acid and fiber, as does my program. The exact ingredients from the package are: Cellulose, Lactobacillus Cultures, L-Lysine, Hydroxypropyl Methylcellulose, Maltodextrin, Magnesium Stearate, Flavor, FD&C Blue Lake, Red Sucrose Specs.None of my products contain artificial colors or sucrose, which breaks down to glucose and fructose and may cause some a problem.The reason that this product will not work for everyone or only to a limited degree is because there are patients that will need the bifidus cultures, other amino acids pertinent to the gut and the temporary, hopefully temporary, removal of certain foods that they have become intolerant of or allergic to. If you were to experiment and stop taking the product, I would suspect that you would lose any benefit that you have experienced. That would tell us that the lactobacillus cultures in the product are transient and not the specific strains that a human would need. Great way to build repeat business, similar to what Garden of Life is doing with Primal Defense.Thanks for confirming the basics of my program with the comments about your success with DA-IBS.Difference is that you are finished with my the product portion of my protocol in a few months, though dietary exclusions may need to be continued.I must say one more time, as I have said through private email to you, that I will be happy to provide for you all of my products and my time...at no charge to you whatsoever...and let's follow my exact program and see if it works for you the way I say it works for everyone. I will also pay for any necessary lab tests. It would also provide a possibility that you could report that it didn't work. I'm willing to take that chance, are you ready to eliminate all your symptoms?


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## eric (Jul 8, 1999)

Jeff, I thought you suffered from IBD and IBS?I know research on IBD and probiotics has been promising and shown to help as they help repair immune cells and promote benefical bacteria.Maybe its helping your IBD and that is also helping your IBS and your whole system?I believe you know anyway I am not opposed to probiotics at all for either conditions or in general."I think it could help alot(but so does meditation, music therapy, yoga)."I agree those things help very much, yet there are important differences between them and HT and also they have not been as researched as HT.They also share many similarities. All of them are good. "microscopic lenses necessary to detect it(Ken is lucky!), "I doubt ken had his colon wall peeled away to get to the mast cells and that they used those electromagnetic micrscopes on him.I would guess his doctor found inflammation on the outside of the colon wall, he could see with a colonoscopy.But I am not diagnosing him, that is his doctors job and I would be asking my doctor that question personally. Why do I have inflammation and what role is there for it in my IBS and what other reasons there maybe for it?"Why can't we PI IBSr's down-regulate the microscopic inflammation?"they do downregulate from the brain through stressors and that is a part of the picuture believed to cause inflammed mast cells and then IBS symptoms, according to one Dr mayer you quote all the time and many other IBS researchers."Since hypnotherapy tapes, as opposed to hypnotherapy with a therapist, have NOT been clinically proven, does this mean discussing the tapes should be steered away from?"Hypnotherapy with a therapist for IBS uses specific scripts that they say to their patients.The tapes for IBS uses specific IBS scripts in audio to the patient.One study has been done and one is just being finnished and hypnotherapy for IBS using audio tapes have been clinically studied and more studies are being done.I have also said this before, it is the scripts for HT and IBS that are important. All HT is also self hypnosis. Why not learn about it all?They have also studied it in groups."These researchers further found that hypnosis treatment for IBS in groups of up to 8 patients seems as effective as individual therap" http://www.ibshypnosis.com/IBSresearch.html I too have numerous conversations with Olafur S. Palsson at UNC and over the years he has helped me out tremedously on HT and IBS, as well as Mike and his fifteen years of expertise and training and referals from doctors and gastroenterologists. Or why he put tapes out to help IBS suffers in the first place? Out of compassion to help and that he was helping through his clinic.EditorialsThe growing case for hypnosis as adjunctive therapy for functional gastrointestinal disordersOlafur S. Palsson MEDLINE LOOKUP William E. Whitehead MEDLINE LOOKUP "It is unknown whether hypnotherapy for FD and IBS can be administered in an automated home-treatment format. *Hypnosis is unlike most other psychologic treatments because it is largely a one-way talk therapy with very limited interactivity. For this reason, it can be used without a live therapist, and this is commonly done in the form of audiotaped home practice sessions that patients use between clinic visits.* The availability and affordability of this therapy would be vastly increased if the same kind of face-to-face hypnosis treatment found effective for FD and IBS would also help patients when administered exclusively in a home-treatment audio format. No data have been presented to date to make it possible to conclude whether this is feasible.""Int J Colorectal Dis. 2000 Nov;15(5-6):328-34. Related Articles, Links Hypnotherapy and therapeutic audiotape: effective in previously unsuccessfully treated irritable bowel syndrome?Forbes A, MacAuley S, Chiotakakou-Faliakou E.St Mark's Hospital, Watford Road, Harrow HA1 3UJ, UK. alastair.forbes###ic.ac.uk"The tapes have been here before me and almost since the begining of the bb. Mike is ahead of his time really.They have helped all these people also and have proven themselves here and else where already. They can work, they can really work. There is also a very samll amount of people in the world trained to do HT for IBS its AN OPTION for people who may not be able to find one or who is housebound or someone who wants to try this first then maybe see one or someone who wants to relieve their symptoms at home or someone who wants to save money perhaps. A lot of people helped do not post anymore either. Its also safe. http://www.ibsgroup.org/ubb/ultimatebb.php...c;f=11;t=000017 I am sure glad I did it myself and I have hundreds of people thanking me for helping them learn about it and it helping them. Some have learned the technique to help others.So, I say again why is this a problem for Hypnotherapy and not CBT or Yoga or Music therapy?Maybe reading this with a understanding and compassion and how HT helps IBSers would help. Its as valid a treatment for IBS as any and maybe more effective then many.EditorialsThe growing case for hypnosis as adjunctive therapy for functional gastrointestinal disorders http://www2.gastrojournal.org/scripts/om.d...232132&nav=full I also know for a fact, Mike deserves some respect and even admiration for sure for all the IBSers he has helped over the last fifteen years, using a researched based treatment.


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## eric (Jul 8, 1999)

Jeff, I thought you suffered from IBD and IBS?I know research on IBD and probiotics has been promising and shown to help as they help repair immune cells and promote benefical bacteria.Maybe its helping your IBD and that is also helping your IBS and your whole system?I believe you know anyway I am not opposed to probiotics at all for either conditions or in general."I think it could help alot(but so does meditation, music therapy, yoga)."I agree those things help very much, yet there are important differences between them and HT and also they have not been as researched as HT.They also share many similarities. All of them are good. "microscopic lenses necessary to detect it(Ken is lucky!), "I doubt ken had his colon wall peeled away to get to the mast cells and that they used those electromagnetic micrscopes on him.I would guess his doctor found inflammation on the outside of the colon wall, he could see with a colonoscopy.But I am not diagnosing him, that is his doctors job and I would be asking my doctor that question personally. Why do I have inflammation and what role is there for it in my IBS and what other reasons there maybe for it?"Why can't we PI IBSr's down-regulate the microscopic inflammation?"they do downregulate from the brain through stressors and that is a part of the picuture believed to cause inflammed mast cells and then IBS symptoms, according to one Dr mayer you quote all the time and many other IBS researchers."Since hypnotherapy tapes, as opposed to hypnotherapy with a therapist, have NOT been clinically proven, does this mean discussing the tapes should be steered away from?"Hypnotherapy with a therapist for IBS uses specific scripts that they say to their patients.The tapes for IBS uses specific IBS scripts in audio to the patient.One study has been done and one is just being finnished and hypnotherapy for IBS using audio tapes have been clinically studied and more studies are being done.I have also said this before, it is the scripts for HT and IBS that are important. All HT is also self hypnosis. Why not learn about it all?They have also studied it in groups."These researchers further found that hypnosis treatment for IBS in groups of up to 8 patients seems as effective as individual therap" http://www.ibshypnosis.com/IBSresearch.html I too have numerous conversations with Olafur S. Palsson at UNC and over the years he has helped me out tremedously on HT and IBS, as well as Mike and his fifteen years of expertise and training and referals from doctors and gastroenterologists. Or why he put tapes out to help IBS suffers in the first place? Out of compassion to help and that he was helping through his clinic.EditorialsThe growing case for hypnosis as adjunctive therapy for functional gastrointestinal disordersOlafur S. Palsson MEDLINE LOOKUP William E. Whitehead MEDLINE LOOKUP "It is unknown whether hypnotherapy for FD and IBS can be administered in an automated home-treatment format. *Hypnosis is unlike most other psychologic treatments because it is largely a one-way talk therapy with very limited interactivity. For this reason, it can be used without a live therapist, and this is commonly done in the form of audiotaped home practice sessions that patients use between clinic visits.* The availability and affordability of this therapy would be vastly increased if the same kind of face-to-face hypnosis treatment found effective for FD and IBS would also help patients when administered exclusively in a home-treatment audio format. No data have been presented to date to make it possible to conclude whether this is feasible.""Int J Colorectal Dis. 2000 Nov;15(5-6):328-34. Related Articles, Links Hypnotherapy and therapeutic audiotape: effective in previously unsuccessfully treated irritable bowel syndrome?Forbes A, MacAuley S, Chiotakakou-Faliakou E.St Mark's Hospital, Watford Road, Harrow HA1 3UJ, UK. alastair.forbes###ic.ac.uk"The tapes have been here before me and almost since the begining of the bb. Mike is ahead of his time really.They have helped all these people also and have proven themselves here and else where already. They can work, they can really work. There is also a very samll amount of people in the world trained to do HT for IBS its AN OPTION for people who may not be able to find one or who is housebound or someone who wants to try this first then maybe see one or someone who wants to relieve their symptoms at home or someone who wants to save money perhaps. A lot of people helped do not post anymore either. Its also safe. http://www.ibsgroup.org/ubb/ultimatebb.php...c;f=11;t=000017 I am sure glad I did it myself and I have hundreds of people thanking me for helping them learn about it and it helping them. Some have learned the technique to help others.So, I say again why is this a problem for Hypnotherapy and not CBT or Yoga or Music therapy?Maybe reading this with a understanding and compassion and how HT helps IBSers would help. Its as valid a treatment for IBS as any and maybe more effective then many.EditorialsThe growing case for hypnosis as adjunctive therapy for functional gastrointestinal disorders http://www2.gastrojournal.org/scripts/om.d...232132&nav=full I also know for a fact, Mike deserves some respect and even admiration for sure for all the IBSers he has helped over the last fifteen years, using a researched based treatment.


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## eric (Jul 8, 1999)

People usally try hypno after its explained to them for IBS and after standard medical care fails to make them feel better. I believe as well as many others it should be a first line treatment on IBS symptoms, usaing a safe and natural method, which is not avasive and shown to really work for those it works for and that is substanstial, with a substanstial reduction in global symptoms.


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## eric (Jul 8, 1999)

People usally try hypno after its explained to them for IBS and after standard medical care fails to make them feel better. I believe as well as many others it should be a first line treatment on IBS symptoms, usaing a safe and natural method, which is not avasive and shown to really work for those it works for and that is substanstial, with a substanstial reduction in global symptoms.


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## Kacebece3 (Apr 17, 2002)

FYI. Eric I did ask my doctor what was causing the inflamation. The answer was " I don't know" he did say some people have this after a course of antibiotics but in my case that was in the distant past. also a tissue sample was taken from my bowel wall I do not know what was done with it or did I ask. We tried mesalamine(hope that is spelled rite) it did help but the side effects were as bad as the condition its self. It is true I also suffer with diverticulosis but the symptoms I have are consistant with IBS and not that condition. What I'm trying to say is the medical field does not know what causes IBS and more and more research is leaning towards restoring intestinal flora and rebuilding bowel health to help this condition.Ken


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## Kacebece3 (Apr 17, 2002)

FYI. Eric I did ask my doctor what was causing the inflamation. The answer was " I don't know" he did say some people have this after a course of antibiotics but in my case that was in the distant past. also a tissue sample was taken from my bowel wall I do not know what was done with it or did I ask. We tried mesalamine(hope that is spelled rite) it did help but the side effects were as bad as the condition its self. It is true I also suffer with diverticulosis but the symptoms I have are consistant with IBS and not that condition. What I'm trying to say is the medical field does not know what causes IBS and more and more research is leaning towards restoring intestinal flora and rebuilding bowel health to help this condition.Ken


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## captaincolon (Jul 6, 2004)

> quoter. Dahlman wrote to Jeffrey Roberts:....I must say one more time, as I have said through private email to you, that I will be happy to provide for you all of my products and my time...at no charge to you whatsoever...and let's follow my exact program and see if it works for you the way I say it works for everyone. I will also pay for any necessary lab tests. It would also provide a possibility that you could report that it didn't work. I'm willing to take that chance, are you ready to eliminate all your symptoms?


That's a great idea, Dr. D., and a very generous offer. It's a testament to your belief in the efficacy of your program. I for one really hope Jeffrey takes you up on it, he has nothing to lose. The results would prove to be very interesting and helpful to many of us here, I'm sure. I think that even Mr. Flux would approve of it (thank goodness







), as I think that even he would have to admit Jeffrey is a "real person", not connected to you, and would give your program an unbiased trial...-Captain Colon


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## captaincolon (Jul 6, 2004)

> quoter. Dahlman wrote to Jeffrey Roberts:....I must say one more time, as I have said through private email to you, that I will be happy to provide for you all of my products and my time...at no charge to you whatsoever...and let's follow my exact program and see if it works for you the way I say it works for everyone. I will also pay for any necessary lab tests. It would also provide a possibility that you could report that it didn't work. I'm willing to take that chance, are you ready to eliminate all your symptoms?


That's a great idea, Dr. D., and a very generous offer. It's a testament to your belief in the efficacy of your program. I for one really hope Jeffrey takes you up on it, he has nothing to lose. The results would prove to be very interesting and helpful to many of us here, I'm sure. I think that even Mr. Flux would approve of it (thank goodness







), as I think that even he would have to admit Jeffrey is a "real person", not connected to you, and would give your program an unbiased trial...-Captain Colon


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## Talissa (Apr 10, 2004)

Jeff, the DA-IBS is great isn't it? For me, it was wonderful being able to eat (just about) like a normal again.Re: inflammation, this is not new, but is interesting & probably bears repeating:Medscape, 07/15/2003 Sylvie Bradesi, PhD, James A. McRoberts, Ph.D, Peter A. Anton, MD, Emeran A. Mayer, MD"The recent observation of an activated immune system in some IBS patients associated with persistent low-grade mucosal inflammation provides evidence for the reconsideration of the symptom-criteria-based diagnosis of functional bowel disorders. *The development and use of biologic markers identifying low-grade inflammation would improve the characterization of subsets of IBS patients * in whom peripheral mechanisms may participate in specific symptom genesis and could be considered in the choice of the therapy. http://www.medscape.com/viewarticle/457728_5


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## Talissa (Apr 10, 2004)

Jeff, the DA-IBS is great isn't it? For me, it was wonderful being able to eat (just about) like a normal again.Re: inflammation, this is not new, but is interesting & probably bears repeating:Medscape, 07/15/2003 Sylvie Bradesi, PhD, James A. McRoberts, Ph.D, Peter A. Anton, MD, Emeran A. Mayer, MD"The recent observation of an activated immune system in some IBS patients associated with persistent low-grade mucosal inflammation provides evidence for the reconsideration of the symptom-criteria-based diagnosis of functional bowel disorders. *The development and use of biologic markers identifying low-grade inflammation would improve the characterization of subsets of IBS patients * in whom peripheral mechanisms may participate in specific symptom genesis and could be considered in the choice of the therapy. http://www.medscape.com/viewarticle/457728_5


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## eric (Jul 8, 1999)

kacebace, diverticulosis causes inflammation in the gi tract.A person can have both IBS and diverticulosis. I know quite a few people who have both, but that doesn't mean your IBS is an inflammatory bowel disorder. You have coexisting digestive problems and your issues may not be all the issues of "classic" IBSers, in which there is not a comorbid condition."IBS is not a diseaseAlthough the symptoms of IBS may be severe, the disorder itself is not a serious one. There is no actual disease present in the colon. In fact, an operation performed on the abdomen would reveal a perfectly normal appearing bowel. (it needs to be mentioned here, it looks normal from the outside using a colonoscopy, it isn't until they look with microscopic tools they find subtle changes in the gi tract.)Rather, it is a problem of abnormal function. The condition usually begins in young people, usually below 40 and often in the teens. The symptoms may wax and wane, being particularly severe at some times and absent at others. Over the years, the symptoms tend to become less intense. IBS is extremely common and is present in perhaps half the patients that see a specialist in gastroenterology. It tends to run in families. The disorder does not lead to cancer. Prolonged contractions of the colon, however, may lead to diverticulosis, a disorder in which balloon-like pockets push out from the bowel wall because of excessive, prolonged contractions. " http://www.gicare.com/pated/ecdgs03.htm I agree that restoring gut flora is a healthy thing and it may help IBS, but the studies show a reduction in bloating and possible pain, that would be consitent with helping abnormal transit leading to abnormal gut flora, as well as protection from bacteria we are subjected to EVEYDAY. I have not personally seen a study that showed it helped global IBS symptoms or that it caused IBS. Some alternative people here really want you to believe that however. But they don't have hard evidence to back that up.They have also made great strides in understanding IBS.They also know there seems to be something wrong with serotonin dysregulation and that in part helps explain d and c and d/c and also the singlaing to the brain. They have also made great strides in the last five years on mechanisms causing the macroscopic inflammation of mast cells.The gut flora research is still in the early stages really. But there is a lot here about how infection can cause inflammation in general as opposed to how brain gut axis dysfunction can cause inflammation from a previous infection, PI IBS leading to IBS after an infection has been resolved.There is also no research saying probiotics can resolve the serotonin issues in IBS or the mast cell issues in IBS. Two majorally important areas of research in IBS.One of the most important areas of IBS research is why there is viceral hypersensitivity.and why"Neurologic correlates: in most people, stimuli from intestine registered in anterior cingulate gyrus and easily ignored; in patients with IBS, stimuli from intestine registered in prefrontal cortex and difficult to ignore Pain gate: filtration system in spinal column; IBS patients have dysfunctional pain gate, causing them to feel every little stimulus from gut; pain can be managed using SSEX (ie, Stress, Sleep, Endorphins or eXercise); stressï¿½pain gets worse when patients under stress; stress management using cognitive therapy and self-guided imagery works extremely well; sleepï¿½patients have poor sleep patterns and often feel fatigue because they do not sleep well and wake up with pain; exerciseï¿½induces endorphins that can block receptors in pain gate; unusual to see athlete with IBS ."They have to be able to tie the gut flora research into,why do more women then men have IBS?Can it cause rectal hypersensitivity?can it cause viceral hypersensitivity?can it impair the Anterior cinculate cortex?Can it impair the prefrontal cortex?What are the pathways for gut flora to alter bidirectional communication between the brain and the gut?Why is there serotonin dysregulation in the vast majority of IBSers presenting to gastroenterologist?Why is there an increase in stress hormones?Why is there an altered stress responce in IBS?Why does IBS effect rem sleep?Is functional abdominal pain syndrome, and functional constipation or functional d, all gut flora related.These are some things they already know. What are all the mechanisms for overlapping functional gi disorders of which there is some thirty of them and which they frequently overlap? Is functional dyspesia a gut flora issues also, or is there some mechanisms effecting the autonomic nervous system and the central nervous syste. They know both are operational to cause symptoms.So while gut flora is very important and an area of study in IBS, much work has been done on bacteria and IBS. But ther are many more issues to the big picture."The development and use of biologic markers identifying low-grade inflammation would improve the characterization of subsets of IBS patients in whom peripheral mechanisms may participate in specific symptom genesis and could be considered in the choice of the therapy."Noticed it said some, not all!That they can find subsets of IBSers with specific biological markers, like inflammation or altered serotonin gene transporters or impairment of the anterior cinculate cortex is a good step in the right direction to work with subgroups of IBS patients, however this does not mean they have found a unifiying biological marker for all IBSers yet.Infection and inflammation are usally associated with disease and a pathogen. They have not yet classified IBS as a disease, nor found a specific pathogen.There is also still a ton of hormones and neurotransmitters and stress hormones and brain gut interactions in general they need to research just as musch as gut flora, they need to know is it possible altered gut flora could create IBS. They know from post infection IBS studies quite a few pathogens can intiate IBS and know maybe even a virus they are studying.They can also create types of IBS in mice.So while its important, it just as important to view the big picture in IBS, which then shows some major patterns to the condition. "Inflammation Intestinal inflammation can cause neurological changes with effects on GI motility and visceral perception. Structural changes to the enteric nervous system are not restricted to areas of active inflammation. Functional abnormalities can persist long after resolution of the inflammation. Many patients with acute gastroenteritis develop chronic functional GI symptoms. Brain PhysiologyStress reproducibly alters gastrointestinal motility and sensation. The release of corticotropin releasing factor from the hypothalamus may mediate the stress response. Brain centers important in mediating visceral pain include the thalamus (general sensory), insular cortex (visceral sensory), anterior cingulate cortex (general pain awareness), and prefrontal cortex (general pain processing). Visceral pain in IBS is associated with increased prefrontal cortex activation. The normal correlation between subjective pain intensity and activation of the anterior cingulate and insula cortices is lost in IBS. The limbic system is involved in emotion, mood, and visceral autonomic control. Limbic abnormalities are seen in depression and IBS. Thus, this system is a possible site of convergence where emotional disturbance provokes intestinal dysfunction. "This is as important as gut flora issues.The great strides they have been making on IBS, gets lost in tunnel vision focuses.You might also want to click this graph, which is part of what Tal, posted above."Figure 1. (click image to zoom) * Brain-gut immune interactions in irritable bowel syndrome and inflammatory bowel disease: effect of chronic stress on the mucosal immune system.* *Acute stress causes increases in the activity of the hypothalamic-pituitary-adrenal (HPA) axis and of the two branches of the autonomic nervous system (ANS), the sympathetic nervous system (SNS), and the parasympathetic (vagal) system. In patients with irritable bowel syndrome, the peripherally acting products of each of these pathways (cortisol, CORT; norepinephrine, NE; acetylcholine, Ach) can inhibit the mucosal immune system, especially Th1-type responses. * This results in a temporary shift toward Th2 cytokine responses (IL-4 and others) that are not as strongly inhibited and that can further inhibit Th1 responses. In patients with inflammatory bowel diseases, the corticotropin-releasing factor (CRF) response may be blunted, leading to diminished CORT and NE release. These changes favor the production of Th1 cytokines and the proliferation of macrophages, natural killer (NK) cells, and cytotoxic T cells (Tc). TNF, which is produced by activated macrophages but can also be released by activated mast cells, stimulates the production of IL-1 (in the Th1 pathway) and IL-6 (by lymphoid and nonlymphoid tissues). *With chronic stress in both types of patients, the shift to a Th1 response becomes predominant, with positive feedback loops developing between the gut and the brain.* The restraints on immune cell proliferation and activation are compromised by blunting of the HPA axis response due to downregulation of pituitary CRF1 receptors, decreased vagal tone, and downregulation of 2-adrenergic receptors (2-AR) on Th1 immune cells by chronically elevated catecholamines. Circulating levels of TNF-, IL-1, and IL-6 increase to concentrations that synergistically stimulate CRF production in the PVN of the hypothalamus. In irritable bowel syndrome, TNF and IL-1 sensitize primary afferent terminals through long-lasting effects on gene expression, including the expression of neurokinin receptors. Locally acting mast cell products (tryptase and histamine) and proinflammatory compounds (PGE2) can also sensitize primary afferents. *Both IFN (Th1 cytokine), which is produced by NK cells in response to TNF, and IL-4 (a Th2 cytokine) have been shown to decrease mucosal barrier function by increasing epithelial permeability,54,55 thus perpetuating a local inflammatory response by allowing entry of bacteria and bacterial products. Subjective pain responses to peripheral sensitization of visceral afferents in irritable bowel syndrome and inflammatory bowel diseases are likely to be modulated differentially by endogenous pain modulation pathways* . DMN, dorsal motor nucleus of the vagus; ACTH, adrenocorticotropin hormone. " *"Small intestinal permeability is abnormal in a wide variety of conditions affecting the small intestine, including celiac disease, Crohn disease, and intestinal infections.* 18** Interestingly, gut permeability assessed by the lactulose/mannitol ratio is significantly elevated in PI-IBS patients.15 *This functional alteration of the intestinal barrier function may be a cause or consequence of inflammation, and a direct link between increased intestinal permeability and the exaggerated immune activation in IBD still needs to be confirmed.* *In addition to a causative role of peripheral factors, gut permeability changes in animal models have also been reported in response to various stressors. For example, in a rat model of chronic stress, an increase in intestinal epithelial permeability, associated with an increase in mucosal neutrophils and mast cells, has been demonstrated.34** In this model, the combination of stress-induced increases in intestinal permeability, allowing easier access of antigens to gut-associated macrophages and dendritic cells, together with stress-induced changes in HPA axis responsiveness and cytokine profiles, resulted in the development of colitis, without any additional chemical or immunologic manipulations. Rats with a history of aversive early life events were more susceptible to these stress-induced changes in gut permeability,35* possibly related to early programming of the HPA axis.31** http://www.medscape.com/viewarticle/457728_4 a note about above" gut permeability assessed by the lactulose/mannitol ratio is significantly elevated in PI-IBS patients"These are PI IBS patients with a previous infection and inflammation from infection, some from dysentary and some from other enteric infections. These patients have an intial infection that resolves and then leads to IBS. In these patients there is an increase in Mast cells embeded in the gut and very importantly an increase in ec cells that store the majority of serotonin in the gut, which is responsible for the control of the gi tract.When the 5ht 3 and 5ht 4 cells are manipulated in IBS patients with the new IBS drugs their symptoms can be altered. That's important to know and understand also in the big picture of IBS and it helps explain in part motility issues in IBS. They have researched and know a lot about all this already.IBS: Improving Diagnosis, Serotonin Signaling, and Implications for Treatment"IntroductionMany patients with irritable bowel syndrome (IBS) have walked into their physician's office and said, "The last doctor told me my symptoms were all in my head." Those physicians may have been right, but not in a way they anticipated.Over the past 50 years, evolving conceptual mechanisms have been proposed to explain the pathophysiology of IBS. These mechanisms have ranged from a purely psychological disorder to such physiologic conditions as a primary abnormality in gastrointestinal (GI) motility or visceral hypersensitivity. *However, recent scientific data have increasingly supported that a dysregulation in brain-gut interactions resulting in alterations in GI motility, secretion, and sensation is the principal pathophysiologic mechanism underlying IBS.* 1 Brain-gut interactions are mediated largely by the autonomic nervous system, which is comprised of the parasympathetic (vagal and sacral parasympathetic), sympathetic, and enteric nervous systems (ENS). Many factors (both central and peripheral) may contribute to an altered brain-gut axis, including genetic predisposition, chronic stress, inflammation/infection, and environmental parameters.1 *These alterations may subsequently lead to disturbances in intestinal motility, visceral sensitivity, and mucosal immune response and permeability. In IBS, these disturbances result in symptoms of abdominal pain or discomfort and altered bowel function, the defining characteristics of this disorder.2* *There are many neurotransmitters and hormones that mediate bidirectional brain-gut communication. Serotonin (5-hydroxytryptamine[5-HT) is one of the key mediators of gut motility, secretion, and sensation. Most of the serotonin is localized in the GI tract and is found in enterochromaffin (EC) cells and enteric neurons.3 EC cells sense luminal factors such as food or mechanical distension in the gut, and release serotonin; 5-HT receptors on intrinsic primary afferent neurons (IPANs) as well as extrinsic spinal or vagal afferent neurons are activated. The ENS regulates secretion and peristalsis, whereas vagal and spinal afferents modulate nonpainful and painful sensations, respectively"* http://www.medscape.com/viewarticle/463521 Serotonin can also be manipulated between the brain and the gut through relaxation techniques.The stress responce and mast cells and chronic stress can also be manipulated through relaxation techniques. also Dr Mayer from the above article has recently written a new one, I will post when it becomes avaiable.His IBS model, is in part based on altered stress ciruits, but I am not sure Tal, has figured that out yet?I also have to say this is all extremely complicated.


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## eric (Jul 8, 1999)

kacebace, diverticulosis causes inflammation in the gi tract.A person can have both IBS and diverticulosis. I know quite a few people who have both, but that doesn't mean your IBS is an inflammatory bowel disorder. You have coexisting digestive problems and your issues may not be all the issues of "classic" IBSers, in which there is not a comorbid condition."IBS is not a diseaseAlthough the symptoms of IBS may be severe, the disorder itself is not a serious one. There is no actual disease present in the colon. In fact, an operation performed on the abdomen would reveal a perfectly normal appearing bowel. (it needs to be mentioned here, it looks normal from the outside using a colonoscopy, it isn't until they look with microscopic tools they find subtle changes in the gi tract.)Rather, it is a problem of abnormal function. The condition usually begins in young people, usually below 40 and often in the teens. The symptoms may wax and wane, being particularly severe at some times and absent at others. Over the years, the symptoms tend to become less intense. IBS is extremely common and is present in perhaps half the patients that see a specialist in gastroenterology. It tends to run in families. The disorder does not lead to cancer. Prolonged contractions of the colon, however, may lead to diverticulosis, a disorder in which balloon-like pockets push out from the bowel wall because of excessive, prolonged contractions. " http://www.gicare.com/pated/ecdgs03.htm I agree that restoring gut flora is a healthy thing and it may help IBS, but the studies show a reduction in bloating and possible pain, that would be consitent with helping abnormal transit leading to abnormal gut flora, as well as protection from bacteria we are subjected to EVEYDAY. I have not personally seen a study that showed it helped global IBS symptoms or that it caused IBS. Some alternative people here really want you to believe that however. But they don't have hard evidence to back that up.They have also made great strides in understanding IBS.They also know there seems to be something wrong with serotonin dysregulation and that in part helps explain d and c and d/c and also the singlaing to the brain. They have also made great strides in the last five years on mechanisms causing the macroscopic inflammation of mast cells.The gut flora research is still in the early stages really. But there is a lot here about how infection can cause inflammation in general as opposed to how brain gut axis dysfunction can cause inflammation from a previous infection, PI IBS leading to IBS after an infection has been resolved.There is also no research saying probiotics can resolve the serotonin issues in IBS or the mast cell issues in IBS. Two majorally important areas of research in IBS.One of the most important areas of IBS research is why there is viceral hypersensitivity.and why"Neurologic correlates: in most people, stimuli from intestine registered in anterior cingulate gyrus and easily ignored; in patients with IBS, stimuli from intestine registered in prefrontal cortex and difficult to ignore Pain gate: filtration system in spinal column; IBS patients have dysfunctional pain gate, causing them to feel every little stimulus from gut; pain can be managed using SSEX (ie, Stress, Sleep, Endorphins or eXercise); stressï¿½pain gets worse when patients under stress; stress management using cognitive therapy and self-guided imagery works extremely well; sleepï¿½patients have poor sleep patterns and often feel fatigue because they do not sleep well and wake up with pain; exerciseï¿½induces endorphins that can block receptors in pain gate; unusual to see athlete with IBS ."They have to be able to tie the gut flora research into,why do more women then men have IBS?Can it cause rectal hypersensitivity?can it cause viceral hypersensitivity?can it impair the Anterior cinculate cortex?Can it impair the prefrontal cortex?What are the pathways for gut flora to alter bidirectional communication between the brain and the gut?Why is there serotonin dysregulation in the vast majority of IBSers presenting to gastroenterologist?Why is there an increase in stress hormones?Why is there an altered stress responce in IBS?Why does IBS effect rem sleep?Is functional abdominal pain syndrome, and functional constipation or functional d, all gut flora related.These are some things they already know. What are all the mechanisms for overlapping functional gi disorders of which there is some thirty of them and which they frequently overlap? Is functional dyspesia a gut flora issues also, or is there some mechanisms effecting the autonomic nervous system and the central nervous syste. They know both are operational to cause symptoms.So while gut flora is very important and an area of study in IBS, much work has been done on bacteria and IBS. But ther are many more issues to the big picture."The development and use of biologic markers identifying low-grade inflammation would improve the characterization of subsets of IBS patients in whom peripheral mechanisms may participate in specific symptom genesis and could be considered in the choice of the therapy."Noticed it said some, not all!That they can find subsets of IBSers with specific biological markers, like inflammation or altered serotonin gene transporters or impairment of the anterior cinculate cortex is a good step in the right direction to work with subgroups of IBS patients, however this does not mean they have found a unifiying biological marker for all IBSers yet.Infection and inflammation are usally associated with disease and a pathogen. They have not yet classified IBS as a disease, nor found a specific pathogen.There is also still a ton of hormones and neurotransmitters and stress hormones and brain gut interactions in general they need to research just as musch as gut flora, they need to know is it possible altered gut flora could create IBS. They know from post infection IBS studies quite a few pathogens can intiate IBS and know maybe even a virus they are studying.They can also create types of IBS in mice.So while its important, it just as important to view the big picture in IBS, which then shows some major patterns to the condition. "Inflammation Intestinal inflammation can cause neurological changes with effects on GI motility and visceral perception. Structural changes to the enteric nervous system are not restricted to areas of active inflammation. Functional abnormalities can persist long after resolution of the inflammation. Many patients with acute gastroenteritis develop chronic functional GI symptoms. Brain PhysiologyStress reproducibly alters gastrointestinal motility and sensation. The release of corticotropin releasing factor from the hypothalamus may mediate the stress response. Brain centers important in mediating visceral pain include the thalamus (general sensory), insular cortex (visceral sensory), anterior cingulate cortex (general pain awareness), and prefrontal cortex (general pain processing). Visceral pain in IBS is associated with increased prefrontal cortex activation. The normal correlation between subjective pain intensity and activation of the anterior cingulate and insula cortices is lost in IBS. The limbic system is involved in emotion, mood, and visceral autonomic control. Limbic abnormalities are seen in depression and IBS. Thus, this system is a possible site of convergence where emotional disturbance provokes intestinal dysfunction. "This is as important as gut flora issues.The great strides they have been making on IBS, gets lost in tunnel vision focuses.You might also want to click this graph, which is part of what Tal, posted above."Figure 1. (click image to zoom) * Brain-gut immune interactions in irritable bowel syndrome and inflammatory bowel disease: effect of chronic stress on the mucosal immune system.* *Acute stress causes increases in the activity of the hypothalamic-pituitary-adrenal (HPA) axis and of the two branches of the autonomic nervous system (ANS), the sympathetic nervous system (SNS), and the parasympathetic (vagal) system. In patients with irritable bowel syndrome, the peripherally acting products of each of these pathways (cortisol, CORT; norepinephrine, NE; acetylcholine, Ach) can inhibit the mucosal immune system, especially Th1-type responses. * This results in a temporary shift toward Th2 cytokine responses (IL-4 and others) that are not as strongly inhibited and that can further inhibit Th1 responses. In patients with inflammatory bowel diseases, the corticotropin-releasing factor (CRF) response may be blunted, leading to diminished CORT and NE release. These changes favor the production of Th1 cytokines and the proliferation of macrophages, natural killer (NK) cells, and cytotoxic T cells (Tc). TNF, which is produced by activated macrophages but can also be released by activated mast cells, stimulates the production of IL-1 (in the Th1 pathway) and IL-6 (by lymphoid and nonlymphoid tissues). *With chronic stress in both types of patients, the shift to a Th1 response becomes predominant, with positive feedback loops developing between the gut and the brain.* The restraints on immune cell proliferation and activation are compromised by blunting of the HPA axis response due to downregulation of pituitary CRF1 receptors, decreased vagal tone, and downregulation of 2-adrenergic receptors (2-AR) on Th1 immune cells by chronically elevated catecholamines. Circulating levels of TNF-, IL-1, and IL-6 increase to concentrations that synergistically stimulate CRF production in the PVN of the hypothalamus. In irritable bowel syndrome, TNF and IL-1 sensitize primary afferent terminals through long-lasting effects on gene expression, including the expression of neurokinin receptors. Locally acting mast cell products (tryptase and histamine) and proinflammatory compounds (PGE2) can also sensitize primary afferents. *Both IFN (Th1 cytokine), which is produced by NK cells in response to TNF, and IL-4 (a Th2 cytokine) have been shown to decrease mucosal barrier function by increasing epithelial permeability,54,55 thus perpetuating a local inflammatory response by allowing entry of bacteria and bacterial products. Subjective pain responses to peripheral sensitization of visceral afferents in irritable bowel syndrome and inflammatory bowel diseases are likely to be modulated differentially by endogenous pain modulation pathways* . DMN, dorsal motor nucleus of the vagus; ACTH, adrenocorticotropin hormone. " *"Small intestinal permeability is abnormal in a wide variety of conditions affecting the small intestine, including celiac disease, Crohn disease, and intestinal infections.* 18** Interestingly, gut permeability assessed by the lactulose/mannitol ratio is significantly elevated in PI-IBS patients.15 *This functional alteration of the intestinal barrier function may be a cause or consequence of inflammation, and a direct link between increased intestinal permeability and the exaggerated immune activation in IBD still needs to be confirmed.* *In addition to a causative role of peripheral factors, gut permeability changes in animal models have also been reported in response to various stressors. For example, in a rat model of chronic stress, an increase in intestinal epithelial permeability, associated with an increase in mucosal neutrophils and mast cells, has been demonstrated.34** In this model, the combination of stress-induced increases in intestinal permeability, allowing easier access of antigens to gut-associated macrophages and dendritic cells, together with stress-induced changes in HPA axis responsiveness and cytokine profiles, resulted in the development of colitis, without any additional chemical or immunologic manipulations. Rats with a history of aversive early life events were more susceptible to these stress-induced changes in gut permeability,35* possibly related to early programming of the HPA axis.31** http://www.medscape.com/viewarticle/457728_4 a note about above" gut permeability assessed by the lactulose/mannitol ratio is significantly elevated in PI-IBS patients"These are PI IBS patients with a previous infection and inflammation from infection, some from dysentary and some from other enteric infections. These patients have an intial infection that resolves and then leads to IBS. In these patients there is an increase in Mast cells embeded in the gut and very importantly an increase in ec cells that store the majority of serotonin in the gut, which is responsible for the control of the gi tract.When the 5ht 3 and 5ht 4 cells are manipulated in IBS patients with the new IBS drugs their symptoms can be altered. That's important to know and understand also in the big picture of IBS and it helps explain in part motility issues in IBS. They have researched and know a lot about all this already.IBS: Improving Diagnosis, Serotonin Signaling, and Implications for Treatment"IntroductionMany patients with irritable bowel syndrome (IBS) have walked into their physician's office and said, "The last doctor told me my symptoms were all in my head." Those physicians may have been right, but not in a way they anticipated.Over the past 50 years, evolving conceptual mechanisms have been proposed to explain the pathophysiology of IBS. These mechanisms have ranged from a purely psychological disorder to such physiologic conditions as a primary abnormality in gastrointestinal (GI) motility or visceral hypersensitivity. *However, recent scientific data have increasingly supported that a dysregulation in brain-gut interactions resulting in alterations in GI motility, secretion, and sensation is the principal pathophysiologic mechanism underlying IBS.* 1 Brain-gut interactions are mediated largely by the autonomic nervous system, which is comprised of the parasympathetic (vagal and sacral parasympathetic), sympathetic, and enteric nervous systems (ENS). Many factors (both central and peripheral) may contribute to an altered brain-gut axis, including genetic predisposition, chronic stress, inflammation/infection, and environmental parameters.1 *These alterations may subsequently lead to disturbances in intestinal motility, visceral sensitivity, and mucosal immune response and permeability. In IBS, these disturbances result in symptoms of abdominal pain or discomfort and altered bowel function, the defining characteristics of this disorder.2* *There are many neurotransmitters and hormones that mediate bidirectional brain-gut communication. Serotonin (5-hydroxytryptamine[5-HT) is one of the key mediators of gut motility, secretion, and sensation. Most of the serotonin is localized in the GI tract and is found in enterochromaffin (EC) cells and enteric neurons.3 EC cells sense luminal factors such as food or mechanical distension in the gut, and release serotonin; 5-HT receptors on intrinsic primary afferent neurons (IPANs) as well as extrinsic spinal or vagal afferent neurons are activated. The ENS regulates secretion and peristalsis, whereas vagal and spinal afferents modulate nonpainful and painful sensations, respectively"* http://www.medscape.com/viewarticle/463521 Serotonin can also be manipulated between the brain and the gut through relaxation techniques.The stress responce and mast cells and chronic stress can also be manipulated through relaxation techniques. also Dr Mayer from the above article has recently written a new one, I will post when it becomes avaiable.His IBS model, is in part based on altered stress ciruits, but I am not sure Tal, has figured that out yet?I also have to say this is all extremely complicated.


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## Kacebece3 (Apr 17, 2002)

kacebace, diverticulosis causes inflammation in the gi tract.Eric, when diverticuli become inflamed this is the begining of diverticulosis, not very pleasant, been there. My gastro doc assured me that I do not have colitis or chrons. The CT scans, blood work, colonoscopy, and more confirmed no diverticulitis present. What was found is low grade inflamation away from the diverticuli, to date the cause is unknown. Again the symptoms I have are consistant with IBS-c. This is what my gastro doc determined after 3 years of working with me. I agree with you that I may have more than one thing going on, but hey lets face it, I have been reading alot about the bowels for years, but I still hurt. The probiotics that Dr. Dahlman uses are helping me thats what counts, I also got help from DA, And you will like this, what got me started in this direction was a homeopath, yep she used probiotics also and again I got better results from this than from the medical field. GO FIGURE???? It has become very clear to me my bowel is not healthy so it is logical to feed it the nutients needed to restore health and get the flora back to what normal people have.Later Ken


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## Kacebece3 (Apr 17, 2002)

kacebace, diverticulosis causes inflammation in the gi tract.Eric, when diverticuli become inflamed this is the begining of diverticulosis, not very pleasant, been there. My gastro doc assured me that I do not have colitis or chrons. The CT scans, blood work, colonoscopy, and more confirmed no diverticulitis present. What was found is low grade inflamation away from the diverticuli, to date the cause is unknown. Again the symptoms I have are consistant with IBS-c. This is what my gastro doc determined after 3 years of working with me. I agree with you that I may have more than one thing going on, but hey lets face it, I have been reading alot about the bowels for years, but I still hurt. The probiotics that Dr. Dahlman uses are helping me thats what counts, I also got help from DA, And you will like this, what got me started in this direction was a homeopath, yep she used probiotics also and again I got better results from this than from the medical field. GO FIGURE???? It has become very clear to me my bowel is not healthy so it is logical to feed it the nutients needed to restore health and get the flora back to what normal people have.Later Ken


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## Kacebece3 (Apr 17, 2002)

Eric, when diverticuli become inflamed this is the begining of diverticulosis.correction this should say....this is the begining of diverticulitis.....sorry bout that.Ken


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## Kacebece3 (Apr 17, 2002)

Eric, when diverticuli become inflamed this is the begining of diverticulosis.correction this should say....this is the begining of diverticulitis.....sorry bout that.Ken


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## stinky too (May 21, 1999)

Ken I haven't been following your post much. So how is Dr. D's program working for you?Seem to be so much conflicting advice on the board these days.


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## stinky too (May 21, 1999)

Ken I haven't been following your post much. So how is Dr. D's program working for you?Seem to be so much conflicting advice on the board these days.


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## Kacebece3 (Apr 17, 2002)

Hi Joycein OH, It will be week three this Saturday. After two weeks of some improvement I had a set back last weekend over it now and tonite I'm actually pain free kinda wierd its a great feeling and very rare. It is realy to early to give a good report time will be the true test. Spoke with Dr.Dahlman last Thursday he listens and offers good advice based on his education and experiences in dealing with people. I will post this weekend about further progress.Later Ken


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## Kacebece3 (Apr 17, 2002)

Hi Joycein OH, It will be week three this Saturday. After two weeks of some improvement I had a set back last weekend over it now and tonite I'm actually pain free kinda wierd its a great feeling and very rare. It is realy to early to give a good report time will be the true test. Spoke with Dr.Dahlman last Thursday he listens and offers good advice based on his education and experiences in dealing with people. I will post this weekend about further progress.Later Ken


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## eric (Jul 8, 1999)

100 Trillion Bacteria in Your Gut: Learn How to Keep the Good Kind There.By Dr. Joseph Mercola with Rachael DroegeYou probably don't think about your gut very often but this may make you start--the bacteria in your bowels outnuber the cells in your body by a factor of 10 to one. This gut flora has incredible power over your immune system, which, of course, is your body's natural defense system that keeps you healthy. In other words, the health of your body is largely tied into the health of your gut, and it's hard to have one be healthy if the other is not.One of the reasons why your gut has so much power has to do with the 100 trillion bacteria--about three pounds worth--that line your intestinal tract. This is an extremely complex living system that aggressively protects your body from outside offenders. However, if you are eating as many sugars as the typical American (about 175 pounds per year) then you are feeding the "bad" bacteria, which are more likely to cause disease than promote health, rather than promoting the "good" bacteria that help protect you from disease. Exposure to chemicals will also contribute to this disruption in your gut microflora, and over time the imbalance will lead to illness. A large part of the influence of the "bad" bacteria is on the intestinal lining (mucousal barrier) that is over 300 square meters, or about the size of a tennis court.Beneficial bacteria in your gut can help to boost the immune system, prevent allergic inflammation and food allergy, clear up eczema in children and heal the intestines from a variety of ailments. Fortunately, you can influence the composition of the good and bad bacteria in your gut by optimizing your diet and supplementing it with a high-quality probiotic, or good bacteria. As written in a report in the October 2003 American Journal of Clinical Nutrition, ï¿½probiotics can act as partners of the defense system of the intestine.ï¿½The typical American diet is so full of sugar and grains that--although I donï¿½t often recommend supplements--nearly everyone can benefit from probiotics. You should look for a high potency, multi-strain variety, which can be found in most health food stores. Since the best type of probiotic to use can become highly specific, you may want to discuss the varieties with an experienced health food store employee. I recommend probiotics to nearly all of our new patients, as it is a helpful start for their health recovery. This is not a lifetime recommendation, however. Once you are eating the right foods it is generally possible to maintain a healthy bacterial balance in your gut without the use of probiotics. On a side note, probiotics are especially helpful when you are traveling in the event you get an infectious diarrhea. Typically, large doses of a high-quality probiotic--about one-half to one full bottle in one day--are quite useful for a rapid resolution of the diarrhea. http://www.fmscommunity.org/ibs.htm#ibs1


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## eric (Jul 8, 1999)

100 Trillion Bacteria in Your Gut: Learn How to Keep the Good Kind There.By Dr. Joseph Mercola with Rachael DroegeYou probably don't think about your gut very often but this may make you start--the bacteria in your bowels outnuber the cells in your body by a factor of 10 to one. This gut flora has incredible power over your immune system, which, of course, is your body's natural defense system that keeps you healthy. In other words, the health of your body is largely tied into the health of your gut, and it's hard to have one be healthy if the other is not.One of the reasons why your gut has so much power has to do with the 100 trillion bacteria--about three pounds worth--that line your intestinal tract. This is an extremely complex living system that aggressively protects your body from outside offenders. However, if you are eating as many sugars as the typical American (about 175 pounds per year) then you are feeding the "bad" bacteria, which are more likely to cause disease than promote health, rather than promoting the "good" bacteria that help protect you from disease. Exposure to chemicals will also contribute to this disruption in your gut microflora, and over time the imbalance will lead to illness. A large part of the influence of the "bad" bacteria is on the intestinal lining (mucousal barrier) that is over 300 square meters, or about the size of a tennis court.Beneficial bacteria in your gut can help to boost the immune system, prevent allergic inflammation and food allergy, clear up eczema in children and heal the intestines from a variety of ailments. Fortunately, you can influence the composition of the good and bad bacteria in your gut by optimizing your diet and supplementing it with a high-quality probiotic, or good bacteria. As written in a report in the October 2003 American Journal of Clinical Nutrition, ï¿½probiotics can act as partners of the defense system of the intestine.ï¿½The typical American diet is so full of sugar and grains that--although I donï¿½t often recommend supplements--nearly everyone can benefit from probiotics. You should look for a high potency, multi-strain variety, which can be found in most health food stores. Since the best type of probiotic to use can become highly specific, you may want to discuss the varieties with an experienced health food store employee. I recommend probiotics to nearly all of our new patients, as it is a helpful start for their health recovery. This is not a lifetime recommendation, however. Once you are eating the right foods it is generally possible to maintain a healthy bacterial balance in your gut without the use of probiotics. On a side note, probiotics are especially helpful when you are traveling in the event you get an infectious diarrhea. Typically, large doses of a high-quality probiotic--about one-half to one full bottle in one day--are quite useful for a rapid resolution of the diarrhea. http://www.fmscommunity.org/ibs.htm#ibs1


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## Kacebece3 (Apr 17, 2002)

Interesting post Eric, were do the beneficial bacteria come from in the first place?Ken


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## Kacebece3 (Apr 17, 2002)

Interesting post Eric, were do the beneficial bacteria come from in the first place?Ken


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## bonniei (Jan 25, 2001)

> quote:Typically, large doses of a high-quality probiotic--about one-half to one full bottle in one day--are quite useful for a rapid resolution of the diarrhea


That sounds like a huge amount. One half to one full bottle? How much is that?


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## bonniei (Jan 25, 2001)

> quote:Typically, large doses of a high-quality probiotic--about one-half to one full bottle in one day--are quite useful for a rapid resolution of the diarrhea


That sounds like a huge amount. One half to one full bottle? How much is that?


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## Talissa (Apr 10, 2004)

For traveller's diarrhea, this is good advice at the end of the article. But you're right Bonnie, it isn't too clear...how many are in the bottle? What should the exact dose be? Specific strains? What do the authors consider "high-quality"?This article was written back when Mercola still recommended "Flora Source"(now called iFlora). He now recommends "Primal Defense", which I hope he changes his mind about soon. The HSO spores of PD are not allowed to be sold in Europe due to the unkowns of soil contamination & the long life of spores w/i the intestinal tract.Sorry to go off topic, rambling away...


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## Talissa (Apr 10, 2004)

For traveller's diarrhea, this is good advice at the end of the article. But you're right Bonnie, it isn't too clear...how many are in the bottle? What should the exact dose be? Specific strains? What do the authors consider "high-quality"?This article was written back when Mercola still recommended "Flora Source"(now called iFlora). He now recommends "Primal Defense", which I hope he changes his mind about soon. The HSO spores of PD are not allowed to be sold in Europe due to the unkowns of soil contamination & the long life of spores w/i the intestinal tract.Sorry to go off topic, rambling away...


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## eric (Jul 8, 1999)

Ken some benefical bacteria come from the foods we eat, like yogurt or fermented foods.But actually that is a good question.I will have to look at in some more indepth."Take some good bacteria and call me in the morning. Who'd have thought they'd hear that advice from their doctor? Yet there's increasing evidence that probiotics in food and nutritional supplements can help fight off the bad guys. Ed Balli RN MS NICOLE JOHNSTON Tuesday, January 16, 2001 If you want to be the picture of health, finish your bacteria -- words of wisdom you likely never heard from mom. But there's growing scientific evidence that suggests one way to ward off illness is to consume good bacteria, known as probiotics, to fight off the bad microbes for you. In other words, if you want to beat them -- eat them. Seem preposterous? It isn't when you consider that our bodies are home to 100 trillion bacterial cells that outnumber the body's cells 10 to one. The human gut houses nearly 500 different species of microbes alone. These good bacteria, called the normal flora, live in relative harmony with each other. But any insult that disrupts this balance can tip the scale in favour of conditions that allow one variety of microbe to grow like a house afire, while others get killed off. This is why diarrhea occasionally kicks in during a course of antibiotic therapy. As the antibiotic kills off or inhibits the offending bug, some of the good microbes in the gut also get walloped. Consequently, a diarrhea-causing type of bacteria that resides in the gut can overgrow, making us race for the washroom. This is where probiotics, also called biotherapeutic agents, enter the picture. Probiotics are essentially live bacteria that are consumed as a nutritional supplement for their health-promoting benefits. They help maintain microbial balance and prevent other bugs from giving us grief. They come in either a pill-form, as a powder, or as a component of dairy products. The most common bacteria used are Lactobacillus and Bifidobacterium. Antibiotics, on the other hand, are drugs that kill or inhibit bacteria. "Probiotics provide an extra layer of strength," says Dr. Mary Ellen Sanders, a leading expert on probiotics at California Polytechnic State University, and a consultant for her company Dairy and Food Culture Technologies in Littleton, Colo. They act the role of "soldiers in your intestinal tract to combat pathogens [disease-causing bacteria] that may be there." Furthermore, they improve the gut barrier by keeping the cells that line the gut healthy, she adds. Nevertheless, consuming probiotics hasn't caught on well in North America. Despite being a multibillion dollar business in Europe and Asia, North Americans still haven't sunk their teeth into the idea of consuming beneficial bacteria. The Japanese, for instance, drink to their intestinal health with a probiotic drink called Yakult, consumed by more than 24 million people daily. But some companies are trying their hand at the American market. In Denver, Colo., the Dannon Co., a major yogurt producer, is currently test-marketing a probiotic drink called Actimel. Another company, ConAgra, sells one of the best studied probiotic strains, Lactobacillus GG, in a capsule form called Culturelle. In Canada, probiotic research is only carried out in a small number of labs. Consuming microbes isn't so radical an idea, though. Yogurt and fermented foods have been around for thousands of years. But the idea of deliberately taking bacteria to boost your health was spawned a century ago by one forward-thinking Russian scientist. Elie Metchnikoff was struck by the long, healthy lives led by Bulgarian peasants, and reasoned that Lactobacillus contained in the fermented foods they ate was the answer. In recent years, however, scientists have discovered that probiotics can be used to control lactose intolerance, lower blood pressure and cholesterol, diminish food allergy, reduce the symptoms of inflammatory bowel disease, and give the immune system a beneficial boost. A number of studies have found that probiotics can even decrease the duration and severity of diarrheal disease. Lactobacillus GG was found to be very effective at treating diarrhea in children caused by rotavirus -- for which antibiotics don't work. And just recently, researchers at the Lawson Health Research Institute at the University of Western Ontario in London, have shown that probiotics can be used to successfully treat recurrent vaginal, urinary tract and bladder infections, as well as prevent wounds from becoming infected. Dr. Gregor Reid, a microbiologist and associate director of the Lawson Health Research Institute, and Dr. Andrew Bruce, former chair of urology at the University of Toronto, have devised a mixture of two probiotic strains, Lactobacillus rhamnosus GR-1 and Lactobacillus fermentum RC-14 for treating these infections. For 50-year-old motivational speaker Jane Boucher Arntz of Dayton, Ohio, four years of chronic bladder and yeast infections made life unbearable. "It wasn't like they came and went," she says. "The came and stayed. I had a constant feeling of being poisoned from head to toe." During the four years she sought treatment, antibiotics failed to solve the problem, trips to numerous specialists resulted in recommendations that ran the gamut from having part of her colon removed, to taking male hormones -- even to seeing a psychiatrist. With no remedy and $180,000 (U.S.) in expenses later, Ms. Boucher Arntz enrolled in a small clinical trial conducted by Dr. Reid and Dr. Bruce to study the effect of their probiotic mixture on urogenital infections. Ms. Boucher Arntz drank the 3 millilitre probiotic cocktail twice a day, and within a week the chronic pain lessened. In the two years since the study, her infections have disappeared. She still takes the mixture daily to prevent a recurrence. "I had terrible pelvic pain," she recalls. "I don't have that any more. I have a life now." Antibiotics, medications, illness, hormonal fluctuations, dietary changes, spermicides, vaginal microbicides and even can throw off the normal flora, causing urogenital infections if the woman's own lactobacilli is killed off. Six of the 10 women enrolled in the study saw their infections clear up within one week of drinking the cocktails. The findings are to published in the journal FEMS Immunology and Medical Microbiology. With antibiotic resistance on the rise, probiotics can be a natural alternative -- even a useful addition to standard antibiotic therapy. "There's a population of women that will benefit from this -- no question," Dr. Reid says. Putting these two lactobacilli strains to another test, research led by biochemist Dr. Jeffrey Howard, along with Dr. Reid and surgeon Dr. Bing Siang Gan, found that the RC-14 strain prevented infection of surgical wounds in rats. When Staphylococcus aureus (commonly known as staph) -- a notorious culprit in skin infections -- was added to a surgical implant and embedded under the skin, all nine rats became infected. But when they added staph plus Lactobacillus RC-14 (or a protein RC-14 secretes) to the implant, no infection occurred. These findings were presented in December at the American Society for Cell Biology meeting in San Francisco. The ability of staph to stick to its target is necessary to set up infection. Compounds made by lactobacilli prevent the staph from doing that. "The compounds appear to compete for binding sites with Staphylococcus aureus," says Dr. Howard, not unlike people competing for seats on a subway train during rush hour. Essentially, the lactobacilli take up the seats while the staph bugs slip out the doors. With multidrug-resistant staph looming in hospitals and the community, the results couldn't be more timely. "This one is potentially very big, as it opens up the possibility of an entire new paradigm in the treatment of infection," says Dr. Gan. Until now, treating infections has meant either boosting our defenses or targeting the offending microbe with antibiotics. But these findings show that we can interfere with the environment that is needed for the infection to proceed, he says. But buyer, beware. If you thought all lactobacilli or other microbes were created equal -- think again. Like some natural supplements on the market, some probiotics on the market amount to little more than snake oil. While most manufacturers put "viability counts" (meaning the number of live organisms present) on their labels, testing in independent labs has found that the numbers often come up short of what's claimed, says Dr. Sanders. Other microbes have even been detected. And grocery-store yogurt comes up short as well -- it has no where near the number needed to produce a therapeutic effect. Only seven strains of lactobacilli have scientific data to support their health claims, says Dr. Reid. Before buying a particular supplement, contact the company and ask them if they have clinical data on the particular strain contained in their product, and not lactobacilli in general. To reap a health benefit, "the customer has to ask questions first," he advises. Nicole Johnston is a science writer and PhD student in biochemistry at McMaster University in Hamilton.


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## eric (Jul 8, 1999)

Ken some benefical bacteria come from the foods we eat, like yogurt or fermented foods.But actually that is a good question.I will have to look at in some more indepth."Take some good bacteria and call me in the morning. Who'd have thought they'd hear that advice from their doctor? Yet there's increasing evidence that probiotics in food and nutritional supplements can help fight off the bad guys. Ed Balli RN MS NICOLE JOHNSTON Tuesday, January 16, 2001 If you want to be the picture of health, finish your bacteria -- words of wisdom you likely never heard from mom. But there's growing scientific evidence that suggests one way to ward off illness is to consume good bacteria, known as probiotics, to fight off the bad microbes for you. In other words, if you want to beat them -- eat them. Seem preposterous? It isn't when you consider that our bodies are home to 100 trillion bacterial cells that outnumber the body's cells 10 to one. The human gut houses nearly 500 different species of microbes alone. These good bacteria, called the normal flora, live in relative harmony with each other. But any insult that disrupts this balance can tip the scale in favour of conditions that allow one variety of microbe to grow like a house afire, while others get killed off. This is why diarrhea occasionally kicks in during a course of antibiotic therapy. As the antibiotic kills off or inhibits the offending bug, some of the good microbes in the gut also get walloped. Consequently, a diarrhea-causing type of bacteria that resides in the gut can overgrow, making us race for the washroom. This is where probiotics, also called biotherapeutic agents, enter the picture. Probiotics are essentially live bacteria that are consumed as a nutritional supplement for their health-promoting benefits. They help maintain microbial balance and prevent other bugs from giving us grief. They come in either a pill-form, as a powder, or as a component of dairy products. The most common bacteria used are Lactobacillus and Bifidobacterium. Antibiotics, on the other hand, are drugs that kill or inhibit bacteria. "Probiotics provide an extra layer of strength," says Dr. Mary Ellen Sanders, a leading expert on probiotics at California Polytechnic State University, and a consultant for her company Dairy and Food Culture Technologies in Littleton, Colo. They act the role of "soldiers in your intestinal tract to combat pathogens [disease-causing bacteria] that may be there." Furthermore, they improve the gut barrier by keeping the cells that line the gut healthy, she adds. Nevertheless, consuming probiotics hasn't caught on well in North America. Despite being a multibillion dollar business in Europe and Asia, North Americans still haven't sunk their teeth into the idea of consuming beneficial bacteria. The Japanese, for instance, drink to their intestinal health with a probiotic drink called Yakult, consumed by more than 24 million people daily. But some companies are trying their hand at the American market. In Denver, Colo., the Dannon Co., a major yogurt producer, is currently test-marketing a probiotic drink called Actimel. Another company, ConAgra, sells one of the best studied probiotic strains, Lactobacillus GG, in a capsule form called Culturelle. In Canada, probiotic research is only carried out in a small number of labs. Consuming microbes isn't so radical an idea, though. Yogurt and fermented foods have been around for thousands of years. But the idea of deliberately taking bacteria to boost your health was spawned a century ago by one forward-thinking Russian scientist. Elie Metchnikoff was struck by the long, healthy lives led by Bulgarian peasants, and reasoned that Lactobacillus contained in the fermented foods they ate was the answer. In recent years, however, scientists have discovered that probiotics can be used to control lactose intolerance, lower blood pressure and cholesterol, diminish food allergy, reduce the symptoms of inflammatory bowel disease, and give the immune system a beneficial boost. A number of studies have found that probiotics can even decrease the duration and severity of diarrheal disease. Lactobacillus GG was found to be very effective at treating diarrhea in children caused by rotavirus -- for which antibiotics don't work. And just recently, researchers at the Lawson Health Research Institute at the University of Western Ontario in London, have shown that probiotics can be used to successfully treat recurrent vaginal, urinary tract and bladder infections, as well as prevent wounds from becoming infected. Dr. Gregor Reid, a microbiologist and associate director of the Lawson Health Research Institute, and Dr. Andrew Bruce, former chair of urology at the University of Toronto, have devised a mixture of two probiotic strains, Lactobacillus rhamnosus GR-1 and Lactobacillus fermentum RC-14 for treating these infections. For 50-year-old motivational speaker Jane Boucher Arntz of Dayton, Ohio, four years of chronic bladder and yeast infections made life unbearable. "It wasn't like they came and went," she says. "The came and stayed. I had a constant feeling of being poisoned from head to toe." During the four years she sought treatment, antibiotics failed to solve the problem, trips to numerous specialists resulted in recommendations that ran the gamut from having part of her colon removed, to taking male hormones -- even to seeing a psychiatrist. With no remedy and $180,000 (U.S.) in expenses later, Ms. Boucher Arntz enrolled in a small clinical trial conducted by Dr. Reid and Dr. Bruce to study the effect of their probiotic mixture on urogenital infections. Ms. Boucher Arntz drank the 3 millilitre probiotic cocktail twice a day, and within a week the chronic pain lessened. In the two years since the study, her infections have disappeared. She still takes the mixture daily to prevent a recurrence. "I had terrible pelvic pain," she recalls. "I don't have that any more. I have a life now." Antibiotics, medications, illness, hormonal fluctuations, dietary changes, spermicides, vaginal microbicides and even can throw off the normal flora, causing urogenital infections if the woman's own lactobacilli is killed off. Six of the 10 women enrolled in the study saw their infections clear up within one week of drinking the cocktails. The findings are to published in the journal FEMS Immunology and Medical Microbiology. With antibiotic resistance on the rise, probiotics can be a natural alternative -- even a useful addition to standard antibiotic therapy. "There's a population of women that will benefit from this -- no question," Dr. Reid says. Putting these two lactobacilli strains to another test, research led by biochemist Dr. Jeffrey Howard, along with Dr. Reid and surgeon Dr. Bing Siang Gan, found that the RC-14 strain prevented infection of surgical wounds in rats. When Staphylococcus aureus (commonly known as staph) -- a notorious culprit in skin infections -- was added to a surgical implant and embedded under the skin, all nine rats became infected. But when they added staph plus Lactobacillus RC-14 (or a protein RC-14 secretes) to the implant, no infection occurred. These findings were presented in December at the American Society for Cell Biology meeting in San Francisco. The ability of staph to stick to its target is necessary to set up infection. Compounds made by lactobacilli prevent the staph from doing that. "The compounds appear to compete for binding sites with Staphylococcus aureus," says Dr. Howard, not unlike people competing for seats on a subway train during rush hour. Essentially, the lactobacilli take up the seats while the staph bugs slip out the doors. With multidrug-resistant staph looming in hospitals and the community, the results couldn't be more timely. "This one is potentially very big, as it opens up the possibility of an entire new paradigm in the treatment of infection," says Dr. Gan. Until now, treating infections has meant either boosting our defenses or targeting the offending microbe with antibiotics. But these findings show that we can interfere with the environment that is needed for the infection to proceed, he says. But buyer, beware. If you thought all lactobacilli or other microbes were created equal -- think again. Like some natural supplements on the market, some probiotics on the market amount to little more than snake oil. While most manufacturers put "viability counts" (meaning the number of live organisms present) on their labels, testing in independent labs has found that the numbers often come up short of what's claimed, says Dr. Sanders. Other microbes have even been detected. And grocery-store yogurt comes up short as well -- it has no where near the number needed to produce a therapeutic effect. Only seven strains of lactobacilli have scientific data to support their health claims, says Dr. Reid. Before buying a particular supplement, contact the company and ask them if they have clinical data on the particular strain contained in their product, and not lactobacilli in general. To reap a health benefit, "the customer has to ask questions first," he advises. Nicole Johnston is a science writer and PhD student in biochemistry at McMaster University in Hamilton.


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## eric (Jul 8, 1999)

You know many eople hear the word bacteria and as this states they are usally associated with "dirt, Disease and death."But the system has evolved for millions of years to work and work well to protect us.In someways the more your exposed to them the healthier you can be really as the immune system creates antigens to the bad ones.Also they are different for someone in cal and someone in NY, they protect us from our unique environments and even our households.Bacteria: More Than PathogensBy Trudy M. Wassenaar Bacteria are usually associated with dirt, disease, and death. Misunderstood bacteria Bacteria suffer from negative public relations. You probably associate bacteria with the three D's: dirt, disease and death. And indeed, for centuries bacterial infections were the major cause of infant and child mortality worldwide. Child mortality began to decline after people were educated about better hygiene. The decline continued with the introduction of antibiotics for better treatment and vaccination for prevention of common deadly diseases.Bacteria are certainly involved in dirt, disease and death, to which we should add decay. Spoilage of leftover food, decomposition of garden cuttings, decay of dead bodies, or smelly water in a forgotten vase, are all the result of bacterial activity. As is body odor, caries, strep throat, or bubonic plague, to name a few diseases from both ends of the spectrum. No wonder that bacteria receive a bad press. Bacteria that caused large-scale disease in our history may be close to extinction. Commercials want us to believe that the only good bacterium is a dead bacterium. Antimicrobial agents are added to tooth paste, soaps, detergents, and plastics. There is no Society for the Protection of Bacteria, although there is a satirical initiative for the Ethical Treatment of Bacteria.1 Some bacteria may even hover on the edge of extinction, and it is no coincidence that these are pathogenic (disease-causing) bacteria such as Salmonella typhi (the cause of typhoid fever) or Yersinia pestis (the cause of plague). Fortunately for the little critters, populations survive in remote areas where they are not efficiently hunted with vaccines and antimicrobials, and people are still at risk for the diseases they cause in these places. The bacterial kingdom It is about time we take a closer look at the Bacterial Kingdom, with capitals. For a Kingdom it is, biologically speaking, and the ancient lineage, diversity, and evolutionary power of its inhabitants deserve royal treatment rather than disgust. A bacterium differs from a virus in its structure and in the way it inhabits a host. Before kindling fascination for the world of bacteria, a common misconception must be cleared: bacteria are not viruses. Whereas most bacteria live as independent cells with a membrane to separate them from the outside world, viruses can only multiply inside, and to the detriment of, the cells they infect. Interestingly, some viruses, called bacteriophages, have specialized to infect bacteria.2,3 Viruses consist only of genetic material (DNA or RNA) surrounded by a protein shell. They cannot metabolize and once inside a host cell, their genetic material hijacks the cell's machinery to produce replicas of the virus. Bacteria are much more similar to you and me. They exhibit the basic characteristics of all living things -- they breathe, metabolize, produce waste, and maintain a membrane potential. However, they do not have a nucleus in which their DNA is separated from the rest of the cell, as plants and animals do, and that is the major distinction between prokaryotes (a type of cell that most microorganisms are made of, including all bacteria) and eukaryotes (a different type of cell making up nucleated microorganisms, such as yeasts, or cells in an organism, e.g., human). Both viruses and bacteria can cause disease. However, not all types of viruses cause disease in humans, and not all bacteria cause disease. The majority of bacteria are harmless and some are beneficial. Another common misconception is that all bacteria are bad for you. Some bacteria you'd better not meet, but the majority of them are completely harmless, and some are highly beneficial to us. Confusingly, certain bacteria can be beneficial to some animals, and pathogenic to others. More commonly, pathogenic bacteria are harmful only to a limited number of hosts, or even only to one, whereas they live happily within other hosts without causing trouble. If the suffering host happens to be human, the culprit bacteria are called human pathogens; however, from the bacterial point of view, humans are just the wrong host to be in. So who is to blame for the disease? Harmless bacteria can become deadly in certain circumstances. Most bacteria are completely harmless Although a tree can kill a person when it falls, we usually don't regard trees as harmful. The same is true for most bacteria -- although they may cause problems under specific conditions, they usually live their lives without interfering with ours. An example is Pseudomonas aeruginosa, which commonly lives in soil without doing harm. However, if it is inhaled by a person with Cystic Fibrosis, it can colonize their lungs and cause lethal infections.4 The human body is not the natural environment for many bacteria. For many bacteria, the human body is not the right place to live in at all. They couldn't cope with the lack of oxygen (inside our cells the oxygen concentration is lower than that of air) or with the presence of oxygen (for bacteria that live in oxygen-deprived environments, oxygen is toxic). They couldn't withstand our defense mechanisms such as the salt present on our skin and in our tears, the lack of iron (a smart device keeps iron, a vital element to all living organisms, inaccessible to most microorganisms in our body), or with the toxic radicals that cells release when under attack of bacteria. It could be too warm for them, or too cold, as certain bacteria have specific temperature requirements to grow. Or they could be deprived of food, as the members of the Bacterial Kingdom have specialized to live on almost anything, but each species has specific nutrient needs. In conclusion, we have little to fear from most bacteria that we encounter. Our bodies can resist most bacterial attacks. It is no big surprise that we are relatively inert to bacteria. After all, mammals have evolved in the presence of bacteria, and have developed specialized strategies to keep bacteria under control. In contrast to what your mother taught you, soap is not essential to survive. Our body can resist the bombardment of bacteria it receives every day quite efficiently. Just as well that we can't see them (for the idea is unpleasant) but with every breath of air, every bite we take, little bugs are unknowingly entering our body. And this shouldn't worry you in the least. As long as you keep the troublemakers -- the real pathogens -- out. The human body is home to millions of beneficial bacteria. We couldn't live without bacteria We house millions of bacteria on our skin and in our nose, mouth, and gut:up to 500 species can be found as normal oral flora5 there can easily be 25 species living in a single mouth a milliliter of saliva can contain as many as 40 million (4 x 107) bacterial cells6 108 bacterial cells present in the cecum (the initial part of the colon) per milliliter of content is normal and many of these species are different from those found in the mouth7 Strictly speaking, the inside of our mouth, stomach and intestines are part of our outer surfaces. Although they are inside our body, their surfaces are in direct contact with the outside world, and as food particles pass the mucosal inner lining of our intestines, hitchhiking bacteria can stay there and multiply. We are born sterile (free of bacteria) but within hours we are colonized by our little friends, not to be left alone again. Antibiotics can wipe out our body's beneficial bacteria, causing unwanted health consequences. Without bacteria we would not survive. They help us digest our food, produce vitamins, and occupy niches that would otherwise be available for competing pathogens. This competitive effect becomes apparent when we wipe out a large proportion of our intestinal flora, for instance by an antibiotic that is prescribed to treat a bacterial infection. Diarrhea is frequently the unwanted result, as 'foreign' bacteria take their chance to occupy the 'empty' niches. Healthy bacteria take over in time, so that in most cases the side effects of antibiotics are soon gone. Bacterial populations grow into a state of equilibrium until some external factor disturbs it again. Certain foods and the way we process food depend on bacteria. We can buy supplements or foods with beneficial bacteria. Certain bacteria are good for you For centuries, people have eaten certain food deliberately for the bacteria it contains and have used bacteria in food preparation.The best-known example is the consumption of yogurt and other fermented milk products, which have the combined effect of reducing spoilage, and enhancing tolerance for partially lactose-intolerant individuals. A major industry has developed to produce bacterial preparations, in the form of powders, drinks, and dairy products; all sold as healthy and beneficial (and sometimes tasty) supplements. Although some of their promises are unrealistic (some products don't even contain viable bacteria), it is generally accepted that certain bacteria are beneficial, especially when intestinal flora is unbalanced (as with antibiotic-associated diarrhea). The most commonly used bacterial species as so-called probiotics are lactobacilli and bifidobacterium.8 A number of bacterial species are required for the preparation of food, and may or may not arrive on our plate alive.9 Notably, many cheese varieties are dependent on their characteristic bacterial starter culture. Fermenting bacteria are required to produce sausages and sauerkraut; they even help cacao and coffee beans to attain their desired flavor.10 Conclusion: Bacteria are essential to human health and the world's ecosystems. Earth: the planet of bacteria In a gram of soil, approximately 108 bacteria are present11 and these are estimated to represent over 10,000 species. Interestingly, there are more than 1030 bacteria on earth, compared with fewer than 1010 humans.12 Bacteria were the first living organisms found on Earth. They inhabit deserts, ice caps, oceans and hot springs. The number of bacterial species worldwide is estimated to be more than a thousand million.11 Their individual sizes may be insignificant, but their number and diversity is unimaginably large. Bacteria contribute substantially to the total biomass in marine environments.13 And, since oceans cover 70% of our planet's surface, bacteria make up a significant part of the total biomass on Earth. These facts are truly impressive for organisms so small that they are invisible to the eye. It is to our advantage to look at bacteria as more than just pathogens. ï¿½ 2002, American Institute of Biological Sciences. Educators have permission to reprint articles for classroom use; other users, please contact editor for reprint permission. See reprint policy. About the author: Trudy Wassenaar, Ph.D., is a molecular biologist specializing in microbiology. She has done research at the University of Amsterdam and the University of Utrecht (The Netherlands), as well as at the University of Mainz (Germany), for over 15 years. In 2000, she founded a consulting company to assist research groups in academia and governmental agencies with the development of research strategies and dissemination of results. She is Curator of the Virtual Museum of Bacteria (supported by the Foundation for Bacteriology). http://www.bacteriamuseum.org/homepageTW.shtml


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## eric (Jul 8, 1999)

You know many eople hear the word bacteria and as this states they are usally associated with "dirt, Disease and death."But the system has evolved for millions of years to work and work well to protect us.In someways the more your exposed to them the healthier you can be really as the immune system creates antigens to the bad ones.Also they are different for someone in cal and someone in NY, they protect us from our unique environments and even our households.Bacteria: More Than PathogensBy Trudy M. Wassenaar Bacteria are usually associated with dirt, disease, and death. Misunderstood bacteria Bacteria suffer from negative public relations. You probably associate bacteria with the three D's: dirt, disease and death. And indeed, for centuries bacterial infections were the major cause of infant and child mortality worldwide. Child mortality began to decline after people were educated about better hygiene. The decline continued with the introduction of antibiotics for better treatment and vaccination for prevention of common deadly diseases.Bacteria are certainly involved in dirt, disease and death, to which we should add decay. Spoilage of leftover food, decomposition of garden cuttings, decay of dead bodies, or smelly water in a forgotten vase, are all the result of bacterial activity. As is body odor, caries, strep throat, or bubonic plague, to name a few diseases from both ends of the spectrum. No wonder that bacteria receive a bad press. Bacteria that caused large-scale disease in our history may be close to extinction. Commercials want us to believe that the only good bacterium is a dead bacterium. Antimicrobial agents are added to tooth paste, soaps, detergents, and plastics. There is no Society for the Protection of Bacteria, although there is a satirical initiative for the Ethical Treatment of Bacteria.1 Some bacteria may even hover on the edge of extinction, and it is no coincidence that these are pathogenic (disease-causing) bacteria such as Salmonella typhi (the cause of typhoid fever) or Yersinia pestis (the cause of plague). Fortunately for the little critters, populations survive in remote areas where they are not efficiently hunted with vaccines and antimicrobials, and people are still at risk for the diseases they cause in these places. The bacterial kingdom It is about time we take a closer look at the Bacterial Kingdom, with capitals. For a Kingdom it is, biologically speaking, and the ancient lineage, diversity, and evolutionary power of its inhabitants deserve royal treatment rather than disgust. A bacterium differs from a virus in its structure and in the way it inhabits a host. Before kindling fascination for the world of bacteria, a common misconception must be cleared: bacteria are not viruses. Whereas most bacteria live as independent cells with a membrane to separate them from the outside world, viruses can only multiply inside, and to the detriment of, the cells they infect. Interestingly, some viruses, called bacteriophages, have specialized to infect bacteria.2,3 Viruses consist only of genetic material (DNA or RNA) surrounded by a protein shell. They cannot metabolize and once inside a host cell, their genetic material hijacks the cell's machinery to produce replicas of the virus. Bacteria are much more similar to you and me. They exhibit the basic characteristics of all living things -- they breathe, metabolize, produce waste, and maintain a membrane potential. However, they do not have a nucleus in which their DNA is separated from the rest of the cell, as plants and animals do, and that is the major distinction between prokaryotes (a type of cell that most microorganisms are made of, including all bacteria) and eukaryotes (a different type of cell making up nucleated microorganisms, such as yeasts, or cells in an organism, e.g., human). Both viruses and bacteria can cause disease. However, not all types of viruses cause disease in humans, and not all bacteria cause disease. The majority of bacteria are harmless and some are beneficial. Another common misconception is that all bacteria are bad for you. Some bacteria you'd better not meet, but the majority of them are completely harmless, and some are highly beneficial to us. Confusingly, certain bacteria can be beneficial to some animals, and pathogenic to others. More commonly, pathogenic bacteria are harmful only to a limited number of hosts, or even only to one, whereas they live happily within other hosts without causing trouble. If the suffering host happens to be human, the culprit bacteria are called human pathogens; however, from the bacterial point of view, humans are just the wrong host to be in. So who is to blame for the disease? Harmless bacteria can become deadly in certain circumstances. Most bacteria are completely harmless Although a tree can kill a person when it falls, we usually don't regard trees as harmful. The same is true for most bacteria -- although they may cause problems under specific conditions, they usually live their lives without interfering with ours. An example is Pseudomonas aeruginosa, which commonly lives in soil without doing harm. However, if it is inhaled by a person with Cystic Fibrosis, it can colonize their lungs and cause lethal infections.4 The human body is not the natural environment for many bacteria. For many bacteria, the human body is not the right place to live in at all. They couldn't cope with the lack of oxygen (inside our cells the oxygen concentration is lower than that of air) or with the presence of oxygen (for bacteria that live in oxygen-deprived environments, oxygen is toxic). They couldn't withstand our defense mechanisms such as the salt present on our skin and in our tears, the lack of iron (a smart device keeps iron, a vital element to all living organisms, inaccessible to most microorganisms in our body), or with the toxic radicals that cells release when under attack of bacteria. It could be too warm for them, or too cold, as certain bacteria have specific temperature requirements to grow. Or they could be deprived of food, as the members of the Bacterial Kingdom have specialized to live on almost anything, but each species has specific nutrient needs. In conclusion, we have little to fear from most bacteria that we encounter. Our bodies can resist most bacterial attacks. It is no big surprise that we are relatively inert to bacteria. After all, mammals have evolved in the presence of bacteria, and have developed specialized strategies to keep bacteria under control. In contrast to what your mother taught you, soap is not essential to survive. Our body can resist the bombardment of bacteria it receives every day quite efficiently. Just as well that we can't see them (for the idea is unpleasant) but with every breath of air, every bite we take, little bugs are unknowingly entering our body. And this shouldn't worry you in the least. As long as you keep the troublemakers -- the real pathogens -- out. The human body is home to millions of beneficial bacteria. We couldn't live without bacteria We house millions of bacteria on our skin and in our nose, mouth, and gut:up to 500 species can be found as normal oral flora5 there can easily be 25 species living in a single mouth a milliliter of saliva can contain as many as 40 million (4 x 107) bacterial cells6 108 bacterial cells present in the cecum (the initial part of the colon) per milliliter of content is normal and many of these species are different from those found in the mouth7 Strictly speaking, the inside of our mouth, stomach and intestines are part of our outer surfaces. Although they are inside our body, their surfaces are in direct contact with the outside world, and as food particles pass the mucosal inner lining of our intestines, hitchhiking bacteria can stay there and multiply. We are born sterile (free of bacteria) but within hours we are colonized by our little friends, not to be left alone again. Antibiotics can wipe out our body's beneficial bacteria, causing unwanted health consequences. Without bacteria we would not survive. They help us digest our food, produce vitamins, and occupy niches that would otherwise be available for competing pathogens. This competitive effect becomes apparent when we wipe out a large proportion of our intestinal flora, for instance by an antibiotic that is prescribed to treat a bacterial infection. Diarrhea is frequently the unwanted result, as 'foreign' bacteria take their chance to occupy the 'empty' niches. Healthy bacteria take over in time, so that in most cases the side effects of antibiotics are soon gone. Bacterial populations grow into a state of equilibrium until some external factor disturbs it again. Certain foods and the way we process food depend on bacteria. We can buy supplements or foods with beneficial bacteria. Certain bacteria are good for you For centuries, people have eaten certain food deliberately for the bacteria it contains and have used bacteria in food preparation.The best-known example is the consumption of yogurt and other fermented milk products, which have the combined effect of reducing spoilage, and enhancing tolerance for partially lactose-intolerant individuals. A major industry has developed to produce bacterial preparations, in the form of powders, drinks, and dairy products; all sold as healthy and beneficial (and sometimes tasty) supplements. Although some of their promises are unrealistic (some products don't even contain viable bacteria), it is generally accepted that certain bacteria are beneficial, especially when intestinal flora is unbalanced (as with antibiotic-associated diarrhea). The most commonly used bacterial species as so-called probiotics are lactobacilli and bifidobacterium.8 A number of bacterial species are required for the preparation of food, and may or may not arrive on our plate alive.9 Notably, many cheese varieties are dependent on their characteristic bacterial starter culture. Fermenting bacteria are required to produce sausages and sauerkraut; they even help cacao and coffee beans to attain their desired flavor.10 Conclusion: Bacteria are essential to human health and the world's ecosystems. Earth: the planet of bacteria In a gram of soil, approximately 108 bacteria are present11 and these are estimated to represent over 10,000 species. Interestingly, there are more than 1030 bacteria on earth, compared with fewer than 1010 humans.12 Bacteria were the first living organisms found on Earth. They inhabit deserts, ice caps, oceans and hot springs. The number of bacterial species worldwide is estimated to be more than a thousand million.11 Their individual sizes may be insignificant, but their number and diversity is unimaginably large. Bacteria contribute substantially to the total biomass in marine environments.13 And, since oceans cover 70% of our planet's surface, bacteria make up a significant part of the total biomass on Earth. These facts are truly impressive for organisms so small that they are invisible to the eye. It is to our advantage to look at bacteria as more than just pathogens. ï¿½ 2002, American Institute of Biological Sciences. Educators have permission to reprint articles for classroom use; other users, please contact editor for reprint permission. See reprint policy. About the author: Trudy Wassenaar, Ph.D., is a molecular biologist specializing in microbiology. She has done research at the University of Amsterdam and the University of Utrecht (The Netherlands), as well as at the University of Mainz (Germany), for over 15 years. In 2000, she founded a consulting company to assist research groups in academia and governmental agencies with the development of research strategies and dissemination of results. She is Curator of the Virtual Museum of Bacteria (supported by the Foundation for Bacteriology). http://www.bacteriamuseum.org/homepageTW.shtml


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## Talissa (Apr 10, 2004)

This came out yesterday, and they used 200 billion cells daily to treat UC in the study...maybe I'm not at 100% because I only take 6-10 billion daily??? I don't think my IBS needs as much as for UC but it probably wouldn't hurt to upgrade to custom probiotics or metagenics(25-50 billion per dose, human strain)?? Anyways, here's the article~ï¿½Restoring probiotic bacteria appears to remedy gut diseaseï¿½ 18/08/2004 - A probiotic treatment almost reversed many of the symptoms of the gut disease ulcerative colitis in a small trial, report researchers at the University of Dundee in Scotland.The treatment, developed by the researchers from a bacterial strain isolated from the gut lining of healthy people, contains several million more bacteria than typically found in probiotic foods (200 billion daily), but the study does underline the role of bacteria in gut health. Ulcerative colitis is one of the UK's most common forms of inflammatory bowel disease and affects an estimated 50,000 people in the UK, with a particularly high incidence in north east Scotland. The acute and chronic disease causes inflammation and sores, called ulcers, in the lining of the large bowel. Professor George Macfarlane and colleagues have found that the bowel wall of healthy people contained 30 times the amount of a specific type of probiotic bacteria than in colitis patients. They developed a probiotic, which will be patented by the university, and gave it to 18 colitis patients as a substitute for the anti-inflammatory effects normally gained from the ï¿½friendly bacteriaï¿½ in healthy people. The trial results were dramatic showing that the symbiotic (the probiotic taken with food) had a highly significant effect on inflammatory molecules in the bowel wall, largely reducing the pain and discomfort commonly experienced by ulcerative colitis patients. Molecular and clinical tests showed that many symptoms associated with colitis were reduced to near normal levels. Professor George Macfarlane told NutraIngredients.com: ï¿½Different species behave in different ways so I donï¿½t know if other probiotics would have a similar effect. Also you would have to eat gallons of yoghurt to get the amounts of bacteria we used.But he added that animal studies have confirmed the role of the intestinal microflora in gut disease and other research shows how bacteria can reduce toxins in the gut." http://www.foodnavigator.com/news/news-NG.asp?id=54224


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## Talissa (Apr 10, 2004)

This came out yesterday, and they used 200 billion cells daily to treat UC in the study...maybe I'm not at 100% because I only take 6-10 billion daily??? I don't think my IBS needs as much as for UC but it probably wouldn't hurt to upgrade to custom probiotics or metagenics(25-50 billion per dose, human strain)?? Anyways, here's the article~ï¿½Restoring probiotic bacteria appears to remedy gut diseaseï¿½ 18/08/2004 - A probiotic treatment almost reversed many of the symptoms of the gut disease ulcerative colitis in a small trial, report researchers at the University of Dundee in Scotland.The treatment, developed by the researchers from a bacterial strain isolated from the gut lining of healthy people, contains several million more bacteria than typically found in probiotic foods (200 billion daily), but the study does underline the role of bacteria in gut health. Ulcerative colitis is one of the UK's most common forms of inflammatory bowel disease and affects an estimated 50,000 people in the UK, with a particularly high incidence in north east Scotland. The acute and chronic disease causes inflammation and sores, called ulcers, in the lining of the large bowel. Professor George Macfarlane and colleagues have found that the bowel wall of healthy people contained 30 times the amount of a specific type of probiotic bacteria than in colitis patients. They developed a probiotic, which will be patented by the university, and gave it to 18 colitis patients as a substitute for the anti-inflammatory effects normally gained from the ï¿½friendly bacteriaï¿½ in healthy people. The trial results were dramatic showing that the symbiotic (the probiotic taken with food) had a highly significant effect on inflammatory molecules in the bowel wall, largely reducing the pain and discomfort commonly experienced by ulcerative colitis patients. Molecular and clinical tests showed that many symptoms associated with colitis were reduced to near normal levels. Professor George Macfarlane told NutraIngredients.com: ï¿½Different species behave in different ways so I donï¿½t know if other probiotics would have a similar effect. Also you would have to eat gallons of yoghurt to get the amounts of bacteria we used.But he added that animal studies have confirmed the role of the intestinal microflora in gut disease and other research shows how bacteria can reduce toxins in the gut." http://www.foodnavigator.com/news/news-NG.asp?id=54224


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## SpAsMaN* (May 11, 2002)

Talissa,it looks promising.I can't wait to try a probiotic who is EFFECTVE in IBS.


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## SpAsMaN* (May 11, 2002)

Talissa,it looks promising.I can't wait to try a probiotic who is EFFECTVE in IBS.


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## Talissa (Apr 10, 2004)

Hey spasman, It does look good, will be interesting when the product comes out.Btw, in search of genuine testimonials, I just did searches on Custom Probiotics, as well as Metagenics brand probiotics like Ultra Flora. I found 2 testimonials(at sites not selling them) that were fairly enthusiastic abt Custom Probiotics.I found LOTS of testimonials at sites not selling Metagenics brand probiotics. Like kel, they all talk about their RECOVERY due to Metagenics, and in many cases this was in conjunction with elimination/reduction of wheat and dairy. Dr Dahlman recommends all of this. I just wish I could buy Metagenics brand online, not have to go through a physician!! May be breaking down & emailing Dr D soon...Oh well, in the interest of sharing,







TalissaPS...Why doesn't this bb come up in these searches??


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## Talissa (Apr 10, 2004)

Hey spasman, It does look good, will be interesting when the product comes out.Btw, in search of genuine testimonials, I just did searches on Custom Probiotics, as well as Metagenics brand probiotics like Ultra Flora. I found 2 testimonials(at sites not selling them) that were fairly enthusiastic abt Custom Probiotics.I found LOTS of testimonials at sites not selling Metagenics brand probiotics. Like kel, they all talk about their RECOVERY due to Metagenics, and in many cases this was in conjunction with elimination/reduction of wheat and dairy. Dr Dahlman recommends all of this. I just wish I could buy Metagenics brand online, not have to go through a physician!! May be breaking down & emailing Dr D soon...Oh well, in the interest of sharing,







TalissaPS...Why doesn't this bb come up in these searches??


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## kel1059 (Feb 28, 2003)

(Professor George Macfarlane and colleagues have found that the bowel wall of healthy people contained 30 times the amount of a specific type of probiotic bacteria than in colitis patients)Good find. I just posted it in the UC/ crohn's forum.I guess it goes to show that not all probiotics are created equal.If the medical establishment (big pharm) really cared about helping people they would devote more time to understanding gut flora as opposed to symptom suppressing drugs.


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## kel1059 (Feb 28, 2003)

(Professor George Macfarlane and colleagues have found that the bowel wall of healthy people contained 30 times the amount of a specific type of probiotic bacteria than in colitis patients)Good find. I just posted it in the UC/ crohn's forum.I guess it goes to show that not all probiotics are created equal.If the medical establishment (big pharm) really cared about helping people they would devote more time to understanding gut flora as opposed to symptom suppressing drugs.


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## drdahlman (Nov 6, 2000)

Taking a half a bottle of good bacteria would be a complete waste as most of them would pass out of the body and never make it to the cell wall of the gut.Babies are born with a sterile gut and it is populated by the beneficial bacteria through bacteria on fresh fruits and vegetables (raw) and from the skin of other humans that they touch. All humans have bacteria and yeast (candida) living on the skin. Breast feeding becomes even more important because of the amount of time the baby spends with their mouth attached to Mom. Babies will, as a reflex, lickyour face, your shoulder or your finger and ingest these organisms through this kind of contact with anyone around them.


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## drdahlman (Nov 6, 2000)

Taking a half a bottle of good bacteria would be a complete waste as most of them would pass out of the body and never make it to the cell wall of the gut.Babies are born with a sterile gut and it is populated by the beneficial bacteria through bacteria on fresh fruits and vegetables (raw) and from the skin of other humans that they touch. All humans have bacteria and yeast (candida) living on the skin. Breast feeding becomes even more important because of the amount of time the baby spends with their mouth attached to Mom. Babies will, as a reflex, lickyour face, your shoulder or your finger and ingest these organisms through this kind of contact with anyone around them.


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## anmegrl (Jul 4, 2004)

Doesn't VSL make probiotics with a very high amount of beneficial strands? If I remember from the website, theirs has 450 billion. Some IBSers reported good results but it is expensive.Oh, found the website - http://www.vsl3.com/vsl3/index.htm. And as far as I know, you can order Metagenics products online without a doctor like at this place: http://www.ediblenature.com/index.html But you may want to call and ask just to be sure.


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## anmegrl (Jul 4, 2004)

Doesn't VSL make probiotics with a very high amount of beneficial strands? If I remember from the website, theirs has 450 billion. Some IBSers reported good results but it is expensive.Oh, found the website - http://www.vsl3.com/vsl3/index.htm. And as far as I know, you can order Metagenics products online without a doctor like at this place: http://www.ediblenature.com/index.html But you may want to call and ask just to be sure.


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## eric (Jul 8, 1999)

Probiotics have a different success rate in IBD conditions then in IBS. In IBD conditions where the OUTSIDE of the gut wall is inflammed they have been shown to help, but in IBS the outer gut wall is not inflammed. In IBS they have been shown to help SOMEWHAT for different reasons on bloating and pain.VSL did there own IBS studies.EFFECT OF A PROBIOTIC, VSL#3, IN DIARRHEA-PREDOMINANT IRRITABLE BOWEL SYNDROME: A RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED TRIALH. Jae Kim, M.D. Michael Camilleri, M.D., FACG, Sanna McKinzie, M.S., Duane Burton, George M. Thomforde and Alan R. Zinsmeister, Ph.D.Clinical Enteric Neuroscience Translational & Epidemiological Research (C.E.N.T.E.R.) Program, Mayo Clinic Rochester, MNPurpose Recent clinical studies have demonstrated that the probiotics are efficacious in treating various diarrheal illnesses. The influence of probiotic on gastrointestinal transit in patients with irritable bowel syndrome (IBS) is unclear. We investigated the effect of VSL#3 on the gastrointestinal transit and symptoms of patients with diarrhea-predominant IBS.Methods Patients fulfilling the Rome II criteria with diarrhea-predominant symptoms and without a history of organic gastrointestinal disease were recruited. Twenty-five patients were randomly assigned to VSL#3 powder or matching placebo twice daily for 8 weeks after a 2 week baseline period to assess symptoms. The VSL#3 group received 450 billion lyophilized bacteria per day. Pre- and post-treatment gastrointestinal transit measurements were performed in all patients. Patients recorded their bowel function and symptoms daily for the entire study. The primary endpoint of the study was colonic geometric center at 24 hours, and secondary endpoints were; gastric emptying at 2 and 4 hours, colonic filling at 6 hours, colonic geometric center at 48 hours, proportion of responders, and individual symptoms and bowel functions. *Results There were no significant differences of the mean gastrointestinal transit measurements between the two groups, pre- and post-therapy. Overall, individual IBS symptoms and satisfactory relief of IBS were not different between VSL#3 and placebo group;* *however, abdominal bloating was significantly reduced in the VSL#3 group * (post vs pre, P = 0.04) and not in the placebo group (post vs pre, P = 0.78). *The scores for flatulence, abdominal pain, and urgency were not significantly reduced in patients treated with VSL#3.* All patients tolerated the VSL#3 well. One patient, who was later shown to be randomized to placebo, withdrew from the study due to a severe abdominal pain.Conclusion VSL#3 appears promising in the relief of abdominal bloating in patients with diarrhea-predominant IBS. *This effect is unrelated to alteration in gastrointestinal or colon transit.* Am J gastroenterol. 2002; 97(9): A830


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## eric (Jul 8, 1999)

Probiotics have a different success rate in IBD conditions then in IBS. In IBD conditions where the OUTSIDE of the gut wall is inflammed they have been shown to help, but in IBS the outer gut wall is not inflammed. In IBS they have been shown to help SOMEWHAT for different reasons on bloating and pain.VSL did there own IBS studies.EFFECT OF A PROBIOTIC, VSL#3, IN DIARRHEA-PREDOMINANT IRRITABLE BOWEL SYNDROME: A RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED TRIALH. Jae Kim, M.D. Michael Camilleri, M.D., FACG, Sanna McKinzie, M.S., Duane Burton, George M. Thomforde and Alan R. Zinsmeister, Ph.D.Clinical Enteric Neuroscience Translational & Epidemiological Research (C.E.N.T.E.R.) Program, Mayo Clinic Rochester, MNPurpose Recent clinical studies have demonstrated that the probiotics are efficacious in treating various diarrheal illnesses. The influence of probiotic on gastrointestinal transit in patients with irritable bowel syndrome (IBS) is unclear. We investigated the effect of VSL#3 on the gastrointestinal transit and symptoms of patients with diarrhea-predominant IBS.Methods Patients fulfilling the Rome II criteria with diarrhea-predominant symptoms and without a history of organic gastrointestinal disease were recruited. Twenty-five patients were randomly assigned to VSL#3 powder or matching placebo twice daily for 8 weeks after a 2 week baseline period to assess symptoms. The VSL#3 group received 450 billion lyophilized bacteria per day. Pre- and post-treatment gastrointestinal transit measurements were performed in all patients. Patients recorded their bowel function and symptoms daily for the entire study. The primary endpoint of the study was colonic geometric center at 24 hours, and secondary endpoints were; gastric emptying at 2 and 4 hours, colonic filling at 6 hours, colonic geometric center at 48 hours, proportion of responders, and individual symptoms and bowel functions. *Results There were no significant differences of the mean gastrointestinal transit measurements between the two groups, pre- and post-therapy. Overall, individual IBS symptoms and satisfactory relief of IBS were not different between VSL#3 and placebo group;* *however, abdominal bloating was significantly reduced in the VSL#3 group * (post vs pre, P = 0.04) and not in the placebo group (post vs pre, P = 0.78). *The scores for flatulence, abdominal pain, and urgency were not significantly reduced in patients treated with VSL#3.* All patients tolerated the VSL#3 well. One patient, who was later shown to be randomized to placebo, withdrew from the study due to a severe abdominal pain.Conclusion VSL#3 appears promising in the relief of abdominal bloating in patients with diarrhea-predominant IBS. *This effect is unrelated to alteration in gastrointestinal or colon transit.* Am J gastroenterol. 2002; 97(9): A830


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## Talissa (Apr 10, 2004)

Anmegrl, Thanks for the website. They do carry Metagenics, and as a bonus, they ship international! Woohoo! T-


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## Talissa (Apr 10, 2004)

Anmegrl, Thanks for the website. They do carry Metagenics, and as a bonus, they ship international! Woohoo! T-


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## Kacebece3 (Apr 17, 2002)

Hey Eric you poated "Probiotics have a different success rate in IBD conditions then in IBS. In IBD conditions where the OUTSIDE of the gut wall is inflammed they have been shown to help, but in IBS the outer gut wall is not inflammed." So what does it mean if the inner gut wall is inflamed?Later Ken


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## Kacebece3 (Apr 17, 2002)

Hey Eric you poated "Probiotics have a different success rate in IBD conditions then in IBS. In IBD conditions where the OUTSIDE of the gut wall is inflammed they have been shown to help, but in IBS the outer gut wall is not inflammed." So what does it mean if the inner gut wall is inflamed?Later Ken


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## Kacebece3 (Apr 17, 2002)

Hey Eric you posted "Probiotics have a different success rate in IBD conditions then in IBS. In IBD conditions where the OUTSIDE of the gut wall is inflammed they have been shown to help, but in IBS the outer gut wall is not inflammed." So what does it mean if the inner gut wall is inflammed?Later Ken


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## Kacebece3 (Apr 17, 2002)

Hey Eric you posted "Probiotics have a different success rate in IBD conditions then in IBS. In IBD conditions where the OUTSIDE of the gut wall is inflammed they have been shown to help, but in IBS the outer gut wall is not inflammed." So what does it mean if the inner gut wall is inflammed?Later Ken


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## eric (Jul 8, 1999)

Ken, in post infection IBS studies, thay have found after the RESOLUTION of an enteric infection, there were specific cells inflamed called mast cells in a subgroup of IBSers. They have a ton of research on all this in regards to IBS and a lot more being done.More is being done on all IBSers. All people don't come down with IBS, after a gut infection, but they found people under stress at the time of infection, could intiate IBS. They have even shown this with animal models.It is also believed due to the connnections between the HPA axis fighting infections and being the stress system escpecially the fight or flight. That after the infection, chronic stressors ( a real or perceived threat to the homeostasis of the organsim)inflames the cells without a pathogen.Which is one reason why I posted this recently.FYIDig Dis Sci. 2004 Jun;49(6):1046-53. Related Articles, Links Patients and nonconsulters with irritable bowel syndrome reporting a parental history of bowel problems have more impaired psychological distress.Kanazawa M, Endo Y, Whitehead WE, Kano M, Hongo M, Fukudo S.Center for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, North Carolina 27599-7080, USA. mkanazw###med.unc.eduLittle is known about the prevalence and risk factors for development of irritable bowel syndrome (IBS) in Japan. In the United States, it is reported that heredity and social learning contribute to the development of IBS. Our aims were (1) to estimate the prevalence of IBS, (2) to confirm that subjects with IBS are more likely to have parents with a history of bowel problems, (3) to confirm that gastroenteritis is a risk factor for IBS, and (4) to determine whether these two risk factors interact with psychological distress. Prevalence was estimated from a sample of 417 young adults seen for annual health screening examinations. To evaluate risk factors related to consulting physicians, the 46 subjects who fulfilled Rome II diagnostic criteria for IBS but denied ever having seen a physician about these symptoms (IBS non-consulters) were compared to the 317 subjects who did not meet the criteria for IBS (controls) and to a group of 56 patients diagnosed with IBS by gastroenterologists (IBS patients). All subjects completed the Gastrointestinal Symptoms Rating Scale, the State-Trait Anxiety Inventory, the Self-Rating Depression Scale, the Perceived Stress Scale, and the SF-36 quality of life scale. Fourteen and two-tenths percent (15.5% of females and 12.9% of males) of the community sample met the criteria for IBS diagnosis, of whom 22% consulted physicians. IBS patients and IBS nonconsulters were more likely than controls to have a parental history (33.9 vs. 12.6%, P 0.001, for patients and 26.1 vs. 12.6%, P 0.01, for nonconsulters) and were more likely to report an infective history compared to controls (44.6 vs. 16.1%, P 0.001, for patients and 32.6 vs. 16.1%, P 0.01, for nonconsulters). Two-way analysis of variance showed that the parental history was associated with a significantly greater impact on symptoms of indigestion, diarrhea, constipation, state and trait anxiety, and the SF-36 scales for social functioning and role emotional and that an infective history was associated with a greater impact on bodily pain. Both a parental history of bowel problems and a history of acute gastroenteritis are significant risk factors for development of IBS in Japan, as reported for the United States. Moreover, patients with such a family history show more psychological distress than other patients.PMID: 15309899Gastroenterology. 2003 Dec;125(6):1651-9. Related Articles, Links Relative importance of enterochromaffin cell hyperplasia, anxiety, and depression in postinfectious IBS.Dunlop SP, Jenkins D, Neal KR, Spiller RC.Wolfson Digestive Diseases Centre, University Hospital, Nottingham, England.BACKGROUND & AIMS: Both psychological and mucosal changes (increased enterochromaffin EC cells and T lymphocytes) have been associated with postinfectious irritable bowel syndrome (PI-IBS). However, previous studies have been underpowered to determine the relative importance of these changes in predicting the development of PI-IBS. Our aim was to prospectively determine the relative importance of both psychological and histologic factors in the development of PI-IBS after Campylobacter infection. METHODS: Questionnaires detailing psychological and bowel symptoms were sent to 1977 patients 3 months after infection. Twenty-eight patients with new-onset PI-IBS, 28 age- and sex-matched patient controls who were asymptomatic after infection, and 34 healthy volunteers underwent rectal biopsy, which was assessed for serotonin-containing EC cells, mast cells, and lamina propria T lymphocytes. RESULTS: PI-IBS, predominantly of the diarrhea-predominant subtype, occurred in 103 of 747 (13.8%) of those infected. EC cell counts per high-power field (hpf) were higher in patients with PI-IBS (35.8 +/- 1.2) compared with patient controls (30.6 +/- 1.9; P = 0.022) and volunteers (29.1 +/- 1.8; P = 0.006). Lamina propria T lymphocytes per hpf were higher in patients with PI-IBS (127.1 +/- 8.7) and patient controls (113.4 +/- 6.2) in contrast to healthy volunteers (97.1 +/- 5.7) (P = 0.006 and P = 0.058, respectively). Anxiety, depression, and fatigue were significantly increased in patients with PI-IBS compared with patient controls. Multivariate analysis indicated that increased EC cell counts and depression were equally important predictors of developing PI-IBS (relative risk, 3.8 and 3.2 for each standard deviation increase in respective values). CONCLUSIONS: Both increased EC cells and depression are important independent predictors of developing PI-IBS.PMID: 14724817 Also in PI IBS after resolution of the intial infection, they find an increase of mast cells and EC cells and the enterochromaffin cells (EC Cells) store the majoirty of the serotonin in the gut, which is used to intiate peristalsis.Serotonin is majorally implicated in IBS and almost all IBS patinets presenting to gastroenterologists effectively demonstrate serotonin dysregulation."IntroductionMany patients with irritable bowel syndrome (IBS) have walked into their physician's office and said, "The last doctor told me my symptoms were all in my head." Those physicians may have been right, but not in a way they anticipated.Over the past 50 years, evolving conceptual mechanisms have been proposed to explain the pathophysiology of IBS. These mechanisms have ranged from a purely psychological disorder to such physiologic conditions as a primary abnormality in gastrointestinal (GI) motility or visceral hypersensitivity. However, recent scientific data have increasingly supported that a dysregulation in brain-gut interactions resulting in alterations in GI motility, secretion, and sensation is the principal pathophysiologic mechanism underlying IBS.1 Brain-gut interactions are mediated largely by the autonomic nervous system, which is comprised of the parasympathetic (vagal and sacral parasympathetic), sympathetic, and enteric nervous systems (ENS). Many factors (both central and peripheral) may contribute to an altered brain-gut axis, including genetic predisposition, chronic stress, inflammation/infection, and environmental parameters.1 These alterations may subsequently lead to disturbances in intestinal motility, visceral sensitivity, and mucosal immune response and permeability. In IBS, these disturbances result in symptoms of abdominal pain or discomfort and altered bowel function, the defining characteristics of this disorder.2There are many neurotransmitters and hormones that mediate bidirectional brain-gut communication. Serotonin (5-hydroxytryptamine 5-HT) is one of the key mediators of gut motility, secretion, and sensation. Most of the serotonin is localized in the GI tract and is found in enterochromaffin (EC) cells and enteric neurons.3 EC cells sense luminal factors such as food or mechanical distension in the gut, and release serotonin; 5-HT receptors on intrinsic primary afferent neurons (IPANs) as well as extrinsic spinal or vagal afferent neurons are activated. The ENS regulates secretion and peristalsis, whereas vagal and spinal afferents modulate nonpainful and painful sensations, respectively.4 There are at least 7 main classes of 5-HT receptors. Particularly important for lower gut function and regulation are the 5-HT1P, 5-HT3, and 5-HT4 receptors." http://www.medscape.com/viewarticle/463521 So its not just mast cells here we talking about in PI IBS or the full clinical experssion of IBS either. Serotonin is also involved in signaling to the brain sensations and hence pain.Also as I have said many times, inflammation cannot be the diagnostic marker for ALL ibsers, because it does not always produce pain a must for IBS. However they believe the mast cells contribute to pain."Gastroenterology. 2004 Mar;126(3):693-702. Related Articles, Links Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome.Barbara G, Stanghellini V, De Giorgio R, Cremon C, Cottrell GS, Santini D, Pasquinelli G, Morselli-Labate AM, Grady EF, Bunnett NW, Collins SM, Corinaldesi R.Departmentof Internal Medicine and Gastroenterology, and CRBA, University of Bologna, Italy. gbarbara###med.unibo.itBACKGROUND & AIMS: The mechanisms underlying abdominal pain perception in irritable bowel syndrome (IBS) are poorly understood. Intestinal mast cell infiltration may perturb nerve function leading to symptom perception. We assessed colonic mast cell infiltration, mediator release, and spatial interactions with mucosal innervation and their correlation with abdominal pain in IBS patients. METHODS: IBS patients were diagnosed according to Rome II criteria and abdominal pain quantified according to a validated questionnaire. Colonic mucosal mast cells were identified immunohistochemically and quantified with a computer-assisted counting method. Mast cell tryptase and histamine release were analyzed immunoenzymatically. Intestinal nerve to mast cell distance was assessed with electron microscopy. RESULTS: Thirty-four out of 44 IBS patients (77%) showed an increased area of mucosa occupied by mast cells as compared with controls (9.2% +/- 2.5% vs. 3.3 +/- 0.8%, respectively; P 0.001). There was a 150% increase in the number of degranulating mast cells (4.76 +/- 3.18/field vs. 2.42 +/- 2.26/field, respectively; P = 0.026). Mucosal content of tryptase was increased in IBS and mast cells spontaneously released more tryptase (3.22 +/- 3.48 pmol/min/mg vs. 0.87 +/- 0.65 pmol/min/mg, respectively; P = 0.015) and histamine (339.7 +/- 59.0 ng/g vs. 169.3 +/- 130.6 ng/g, respectively; P = 0.015). Mast cells located within 5 microm of nerve fibers were 7.14 +/- 3.87/field vs. 2.27 +/- 1.63/field in IBS vs. controls (P 0.001). Only mast cells in close proximity to nerves were significantly correlated with severity and frequency of abdominal pain/discomfort (P 0.001 and P = 0.003, respectively). CONCLUSIONS: Colonic mast cell infiltration and mediator release in proximity to mucosal innervation may contribute to abdominal pain perception in IBS patients.PMID: 14988823Neurogastroenterol Motil. 2000 Oct;12(5):449-57. Related Articles, Links Increased mast cells in the irritable bowel syndrome.O'Sullivan M, Clayton N, Breslin NP, Harman I, Bountra C, McLaren A, O'Morain CA.Adelaide & Meath Hospitals, Trinity College Dublin, Ireland.Mast cells (MC) release potent mediators which alter enteric nerve and smooth muscle function and may play a role in the pathogenesis of the irritable bowel syndrome (IBS). The aim of this study was to determine if MC were increased in the colon of IBS patients compared to controls. Biopsy specimens were obtained from the caecum, ascending colon, descending colon and rectum of 28 patients: 14 IBS (Rome criteria); seven normal; and seven inflammatory controls. Tissue was stained immunohistochemically using a monoclonal mouse antibody for human mast cell tryptase (AA1). Tissue area occupied by tryptase-positive MC (volume density of mast cells) was quantified by image analysis. The number of plasma cells, lymphocytes, eosinophils, neutrophils and macrophages were each graded semiquantitatively (0-4) in haematoxylin and eosin stained sections. Mast cell volume density was significantly (P 0.05) higher in IBS (0.91 +/- 0.18; CI 0.79; 1.0) than normal controls (0.55 +/- 0.14; CI 0.40; 0.69) in the caecum but not at other sites. Apart from MC, there was no evidence of increased cellular infiltrate in the IBS group. MC were significantly increased in the caecum of IBS patients compared to controls. The multiple effects of the intestinal mast cell alone, or as a participant of a persistent inflammatory response, may be fundamental to the pathogenesis of IBS.PMID: 11012945There is way more on all this then I am posting now.They also have good research that the mast cells are connected to bladder problems in some IBSers.However, it is very important that the inflammation seen in sub groups of IBSers, is not like an IBD disease. It is macroscopic inflammation of specific cells that already have a ton of research on and are doing a lot more.They also know that stress can induced colonic epithelial barrier dysfunction in both animals and humans.Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat http://gut.bmjjournals.com/cgi/content/full/48/5/630 If you do a search on the HPA axis and stress and mast cells you'll find a lot of info, if you do one on infections and the HPA axis and mast cells you will find a whole lot more info.Mast cells are typically associated with allergies also, but they have found chronic stress can degradulated mast cells WITHOUT A PATHOGEN and this is a big area of IBS research at the moment as well and one they have been researching for many years now. How many IBSers do you think, view either conciously or subconciously that their IBS and symptoms like pain for example or when the IBS will hit ect.. are (a threat to the homeostasis of the organsim either real or perceieved)?


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## Talissa (Apr 10, 2004)

Ken,Interesting point. The inner intestinal wall is where the beneficial/probitics and pathogenic bacteria interact, along with other immune system cells.And with regards to IBS:"Attention has been directed to the putative role of low grade mucosal inflammation in irritable bowel syndrome (IBS) on the basis of evidence showing that some patients with IBS have an increased number of inflammatory cells in the colonic and ileal mucosa. Previous episodes of infectious enteritis, genetic factors, undiagnosed food allergies, and *changes in bacterial microflora* may all play a role in promoting and perpetuating this low grade inflammatory process." http://gut.bmjjournals.com/cgi/content/full/51/suppl_1/i41 The following info suggests that although the increase in cells is much less in IBS, there's an increase in the same cell types as in IBD~(July 2003)"Even though the magnitude of changes in cell numbers was far less than observed in patients with IBD, the increased numbers of IEL, T cells, IL-2 receptor expressing cells, suppressor/cytotoxic T cells, and NK cells were consistent with an increased inflammatory cell presence in a subset of patients with altered bowel habits who met the symptom-based Rome criteria for IBS. " http://www.medscape.com/viewarticle/457728_2 It doesn't specify the outer wall vs the inner, mucosal wall that lines the intestines...And further in the same article, they say that probiotic treatment for both IBS & IBD look promising, but are still preliminary. It surely doesn't say that probiotic treatments are more successful in one over the other~"Based on the concept of altered interactions between the colonic flora and the gut-associated immune system, probiotics have been proposed as an alternative strategy for the treatment of several gastrointestinal diseases, including IBD[39] and more recently IBS.[40, 41] *However, the reported results are conflicting, and only a small number of double-blind controlled clinical trials support a beneficial health effect in IBD or IBS.[42] * The epithelium has recently been recognized as playing an important role in innate immune responses in response to intestinal microorganisms.[43, 44] http://www.medscape.com/viewarticle/457728_4 The mucosal layer is the innermost layer of the gatrointestinal wall. It is primarily composed of epithelial tissue.The submucosa is the second layer and lies directly beneath the mucosal layer. The inflammation in IBS is often referred to as "low grade mucosal inflammation."The serosa is comprised of simple squamous epithelium that forms the outer layer of the GI wall (below the diaphram).So is it true? Is the inflammation in IBD only in the outer wall, the serosa???I don't think so, from what I've read.T-


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## eric (Jul 8, 1999)

Ken, in post infection IBS studies, thay have found after the RESOLUTION of an enteric infection, there were specific cells inflamed called mast cells in a subgroup of IBSers. They have a ton of research on all this in regards to IBS and a lot more being done.More is being done on all IBSers. All people don't come down with IBS, after a gut infection, but they found people under stress at the time of infection, could intiate IBS. They have even shown this with animal models.It is also believed due to the connnections between the HPA axis fighting infections and being the stress system escpecially the fight or flight. That after the infection, chronic stressors ( a real or perceived threat to the homeostasis of the organsim)inflames the cells without a pathogen.Which is one reason why I posted this recently.FYIDig Dis Sci. 2004 Jun;49(6):1046-53. Related Articles, Links Patients and nonconsulters with irritable bowel syndrome reporting a parental history of bowel problems have more impaired psychological distress.Kanazawa M, Endo Y, Whitehead WE, Kano M, Hongo M, Fukudo S.Center for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, North Carolina 27599-7080, USA. mkanazw###med.unc.eduLittle is known about the prevalence and risk factors for development of irritable bowel syndrome (IBS) in Japan. In the United States, it is reported that heredity and social learning contribute to the development of IBS. Our aims were (1) to estimate the prevalence of IBS, (2) to confirm that subjects with IBS are more likely to have parents with a history of bowel problems, (3) to confirm that gastroenteritis is a risk factor for IBS, and (4) to determine whether these two risk factors interact with psychological distress. Prevalence was estimated from a sample of 417 young adults seen for annual health screening examinations. To evaluate risk factors related to consulting physicians, the 46 subjects who fulfilled Rome II diagnostic criteria for IBS but denied ever having seen a physician about these symptoms (IBS non-consulters) were compared to the 317 subjects who did not meet the criteria for IBS (controls) and to a group of 56 patients diagnosed with IBS by gastroenterologists (IBS patients). All subjects completed the Gastrointestinal Symptoms Rating Scale, the State-Trait Anxiety Inventory, the Self-Rating Depression Scale, the Perceived Stress Scale, and the SF-36 quality of life scale. Fourteen and two-tenths percent (15.5% of females and 12.9% of males) of the community sample met the criteria for IBS diagnosis, of whom 22% consulted physicians. IBS patients and IBS nonconsulters were more likely than controls to have a parental history (33.9 vs. 12.6%, P 0.001, for patients and 26.1 vs. 12.6%, P 0.01, for nonconsulters) and were more likely to report an infective history compared to controls (44.6 vs. 16.1%, P 0.001, for patients and 32.6 vs. 16.1%, P 0.01, for nonconsulters). Two-way analysis of variance showed that the parental history was associated with a significantly greater impact on symptoms of indigestion, diarrhea, constipation, state and trait anxiety, and the SF-36 scales for social functioning and role emotional and that an infective history was associated with a greater impact on bodily pain. Both a parental history of bowel problems and a history of acute gastroenteritis are significant risk factors for development of IBS in Japan, as reported for the United States. Moreover, patients with such a family history show more psychological distress than other patients.PMID: 15309899Gastroenterology. 2003 Dec;125(6):1651-9. Related Articles, Links Relative importance of enterochromaffin cell hyperplasia, anxiety, and depression in postinfectious IBS.Dunlop SP, Jenkins D, Neal KR, Spiller RC.Wolfson Digestive Diseases Centre, University Hospital, Nottingham, England.BACKGROUND & AIMS: Both psychological and mucosal changes (increased enterochromaffin EC cells and T lymphocytes) have been associated with postinfectious irritable bowel syndrome (PI-IBS). However, previous studies have been underpowered to determine the relative importance of these changes in predicting the development of PI-IBS. Our aim was to prospectively determine the relative importance of both psychological and histologic factors in the development of PI-IBS after Campylobacter infection. METHODS: Questionnaires detailing psychological and bowel symptoms were sent to 1977 patients 3 months after infection. Twenty-eight patients with new-onset PI-IBS, 28 age- and sex-matched patient controls who were asymptomatic after infection, and 34 healthy volunteers underwent rectal biopsy, which was assessed for serotonin-containing EC cells, mast cells, and lamina propria T lymphocytes. RESULTS: PI-IBS, predominantly of the diarrhea-predominant subtype, occurred in 103 of 747 (13.8%) of those infected. EC cell counts per high-power field (hpf) were higher in patients with PI-IBS (35.8 +/- 1.2) compared with patient controls (30.6 +/- 1.9; P = 0.022) and volunteers (29.1 +/- 1.8; P = 0.006). Lamina propria T lymphocytes per hpf were higher in patients with PI-IBS (127.1 +/- 8.7) and patient controls (113.4 +/- 6.2) in contrast to healthy volunteers (97.1 +/- 5.7) (P = 0.006 and P = 0.058, respectively). Anxiety, depression, and fatigue were significantly increased in patients with PI-IBS compared with patient controls. Multivariate analysis indicated that increased EC cell counts and depression were equally important predictors of developing PI-IBS (relative risk, 3.8 and 3.2 for each standard deviation increase in respective values). CONCLUSIONS: Both increased EC cells and depression are important independent predictors of developing PI-IBS.PMID: 14724817 Also in PI IBS after resolution of the intial infection, they find an increase of mast cells and EC cells and the enterochromaffin cells (EC Cells) store the majoirty of the serotonin in the gut, which is used to intiate peristalsis.Serotonin is majorally implicated in IBS and almost all IBS patinets presenting to gastroenterologists effectively demonstrate serotonin dysregulation."IntroductionMany patients with irritable bowel syndrome (IBS) have walked into their physician's office and said, "The last doctor told me my symptoms were all in my head." Those physicians may have been right, but not in a way they anticipated.Over the past 50 years, evolving conceptual mechanisms have been proposed to explain the pathophysiology of IBS. These mechanisms have ranged from a purely psychological disorder to such physiologic conditions as a primary abnormality in gastrointestinal (GI) motility or visceral hypersensitivity. However, recent scientific data have increasingly supported that a dysregulation in brain-gut interactions resulting in alterations in GI motility, secretion, and sensation is the principal pathophysiologic mechanism underlying IBS.1 Brain-gut interactions are mediated largely by the autonomic nervous system, which is comprised of the parasympathetic (vagal and sacral parasympathetic), sympathetic, and enteric nervous systems (ENS). Many factors (both central and peripheral) may contribute to an altered brain-gut axis, including genetic predisposition, chronic stress, inflammation/infection, and environmental parameters.1 These alterations may subsequently lead to disturbances in intestinal motility, visceral sensitivity, and mucosal immune response and permeability. In IBS, these disturbances result in symptoms of abdominal pain or discomfort and altered bowel function, the defining characteristics of this disorder.2There are many neurotransmitters and hormones that mediate bidirectional brain-gut communication. Serotonin (5-hydroxytryptamine 5-HT) is one of the key mediators of gut motility, secretion, and sensation. Most of the serotonin is localized in the GI tract and is found in enterochromaffin (EC) cells and enteric neurons.3 EC cells sense luminal factors such as food or mechanical distension in the gut, and release serotonin; 5-HT receptors on intrinsic primary afferent neurons (IPANs) as well as extrinsic spinal or vagal afferent neurons are activated. The ENS regulates secretion and peristalsis, whereas vagal and spinal afferents modulate nonpainful and painful sensations, respectively.4 There are at least 7 main classes of 5-HT receptors. Particularly important for lower gut function and regulation are the 5-HT1P, 5-HT3, and 5-HT4 receptors." http://www.medscape.com/viewarticle/463521 So its not just mast cells here we talking about in PI IBS or the full clinical experssion of IBS either. Serotonin is also involved in signaling to the brain sensations and hence pain.Also as I have said many times, inflammation cannot be the diagnostic marker for ALL ibsers, because it does not always produce pain a must for IBS. However they believe the mast cells contribute to pain."Gastroenterology. 2004 Mar;126(3):693-702. Related Articles, Links Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome.Barbara G, Stanghellini V, De Giorgio R, Cremon C, Cottrell GS, Santini D, Pasquinelli G, Morselli-Labate AM, Grady EF, Bunnett NW, Collins SM, Corinaldesi R.Departmentof Internal Medicine and Gastroenterology, and CRBA, University of Bologna, Italy. gbarbara###med.unibo.itBACKGROUND & AIMS: The mechanisms underlying abdominal pain perception in irritable bowel syndrome (IBS) are poorly understood. Intestinal mast cell infiltration may perturb nerve function leading to symptom perception. We assessed colonic mast cell infiltration, mediator release, and spatial interactions with mucosal innervation and their correlation with abdominal pain in IBS patients. METHODS: IBS patients were diagnosed according to Rome II criteria and abdominal pain quantified according to a validated questionnaire. Colonic mucosal mast cells were identified immunohistochemically and quantified with a computer-assisted counting method. Mast cell tryptase and histamine release were analyzed immunoenzymatically. Intestinal nerve to mast cell distance was assessed with electron microscopy. RESULTS: Thirty-four out of 44 IBS patients (77%) showed an increased area of mucosa occupied by mast cells as compared with controls (9.2% +/- 2.5% vs. 3.3 +/- 0.8%, respectively; P 0.001). There was a 150% increase in the number of degranulating mast cells (4.76 +/- 3.18/field vs. 2.42 +/- 2.26/field, respectively; P = 0.026). Mucosal content of tryptase was increased in IBS and mast cells spontaneously released more tryptase (3.22 +/- 3.48 pmol/min/mg vs. 0.87 +/- 0.65 pmol/min/mg, respectively; P = 0.015) and histamine (339.7 +/- 59.0 ng/g vs. 169.3 +/- 130.6 ng/g, respectively; P = 0.015). Mast cells located within 5 microm of nerve fibers were 7.14 +/- 3.87/field vs. 2.27 +/- 1.63/field in IBS vs. controls (P 0.001). Only mast cells in close proximity to nerves were significantly correlated with severity and frequency of abdominal pain/discomfort (P 0.001 and P = 0.003, respectively). CONCLUSIONS: Colonic mast cell infiltration and mediator release in proximity to mucosal innervation may contribute to abdominal pain perception in IBS patients.PMID: 14988823Neurogastroenterol Motil. 2000 Oct;12(5):449-57. Related Articles, Links Increased mast cells in the irritable bowel syndrome.O'Sullivan M, Clayton N, Breslin NP, Harman I, Bountra C, McLaren A, O'Morain CA.Adelaide & Meath Hospitals, Trinity College Dublin, Ireland.Mast cells (MC) release potent mediators which alter enteric nerve and smooth muscle function and may play a role in the pathogenesis of the irritable bowel syndrome (IBS). The aim of this study was to determine if MC were increased in the colon of IBS patients compared to controls. Biopsy specimens were obtained from the caecum, ascending colon, descending colon and rectum of 28 patients: 14 IBS (Rome criteria); seven normal; and seven inflammatory controls. Tissue was stained immunohistochemically using a monoclonal mouse antibody for human mast cell tryptase (AA1). Tissue area occupied by tryptase-positive MC (volume density of mast cells) was quantified by image analysis. The number of plasma cells, lymphocytes, eosinophils, neutrophils and macrophages were each graded semiquantitatively (0-4) in haematoxylin and eosin stained sections. Mast cell volume density was significantly (P 0.05) higher in IBS (0.91 +/- 0.18; CI 0.79; 1.0) than normal controls (0.55 +/- 0.14; CI 0.40; 0.69) in the caecum but not at other sites. Apart from MC, there was no evidence of increased cellular infiltrate in the IBS group. MC were significantly increased in the caecum of IBS patients compared to controls. The multiple effects of the intestinal mast cell alone, or as a participant of a persistent inflammatory response, may be fundamental to the pathogenesis of IBS.PMID: 11012945There is way more on all this then I am posting now.They also have good research that the mast cells are connected to bladder problems in some IBSers.However, it is very important that the inflammation seen in sub groups of IBSers, is not like an IBD disease. It is macroscopic inflammation of specific cells that already have a ton of research on and are doing a lot more.They also know that stress can induced colonic epithelial barrier dysfunction in both animals and humans.Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat http://gut.bmjjournals.com/cgi/content/full/48/5/630 If you do a search on the HPA axis and stress and mast cells you'll find a lot of info, if you do one on infections and the HPA axis and mast cells you will find a whole lot more info.Mast cells are typically associated with allergies also, but they have found chronic stress can degradulated mast cells WITHOUT A PATHOGEN and this is a big area of IBS research at the moment as well and one they have been researching for many years now. How many IBSers do you think, view either conciously or subconciously that their IBS and symptoms like pain for example or when the IBS will hit ect.. are (a threat to the homeostasis of the organsim either real or perceieved)?


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## Talissa (Apr 10, 2004)

Ken,Interesting point. The inner intestinal wall is where the beneficial/probitics and pathogenic bacteria interact, along with other immune system cells.And with regards to IBS:"Attention has been directed to the putative role of low grade mucosal inflammation in irritable bowel syndrome (IBS) on the basis of evidence showing that some patients with IBS have an increased number of inflammatory cells in the colonic and ileal mucosa. Previous episodes of infectious enteritis, genetic factors, undiagnosed food allergies, and *changes in bacterial microflora* may all play a role in promoting and perpetuating this low grade inflammatory process." http://gut.bmjjournals.com/cgi/content/full/51/suppl_1/i41 The following info suggests that although the increase in cells is much less in IBS, there's an increase in the same cell types as in IBD~(July 2003)"Even though the magnitude of changes in cell numbers was far less than observed in patients with IBD, the increased numbers of IEL, T cells, IL-2 receptor expressing cells, suppressor/cytotoxic T cells, and NK cells were consistent with an increased inflammatory cell presence in a subset of patients with altered bowel habits who met the symptom-based Rome criteria for IBS. " http://www.medscape.com/viewarticle/457728_2 It doesn't specify the outer wall vs the inner, mucosal wall that lines the intestines...And further in the same article, they say that probiotic treatment for both IBS & IBD look promising, but are still preliminary. It surely doesn't say that probiotic treatments are more successful in one over the other~"Based on the concept of altered interactions between the colonic flora and the gut-associated immune system, probiotics have been proposed as an alternative strategy for the treatment of several gastrointestinal diseases, including IBD[39] and more recently IBS.[40, 41] *However, the reported results are conflicting, and only a small number of double-blind controlled clinical trials support a beneficial health effect in IBD or IBS.[42] * The epithelium has recently been recognized as playing an important role in innate immune responses in response to intestinal microorganisms.[43, 44] http://www.medscape.com/viewarticle/457728_4 The mucosal layer is the innermost layer of the gatrointestinal wall. It is primarily composed of epithelial tissue.The submucosa is the second layer and lies directly beneath the mucosal layer. The inflammation in IBS is often referred to as "low grade mucosal inflammation."The serosa is comprised of simple squamous epithelium that forms the outer layer of the GI wall (below the diaphram).So is it true? Is the inflammation in IBD only in the outer wall, the serosa???I don't think so, from what I've read.T-


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## Talissa (Apr 10, 2004)

The info on the wall layers can be found here: http://hmi.sinclair.edu/module_lesson.asp?...10&LessonID=131


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## Talissa (Apr 10, 2004)

The info on the wall layers can be found here: http://hmi.sinclair.edu/module_lesson.asp?...10&LessonID=131


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## Talissa (Apr 10, 2004)

Well, no,the inflammation in IBD is NOT in the outer wall as Eric said, but the inner wall, the mucosal layer, just like in IBS.But with IBS, the inflammation is "low grade" in the mucosal layer.Ex of over 2000 sites which discuss the mucosal inflammation of IBD:


> quoteTNF-) was among the first mucosal cytokines identified as critical in the development and amplification of mucosal inflammation in IBD.[26]


So really, the inflammation is just higher in IBD, not in a different layer.And probiotic treatments in clinical settings are in the early stages for _BOTH_ IBS & IBD.


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## Talissa (Apr 10, 2004)

Well, no,the inflammation in IBD is NOT in the outer wall as Eric said, but the inner wall, the mucosal layer, just like in IBS.But with IBS, the inflammation is "low grade" in the mucosal layer.Ex of over 2000 sites which discuss the mucosal inflammation of IBD:


> quoteTNF-) was among the first mucosal cytokines identified as critical in the development and amplification of mucosal inflammation in IBD.[26]


So really, the inflammation is just higher in IBD, not in a different layer.And probiotic treatments in clinical settings are in the early stages for _BOTH_ IBS & IBD.


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## eric (Jul 8, 1999)

The above info is the layers in general, not IBS mast cell images just fyi.Activated Mast Cells in Proximity to Colonic Nerves Correlate With Abdominal Pain in Irritable Bowel SyndromeGIOVANNI BARBARA,* VINCENZO STANGHELLINI,* ROBERTO DE GIORGIO,* CESARE CREMON,*GRAEME S. COTTRELL,ï¿½ DONATELLA SANTINI,ï¿½ GIANANDREA PASQUINELLI,ï¿½ANTONIO M. MORSELLIï¿½LABATE,* EILEEN F. GRADY,ï¿½ NIGEL W. BUNNETT,ï¿½STEPHEN M. COLLINS,ï¿½ and ROBERTO CORINALDESI**Department of Internal Medicine and Gastroenterology, and CRBA, University of Bologna, Bologna, Italy; ï¿½Departments of Surgery andPhysiology, University of California San Francisco, San Francisco, California; ï¿½Department of Pathology, University of Bologna, Bologna, Italy;and ï¿½Division of Gastroenterology, McMaster University, Ontario, CanadaBackground & Aims: The mechanisms underlying abdominal pain perception in irritable bowel syndrome (IBS) are poorly understood. Intestinal mast cell inﬁltration may perturb nerve function leading to symptom perception. We assessed colonic mast cell inﬁltration, mediator release, and spatial interactions with mucosal innervation and their correlation with abdominal pain in IBS patients. Methods: IBS patients were diagnosed accordingto Rome II criteria and abdominal pain quanti-ﬁed according to a validated questionnaire. Colonic mucosalmast cells were identiﬁed immunohistochemicallyand quantiﬁed with a computer-assisted countingmethod. Mast cell tryptase and histamine release wereanalyzed immunoenzymatically. Intestinal nerve to mastcell distance was assessed with electron microscopy.Results: Thirty-four out of 44 IBS patients (77%) showedan increased area of mucosa occupied by mast cells ascompared with controls (9.2%  2.5% vs. 3.3  0.8%,respectively; P 0.001). There was a 150% increase inthe number of degranulating mast cells (4.76  3.18/ﬁeld vs. 2.42  2.26/ﬁeld, respectively; P  0.026).Mucosal content of tryptase was increased in IBS andmast cells spontaneously released more tryptase(3.22  3.48 pmol/min/mg vs. 0.87  0.65 pmol/min/mg, respectively; P  0.015) and histamine (339.7 59.0 ng/g vs. 169.3  130.6 ng/g, respectively; P 0.015). Mast cells located within 5 m of nerve ﬁberswere 7.14  3.87/ﬁeld vs. 2.27  1.63/ﬁeld in IBS vs.controls (P 0.001). Only mast cells in close proximityto nerves were signiﬁcantly correlated with severity andfrequency of abdominal pain/discomfort (P 0.001and P  0.003, respectively). Conclusions: Colonic mastcell inﬁltration and mediator release in proximity tomucosal innervation may contribute to abdominal painperception in IBS patients.Irritable bowel syndrome (IBS) is one of the mostcommon gastrointestinal disorders seen in primarycare and specialist practice characterized by abdominaldiscomfort or pain and disturbed defecation that cannotbe explained by structural or biochemical abnormalities.1Abdominal pain/discomfort is the hallmark symptomof IBS,1 which correlates with the overall severity of thedisease.2 The pathogenesis of IBS symptoms is looselyunderstood. Although gut motor abnormalities may accountfor alterations in gut transit, they are poorlycorrelated with patientsï¿½ abdominal pain/discomfort.3There is general agreement that increased sensitivity tostimuli arising from the gut wall (i.e., visceral hypersensitivity)contributes to abdominal pain/discomfort in atleast a subset of IBS patients.4 Several mechanisms arethought to be involved in the visceral hypersensitivity ofIBS patients,5 including (1) modulatory effect of thecentral nervous system in response to information conveyedfrom the gut, (2) hyperexcitability of dorsal hornneurons in the central limb of the visceral afferent pathway,and (3) sensitization of sensory neural endings at theend-organ level.The causes underlying the end-organ hypersensitivityin IBS are only partially understood. It has been hypothesizedthat a low-grade inflammatory response at thelevel of the gut wall could be involved.5,6 Consistentwith this hypothesis is evidence that at least certainsubsets of IBS patients have an increased number ofinflammatory cells in the colonic7 and ileal8 mucosa aswell as in muscularis externa of jejunum.9 Also, IBS maydevelop after a bout of acute infectious gastroenteritis6,10,11and during periods of remission from inflammatorybowel disease.12 However, these previous studies doAbbreviations used in this paper: BABIM, bis(5-amidino-2-benzimidazolyl)methane; BSA, bovine serum albumin; IBS, irritable bowelsyndrome; PAR, proteinase-activated receptors; SBTI, soybean trypsininhibitor.ï¿½ 2004 by the American Gastroenterological Association0016-5085/04/$30.00doi:10.1053/j.gastro.2003.11.055GASTROENTEROLOGY 2004;126:693ï¿½702not provide insights into the possible mechanisms involvedin the altered sensory-motor function of IBS.A number of reasons raise the hypothesis that mastcells could be involved in the disturbed sensory-motorfunction of IBS. First, an increased number of these cellshas been detected in the colonic7,13 and ileal8 mucosa ofIBS patients. Second, in the human intestine, mast cellslie in close proximity to mucosal innervation.14,15 Third,animal studies demonstrated that, upon activation, mastcells release mediators that cause increased excitability ofenteric16,17 and primary afferent neurons,18 leading tovisceral hypersensitivity19 and abnormal gut motor function.20Tryptase and histamine are two major inflammatorymediators released during mast cell degranulation.21Tryptase, like other proteases, signals to cells throughproteinase activated receptors (PARs).22 Proteases cleavewithin the extracellular N-terminal tails of PARs toexpose tethered ligand domains that bind and activatecleaved receptors.22 Of the 4 cloned PARs, tryptaseselectively activates PAR-2.17,23 Mast cell tryptase inducesactivation of PAR-2 located on enteric nerves andvisceral afferents causing long-lasting neuronal hyperexcitability.16,17,24 Histamine can also activate visceral afferents18and enteric neurons25 via interaction with H1 orH2 receptors.26,27 Thus, both tryptase and histamine arecandidate mediators for disturbed gut sensory-motorfunction.The aims of the present study were to assess theimpact of colonic mast cell infiltration and activation, aswell as mast cell-to-mucosal innervation relationship onthe severity and frequency of abdominal pain/discomfortof IBS patients.Materials and MethodsPatientsIBS patients were all seen in the Department of InternalMedicine and Gastroenterology of the University of Bolognaand met the Rome II criteria.1 Healthy controls wererecruited by public advertisement and included in the studyafter thorough exclusion of gastrointestinal complaints. Noneof the study participants were taking nonsteroidal anti-inflammatorydrugs or other anti-inflammatory drugs (includingmast cell stabilizers, immunosuppressants, and steroids); hadundergone major abdominal surgery; or had any organic syndrome,asthma, celiac disease (excluded by detection of antitransglutaminaseand anti-endomysial antibodies), allergic diseases(including exclusion of a history of food allergies and, bypresence of food specific IgE antibodies), intestinal bacterial ormycotic contamination, metabolic or psychiatric disease asdiagnosed by history taking, consultations, and appropriatelaboratory tests. They all gave written informed consent, andthe study was approved by the local Ethical Committee andconducted in accordance with the Declaration of Helsinki.All participants underwent left colonoscopy after cleansingof distal colon with two 500-mL water enemas performed theevening before and the morning of the procedure. In all cases,4 mucosal biopsy specimens were obtained from the proximaldescending colon. Two biopsy specimens were used for routineH&E histology and immunohistochemistry and 2 for electronmicroscopy. In 36 unselected cases, 4 additional biopsy specimenscould be obtained for histamine and tryptase releaseassays and tryptase Western blotting.Symptom QuestionnaireEach patient completed a modified version of theBowel Disease Questionnaire (BDQ) to evaluate symptoms.28An Italian version of the questionnaire has been previouslyused in IBS studies in our country.29Patients were asked to score frequency and severity of theirsymptoms over the last 2 weeks before interview. In fact,recollection is poor beyond this limit, and shorter periodsmight not appropriately reflect the usual clinical picture andthis time frame has been previously shown to be a reliablepredictor of average pain intensity.30 The severity of abdominalpain/discomfort was graded 0ï¿½4 according to its influenceon patientsï¿½ usual activities: 0, absent; 1, mild (not influencingusual activities); 2, relevant (diverting from, but not urgingmodification of, usual activities); 3, severe (influencing usualactivities markedly enough to urge modifications); 4, extremelysevere (precluding daily activities). The frequency ofabdominal pain/discomfort was graded 0ï¿½4 according to thefollowing scale: 0, absent; 1, up to 1 day/week; 2, 2 or 3days/week; 3, 4ï¿½6 days/week; 4, daily. Furthermore, the followingsymptoms were assessed as present/absent: diarrhea,constipation, bloating/distention, flatulence, relief of abdominalpain/discomfort by defecation or passage of air per rectum,mucus in stool, onset of symptoms associated with a change infrequency (or form) of stool, hard or lumpy stool, loose orwatery stool, straining during a bowel movement, urgency,and feeling of incomplete bowel movement.Histology and ImmunohistochemistryBiopsy specimens were fixed in buffered 10% formalinand processed for either H&E histology or immunohistochemistry.For the latter, paraffin-embedded specimens were cutwith a microtome at 3ï¿½4 m, mounted on to gelatin-coatedslides, and processed either for immunohistochemistry or indirectimmunofluorescence using widely applied methods.Briefly, for single-labeling immunohistochemistry, followingantigen unmasking, randomly selected sections were incubatedwith mouse monoclonal antibodies directed against tryptase(mast cell marker; diluted at 1:2000; Dakopatts Glostrup,Denmark) overnight at 4ï¿½C. Following thorough washingwith PBS, slides were reincubated for 2 hours at room temperaturewith secondary biotinylated anti-mouse-rabbit antibodies(1:200; Dakopatts Glostrup, Denmark) followed bystreptavidin-horseradish peroxidase conjugate. For immuno-694 BARBARA ET AL. GASTROENTEROLOGY Vol. 126, No. 3fluorescence, slides were processed as described above with theonly difference that sections were reincubated for 2 hours atroom temperature with rhodamine or fluoresceine-conjugatedsecondary antibodies (1:100; Dakopatts Glostrup).Mast Cell CountsAll histologic sections were evaluated by an expertpathologist (D.S.), who was unaware of the diagnosis, forexclusion of overt mucosal inflammation or microscopic colitis.Quantification of inflammatory cells was performed on sectionsimmunostained for mast cells with a Leitz Dialux microscope(equipped with a Ploem epi-illumination system with ï¿½N2ï¿½filter cube to detect rhodamine fluorescence) in blind fashionusing a computer-assisted analysis system (Cytometrica###software;C&V, Bologna, Italy). Measurements were performed using amodification of a previously published method.31 Briefly, microscopicfields were digitized and randomly sampled with the aid ofa grid (0.5 mm2) located below the slide. A stereological gridcontaining cross-shaped points was overlaid on the digitizedsampled fields by the computer software and used to determinethe area occupied by mast cells over that occupied by laminapropria (i.e., number of points hitting the cells divided by thetotal number of cross-shaped points in the lamina propria).Electron MicroscopyBiopsy specimens were fixed in cacodylate-buffered2.5% glutaraldehyde for 4 to 6 hours at 4ï¿½C and postfixed in1% osmium tetroxide for 1 hour at 4ï¿½C. After dehydration andembedding in araldite, semithin sections were stained withtoluidine blue and examined under a light microscope. Apathologist (G.P.) performed a blind analysis of all sections.Representative portions of the intestinal mucosa (i.e., absenceof artifacts) were selected for ultrathin sectioning. Thin sectionswere collected on 200 mesh grids, stained with uranylacetate and lead citrate, and observed with a Philips 410 Ttransmission electron microscope. After exclusion of fieldsexclusively comprising epithelial structures, 10 randomly selectedfields of the intestinal mucosa measuring 90 m2 wereexamined for each sample. In each field (9100 magnification),the following parameters were recorded: total number ofmast cells, number of mast cells with degranulation features(i.e., labyrinthic membranous arrays or clearing of individualgranules), and number of mast cells located within 5 m ofnerve fibers.Tryptase Western BlottingMucosal biopsy specimens were frozen in liquid nitrogenand then rinsed in PBS. Biopsy specimens were thenhomogenized in Camiolo buffer (75 mmol/L potassium acetate,300 mmol/L NaCl, 100 mmol/L L-arginine, 10 mmol/LEDTA, 0.25% Triton X-100, pH 7.4) for 1 minute at 4ï¿½C.The homogenized sample was then centrifuged at 3000 rpmfor 15 minutes at 4ï¿½C. The supernatant was then transferred toa fresh tube and assayed for protein content. Protein concentrationswere determined using the bicinchoninic acid assay,32with bovine serum albumin (BSA) as standard. The methodwas adapted for use in 96-well microtiter plates. Equalamounts of protein (15 g) from each patient were separatedusing a 7%ï¿½17% PAGE. After electrophoresis, proteins weretransferred to a polyvinylidene fluoride membrane (Millipore,Billerica, MA) and then blocked (1X PBS, 2% BSA, 5% milkpowder, 0.1% Tween 20) for 1 hour at room temperature. Themembrane was then incubated overnight at 4ï¿½C with ananti-human mast cell tryptase antibody (1:5000; Chemicon,Temecula, CA). After washing (1X PBS, 0.1% Tween 20), themembrane was incubated for 1 hour at room temperature witha goat anti-mouse-horseradish peroxidase antibody (1:10,000;Jackson Laboratories, West Grove, PA). Following a secondwash, immunoreactive proteins were visualized by chemiluminescence(ECL kit, Amersham-Pharmacia, Piscataway, NJ).Results are representative of 3 separate blots.Tryptase and Histamine ReleaseSpontaneous release of tryptase and histamine frommucosal biopsy specimens was evaluated using a modificationof a previously described method.33 Briefly, upon removal,mucosal biopsy specimens were rapidly immersed in hardplastic tubes containing 2 mL of Hanksï¿½ solution (37ï¿½C) andcontinuously oxygenated (95% O2/5% CO2). After 25-minuteincubation, 200 L of the bathing solution was removed.Samples to be processed for histamine assay only were immediatelyheated at 95ï¿½C to avoid rapid denaturation of histamineby degrading enzymes (histaminases). All samples werecentrifuged at 200g for 10 minutes, and 150 L of supernatantwere aliquoted and stored at 70ï¿½C until the assay. At the endof the release experiment, biopsy specimens were blotted andweighed. For tryptase activity triplicate aliquots (10 L) of thesupernatants were added to 200 L of buffer (50 mmol/LTris/HCl, pH 7.6, 120 mmol/L NaCl, 20 g/mL heparin)containing 0.5 mmol/L substrate (tosyl-Glycine-Proline-Arginine-pNitroanilide) and incubated at room temperature for 17hours ( inhibitors as indicated). Cleavage of the substrate wasmeasured using a microtiter plate reader (absorbance 405 nm)and normalized to the weight of the biopsy specimens used ineach case. Histamine was detected from triplicate aliquots (50L) of the supernatants using a highly selective enzyme-linkedimmunoassay (Immunotech, Marseille, France) according tothe manufacturerï¿½s directions. Histamine was measured usinga microtiter plate reader (absorbance 405 nm) and normalizedto the weight of the biopsy specimens.Data Expression and Statistical AnalysisUnless otherwise stated, data are reported as meanvalues  standard deviation (SD). Data relative to electronmicroscopy studies are presented as mean values  SD relativeto 10 electron microscopic fields. Data were analyzed by meansof the Mannï¿½Whitney U and the Yatesï¿½ corrected 2 tests.Correlations were analyzed using the Spearman rank correlationtest. Analyses were done by running the SPSS/PC (SPSS,Inc, Chicago, IL) statistical package on a personal computer.Two-tailed P values less than 0.05 were considered statisticallysignificant.March 2004 NEUROIMMUNE INTERACTIONS AND IBS 695ResultsPatientsForty-four consecutive patients with IBS (aged22ï¿½75 years; mean, 40.1 years; 31 females, 13 males) aswell as 22 healthy controls (aged 20ï¿½71 years; mean,32.5 years; 12 females, 10 males) participated in thestudy. All patients complained of abdominal pain/discomfort(severity score: 1.78  1.15; frequency score:2.20  1.49; mean  SD); 50% had diarrhea and 50%constipation; furthermore, the most frequently associatedsymptom was bloating (97.8%).Mast Cell CountsThirty-four (77.3%) of the 44 IBS patients had anincreased mucosal cell area occupied by mast cells (i.e.,greater than the mean  2SD of controls: 4.8%). Asshown in Table 1 and Figure 1, the mean area of mucosaoccupied by tryptase positive mast cells was 181%greater in IBS patients with respect to healthy controls.The mucosal area occupied by mast cells was not differentin diarrhea and constipation predominant subgroups(P  0.096). A significant increase in the mean areaoccupied by mast cells was identified in both male andfemale IBS patients, compared with the respective controlgroups (Table 1). However, the mean area occupiedby mast cells in female IBS patients was 43% greaterthan that observed in male IBS patients (Table 1).Mast Cell DegranulationTo assess the state of activation of mast cells, wequantified the number of mast cells showing ultrastructuralfeatures of degranulation, including labyrinthicmembranous arrays and clearing of individual granules.Degranulating mast cells could be observed in samplesfrom both IBS patients and controls. However, quantitativeanalysis of degranulating mast cells showed a150% significant increase in IBS patients with respect tocontrols (4.76  3.18 cells/10 fields vs. 2.42  2.26cells/10 fields, respectively, P  0.026).Tryptase Western BlotsWe quantified the total amount of tryptase, themajor protease contained in mast cell secretory granules.Using an antibody directed against human mast celltryptase, we found a 35-kilodalton broad band on Westernblots (Figure 2). All controls had the same molecularweight band, which is the expected size for tryptase(Figure 2). Only 1 out of 6 controls had an elevated levelof tryptase (Figure 2). In sharp contrast, 5 out of 6 biopsyTable 1. Mucosal Mast Cell CountsAll Female MaleP value(male vs. female) Diarrhea ConstipationP value(vs. diarrhea)Controls (n  22) 3.3  0.8 3.4  0.5 3.1  0.9 NS ï¿½ ï¿½ NAIBS (n  44) 9.2  2.5a 10.0  2.3b 7.0  1.6c 0.001 8.6  2.7 9.7  2.1 NSNS, not significant, P 0.05; NA, not applicable.aSignificant difference vs. controls (P  0.001).bSignificant difference vs. controls (P  0.001).cSignificant difference vs. controls (P  0.001).Figure 1. Representative photomicrographs showing tryptase positive mast cells in the colonic mucosa of a healthy control (A) and an IBSpatient (







. Note the higher number of positive mast cells in the IBS patient as compared with the control. (bar  25 m.)696 BARBARA ET AL. GASTROENTEROLOGY Vol. 126, No. 3specimens obtained from patients with IBS containedmuch higher levels of immunoreactive tryptase (Figure2). Because of the broad range of molecular weight, wedid not quantify the increase in intensity.Tryptase ReleaseThe level of tryptase activity that was spontaneouslyreleased from mucosal biopsy specimens was quantified inthe cleared supernatants obtained by a 25-minute incubationof biopsy specimens in oxygenated buffer using anenzymatic assay. As shown in Figure 3, the level of tryptaseactivity in IBS patients was 3.7 times higher than thatfound in healthy controls (P  0.015). Both in control andIBS samples, this activity was significantly inhibited by theaddition of the tryptase inhibitor bis(5-amidino-2-benzimidazolyl)methane (BABIM; 100 mol/L) (P  0.013 andP  0.003, respectively), but not by the trypsin inhibitorsoybean trypsin inhibitor (SBTI; 50 g/mL) (P  0.794and P0.594, respectively), thus showing that the activitymeasured in the assay was specific for tryptase.Histamine ReleaseThe spontaneous release of histamine from mucosalbiopsy specimens of IBS patients and controls wasmeasured in the cleared supernatants obtained by a 25-minute incubation of biopsy specimens in oxygenatedbuffer using an enzymatic assay. As shown in Figure 4,histamine activity in IBS patients was significantly increasedby 101% over the activity found in controls (P 0.015).Mast Cellï¿½Nerve InteractionsIn the colonic mucosa of both healthy controlsand IBS patients, mast cells were frequently found inclose proximity to intestinal nerves (Figure 5Aï¿½D) andmembrane-membrane contacts were occasionally observedin both groups (Figure 5B). Mast cells undergoingactive degranulation in proximity to nerve trunks werealso occasionally identified (Figure 5Bï¿½D). Because in-flammatory mediators (i.e., histamine and tryptase) re-Figure 2. Representative immunoelectrophoretic analysis of tryptasein human colonic mucosal biopsies. Protein was isolated from humanmucosal biopsies, and 15 g was subjected to SDS-PAGE followed byincubation with an anti-human mast cell tryptase antibody. Note theelevated level of tryptase in 5 out of 6 biopsy specimens obtainedfrom IBS patients as compared with the low level of tryptase obtainedin the majority (5 out of 6) of controls.Figure 3. Tryptase release from colonic mucosal biopsy specimens inhealthy controls and IBS patients. Tryptase activity was measured inthe cleared supernatants obtained by a 25-minute incubation of biopsyspecimens in oxygenated buffer using an enzymatic assay.Tryptase activity was measured in the absence (open bars) or presenceof the tryptase inhibitor BABIM (100 mol/L) (hatched bars) orthe trypsin inhibitor SBTI (shaded bars) (50 g/mL). Note the significantincreased release of tryptase from IBS samples as comparedwith controls and the significant inhibition of tryptase activity in thepresence of BABIM but not SBTI. *Significant difference from controls(P  0.015). #Significant difference from samples not exposed toBABIM. Values represent means  standard error.Figure 4. Spontaneous histamine release from colonic mucosal biopsiesin healthy controls and IBS patients. Histamine activity wasmeasured in the cleared supernatants obtained by a 25-minute incubationof biopsy specimens in oxygenated buffer using an enzymaticassay. ï¿½Significant difference from controls (P  0.015).March 2004 NEUROIMMUNE INTERACTIONS AND IBS 697leased by activated mast cells are more likely to affectneural function if they are in close proximity to thenerves, we investigated the spatial relationships occurringbetween mast cells and nerves. The number of mastcells per 10 fields 5 m from nerves was 223% greaterin IBS patients compared with healthy controls (7.14 3.87 cells/10 fields vs. 2.27  1.63 cells/10 fields, respectively,P  0.001). Interestingly, a positive signifi-cant correlation was found between nerve-to-mast cellproximity and rate of degranulation of mast cells (r 0.72, P  0.002) (Figure 6).Mast Cell and Symptom CorrelationThe correlation between mast cell parameters andseverity and frequency of abdominal pain/discomfort isreported in Table 2. A significant correlation was foundbetween vicinity of mast cells to nerves and both severityand frequency of abdominal pain/discomfort (r  0.75,P  0.001 and r  0.70, P  0.003, respectively) (Table2 and Figure 7). There was no correlation between severityor frequency of abdominal pain/discomfort andlamina propria area occupied by mast cells, release oftryptase and histamine, and number of degranulatedmast cells per field (Table 2).DiscussionIn this study, we demonstrated that severity andfrequency of perceived abdominal painful sensations arecorrelated with the presence of activated mast cells inproximity of nerve endings in the gut wall. Furthermore,we showed increased histamine and tryptase release bythe colonic mucosa of IBS patients. Because these mastcell mediators are known to alter enteric nervous systemphysiology and induce visceral hypersensitivity,19,34 theirincreased release in close proximity to colonic innervationsuggests that these mediators contribute to thedisturbed sensory-motor function of IBS.The role of mucosal inflammation in symptom perceptionin gastrointestinal diseases remains far from beingfully understood. The rationale for testing the impactof intestinal inflammation on the development of visceralhypersensitivity and symptom generation in humansTable 2. Correlation Between Mast Cell Parameters andAbdominal Pain/Discomfort in IBS PatientsAbdominal pain/discomfortSeverity Frequencyr P r PMucosal area occupied bymast cells0.07 0.64 0.11 0.48Histamine release 0.12 0.16 0.35 0.35Tryptase release 0.08 0.74 0.13 0.59Degranulated mast cells 0.42 0.11 0.29 0.27Mast cells 5 m from nerves 0.75 0.001 0.70 0.003Figure 5. Electron micrographs showing association between nervefibers (arrows) and mast cells (MC) in the colonic mucosa of healthycontrols (A) and IBS patients (Bï¿½D). (A) Nerve fibers (arrows) and aresting mast cell (MC) showing its characteristic granules in a healthycontrol. (







Electron micrograph obtained from an IBS patient showingmembrane-membrane contacts (asterisk) between a degranulatingmast cell (MC) and a nerve fiber (arrow). © Electron micrographobtained from an IBS patient showing multiple nerve fibers (arrows)located 5 m from a degranulating mast cell (MC). (D) The typicalappearance of a degranulating (arrowheads) mast cell (MC) in closevicinity (5 m) to a nerve fiber. (bar  5 m in A,C,D; 2 m in B.)Figure 6. Correlation between the number of degranulated mast cellsand the number of mast cells located within 5 m of nerves in thecolonic mucosa of IBS patients (r  0.72; P  0.002). The number ofmast cells is relative to 10 electron microscopy fields as described inthe Materials and Methods section.698 BARBARA ET AL. GASTROENTEROLOGY Vol. 126, No. 3originates from abundant data in animal models.34 Visceralhypersensitivity has been shown to be associatedwith colonic mucosal inflammation in different gut conditions,although conflicting results have also been published.Gwee et al. demonstrated a chronic inflammatoryinfiltrate in the rectal mucosa of patients with postinfectiousIBS who also experienced urgency and discomfortat lower volumes of rectal distention than matched controls.35 In keeping with these findings, patients withactive ulcerative colitis reported non-noxious and noxioussensations at lower rectal distention volumes thanthose applied to controls.36 In contrast, Chang et al.showed a decreased rectal sensitivity in patients withmild to moderate ulcerative colitis.37 These previousfindings are difficult to compare and reconcile with thoseobtained in the present study. Indeed, the inflammatoryresponse of inflammatory bowel disease and gastrointestinalinfection (i.e., postinfectious IBS) could be substantiallydifferent, in terms of type and severity of immuneactivation, from that observed in our patients with nonspecificIBS. Furthermore, these previous studies providedno information on the relationship between theimmune response and mucosal neural supply.We showed a marked (180%) increase in colonicmucosal area occupied by mast cells in as many as threequarters of IBS patients, regardless of bowel habit. Thesedata are in keeping with the general assumption thatmast cells are increased in the mucosa of small8 and largeintestine6,7,13 of IBS patients. However, we found substantialdifferences with these previous studies. For example,Oï¿½Sullivan et al. found that increased mast cellscould be detected in the cecum but not in the left colon13and Chadwick et al. found that a significant mast cellinfiltration could be detected only in IBS patients withconstipation but not with diarrhea.7 We believe thatdifferences in study design make it difficult to compareour findings with those of these previous studies. Wetried to avoid possible confounding factors: first, weincluded a specifically selected healthy control population,which, unlike previous studies, was not recruitedfrom patients undergoing colonoscopy for ï¿½otherï¿½ intestinaldiseases (i.e., polyps, bleeding); second, we used areliable computerized method31 to quantify immunolabeledmast cells; and, third, we obtained colonic biopsyspecimens from unprepared colons to avoid the knownproinflammatory effects of large bowel preparations.38A similar degree of mast cell infiltration was found inIBS patients with diarrhea and constipation. A mechanisticinterpretation as to how increased mast cells areinvolved in such contrasting bowel habit patterns iscurrently lacking. Evidence indicates that mastocytosismay be responsible for diarrhea caused by increasedneuronal secretomotor function39; however, we hypothesizethat mast cells may also lead to altered entericneuron function in constipated patients as a result ofexcessive segmental contractile colonic motor activity.These motor changes would ultimately induce a slow,rather than an accelerated, colonic transit. In line withthis hypothesis, it is interesting to note that both diarrheaand constipation can occur in patients with ulcerativecolitis, particularly when in remission,40 and withpostinfectious IBS,6,10 which are both associated with anintestinal inflammatory component.Our data show that mast cell increase was genderdependent, which is in keeping with the knowledge thatthe immune system differs between males and females.41For example, a greater number of mast cells has beendescribed in the colonic mucosa of female as comparedwith male rats.42 Several lines of evidence indicate thatgonadal steroids are involved in gender-related differencesin immune responses41 and, particularly, in tissuemast cell infiltration.43 Taken together, these data raisethe hypothesis that gender-dependent differences in immuneresponses are involved in the observed higherprevalence of IBS in females, in the described genderrelateddifferences in IBS pathophysiology, and in theknown effects of the menstrual cycle in the modulation ofrectal sensitivity.44Although previous studies have demonstrated an increasednumber of mast cells in the colonic13 and ileal8mucosa of IBS patients, the state of mast cell activationand mediator release has never been assessed. Studies inanimals have provided evidence that mast cell activationtriggers visceral hypersensitivity and gastrointestinalmotor dysfunction.4,19,20 Mast cell degranulation in therat rectum is associated with a delayed (6ï¿½12 hours)Figure 7. Correlation between severity (A) and frequency (







of abdominalpain and the number of mast cells located within 5 m ofnerves in the colonic mucosa of IBS patients (r  0.75, P  0.001and r  0.70, P  0.003, respectively). The number of mast cells isrelative to 10 electron microscopy fields as described in the Materialsand Methods section.March 2004 NEUROIMMUNE INTERACTIONS AND IBS 699occurrence of a lowered threshold for induction of painfollowing rectal mechanical distention.45 This is likelydue to mast cell-induced increased firing of sensorynerves.18 Our ultrastructural data are in keeping withthis paradigm because we showed that mast cells of IBSpatients display a significantly greater rate of activation,as demonstrated by an increased number of cells showinglabyrinthic membranous arrays and clearing of individualgranules and by greater release of histamine and tryptase.To support further a role for mast cells in IBS pathophysiology,we measured the content and release of mastcell mediators by colonic mucosal biopsy specimens. Ourtryptase Western blotting experiments showed that colonicbiopsy specimens of IBS patients contained a largeramount of tryptase in comparison with controls, whichwell correlates with the increased total number of mastcells. Furthermore, our functional data demonstrated anenhanced release of tryptase in IBS patients. The speci-ficity of the tryptase activity detected by our assay wasconfirmed by the experiments showing that preincubationof samples with the tryptase inhibitor BABIM significantlysuppressed tryptase activity, whereas the trypsininhibitor SBTI had no effect. The increased release oftryptase in IBS patients suggests that this mediator mayaffect both extrinsic afferent and enteric neurons withlong-lasting effects on secretomotor function and visceralhypersensitivity, as supported by evidence in experimentalmodels.24,46,47 Furthermore, mast cells are by far thelargest storage site of histamine in the human body, andits release has been reported to be a reliable indicator ofmast cell degranulation.48 Histamine is known to activateenteric and extrinsic neurons.19 For example, prolongedexposure of guinea pig submucosal neurons tohistamine resulted in a marked neuronal activation.25Similarly, histamine has been demonstrated to causeactivation of abdominal visceral C-fiber afferents,26 aneffect likely mediated by H1 or H2 receptors expressed onprimary sensory neurons.49 These data, taken in conjunctionwith our demonstration of 80% increase in thespontaneous release of histamine from mucosal biopsyspecimens, suggest that histamine, in addition totryptase, could be involved in sensory-motor dysfunctionin IBS.In the human intestine, mast cells lie in proximity tonerves supplying the gut mucosa.15 This close spatialassociation has been indicated to be of functional relevancefor the crosstalk between the immune and nervoussystem of the gut.14 In the present study, we found thatmast cells of IBS patients were located in closer vicinityto mucosal innervation (with occasional membranemembranecontacts), suggesting that mediators releasedby mast cells, including tryptase and histamine, have anincreased potential to affect neural function. In keepingwith this hypothesis, we found a significant correlationbetween abdominal pain/discomfort (both severity andfrequency) and vicinity of mast cells to nerves supplyingthe colonic mucosal. In addition to these findings, previousstudies indicate that mast cell infiltration of thehuman gut wall is associated with abdominal pain andthat therapy targeting mast cells can improve abdominalpain perception both in systemic mastocytosis50 and inIBS.51 Taken together, these data strongly support amechanistic role for mast cell involvement in visceralnociception in IBS. On the other hand, no statisticalcorrelation was found between tryptase and histaminerelease and abdominal pain/discomfort. Different factorsmay account for this lack of correlation. First, althoughwe primarily assessed histamine and tryptase, mast cellsare known to release a wide variety of biologic substancesthat sensitize sensory nerves.19,21 This raises the possibilitythat combinations of these substances are necessary totrigger sensory nerve firing up to the level of abdominalpain/discomfort perception. Second, because mast cellsthat lie in close proximity to nerves correlate with abdominalpain/discomfort and show an increased rate ofdegranulation, it is conceivable that only the release ofhistamine and tryptase in close proximity to nerves isrelevant for abdominal pain/discomfort development.However, in this study, we detected the amount of eachmediator released from the pool of the mast cells ratherthan that in close proximity to nerves. Third, in keepingwith the Rome II criteria, the symptom questionnaireused in the present study did not discriminate betweenpain and discomfort, which were considered as a singlesymptom. Previous studies demonstrated that repetitivenoxious sigmoid balloon distention evoked visceral hypersensitivityonly in patients with abdominal pain butnot in those with nonpainful symptoms (e.g., discomfort,bloating, and sensation of gas).52 Thus, the possibilitythat the increased release of histamine and tryptase observedin our patients correlates with abdominal pain,but not with discomfort, needs further evaluation.The causes of a prominent colonic mast cell infiltrateand activation observed in IBS patients are unknown.Data suggest that factors including previous episodes ofinfectious enteritis35 and undiagnosed food allergies53may contribute either individually or in combination. Inthis study, we discarded the possibility to investigatepostinfectious IBS to avoid the bias related to retrospectiveanalyses. A prospective assessment of such a correlationis needed. The classical type of activation of mucosalmast cells is through an IgE-dependent (allergy)700 BARBARA ET AL. GASTROENTEROLOGY Vol. 126, No. 3mechanism.21 In our patients, we excluded the influenceof food allergies by means of history taking and foodspecificIgE antibodies. However, food allergy diagnosisremains elusive, and we cannot exclude that at least someof our patients suffered from a subclinical form of allergicgut disease.53 On the other hand, it is now widelyaccepted that mast cells can also respond to a nonï¿½IgEdependentstimulation.21 The best-known triggers ofthis alternative way of activation include bacterial toxins,neurotransmitters, and stress,54 all of which may beinvolved in IBS pathophysiology.5In conclusion, these results provide the rationale forconsidering nerve-mast cell interactions as a mechanismfor abdominal pain/discomfort generation in IBS and,hence, as a target for therapy.References1. Thompson WG, Longstreth GF, Drossman DA, Heaton KW, IrvineEJ, Muller-Lissner SA. Functional bowel disorders and functionalabdominal pain. Gut 1999;45(suppl 2):S43ï¿½S47.2. Sandler RS, Drossman DA, Nathan HP, McKee DC. Symptomcomplaints and health care seeking behavior in subjects withbowel dysfunction. Gastroenterology 1984;87:314ï¿½318.3. Stanghellini V, Cogliandro R, Barbara G, De Giorgio R, CogliandroL, Corinaldesi R. Motor function and dysfunction in functionaldyspepsia and irritable bowel syndrome. In: Holtmann G, TalleyNJ, eds. Gastrointestinal inflammation and disturbed gut function:the challenge of new concepts. Dordrecht: Kluwer AcademicPublishers, 2003:176ï¿½186.4. Camilleri M. Management of the irritable bowel syndrome. Gastroenterology2001;120:652ï¿½668.5. Barbara G, De Giorgio R, Stanghellini V, Cremon C, Corinaldesi R.A role for inflammation in irritable bowel syndrome? Gut 2002;51(suppl 1):i41ï¿½i44.6. Spiller RC. Postinfectious irritable bowel syndrome. Gastroenterology2003;124:1662ï¿½1671.7. Chadwick VS, Chen W, Shu D, Paulus B, Bethwaite P, Tie A,Wilson I. Activation of the mucosal immune system in irritablebowel syndrome. Gastroenterology 2002;122:1778ï¿½1783.8. Weston AP, Biddle WL, Bhatia PS, Miner PB Jr. Terminal ilealmucosal mast cells in irritable bowel syndrome. Dig Dis Sci1993;38:1590ï¿½1595.9. Tornblom H, Lindberg G, Nyberg B, Veress B. Full-thickness biopsyof the jejunum reveals inflammation and enteric neuropathyin irritable bowel syndrome. Gastroenterology 2002;123:1972ï¿½1979.10. Gwee KA, Graham JC, McKendrick MW, Collins SM, Marshall JS,Walters SJ, Read NW. Psychometric scores and persistence ofirritable bowel after infectious diarrhea. Lancet 1996;347:150ï¿½153.11. Neal KR, Hebden J, Spiller R. Prevalence of gastrointestinalsymptoms six months after bacterial gastroenteritis and riskfactors for development of the irritable bowel syndrome: postalsurvey of patients. BMJ 1997;314:779ï¿½782.12. Isgar B, Harman M, Kaye MD, Whorwell PJ. Symptoms of irritablebowel syndrome in ulcerative colitis in remission. Gut 1983;24:190ï¿½192.13. Oï¿½Sullivan M, Clayton N, Breslin NP, Harman I, Bountra C,McLaren A, Oï¿½Morain CA. Increased mast cells in the irritablebowel syndrome. Neurogastroenterol Motil 2000;12:449ï¿½457.14. Stead RH, Dixon MF, Bramwell NH, Riddell RH, Bienenstock J.Mast cells are closely apposed to nerves in the human gastrointestinalmucosa. Gastroenterology 1989;97:575ï¿½585.15. Stead RH, Tomioka M, Quinonez G, Simon GT, Felten SY, BienenstockJ. Intestinal mucosal mast cells in normal and nematodeinfectedrat intestines are in intimate contact with peptidergicnerves. Proc Natl Acad Sci U S A 1987;84:2975ï¿½2979.16. Reed DE, Barajas-Lopez C, Cottrell G, Velazquez-Rocha S, Dery O,Grady EF, Bunnett NW, Vanner SJ. Mast cell tryptase and proteinase-activated receptor 2 induce hyperexcitability of guinea-pigsubmucosal neurons. J Physiol 2003;547:531ï¿½542.17. Gao C, Liu S, Hu HZ, Gao N, Kim G, Xia Y, Wood JD. Serineproteases excite myenteric neurons through protease-activatedreceptors in guinea pig small intestine. Gastroenterology 2002;123:1554ï¿½1564.18. Nozdrachev AD, Akoev GN, Filippova LV, Sherman NO, LioudynoMI, Makarov FN. Changes in afferent impulse activity of smallintestine mesenteric nerves in response to antigen challenge.Neuroscience 1999;94:1339ï¿½1342.19. Bueno L, Fioramonti J, Delvaux M, Frexinos J. Mediators andpharmacology of visceral sensitivity: from basic to clinical investigations.Gastroenterology 1997;112:1714ï¿½1743.20. Castex N, Fioramonti J, Fargeas MJ, More J, Bueno L. Role of5-HT3 receptors and afferent fibers in the effects of mast celldegranulation on colonic motility in rats. Gastroenterology 1994;107:976ï¿½984.21. Metcalfe DD, Baram D, Mekori YA. Mast cells. Physiol Rev 1997;77:1033ï¿½1079.22. Macfarlane SR, Seatter MJ, Kanke T, Hunter GD, Plevin R. Proteinase-activated receptors. Pharmacol Rev 2001;53:245ï¿½282.23. Molino M, Barnathan ES, Numerof R, Clark J, Dreyer M, CumashiA, Hoxie JA, Schechter N, Woolkalis M, Brass LF. Interactions ofmast cell tryptase with thrombin receptors and PAR-2. J BiolChem 1997;272:4043ï¿½4049.24. Coelho AM, Vergnolle N, Guiard B, Fioramonti J, Bueno L. Proteinasesand proteinase-activated receptor 2: a possible role topromote visceral hyperalgesia in rats. Gastroenterology 2002;122:1035ï¿½1047.25. Tamura K, Wood JD. Effects of prolonged exposure to histamineon guinea pig intestinal neurons. Dig Dis Sci 1992;37:1084ï¿½1088.26. Fu LW, Pan HL, Longhurst JC. Endogenous histamine stimulatesischemically sensitive abdominal visceral afferents through H1receptors. Am J Physiol 1997;273:H2726ï¿½H2737.27. Liu S, Hu HZ, Gao N, Gao C, Wang G, Wang X, Peck OC, Kim G,Gao X, Xia Y, Wood JD. Neuroimmune interactions in guinea pigstomach and small intestine. Am J Physiol Gastrointest LiverPhysiol 2003;284:G154ï¿½G164.28. Talley NJ, Phillips SF, Melton J III, Wiltgen C, Zinsmeister AR. Apatient questionnaire to identify bowel disease. Ann Intern Med1989;111:671ï¿½674.29. Neri M, Laterza F, Howell S, Di Gioacchino M, Festi D, Ballone E,Cuccurullo F, Talley NJ. Symptoms discriminate irritable bowelsyndrome from organic gastrointestinal diseases and food allergy.Eur J Gastroenterol Hepatol 2000;12:981ï¿½988.30. Jensen MP, Turner LR, Turner JA, Romano JM. The use of multiple-item scales for pain intensity measurement in chronic painpatients. Pain 1996;67:35ï¿½40.31. Lee E, Schiller LR, Fordtran JS. Quantification of colonic laminapropria cells by means of a morphometric point-counting method.Gastroenterology 1988;94:409ï¿½418.32. Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH,Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC.Measurement of protein using bicinchoninic acid. Anal Biochem1985;150:76ï¿½85.33. Raithel M, Schneider HT, Hahn EG. Effect of substance P onhistamine secretion from gut mucosa in inflammatory bowel disease.Scand J Gastroenterol 1999;34:496ï¿½503.March 2004 NEUROIMMUNE INTERACTIONS AND IBS 70134. Collins SM. The immunomodulation of enteric neuromuscularfunction: implications for motility and inflammatory disorders.Gastroenterology 1996;111:1683ï¿½1699.35. Gwee KA, Leong YL, Graham C, McKendrick MW, Collins SM,Walters SJ, Underwood JE, Read NW. The role of psychologicaland biological factors in postinfective gut dysfunction. Gut 1999;44:400ï¿½406.36. Rao SS, Read NW, Davison PA, Bannister JJ, Holdsworth CD.Anorectal sensitivity and responses to rectal distention in patientswith ulcerative colitis. Gastroenterology 1987;93:1270ï¿½1275.37. Chang L, Munakata J, Mayer EA, Schmulson MJ, Johnson TD,Bernstein CN, Saba L, Naliboff B, Anton PA, Matin K. Perceptualresponses in patients with inflammatory and functional boweldisease. Gut 2000;47:497ï¿½505.38. Pockros PJ, Foroozan P. Golytely lavage versus a standardcolonoscopy preparation. Effect on normal colonic mucosal histology.Gastroenterology 1985;88:545ï¿½548.39. Wood JD. Neuropathophysiology of irritable bowel syndrome.J Clin Gastroenterol 2002;35(suppl 1):S11ï¿½S22.40. Rao SS, Holdsworth CD, Read NW. Symptoms and stool patternsin patients with ulcerative colitis. Gut 1988;29:342ï¿½345.41. Schuurs AH, Verheul HA. Effects of gender and sex steroids onthe immune response. J Steroid Biochem 1990;35:157ï¿½172.42. Bradesi S, Eutamene H, Theodorou V, Fioramonti J, B


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## eric (Jul 8, 1999)

The above info is the layers in general, not IBS mast cell images just fyi.Activated Mast Cells in Proximity to Colonic Nerves Correlate With Abdominal Pain in Irritable Bowel SyndromeGIOVANNI BARBARA,* VINCENZO STANGHELLINI,* ROBERTO DE GIORGIO,* CESARE CREMON,*GRAEME S. COTTRELL,ï¿½ DONATELLA SANTINI,ï¿½ GIANANDREA PASQUINELLI,ï¿½ANTONIO M. MORSELLIï¿½LABATE,* EILEEN F. GRADY,ï¿½ NIGEL W. BUNNETT,ï¿½STEPHEN M. COLLINS,ï¿½ and ROBERTO CORINALDESI**Department of Internal Medicine and Gastroenterology, and CRBA, University of Bologna, Bologna, Italy; ï¿½Departments of Surgery andPhysiology, University of California San Francisco, San Francisco, California; ï¿½Department of Pathology, University of Bologna, Bologna, Italy;and ï¿½Division of Gastroenterology, McMaster University, Ontario, CanadaBackground & Aims: The mechanisms underlying abdominal pain perception in irritable bowel syndrome (IBS) are poorly understood. Intestinal mast cell inﬁltration may perturb nerve function leading to symptom perception. We assessed colonic mast cell inﬁltration, mediator release, and spatial interactions with mucosal innervation and their correlation with abdominal pain in IBS patients. Methods: IBS patients were diagnosed accordingto Rome II criteria and abdominal pain quanti-ﬁed according to a validated questionnaire. Colonic mucosalmast cells were identiﬁed immunohistochemicallyand quantiﬁed with a computer-assisted countingmethod. Mast cell tryptase and histamine release wereanalyzed immunoenzymatically. Intestinal nerve to mastcell distance was assessed with electron microscopy.Results: Thirty-four out of 44 IBS patients (77%) showedan increased area of mucosa occupied by mast cells ascompared with controls (9.2%  2.5% vs. 3.3  0.8%,respectively; P 0.001). There was a 150% increase inthe number of degranulating mast cells (4.76  3.18/ﬁeld vs. 2.42  2.26/ﬁeld, respectively; P  0.026).Mucosal content of tryptase was increased in IBS andmast cells spontaneously released more tryptase(3.22  3.48 pmol/min/mg vs. 0.87  0.65 pmol/min/mg, respectively; P  0.015) and histamine (339.7 59.0 ng/g vs. 169.3  130.6 ng/g, respectively; P 0.015). Mast cells located within 5 m of nerve ﬁberswere 7.14  3.87/ﬁeld vs. 2.27  1.63/ﬁeld in IBS vs.controls (P 0.001). Only mast cells in close proximityto nerves were signiﬁcantly correlated with severity andfrequency of abdominal pain/discomfort (P 0.001and P  0.003, respectively). Conclusions: Colonic mastcell inﬁltration and mediator release in proximity tomucosal innervation may contribute to abdominal painperception in IBS patients.Irritable bowel syndrome (IBS) is one of the mostcommon gastrointestinal disorders seen in primarycare and specialist practice characterized by abdominaldiscomfort or pain and disturbed defecation that cannotbe explained by structural or biochemical abnormalities.1Abdominal pain/discomfort is the hallmark symptomof IBS,1 which correlates with the overall severity of thedisease.2 The pathogenesis of IBS symptoms is looselyunderstood. Although gut motor abnormalities may accountfor alterations in gut transit, they are poorlycorrelated with patientsï¿½ abdominal pain/discomfort.3There is general agreement that increased sensitivity tostimuli arising from the gut wall (i.e., visceral hypersensitivity)contributes to abdominal pain/discomfort in atleast a subset of IBS patients.4 Several mechanisms arethought to be involved in the visceral hypersensitivity ofIBS patients,5 including (1) modulatory effect of thecentral nervous system in response to information conveyedfrom the gut, (2) hyperexcitability of dorsal hornneurons in the central limb of the visceral afferent pathway,and (3) sensitization of sensory neural endings at theend-organ level.The causes underlying the end-organ hypersensitivityin IBS are only partially understood. It has been hypothesizedthat a low-grade inflammatory response at thelevel of the gut wall could be involved.5,6 Consistentwith this hypothesis is evidence that at least certainsubsets of IBS patients have an increased number ofinflammatory cells in the colonic7 and ileal8 mucosa aswell as in muscularis externa of jejunum.9 Also, IBS maydevelop after a bout of acute infectious gastroenteritis6,10,11and during periods of remission from inflammatorybowel disease.12 However, these previous studies doAbbreviations used in this paper: BABIM, bis(5-amidino-2-benzimidazolyl)methane; BSA, bovine serum albumin; IBS, irritable bowelsyndrome; PAR, proteinase-activated receptors; SBTI, soybean trypsininhibitor.ï¿½ 2004 by the American Gastroenterological Association0016-5085/04/$30.00doi:10.1053/j.gastro.2003.11.055GASTROENTEROLOGY 2004;126:693ï¿½702not provide insights into the possible mechanisms involvedin the altered sensory-motor function of IBS.A number of reasons raise the hypothesis that mastcells could be involved in the disturbed sensory-motorfunction of IBS. First, an increased number of these cellshas been detected in the colonic7,13 and ileal8 mucosa ofIBS patients. Second, in the human intestine, mast cellslie in close proximity to mucosal innervation.14,15 Third,animal studies demonstrated that, upon activation, mastcells release mediators that cause increased excitability ofenteric16,17 and primary afferent neurons,18 leading tovisceral hypersensitivity19 and abnormal gut motor function.20Tryptase and histamine are two major inflammatorymediators released during mast cell degranulation.21Tryptase, like other proteases, signals to cells throughproteinase activated receptors (PARs).22 Proteases cleavewithin the extracellular N-terminal tails of PARs toexpose tethered ligand domains that bind and activatecleaved receptors.22 Of the 4 cloned PARs, tryptaseselectively activates PAR-2.17,23 Mast cell tryptase inducesactivation of PAR-2 located on enteric nerves andvisceral afferents causing long-lasting neuronal hyperexcitability.16,17,24 Histamine can also activate visceral afferents18and enteric neurons25 via interaction with H1 orH2 receptors.26,27 Thus, both tryptase and histamine arecandidate mediators for disturbed gut sensory-motorfunction.The aims of the present study were to assess theimpact of colonic mast cell infiltration and activation, aswell as mast cell-to-mucosal innervation relationship onthe severity and frequency of abdominal pain/discomfortof IBS patients.Materials and MethodsPatientsIBS patients were all seen in the Department of InternalMedicine and Gastroenterology of the University of Bolognaand met the Rome II criteria.1 Healthy controls wererecruited by public advertisement and included in the studyafter thorough exclusion of gastrointestinal complaints. Noneof the study participants were taking nonsteroidal anti-inflammatorydrugs or other anti-inflammatory drugs (includingmast cell stabilizers, immunosuppressants, and steroids); hadundergone major abdominal surgery; or had any organic syndrome,asthma, celiac disease (excluded by detection of antitransglutaminaseand anti-endomysial antibodies), allergic diseases(including exclusion of a history of food allergies and, bypresence of food specific IgE antibodies), intestinal bacterial ormycotic contamination, metabolic or psychiatric disease asdiagnosed by history taking, consultations, and appropriatelaboratory tests. They all gave written informed consent, andthe study was approved by the local Ethical Committee andconducted in accordance with the Declaration of Helsinki.All participants underwent left colonoscopy after cleansingof distal colon with two 500-mL water enemas performed theevening before and the morning of the procedure. In all cases,4 mucosal biopsy specimens were obtained from the proximaldescending colon. Two biopsy specimens were used for routineH&E histology and immunohistochemistry and 2 for electronmicroscopy. In 36 unselected cases, 4 additional biopsy specimenscould be obtained for histamine and tryptase releaseassays and tryptase Western blotting.Symptom QuestionnaireEach patient completed a modified version of theBowel Disease Questionnaire (BDQ) to evaluate symptoms.28An Italian version of the questionnaire has been previouslyused in IBS studies in our country.29Patients were asked to score frequency and severity of theirsymptoms over the last 2 weeks before interview. In fact,recollection is poor beyond this limit, and shorter periodsmight not appropriately reflect the usual clinical picture andthis time frame has been previously shown to be a reliablepredictor of average pain intensity.30 The severity of abdominalpain/discomfort was graded 0ï¿½4 according to its influenceon patientsï¿½ usual activities: 0, absent; 1, mild (not influencingusual activities); 2, relevant (diverting from, but not urgingmodification of, usual activities); 3, severe (influencing usualactivities markedly enough to urge modifications); 4, extremelysevere (precluding daily activities). The frequency ofabdominal pain/discomfort was graded 0ï¿½4 according to thefollowing scale: 0, absent; 1, up to 1 day/week; 2, 2 or 3days/week; 3, 4ï¿½6 days/week; 4, daily. Furthermore, the followingsymptoms were assessed as present/absent: diarrhea,constipation, bloating/distention, flatulence, relief of abdominalpain/discomfort by defecation or passage of air per rectum,mucus in stool, onset of symptoms associated with a change infrequency (or form) of stool, hard or lumpy stool, loose orwatery stool, straining during a bowel movement, urgency,and feeling of incomplete bowel movement.Histology and ImmunohistochemistryBiopsy specimens were fixed in buffered 10% formalinand processed for either H&E histology or immunohistochemistry.For the latter, paraffin-embedded specimens were cutwith a microtome at 3ï¿½4 m, mounted on to gelatin-coatedslides, and processed either for immunohistochemistry or indirectimmunofluorescence using widely applied methods.Briefly, for single-labeling immunohistochemistry, followingantigen unmasking, randomly selected sections were incubatedwith mouse monoclonal antibodies directed against tryptase(mast cell marker; diluted at 1:2000; Dakopatts Glostrup,Denmark) overnight at 4ï¿½C. Following thorough washingwith PBS, slides were reincubated for 2 hours at room temperaturewith secondary biotinylated anti-mouse-rabbit antibodies(1:200; Dakopatts Glostrup, Denmark) followed bystreptavidin-horseradish peroxidase conjugate. For immuno-694 BARBARA ET AL. GASTROENTEROLOGY Vol. 126, No. 3fluorescence, slides were processed as described above with theonly difference that sections were reincubated for 2 hours atroom temperature with rhodamine or fluoresceine-conjugatedsecondary antibodies (1:100; Dakopatts Glostrup).Mast Cell CountsAll histologic sections were evaluated by an expertpathologist (D.S.), who was unaware of the diagnosis, forexclusion of overt mucosal inflammation or microscopic colitis.Quantification of inflammatory cells was performed on sectionsimmunostained for mast cells with a Leitz Dialux microscope(equipped with a Ploem epi-illumination system with ï¿½N2ï¿½filter cube to detect rhodamine fluorescence) in blind fashionusing a computer-assisted analysis system (Cytometrica###software;C&V, Bologna, Italy). Measurements were performed using amodification of a previously published method.31 Briefly, microscopicfields were digitized and randomly sampled with the aid ofa grid (0.5 mm2) located below the slide. A stereological gridcontaining cross-shaped points was overlaid on the digitizedsampled fields by the computer software and used to determinethe area occupied by mast cells over that occupied by laminapropria (i.e., number of points hitting the cells divided by thetotal number of cross-shaped points in the lamina propria).Electron MicroscopyBiopsy specimens were fixed in cacodylate-buffered2.5% glutaraldehyde for 4 to 6 hours at 4ï¿½C and postfixed in1% osmium tetroxide for 1 hour at 4ï¿½C. After dehydration andembedding in araldite, semithin sections were stained withtoluidine blue and examined under a light microscope. Apathologist (G.P.) performed a blind analysis of all sections.Representative portions of the intestinal mucosa (i.e., absenceof artifacts) were selected for ultrathin sectioning. Thin sectionswere collected on 200 mesh grids, stained with uranylacetate and lead citrate, and observed with a Philips 410 Ttransmission electron microscope. After exclusion of fieldsexclusively comprising epithelial structures, 10 randomly selectedfields of the intestinal mucosa measuring 90 m2 wereexamined for each sample. In each field (9100 magnification),the following parameters were recorded: total number ofmast cells, number of mast cells with degranulation features(i.e., labyrinthic membranous arrays or clearing of individualgranules), and number of mast cells located within 5 m ofnerve fibers.Tryptase Western BlottingMucosal biopsy specimens were frozen in liquid nitrogenand then rinsed in PBS. Biopsy specimens were thenhomogenized in Camiolo buffer (75 mmol/L potassium acetate,300 mmol/L NaCl, 100 mmol/L L-arginine, 10 mmol/LEDTA, 0.25% Triton X-100, pH 7.4) for 1 minute at 4ï¿½C.The homogenized sample was then centrifuged at 3000 rpmfor 15 minutes at 4ï¿½C. The supernatant was then transferred toa fresh tube and assayed for protein content. Protein concentrationswere determined using the bicinchoninic acid assay,32with bovine serum albumin (BSA) as standard. The methodwas adapted for use in 96-well microtiter plates. Equalamounts of protein (15 g) from each patient were separatedusing a 7%ï¿½17% PAGE. After electrophoresis, proteins weretransferred to a polyvinylidene fluoride membrane (Millipore,Billerica, MA) and then blocked (1X PBS, 2% BSA, 5% milkpowder, 0.1% Tween 20) for 1 hour at room temperature. Themembrane was then incubated overnight at 4ï¿½C with ananti-human mast cell tryptase antibody (1:5000; Chemicon,Temecula, CA). After washing (1X PBS, 0.1% Tween 20), themembrane was incubated for 1 hour at room temperature witha goat anti-mouse-horseradish peroxidase antibody (1:10,000;Jackson Laboratories, West Grove, PA). Following a secondwash, immunoreactive proteins were visualized by chemiluminescence(ECL kit, Amersham-Pharmacia, Piscataway, NJ).Results are representative of 3 separate blots.Tryptase and Histamine ReleaseSpontaneous release of tryptase and histamine frommucosal biopsy specimens was evaluated using a modificationof a previously described method.33 Briefly, upon removal,mucosal biopsy specimens were rapidly immersed in hardplastic tubes containing 2 mL of Hanksï¿½ solution (37ï¿½C) andcontinuously oxygenated (95% O2/5% CO2). After 25-minuteincubation, 200 L of the bathing solution was removed.Samples to be processed for histamine assay only were immediatelyheated at 95ï¿½C to avoid rapid denaturation of histamineby degrading enzymes (histaminases). All samples werecentrifuged at 200g for 10 minutes, and 150 L of supernatantwere aliquoted and stored at 70ï¿½C until the assay. At the endof the release experiment, biopsy specimens were blotted andweighed. For tryptase activity triplicate aliquots (10 L) of thesupernatants were added to 200 L of buffer (50 mmol/LTris/HCl, pH 7.6, 120 mmol/L NaCl, 20 g/mL heparin)containing 0.5 mmol/L substrate (tosyl-Glycine-Proline-Arginine-pNitroanilide) and incubated at room temperature for 17hours ( inhibitors as indicated). Cleavage of the substrate wasmeasured using a microtiter plate reader (absorbance 405 nm)and normalized to the weight of the biopsy specimens used ineach case. Histamine was detected from triplicate aliquots (50L) of the supernatants using a highly selective enzyme-linkedimmunoassay (Immunotech, Marseille, France) according tothe manufacturerï¿½s directions. Histamine was measured usinga microtiter plate reader (absorbance 405 nm) and normalizedto the weight of the biopsy specimens.Data Expression and Statistical AnalysisUnless otherwise stated, data are reported as meanvalues  standard deviation (SD). Data relative to electronmicroscopy studies are presented as mean values  SD relativeto 10 electron microscopic fields. Data were analyzed by meansof the Mannï¿½Whitney U and the Yatesï¿½ corrected 2 tests.Correlations were analyzed using the Spearman rank correlationtest. Analyses were done by running the SPSS/PC (SPSS,Inc, Chicago, IL) statistical package on a personal computer.Two-tailed P values less than 0.05 were considered statisticallysignificant.March 2004 NEUROIMMUNE INTERACTIONS AND IBS 695ResultsPatientsForty-four consecutive patients with IBS (aged22ï¿½75 years; mean, 40.1 years; 31 females, 13 males) aswell as 22 healthy controls (aged 20ï¿½71 years; mean,32.5 years; 12 females, 10 males) participated in thestudy. All patients complained of abdominal pain/discomfort(severity score: 1.78  1.15; frequency score:2.20  1.49; mean  SD); 50% had diarrhea and 50%constipation; furthermore, the most frequently associatedsymptom was bloating (97.8%).Mast Cell CountsThirty-four (77.3%) of the 44 IBS patients had anincreased mucosal cell area occupied by mast cells (i.e.,greater than the mean  2SD of controls: 4.8%). Asshown in Table 1 and Figure 1, the mean area of mucosaoccupied by tryptase positive mast cells was 181%greater in IBS patients with respect to healthy controls.The mucosal area occupied by mast cells was not differentin diarrhea and constipation predominant subgroups(P  0.096). A significant increase in the mean areaoccupied by mast cells was identified in both male andfemale IBS patients, compared with the respective controlgroups (Table 1). However, the mean area occupiedby mast cells in female IBS patients was 43% greaterthan that observed in male IBS patients (Table 1).Mast Cell DegranulationTo assess the state of activation of mast cells, wequantified the number of mast cells showing ultrastructuralfeatures of degranulation, including labyrinthicmembranous arrays and clearing of individual granules.Degranulating mast cells could be observed in samplesfrom both IBS patients and controls. However, quantitativeanalysis of degranulating mast cells showed a150% significant increase in IBS patients with respect tocontrols (4.76  3.18 cells/10 fields vs. 2.42  2.26cells/10 fields, respectively, P  0.026).Tryptase Western BlotsWe quantified the total amount of tryptase, themajor protease contained in mast cell secretory granules.Using an antibody directed against human mast celltryptase, we found a 35-kilodalton broad band on Westernblots (Figure 2). All controls had the same molecularweight band, which is the expected size for tryptase(Figure 2). Only 1 out of 6 controls had an elevated levelof tryptase (Figure 2). In sharp contrast, 5 out of 6 biopsyTable 1. Mucosal Mast Cell CountsAll Female MaleP value(male vs. female) Diarrhea ConstipationP value(vs. diarrhea)Controls (n  22) 3.3  0.8 3.4  0.5 3.1  0.9 NS ï¿½ ï¿½ NAIBS (n  44) 9.2  2.5a 10.0  2.3b 7.0  1.6c 0.001 8.6  2.7 9.7  2.1 NSNS, not significant, P 0.05; NA, not applicable.aSignificant difference vs. controls (P  0.001).bSignificant difference vs. controls (P  0.001).cSignificant difference vs. controls (P  0.001).Figure 1. Representative photomicrographs showing tryptase positive mast cells in the colonic mucosa of a healthy control (A) and an IBSpatient (







. Note the higher number of positive mast cells in the IBS patient as compared with the control. (bar  25 m.)696 BARBARA ET AL. GASTROENTEROLOGY Vol. 126, No. 3specimens obtained from patients with IBS containedmuch higher levels of immunoreactive tryptase (Figure2). Because of the broad range of molecular weight, wedid not quantify the increase in intensity.Tryptase ReleaseThe level of tryptase activity that was spontaneouslyreleased from mucosal biopsy specimens was quantified inthe cleared supernatants obtained by a 25-minute incubationof biopsy specimens in oxygenated buffer using anenzymatic assay. As shown in Figure 3, the level of tryptaseactivity in IBS patients was 3.7 times higher than thatfound in healthy controls (P  0.015). Both in control andIBS samples, this activity was significantly inhibited by theaddition of the tryptase inhibitor bis(5-amidino-2-benzimidazolyl)methane (BABIM; 100 mol/L) (P  0.013 andP  0.003, respectively), but not by the trypsin inhibitorsoybean trypsin inhibitor (SBTI; 50 g/mL) (P  0.794and P0.594, respectively), thus showing that the activitymeasured in the assay was specific for tryptase.Histamine ReleaseThe spontaneous release of histamine from mucosalbiopsy specimens of IBS patients and controls wasmeasured in the cleared supernatants obtained by a 25-minute incubation of biopsy specimens in oxygenatedbuffer using an enzymatic assay. As shown in Figure 4,histamine activity in IBS patients was significantly increasedby 101% over the activity found in controls (P 0.015).Mast Cellï¿½Nerve InteractionsIn the colonic mucosa of both healthy controlsand IBS patients, mast cells were frequently found inclose proximity to intestinal nerves (Figure 5Aï¿½D) andmembrane-membrane contacts were occasionally observedin both groups (Figure 5B). Mast cells undergoingactive degranulation in proximity to nerve trunks werealso occasionally identified (Figure 5Bï¿½D). Because in-flammatory mediators (i.e., histamine and tryptase) re-Figure 2. Representative immunoelectrophoretic analysis of tryptasein human colonic mucosal biopsies. Protein was isolated from humanmucosal biopsies, and 15 g was subjected to SDS-PAGE followed byincubation with an anti-human mast cell tryptase antibody. Note theelevated level of tryptase in 5 out of 6 biopsy specimens obtainedfrom IBS patients as compared with the low level of tryptase obtainedin the majority (5 out of 6) of controls.Figure 3. Tryptase release from colonic mucosal biopsy specimens inhealthy controls and IBS patients. Tryptase activity was measured inthe cleared supernatants obtained by a 25-minute incubation of biopsyspecimens in oxygenated buffer using an enzymatic assay.Tryptase activity was measured in the absence (open bars) or presenceof the tryptase inhibitor BABIM (100 mol/L) (hatched bars) orthe trypsin inhibitor SBTI (shaded bars) (50 g/mL). Note the significantincreased release of tryptase from IBS samples as comparedwith controls and the significant inhibition of tryptase activity in thepresence of BABIM but not SBTI. *Significant difference from controls(P  0.015). #Significant difference from samples not exposed toBABIM. Values represent means  standard error.Figure 4. Spontaneous histamine release from colonic mucosal biopsiesin healthy controls and IBS patients. Histamine activity wasmeasured in the cleared supernatants obtained by a 25-minute incubationof biopsy specimens in oxygenated buffer using an enzymaticassay. ï¿½Significant difference from controls (P  0.015).March 2004 NEUROIMMUNE INTERACTIONS AND IBS 697leased by activated mast cells are more likely to affectneural function if they are in close proximity to thenerves, we investigated the spatial relationships occurringbetween mast cells and nerves. The number of mastcells per 10 fields 5 m from nerves was 223% greaterin IBS patients compared with healthy controls (7.14 3.87 cells/10 fields vs. 2.27  1.63 cells/10 fields, respectively,P  0.001). Interestingly, a positive signifi-cant correlation was found between nerve-to-mast cellproximity and rate of degranulation of mast cells (r 0.72, P  0.002) (Figure 6).Mast Cell and Symptom CorrelationThe correlation between mast cell parameters andseverity and frequency of abdominal pain/discomfort isreported in Table 2. A significant correlation was foundbetween vicinity of mast cells to nerves and both severityand frequency of abdominal pain/discomfort (r  0.75,P  0.001 and r  0.70, P  0.003, respectively) (Table2 and Figure 7). There was no correlation between severityor frequency of abdominal pain/discomfort andlamina propria area occupied by mast cells, release oftryptase and histamine, and number of degranulatedmast cells per field (Table 2).DiscussionIn this study, we demonstrated that severity andfrequency of perceived abdominal painful sensations arecorrelated with the presence of activated mast cells inproximity of nerve endings in the gut wall. Furthermore,we showed increased histamine and tryptase release bythe colonic mucosa of IBS patients. Because these mastcell mediators are known to alter enteric nervous systemphysiology and induce visceral hypersensitivity,19,34 theirincreased release in close proximity to colonic innervationsuggests that these mediators contribute to thedisturbed sensory-motor function of IBS.The role of mucosal inflammation in symptom perceptionin gastrointestinal diseases remains far from beingfully understood. The rationale for testing the impactof intestinal inflammation on the development of visceralhypersensitivity and symptom generation in humansTable 2. Correlation Between Mast Cell Parameters andAbdominal Pain/Discomfort in IBS PatientsAbdominal pain/discomfortSeverity Frequencyr P r PMucosal area occupied bymast cells0.07 0.64 0.11 0.48Histamine release 0.12 0.16 0.35 0.35Tryptase release 0.08 0.74 0.13 0.59Degranulated mast cells 0.42 0.11 0.29 0.27Mast cells 5 m from nerves 0.75 0.001 0.70 0.003Figure 5. Electron micrographs showing association between nervefibers (arrows) and mast cells (MC) in the colonic mucosa of healthycontrols (A) and IBS patients (Bï¿½D). (A) Nerve fibers (arrows) and aresting mast cell (MC) showing its characteristic granules in a healthycontrol. (







Electron micrograph obtained from an IBS patient showingmembrane-membrane contacts (asterisk) between a degranulatingmast cell (MC) and a nerve fiber (arrow). © Electron micrographobtained from an IBS patient showing multiple nerve fibers (arrows)located 5 m from a degranulating mast cell (MC). (D) The typicalappearance of a degranulating (arrowheads) mast cell (MC) in closevicinity (5 m) to a nerve fiber. (bar  5 m in A,C,D; 2 m in B.)Figure 6. Correlation between the number of degranulated mast cellsand the number of mast cells located within 5 m of nerves in thecolonic mucosa of IBS patients (r  0.72; P  0.002). The number ofmast cells is relative to 10 electron microscopy fields as described inthe Materials and Methods section.698 BARBARA ET AL. GASTROENTEROLOGY Vol. 126, No. 3originates from abundant data in animal models.34 Visceralhypersensitivity has been shown to be associatedwith colonic mucosal inflammation in different gut conditions,although conflicting results have also been published.Gwee et al. demonstrated a chronic inflammatoryinfiltrate in the rectal mucosa of patients with postinfectiousIBS who also experienced urgency and discomfortat lower volumes of rectal distention than matched controls.35 In keeping with these findings, patients withactive ulcerative colitis reported non-noxious and noxioussensations at lower rectal distention volumes thanthose applied to controls.36 In contrast, Chang et al.showed a decreased rectal sensitivity in patients withmild to moderate ulcerative colitis.37 These previousfindings are difficult to compare and reconcile with thoseobtained in the present study. Indeed, the inflammatoryresponse of inflammatory bowel disease and gastrointestinalinfection (i.e., postinfectious IBS) could be substantiallydifferent, in terms of type and severity of immuneactivation, from that observed in our patients with nonspecificIBS. Furthermore, these previous studies providedno information on the relationship between theimmune response and mucosal neural supply.We showed a marked (180%) increase in colonicmucosal area occupied by mast cells in as many as threequarters of IBS patients, regardless of bowel habit. Thesedata are in keeping with the general assumption thatmast cells are increased in the mucosa of small8 and largeintestine6,7,13 of IBS patients. However, we found substantialdifferences with these previous studies. For example,Oï¿½Sullivan et al. found that increased mast cellscould be detected in the cecum but not in the left colon13and Chadwick et al. found that a significant mast cellinfiltration could be detected only in IBS patients withconstipation but not with diarrhea.7 We believe thatdifferences in study design make it difficult to compareour findings with those of these previous studies. Wetried to avoid possible confounding factors: first, weincluded a specifically selected healthy control population,which, unlike previous studies, was not recruitedfrom patients undergoing colonoscopy for ï¿½otherï¿½ intestinaldiseases (i.e., polyps, bleeding); second, we used areliable computerized method31 to quantify immunolabeledmast cells; and, third, we obtained colonic biopsyspecimens from unprepared colons to avoid the knownproinflammatory effects of large bowel preparations.38A similar degree of mast cell infiltration was found inIBS patients with diarrhea and constipation. A mechanisticinterpretation as to how increased mast cells areinvolved in such contrasting bowel habit patterns iscurrently lacking. Evidence indicates that mastocytosismay be responsible for diarrhea caused by increasedneuronal secretomotor function39; however, we hypothesizethat mast cells may also lead to altered entericneuron function in constipated patients as a result ofexcessive segmental contractile colonic motor activity.These motor changes would ultimately induce a slow,rather than an accelerated, colonic transit. In line withthis hypothesis, it is interesting to note that both diarrheaand constipation can occur in patients with ulcerativecolitis, particularly when in remission,40 and withpostinfectious IBS,6,10 which are both associated with anintestinal inflammatory component.Our data show that mast cell increase was genderdependent, which is in keeping with the knowledge thatthe immune system differs between males and females.41For example, a greater number of mast cells has beendescribed in the colonic mucosa of female as comparedwith male rats.42 Several lines of evidence indicate thatgonadal steroids are involved in gender-related differencesin immune responses41 and, particularly, in tissuemast cell infiltration.43 Taken together, these data raisethe hypothesis that gender-dependent differences in immuneresponses are involved in the observed higherprevalence of IBS in females, in the described genderrelateddifferences in IBS pathophysiology, and in theknown effects of the menstrual cycle in the modulation ofrectal sensitivity.44Although previous studies have demonstrated an increasednumber of mast cells in the colonic13 and ileal8mucosa of IBS patients, the state of mast cell activationand mediator release has never been assessed. Studies inanimals have provided evidence that mast cell activationtriggers visceral hypersensitivity and gastrointestinalmotor dysfunction.4,19,20 Mast cell degranulation in therat rectum is associated with a delayed (6ï¿½12 hours)Figure 7. Correlation between severity (A) and frequency (







of abdominalpain and the number of mast cells located within 5 m ofnerves in the colonic mucosa of IBS patients (r  0.75, P  0.001and r  0.70, P  0.003, respectively). The number of mast cells isrelative to 10 electron microscopy fields as described in the Materialsand Methods section.March 2004 NEUROIMMUNE INTERACTIONS AND IBS 699occurrence of a lowered threshold for induction of painfollowing rectal mechanical distention.45 This is likelydue to mast cell-induced increased firing of sensorynerves.18 Our ultrastructural data are in keeping withthis paradigm because we showed that mast cells of IBSpatients display a significantly greater rate of activation,as demonstrated by an increased number of cells showinglabyrinthic membranous arrays and clearing of individualgranules and by greater release of histamine and tryptase.To support further a role for mast cells in IBS pathophysiology,we measured the content and release of mastcell mediators by colonic mucosal biopsy specimens. Ourtryptase Western blotting experiments showed that colonicbiopsy specimens of IBS patients contained a largeramount of tryptase in comparison with controls, whichwell correlates with the increased total number of mastcells. Furthermore, our functional data demonstrated anenhanced release of tryptase in IBS patients. The speci-ficity of the tryptase activity detected by our assay wasconfirmed by the experiments showing that preincubationof samples with the tryptase inhibitor BABIM significantlysuppressed tryptase activity, whereas the trypsininhibitor SBTI had no effect. The increased release oftryptase in IBS patients suggests that this mediator mayaffect both extrinsic afferent and enteric neurons withlong-lasting effects on secretomotor function and visceralhypersensitivity, as supported by evidence in experimentalmodels.24,46,47 Furthermore, mast cells are by far thelargest storage site of histamine in the human body, andits release has been reported to be a reliable indicator ofmast cell degranulation.48 Histamine is known to activateenteric and extrinsic neurons.19 For example, prolongedexposure of guinea pig submucosal neurons tohistamine resulted in a marked neuronal activation.25Similarly, histamine has been demonstrated to causeactivation of abdominal visceral C-fiber afferents,26 aneffect likely mediated by H1 or H2 receptors expressed onprimary sensory neurons.49 These data, taken in conjunctionwith our demonstration of 80% increase in thespontaneous release of histamine from mucosal biopsyspecimens, suggest that histamine, in addition totryptase, could be involved in sensory-motor dysfunctionin IBS.In the human intestine, mast cells lie in proximity tonerves supplying the gut mucosa.15 This close spatialassociation has been indicated to be of functional relevancefor the crosstalk between the immune and nervoussystem of the gut.14 In the present study, we found thatmast cells of IBS patients were located in closer vicinityto mucosal innervation (with occasional membranemembranecontacts), suggesting that mediators releasedby mast cells, including tryptase and histamine, have anincreased potential to affect neural function. In keepingwith this hypothesis, we found a significant correlationbetween abdominal pain/discomfort (both severity andfrequency) and vicinity of mast cells to nerves supplyingthe colonic mucosal. In addition to these findings, previousstudies indicate that mast cell infiltration of thehuman gut wall is associated with abdominal pain andthat therapy targeting mast cells can improve abdominalpain perception both in systemic mastocytosis50 and inIBS.51 Taken together, these data strongly support amechanistic role for mast cell involvement in visceralnociception in IBS. On the other hand, no statisticalcorrelation was found between tryptase and histaminerelease and abdominal pain/discomfort. Different factorsmay account for this lack of correlation. First, althoughwe primarily assessed histamine and tryptase, mast cellsare known to release a wide variety of biologic substancesthat sensitize sensory nerves.19,21 This raises the possibilitythat combinations of these substances are necessary totrigger sensory nerve firing up to the level of abdominalpain/discomfort perception. Second, because mast cellsthat lie in close proximity to nerves correlate with abdominalpain/discomfort and show an increased rate ofdegranulation, it is conceivable that only the release ofhistamine and tryptase in close proximity to nerves isrelevant for abdominal pain/discomfort development.However, in this study, we detected the amount of eachmediator released from the pool of the mast cells ratherthan that in close proximity to nerves. Third, in keepingwith the Rome II criteria, the symptom questionnaireused in the present study did not discriminate betweenpain and discomfort, which were considered as a singlesymptom. Previous studies demonstrated that repetitivenoxious sigmoid balloon distention evoked visceral hypersensitivityonly in patients with abdominal pain butnot in those with nonpainful symptoms (e.g., discomfort,bloating, and sensation of gas).52 Thus, the possibilitythat the increased release of histamine and tryptase observedin our patients correlates with abdominal pain,but not with discomfort, needs further evaluation.The causes of a prominent colonic mast cell infiltrateand activation observed in IBS patients are unknown.Data suggest that factors including previous episodes ofinfectious enteritis35 and undiagnosed food allergies53may contribute either individually or in combination. Inthis study, we discarded the possibility to investigatepostinfectious IBS to avoid the bias related to retrospectiveanalyses. A prospective assessment of such a correlationis needed. The classical type of activation of mucosalmast cells is through an IgE-dependent (allergy)700 BARBARA ET AL. GASTROENTEROLOGY Vol. 126, No. 3mechanism.21 In our patients, we excluded the influenceof food allergies by means of history taking and foodspecificIgE antibodies. However, food allergy diagnosisremains elusive, and we cannot exclude that at least someof our patients suffered from a subclinical form of allergicgut disease.53 On the other hand, it is now widelyaccepted that mast cells can also respond to a nonï¿½IgEdependentstimulation.21 The best-known triggers ofthis alternative way of activation include bacterial toxins,neurotransmitters, and stress,54 all of which may beinvolved in IBS pathophysiology.5In conclusion, these results provide the rationale forconsidering nerve-mast cell interactions as a mechanismfor abdominal pain/discomfort generation in IBS and,hence, as a target for therapy.References1. Thompson WG, Longstreth GF, Drossman DA, Heaton KW, IrvineEJ, Muller-Lissner SA. Functional bowel disorders and functionalabdominal pain. Gut 1999;45(suppl 2):S43ï¿½S47.2. Sandler RS, Drossman DA, Nathan HP, McKee DC. Symptomcomplaints and health care seeking behavior in subjects withbowel dysfunction. Gastroenterology 1984;87:314ï¿½318.3. Stanghellini V, Cogliandro R, Barbara G, De Giorgio R, CogliandroL, Corinaldesi R. Motor function and dysfunction in functionaldyspepsia and irritable bowel syndrome. In: Holtmann G, TalleyNJ, eds. Gastrointestinal inflammation and disturbed gut function:the challenge of new concepts. Dordrecht: Kluwer AcademicPublishers, 2003:176ï¿½186.4. Camilleri M. Management of the irritable bowel syndrome. Gastroenterology2001;120:652ï¿½668.5. Barbara G, De Giorgio R, Stanghellini V, Cremon C, Corinaldesi R.A role for inflammation in irritable bowel syndrome? Gut 2002;51(suppl 1):i41ï¿½i44.6. Spiller RC. Postinfectious irritable bowel syndrome. Gastroenterology2003;124:1662ï¿½1671.7. Chadwick VS, Chen W, Shu D, Paulus B, Bethwaite P, Tie A,Wilson I. Activation of the mucosal immune system in irritablebowel syndrome. Gastroenterology 2002;122:1778ï¿½1783.8. Weston AP, Biddle WL, Bhatia PS, Miner PB Jr. Terminal ilealmucosal mast cells in irritable bowel syndrome. Dig Dis Sci1993;38:1590ï¿½1595.9. Tornblom H, Lindberg G, Nyberg B, Veress B. Full-thickness biopsyof the jejunum reveals inflammation and enteric neuropathyin irritable bowel syndrome. Gastroenterology 2002;123:1972ï¿½1979.10. Gwee KA, Graham JC, McKendrick MW, Collins SM, Marshall JS,Walters SJ, Read NW. Psychometric scores and persistence ofirritable bowel after infectious diarrhea. Lancet 1996;347:150ï¿½153.11. Neal KR, Hebden J, Spiller R. Prevalence of gastrointestinalsymptoms six months after bacterial gastroenteritis and riskfactors for development of the irritable bowel syndrome: postalsurvey of patients. BMJ 1997;314:779ï¿½782.12. Isgar B, Harman M, Kaye MD, Whorwell PJ. Symptoms of irritablebowel syndrome in ulcerative colitis in remission. Gut 1983;24:190ï¿½192.13. Oï¿½Sullivan M, Clayton N, Breslin NP, Harman I, Bountra C,McLaren A, Oï¿½Morain CA. Increased mast cells in the irritablebowel syndrome. Neurogastroenterol Motil 2000;12:449ï¿½457.14. Stead RH, Dixon MF, Bramwell NH, Riddell RH, Bienenstock J.Mast cells are closely apposed to nerves in the human gastrointestinalmucosa. Gastroenterology 1989;97:575ï¿½585.15. Stead RH, Tomioka M, Quinonez G, Simon GT, Felten SY, BienenstockJ. Intestinal mucosal mast cells in normal and nematodeinfectedrat intestines are in intimate contact with peptidergicnerves. Proc Natl Acad Sci U S A 1987;84:2975ï¿½2979.16. Reed DE, Barajas-Lopez C, Cottrell G, Velazquez-Rocha S, Dery O,Grady EF, Bunnett NW, Vanner SJ. Mast cell tryptase and proteinase-activated receptor 2 induce hyperexcitability of guinea-pigsubmucosal neurons. J Physiol 2003;547:531ï¿½542.17. Gao C, Liu S, Hu HZ, Gao N, Kim G, Xia Y, Wood JD. Serineproteases excite myenteric neurons through protease-activatedreceptors in guinea pig small intestine. Gastroenterology 2002;123:1554ï¿½1564.18. Nozdrachev AD, Akoev GN, Filippova LV, Sherman NO, LioudynoMI, Makarov FN. Changes in afferent impulse activity of smallintestine mesenteric nerves in response to antigen challenge.Neuroscience 1999;94:1339ï¿½1342.19. Bueno L, Fioramonti J, Delvaux M, Frexinos J. Mediators andpharmacology of visceral sensitivity: from basic to clinical investigations.Gastroenterology 1997;112:1714ï¿½1743.20. Castex N, Fioramonti J, Fargeas MJ, More J, Bueno L. Role of5-HT3 receptors and afferent fibers in the effects of mast celldegranulation on colonic motility in rats. Gastroenterology 1994;107:976ï¿½984.21. Metcalfe DD, Baram D, Mekori YA. Mast cells. Physiol Rev 1997;77:1033ï¿½1079.22. Macfarlane SR, Seatter MJ, Kanke T, Hunter GD, Plevin R. Proteinase-activated receptors. Pharmacol Rev 2001;53:245ï¿½282.23. Molino M, Barnathan ES, Numerof R, Clark J, Dreyer M, CumashiA, Hoxie JA, Schechter N, Woolkalis M, Brass LF. Interactions ofmast cell tryptase with thrombin receptors and PAR-2. J BiolChem 1997;272:4043ï¿½4049.24. Coelho AM, Vergnolle N, Guiard B, Fioramonti J, Bueno L. Proteinasesand proteinase-activated receptor 2: a possible role topromote visceral hyperalgesia in rats. Gastroenterology 2002;122:1035ï¿½1047.25. Tamura K, Wood JD. Effects of prolonged exposure to histamineon guinea pig intestinal neurons. Dig Dis Sci 1992;37:1084ï¿½1088.26. Fu LW, Pan HL, Longhurst JC. Endogenous histamine stimulatesischemically sensitive abdominal visceral afferents through H1receptors. Am J Physiol 1997;273:H2726ï¿½H2737.27. Liu S, Hu HZ, Gao N, Gao C, Wang G, Wang X, Peck OC, Kim G,Gao X, Xia Y, Wood JD. Neuroimmune interactions in guinea pigstomach and small intestine. Am J Physiol Gastrointest LiverPhysiol 2003;284:G154ï¿½G164.28. Talley NJ, Phillips SF, Melton J III, Wiltgen C, Zinsmeister AR. Apatient questionnaire to identify bowel disease. Ann Intern Med1989;111:671ï¿½674.29. Neri M, Laterza F, Howell S, Di Gioacchino M, Festi D, Ballone E,Cuccurullo F, Talley NJ. Symptoms discriminate irritable bowelsyndrome from organic gastrointestinal diseases and food allergy.Eur J Gastroenterol Hepatol 2000;12:981ï¿½988.30. Jensen MP, Turner LR, Turner JA, Romano JM. The use of multiple-item scales for pain intensity measurement in chronic painpatients. Pain 1996;67:35ï¿½40.31. Lee E, Schiller LR, Fordtran JS. Quantification of colonic laminapropria cells by means of a morphometric point-counting method.Gastroenterology 1988;94:409ï¿½418.32. Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH,Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC.Measurement of protein using bicinchoninic acid. Anal Biochem1985;150:76ï¿½85.33. Raithel M, Schneider HT, Hahn EG. Effect of substance P onhistamine secretion from gut mucosa in inflammatory bowel disease.Scand J Gastroenterol 1999;34:496ï¿½503.March 2004 NEUROIMMUNE INTERACTIONS AND IBS 70134. Collins SM. The immunomodulation of enteric neuromuscularfunction: implications for motility and inflammatory disorders.Gastroenterology 1996;111:1683ï¿½1699.35. Gwee KA, Leong YL, Graham C, McKendrick MW, Collins SM,Walters SJ, Underwood JE, Read NW. The role of psychologicaland biological factors in postinfective gut dysfunction. Gut 1999;44:400ï¿½406.36. Rao SS, Read NW, Davison PA, Bannister JJ, Holdsworth CD.Anorectal sensitivity and responses to rectal distention in patientswith ulcerative colitis. Gastroenterology 1987;93:1270ï¿½1275.37. Chang L, Munakata J, Mayer EA, Schmulson MJ, Johnson TD,Bernstein CN, Saba L, Naliboff B, Anton PA, Matin K. Perceptualresponses in patients with inflammatory and functional boweldisease. Gut 2000;47:497ï¿½505.38. Pockros PJ, Foroozan P. Golytely lavage versus a standardcolonoscopy preparation. Effect on normal colonic mucosal histology.Gastroenterology 1985;88:545ï¿½548.39. Wood JD. Neuropathophysiology of irritable bowel syndrome.J Clin Gastroenterol 2002;35(suppl 1):S11ï¿½S22.40. Rao SS, Holdsworth CD, Read NW. Symptoms and stool patternsin patients with ulcerative colitis. Gut 1988;29:342ï¿½345.41. Schuurs AH, Verheul HA. Effects of gender and sex steroids onthe immune response. J Steroid Biochem 1990;35:157ï¿½172.42. Bradesi S, Eutamene H, Theodorou V, Fioramonti J, B


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## Nath (Jan 5, 1999)

Maybe probiotic enema's might be more effective? Obviously not as easy as ingesting the bacteria, but both at the same time might prove more effective.


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## Nath (Jan 5, 1999)

Maybe probiotic enema's might be more effective? Obviously not as easy as ingesting the bacteria, but both at the same time might prove more effective.


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## eric (Jul 8, 1999)

In most IBD conditions, except perhaps miscroscopic colitus inflammtion can be seen with a colonoscopy. They do not see inflammation in IBS with a colonoscopy. The bowel appears totally normal in IBS with a colonoscopy, it isn't until they peel back the layers of the gut wall they find subtle inflamatory cell changes.There are also different types of IBD diseses.Also IBD conditions are DISEASES and IBS is not at this time.also blood tests help to diagnose IBD conditions.There are many things also that seperate the two including some symptoms.And one more time, inflammation cannot be a diagnostic marker in all IBSers!!!! It does not cause pain in everyone who has inflammation!In chrons disease for example they can actually see ulceration of the colon."Crohn's disease is a severe, chronic inflammatory bowel disease. It causes inflammation, ulcers, and bleeding in the digestive tract. Crohn's disease usually affects the small intestine, particularly the last section (called the ileum), but any part of the digestive tract can be affected from the mouth to the anus." http://ehc.healthgate.com/GetContent.asp?s...ocid=/dci/crohn


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## eric (Jul 8, 1999)

In most IBD conditions, except perhaps miscroscopic colitus inflammtion can be seen with a colonoscopy. They do not see inflammation in IBS with a colonoscopy. The bowel appears totally normal in IBS with a colonoscopy, it isn't until they peel back the layers of the gut wall they find subtle inflamatory cell changes.There are also different types of IBD diseses.Also IBD conditions are DISEASES and IBS is not at this time.also blood tests help to diagnose IBD conditions.There are many things also that seperate the two including some symptoms.And one more time, inflammation cannot be a diagnostic marker in all IBSers!!!! It does not cause pain in everyone who has inflammation!In chrons disease for example they can actually see ulceration of the colon."Crohn's disease is a severe, chronic inflammatory bowel disease. It causes inflammation, ulcers, and bleeding in the digestive tract. Crohn's disease usually affects the small intestine, particularly the last section (called the ileum), but any part of the digestive tract can be affected from the mouth to the anus." http://ehc.healthgate.com/GetContent.asp?s...ocid=/dci/crohn


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## eric (Jul 8, 1999)

Sorry did not mean to double post this and try to edit it, but it would not let me.Also their are differet types of IBD dieases and IBD are disases unlike IBS which is not a diases or disease process at this time.Tals information is wrong!!!!!!!!!!"Inflammatory bowel disease (IBD) refers to chronic conditions that cause inflammation in the lining and, in some instances, the wall of the intestine. The two primary types are: Ulcerative Colitis ï¿½ This type causes inflammation and ulcers in the top lining of the colon and rectum. "Crohnï¿½s Disease ï¿½ This type causes inflammation and ulcers in the lining and the wall of any part of the gastrointestinal tract. Crohn's disease usually affects the small intestine, particularly the last section (called the ileum). However, any part of the gastrointestinal tractï¿½from the mouth to the anusï¿½can be affected. The inflammation associated with Crohnï¿½s disease reaches deeper into the layers of the intestinal wall, as opposed to ulcerative colitis, which affects primarily the lining of the intestine. http://polkmedicalcenter.com/healthcontent...E2-00508B62BE1F Colonsocopies see inflammation in IBD conditions, they do not in IBS. Unless someone has inflammation for other reasons.


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## eric (Jul 8, 1999)

Sorry did not mean to double post this and try to edit it, but it would not let me.Also their are differet types of IBD dieases and IBD are disases unlike IBS which is not a diases or disease process at this time.Tals information is wrong!!!!!!!!!!"Inflammatory bowel disease (IBD) refers to chronic conditions that cause inflammation in the lining and, in some instances, the wall of the intestine. The two primary types are: Ulcerative Colitis ï¿½ This type causes inflammation and ulcers in the top lining of the colon and rectum. "Crohnï¿½s Disease ï¿½ This type causes inflammation and ulcers in the lining and the wall of any part of the gastrointestinal tract. Crohn's disease usually affects the small intestine, particularly the last section (called the ileum). However, any part of the gastrointestinal tractï¿½from the mouth to the anusï¿½can be affected. The inflammation associated with Crohnï¿½s disease reaches deeper into the layers of the intestinal wall, as opposed to ulcerative colitis, which affects primarily the lining of the intestine. http://polkmedicalcenter.com/healthcontent...E2-00508B62BE1F Colonsocopies see inflammation in IBD conditions, they do not in IBS. Unless someone has inflammation for other reasons.


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## Talissa (Apr 10, 2004)

You can say I'm wrong Eric, but it doesn't change the fact that... Eric said above


> quote:In IBD conditions where the OUTSIDE of the gut wall is inflammed they have been shown to help, but in IBS the outer gut wall is not inflammed.


Why are you saying I'm wrong, when you are?Let's review:1. The inflammation of both IBS & IBD occur on the inner layer of the intestinal wall.(mucosal layer) It's just low grade/more microscopic in IBS, or rather in the IBS patients that they've biopsied...2. It hasn't been shown that probiotics help the outer wall as opposed to the inner wall. Duh.___________________________You said, "Tals info is wrong!!", and I can't help but wonder, about what???What info was wrong??(pls make sure I actually said/posted whatever it is that I was wrong about)


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## Talissa (Apr 10, 2004)

You can say I'm wrong Eric, but it doesn't change the fact that... Eric said above


> quote:In IBD conditions where the OUTSIDE of the gut wall is inflammed they have been shown to help, but in IBS the outer gut wall is not inflammed.


Why are you saying I'm wrong, when you are?Let's review:1. The inflammation of both IBS & IBD occur on the inner layer of the intestinal wall.(mucosal layer) It's just low grade/more microscopic in IBS, or rather in the IBS patients that they've biopsied...2. It hasn't been shown that probiotics help the outer wall as opposed to the inner wall. Duh.___________________________You said, "Tals info is wrong!!", and I can't help but wonder, about what???What info was wrong??(pls make sure I actually said/posted whatever it is that I was wrong about)


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## Kacebece3 (Apr 17, 2002)

Thanks for the info Talissa, Eric some of your info seems to contradict its self. IBS has no inflamation? Inflamation does not have IBS symptoms? If there is no evidence that chrons or colitis is present but low grade inflamation is and this is acompanied with IBS symptoms it must be a form of IBS.Later Ken


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## Kacebece3 (Apr 17, 2002)

Thanks for the info Talissa, Eric some of your info seems to contradict its self. IBS has no inflamation? Inflamation does not have IBS symptoms? If there is no evidence that chrons or colitis is present but low grade inflamation is and this is acompanied with IBS symptoms it must be a form of IBS.Later Ken


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## SpAsMaN* (May 11, 2002)

Eric,is it the same Barbara article we share?Too bad the photos is not there,it was so clear with them.


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## SpAsMaN* (May 11, 2002)

Eric,is it the same Barbara article we share?Too bad the photos is not there,it was so clear with them.


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## Talissa (Apr 10, 2004)

All I know is that to say the "outer layer of the intestinal wall is inflamed in IBD" is saying something erroneous.It never is in UC & can be in Crohn's~ï¿½Ulcerative colitis is characterized by recurring episodes of inflammation of the mucosal layer of the large bowel not related to an intestinal infection. Crohn's disease is characterized by recurring episodes of suppurative inflammation of any part of the bowel, from the mouth to the anus.ï¿½ http://www.clevelandclinicmeded.com/diseas...atory_bowel.htm


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## Talissa (Apr 10, 2004)

All I know is that to say the "outer layer of the intestinal wall is inflamed in IBD" is saying something erroneous.It never is in UC & can be in Crohn's~ï¿½Ulcerative colitis is characterized by recurring episodes of inflammation of the mucosal layer of the large bowel not related to an intestinal infection. Crohn's disease is characterized by recurring episodes of suppurative inflammation of any part of the bowel, from the mouth to the anus.ï¿½ http://www.clevelandclinicmeded.com/diseas...atory_bowel.htm


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## eric (Jul 8, 1999)

My information contradicts itself. LOLTal, you better check the accuracy of your posts before you post them.Ken, this information takes a long time to learn and you have to read it all carefully or you can make some of the same inaccurate assumtions tal is making. The first is to study how they diagone IBS in the first place because that is super important to waht were talking about here. Specifically through a cluster of symptoms for one, with no alarm signs."If there is no evidence that chrons or colitis is present but low grade inflamation is and this is acompanied with IBS symptoms it must be a form of IBS.What? IBD is a disease! IBS is a functional disorder! The way the digestive system functions. There are biological abnormalities in IBS, inflammation is ONE of them, there are more.Inflamation cannot be the biological marker for IBS!!! People with celiac spriuce and some IBD conditions all have inflammation, but not all have pain. Pain is a MUST for IBS!IBS has no Overt inflammation!! IBS IS NOT AN INFLAMATORY BOWEL DISEASE!!!"All I know is that to say the "outer layer of the intestinal wall is inflamed in IBD" is saying something erroneous."FalseUlcerative Colitis ï¿½ This type causes inflammation and ulcers in the top lining of the colon and rectum. ""Crohnï¿½s Disease ï¿½ This type causes inflammation and ulcers in the lining and the wall of any part of the gastrointestinal tract. Crohn's disease usually affects the small intestine, particularly the last section (called the ileum). However, any part of the gastrointestinal tractï¿½from the mouth to the anusï¿½can be affected. The inflammation associated with Crohnï¿½s disease reaches deeper into the layers of the intestinal wall, as opposed to ulcerative colitis, which affects primarily the lining of the intestine."ULcerations in the digestive lining!!! They can see these with colonoscopies. They cannot see the inflammation in IBS with colonoscopies!!!IBS DOES NOT CAUSE ULCERATIONS OF THE DIGESTIVE SYSTEM!!!!!Sapsman yes that was the study you sent me, I meant to say that soory. Thanks for that."Although conventional histological examination of mucosal biopsies in IBS shows no abnormality, when detailed quantification is undertaken changes are noted. We performed serial rectal biopsies in individuals recovering from Campylobacter gastroenteritis at 2, 6, 12 and 52 weeks. We note initial increases in both inflammatory cells and enteroendocrine cells, which mostly returned towards normal, but remained abnormal in a few markedly symptomatic individuals 8. Similar abnormalities were noted in patients attending the outpatients with a history of post-infectious Irritable Bowel Syndrome. There is a good correlation between the inflammatory cells and the enteroendocrine cells suggesting that cytokines might drive the enteroendocrine cell hyperplasia. The main content of the enteroendocrine cells is 5HT, an agent that stimulates peristalsis and intestinal secretion causing diarrhea in normal subjects. Drugs, which inhibit the action of 5HT such as Alosetron, are likely to show benefit in this group thought they have not been specifically studied.Other authors have noted increased enteroendocrine cells in unselected irritable bowel patients 9 but this needs confirmation. More important than increase in numbers may be the increase in release of 5HT. Several pilot studies 10 including some reported at DDW this year suggested that there was an exaggerated release of 5HT following a meal particularly in those who got meal related symptoms 11." http://www.med.unc.edu/wrkunits/2depts/med..._infectious.htm When they look at the colon in IBS it appears normal on the outside and healthy. When they dig deeper in PI IBS patients and in IBS patients, celluralr changes are noted! Mast cells being one of them and they are inflammed a small cell. I will post some pictures later of them.


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## eric (Jul 8, 1999)

My information contradicts itself. LOLTal, you better check the accuracy of your posts before you post them.Ken, this information takes a long time to learn and you have to read it all carefully or you can make some of the same inaccurate assumtions tal is making. The first is to study how they diagone IBS in the first place because that is super important to waht were talking about here. Specifically through a cluster of symptoms for one, with no alarm signs."If there is no evidence that chrons or colitis is present but low grade inflamation is and this is acompanied with IBS symptoms it must be a form of IBS.What? IBD is a disease! IBS is a functional disorder! The way the digestive system functions. There are biological abnormalities in IBS, inflammation is ONE of them, there are more.Inflamation cannot be the biological marker for IBS!!! People with celiac spriuce and some IBD conditions all have inflammation, but not all have pain. Pain is a MUST for IBS!IBS has no Overt inflammation!! IBS IS NOT AN INFLAMATORY BOWEL DISEASE!!!"All I know is that to say the "outer layer of the intestinal wall is inflamed in IBD" is saying something erroneous."FalseUlcerative Colitis ï¿½ This type causes inflammation and ulcers in the top lining of the colon and rectum. ""Crohnï¿½s Disease ï¿½ This type causes inflammation and ulcers in the lining and the wall of any part of the gastrointestinal tract. Crohn's disease usually affects the small intestine, particularly the last section (called the ileum). However, any part of the gastrointestinal tractï¿½from the mouth to the anusï¿½can be affected. The inflammation associated with Crohnï¿½s disease reaches deeper into the layers of the intestinal wall, as opposed to ulcerative colitis, which affects primarily the lining of the intestine."ULcerations in the digestive lining!!! They can see these with colonoscopies. They cannot see the inflammation in IBS with colonoscopies!!!IBS DOES NOT CAUSE ULCERATIONS OF THE DIGESTIVE SYSTEM!!!!!Sapsman yes that was the study you sent me, I meant to say that soory. Thanks for that."Although conventional histological examination of mucosal biopsies in IBS shows no abnormality, when detailed quantification is undertaken changes are noted. We performed serial rectal biopsies in individuals recovering from Campylobacter gastroenteritis at 2, 6, 12 and 52 weeks. We note initial increases in both inflammatory cells and enteroendocrine cells, which mostly returned towards normal, but remained abnormal in a few markedly symptomatic individuals 8. Similar abnormalities were noted in patients attending the outpatients with a history of post-infectious Irritable Bowel Syndrome. There is a good correlation between the inflammatory cells and the enteroendocrine cells suggesting that cytokines might drive the enteroendocrine cell hyperplasia. The main content of the enteroendocrine cells is 5HT, an agent that stimulates peristalsis and intestinal secretion causing diarrhea in normal subjects. Drugs, which inhibit the action of 5HT such as Alosetron, are likely to show benefit in this group thought they have not been specifically studied.Other authors have noted increased enteroendocrine cells in unselected irritable bowel patients 9 but this needs confirmation. More important than increase in numbers may be the increase in release of 5HT. Several pilot studies 10 including some reported at DDW this year suggested that there was an exaggerated release of 5HT following a meal particularly in those who got meal related symptoms 11." http://www.med.unc.edu/wrkunits/2depts/med..._infectious.htm When they look at the colon in IBS it appears normal on the outside and healthy. When they dig deeper in PI IBS patients and in IBS patients, celluralr changes are noted! Mast cells being one of them and they are inflammed a small cell. I will post some pictures later of them.


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## Talissa (Apr 10, 2004)

Eric, what exactly did I say that was wrong?Put it in quotes or something.If you're going to say I'm wrong, at least back it up...


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## Talissa (Apr 10, 2004)

Eric, what exactly did I say that was wrong?Put it in quotes or something.If you're going to say I'm wrong, at least back it up...


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## Jhouston (Nov 9, 2003)

Eric, You say IBS MUST have pain! Isn't it "pain or discomfort"? I find that to be a gray area. What discomfort is to one person may not be to someone else. What if the same SENSATION is perceived differently? Then one person has IBS and the other does not? If this is true, then it would be a different problem. pain threshold? they need to fix the wording in Rome11 Bloating is uncomfortable for everyone I would think. cannot imagine someone enjoying gas and bloat....lol so if you have one you have the other (gas, bloat = pain, discomfort). Joann


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## Jhouston (Nov 9, 2003)

Eric, You say IBS MUST have pain! Isn't it "pain or discomfort"? I find that to be a gray area. What discomfort is to one person may not be to someone else. What if the same SENSATION is perceived differently? Then one person has IBS and the other does not? If this is true, then it would be a different problem. pain threshold? they need to fix the wording in Rome11 Bloating is uncomfortable for everyone I would think. cannot imagine someone enjoying gas and bloat....lol so if you have one you have the other (gas, bloat = pain, discomfort). Joann


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## kel1059 (Feb 28, 2003)

> quote: If you're going to say I'm wrong, at least back it up...


He gets confused a lot.


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## kel1059 (Feb 28, 2003)

> quote: If you're going to say I'm wrong, at least back it up...


He gets confused a lot.


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## SpAsMaN* (May 11, 2002)

The long post from Eric cames from one of the best IBS lab in the world.It's tough to understand but the original research cames with graphs.Thanks Eric.


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## SpAsMaN* (May 11, 2002)

The long post from Eric cames from one of the best IBS lab in the world.It's tough to understand but the original research cames with graphs.Thanks Eric.


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## Talissa (Apr 10, 2004)

It's the interpretation that's questionable.>>>>>>>>>>>>>>>>Could the confusion lie in that Eric calls (some layer) the "top layer"??And when the mucosal/inner layer is discussed, he considers this to be the "top layer'?If so, He needs to refer to this site again for a quick refresher in anatomy: http://hmi.sinclair.edu/module_lesson.asp?...10&LessonID=131 In the world of science, the mucosal layer IS the innermost layer of the GI tract wall.And UC has inflammation in the INNERMOST/mucosal layer, sometimes also in the second layer, the submucosal layer.Crohn's also has inflammation in the inner layer/mucosal and this layer is also damaged, but it usually also includes inflammation in the other 3 layers, all the wall through to the serosa layer, the "top layer"/outermost.__________________________________FROM MEDSCAPE 2003:"The development and use of biologic markers identifying low-grade inflammation would improve the characterization of subsets of IBS patients" http://www.medscape.com/viewarticle/457728_5 FROM MEDSCAPE 2002:"The field of irritable bowel syndrome (IBS) appears to be entering a new and exciting phase; evidence that at least some aspects of this disorder represent an organic or neurologic bowel disease has firmed, and novel management approaches are currently under investigation." http://www.medscape.com/viewarticle/434526


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## Talissa (Apr 10, 2004)

It's the interpretation that's questionable.>>>>>>>>>>>>>>>>Could the confusion lie in that Eric calls (some layer) the "top layer"??And when the mucosal/inner layer is discussed, he considers this to be the "top layer'?If so, He needs to refer to this site again for a quick refresher in anatomy: http://hmi.sinclair.edu/module_lesson.asp?...10&LessonID=131 In the world of science, the mucosal layer IS the innermost layer of the GI tract wall.And UC has inflammation in the INNERMOST/mucosal layer, sometimes also in the second layer, the submucosal layer.Crohn's also has inflammation in the inner layer/mucosal and this layer is also damaged, but it usually also includes inflammation in the other 3 layers, all the wall through to the serosa layer, the "top layer"/outermost.__________________________________FROM MEDSCAPE 2003:"The development and use of biologic markers identifying low-grade inflammation would improve the characterization of subsets of IBS patients" http://www.medscape.com/viewarticle/457728_5 FROM MEDSCAPE 2002:"The field of irritable bowel syndrome (IBS) appears to be entering a new and exciting phase; evidence that at least some aspects of this disorder represent an organic or neurologic bowel disease has firmed, and novel management approaches are currently under investigation." http://www.medscape.com/viewarticle/434526


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## eric (Jul 8, 1999)

"Inflammatory bowel disease (IBD) is a term encompassing a number of *chronic inflammatory disorders leading to damage of the gastrointestinal tract.* The most common of these disorders are ulcerative colitis and Crohn's disease. " http://www.medscape.com/viewarticle/450824?src=search Crohn's Disease *Crohn's disease is a chronic, recurrent inflammatory disease of the intestinal tract. * The intestinal tract has four major parts: the esophagus, or food tube; the stomach, where food is churned and digested; the long, small bowel, where nutrients, calories, and vitamins are absorbed; and the colon and rectum, where water is absorbed and stool is stored. The two primary sites for Crohn's disease are the ileum, which is the last portion of the small bowel (ileitis, regional enteritis), and the colon (Crohn's colitis). *The condition begins as small, microscopic nests of inflammation which persist and smolder. The lining of the bowel can then become ulcerated and the bowel wall thickened.* Eventually, the bowel may become narrowed or obstructed and surgery would be needed. What Causes Crohn's Disease?There is now evidence of a genetic link as Crohn's frequently shows up in a family group. In addition, there is evidence that the normal bacteria that grow in the lower gut may, in some manner, act to promote inflammation. The body's immune system, which protects it against many different infections, is known to be a factor. There are still a number of unknowns about the cause of the disease. Fortunately, a great deal is known about the disease and especially its treatment. Who Develops Crohn's Disease?The condition occurs in both sexes and among all age groups, although it most frequently begins in young people. Jewish people are at increased risk of developing Crohn's, while African Americans are at decreased risk, which indicates the genetic link in this disease. SymptomsThe symptoms of Crohn's disease depend on where in the intestinal tract the disorder appears. When the ileum (ileitis) is involved, recurrent pain may be experienced in the right lower abdomen. At times, the pain mimics acute appendicitis. When the colon is the site, diarrhea (sometimes bloody) may occur, along with fever and weight loss. Crohn's disease often affects the anal area where there may be a draining sinus tract called a fistula. When the disease is active, fatigue and lethargy appear. In children and adolescents there may be difficulty gaining or maintaining weight. DiagnosisThere is no one conclusive diagnostic test for Crohn's disease. The patient's medical history and physical exam are always helpful. Certain blood and stool tests are performed to arrive at a diagnosis. X-rays of the small intestine and colon (obtained through an upper GI series and barium enema) are usually required. In addition, a visual examination (sigmoidoscopy) of the lining of the rectum and lower bowel is usually necessary. *A more thorough exam of the entire colon (colonoscopy) is often the best way of diagnosing the problem when the disease is in the colon. * There is an inflammatory condition that is a lot harder for them to detect. Miscroscopic colitus.Ulcerative Colitis *Ulcerative colitis is a chronic, recurring disease of the large bowel.* The large bowel (colon) is the 5 to 6 foot segment of intestine that begins in the right-lower abdomen, extends upward and then across to the left side, and downward to the rectum. It dehydrates the liquid stool that enters it and stores the formed stool until a bowel movement occurs. *When ulcerative colitis affects the colon, inflammation and ulcers, or sores, form in the lining of the colon. The disease may involve the entire colon (pancolitis), only the rectum (ulcerative proctitis) or, more commonly, some area between the two. * These conditions left untreated can get very serious and even kill a person. http://www.gicare.com/pated/ecd0001.htm Images of the bowel in IBD conditions. These are graphic!!! http://www-medlib.med.utah.edu/WebPath/TUTORIAL/IBD/IBD.html Where as the inflammation in IBS does not progress and IBS does not lead to anything more serious, such as uclerations or cancer. *"There are no physical findings or diagnostic tests that confirm the diagnosis of IBS. Diagnosis involves identifying certain symptoms consistent with the disorder and excluding other medical conditions that may have a similar clinical presentation. The symptom-based Rome II diagnostic criteria for IBS emphasize a positive diagnosis rather than exhaustive tests to rule out other diseases. These criteria are based on the presentation of a specific set of symptoms. In addition, a detailed history, a physical examination, and limited diagnostic tests help confirm this diagnosis with a high level of confidence. Extensive testing may be reserved for specific situations. "* *"The symptoms of IBS are produced by abnormal functioning of the nerves and muscles of the bowel. In IBS there is no evidence of an organic disease, yet, something -- a "dysregulation" between the brain, the gut, and the central nervous system -- causes the bowel to become "irritated," or overly sensitive to stimuli. Symptoms may occur even in response to normal events. "* "Anemia, bleeding, weight loss, or fever are not characteristic of IBS. You should alert your physician immediately if you are experiencing these symptoms. Other factors that may suggest the presence of an organic disease include awakening from sleep at night, family history of colon cancer or inflammatory bowel disease, and onset of symptoms (or change in symptoms) over the age of 50. http://www.aboutibs.org/characteristics.html By the way bleeding and weight loss are found in IBD conditions where there is OVERT INFLAMATION, but NOT in IBS.Within the last ten years though in IBS specific abnormalities have been detected. Inflammation is not the only one there are many more. But not a marker in all IBSErs. There are ones that are close like the ACC of the brain and rectal hypersensitvity, but still not in all IBSers. This is why I am saying you should spend more time learning about how they diagnose IBS.This is why people see their doctors and they tell them they don't see anything wrong with the bowel and see a cluster of symptoms and diagnose IBS. Which using the rome 11 criteria is a stable diagnoses. So there is not the confusion over the two, one a disease the other GI disorder of function the way the digestive system functions!and one more time, because it doesn't seem to be sinking in here.From the rome websiteIrritable Bowel Syndrome: How far do you go in the Workup?" For example, there is a subgroup of patients, called "post-infectious IBS" who appear to respond to an enteric infection such as campylobactor jejuni with an increased inflammatory cell response (22). This is associated with activating enterochromaffin cells to produce 5HT, and CD3 cells to produce cytokines, which in turn leads to enhanced motility and lowered visceral sensation thresholds (22;23). *But microscopic inflammation cannot be a diagnostic marker for IBS because it does not typically produce pain in those who have it. All patients with active celiac disease have microscopic inflammation, but a large proportion do not have abdominal pain, and patients with ulcerative colitis who also have microscopic inflammation when compared to patients with IBS appear to have higher pain thresholds * (24)." http://www.romecriteria.org/reading1.html "Mast Cells and IBS The mast cell has potential to be a key player in IBS. Although mast cells are most widely known for their role in allergic responses, these cells are normally present throughout the gut and are involved in a range of physiological and pathological activities including mucosal defense mechanisms and inflammation. Mast cells may release an array of inflammatory mediators that act on smooth muscle, nerves and immune cells, which may ultimately result in gastrointestinal dysfunction and symptoms. In addition, mast cells in the gut are located close to nerves providing a structural basis for communication between the gut and the nervous system. In 1993, Weston and colleagues reported increased mast cell numbers in the mucosa of IBS patients(10) - these changes were identified in tissue from the end of the small bowel (terminal ileum). Similarly we identified significant increases in mast cells in IBS patients compared to controls in the colon (specifically at the caecum) (11). There were also trends for increases in other regions of the colon (ascending and descending colon), but no differences could be seen at the rectum. The lack of changes in mast cell infiltration in the rectum has since been confirmed by others (9). Collectively, these studies suggest that mast cells were increased in IBS patients. This may be part of a low-grade inflammatory response, although the components and nature of this response remain poorly understood. ""A Link between Inflamation and Stress *An increase in inflammatory mediators alone is insufficient to explain the pathogenesis of IBS.* From post-infective IBS, we know that the most people who have gastroenteritis and accompanying inflammation do not develop IBS. As discussed earlier, several factors may be important in interacting with the gut insult and in predicting those who develop symptoms - one interesting factor here is the role of stress. Psychological stress is known to affect gut function in normal healthy humans, and in people with IBS stress may trigger or exacerbate symptoms. More recently there is evidence of a link between stress and inflammatory responses. Exposure to stress in both animals and humans has been shown to result in the release of mast cell mediators in the colon (18,19) and in a recent study stress was capable reactivating previous inflammation in rats (15). An important challenge for future work will be to clarify the interaction between inflammation, stress and IBS symptoms." http://www.med.unc.edu/wrkunits/2depts/med...rymediators.htm Joann, I will come back to your question here, pain and discomfort make it kind of harder, because pain is subjective and because there is mild, moderate, and severe IBS. Severe pain IBS is in part associated with higher psycologial distress and the brain and viceral pain have psycophysiological connections and convergences that intertwine and react.


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## eric (Jul 8, 1999)

"Inflammatory bowel disease (IBD) is a term encompassing a number of *chronic inflammatory disorders leading to damage of the gastrointestinal tract.* The most common of these disorders are ulcerative colitis and Crohn's disease. " http://www.medscape.com/viewarticle/450824?src=search Crohn's Disease *Crohn's disease is a chronic, recurrent inflammatory disease of the intestinal tract. * The intestinal tract has four major parts: the esophagus, or food tube; the stomach, where food is churned and digested; the long, small bowel, where nutrients, calories, and vitamins are absorbed; and the colon and rectum, where water is absorbed and stool is stored. The two primary sites for Crohn's disease are the ileum, which is the last portion of the small bowel (ileitis, regional enteritis), and the colon (Crohn's colitis). *The condition begins as small, microscopic nests of inflammation which persist and smolder. The lining of the bowel can then become ulcerated and the bowel wall thickened.* Eventually, the bowel may become narrowed or obstructed and surgery would be needed. What Causes Crohn's Disease?There is now evidence of a genetic link as Crohn's frequently shows up in a family group. In addition, there is evidence that the normal bacteria that grow in the lower gut may, in some manner, act to promote inflammation. The body's immune system, which protects it against many different infections, is known to be a factor. There are still a number of unknowns about the cause of the disease. Fortunately, a great deal is known about the disease and especially its treatment. Who Develops Crohn's Disease?The condition occurs in both sexes and among all age groups, although it most frequently begins in young people. Jewish people are at increased risk of developing Crohn's, while African Americans are at decreased risk, which indicates the genetic link in this disease. SymptomsThe symptoms of Crohn's disease depend on where in the intestinal tract the disorder appears. When the ileum (ileitis) is involved, recurrent pain may be experienced in the right lower abdomen. At times, the pain mimics acute appendicitis. When the colon is the site, diarrhea (sometimes bloody) may occur, along with fever and weight loss. Crohn's disease often affects the anal area where there may be a draining sinus tract called a fistula. When the disease is active, fatigue and lethargy appear. In children and adolescents there may be difficulty gaining or maintaining weight. DiagnosisThere is no one conclusive diagnostic test for Crohn's disease. The patient's medical history and physical exam are always helpful. Certain blood and stool tests are performed to arrive at a diagnosis. X-rays of the small intestine and colon (obtained through an upper GI series and barium enema) are usually required. In addition, a visual examination (sigmoidoscopy) of the lining of the rectum and lower bowel is usually necessary. *A more thorough exam of the entire colon (colonoscopy) is often the best way of diagnosing the problem when the disease is in the colon. * There is an inflammatory condition that is a lot harder for them to detect. Miscroscopic colitus.Ulcerative Colitis *Ulcerative colitis is a chronic, recurring disease of the large bowel.* The large bowel (colon) is the 5 to 6 foot segment of intestine that begins in the right-lower abdomen, extends upward and then across to the left side, and downward to the rectum. It dehydrates the liquid stool that enters it and stores the formed stool until a bowel movement occurs. *When ulcerative colitis affects the colon, inflammation and ulcers, or sores, form in the lining of the colon. The disease may involve the entire colon (pancolitis), only the rectum (ulcerative proctitis) or, more commonly, some area between the two. * These conditions left untreated can get very serious and even kill a person. http://www.gicare.com/pated/ecd0001.htm Images of the bowel in IBD conditions. These are graphic!!! http://www-medlib.med.utah.edu/WebPath/TUTORIAL/IBD/IBD.html Where as the inflammation in IBS does not progress and IBS does not lead to anything more serious, such as uclerations or cancer. *"There are no physical findings or diagnostic tests that confirm the diagnosis of IBS. Diagnosis involves identifying certain symptoms consistent with the disorder and excluding other medical conditions that may have a similar clinical presentation. The symptom-based Rome II diagnostic criteria for IBS emphasize a positive diagnosis rather than exhaustive tests to rule out other diseases. These criteria are based on the presentation of a specific set of symptoms. In addition, a detailed history, a physical examination, and limited diagnostic tests help confirm this diagnosis with a high level of confidence. Extensive testing may be reserved for specific situations. "* *"The symptoms of IBS are produced by abnormal functioning of the nerves and muscles of the bowel. In IBS there is no evidence of an organic disease, yet, something -- a "dysregulation" between the brain, the gut, and the central nervous system -- causes the bowel to become "irritated," or overly sensitive to stimuli. Symptoms may occur even in response to normal events. "* "Anemia, bleeding, weight loss, or fever are not characteristic of IBS. You should alert your physician immediately if you are experiencing these symptoms. Other factors that may suggest the presence of an organic disease include awakening from sleep at night, family history of colon cancer or inflammatory bowel disease, and onset of symptoms (or change in symptoms) over the age of 50. http://www.aboutibs.org/characteristics.html By the way bleeding and weight loss are found in IBD conditions where there is OVERT INFLAMATION, but NOT in IBS.Within the last ten years though in IBS specific abnormalities have been detected. Inflammation is not the only one there are many more. But not a marker in all IBSErs. There are ones that are close like the ACC of the brain and rectal hypersensitvity, but still not in all IBSers. This is why I am saying you should spend more time learning about how they diagnose IBS.This is why people see their doctors and they tell them they don't see anything wrong with the bowel and see a cluster of symptoms and diagnose IBS. Which using the rome 11 criteria is a stable diagnoses. So there is not the confusion over the two, one a disease the other GI disorder of function the way the digestive system functions!and one more time, because it doesn't seem to be sinking in here.From the rome websiteIrritable Bowel Syndrome: How far do you go in the Workup?" For example, there is a subgroup of patients, called "post-infectious IBS" who appear to respond to an enteric infection such as campylobactor jejuni with an increased inflammatory cell response (22). This is associated with activating enterochromaffin cells to produce 5HT, and CD3 cells to produce cytokines, which in turn leads to enhanced motility and lowered visceral sensation thresholds (22;23). *But microscopic inflammation cannot be a diagnostic marker for IBS because it does not typically produce pain in those who have it. All patients with active celiac disease have microscopic inflammation, but a large proportion do not have abdominal pain, and patients with ulcerative colitis who also have microscopic inflammation when compared to patients with IBS appear to have higher pain thresholds * (24)." http://www.romecriteria.org/reading1.html "Mast Cells and IBS The mast cell has potential to be a key player in IBS. Although mast cells are most widely known for their role in allergic responses, these cells are normally present throughout the gut and are involved in a range of physiological and pathological activities including mucosal defense mechanisms and inflammation. Mast cells may release an array of inflammatory mediators that act on smooth muscle, nerves and immune cells, which may ultimately result in gastrointestinal dysfunction and symptoms. In addition, mast cells in the gut are located close to nerves providing a structural basis for communication between the gut and the nervous system. In 1993, Weston and colleagues reported increased mast cell numbers in the mucosa of IBS patients(10) - these changes were identified in tissue from the end of the small bowel (terminal ileum). Similarly we identified significant increases in mast cells in IBS patients compared to controls in the colon (specifically at the caecum) (11). There were also trends for increases in other regions of the colon (ascending and descending colon), but no differences could be seen at the rectum. The lack of changes in mast cell infiltration in the rectum has since been confirmed by others (9). Collectively, these studies suggest that mast cells were increased in IBS patients. This may be part of a low-grade inflammatory response, although the components and nature of this response remain poorly understood. ""A Link between Inflamation and Stress *An increase in inflammatory mediators alone is insufficient to explain the pathogenesis of IBS.* From post-infective IBS, we know that the most people who have gastroenteritis and accompanying inflammation do not develop IBS. As discussed earlier, several factors may be important in interacting with the gut insult and in predicting those who develop symptoms - one interesting factor here is the role of stress. Psychological stress is known to affect gut function in normal healthy humans, and in people with IBS stress may trigger or exacerbate symptoms. More recently there is evidence of a link between stress and inflammatory responses. Exposure to stress in both animals and humans has been shown to result in the release of mast cell mediators in the colon (18,19) and in a recent study stress was capable reactivating previous inflammation in rats (15). An important challenge for future work will be to clarify the interaction between inflammation, stress and IBS symptoms." http://www.med.unc.edu/wrkunits/2depts/med...rymediators.htm Joann, I will come back to your question here, pain and discomfort make it kind of harder, because pain is subjective and because there is mild, moderate, and severe IBS. Severe pain IBS is in part associated with higher psycologial distress and the brain and viceral pain have psycophysiological connections and convergences that intertwine and react.


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## Kacebece3 (Apr 17, 2002)

well I guess I don't have IBS, just have the symptoms...................LOL


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## Kacebece3 (Apr 17, 2002)

well I guess I don't have IBS, just have the symptoms...................LOL


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## eric (Jul 8, 1999)

Why do you say that ken? Because you have inflammation they can see? But you also have another condition which can cause inflammation.Did you get a colonoscopy.I have had four and they have never found a thing with them. I have also had many other tests, upper endoscopy and others. All tests negative. IBS is the most common problem seen by gastro docs.Rome llIrritable Bowel Syndrome: How far do you go in the Workup?Douglas A. Drossman, M.D.Professor of Medicine and PsychiatryCo-Director, UNC Center for Functional GI and Motility DisordersDivision of Digestive DiseasesUniversity of North Carolina at Chapel Hill"Currently, the diagnostic evaluation of patients presenting with IBS symptoms has no simple standard; it is based on the art and science of medicine. Several factors can influence the decision making: a) symptom pattern and severity will influence, for example whether mucosal biopsies are taken for diarrhea-predominant symptoms, or ultrasound or CT are done for pain and weight loss(3),







demographic features such as older age on initial presentation or a family history of IBD or colon cancer may lead to a more extensive (e.g., colonoscopic) evaluation, c) a patient's pain communication style or illness-related behaviors must be appraised in the light of objective screening data; this, for example will reduce the tendency merely to order tests based on urgent requests to "do something" ("furor medicus") (4), and finally d), the clinical setting will influence the prior probability of other medical disorders; so primary care physicians more than gastroenterologists will minimize diagnostic studies, treat the symptoms of IBS, and follow the patient expectantly (5), simply because the likelihood of another serious medical disease in a primary care setting is far less than in a referral practice. Efforts to consolidate these many influences on diagnostic decision making have occurred by creating specific published guidelines obtained by consensus (3;6) (7). Most all authors agree that an initial diagnosis of IBS should be fulfilled by: a) meeting symptom-based diagnostic criteria, such as Rome II (6;8), Rome I (9) (10), or occasionally, Manning (11) criteria, obtaining a negative physical examination, and performing a cost-effective, conservative set of screening studies. These usually include a sigmoidoscopy (or colonoscopy for patients older than 50 years), a few laboratory tests (e.g., CBC, stool for occult blood or ova and parasites) and additional studies if certain "alarm" features are found: fever, an abnormal physical examination, blood in the stool, an abnormal CBC or elevated sedimentation rate, significant weight loss, nocturnal symptoms that awaken the patient, or a family history of cancer or inflammatory bowel disease (12;13). Several prospective studies now offer evidence that the proper application of such recommendations rarely leads to a revision in diagnosis, even for patients followed over many years (14;15) (6). In one study, the positive predictive value for the diagnosis of IBS using Rome I criteria and excluding "red flags" over 1-year follow-up was 98% (12). Of course, the gastroenterologist in referral practice may not be content to accept these probabilities without first excluding those rare conditions overlooked by routine evaluations. So how far should the gastroenterologist go in the workup of patients referred to them who typically present with IBS, and have negative screening studies? One gastroenterologist, recently commented to me: "I order breath hydrogen studies and sprue serologies on all my patients referred with IBS". No doubt this comment reflects the concern that as referral gastroenterologists we have an obligation to contribute additional expertise to the diagnostic effort. Recently, the breath H2 test is being requested more actively by physicians and the public alike possibly because of media attention to a study claiming a 73% rate of bacterial overgrowth in patients with IBS referred for breath H2 testing, and a 50% improvement with antibiotic treatment (16). However, the design limitations of this study, including a high ascertainment bias, use of an uncontrolled and unblinded treatment protocol, and only a 30% follow up rate evaluated over a relatively short period of time, makes it unlikely that clinicians in practice will also obtain such dramatic results. So while this study increases awareness of bacterial overgrowth as an entity that can mimic or exacerbate IBS, clinical experience suggests that the diagnostic yield in general GI practice is probably much lower than reported, perhaps 10% or less. " http://www.romecriteria.org/reading1.html


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## eric (Jul 8, 1999)

Why do you say that ken? Because you have inflammation they can see? But you also have another condition which can cause inflammation.Did you get a colonoscopy.I have had four and they have never found a thing with them. I have also had many other tests, upper endoscopy and others. All tests negative. IBS is the most common problem seen by gastro docs.Rome llIrritable Bowel Syndrome: How far do you go in the Workup?Douglas A. Drossman, M.D.Professor of Medicine and PsychiatryCo-Director, UNC Center for Functional GI and Motility DisordersDivision of Digestive DiseasesUniversity of North Carolina at Chapel Hill"Currently, the diagnostic evaluation of patients presenting with IBS symptoms has no simple standard; it is based on the art and science of medicine. Several factors can influence the decision making: a) symptom pattern and severity will influence, for example whether mucosal biopsies are taken for diarrhea-predominant symptoms, or ultrasound or CT are done for pain and weight loss(3),







demographic features such as older age on initial presentation or a family history of IBD or colon cancer may lead to a more extensive (e.g., colonoscopic) evaluation, c) a patient's pain communication style or illness-related behaviors must be appraised in the light of objective screening data; this, for example will reduce the tendency merely to order tests based on urgent requests to "do something" ("furor medicus") (4), and finally d), the clinical setting will influence the prior probability of other medical disorders; so primary care physicians more than gastroenterologists will minimize diagnostic studies, treat the symptoms of IBS, and follow the patient expectantly (5), simply because the likelihood of another serious medical disease in a primary care setting is far less than in a referral practice. Efforts to consolidate these many influences on diagnostic decision making have occurred by creating specific published guidelines obtained by consensus (3;6) (7). Most all authors agree that an initial diagnosis of IBS should be fulfilled by: a) meeting symptom-based diagnostic criteria, such as Rome II (6;8), Rome I (9) (10), or occasionally, Manning (11) criteria, obtaining a negative physical examination, and performing a cost-effective, conservative set of screening studies. These usually include a sigmoidoscopy (or colonoscopy for patients older than 50 years), a few laboratory tests (e.g., CBC, stool for occult blood or ova and parasites) and additional studies if certain "alarm" features are found: fever, an abnormal physical examination, blood in the stool, an abnormal CBC or elevated sedimentation rate, significant weight loss, nocturnal symptoms that awaken the patient, or a family history of cancer or inflammatory bowel disease (12;13). Several prospective studies now offer evidence that the proper application of such recommendations rarely leads to a revision in diagnosis, even for patients followed over many years (14;15) (6). In one study, the positive predictive value for the diagnosis of IBS using Rome I criteria and excluding "red flags" over 1-year follow-up was 98% (12). Of course, the gastroenterologist in referral practice may not be content to accept these probabilities without first excluding those rare conditions overlooked by routine evaluations. So how far should the gastroenterologist go in the workup of patients referred to them who typically present with IBS, and have negative screening studies? One gastroenterologist, recently commented to me: "I order breath hydrogen studies and sprue serologies on all my patients referred with IBS". No doubt this comment reflects the concern that as referral gastroenterologists we have an obligation to contribute additional expertise to the diagnostic effort. Recently, the breath H2 test is being requested more actively by physicians and the public alike possibly because of media attention to a study claiming a 73% rate of bacterial overgrowth in patients with IBS referred for breath H2 testing, and a 50% improvement with antibiotic treatment (16). However, the design limitations of this study, including a high ascertainment bias, use of an uncontrolled and unblinded treatment protocol, and only a 30% follow up rate evaluated over a relatively short period of time, makes it unlikely that clinicians in practice will also obtain such dramatic results. So while this study increases awareness of bacterial overgrowth as an entity that can mimic or exacerbate IBS, clinical experience suggests that the diagnostic yield in general GI practice is probably much lower than reported, perhaps 10% or less. " http://www.romecriteria.org/reading1.html


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## eric (Jul 8, 1999)

The role of psychological and biological factors in postinfective gut dysfunction http://gut.bmjjournals.com/cgi/content/short/44/3/400 CommentarySee article on page 400Mind over matter in the postinfective irritable bowel http://gut.bmjjournals.com/cgi/content/full/44/3/306


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## eric (Jul 8, 1999)

The role of psychological and biological factors in postinfective gut dysfunction http://gut.bmjjournals.com/cgi/content/short/44/3/400 CommentarySee article on page 400Mind over matter in the postinfective irritable bowel http://gut.bmjjournals.com/cgi/content/full/44/3/306


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## eric (Jul 8, 1999)

Joan, this will help explain the rationale for Rome.The functional gastrointestinal disorders and the Rome II processToward a new understanding of the functional gastrointestinal disorders http://gut.bmjjournals.com/cgi/content/full/45/suppl_2/II1


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## eric (Jul 8, 1999)

Joan, this will help explain the rationale for Rome.The functional gastrointestinal disorders and the Rome II processToward a new understanding of the functional gastrointestinal disorders http://gut.bmjjournals.com/cgi/content/full/45/suppl_2/II1


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## Talissa (Apr 10, 2004)

This was in Gut Magazine last year(opposed to the above references from 1999)2003" _Although we have previously shown that psychosocial factors _ operating at the time of, or prior to, the acute illness appear to predict the development of post-infectious IBS (PI-IBS), *our finding of an increased inflammatory cell number in the rectum persisting for at least three months after the acute infection suggested that there is also an organic component involved in the development of PI-IBS. * To evaluate this further, we measured expressions of interleukin 1ï¿½ (IL-1ï¿½) and its receptor antagonist (IL-1ra) in these patients to provide additional evidence that the pathogenesis of PI-IBS is underpinned by an inflammatory process. Conclusions: These findings indicate that those patients who develop IBS post infection exhibit greater IL-1ï¿½ mRNA expression, both during and after the infection, compared with individuals who do not develop PI-IBS. We conclude that such patients may be susceptible to inflammatory stimuli, and that inflammation may play a role in the pathogenesis of PI-IBS. http://gut.bmjjournals.com/cgi/content/abstract/52/4/523


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## Talissa (Apr 10, 2004)

This was in Gut Magazine last year(opposed to the above references from 1999)2003" _Although we have previously shown that psychosocial factors _ operating at the time of, or prior to, the acute illness appear to predict the development of post-infectious IBS (PI-IBS), *our finding of an increased inflammatory cell number in the rectum persisting for at least three months after the acute infection suggested that there is also an organic component involved in the development of PI-IBS. * To evaluate this further, we measured expressions of interleukin 1ï¿½ (IL-1ï¿½) and its receptor antagonist (IL-1ra) in these patients to provide additional evidence that the pathogenesis of PI-IBS is underpinned by an inflammatory process. Conclusions: These findings indicate that those patients who develop IBS post infection exhibit greater IL-1ï¿½ mRNA expression, both during and after the infection, compared with individuals who do not develop PI-IBS. We conclude that such patients may be susceptible to inflammatory stimuli, and that inflammation may play a role in the pathogenesis of PI-IBS. http://gut.bmjjournals.com/cgi/content/abstract/52/4/523


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## Talissa (Apr 10, 2004)

Gut Mag-- January 2004"Conclusions: BD (bacillary dysentery) is a causative factor in PI-IBS. The immune and nervous system may both play important roles in the pathogenesis of PI-IBS. http://gut.bmjjournals.com/cgi/content/full/53/8/1096 What about mast cells? These researchers from the above study believe it has to do with the immune response..."It is believed that brain-gut interactions play an important role in the pathogenesis of IBS. Possible connections exist between enteric nerves and immune cellular components. In light of the present literature, it was suggested that mast cells could be a possible candidate connecting the local immune response to the neurohormonal system during acute intestinal infection.6,7 "***In case curious, bacillary dysentery(BD) is (often)caused by infection with Shigella dysenteriae, flexneri, boydii or Shigella sonnei. All are enteroinvasive but some strains elaborate a toxin which is enterotoxic, neurotoxic and cytotoxic. The infection leads to an acute inflammation of the colon resulting in diarrhea containing a large number of leucocytes. http://www.thedoctorslounge.net/clinlounge...ns/shigella.htm ***It seems these infections wouldn't result in BD, then IBS if there's a low grade inflammatory response, if dysbiosis wasn't present to begin with. The benficial bacteria defend us against these types of pathogens. When we're low in probiotics along the wall(the mucosal/inner layer), which is dysbiosis, we're vulnerable.


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## Talissa (Apr 10, 2004)

Gut Mag-- January 2004"Conclusions: BD (bacillary dysentery) is a causative factor in PI-IBS. The immune and nervous system may both play important roles in the pathogenesis of PI-IBS. http://gut.bmjjournals.com/cgi/content/full/53/8/1096 What about mast cells? These researchers from the above study believe it has to do with the immune response..."It is believed that brain-gut interactions play an important role in the pathogenesis of IBS. Possible connections exist between enteric nerves and immune cellular components. In light of the present literature, it was suggested that mast cells could be a possible candidate connecting the local immune response to the neurohormonal system during acute intestinal infection.6,7 "***In case curious, bacillary dysentery(BD) is (often)caused by infection with Shigella dysenteriae, flexneri, boydii or Shigella sonnei. All are enteroinvasive but some strains elaborate a toxin which is enterotoxic, neurotoxic and cytotoxic. The infection leads to an acute inflammation of the colon resulting in diarrhea containing a large number of leucocytes. http://www.thedoctorslounge.net/clinlounge...ns/shigella.htm ***It seems these infections wouldn't result in BD, then IBS if there's a low grade inflammatory response, if dysbiosis wasn't present to begin with. The benficial bacteria defend us against these types of pathogens. When we're low in probiotics along the wall(the mucosal/inner layer), which is dysbiosis, we're vulnerable.


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## eric (Jul 8, 1999)

" Importantly, overt colonic inflammation precludes a diagnosis of IBS" http://www.med.unc.edu/wrkunits/2depts/med...rymediators.htm hence the "The role of psychological and biological factors in postinfective gut dysfunction "hence the "after the acute infection "There are subtle organic cells changes, and increases in EC (serotonin) cells and mast cells as I have stated many times now, both are very important to gut function.Stress doesn't cause IBS on its own, but it is a peredicting factor for some of the reasons I keep mentioning.The HPA axis releases chemicals that in turn effect the mast cells in the gut which then in turn release histimine and an array of other mediators. They are very close to the smooth muscle in the gut and the release of toxins from them naturally can inflame the cells.The HPA axis is involved in fighting infectious and the stress responce, the fight or flight.The constant activaing of the cells from bi directional communication and chronic stressors can inflames them and they release toxins onto the smoooth muscle.Chronic stress can also reactivate previous inflammation."organic component involved in the development of PI-IBS."There is a major organic componet in PI IBS, its called enteric infections and they can happen from more then one bacteria in the first place.Its when they resolve and your left with PI IBS which can turn into the full blown clinical experssion of IBS after resolution of the intial infection.Stress can also reactivate previous inflammation after the intial inflammation from the infection has resolved.American Gastroenterological AssociationAGA technical review on irritable bowel syndrome "Definition and classification TOP The Rome classification system1 characterizes the IBS in terms of multiple physiological determinants contributing to a common set of symptoms rather than a single disease entity. It is defined as a ï¿½group of functional bowel disorders in which abdominal discomfort or pain is associated with defecation or a change in bowel habit, and with features of disordered defecation.ï¿½2,3 Table 1 lists the recently revised Rome II diagnostic criteria for IBS.1 --------------------------------------------------------------------------------Table 1. Rome II diagnostic criteria for irritable bowel syndrome3-------------------------------------------------------------------------------- At least 12 weeks, which need not be consecutive, in the preceding 12 months of abdominal discomfort or pain that has 2 of 3 features: 1. Relieved with defecation; and/or 2. Onset associated with a change in frequency of stool; and/or 3. Onset associated with a change in form (appearance) of stool. Symptoms that cumulatively support the diagnosis of IBS: 1. Abnormal stool frequency (for research purposes, ï¿½abnormalï¿½ may be defined as greater than 3 bowel movements per day and less than 3 bowel movements per week); 2. Abnormal stool form (lumpy/hard or loose/watery stool); 3. Abnormal stool passage (straining, urgency, or feeling of incomplete evacuation); 4. Passage of mucus; 5. Bloating or feeling of abdominal distention. NOTE. The diagnosis of a functional bowel disorder always presumes the absence of a structural or biochemical explanation for the symptoms. "Pathophysiology of IBS symptoms TOP The physiological mechanisms responsible for abdominal pain and altered bowel habits occur in healthy control subjects and in persons with IBS. Symptoms can occur in response to a disruption of functioning of the GI tract from an infection, dietary indiscretions (e.g., increased fat or alcohol intake), lifestyle changes (e.g., traveling or vigorous physical activity), or psychologic stress. Among college students and hospital employees, 71% reported that stresses affected their bowel pattern, and 54% reported that stress led to abdominal pain or discomfort.10Abnormal motility in patients with IBS"The differences between IBS patients and healthy controls are quantitative rather than qualitative.Motility observations in the stomach, small intestine, colon, and rectum are qualitatively similar to those in healthy controls. Moreover, only 25%ï¿½75% of IBS patients exhibit the motility ï¿½abnormalitiesï¿½ listed in Table 3, which are considered to differentiate IBS from healthy controls. These motility parameters cannot be used as diagnostic markers.In the ileum, colon, and rectum, IBS patients show an exaggerated response to a variety of provocative stimuli including meals, distention, stress, cholecystokinin, neostigmine, and corticotropin-releasing hormone injection. No corresponding pattern of hyper-reactivity has been shown in the proximal small intestine and stomach, where the response to stress (inhibition of contractions) differs from the response to meals (increase in contractions).There is no consensus on the patterns of motility responsible for diarrhea and constipation, although accelerated transit is seen in diarrhea and slowed transit is seen in constipation. Among IBS patients exhibiting diarrhea and abdominal pain, there are significantly more high-amplitude propagating contractions, which are of higher amplitude than those observed in healthy controls, and these high-amplitude propagating contractions are more likely to be associated with a sensation of pain.Motility abnormalities may interact with low sensory thresholds to produce symptoms: delayed transit of gas causes greater abdominal perception in IBS,29 and IBS patients are more likely than healthy controls to perceive the occurrence of normal migrating motor complexes.30Visceral hypersensitivity in IBSIn 1973, Ritchie first reported that IBS patients have pain at lower volumes and pressures when a balloon is inflated in the bowel.31 This seminal observation has been replicated by a number of research laboratories,31ï¿½36 and the threshold to report pain is below the normal range in 50%ï¿½70% of IBS patients. Consistent with the concept of enhanced perception of visceral events are observations that IBS patients are more likely than controls to notice intestinal contractions37 and gas,29 and their pain thresholds are correlated, albeit weakly, with the amount of clinical pain they experience.32,38,39Enhanced perception of visceral events is documented throughout the GI tract, including the esophagus,40 stomach,41 duodenum,42ï¿½44 and ileum.45 However, IBS patients do not show somatic hypersensitivity to pain42,46,47 and may have elevated48,49 somatic pain thresholds.One study32 noted that when combining other measures of pain sensitivity, such as the intensity with which the pain sensation is described and the location and size of the somatic referral area, up to 95% of patients show evidence of visceral hypersensitivity. The investigators concluded that visceral hypersensitivity might be a biological marker for IBS, although this interpretation has been challenged.38InflammationPreliminary evidence for a possible alteration in gut immune function in IBS comes from both unselected and so-called postinfectious IBS (PI-IBS) patients. In unselected patients, increased numbers of mast cells in the muscularis externa of the colon50 and the ileal and colonic mucosa51,52 have been reported. Increased cellularity of the colonic mucosa and lamina propria has also been described in unselected IBS patients using semiquantitative microscopy.53 In patients with intractable IBS, lymphocytic infiltrates of the myenteric plexus were reported,54 and most recently, preliminary evidence for increased iNOS (nitric oxide synthetase) expression was described.55 For subgroups of IBS, these findings suggest there is an up-regulation of gut immune function. However, methodological deficiencies exist, including the influence of the bowel preparation, the classification of the patients, and the nonquantitative analysis of gut cells. Further studies are needed to explore these intriguing findings.Further support for a possible role of altered gut immune function in IBS comes from recent studies in PI-IBS patients.56ï¿½59 A subset of IBS patients associate the development of IBS symptoms with the onset of gastroenteritis.60ï¿½62 In recent prospective studies, IBS-like symptoms were found in 7%ï¿½30% of patients who recovered from a proven bacterial gastroenteritis.59 Reported risk factors included: female gender, duration of the acute diarrheal illness, and the presence of significant life stressor occurring around the time of the infection. Patients with PI-IBS were found to have a variety of functional alterations, including changes in gut motility,63,64 epithelial function,65,66 and an increase in colonic enterochromaffin cells.66 In addition, evidence for increased expression of interleukin 1 messenger RNA, increased cellularity of lamina propria, and an increase in CD3+ lymphocytes were reported from mucosal biopsy specimens.66 The correlation of IBS symptoms with these observed changes has not been established. Furthermore, because the majority of patients do not develop postinfectious diarrhea and the prevalence of IBS is not higher in countries with high rates of enteric infections, further studies are required to determine if vulnerability factors (such as altered neuroimmune system responsiveness) play a role in the development of PI-IBS in a subset of patients. In addition, psychological distress seems to be an important cofactor in determining who retains symptoms after an enteric infection.67Autonomic activityAbnormalities in extrinsic autonomic innervation of the viscera occur in approximately one fourth of patients with functional bowel disorders.68,69 Aggarwal et al. showed that cardiovagal dysfunction is specifically associated with a constipation-predominant subgroup of patients with IBS, whereas patients with diarrhea-predominant symptoms had evidence of sympathetic adrenergic dysfunction.70 The role of autonomic dysfunction in IBS requires further evaluation.Central nervous system modulationIn general, brain-gut interactions play a prominent role in the modulation of gut function in health and disease.71ï¿½74 Signals from the brain to the gut assure that digestive function is optimized for the overall state of the organism (e.g., sleep vs. wake, stress vs. relaxation).75 Conversely, signals from the gut to the brain play a role primarily in reflex regulation76 as well as in modulation of mood states.77 In addition, certain vagal afferent pathways can influence pain perception.78The CNS modulates motility, secretion, immune function, and blood flow.79 The emotional motor system in the brain80 is a revised name for the limbic system and some paralimbic structures (including the medial prefrontal cortex, amygdala, and hypothalamus) communicate emotional changes via the autonomic nervous system to the gut. The CNS is also essential in the perception of events occurring within the gut. This brain-gut bidirectional communication is largely not perceived consciously. In effect, the CNS functions as a ï¿½filterï¿½ with regard to the perception of peripheral afferent signals, and the threshold for perception can vary depending on the individual's emotional and cognitive state. Most visceral afferent signals reach the brainstem and thalamus, and only a very few are consciously perceived in the cortex.81 However, one recent study82 suggests that low intensity signals are subliminally registered.Modulation of visceral afferent information occurs at multiple levels from the periphery to cortical regions, as shown in Table 4. " Role of psychosocial factors in IBS TOP Research on the psychosocial aspects of patients with IBS has yielded 4 general observations.1001. Psychologic stress exacerbates GI symptoms. Although stressful experiences produce GI symptoms in most individuals, patients with IBS are particularly susceptible.10 Studies of the effects of stressful life events on IBS patients are shown in Table 5. 'With one exception,101 these studies suggest IBS patients report more lifetime and daily stressful events,10,14,102ï¿½107 including severe abuse history,108,109 than medical comparison groups or healthy controls. Furthermore, in IBS patients, stress is strongly associated with symptom onset105,107,110 and symptom severity.109 Even though the effects of stress on gut function are universal, patients with IBS seem to have greater reactivity to stress.72,111 The identification of specific psychological stressors associated with exacerbation of symptoms may help in planning treatment through psychological or psychopharmacological interventions.2. Psychological and psychiatric comorbidity is common among patients with IBS. A large proportion of patients with IBS and other functional bowel disorders have concurrent psychological disturbances. As shown in Table 6, when using standardized research interviews, the prevalence of a psychiatric disorder ranges from 40% to over 90% among patients with IBS/functional bowel disorders in tertiary care centers. ""Other psychological features identified to be greater in IBS include personality style,14,106,112 psychological distress,18,109,113 and altered health beliefs, cognitions, and coping style.114ï¿½117 As indicated below, these findings are not associated with the disorder per se, but their prevalence is over-represented within the health careï¿½seeking subset of patients.3. Psychosocial factors affect health status and clinical outcome. Psychological and sociocultural factors, when present in patients with IBS, will also influence the illness experience and treatment outcome. Psychosocial factors that adversely affect health status and clinical outcome include: (1) a history of emotional, sexual, or physical abuse109,118ï¿½121; (2) stressful life events104,110; (3) chronic social stress122 or anxiety disorder123,124; and (4) maladaptive coping style.119 Some of these psychosocial influences may occur early in life. For example, increased attention by family to a child's illness complaints seems to result in delayed symptom reporting, health care seeking, and health care costs.125ï¿½1294. Psychosocial factors influence which patients consult physicians. This tends to overestimate the true prevalence of psychosocial disturbance when evaluating patients in referral clinical settings. In fact, persons with IBS who do not see physicians are psychologically similar to subjects without bowel complaints.14,18,130" Diagnosis TOP Symptom-based criteriaA diagnosis is based on identifying positive symptoms (e.g., Rome criteria) consistent with the condition (Table 1), and excluding, in a cost-effective manner, other conditions with similar clinical presentations, which may include organic or other functional (e.g., functional diarrhea or bloating, pelvic floor disorders, or slow transit constipation with associated abdominal discomfort relieved with defecation) disorders.3,140 Any needed tests, as suggested by ï¿½alarm features,ï¿½ should be discussed with the patient and set up at the first encounter. When ï¿½alarm featuresï¿½ such as weight loss, refractory diarrhea, and family history of colon cancer are excluded, the specificity of the symptom-based Rome I criteria for IBS exceeds 98% and hence, the risk of missing organic disease is low.141EvaluationA physical examination should be performed on the first visit and on subsequent visits as needed. This is done to exclude findings not consistent with IBS (e.g., enlarged liver, abdominal mass, signs of bowel obstruction) and to meet the patient's expectations of a thorough evaluation. A pelvic examination is often indicated for lower abdominal/pelvic symptoms and/or if there is a change in menstrual pattern. A rectal examination, particularly for patients reporting symptoms of incontinence or dyschezia, can help to identify a lax sphincter or paradoxical pelvic floor muscle contraction. This may require anorectal testing of pelvic floor muscle function.""In general, if Rome criteria are fulfilled, ï¿½alarm signsï¿½ or ï¿½red flagsï¿½ are not present, and screening studies from the referring physician are negative, further testing is not needed. Screening studies are recommended when certain historical information is present143: (1) short symptom duration or worsening severity and trajectory of symptoms, (2) demographic features (e.g., onset in an older patient), (3) family history (e.g., colon cancer or inflammatory bowel disease), and (4) no concurrent psychosocial difficulties or symptom behaviors (particularly the absence of comorbid psychosocial features or health care seeking). We recommend a complete blood count and a stool hemoccult for screening purposes. A sedimentation rate (particularly in a younger patient), serum chemistries, thyroid-stimulating hormone (TSH), and stool for ova and parasites can be ordered based on symptom pattern, geographic area, and relevant clinical features (e.g., predominant diarrhea, areas of endemic infection). However, studies do not generally support a role for these tests without supportive clinical features.144 A colonoscopy is recommended for patients over age 50 (due to higher pretest probability of colon cancer), but in younger patients, performing a colonoscopy or sigmoidoscopy is determined by clinical features suggestive of disease (e.g, if there is significant diarrhea) and may not be indicated. There has been growing interest in the use of antiendomysial (ema) and antigliadin (aga) antibodies to diagnose celiac sprue.145ï¿½147 However, such testing must be put into a clinical perspective as determined by presence of symptom pattern, ethnicity, and other clinical features suggestive of the disease.143In many cases, the therapeutic trial can be undertaken before further diagnostic studies are done and will depend on the symptom subtype and its severity (Figure 2): for constipation, fiber, or an osmotic laxative; for diarrhea, loperamide, or diphenoxylate-atropine and possibly cholestyramine; and for pain/gas/bloating, an anticholinergic, or, if more severe, antidepressant or psychologic treatment may be considered. It needs to be emphasized that patients presenting with typical symptoms and no ï¿½alarmï¿½ signs are rarely found to have another diagnosis,144,148 supporting the benefit of ongoing care and symptomatic management rather than continued diagnostic evaluation.If initial treatment fails, or certain clinical features emerge requiring further evaluation, we recommend the algorithm indicated in Figure 3. Many of these studies are performed by gastroenterologists in specialty centers.In patients with infrequent bowel movements, whole gut transit study by Sitzmark technique or a plain radiography (to evaluate for obstructive signs or fecal retention) is indicated. When symptoms of dyschezia or incomplete evacuation are prominent, suggesting obstruction to defecation, or when the physical examination discloses poor pelvic floor relaxation with straining, further anorectal testing is indicated. This includes anorectal motility testing with balloon expulsion (to evaluate for pelvic floor dyssynergia) or defecography (to evaluate for enterocele or rectocele).If diarrhea is persistent, other tests to consider include: 24-hour stool volume and fat; if increased (>400 mL/day), electrolytes and laxative screen; and small bowel biopsy for giardia lamblia or sprue and colonic biopsy for microscopic colitis. On occasion, transit tests of the small bowel and colon can help evaluate the severity of the motility component of the diarrhea. A therapeutic trial of cholestyramine may also be considered, particularly if symptoms developed or worsened after a cholecystectomy. A jejunal biopsy and aspirate can be done to obtain samples to assess malabsorption (e.g., sprue), or to obtain an aspirate for giardia or for bacterial overgrowth. Colonic biopsies can be considered to evaluate for collagenous or lymphocytic colitis, although the findings may not lead to instituting more effective treatments. Finally, when postprandial symptoms of bloating and gaseousness accompany the diarrhea, a breath H2 study to exclude bacterial overgrowth can be considered.149The persistence of pain-predominant symptoms or severe bloating usually requires plain abdominal radiography during an acute episode to exclude bowel obstruction, an increased gastric air bubble from aerophagia, and/or other abdominal pathology. If negative, additional imaging studies (e.g., small bowel radiography, computerized tomography scan, pelvic ultrasonography) may be recommended, particularly when there are other symptoms or signs present (e.g., vomiting, weight loss, abdominal mass, irregular menses, abnormal chemistries). A balloon distention test may confirm rectal or colonic visceral hypersensitivity, although this test is usually done for investigative purposes." http://www.gastrojournal.org/scripts/om.dl...st1232108#head1 INFLAMMATORY BOWEL DISEASE Interleukin 10 genotypes in irritable bowel syndrome: evidence for an inflammatory component? "Conclusions: These preliminary results suggest that at least some patients with irritable bowel syndrome may be genetically predisposed to produce lower amounts of the anti-inflammatory cytokine interleukin 10. This lends some support to the hypothesis that there may be an inflammatory or genetic component in some cases of this condition and that further studies in specific irritable bowel syndrome subgroups are justified. ""Some Irritable Bowel Patients Genetically Predisposed To Produce Less Interleukin-10A DGReview of :"Interleukin 10 genotypes in irritable bowel syndrome: evidence for an inflammatory component?"Gut01/13/2003By Elda HauschildtSome patients with irritable bowel syndrome (IBS) could be genetically predisposed to produce lower amounts of the anti-inflammatory cytokine, interleukin-10 (IL-10), suggest preliminary research results from the United Kingdom."This lends some support to the hypothesis that there may be an inflammatory or genetic component in some cases of this condition," say investigators from University Hospital of South Manchester and the University of Manchester in Manchester. They suggest further studies in specific IBS subgroups are justified.The researchers explain that inflammation could play a role in the pathogenesis of IBS in some patients, including those who develop symptoms after a dysenteric illness. A possible mechanism is persistent inflammation resulting from an imbalance of cytokines that regulate the inflammatory response.Their study was designed to establish whether there is a genetic predisposition to an altered pattern of anti-inflammatory cytokine production in some IBS patients.DNA was extracted from 230 IBS patients and 450 healthy, ethnically matched controls. The researchers then determined allele and genotype frequencies for IL-10 at the site concerned with the production in lymphocytes. They also examined codons 10 and 25 in transforming growth factor-beta(1) [TGF-beta(1)] in a smaller group of participants.Results indicate that the IBS patients had significantly reduced frequencies of the high producer genotype for IL-10 (21%) compared with controls (32%).The investigators found no apparent relationship with any particular IBS bowel-habit subgroup and note genotypes for TGF-beta(1) were not altered. Gut, 2003;52:91-93. "Interleukin 10 genotypes in irritable bowel syndrome: evidence for an inflammatory component?"" http://www.docguide.com/news/content.nsf/n...5256C8F00214155 "cytokinesNon-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialised glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. ""Cytokines: Stress and Immunity Nicholas P. PlotnikoffRobert E. FaithAnthony J. MurgoRobert A. Good Read it Online! Buy it Today! Studies indicate that the well-known effects of stress hormones-ACTH and corticosteroids-are modulated to a large degree by various cytokines-interferons and interleukins.Cytokines: Stress and Immunity provides a comprehensive overview of contemporary knowledge of the role of cytokines in interreactions between the neuroendocrine and immune systems, and the clinical implications of these interactions. This book examines all cytokines, including interleukins, interferons, enkephalins, and endorphins. With its focus on the immune, central nervous, and endocrine systems, this book will impact a broad range of scientists, including both basic researchers and clinicians." http://www.neurosciencenetbase.com/ejourna...mary.asp?id=879 "interleukin<cytokine, protein> A variety of naturally occuring polypeptides that are members of the family of cytokines which affect functions of specific cell types and are found in small quantities. They are secreted regulatory proteins produced by lymphocytes, monocytes and various other cell types and are released by cells in response to antigenic and non-antigenic stimuli. Interleukins are of the larger class of T-cell products, lymphokines which are now more frequently considered as cytokines. The interleukins, of which there are 12 identified to date, modulate inflammation and immunity by regulating growth, mobility and differentiation of lymphoid and other cells. Included among the cytokines are cachectin and lymphotoxin which are now known as tumour necrosis factor-alpha and tumour necrosis factor-beta, respectively. Interleukin-1 inhibitors are the first well-described proteins involved in the feedback regulation of interleukin activities. The origin and functions of the two most novel cytokines, interleukin-11 and interleukin-12 (also referred to as natural killer cell stimulatory factor), have only recently begun to be understood. " http://medical-dictionary.com/dictionaryresults.php " There is emerging data to suggest that people with IBS may have a genetic predisposition to produce low amounts of anti-inflammatory cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-







(16). Moreover, there is a further preliminary report (17) of dysfunctional mucosal protective mechanisms in IBS characterize by reduced numbers of macrophages. While this data is provisional, it is plausible that people who develop IBS could have poorer defense mechanisms to combat infections or other gut insults." http://www.med.unc.edu/wrkunits/2depts/med...rymediators.htm "The reason to believe that the mast cell might be the link between the brain and gut are the close proximity to nerves and the fact that stress induces degranulation." http://wwwhost.gu.se/cgf/fouschema.html "Jack Wood, PhDProfessor of Physiology and Internal MedicineChairman Emeritus, Department of PhysiologyThe Ohio State University College of Medicine Dr. Wood was the first to use microelectrodes to record the electrical and synaptic behavior of neurons in the enteric nervous system. He coined the term "brain-in-the-gut" in view of emerging evidence that the enteric nervous system had neurophysiological properties like the brain and spinal cord. *In recent years he has focused on signaling interactions between the enteric immune system and the brain-in-the-gut during infectious enteritis and food allergy. In this lecture he shows how the central nervous system, enteric nervous system and intestinal immune system are integrated during physical and emotional stress to produce irritable bowel symptoms of diarrhea and abdominal pain and discomfort. * http://www.conference-cast.com/ibs/Lecture...cfm?LectureID=7


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## eric (Jul 8, 1999)

" Importantly, overt colonic inflammation precludes a diagnosis of IBS" http://www.med.unc.edu/wrkunits/2depts/med...rymediators.htm hence the "The role of psychological and biological factors in postinfective gut dysfunction "hence the "after the acute infection "There are subtle organic cells changes, and increases in EC (serotonin) cells and mast cells as I have stated many times now, both are very important to gut function.Stress doesn't cause IBS on its own, but it is a peredicting factor for some of the reasons I keep mentioning.The HPA axis releases chemicals that in turn effect the mast cells in the gut which then in turn release histimine and an array of other mediators. They are very close to the smooth muscle in the gut and the release of toxins from them naturally can inflame the cells.The HPA axis is involved in fighting infectious and the stress responce, the fight or flight.The constant activaing of the cells from bi directional communication and chronic stressors can inflames them and they release toxins onto the smoooth muscle.Chronic stress can also reactivate previous inflammation."organic component involved in the development of PI-IBS."There is a major organic componet in PI IBS, its called enteric infections and they can happen from more then one bacteria in the first place.Its when they resolve and your left with PI IBS which can turn into the full blown clinical experssion of IBS after resolution of the intial infection.Stress can also reactivate previous inflammation after the intial inflammation from the infection has resolved.American Gastroenterological AssociationAGA technical review on irritable bowel syndrome "Definition and classification TOP The Rome classification system1 characterizes the IBS in terms of multiple physiological determinants contributing to a common set of symptoms rather than a single disease entity. It is defined as a ï¿½group of functional bowel disorders in which abdominal discomfort or pain is associated with defecation or a change in bowel habit, and with features of disordered defecation.ï¿½2,3 Table 1 lists the recently revised Rome II diagnostic criteria for IBS.1 --------------------------------------------------------------------------------Table 1. Rome II diagnostic criteria for irritable bowel syndrome3-------------------------------------------------------------------------------- At least 12 weeks, which need not be consecutive, in the preceding 12 months of abdominal discomfort or pain that has 2 of 3 features: 1. Relieved with defecation; and/or 2. Onset associated with a change in frequency of stool; and/or 3. Onset associated with a change in form (appearance) of stool. Symptoms that cumulatively support the diagnosis of IBS: 1. Abnormal stool frequency (for research purposes, ï¿½abnormalï¿½ may be defined as greater than 3 bowel movements per day and less than 3 bowel movements per week); 2. Abnormal stool form (lumpy/hard or loose/watery stool); 3. Abnormal stool passage (straining, urgency, or feeling of incomplete evacuation); 4. Passage of mucus; 5. Bloating or feeling of abdominal distention. NOTE. The diagnosis of a functional bowel disorder always presumes the absence of a structural or biochemical explanation for the symptoms. "Pathophysiology of IBS symptoms TOP The physiological mechanisms responsible for abdominal pain and altered bowel habits occur in healthy control subjects and in persons with IBS. Symptoms can occur in response to a disruption of functioning of the GI tract from an infection, dietary indiscretions (e.g., increased fat or alcohol intake), lifestyle changes (e.g., traveling or vigorous physical activity), or psychologic stress. Among college students and hospital employees, 71% reported that stresses affected their bowel pattern, and 54% reported that stress led to abdominal pain or discomfort.10Abnormal motility in patients with IBS"The differences between IBS patients and healthy controls are quantitative rather than qualitative.Motility observations in the stomach, small intestine, colon, and rectum are qualitatively similar to those in healthy controls. Moreover, only 25%ï¿½75% of IBS patients exhibit the motility ï¿½abnormalitiesï¿½ listed in Table 3, which are considered to differentiate IBS from healthy controls. These motility parameters cannot be used as diagnostic markers.In the ileum, colon, and rectum, IBS patients show an exaggerated response to a variety of provocative stimuli including meals, distention, stress, cholecystokinin, neostigmine, and corticotropin-releasing hormone injection. No corresponding pattern of hyper-reactivity has been shown in the proximal small intestine and stomach, where the response to stress (inhibition of contractions) differs from the response to meals (increase in contractions).There is no consensus on the patterns of motility responsible for diarrhea and constipation, although accelerated transit is seen in diarrhea and slowed transit is seen in constipation. Among IBS patients exhibiting diarrhea and abdominal pain, there are significantly more high-amplitude propagating contractions, which are of higher amplitude than those observed in healthy controls, and these high-amplitude propagating contractions are more likely to be associated with a sensation of pain.Motility abnormalities may interact with low sensory thresholds to produce symptoms: delayed transit of gas causes greater abdominal perception in IBS,29 and IBS patients are more likely than healthy controls to perceive the occurrence of normal migrating motor complexes.30Visceral hypersensitivity in IBSIn 1973, Ritchie first reported that IBS patients have pain at lower volumes and pressures when a balloon is inflated in the bowel.31 This seminal observation has been replicated by a number of research laboratories,31ï¿½36 and the threshold to report pain is below the normal range in 50%ï¿½70% of IBS patients. Consistent with the concept of enhanced perception of visceral events are observations that IBS patients are more likely than controls to notice intestinal contractions37 and gas,29 and their pain thresholds are correlated, albeit weakly, with the amount of clinical pain they experience.32,38,39Enhanced perception of visceral events is documented throughout the GI tract, including the esophagus,40 stomach,41 duodenum,42ï¿½44 and ileum.45 However, IBS patients do not show somatic hypersensitivity to pain42,46,47 and may have elevated48,49 somatic pain thresholds.One study32 noted that when combining other measures of pain sensitivity, such as the intensity with which the pain sensation is described and the location and size of the somatic referral area, up to 95% of patients show evidence of visceral hypersensitivity. The investigators concluded that visceral hypersensitivity might be a biological marker for IBS, although this interpretation has been challenged.38InflammationPreliminary evidence for a possible alteration in gut immune function in IBS comes from both unselected and so-called postinfectious IBS (PI-IBS) patients. In unselected patients, increased numbers of mast cells in the muscularis externa of the colon50 and the ileal and colonic mucosa51,52 have been reported. Increased cellularity of the colonic mucosa and lamina propria has also been described in unselected IBS patients using semiquantitative microscopy.53 In patients with intractable IBS, lymphocytic infiltrates of the myenteric plexus were reported,54 and most recently, preliminary evidence for increased iNOS (nitric oxide synthetase) expression was described.55 For subgroups of IBS, these findings suggest there is an up-regulation of gut immune function. However, methodological deficiencies exist, including the influence of the bowel preparation, the classification of the patients, and the nonquantitative analysis of gut cells. Further studies are needed to explore these intriguing findings.Further support for a possible role of altered gut immune function in IBS comes from recent studies in PI-IBS patients.56ï¿½59 A subset of IBS patients associate the development of IBS symptoms with the onset of gastroenteritis.60ï¿½62 In recent prospective studies, IBS-like symptoms were found in 7%ï¿½30% of patients who recovered from a proven bacterial gastroenteritis.59 Reported risk factors included: female gender, duration of the acute diarrheal illness, and the presence of significant life stressor occurring around the time of the infection. Patients with PI-IBS were found to have a variety of functional alterations, including changes in gut motility,63,64 epithelial function,65,66 and an increase in colonic enterochromaffin cells.66 In addition, evidence for increased expression of interleukin 1 messenger RNA, increased cellularity of lamina propria, and an increase in CD3+ lymphocytes were reported from mucosal biopsy specimens.66 The correlation of IBS symptoms with these observed changes has not been established. Furthermore, because the majority of patients do not develop postinfectious diarrhea and the prevalence of IBS is not higher in countries with high rates of enteric infections, further studies are required to determine if vulnerability factors (such as altered neuroimmune system responsiveness) play a role in the development of PI-IBS in a subset of patients. In addition, psychological distress seems to be an important cofactor in determining who retains symptoms after an enteric infection.67Autonomic activityAbnormalities in extrinsic autonomic innervation of the viscera occur in approximately one fourth of patients with functional bowel disorders.68,69 Aggarwal et al. showed that cardiovagal dysfunction is specifically associated with a constipation-predominant subgroup of patients with IBS, whereas patients with diarrhea-predominant symptoms had evidence of sympathetic adrenergic dysfunction.70 The role of autonomic dysfunction in IBS requires further evaluation.Central nervous system modulationIn general, brain-gut interactions play a prominent role in the modulation of gut function in health and disease.71ï¿½74 Signals from the brain to the gut assure that digestive function is optimized for the overall state of the organism (e.g., sleep vs. wake, stress vs. relaxation).75 Conversely, signals from the gut to the brain play a role primarily in reflex regulation76 as well as in modulation of mood states.77 In addition, certain vagal afferent pathways can influence pain perception.78The CNS modulates motility, secretion, immune function, and blood flow.79 The emotional motor system in the brain80 is a revised name for the limbic system and some paralimbic structures (including the medial prefrontal cortex, amygdala, and hypothalamus) communicate emotional changes via the autonomic nervous system to the gut. The CNS is also essential in the perception of events occurring within the gut. This brain-gut bidirectional communication is largely not perceived consciously. In effect, the CNS functions as a ï¿½filterï¿½ with regard to the perception of peripheral afferent signals, and the threshold for perception can vary depending on the individual's emotional and cognitive state. Most visceral afferent signals reach the brainstem and thalamus, and only a very few are consciously perceived in the cortex.81 However, one recent study82 suggests that low intensity signals are subliminally registered.Modulation of visceral afferent information occurs at multiple levels from the periphery to cortical regions, as shown in Table 4. " Role of psychosocial factors in IBS TOP Research on the psychosocial aspects of patients with IBS has yielded 4 general observations.1001. Psychologic stress exacerbates GI symptoms. Although stressful experiences produce GI symptoms in most individuals, patients with IBS are particularly susceptible.10 Studies of the effects of stressful life events on IBS patients are shown in Table 5. 'With one exception,101 these studies suggest IBS patients report more lifetime and daily stressful events,10,14,102ï¿½107 including severe abuse history,108,109 than medical comparison groups or healthy controls. Furthermore, in IBS patients, stress is strongly associated with symptom onset105,107,110 and symptom severity.109 Even though the effects of stress on gut function are universal, patients with IBS seem to have greater reactivity to stress.72,111 The identification of specific psychological stressors associated with exacerbation of symptoms may help in planning treatment through psychological or psychopharmacological interventions.2. Psychological and psychiatric comorbidity is common among patients with IBS. A large proportion of patients with IBS and other functional bowel disorders have concurrent psychological disturbances. As shown in Table 6, when using standardized research interviews, the prevalence of a psychiatric disorder ranges from 40% to over 90% among patients with IBS/functional bowel disorders in tertiary care centers. ""Other psychological features identified to be greater in IBS include personality style,14,106,112 psychological distress,18,109,113 and altered health beliefs, cognitions, and coping style.114ï¿½117 As indicated below, these findings are not associated with the disorder per se, but their prevalence is over-represented within the health careï¿½seeking subset of patients.3. Psychosocial factors affect health status and clinical outcome. Psychological and sociocultural factors, when present in patients with IBS, will also influence the illness experience and treatment outcome. Psychosocial factors that adversely affect health status and clinical outcome include: (1) a history of emotional, sexual, or physical abuse109,118ï¿½121; (2) stressful life events104,110; (3) chronic social stress122 or anxiety disorder123,124; and (4) maladaptive coping style.119 Some of these psychosocial influences may occur early in life. For example, increased attention by family to a child's illness complaints seems to result in delayed symptom reporting, health care seeking, and health care costs.125ï¿½1294. Psychosocial factors influence which patients consult physicians. This tends to overestimate the true prevalence of psychosocial disturbance when evaluating patients in referral clinical settings. In fact, persons with IBS who do not see physicians are psychologically similar to subjects without bowel complaints.14,18,130" Diagnosis TOP Symptom-based criteriaA diagnosis is based on identifying positive symptoms (e.g., Rome criteria) consistent with the condition (Table 1), and excluding, in a cost-effective manner, other conditions with similar clinical presentations, which may include organic or other functional (e.g., functional diarrhea or bloating, pelvic floor disorders, or slow transit constipation with associated abdominal discomfort relieved with defecation) disorders.3,140 Any needed tests, as suggested by ï¿½alarm features,ï¿½ should be discussed with the patient and set up at the first encounter. When ï¿½alarm featuresï¿½ such as weight loss, refractory diarrhea, and family history of colon cancer are excluded, the specificity of the symptom-based Rome I criteria for IBS exceeds 98% and hence, the risk of missing organic disease is low.141EvaluationA physical examination should be performed on the first visit and on subsequent visits as needed. This is done to exclude findings not consistent with IBS (e.g., enlarged liver, abdominal mass, signs of bowel obstruction) and to meet the patient's expectations of a thorough evaluation. A pelvic examination is often indicated for lower abdominal/pelvic symptoms and/or if there is a change in menstrual pattern. A rectal examination, particularly for patients reporting symptoms of incontinence or dyschezia, can help to identify a lax sphincter or paradoxical pelvic floor muscle contraction. This may require anorectal testing of pelvic floor muscle function.""In general, if Rome criteria are fulfilled, ï¿½alarm signsï¿½ or ï¿½red flagsï¿½ are not present, and screening studies from the referring physician are negative, further testing is not needed. Screening studies are recommended when certain historical information is present143: (1) short symptom duration or worsening severity and trajectory of symptoms, (2) demographic features (e.g., onset in an older patient), (3) family history (e.g., colon cancer or inflammatory bowel disease), and (4) no concurrent psychosocial difficulties or symptom behaviors (particularly the absence of comorbid psychosocial features or health care seeking). We recommend a complete blood count and a stool hemoccult for screening purposes. A sedimentation rate (particularly in a younger patient), serum chemistries, thyroid-stimulating hormone (TSH), and stool for ova and parasites can be ordered based on symptom pattern, geographic area, and relevant clinical features (e.g., predominant diarrhea, areas of endemic infection). However, studies do not generally support a role for these tests without supportive clinical features.144 A colonoscopy is recommended for patients over age 50 (due to higher pretest probability of colon cancer), but in younger patients, performing a colonoscopy or sigmoidoscopy is determined by clinical features suggestive of disease (e.g, if there is significant diarrhea) and may not be indicated. There has been growing interest in the use of antiendomysial (ema) and antigliadin (aga) antibodies to diagnose celiac sprue.145ï¿½147 However, such testing must be put into a clinical perspective as determined by presence of symptom pattern, ethnicity, and other clinical features suggestive of the disease.143In many cases, the therapeutic trial can be undertaken before further diagnostic studies are done and will depend on the symptom subtype and its severity (Figure 2): for constipation, fiber, or an osmotic laxative; for diarrhea, loperamide, or diphenoxylate-atropine and possibly cholestyramine; and for pain/gas/bloating, an anticholinergic, or, if more severe, antidepressant or psychologic treatment may be considered. It needs to be emphasized that patients presenting with typical symptoms and no ï¿½alarmï¿½ signs are rarely found to have another diagnosis,144,148 supporting the benefit of ongoing care and symptomatic management rather than continued diagnostic evaluation.If initial treatment fails, or certain clinical features emerge requiring further evaluation, we recommend the algorithm indicated in Figure 3. Many of these studies are performed by gastroenterologists in specialty centers.In patients with infrequent bowel movements, whole gut transit study by Sitzmark technique or a plain radiography (to evaluate for obstructive signs or fecal retention) is indicated. When symptoms of dyschezia or incomplete evacuation are prominent, suggesting obstruction to defecation, or when the physical examination discloses poor pelvic floor relaxation with straining, further anorectal testing is indicated. This includes anorectal motility testing with balloon expulsion (to evaluate for pelvic floor dyssynergia) or defecography (to evaluate for enterocele or rectocele).If diarrhea is persistent, other tests to consider include: 24-hour stool volume and fat; if increased (>400 mL/day), electrolytes and laxative screen; and small bowel biopsy for giardia lamblia or sprue and colonic biopsy for microscopic colitis. On occasion, transit tests of the small bowel and colon can help evaluate the severity of the motility component of the diarrhea. A therapeutic trial of cholestyramine may also be considered, particularly if symptoms developed or worsened after a cholecystectomy. A jejunal biopsy and aspirate can be done to obtain samples to assess malabsorption (e.g., sprue), or to obtain an aspirate for giardia or for bacterial overgrowth. Colonic biopsies can be considered to evaluate for collagenous or lymphocytic colitis, although the findings may not lead to instituting more effective treatments. Finally, when postprandial symptoms of bloating and gaseousness accompany the diarrhea, a breath H2 study to exclude bacterial overgrowth can be considered.149The persistence of pain-predominant symptoms or severe bloating usually requires plain abdominal radiography during an acute episode to exclude bowel obstruction, an increased gastric air bubble from aerophagia, and/or other abdominal pathology. If negative, additional imaging studies (e.g., small bowel radiography, computerized tomography scan, pelvic ultrasonography) may be recommended, particularly when there are other symptoms or signs present (e.g., vomiting, weight loss, abdominal mass, irregular menses, abnormal chemistries). A balloon distention test may confirm rectal or colonic visceral hypersensitivity, although this test is usually done for investigative purposes." http://www.gastrojournal.org/scripts/om.dl...st1232108#head1 INFLAMMATORY BOWEL DISEASE Interleukin 10 genotypes in irritable bowel syndrome: evidence for an inflammatory component? "Conclusions: These preliminary results suggest that at least some patients with irritable bowel syndrome may be genetically predisposed to produce lower amounts of the anti-inflammatory cytokine interleukin 10. This lends some support to the hypothesis that there may be an inflammatory or genetic component in some cases of this condition and that further studies in specific irritable bowel syndrome subgroups are justified. ""Some Irritable Bowel Patients Genetically Predisposed To Produce Less Interleukin-10A DGReview of :"Interleukin 10 genotypes in irritable bowel syndrome: evidence for an inflammatory component?"Gut01/13/2003By Elda HauschildtSome patients with irritable bowel syndrome (IBS) could be genetically predisposed to produce lower amounts of the anti-inflammatory cytokine, interleukin-10 (IL-10), suggest preliminary research results from the United Kingdom."This lends some support to the hypothesis that there may be an inflammatory or genetic component in some cases of this condition," say investigators from University Hospital of South Manchester and the University of Manchester in Manchester. They suggest further studies in specific IBS subgroups are justified.The researchers explain that inflammation could play a role in the pathogenesis of IBS in some patients, including those who develop symptoms after a dysenteric illness. A possible mechanism is persistent inflammation resulting from an imbalance of cytokines that regulate the inflammatory response.Their study was designed to establish whether there is a genetic predisposition to an altered pattern of anti-inflammatory cytokine production in some IBS patients.DNA was extracted from 230 IBS patients and 450 healthy, ethnically matched controls. The researchers then determined allele and genotype frequencies for IL-10 at the site concerned with the production in lymphocytes. They also examined codons 10 and 25 in transforming growth factor-beta(1) [TGF-beta(1)] in a smaller group of participants.Results indicate that the IBS patients had significantly reduced frequencies of the high producer genotype for IL-10 (21%) compared with controls (32%).The investigators found no apparent relationship with any particular IBS bowel-habit subgroup and note genotypes for TGF-beta(1) were not altered. Gut, 2003;52:91-93. "Interleukin 10 genotypes in irritable bowel syndrome: evidence for an inflammatory component?"" http://www.docguide.com/news/content.nsf/n...5256C8F00214155 "cytokinesNon-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialised glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. ""Cytokines: Stress and Immunity Nicholas P. PlotnikoffRobert E. FaithAnthony J. MurgoRobert A. Good Read it Online! Buy it Today! Studies indicate that the well-known effects of stress hormones-ACTH and corticosteroids-are modulated to a large degree by various cytokines-interferons and interleukins.Cytokines: Stress and Immunity provides a comprehensive overview of contemporary knowledge of the role of cytokines in interreactions between the neuroendocrine and immune systems, and the clinical implications of these interactions. This book examines all cytokines, including interleukins, interferons, enkephalins, and endorphins. With its focus on the immune, central nervous, and endocrine systems, this book will impact a broad range of scientists, including both basic researchers and clinicians." http://www.neurosciencenetbase.com/ejourna...mary.asp?id=879 "interleukin<cytokine, protein> A variety of naturally occuring polypeptides that are members of the family of cytokines which affect functions of specific cell types and are found in small quantities. They are secreted regulatory proteins produced by lymphocytes, monocytes and various other cell types and are released by cells in response to antigenic and non-antigenic stimuli. Interleukins are of the larger class of T-cell products, lymphokines which are now more frequently considered as cytokines. The interleukins, of which there are 12 identified to date, modulate inflammation and immunity by regulating growth, mobility and differentiation of lymphoid and other cells. Included among the cytokines are cachectin and lymphotoxin which are now known as tumour necrosis factor-alpha and tumour necrosis factor-beta, respectively. Interleukin-1 inhibitors are the first well-described proteins involved in the feedback regulation of interleukin activities. The origin and functions of the two most novel cytokines, interleukin-11 and interleukin-12 (also referred to as natural killer cell stimulatory factor), have only recently begun to be understood. " http://medical-dictionary.com/dictionaryresults.php " There is emerging data to suggest that people with IBS may have a genetic predisposition to produce low amounts of anti-inflammatory cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-







(16). Moreover, there is a further preliminary report (17) of dysfunctional mucosal protective mechanisms in IBS characterize by reduced numbers of macrophages. While this data is provisional, it is plausible that people who develop IBS could have poorer defense mechanisms to combat infections or other gut insults." http://www.med.unc.edu/wrkunits/2depts/med...rymediators.htm "The reason to believe that the mast cell might be the link between the brain and gut are the close proximity to nerves and the fact that stress induces degranulation." http://wwwhost.gu.se/cgf/fouschema.html "Jack Wood, PhDProfessor of Physiology and Internal MedicineChairman Emeritus, Department of PhysiologyThe Ohio State University College of Medicine Dr. Wood was the first to use microelectrodes to record the electrical and synaptic behavior of neurons in the enteric nervous system. He coined the term "brain-in-the-gut" in view of emerging evidence that the enteric nervous system had neurophysiological properties like the brain and spinal cord. *In recent years he has focused on signaling interactions between the enteric immune system and the brain-in-the-gut during infectious enteritis and food allergy. In this lecture he shows how the central nervous system, enteric nervous system and intestinal immune system are integrated during physical and emotional stress to produce irritable bowel symptoms of diarrhea and abdominal pain and discomfort. * http://www.conference-cast.com/ibs/Lecture...cfm?LectureID=7


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## Talissa (Apr 10, 2004)

> quote:" Importantly, overt colonic inflammation precludes a diagnosis of IBS"


Has anyone here said otherwise?Nope.No one is saying otherwise.If there's OVERT inflammation, it isn't IBS. It's IBD.If there's LOW GRADE inflammation, this has been seen in IBS patients.>>>>>>>>>>>>>>>>>>>>>>>>.Stress, like infection, brings on an immune response. Mast cells, B-cells, T-cells, etc. People can get colds from stress. The immune system is in overdrive. Beneficial bacterium are lowered from the cortisol released during stress. Pathogens formally kept in check go nuts. They love it!


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## Talissa (Apr 10, 2004)

> quote:" Importantly, overt colonic inflammation precludes a diagnosis of IBS"


Has anyone here said otherwise?Nope.No one is saying otherwise.If there's OVERT inflammation, it isn't IBS. It's IBD.If there's LOW GRADE inflammation, this has been seen in IBS patients.>>>>>>>>>>>>>>>>>>>>>>>>.Stress, like infection, brings on an immune response. Mast cells, B-cells, T-cells, etc. People can get colds from stress. The immune system is in overdrive. Beneficial bacterium are lowered from the cortisol released during stress. Pathogens formally kept in check go nuts. They love it!


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## Talissa (Apr 10, 2004)

This is interesting regarding Serotonin, IBS, UC, & the similarities~Gastroenterology. 2004 Jun"Despite being pathophysiologically divergent, ulcerative colitis (UC) and irritable bowel syndrome (IBS) are both associated with clinical symptoms that include alterations in the normal patterns of motility, secretion, and sensation. Our aim was to test whether enteric 5-HT signaling is defective in these disorders...CONCLUSIONS: These data show that UC and IBS are associated with similar molecular changes in serotonergic signaling mechanisms. While UC and IBS have distinct pathophysiologic properties, these data suggest that shared defects in 5-HT signaling may underlie the altered motility, secretion, and sensation. *These findings represent the first demonstration of significant molecular alterations specific to the gut in patients with IBS and support the assertion that disordered gastrointestinal function in IBS involves changes intrinsic to the bowel."* http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=15188158 ("changes intrinsic to the bowel"...doesn't that mean that like UC, its an ORGANIC disease? )


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## Talissa (Apr 10, 2004)

This is interesting regarding Serotonin, IBS, UC, & the similarities~Gastroenterology. 2004 Jun"Despite being pathophysiologically divergent, ulcerative colitis (UC) and irritable bowel syndrome (IBS) are both associated with clinical symptoms that include alterations in the normal patterns of motility, secretion, and sensation. Our aim was to test whether enteric 5-HT signaling is defective in these disorders...CONCLUSIONS: These data show that UC and IBS are associated with similar molecular changes in serotonergic signaling mechanisms. While UC and IBS have distinct pathophysiologic properties, these data suggest that shared defects in 5-HT signaling may underlie the altered motility, secretion, and sensation. *These findings represent the first demonstration of significant molecular alterations specific to the gut in patients with IBS and support the assertion that disordered gastrointestinal function in IBS involves changes intrinsic to the bowel."* http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=15188158 ("changes intrinsic to the bowel"...doesn't that mean that like UC, its an ORGANIC disease? )


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## Kacebece3 (Apr 17, 2002)

Well Eric I do fit the Rome criteria for diagnosing IBS. I'm sure my Docs came to this conclusion after performing tests to eliminate other problems. MY doc said all tests are normal, you do have some low grade inflamation, the symptoms you describe are consistant with people we say have IBS. So is the inflamation a result of stool staying in the bowel to long? Is the inflamation causing IBS symptoms? Is IBS causing the inflamation? Or is both conditions coexisting happily together independent of each other? It doesn't matter which, witch is which, I want to be free of this miserable condition. Probiotics so far have been a help, I've been on Dr. Dahlman's program 3 weeks tommorow and the pain level has dropped enough for me to start doing things kinda like normal, I'm not saying cured far from it just getting better. I'm anxious to see what results I will have in 3 more weeks, hope I can post the same results GRET and KEL posted.Later Ken


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## Kacebece3 (Apr 17, 2002)

Well Eric I do fit the Rome criteria for diagnosing IBS. I'm sure my Docs came to this conclusion after performing tests to eliminate other problems. MY doc said all tests are normal, you do have some low grade inflamation, the symptoms you describe are consistant with people we say have IBS. So is the inflamation a result of stool staying in the bowel to long? Is the inflamation causing IBS symptoms? Is IBS causing the inflamation? Or is both conditions coexisting happily together independent of each other? It doesn't matter which, witch is which, I want to be free of this miserable condition. Probiotics so far have been a help, I've been on Dr. Dahlman's program 3 weeks tommorow and the pain level has dropped enough for me to start doing things kinda like normal, I'm not saying cured far from it just getting better. I'm anxious to see what results I will have in 3 more weeks, hope I can post the same results GRET and KEL posted.Later Ken


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## eric (Jul 8, 1999)

Ken, are you saying your not really interested in what causes IBS, you just want to be 'cured'.How long have you had it?Also six months is the usaual time to see if something works. Three weeks six weeks and even three months is not long enough time wise, because there is a high placebo rate in IBS regardless of the treatment at three months, between 30 and 80 percent.PathophysiologyAltered Serotonin Signaling?The pathogenesis of IBS remains obscure, and in particular, an explanation for alternating diarrhea and constipation has been elusive. In arguably one of the most important papers presented during this year's meeting, Moses and colleagues[21] studied potential deregulation of the gut's serotonin transporter in IBS. It is known that serotonin (5-hydroxytryptamine or 5HT) is released from enteroendocrine (or enterochromaffin) cells in response to either chemical or mechanical stimulation of the gut mucosa. Serotonin in turn initiates peristalsis, and then the serotonin released is taken up in health by a highly selective serotonin transporter (SERT). One potential mechanism that could explain altered bowel function in IBS is an abnormality in the serotonin transporter itself. The study authors evaluated this hypothesis in patients with IBS with constipation and IBS with diarrhea compared with patients with ulcerative colitis and healthy controls. They were able to convincing show on blinded review that SERT immunoreactivity was less intense in patients with IBS with constipation and patients with ulcerative colitis. If these findings are indeed correct, they represent a landmark observation. The findings suggest that patients with constipation and IBS may have a reduced capacity to reuptake serotonin, leading to excess free serotonin and then desensitization of these receptors, thus reducing motor function. In contrast, in the setting of diarrhea, serotonin uptake was normal. If the underlying abnormality in serotonin transporter function alternated, then this would in turn explain alternating constipation and diarrhea. These data strongly suggest that IBS is a "real" gut disease and a potential diagnostic disease marker. They also suggest that it is valid to subdivide IBS into constipation and diarrhea symptom subgroups. This study also provides additional rationale for the use of serotonin-modulating agents in IBS and provides a new target for drug modulation. Confirmation of these very exciting initial findings in larger patient samples is awaited with great interest.Ask The Expert.Image of a cadeusus. .General Medical Questions.Q: I have suffered from irritable-bowel syndrome for many years. I get diarrhea. The doctors I've seen have offered little help. Recently, my daughter suggested I try an over-the-counter medicine called "5-Hydroxy-tryptophan," made by a company called Natrol Inc. My daughter says it is a mild antidepressant. It seems to have helped quite a bit, but it also seems to slow me down and make me feel tired. Can you give me any information on this? What is it, exactly, and are there any serious side effects? The only other medicine I take is Synthroid....The Trusted Source..Harold J. DeMonaco, M.S.Harold J. DeMonaco, M.S., is senior analyst, Innovative Diagnostics and Therapeutics, and the chair of the Human Research Committee at the Massachusetts General Hospital. He is author of over 20 publications in the pharmacy and medical literature and routinely reviews manuscript submissions for eight medical journals...June 19, 2001.A:Irritable bowel syndrome is now recognized as a disorder of serotonin activity. Serotonin is a neurotransmitter in the brain that regulates sleep, mood (depression, anxiety), aggression, appetite, temperature, sexual behavior and pain sensation. Serotonin also acts as a neurotransmitter in the gastrointestinal tract.Excessive serotonin activity in the gastrointestinal system (enteric nervous system) is thought to cause the diarrhea of irritable-bowel syndrome. The enteric nervous system detects bowel distension (expansion) on the basis of pressure-sensitive cells in the bowel lumen (opening). Once activated, these pressure-sensitive cells promote the release of serotonin, which in turn promotes both secretory function and peristaltic function (the contractions of the intestines that force the contents outward). At least four serotonergic receptors have been identified to be participants in the secretory and peristaltic response.Patients with diarrhea-predominant IBS may have higher levels of serotonin after eating than do people without the disorder. This recognition led to the development of the first drug used specifically to treat diarrheal symptoms of IBS, alosetron (also known as Lotronex). Alosetron blocked the specific serotonin receptors responsible for recognizing bowel distention. In doing so, it blocked the effects of serotonin and reduced both bowel secretions and peristalsis. Constipation was the most common side effect seen. (Note: Alosetron was removed from the market by the manufacturer after repeated reports of a dangerous condition known as ischemic colitis became known.) Tegaserod (Zelmac) is another drug under development and under review by the U.S. Food and Drug Administration for approval. Tegaserod is indicated for the treatment of constipation-predominant IBS and works to increase enteric nervous system serotonin activity.So, increasing serotonin activity in the enteric nervous system produces increased bowel secretions and peristalsis (and potentially diarrhea), whereas depressing serotonin activity produces reduced secretions and reduce peristalsis (and potentially constipation). Increasing serotonin activity in the brain would increase awareness and, in higher doses, produce anxiety, insomnia and restlessness. So I would have expected exactly the opposite effects of those that you experienced.I am unable to identify any possible drug interactions between 5-HTP and Synthroid (levothyroxine) but the symptoms described suggest a check with your doctor may be in order. Persistent feelings of tiredness and constipation may be signs of an underactive thyroid (hypothyroidism).June 19, 2001 From Medscape GastroenterologyMEDLINE Abstracts: Serotonin Signaling and Visceral Hypersensitivity in IBSPosted 10/23/2003 What's new concerning the role of serotonin signaling and mechanisms of visceral hypersensitivity in the pathophysiology of irritable bowel syndrome (IBS)? Find out in this easy-to-navigate collection of recent MEDLINE abstracts compiled by the editors at Medscape Gastroenterology.--------------------------------------------------------------------------------Serotonin and Its Implication for the Management of Irritable Bowel SyndromeGershon MDRev Gastroenterol Disord. 2003;3(suppl 2):S25-S34Our understanding of the enteric nervous system (ENS) has evolved from the "classical" view, in which the brain controls all enteric behavior, to the current view, which holds that enteric innervation is one of local control within the bowel, modified by a bidirectional "dialogue" with the brain. The ENS independently controls enteric reflexes through intrinsic primary afferent neurons, which monitor intraluminal conditions. This monitoring is accomplished through the use of enteroendocrine cells in the mucosa, the best known of which are the serotonin-containing enterochromaffin cells. This article describes the roles that serotonin, specific serotonin-receptor subtypes, and the serotonin reuptake transporter play in the ENS and in the communication between the ENS and central nervous system. The way in which these findings have implicated serotonin in irritable bowel syndrome is discussed.Systematic Review: Serotonergic Modulators in the Treatment of Irritable Bowel Syndrome--Influence on Psychiatric and Gastrointestinal SymptomsKilkens TO, Honig A, Rozendaal N, Van Nieuwenhoven MA, Brummer RJAliment Pharmacol Ther. 2003 ;17:43-51Background: Both central and peripheral serotonergic modulators are used in the treatment of irritable bowel syndrome. The majority of patients with irritable bowel syndrome presenting to a gastroenterologist demonstrate affective dysregulation. Serotonin may play a regulatory role in both gastrointestinal motility and sensitivity, as well as in affective dysregulation, in irritable bowel syndrome.Aim: To analyse, systematically, randomized controlled trials studying the influence of serotonergic modulators on both gastrointestinal and psychiatric symptoms in irritable bowel syndrome, in order to elucidate baseline irritable bowel syndrome symptomatology and possible differential effects of serotonergic modulation on this symptomatology.Methods: A standardized qualitative analysis was performed of studies investigating the influence of serotonergic modulators on both gastrointestinal and psychiatric symptoms in irritable bowel syndrome using a blind review approach. The studies were ranked according to their total quality score (maximum 100 points).Results: Eleven studies fulfilled the entry criteria, six of which scored above 55 points. An association between gastroenterological and psychiatric changes was present in five of the six studies.Conclusions: The results strengthen the serotonergic association between gastroenterological and psychiatric symptoms. Adjusted guidelines for combined gastrointestinal and psychiatric assessments are recommended in order to further elucidate the serotonergic interaction between gastrointestinal and psychiatric symptoms.Tegaserod and Other Serotonergic Agents: What Is the Evidence?Chey WDRev Gastroenterol Disord. 2003;3(suppl 2):S35-S40Through effects on gastrointestinal motor and secretory function as well as visceral sensation, serotonin (5-HT) plays a key role in the pathogenesis of irritable bowel syndrome (IBS). In particular, 5-HT3 and 5-HT4 receptors appear to be very important in IBS. This article critically appraises the evidence supporting the use of the 5-HT3 receptor antagonist alosetron in the treatment of women with diarrhea-predominant IBS. The safety profile and restricted-use program for alosetron is also reviewed. This discussion is followed by a comprehensive review of the efficacy and safety data in support of tegaserod for women with constipation-predominant IBS.Sex Differences of Brain Serotonin Synthesis in Patients With Irritable Bowel Syndrome Using Alpha-11C Methyl-L-Tryptophan, Positron Emission Tomography and Statistical Parametric MappingNakai A, Kumakura Y, Boivin M, et alCan J Gastroenterol. 2003;17:191-196Background: Irritable bowel syndrome (IBS) is the most common functional bowel disorder and has a strong predominance in women. Recent data suggest that the brain may play an important role in the pathophysiology of IBS in the brain-gut axis. It is strongly suspected that serotonin (5-HT), a neurotransmitter found in the brain and gut, may be related to the pathophysiology of IBS. It is reported that a 5-HT3 antagonist is effective only in female patients with diarrhea-predominant IBS.Objective: In the present study, 5-HT synthesis was measured using positron emission tomography, with alpha-11Cmethyl-L-tryptophan as the tracer, in patients with IBS. The aim of the present study was to compare 5-HT synthesis in the IBS patients with that in the controls, and to compare 5-HT synthesis between male and female IBS patients.Methods: Six male and six female nonconstipated IBS patients were scanned. Age-matched healthy volunteers were scanned as controls. Eighty minute dynamic scans were performed. Functional 5-HT synthesis images were analyzed using statistical parametric mapping.Results: 5-HT synthesis was greater only in the female IBS patients in the right medial temporal gyrus (multimodal sensory association cortex) compared with the female controls (P 0.001).Conclusions: The greater brain 5-HT synthesis in the female IBS patients than in the controls may be related to the pathological visceral pain processing of the IBS patients, a larger female predominance of the disorder, and the sex difference of the efficacy of the 5-HT3 antagonist in treatment.Sex-Related Differences in IBS Patients: Central Processing of Visceral StimuliNaliboff BD, Berman S, Chang L, et alGastroenterology. 2003;124:1738-1747Background & Aims: Women have a higher prevalence of irritable bowel syndrome (IBS) and possible differences in response to treatment, suggesting sex-related differences in underlying pathophysiology. The aim of this study was to determine possible sex-related differences in brain responses to a visceral and a psychological stressor in IBS.Methods: Regional cerebral blood flow measurements using H(2)(15)O positron emission tomography were compared across 23 female and 19 male nonconstipated patients with IBS during a visceral stimulus (moderate rectal inflation) and a psychological stimulus (anticipation of a visceral stimulus).Results: In response to the visceral stimulus, women showed greater activation in the ventromedial prefrontal cortex, right anterior cingulate cortex, and left amygdala, whereas men showed greater activation of the right dorsolateral prefrontal cortex, insula, and dorsal pons/periaqueductal gray. Similar differences were observed during the anticipation condition. Men also reported higher arousal and lower fatigue.Conclusions: Male and female patients with IBS differ in activation of brain networks concerned with cognitive, autonomic, and antinociceptive responses to delivered and anticipated aversive visceral stimuli.Functional Brain Imaging in Irritable Bowel Syndrome With Rectal Balloon-Distention by Using fMRIYuan YZ, Tao RJ, Xu B, et alWorld J Gastroenterol. 2003;9:1356-1360Aim: Irritable bowel syndrome (IBS) is characterized by abdominal pain and changes in stool habits. Visceral hypersensitivity is a key factor in the pathophysiology of IBS. The aim of this study was to examine the effect of rectal balloon-distention stimulus by blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) in visceral pain center and to compare the distribution, extent, and intensity of activated areas between IBS patients and normal controls.Methods: Twenty-six patients with IBS and eleven normal controls were tested for rectal sensation, and the subjective pain intensity at 90 ml and 120 ml rectal balloon-distention was reported by using Visual Analogue Scale. Then, BOLD-fMRI was performed at 30 ml, 60 ml, 90 ml, and 120 ml rectal balloon-distention in all subjects.Results: Rectal distention stimulation increased the activity of anterior cingulate cortex (35/37), insular cortex (37/37), prefrontal cortex (37/37), and thalamus (35/37) in most cases. At 120 ml of rectal balloon-distention, the activation area and percentage change in MR signal intensity of the regions of interest (ROI) at IC, PFC, and THAL were significantly greater in patients with IBS than that in controls. Score of pain sensation at 90 ml and 120 ml rectal balloon-distention was significantly higher in patients with IBS than that in controls.Conclusion: Using fMRI, some patients with IBS can be detected having visceral hypersensitivity in response to painful rectal balloon-distention. fMRI is an objective brain imaging technique to measure the change in regional cerebral activation more precisely. In this study, IC and PFC of the IBS patients were the major loci of the CNS processing of visceral perception.Role of Visceral Sensitivity in the Pathophysiology of Irritable Bowel SyndromeDelvaux MGut. 2002;51(suppl 1):i67-i71Visceral hypersensitivity has been recognised as a characteristic of patients with irritable bowel syndrome (IBS). It may be involved in the pathogenesis of abdominal pain/discomfort, and seems to result from the sensitisation of nerve afferent pathways originating from the gastrointestinal tract. From a clinical point of view, hypersensitivity, although frequent, is not a constant finding among patients with IBS and cannot therefore be considered as a diagnostic marker of the condition. The advances made in understanding visceral hypersensitivity in patients with IBS are reviewed: the factors that influence abdominal distension are defined and different therapeutic perspectives are examined.www.medscape.com/viewarti...02/7001/-1 Distinctive Features of Postinfective Irritable Bowel Syndrome Laurie Barclay, MDJuly 25, 2003 ï¿½ Patients with postinfective irritable bowel syndrome (PI-IBS) have more diarrheal symptoms, fewer psychiatric symptoms, and a greater increase in serotonin-containing enterochromaffin (EC) cells than those whose IBS did not start after an infectious disease, according to the results of a study published in the July issue of the American Journal of Gastroenterology. The investigators speculate that subclassifying patients may allow for better and more specific therapies for some patients with IBS. "IBS patients are heterogeneous, both in symptoms and in etiology, and progress in understanding pathogenesis has been limited for lack of objective measures to allow meaningful subdivision," write Simon P. Dunlop, MSc, from University Hospital in Nottingham, U.K., and colleagues. "Recently there has been progress in defining one subgroup of patients, i.e., those developing IBS symptoms after an episode of infective gastroenteritis."In this study, 75 consecutive IBS outpatients and 36 healthy controls completed a questionnaire and had a full diagnostic workup including rectal biopsy. Of the 75 patients with IBS, 23 had onset of symptoms after an infectious illness and 52 did not.Predominance of diarrhea occurred in 70% of PI-IBS patients and in 42% of nonï¿½PI-IBS patients (P = .03), and previous treatment for anxiety or depression occurred in 26% of PI-IBS patients and in 54% of the nonï¿½PI-IBS group (P = .02). Using conventional criteria, biopsy results for all patients were normal, but there were increased EC cells in the PI-IBS group compared with the nonï¿½PI-IBS group (P = .017) and with controls (P = .02). Lamina propria T lymphocytes were increased in PI-IBS (P = .026) and in nonï¿½PI-IBS (P = .011) patients compared with control patients, and mast cells were increased in nonï¿½PI-IBS patients (P = .054) compared with control patients.The authors do not recommend rectal biopsy in all patients, but they note that "these group differences are important, as they suggest that different types of IBS may have different pathogenic mechanisms. By defining different 'key players' such as mast cells, lymphocytes, and EC cells, they suggest new specific pharmacological targets for therapy. They also suggest new objective measures such as plasma serotonin or serum tryptase with which we can seek to subclassify IBS and to identify those individuals who will respond to specific therapies."AstraZeneca supported this work through an educational grant.Am J Gastroenterol. 2003;98:1578-1583Reviewed by Gary D. Vogin, MD


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## eric (Jul 8, 1999)

Ken, are you saying your not really interested in what causes IBS, you just want to be 'cured'.How long have you had it?Also six months is the usaual time to see if something works. Three weeks six weeks and even three months is not long enough time wise, because there is a high placebo rate in IBS regardless of the treatment at three months, between 30 and 80 percent.PathophysiologyAltered Serotonin Signaling?The pathogenesis of IBS remains obscure, and in particular, an explanation for alternating diarrhea and constipation has been elusive. In arguably one of the most important papers presented during this year's meeting, Moses and colleagues[21] studied potential deregulation of the gut's serotonin transporter in IBS. It is known that serotonin (5-hydroxytryptamine or 5HT) is released from enteroendocrine (or enterochromaffin) cells in response to either chemical or mechanical stimulation of the gut mucosa. Serotonin in turn initiates peristalsis, and then the serotonin released is taken up in health by a highly selective serotonin transporter (SERT). One potential mechanism that could explain altered bowel function in IBS is an abnormality in the serotonin transporter itself. The study authors evaluated this hypothesis in patients with IBS with constipation and IBS with diarrhea compared with patients with ulcerative colitis and healthy controls. They were able to convincing show on blinded review that SERT immunoreactivity was less intense in patients with IBS with constipation and patients with ulcerative colitis. If these findings are indeed correct, they represent a landmark observation. The findings suggest that patients with constipation and IBS may have a reduced capacity to reuptake serotonin, leading to excess free serotonin and then desensitization of these receptors, thus reducing motor function. In contrast, in the setting of diarrhea, serotonin uptake was normal. If the underlying abnormality in serotonin transporter function alternated, then this would in turn explain alternating constipation and diarrhea. These data strongly suggest that IBS is a "real" gut disease and a potential diagnostic disease marker. They also suggest that it is valid to subdivide IBS into constipation and diarrhea symptom subgroups. This study also provides additional rationale for the use of serotonin-modulating agents in IBS and provides a new target for drug modulation. Confirmation of these very exciting initial findings in larger patient samples is awaited with great interest.Ask The Expert.Image of a cadeusus. .General Medical Questions.Q: I have suffered from irritable-bowel syndrome for many years. I get diarrhea. The doctors I've seen have offered little help. Recently, my daughter suggested I try an over-the-counter medicine called "5-Hydroxy-tryptophan," made by a company called Natrol Inc. My daughter says it is a mild antidepressant. It seems to have helped quite a bit, but it also seems to slow me down and make me feel tired. Can you give me any information on this? What is it, exactly, and are there any serious side effects? The only other medicine I take is Synthroid....The Trusted Source..Harold J. DeMonaco, M.S.Harold J. DeMonaco, M.S., is senior analyst, Innovative Diagnostics and Therapeutics, and the chair of the Human Research Committee at the Massachusetts General Hospital. He is author of over 20 publications in the pharmacy and medical literature and routinely reviews manuscript submissions for eight medical journals...June 19, 2001.A:Irritable bowel syndrome is now recognized as a disorder of serotonin activity. Serotonin is a neurotransmitter in the brain that regulates sleep, mood (depression, anxiety), aggression, appetite, temperature, sexual behavior and pain sensation. Serotonin also acts as a neurotransmitter in the gastrointestinal tract.Excessive serotonin activity in the gastrointestinal system (enteric nervous system) is thought to cause the diarrhea of irritable-bowel syndrome. The enteric nervous system detects bowel distension (expansion) on the basis of pressure-sensitive cells in the bowel lumen (opening). Once activated, these pressure-sensitive cells promote the release of serotonin, which in turn promotes both secretory function and peristaltic function (the contractions of the intestines that force the contents outward). At least four serotonergic receptors have been identified to be participants in the secretory and peristaltic response.Patients with diarrhea-predominant IBS may have higher levels of serotonin after eating than do people without the disorder. This recognition led to the development of the first drug used specifically to treat diarrheal symptoms of IBS, alosetron (also known as Lotronex). Alosetron blocked the specific serotonin receptors responsible for recognizing bowel distention. In doing so, it blocked the effects of serotonin and reduced both bowel secretions and peristalsis. Constipation was the most common side effect seen. (Note: Alosetron was removed from the market by the manufacturer after repeated reports of a dangerous condition known as ischemic colitis became known.) Tegaserod (Zelmac) is another drug under development and under review by the U.S. Food and Drug Administration for approval. Tegaserod is indicated for the treatment of constipation-predominant IBS and works to increase enteric nervous system serotonin activity.So, increasing serotonin activity in the enteric nervous system produces increased bowel secretions and peristalsis (and potentially diarrhea), whereas depressing serotonin activity produces reduced secretions and reduce peristalsis (and potentially constipation). Increasing serotonin activity in the brain would increase awareness and, in higher doses, produce anxiety, insomnia and restlessness. So I would have expected exactly the opposite effects of those that you experienced.I am unable to identify any possible drug interactions between 5-HTP and Synthroid (levothyroxine) but the symptoms described suggest a check with your doctor may be in order. Persistent feelings of tiredness and constipation may be signs of an underactive thyroid (hypothyroidism).June 19, 2001 From Medscape GastroenterologyMEDLINE Abstracts: Serotonin Signaling and Visceral Hypersensitivity in IBSPosted 10/23/2003 What's new concerning the role of serotonin signaling and mechanisms of visceral hypersensitivity in the pathophysiology of irritable bowel syndrome (IBS)? Find out in this easy-to-navigate collection of recent MEDLINE abstracts compiled by the editors at Medscape Gastroenterology.--------------------------------------------------------------------------------Serotonin and Its Implication for the Management of Irritable Bowel SyndromeGershon MDRev Gastroenterol Disord. 2003;3(suppl 2):S25-S34Our understanding of the enteric nervous system (ENS) has evolved from the "classical" view, in which the brain controls all enteric behavior, to the current view, which holds that enteric innervation is one of local control within the bowel, modified by a bidirectional "dialogue" with the brain. The ENS independently controls enteric reflexes through intrinsic primary afferent neurons, which monitor intraluminal conditions. This monitoring is accomplished through the use of enteroendocrine cells in the mucosa, the best known of which are the serotonin-containing enterochromaffin cells. This article describes the roles that serotonin, specific serotonin-receptor subtypes, and the serotonin reuptake transporter play in the ENS and in the communication between the ENS and central nervous system. The way in which these findings have implicated serotonin in irritable bowel syndrome is discussed.Systematic Review: Serotonergic Modulators in the Treatment of Irritable Bowel Syndrome--Influence on Psychiatric and Gastrointestinal SymptomsKilkens TO, Honig A, Rozendaal N, Van Nieuwenhoven MA, Brummer RJAliment Pharmacol Ther. 2003 ;17:43-51Background: Both central and peripheral serotonergic modulators are used in the treatment of irritable bowel syndrome. The majority of patients with irritable bowel syndrome presenting to a gastroenterologist demonstrate affective dysregulation. Serotonin may play a regulatory role in both gastrointestinal motility and sensitivity, as well as in affective dysregulation, in irritable bowel syndrome.Aim: To analyse, systematically, randomized controlled trials studying the influence of serotonergic modulators on both gastrointestinal and psychiatric symptoms in irritable bowel syndrome, in order to elucidate baseline irritable bowel syndrome symptomatology and possible differential effects of serotonergic modulation on this symptomatology.Methods: A standardized qualitative analysis was performed of studies investigating the influence of serotonergic modulators on both gastrointestinal and psychiatric symptoms in irritable bowel syndrome using a blind review approach. The studies were ranked according to their total quality score (maximum 100 points).Results: Eleven studies fulfilled the entry criteria, six of which scored above 55 points. An association between gastroenterological and psychiatric changes was present in five of the six studies.Conclusions: The results strengthen the serotonergic association between gastroenterological and psychiatric symptoms. Adjusted guidelines for combined gastrointestinal and psychiatric assessments are recommended in order to further elucidate the serotonergic interaction between gastrointestinal and psychiatric symptoms.Tegaserod and Other Serotonergic Agents: What Is the Evidence?Chey WDRev Gastroenterol Disord. 2003;3(suppl 2):S35-S40Through effects on gastrointestinal motor and secretory function as well as visceral sensation, serotonin (5-HT) plays a key role in the pathogenesis of irritable bowel syndrome (IBS). In particular, 5-HT3 and 5-HT4 receptors appear to be very important in IBS. This article critically appraises the evidence supporting the use of the 5-HT3 receptor antagonist alosetron in the treatment of women with diarrhea-predominant IBS. The safety profile and restricted-use program for alosetron is also reviewed. This discussion is followed by a comprehensive review of the efficacy and safety data in support of tegaserod for women with constipation-predominant IBS.Sex Differences of Brain Serotonin Synthesis in Patients With Irritable Bowel Syndrome Using Alpha-11C Methyl-L-Tryptophan, Positron Emission Tomography and Statistical Parametric MappingNakai A, Kumakura Y, Boivin M, et alCan J Gastroenterol. 2003;17:191-196Background: Irritable bowel syndrome (IBS) is the most common functional bowel disorder and has a strong predominance in women. Recent data suggest that the brain may play an important role in the pathophysiology of IBS in the brain-gut axis. It is strongly suspected that serotonin (5-HT), a neurotransmitter found in the brain and gut, may be related to the pathophysiology of IBS. It is reported that a 5-HT3 antagonist is effective only in female patients with diarrhea-predominant IBS.Objective: In the present study, 5-HT synthesis was measured using positron emission tomography, with alpha-11Cmethyl-L-tryptophan as the tracer, in patients with IBS. The aim of the present study was to compare 5-HT synthesis in the IBS patients with that in the controls, and to compare 5-HT synthesis between male and female IBS patients.Methods: Six male and six female nonconstipated IBS patients were scanned. Age-matched healthy volunteers were scanned as controls. Eighty minute dynamic scans were performed. Functional 5-HT synthesis images were analyzed using statistical parametric mapping.Results: 5-HT synthesis was greater only in the female IBS patients in the right medial temporal gyrus (multimodal sensory association cortex) compared with the female controls (P 0.001).Conclusions: The greater brain 5-HT synthesis in the female IBS patients than in the controls may be related to the pathological visceral pain processing of the IBS patients, a larger female predominance of the disorder, and the sex difference of the efficacy of the 5-HT3 antagonist in treatment.Sex-Related Differences in IBS Patients: Central Processing of Visceral StimuliNaliboff BD, Berman S, Chang L, et alGastroenterology. 2003;124:1738-1747Background & Aims: Women have a higher prevalence of irritable bowel syndrome (IBS) and possible differences in response to treatment, suggesting sex-related differences in underlying pathophysiology. The aim of this study was to determine possible sex-related differences in brain responses to a visceral and a psychological stressor in IBS.Methods: Regional cerebral blood flow measurements using H(2)(15)O positron emission tomography were compared across 23 female and 19 male nonconstipated patients with IBS during a visceral stimulus (moderate rectal inflation) and a psychological stimulus (anticipation of a visceral stimulus).Results: In response to the visceral stimulus, women showed greater activation in the ventromedial prefrontal cortex, right anterior cingulate cortex, and left amygdala, whereas men showed greater activation of the right dorsolateral prefrontal cortex, insula, and dorsal pons/periaqueductal gray. Similar differences were observed during the anticipation condition. Men also reported higher arousal and lower fatigue.Conclusions: Male and female patients with IBS differ in activation of brain networks concerned with cognitive, autonomic, and antinociceptive responses to delivered and anticipated aversive visceral stimuli.Functional Brain Imaging in Irritable Bowel Syndrome With Rectal Balloon-Distention by Using fMRIYuan YZ, Tao RJ, Xu B, et alWorld J Gastroenterol. 2003;9:1356-1360Aim: Irritable bowel syndrome (IBS) is characterized by abdominal pain and changes in stool habits. Visceral hypersensitivity is a key factor in the pathophysiology of IBS. The aim of this study was to examine the effect of rectal balloon-distention stimulus by blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) in visceral pain center and to compare the distribution, extent, and intensity of activated areas between IBS patients and normal controls.Methods: Twenty-six patients with IBS and eleven normal controls were tested for rectal sensation, and the subjective pain intensity at 90 ml and 120 ml rectal balloon-distention was reported by using Visual Analogue Scale. Then, BOLD-fMRI was performed at 30 ml, 60 ml, 90 ml, and 120 ml rectal balloon-distention in all subjects.Results: Rectal distention stimulation increased the activity of anterior cingulate cortex (35/37), insular cortex (37/37), prefrontal cortex (37/37), and thalamus (35/37) in most cases. At 120 ml of rectal balloon-distention, the activation area and percentage change in MR signal intensity of the regions of interest (ROI) at IC, PFC, and THAL were significantly greater in patients with IBS than that in controls. Score of pain sensation at 90 ml and 120 ml rectal balloon-distention was significantly higher in patients with IBS than that in controls.Conclusion: Using fMRI, some patients with IBS can be detected having visceral hypersensitivity in response to painful rectal balloon-distention. fMRI is an objective brain imaging technique to measure the change in regional cerebral activation more precisely. In this study, IC and PFC of the IBS patients were the major loci of the CNS processing of visceral perception.Role of Visceral Sensitivity in the Pathophysiology of Irritable Bowel SyndromeDelvaux MGut. 2002;51(suppl 1):i67-i71Visceral hypersensitivity has been recognised as a characteristic of patients with irritable bowel syndrome (IBS). It may be involved in the pathogenesis of abdominal pain/discomfort, and seems to result from the sensitisation of nerve afferent pathways originating from the gastrointestinal tract. From a clinical point of view, hypersensitivity, although frequent, is not a constant finding among patients with IBS and cannot therefore be considered as a diagnostic marker of the condition. The advances made in understanding visceral hypersensitivity in patients with IBS are reviewed: the factors that influence abdominal distension are defined and different therapeutic perspectives are examined.www.medscape.com/viewarti...02/7001/-1 Distinctive Features of Postinfective Irritable Bowel Syndrome Laurie Barclay, MDJuly 25, 2003 ï¿½ Patients with postinfective irritable bowel syndrome (PI-IBS) have more diarrheal symptoms, fewer psychiatric symptoms, and a greater increase in serotonin-containing enterochromaffin (EC) cells than those whose IBS did not start after an infectious disease, according to the results of a study published in the July issue of the American Journal of Gastroenterology. The investigators speculate that subclassifying patients may allow for better and more specific therapies for some patients with IBS. "IBS patients are heterogeneous, both in symptoms and in etiology, and progress in understanding pathogenesis has been limited for lack of objective measures to allow meaningful subdivision," write Simon P. Dunlop, MSc, from University Hospital in Nottingham, U.K., and colleagues. "Recently there has been progress in defining one subgroup of patients, i.e., those developing IBS symptoms after an episode of infective gastroenteritis."In this study, 75 consecutive IBS outpatients and 36 healthy controls completed a questionnaire and had a full diagnostic workup including rectal biopsy. Of the 75 patients with IBS, 23 had onset of symptoms after an infectious illness and 52 did not.Predominance of diarrhea occurred in 70% of PI-IBS patients and in 42% of nonï¿½PI-IBS patients (P = .03), and previous treatment for anxiety or depression occurred in 26% of PI-IBS patients and in 54% of the nonï¿½PI-IBS group (P = .02). Using conventional criteria, biopsy results for all patients were normal, but there were increased EC cells in the PI-IBS group compared with the nonï¿½PI-IBS group (P = .017) and with controls (P = .02). Lamina propria T lymphocytes were increased in PI-IBS (P = .026) and in nonï¿½PI-IBS (P = .011) patients compared with control patients, and mast cells were increased in nonï¿½PI-IBS patients (P = .054) compared with control patients.The authors do not recommend rectal biopsy in all patients, but they note that "these group differences are important, as they suggest that different types of IBS may have different pathogenic mechanisms. By defining different 'key players' such as mast cells, lymphocytes, and EC cells, they suggest new specific pharmacological targets for therapy. They also suggest new objective measures such as plasma serotonin or serum tryptase with which we can seek to subclassify IBS and to identify those individuals who will respond to specific therapies."AstraZeneca supported this work through an educational grant.Am J Gastroenterol. 2003;98:1578-1583Reviewed by Gary D. Vogin, MD


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## Nath (Jan 5, 1999)

I thought reuptake was a problem in D as well as C? The difference being that C's become desenitized while D's do not.


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## Nath (Jan 5, 1999)

I thought reuptake was a problem in D as well as C? The difference being that C's become desenitized while D's do not.


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## Kacebece3 (Apr 17, 2002)

I don't think the cause of IBS is known, just a lot of research that has not found a reason. We have a lot of promising results but they are just that, promises. Eric I would like to know what causes IBS, to say otherwise just is not true. Modern medicine just does not have the answer....not yet anyway. So I will try and give the body I live in the chance to cure itself, I feel I have a better chance that way. Holistic medicine makes sense to me. I did not all ways have this problem so something has changed to cause it.Later Ken


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## Kacebece3 (Apr 17, 2002)

I don't think the cause of IBS is known, just a lot of research that has not found a reason. We have a lot of promising results but they are just that, promises. Eric I would like to know what causes IBS, to say otherwise just is not true. Modern medicine just does not have the answer....not yet anyway. So I will try and give the body I live in the chance to cure itself, I feel I have a better chance that way. Holistic medicine makes sense to me. I did not all ways have this problem so something has changed to cause it.Later Ken


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## Kacebece3 (Apr 17, 2002)

Eric,,FYI I have had constipation since my teen years it was livible until I was hospitalized with a staph infection, lots of atibiotics and 7 days later released. that happened in 1988 so I have been dealing with miserable IBS-c for 16 years I'm 53 now.


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## Kacebece3 (Apr 17, 2002)

Eric,,FYI I have had constipation since my teen years it was livible until I was hospitalized with a staph infection, lots of atibiotics and 7 days later released. that happened in 1988 so I have been dealing with miserable IBS-c for 16 years I'm 53 now.


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## Guest (Aug 22, 2004)

Hi eric, I just dropped in to say Hi and hope you are well and also to boost what you have posted here for IBS sufferers.....







Eric has been around here for a very long time and it's been my experience that when it comes to information about IBS... he is the one with the facts from the world's foremost authorities as well as the experience in helping people who have IBS, so he's a good person to listen to.Just a note that I've had some good experience with probiotics...mostly in the form of yogurt, however... but I don't take acidophillus on a regular basis as chronic use tends to cause me more problems.Eric was also instrumental in getting me to try the hypnotherapy which started me on my pathway towards healing.Keep bringing us accurate information as you always do.Evie


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## Guest (Aug 22, 2004)

Hi eric, I just dropped in to say Hi and hope you are well and also to boost what you have posted here for IBS sufferers.....







Eric has been around here for a very long time and it's been my experience that when it comes to information about IBS... he is the one with the facts from the world's foremost authorities as well as the experience in helping people who have IBS, so he's a good person to listen to.Just a note that I've had some good experience with probiotics...mostly in the form of yogurt, however... but I don't take acidophillus on a regular basis as chronic use tends to cause me more problems.Eric was also instrumental in getting me to try the hypnotherapy which started me on my pathway towards healing.Keep bringing us accurate information as you always do.Evie


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## Talissa (Apr 10, 2004)

August 2004Canadian Journal of Gastroenterology"As the role of bacterial communication within the gut (bacterial-epithelial cross-talk) is clarified, physicians should be able to modulate gut immune responses, for example, by the use of probiotics.ï¿½ http://awww.patientlinx.com/GILinx/theaart...=1026205&ok=yes _____________________________Gut 2004ï¿½With emerging evidence supporting a role for inflammation and immune activation in IBS, studies are encouraged to address the influence of the microbial environment on the epidemiology and clinical expression of IBS across the globe. http://gut.bmjjournals.com/cgi/content/full/53/8/1068 _____________________________Curr Issues Intest Microbiol. 2002 Marï¿½Disturbances in the mucosal immune system are reflected in the composition of the gut microbiota and vice versa. ï¿½ http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=12022809


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## Talissa (Apr 10, 2004)

August 2004Canadian Journal of Gastroenterology"As the role of bacterial communication within the gut (bacterial-epithelial cross-talk) is clarified, physicians should be able to modulate gut immune responses, for example, by the use of probiotics.ï¿½ http://awww.patientlinx.com/GILinx/theaart...=1026205&ok=yes _____________________________Gut 2004ï¿½With emerging evidence supporting a role for inflammation and immune activation in IBS, studies are encouraged to address the influence of the microbial environment on the epidemiology and clinical expression of IBS across the globe. http://gut.bmjjournals.com/cgi/content/full/53/8/1068 _____________________________Curr Issues Intest Microbiol. 2002 Marï¿½Disturbances in the mucosal immune system are reflected in the composition of the gut microbiota and vice versa. ï¿½ http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=12022809


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## Talissa (Apr 10, 2004)

MEDSCAPE Medical Newsï¿½May 21, 2003 (Orlando) ï¿½ Probiotic therapy, primarily in the form of Lactobacillus acidophilus and Bifidobacteria infantis, significantly improves symptoms and quality of life in patients with irritable bowel syndrome (IBS) and other bowel disorders, researchers reported in a number of presentations here at Digestive Disease Week 2003.In a study designed to assess the efficacy of probiotics alone or in combination with antibiotics in patients with IBS, Stephen M. Faber, MD, from Albemarle Gastroenterology Associates, PC, in Elizabeth City, North Carolina, evaluated treatment in 44 patients with IBS. Twenty patients received probiotics alone and 24 received ciprofloxacin 500 mg twice daily for one week and two probiotic formulations, Lactobacillus (NCFM) 10 billion/g and Bifidobacteia infantis (Bifdo), 10 billion/g for four weeks. Patients completed the IBS-Quality of Life (IBS-QOL) questionnaire and the Symptom Frequency Index (SFI) before and after treatment. For the study group as a whole, IBS-QOL scores averaged 66.2 before treatment and 84.6 after treatment. SFI scores before treatment averaged 38, decreasing to 18 after treatment. In patients who received both probiotics and antibiotics, IBS-QOL scores averaged 67.6 before and 87.8 after treatment. SFI scores averaged 35 at baseline, decreasing to 18 after treatment.In the probiotic-only group, baseline IBS-QOL scores were 69.3, increasing to 86.4 after treatment. SFI scores were 39 at baseline and 17 after treatment.Differences in IBS-QOL and SFI scores between probiotic plus antibiotic treatment and probiotic-only treatment were statistically insignificant, Dr. Faber reported.A retrospective look at IBS patients treated with probiotics indicates that there is a deficiency of Lactobacillus in the gut flora in patients with IBS, Dr. Faber noted, "but we're not ready to call IBS an infectious disease."Dr. Fedorak said that probiotic therapy was not associated with any adverse clinical or biochemical events. "I haven't heard of getting into trouble with probiotics," Dr. Faber told Medscape. "These are organisms that are supposed to be in the gut. The body knows how to control them, so it doesn't seem that you can overtreat."While probiotics have been recognized as beneficial components of food, Dr. Fedorak pointed out that "we don't use it as a food product anymore but as a treatment.But Dr. Fedorak cautioned that "we don't know how they work. They appear to strengthen the mucosal barrier of the bowel and improve immune function. ï¿½ http://www.medscape.com/viewarticle/455964?src=search >>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>Interestingly, Ultra Flora Plus contains 2 probiotic types similar to the one used in the above study.Unfortunately, we don't know the exact strain sub-type.Maybe if they'd taken more daily, the improvement would've been even better.And maybe if the study had been longer, we'd have seen a bigger difference in the improvements...say 3 months like Dr D recommends(but yes, I know he recommends the newer probiotics by Metagenics--which combined also provide the 2 probiotic types used in the study.)Hmmm, wish I had that crystal ball to know exactly what strains to take in what amount for what length of time!!!In the meantime, I'll enjoy my 3 solids p/day while taking DA-IBS, Kyo Dophilus, & high dosed Metamucil. It used to be 7-14 times loose/watery daily, so I really can't complain!Will be ordering Metagenics soon no doubt.Still searching,Talkative Talissa


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## Talissa (Apr 10, 2004)

MEDSCAPE Medical Newsï¿½May 21, 2003 (Orlando) ï¿½ Probiotic therapy, primarily in the form of Lactobacillus acidophilus and Bifidobacteria infantis, significantly improves symptoms and quality of life in patients with irritable bowel syndrome (IBS) and other bowel disorders, researchers reported in a number of presentations here at Digestive Disease Week 2003.In a study designed to assess the efficacy of probiotics alone or in combination with antibiotics in patients with IBS, Stephen M. Faber, MD, from Albemarle Gastroenterology Associates, PC, in Elizabeth City, North Carolina, evaluated treatment in 44 patients with IBS. Twenty patients received probiotics alone and 24 received ciprofloxacin 500 mg twice daily for one week and two probiotic formulations, Lactobacillus (NCFM) 10 billion/g and Bifidobacteia infantis (Bifdo), 10 billion/g for four weeks. Patients completed the IBS-Quality of Life (IBS-QOL) questionnaire and the Symptom Frequency Index (SFI) before and after treatment. For the study group as a whole, IBS-QOL scores averaged 66.2 before treatment and 84.6 after treatment. SFI scores before treatment averaged 38, decreasing to 18 after treatment. In patients who received both probiotics and antibiotics, IBS-QOL scores averaged 67.6 before and 87.8 after treatment. SFI scores averaged 35 at baseline, decreasing to 18 after treatment.In the probiotic-only group, baseline IBS-QOL scores were 69.3, increasing to 86.4 after treatment. SFI scores were 39 at baseline and 17 after treatment.Differences in IBS-QOL and SFI scores between probiotic plus antibiotic treatment and probiotic-only treatment were statistically insignificant, Dr. Faber reported.A retrospective look at IBS patients treated with probiotics indicates that there is a deficiency of Lactobacillus in the gut flora in patients with IBS, Dr. Faber noted, "but we're not ready to call IBS an infectious disease."Dr. Fedorak said that probiotic therapy was not associated with any adverse clinical or biochemical events. "I haven't heard of getting into trouble with probiotics," Dr. Faber told Medscape. "These are organisms that are supposed to be in the gut. The body knows how to control them, so it doesn't seem that you can overtreat."While probiotics have been recognized as beneficial components of food, Dr. Fedorak pointed out that "we don't use it as a food product anymore but as a treatment.But Dr. Fedorak cautioned that "we don't know how they work. They appear to strengthen the mucosal barrier of the bowel and improve immune function. ï¿½ http://www.medscape.com/viewarticle/455964?src=search >>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>Interestingly, Ultra Flora Plus contains 2 probiotic types similar to the one used in the above study.Unfortunately, we don't know the exact strain sub-type.Maybe if they'd taken more daily, the improvement would've been even better.And maybe if the study had been longer, we'd have seen a bigger difference in the improvements...say 3 months like Dr D recommends(but yes, I know he recommends the newer probiotics by Metagenics--which combined also provide the 2 probiotic types used in the study.)Hmmm, wish I had that crystal ball to know exactly what strains to take in what amount for what length of time!!!In the meantime, I'll enjoy my 3 solids p/day while taking DA-IBS, Kyo Dophilus, & high dosed Metamucil. It used to be 7-14 times loose/watery daily, so I really can't complain!Will be ordering Metagenics soon no doubt.Still searching,Talkative Talissa


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## Kacebece3 (Apr 17, 2002)

Hi Talissa, of the brands of probiotics I have tried Metagenics have given me the best results. It would be cool if research would give this type of therapy a long term study. I have completed 3 weeks of using metagenics and am having promising results.Later Ken


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## Kacebece3 (Apr 17, 2002)

Hi Talissa, of the brands of probiotics I have tried Metagenics have given me the best results. It would be cool if research would give this type of therapy a long term study. I have completed 3 weeks of using metagenics and am having promising results.Later Ken


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## eric (Jul 8, 1999)

Thanks Evie, hope your doing well.PROBIOTICS AND GUT ECOLOGY March 8-10, 2002 Scottsdale, Arizona In March 2002 over 100 scientists and clinical investigators from around the world met in Scottsdale, Arizona, to review, discuss, and debate the role of probiotics in intestinal homeostasis, with particular emphasis on inflammatory bowel disease (IBD). Research in the past decade has led to recognition of the critical importance the normal intestinal microflora plays in bowel inflammation and mucosal immune regulation. During the same period of time, interest in the potential health benefits of manipulating the gut flora with probiotics has sharply increased. The goal for this gathering, therefore, was to critically analyze the most up-to-date information on the in vitro and in vivo effects of probiotics. After setting the foundation of knowledge with an overview of gut ecology and its relationship to intestinal immune function, the discussion focused on probiotic modulation of inflammation in animal models of IBD and steatohepatitis. This was followed by an evaluation of the potential mechanisms of action explaining the multiple effects of probiotics. The meeting then concluded with a critical appraisal of the data from clinical trials where probiotic therapy was used in patients with IBD and irritable bowel syndrome. http://216.109.117.135/search/cache?p=prob...AD6FD0D7C&icp=1 Science EducationScience articles that you can understandProbiotics: A Friend or Foe to People with Inflammatory Bowel Diseases? http://www.bact.wisc.edu:8080/ScienceEd/st...storyReader$118


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## eric (Jul 8, 1999)

Thanks Evie, hope your doing well.PROBIOTICS AND GUT ECOLOGY March 8-10, 2002 Scottsdale, Arizona In March 2002 over 100 scientists and clinical investigators from around the world met in Scottsdale, Arizona, to review, discuss, and debate the role of probiotics in intestinal homeostasis, with particular emphasis on inflammatory bowel disease (IBD). Research in the past decade has led to recognition of the critical importance the normal intestinal microflora plays in bowel inflammation and mucosal immune regulation. During the same period of time, interest in the potential health benefits of manipulating the gut flora with probiotics has sharply increased. The goal for this gathering, therefore, was to critically analyze the most up-to-date information on the in vitro and in vivo effects of probiotics. After setting the foundation of knowledge with an overview of gut ecology and its relationship to intestinal immune function, the discussion focused on probiotic modulation of inflammation in animal models of IBD and steatohepatitis. This was followed by an evaluation of the potential mechanisms of action explaining the multiple effects of probiotics. The meeting then concluded with a critical appraisal of the data from clinical trials where probiotic therapy was used in patients with IBD and irritable bowel syndrome. http://216.109.117.135/search/cache?p=prob...AD6FD0D7C&icp=1 Science EducationScience articles that you can understandProbiotics: A Friend or Foe to People with Inflammatory Bowel Diseases? http://www.bact.wisc.edu:8080/ScienceEd/st...storyReader$118


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## Kacebece3 (Apr 17, 2002)

Eric good info. cant seem to get in this site though. http://www.bact.wisc.edu:8080/ScienceEd/st...storyReader$118


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## Kacebece3 (Apr 17, 2002)

Eric good info. cant seem to get in this site though. http://www.bact.wisc.edu:8080/ScienceEd/st...storyReader$118


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## Talissa (Apr 10, 2004)

Hey Ken, thanks for the feedback. I'm looking very forward to giving those probiotics a try soon, when I run low on the kyo, definitely. And you're right--Eric, thanks for a good, very interesting article...(first one)This was particularly interesting and -may- just be the definitive answer to why we can't down-regulate the (low grade)inflammation~"The peaceful coexistence of humans with bacteria can be transiently broken by environmental triggers, transient infections, self-limiting infections, and non-steroidal anti-inflammatory drugs, all resulting in inflammation. The normal, genetically resistant host heals completely, due to down-regulation of inflammatory responses. However, the genetically susceptible host, defective for either immunoregulation or repair mechanisms, develops chronic inflammation due to the constant antigenic stimulation from the luminal bacteria. "....Now my question is, will a certain probiotic strain be enough to correct this genetic predisposition for chronic inflammation? It seems to have in the study I posted regarding UC and probiotics. My instinct is saying "yes"._________________________________But would a natural anti-inflammatory mix for allergies help as well? I have already ordered a product called "Aller-Max" by Allergy Research Group, so after trying that, at least I'll know for me whether or not it helps.It contains histidine & zinc, and this combo helped clear another IBSr of her IBS(Jan's tale): http://www.ibstales.com/women_and_diarrhea_11.htm And histidine is being studied here for post infectious IBS~"Our preliminary studies have indicated that administration of L-histidine in supraphysiologic doses blocks synthesis of proinflammatory cytokines (e.g., TNF and IL-6). Further, we have shown that L-histidine chemically react with PGE2, a proinflammatory eicosanoid released during experimental cholera and salmonellosis. A clinical trial in Bangladesh is being planned, as a result of our preliminary studies. In short, antioxidants tend to modulate the acute inflammatory response and results in tissue protection."  http://microbiology.utmb.edu/faculty/peterson/homepage.htm Aren't antioxidants what was in Mark's/overitnow's product that got him to 100%?? He sells it now, but I truly believe it helped him. He believes it helped by increasing blood circulation however. You never know...


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## Talissa (Apr 10, 2004)

Hey Ken, thanks for the feedback. I'm looking very forward to giving those probiotics a try soon, when I run low on the kyo, definitely. And you're right--Eric, thanks for a good, very interesting article...(first one)This was particularly interesting and -may- just be the definitive answer to why we can't down-regulate the (low grade)inflammation~"The peaceful coexistence of humans with bacteria can be transiently broken by environmental triggers, transient infections, self-limiting infections, and non-steroidal anti-inflammatory drugs, all resulting in inflammation. The normal, genetically resistant host heals completely, due to down-regulation of inflammatory responses. However, the genetically susceptible host, defective for either immunoregulation or repair mechanisms, develops chronic inflammation due to the constant antigenic stimulation from the luminal bacteria. "....Now my question is, will a certain probiotic strain be enough to correct this genetic predisposition for chronic inflammation? It seems to have in the study I posted regarding UC and probiotics. My instinct is saying "yes"._________________________________But would a natural anti-inflammatory mix for allergies help as well? I have already ordered a product called "Aller-Max" by Allergy Research Group, so after trying that, at least I'll know for me whether or not it helps.It contains histidine & zinc, and this combo helped clear another IBSr of her IBS(Jan's tale): http://www.ibstales.com/women_and_diarrhea_11.htm And histidine is being studied here for post infectious IBS~"Our preliminary studies have indicated that administration of L-histidine in supraphysiologic doses blocks synthesis of proinflammatory cytokines (e.g., TNF and IL-6). Further, we have shown that L-histidine chemically react with PGE2, a proinflammatory eicosanoid released during experimental cholera and salmonellosis. A clinical trial in Bangladesh is being planned, as a result of our preliminary studies. In short, antioxidants tend to modulate the acute inflammatory response and results in tissue protection." http://microbiology.utmb.edu/faculty/peterson/homepage.htm Aren't antioxidants what was in Mark's/overitnow's product that got him to 100%?? He sells it now, but I truly believe it helped him. He believes it helped by increasing blood circulation however. You never know...


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## Jhouston (Nov 9, 2003)

Read somewhere on the board.. probiotics may compete with each other? so the new metagenics has them separated in 2 bottles. I think? Joann


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## Jhouston (Nov 9, 2003)

Read somewhere on the board.. probiotics may compete with each other? so the new metagenics has them separated in 2 bottles. I think? Joann


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## Guest (Aug 23, 2004)

All,this is very interesting thread. good points by both Talissa and Eric.Nath, they have done probiotic enemas. Infact, some years ago, someone posted instructions where you find a healhty person - take their BM and mix it in a blender with some other ingredients to enhance the good bacteria - and then give yourself an enema with it. That did NOT go over well here on the board!! But I thought it was an interesting idea - and would do it if it helped!really liked this statement from Kel:"If the medical establishment (big pharm) really cared about helping people they would devote more time to understanding gut flora as opposed to symptom suppressing drugs."


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## Guest (Aug 23, 2004)

All,this is very interesting thread. good points by both Talissa and Eric.Nath, they have done probiotic enemas. Infact, some years ago, someone posted instructions where you find a healhty person - take their BM and mix it in a blender with some other ingredients to enhance the good bacteria - and then give yourself an enema with it. That did NOT go over well here on the board!! But I thought it was an interesting idea - and would do it if it helped!really liked this statement from Kel:"If the medical establishment (big pharm) really cared about helping people they would devote more time to understanding gut flora as opposed to symptom suppressing drugs."


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## AlphaMale (Jan 21, 2004)

Thank you for the posting such wealth of information about the good bacteria.


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## AlphaMale (Jan 21, 2004)

Thank you for the posting such wealth of information about the good bacteria.


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## peardrops (Jan 3, 2004)

I've read quite a bit on Human Probiotics Infusion. It has been used for treating people with relapsing, severe c-diff infection. I'm sure I read about it on www.cdiffsupport.com/discus/ Didn't Spasman post something about a clinic in Australia doing it? The site I've quoted is for people with c-diff but there is some useful information there on probiotics. I think if my c-diff had continued I would have been willing to try anything!


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## peardrops (Jan 3, 2004)

I've read quite a bit on Human Probiotics Infusion. It has been used for treating people with relapsing, severe c-diff infection. I'm sure I read about it on www.cdiffsupport.com/discus/ Didn't Spasman post something about a clinic in Australia doing it? The site I've quoted is for people with c-diff but there is some useful information there on probiotics. I think if my c-diff had continued I would have been willing to try anything!


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## SpAsMaN* (May 11, 2002)

Peardrop,don't worry about c-diff.The Probiotic therapy clinic in Australia cure 100% of the case of C-diff.Also,a new probiotic from Quebec claims to figth C-Diff also.The product is BIO-K + and it make the news here but for IBS i don't know that it works because one week trial didn't do anything to me.


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## SpAsMaN* (May 11, 2002)

Peardrop,don't worry about c-diff.The Probiotic therapy clinic in Australia cure 100% of the case of C-diff.Also,a new probiotic from Quebec claims to figth C-Diff also.The product is BIO-K + and it make the news here but for IBS i don't know that it works because one week trial didn't do anything to me.


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## peardrops (Jan 3, 2004)

I've not heard of Bio-K. I've found some info on it and probiotics in general at www.askwaltstollmd.com/archives/probiotics.html


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## peardrops (Jan 3, 2004)

I've not heard of Bio-K. I've found some info on it and probiotics in general at www.askwaltstollmd.com/archives/probiotics.html


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## Talissa (Apr 10, 2004)

I haven't heard of Bio-K either. Thanks for the link Pear. Here's a press release: http://www.cnw.ca/en/releases/archive/Augu...4/19/c2638.html Spasman, Je suis dï¿½solï¿½ qu'il n'a pas travaillï¿½ pour vous. Maybe you should've taken it for at least a month?? (I'm learning French juste pour vous







)


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## Talissa (Apr 10, 2004)

I haven't heard of Bio-K either. Thanks for the link Pear. Here's a press release: http://www.cnw.ca/en/releases/archive/Augu...4/19/c2638.html Spasman, Je suis dï¿½solï¿½ qu'il n'a pas travaillï¿½ pour vous. Maybe you should've taken it for at least a month?? (I'm learning French juste pour vous







)


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## Nath (Jan 5, 1999)

Joan, Id hate to even imagine what most of us would get upto if we thought it would do any good


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## Nath (Jan 5, 1999)

Joan, Id hate to even imagine what most of us would get upto if we thought it would do any good


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## Talissa (Apr 10, 2004)

Nath, lol, that's so true!Hey guys, just fyi, I found this info on another amino acid lysine, which is in the probiotic Digestive Advantage IBS~"L-Lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in rats""...An increase in nutritional load of L-lysine might be a useful tool in treating stress-induced anxiety and 5-HT-related diarrhea-type intestinal dysfunctions." http://www.pubmedcentral.nih.gov/articlere...ertype=abstract This was news to me.(also want to add that if thinking of taking l-lysine, should never take more than 500 mg(1/2 gram) per day. If you take 20 times that, it can actually cause diarrhea & is unhealthy. L-histidine is best taken at 200-250 mg/day, always taken with zinc)Joan, I also loved kel's statement~


> quote:"If the medical establishment (big pharm) really cared about helping people they would devote more time to understanding gut flora as opposed to symptom suppressing drugs."


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## Talissa (Apr 10, 2004)

Nath, lol, that's so true!Hey guys, just fyi, I found this info on another amino acid lysine, which is in the probiotic Digestive Advantage IBS~"L-Lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in rats""...An increase in nutritional load of L-lysine might be a useful tool in treating stress-induced anxiety and 5-HT-related diarrhea-type intestinal dysfunctions." http://www.pubmedcentral.nih.gov/articlere...ertype=abstract This was news to me.(also want to add that if thinking of taking l-lysine, should never take more than 500 mg(1/2 gram) per day. If you take 20 times that, it can actually cause diarrhea & is unhealthy. L-histidine is best taken at 200-250 mg/day, always taken with zinc)Joan, I also loved kel's statement~


> quote:"If the medical establishment (big pharm) really cared about helping people they would devote more time to understanding gut flora as opposed to symptom suppressing drugs."


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## eric (Jul 8, 1999)

""If the medical establishment (big pharm) really cared about helping people they would devote more time to understanding gut flora as opposed to symptom suppressing drugs." The creation of the new drugs are targeted to malfunctioning of certain gut reeptors 5ht3 and 5ht4, that they KNOW are NOT Functioning right. This is very important research. The research on the one hundred million nerve fibers that control digestion from the gut to the brain and back is as important to research as gut flora. Both are extermely complex issues here and both are being actively investigated. Its not a competition.also for bacteria infections, which IBS is not at this time.""We now know quite a lot about the library of programs run by the gut brain," says Jackie Wood, professor of physiology and cell biology and of internal medicine at Ohio State University. "For example, when the bowel is empty, one particular program runs." Called the migrating motor complex (MMC), this involves a series of movements running from the stomach to the end of the small intestine, which is believed to function in keeping the potentially dangerous bacteria stored in the colon from moving upwards rather than out. At least 500 different species of deadly bacteria have been found to inhabit a person's colon at any given time; "traveler's diarrhea" often results when this mix is changed through exposure to new pathogens. If this happens, the gut runs a program designed to expel as much of its contents as quickly as possible ï¿½ unpleasant for the vacationer, but much better than a fatal infection. "Another program involves a flood of serotonin throughout the entire circuit, which produces the digestive pattern that mixes and stirs the contents," says Wood. " http://www.kiwiterapi.dk/whiplash/frames/gutthoughts.htm D is the result of bacteria in the gut as the body try's to expel the pathogen.In C the slow transit can lead to the food staying longer in the colon and fermentation of the contents in the bowel and hence a change in gut flora.This second program.""Another program involves a flood of serotonin throughout the entire circuit, which produces the digestive pattern that mixes and stirs the contents," says Wood. ""Is not functioning right in IBS.It maybe more from damage due to gut insults and possibly in part genetics, that cause the intial gut changes, then what most people think when they think disease processes.


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## eric (Jul 8, 1999)

""If the medical establishment (big pharm) really cared about helping people they would devote more time to understanding gut flora as opposed to symptom suppressing drugs." The creation of the new drugs are targeted to malfunctioning of certain gut reeptors 5ht3 and 5ht4, that they KNOW are NOT Functioning right. This is very important research. The research on the one hundred million nerve fibers that control digestion from the gut to the brain and back is as important to research as gut flora. Both are extermely complex issues here and both are being actively investigated. Its not a competition.also for bacteria infections, which IBS is not at this time.""We now know quite a lot about the library of programs run by the gut brain," says Jackie Wood, professor of physiology and cell biology and of internal medicine at Ohio State University. "For example, when the bowel is empty, one particular program runs." Called the migrating motor complex (MMC), this involves a series of movements running from the stomach to the end of the small intestine, which is believed to function in keeping the potentially dangerous bacteria stored in the colon from moving upwards rather than out. At least 500 different species of deadly bacteria have been found to inhabit a person's colon at any given time; "traveler's diarrhea" often results when this mix is changed through exposure to new pathogens. If this happens, the gut runs a program designed to expel as much of its contents as quickly as possible ï¿½ unpleasant for the vacationer, but much better than a fatal infection. "Another program involves a flood of serotonin throughout the entire circuit, which produces the digestive pattern that mixes and stirs the contents," says Wood. " http://www.kiwiterapi.dk/whiplash/frames/gutthoughts.htm D is the result of bacteria in the gut as the body try's to expel the pathogen.In C the slow transit can lead to the food staying longer in the colon and fermentation of the contents in the bowel and hence a change in gut flora.This second program.""Another program involves a flood of serotonin throughout the entire circuit, which produces the digestive pattern that mixes and stirs the contents," says Wood. ""Is not functioning right in IBS.It maybe more from damage due to gut insults and possibly in part genetics, that cause the intial gut changes, then what most people think when they think disease processes.


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## SpAsMaN* (May 11, 2002)

Talissa,good strart but:Je suis dï¿½solï¿½ qu'il n'a pas travaillï¿½ pour vous."travaillï¿½" cannot be translate word for word with english unfortunaly.The real term for this is "fonctionnï¿½"."Travaillï¿½" only mean Working at the JOB.Long way to go!!!LOL Tal,i correct you and you correct me.







BIO-K is in yagourt form but taste bad.Some naturopath claims that it help to figth the bad bacterias.I wonder if one month of BIO-K would do anything.


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## SpAsMaN* (May 11, 2002)

Talissa,good strart but:Je suis dï¿½solï¿½ qu'il n'a pas travaillï¿½ pour vous."travaillï¿½" cannot be translate word for word with english unfortunaly.The real term for this is "fonctionnï¿½"."Travaillï¿½" only mean Working at the JOB.Long way to go!!!LOL Tal,i correct you and you correct me.







BIO-K is in yagourt form but taste bad.Some naturopath claims that it help to figth the bad bacterias.I wonder if one month of BIO-K would do anything.


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## SpAsMaN* (May 11, 2002)

Tal,for the phrase and the little words,i'm impress.







For BIO-K again,it is REAL,the researchers(Dr.)have explain in the news that it really figth C-Diff.I will do the web search in french for an abstract.IBS is a full time job.


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## SpAsMaN* (May 11, 2002)

Tal,for the phrase and the little words,i'm impress.







For BIO-K again,it is REAL,the researchers(Dr.)have explain in the news that it really figth C-Diff.I will do the web search in french for an abstract.IBS is a full time job.


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## SpAsMaN* (May 11, 2002)

BIO-K,C-diff: http://chealth.canoe.ca/health_news_detail.asp?news_id=11426 http://www.canoe.ca/NewsStand/CalgarySun/N.../20/592824.html IBS:I think that D predominant may have a bacterial issue,for the others,i think this is an electricity dysfunction.(see my post in the main menu).


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## SpAsMaN* (May 11, 2002)

BIO-K,C-diff: http://chealth.canoe.ca/health_news_detail.asp?news_id=11426 http://www.canoe.ca/NewsStand/CalgarySun/N.../20/592824.html IBS:I think that D predominant may have a bacterial issue,for the others,i think this is an electricity dysfunction.(see my post in the main menu).


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## Talissa (Apr 10, 2004)

Probiotics _can_ change genetic behavior, acc to this article:"What they all do and how they interact is just beginning to be unravelled, but they can certainly turn genes on and off. ï¿½The microbes, the immune system and the cells of the intestine are all intertwined,ï¿½ says Jeff Gordon, of Washington University in St Louis, Missouri. Two years ago he published a paper in the journal _Science_ reporting that just one strain of probiotics was involved in changing the behaviour of a dozen or more genes, particularly those involved with absorbing and metabolising sugars and fats and controlling cell repair. " http://www.timesonline.co.uk/article/0,,8126-990512,00.html This was also interesting re: inflammation & probiotics~"It's interesting that the organisms we are studying are non-pathogenic and have no ability to elicit inflammation themselves, yet they are able to block inflammatory pathways and create tolerance for themselves and perhaps other organisms," said Dr. Neish. "It turns out that some non-pathogenic bacteria have a significant reciprocal ecological interaction with the host." http://www.upwardquest.com/01-good-bacteri...intestinal.html In the back of my mind, I was afraid that by destroying our innate beneficial bacteria(via man-made drugs, poor diet, etc) which normally controls inflammatory response, that once its gone, its gone. In other words, I thought that purchased probiotics may help prevent something like IBS, but not be able to send it into remission.I'm glad the back of my mind was probably wrong.







______________________________Spasman, Je suis dï¿½solï¿½ que je n'aie pas parlï¿½ franï¿½ais correct. Merci pour votre aide! (Je continuerai ï¿½ fonctionner ï¿½ elle.)


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## Talissa (Apr 10, 2004)

Probiotics _can_ change genetic behavior, acc to this article:"What they all do and how they interact is just beginning to be unravelled, but they can certainly turn genes on and off. ï¿½The microbes, the immune system and the cells of the intestine are all intertwined,ï¿½ says Jeff Gordon, of Washington University in St Louis, Missouri. Two years ago he published a paper in the journal _Science_ reporting that just one strain of probiotics was involved in changing the behaviour of a dozen or more genes, particularly those involved with absorbing and metabolising sugars and fats and controlling cell repair. " http://www.timesonline.co.uk/article/0,,8126-990512,00.html This was also interesting re: inflammation & probiotics~"It's interesting that the organisms we are studying are non-pathogenic and have no ability to elicit inflammation themselves, yet they are able to block inflammatory pathways and create tolerance for themselves and perhaps other organisms," said Dr. Neish. "It turns out that some non-pathogenic bacteria have a significant reciprocal ecological interaction with the host." http://www.upwardquest.com/01-good-bacteri...intestinal.html In the back of my mind, I was afraid that by destroying our innate beneficial bacteria(via man-made drugs, poor diet, etc) which normally controls inflammatory response, that once its gone, its gone. In other words, I thought that purchased probiotics may help prevent something like IBS, but not be able to send it into remission.I'm glad the back of my mind was probably wrong.







______________________________Spasman, Je suis dï¿½solï¿½ que je n'aie pas parlï¿½ franï¿½ais correct. Merci pour votre aide! (Je continuerai ï¿½ fonctionner ï¿½ elle.)


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## Kacebece3 (Apr 17, 2002)

Thanks for the info Talissa, really goooood stuff.Ken


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## Kacebece3 (Apr 17, 2002)

Thanks for the info Talissa, really goooood stuff.Ken


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## SpAsMaN* (May 11, 2002)

Tal,i think you love me







Do you remember the song:All we need is love...If that was true.Tal,the verb "fonctionner", is "to function" in English.Your last sentence was wrong again.It is almost impossible to explain how to use it.I hope you get it now with the word in English.You can use "travaillï¿½" when you do a task.I think it is clear now.Now,back to WORK.(not to function).







Tu est presque parfaite!


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## SpAsMaN* (May 11, 2002)

Tal,i think you love me







Do you remember the song:All we need is love...If that was true.Tal,the verb "fonctionner", is "to function" in English.Your last sentence was wrong again.It is almost impossible to explain how to use it.I hope you get it now with the word in English.You can use "travaillï¿½" when you do a task.I think it is clear now.Now,back to WORK.(not to function).







Tu est presque parfaite!


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## SpAsMaN* (May 11, 2002)

I've almost lost interest in Probiotics since many failed.Which do you think it's the best to try?


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## SpAsMaN* (May 11, 2002)

I've almost lost interest in Probiotics since many failed.Which do you think it's the best to try?


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## Guest (Aug 24, 2004)

I just talked to my gastroenterologist in San Francisco about getting Low Dose Naltrexone. He said, I'd like you to try something else first and prescribed me a drug to fight INFLAMMATION as he says there is growing evidence that the low grade inflammation found in ibs triggers a response along nervous system etc and causes IBS symptoms said probiotics help along same lines and suggested i do VSL and another new strain.so i will be picking up my anti-inflammatory and probiotics tonite!WOW!!


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## Guest (Aug 24, 2004)

I just talked to my gastroenterologist in San Francisco about getting Low Dose Naltrexone. He said, I'd like you to try something else first and prescribed me a drug to fight INFLAMMATION as he says there is growing evidence that the low grade inflammation found in ibs triggers a response along nervous system etc and causes IBS symptoms said probiotics help along same lines and suggested i do VSL and another new strain.so i will be picking up my anti-inflammatory and probiotics tonite!WOW!!


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## SpAsMaN* (May 11, 2002)

VSL #3 is a waste of money and extremely expensive.But i'm curious what is the "anti-inflammatory drug" he prescribe.Let us know how it turns. Anti-inflammatory drug seems promising but i don't think a clinical trial to prove it.They usually are terrible for the G.I. tract.I doubt about the knowledges of this doc.I guess you will be worst.Sorry,i'm negative or realist.


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## SpAsMaN* (May 11, 2002)

VSL #3 is a waste of money and extremely expensive.But i'm curious what is the "anti-inflammatory drug" he prescribe.Let us know how it turns. Anti-inflammatory drug seems promising but i don't think a clinical trial to prove it.They usually are terrible for the G.I. tract.I doubt about the knowledges of this doc.I guess you will be worst.Sorry,i'm negative or realist.


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## scottyswotty (Jun 29, 2000)

Spasman - you talk a lot about wanting an anti-inflammatory.Have you tried Ibsacol yet? ie for 2 months? I know you prefer the orthodox approach (medical doctor) but ibsacol works on the inflammatory pathways. Worth a shot?


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## scottyswotty (Jun 29, 2000)

Spasman - you talk a lot about wanting an anti-inflammatory.Have you tried Ibsacol yet? ie for 2 months? I know you prefer the orthodox approach (medical doctor) but ibsacol works on the inflammatory pathways. Worth a shot?


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## SpAsMaN* (May 11, 2002)

Scotty,i will check my mail,IBSACOL is on the way.My expectation are low.An undercover member agreed to send my a sample.


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## SpAsMaN* (May 11, 2002)

Scotty,i will check my mail,IBSACOL is on the way.My expectation are low.An undercover member agreed to send my a sample.


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## scottyswotty (Jun 29, 2000)

> quote: My expectation are low.


well you can't really be disappointed then.







You need to try it for about 4 weeks though at 4 capsules, 3 times a day.


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## scottyswotty (Jun 29, 2000)

> quote: My expectation are low.


well you can't really be disappointed then.







You need to try it for about 4 weeks though at 4 capsules, 3 times a day.


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## AlphaMale (Jan 21, 2004)

> quote:I've almost lost interest in Probiotics since many failed.Which do you think it's the best to try?


Home made yougortAny one tried to grow good bacteria at home.


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## AlphaMale (Jan 21, 2004)

> quote:I've almost lost interest in Probiotics since many failed.Which do you think it's the best to try?


Home made yougortAny one tried to grow good bacteria at home.


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## eric (Jul 8, 1999)

I posted this eariler in this thread.EFFECT OF A PROBIOTIC, VSL#3, IN DIARRHEA-PREDOMINANT IRRITABLE BOWEL SYNDROME: A RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED TRIALH. Jae Kim, M.D. Michael Camilleri, M.D., FACG, Sanna McKinzie, M.S., Duane Burton, George M. Thomforde and Alan R. Zinsmeister, Ph.D.Clinical Enteric Neuroscience Translational & Epidemiological Research (C.E.N.T.E.R.) Program, Mayo Clinic Rochester, MNPurpose Recent clinical studies have demonstrated that the probiotics are efficacious in treating various diarrheal illnesses. The influence of probiotic on gastrointestinal transit in patients with irritable bowel syndrome (IBS) is unclear. We investigated the effect of VSL#3 on the gastrointestinal transit and symptoms of patients with diarrhea-predominant IBS.Methods Patients fulfilling the Rome II criteria with diarrhea-predominant symptoms and without a history of organic gastrointestinal disease were recruited. Twenty-five patients were randomly assigned to VSL#3 powder or matching placebo twice daily for 8 weeks after a 2 week baseline period to assess symptoms. The VSL#3 group received 450 billion lyophilized bacteria per day. Pre- and post-treatment gastrointestinal transit measurements were performed in all patients. Patients recorded their bowel function and symptoms daily for the entire study. The primary endpoint of the study was colonic geometric center at 24 hours, and secondary endpoints were; gastric emptying at 2 and 4 hours, colonic filling at 6 hours, colonic geometric center at 48 hours, proportion of responders, and individual symptoms and bowel functions. *Results There were no significant differences of the mean gastrointestinal transit measurements between the two groups, pre- and post-therapy. Overall, individual IBS symptoms and satisfactory relief of IBS were not different between VSL#3 and placebo group; however, abdominal bloating was significantly reduced in the VSL#3 group (post vs pre, P = 0.04) and not in the placebo group * (post vs pre, P = 0.78). *The scores for flatulence, abdominal pain, and urgency were not significantly reduced in patients treated with VSL#3.* All patients tolerated the VSL#3 well. One patient, who was later shown to be randomized to placebo, withdrew from the study due to a severe abdominal pain. *Conclusion VSL#3 appears promising in the relief of abdominal bloating in patients with diarrhea-predominant IBS. This effect is unrelated to alteration in gastrointestinal or colon transit. * Am J gastroenterol. 2002; 97(9): A830according to this randomized control study VSL probiotics helped bloating in D IBSers and that was it and it was not better then placebo. Although and I keep mentioning that the bowel works by pressure sensitve cells, that bloating can cause pain because it distends the colon, so it might help with pain also some."This effect is unrelated to alteration in gastrointestinal or colon transit. "We have already talked a lot about inflammation of mast cells in IBS here. There are many triggers that degrandulate mast cells so they become inflammed. Medicince foods and stress are some, but even cold weather can degrandulate them.I also have to say this again, inflammation cannot be the biological marker for all IBSers."Curr Gastroenterol Rep. 2003 Aug;5(4):331-6. Related Articles, Links Current insights into the pathophysiology of irritable bowel syndrome.Schwetz I, Bradesi S, Mayer EA.Center of Neurovisceral Sciences and Women's Health, CURE: Digestive Diseases Research Center, David Geffen School of Medicine at UCLA, VAGLAHS, Bldg. 115, Room 223, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA. emayer###ucla.eduRecent reports have emphasized the possible role of mucosal immune activation and inflammation in neuropathic changes in the pathophysiology of irritable bowel syndrome (IBS). However, novel findings using functional brain imaging techniques have underlined the importance of altered perception of visceral stimuli to symptom generation in IBS. These new developments have rekindled an old debate on peripheral versus central mechanisms in the pathophysiology of IBS. In this review we discuss the latest findings in light of these two concepts. *In addition, we provide evidence for the hypothesis that, in the absence of alterations in endogenous pain modulation systems and changes in visceral perception, chronic inflammatory mucosal changes in the gut are not a plausible mechanism to explain the presence of chronic abdominal pain, a cardinal IBS symptom.* Publication Types: Review Review, Tutorial PMID: 12864964 It can contribute to pain, but with out "alterations in endogenous pain modulation systems and changes in visceral perception"Which they already find in IBS, it cannot explain chronic pain in IBS. Other systems are impaired in IBS and something else is going on.They also know when D IBSers eat there is an increase in serotonin in the gut. The increase causes d. IBS has three subgroups as we all know, d IBS and c IBS and alternating. They are connected to the same problem of those gut receptors that either cause d or c or alternating. They have known this for quite some time now.IN PI IBS there is an increase of those cells that conntain it and release it and they are no more or less important then mast cells. Its all connected.Dr Spiller is one of the world leaders in PI IBS."Distinctive clinical, psychological, and histological features of postinfective irritable bowel syndrome.Dunlop SP, Jenkins D, Spiller RC.Division of Divisions of Gastroenterology, University Hospital, Nottingham, United Kingdom.OBJECTIVE: Irritable bowel syndrome *after * gastroenteritis is well recognized. Our aim was to determine whether postinfective IBS (PI-IBS) has histological or clinical features that are distinct from those of IBS patients with no history of preceding infection. METHODS: A total of 75 consecutive IBS outpatients and 36 healthy control subjects completed a questionnaire detailing symptoms, mode of onset, and previous psychiatric history. All underwent a full diagnostic workup including rectal biopsy, which included immunostaining and quantification for lamina propria or intraepithelial T lymphocytes, serotonin-containing enterochromaffin (EC), and mast cells. Patients were divided according to onset of symptoms into PI-IBS (n = 23) or non-PI-IBS (n = 52) patients. RESULTS: Diarrhea predominance occurred more frequently in PI-IBS (70%) than in non-PI-IBS (42%) patients (p = 0.03). A history of previous treatment for anxiety or depression was present in 26% of PI-IBS patients compared to 54% of non-PI-IBS (p = 0.02). Biopsy results for all patients were normal using conventional criteria; however, quantification revealed that PI-IBS showed increased EC cells compared to those of non-PI-IBS patients (p = 0.017) and controls (p = 0.02). Lamina propria T lymphocytes were increased in PI-IBS (p = 0.026) and non-PI-IBS (p = 0.011) patients compared to controls. Mast cells were increased in non-PI-IBS patients (p = 0.054) compared to controls. *CONCLUSIONS: Individuals with PI-IBS are a clinically distinct subgroup characterized by diarrheal symptoms, less psychiatric illness, and increased serotonin-containing EC cells compared to those with non-PI-IBS.* PMID: 12873581Serotonin is also part of the anxiety issues in IBS.Also, when they pet scanned people on lotronex, they found it effected some of the same areas in IBS that were impaired in the brain.They can also give rats basically IBS.Am J Physiol Gastrointest Liver Physiol. 2001 Apr;280(4):G519-24. Related Articles, Links V. Stress and irritable bowel syndrome.Mayer EA, Naliboff BD, Chang L, Coutinho SV.UCLA/CURE Neuroenteric Disease Program, Departments of Medicine, Physiology, and Biobehavioral Sciences, UCLA School of Medicine, Los Angeles, California 90024, USA. emayer###ucla.eduDifferent types of stress play important roles in the onset and modulation of irritable bowel syndrome (IBS) symptoms. The physiological effects of psychological and physical stressors on gut function and brain-gut interactions are mediated by outputs of the emotional motor system in terms of autonomic, neuroendocrine, attentional, and pain modulatory responses. IBS patients show an enhanced responsiveness of this system manifesting in altered modulation of gastrointestinal motility and secretion and in alterations in the perception of visceral events. Functional brain imaging techniques are beginning to identify brain circuits involved in the perceptual alterations. Animal models have recently been proposed that mimic key features of the human syndrome.Publication Types: Review Review, Tutorial PMID: 11254476Its also important to understand gut permeability at the time of infection in PI IBS. Not all IBSers have intestinal permeability. People who have been infected by an enteric infection that leads to IBS have altered gut permeability at those stages do to the inflammtion of the INTIAL INFECTION.This was from 2001 and they actually know more now."Can J Gastroenterol. 2001 Oct;15 Suppl B:14B-16B. Related Articles, Links Peripheral mechanisms of symptom generation in irritable bowel syndrome.Collins SM.Division of Gastroenterology, McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada. scollins###mcmaster.caThere is considerable interest in the mechanisms that underlie symptom generation in irritable bowel syndrome (IBS) and particularly those mechanisms peripheral to higher centres in the nervous system. While the central nervous system is important in IBS, it is restricted largely to the role of behaviour in stress perception and symptom reporting. The gut and the autonomic nervous system are principal areas of research in identifying mechanisms underlying symptom generation and in the identification of new targets for drug development. While motility changes occur in IBS, they are neither specific nor predictable, and this is one reason why drugs aimed at influencing motility patterns have enjoyed limited success to date. This success has prompted interest in sensory physiology to explain pain and other discomforts expressed by patients with IBS. Patients with IBS exhibit intolerance to rectal distension and other manoeuvres of the gut, while exhibiting normal or raised thresholds for somatic pain. The mechanisms underlying the development of hyperalgesia or allodynia in the gut remain to be determined. In other systems and experimental models, low grade inflammation is a predictable inducer of these states, and recent evidence suggests that a subpopulation of patients with IBS develop chronic symptoms after acute gastroenteritis. This and other inflammatory stimuli may induce a hyperalgesic state and alter motor function in patients with IBS. Substances that mediate these changes are not fully understood, but there is growing recognition of the role of serotonin as a sensitizing agent.Publication Types: Review Review, Tutorial PMID: 11694910The brain can effect the gut and the gut effects the brain in IBS, both are operational to cause the symptoms.Dig Dis. 2001;19(3):212-8. Related Articles, Links Basic pathophysiologic mechanisms in irritable bowel syndrome.Mayer EA, Naliboff BD, Chang L.UCLA/CURE Neuroenteric Disease Program, Department of Medicine, Physiology and Biobehavioral Sciences, UCLA School of Medicine, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA. emayer###ucla.eduConverging evidence supports the concept that the irritable bowel syndrome (IBS) symptom complex results from altered regulation of gastrointestinal motility and epithelial function, as well as an altered perception of visceral events. Despite similar symptoms, there is likely heterogeneity of underlying dysfunction and pathogenesis in different subgroups of IBS patients: the syndrome may be produced by primary alterations in the central nervous system (CNS; top down model), or by primary alterations in the periphery (bottom up model), or by a combination of both. One plausible mechanism by which alterations in the CNS result in symptoms, is the enhanced responsiveness of central stress/emotion circuits. The physiological effects of psychological and physical stressors on gut function and brain-gut interactions are mediated by outputs of the emotional motor system in terms of autonomic, neuroendocrine, attentional and pain modulatory responses. IBS patients show an enhanced responsiveness of this system manifesting in altered modulation of gastrointestinal motility, secretion, immune function and in alterations in the perceptual and emotional response to visceral events. Copyright 2001 S. Karger AG, BaselPublication Types: Review Review, Tutorial PMID: 11752839 I have been saying this for years know, mast cells and EC cells (that store serotonin) are very problematic in IBS, not totally understood yet, but very much implicated one way or another, regardless. Stress on the psycophysiological level also seems to be very very important in both the condition itself and in treating it.There is a lot of threads and talk on altered gut permeability and there is a lot of research on IBS pointing to chronic stressors, both physical and mental leading to increased permeability, but not much on stress reduction to combat it, more on probiotics, which I am all for in IBS, although not quite as "Thrilled" with the results from studies which have not shown major impacts on IBS, more a prevention and over all gut health role, along with a possible decrease in Bloating and possibly pain, which of course is very helpful for sure.Many times I see this role blown out of purportion on the bb. I agree they need to be studied and they are being studied, but its is way to early to call IBS an altered gut flora "disease." They have a role as do the many neurotramsitters and gases and hormones and other chemicals and even systems, like the colonic pacemaker and many others and all kinds of other issues that need to be studied in IBS and added to the vast library of IBS infromation that has already been gathered in regards to the big picture of IBS. However, there is already quite a bit known now.For example, people here can implicate and post all kinds of studies on bacteria and IBS, but the ACC of the brain is impaired in IBS and the researchers have to find and learn how impairment of ACC and other brain regions can be effected and HOW that happens in IBS, due to gut flora, thay have already with other systems and chemicals done some major research. That is one example, another would be rectal sensitivity and many more.Tals post above shows how gut flora can altered gene expression for example. Probiotics are benefical bacteria for the most part, but that is why they are more cautious in there role in IBS, because they are not sure all of the roles and what each specific strain does, like many other things that are majorally complex in brain gut communications and IBS and all the things gut flora does do good or bad. Many of them have been shown to be benefical and harmless, however there have not been enough studies and enough long term studies for them to sort it all out yet. So its still basically we don't know, we think they help, these are possible ways they might help and this is what we have shown so far to help and you can try them if you want.Curr Treat Options Gastroenterol. 2003 Aug;6(4):283-288. Related Articles, Links Probiotics, Irritable Bowel Syndrome, and Inflammatory Bowel Disease.Floch MH.Department of Medicine, Yale University School of Medicine, 30 Stevens Street, Suite E, Norwalk, CT 06850, USA. martinfloch###snet.netProbiotics are live, microbial food supplements that benefit the host animal by improving intestinal microbial balance. Their major role in preventing and treating gastrointestinal disease appears to be from their effect on the immune process, protection against abnormal invasive bacteria, and in the production of short-chain fatty acids from starch and non-starch polysaccharides. Probiotic microorganisms are administered in food supplements and yogurts. They are also now sold in the form of capsules and powders. There is great variation in the microorganisms in the various supplements. It is important to understand that all probiotic products are different. Some contain a single organism and others contain multiple organisms. Therapeutic results have been achieved with various probiotics in different diseases. In the treatment of inflammatory bowel diseases (IBD), success has been reported with Escherichia coli Nissle strain in ulcerative colitis, and with a multiple organism product, VSL#3 (VSL Pharmaceuticals, Fort Lauderdale, FL), in Crohn's disease and pouchitis. Initial reports in irritable bowel syndrome (IBS) have resulted in encouraging results with the use of E. coli Nissle strain, and recently with multiple organism probiotic supplements. However, caution must still apply to the use of probiotics in IBD and IBS because the reports and the number of patients treated are limited.PMID: 12846937 This one in this study did not do anything."Dig Dis Sci. 2002 Nov;47(11):2615-20. Related Articles, Links Effect of Lactobacillus plantarum 299v on colonic fermentation and symptoms of irritable bowel syndrome.Sen S, Mullan MM, Parker TJ, Woolner JT, Tarry SA, Hunter JO.Department of Gastroenterology, Addenbrooke's Hospital, Cambridge, UK.A number of recent clinical trials have promoted the use of probiotic bacteria as a treatment for irritable bowel syndrome (IBS). The recent demonstration of abnormal colonic fermentation in some patients with this condition provides an opportunity for the objective assessment of the therapeutic value of these bacteria. This study was designed to investigate the effects of Lactobacillus plantarum 299V on colonic fermentation. We conducted a double-blind, placebo-controlled, cross-over, four-week trial of Lactobacillus plantarum 299V in 12 previously untreated patients with IBS. Symptoms were assessed daily by a validated composite score and fermentation by 24-hr indirect calorimetry in a 1.4-m3 canopy followed by breath hydrogen determination for 3 hr after 20 ml of lactulose. On placebo, the median symptom score was 8.5 6.25-11.25 interquartile range (IQR), the median maximum rate of gas production was 0.55 ml/min (0.4-1.1 IQR), and the median hydrogen production was 189.7 ml/24 hr (118.3-291.1 IQR). On Lactobacillus plantarum 299V the median symptom score was 8 (6.75-13.5 IQR), the median maximum rate of gas production 0.92 ml/min (0.45-1.5 IQR), and the median hydrogen production 208.2 ml/24 hr (146-350.9 IQR). There was no significant difference. Breath hydrogen excretion after lactulose was reduced by the probiotic (median at 120 min, 6 ppm; placebo, 17 ppm; P = 0.019). In conclusion, Lactobacillus plantarum 299V in this study did not appear to alter colonic fermentation or improve symptoms in patients with the irritable bowel syndrome.Publication Types: Clinical TrialPMID: 12452404 Br J Nutr. 2002 Sep;88 Suppl 1:S67-72. Related Articles, Links A review of the role of the gut microflora in irritable bowel syndrome and the effects of probiotics.Madden JA, Hunter JO.Gastroenterology Research Unit, Unit E7, Box 201 A, Addenbrookes NHS Trust, Hill's Road, CB2 2QQ, Cambridge, UK.Irritable bowel syndrome (IBS) is a multi-factorial gastrointestinal condition affecting 8-22 % of the population with a higher prevalence in women and accounting for 20-50 % of referrals to gastroenterology clinics. It is characterised by abdominal pain, excessive flatus, variable bowel habit and abdominal bloating for which there is no evidence of detectable organic disease. Suggested aetiologies include gut motility and psychological disorders, psychophysiological phenomena and colonic malfermentation. The faecal microflora in IBS has been shown to be abnormal with higher numbers of facultative organisms and low numbers of lactobacilli and bifidobacteria. Although there is no evidence of food allergy in IBS, food intolerance has been identified and exclusion diets are beneficial to many IBS patients. Food intolerance may be due to abnormal fermentation of food residues in the colon, as a result of disruption of the normal flora. The role of probiotics in IBS has not been clearly defined. *Some studies have shown improvements in pain and flatulence in response to probiotic administration, whilst others have shown no symptomatic improvement. It is possible that the future role of probiotics in IBS will lie in prevention, rather than cure.* Publication Types: Review Review, Tutorial PMID: 12215182


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## eric (Jul 8, 1999)

I posted this eariler in this thread.EFFECT OF A PROBIOTIC, VSL#3, IN DIARRHEA-PREDOMINANT IRRITABLE BOWEL SYNDROME: A RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED TRIALH. Jae Kim, M.D. Michael Camilleri, M.D., FACG, Sanna McKinzie, M.S., Duane Burton, George M. Thomforde and Alan R. Zinsmeister, Ph.D.Clinical Enteric Neuroscience Translational & Epidemiological Research (C.E.N.T.E.R.) Program, Mayo Clinic Rochester, MNPurpose Recent clinical studies have demonstrated that the probiotics are efficacious in treating various diarrheal illnesses. The influence of probiotic on gastrointestinal transit in patients with irritable bowel syndrome (IBS) is unclear. We investigated the effect of VSL#3 on the gastrointestinal transit and symptoms of patients with diarrhea-predominant IBS.Methods Patients fulfilling the Rome II criteria with diarrhea-predominant symptoms and without a history of organic gastrointestinal disease were recruited. Twenty-five patients were randomly assigned to VSL#3 powder or matching placebo twice daily for 8 weeks after a 2 week baseline period to assess symptoms. The VSL#3 group received 450 billion lyophilized bacteria per day. Pre- and post-treatment gastrointestinal transit measurements were performed in all patients. Patients recorded their bowel function and symptoms daily for the entire study. The primary endpoint of the study was colonic geometric center at 24 hours, and secondary endpoints were; gastric emptying at 2 and 4 hours, colonic filling at 6 hours, colonic geometric center at 48 hours, proportion of responders, and individual symptoms and bowel functions. *Results There were no significant differences of the mean gastrointestinal transit measurements between the two groups, pre- and post-therapy. Overall, individual IBS symptoms and satisfactory relief of IBS were not different between VSL#3 and placebo group; however, abdominal bloating was significantly reduced in the VSL#3 group (post vs pre, P = 0.04) and not in the placebo group * (post vs pre, P = 0.78). *The scores for flatulence, abdominal pain, and urgency were not significantly reduced in patients treated with VSL#3.* All patients tolerated the VSL#3 well. One patient, who was later shown to be randomized to placebo, withdrew from the study due to a severe abdominal pain. *Conclusion VSL#3 appears promising in the relief of abdominal bloating in patients with diarrhea-predominant IBS. This effect is unrelated to alteration in gastrointestinal or colon transit. * Am J gastroenterol. 2002; 97(9): A830according to this randomized control study VSL probiotics helped bloating in D IBSers and that was it and it was not better then placebo. Although and I keep mentioning that the bowel works by pressure sensitve cells, that bloating can cause pain because it distends the colon, so it might help with pain also some."This effect is unrelated to alteration in gastrointestinal or colon transit. "We have already talked a lot about inflammation of mast cells in IBS here. There are many triggers that degrandulate mast cells so they become inflammed. Medicince foods and stress are some, but even cold weather can degrandulate them.I also have to say this again, inflammation cannot be the biological marker for all IBSers."Curr Gastroenterol Rep. 2003 Aug;5(4):331-6. Related Articles, Links Current insights into the pathophysiology of irritable bowel syndrome.Schwetz I, Bradesi S, Mayer EA.Center of Neurovisceral Sciences and Women's Health, CURE: Digestive Diseases Research Center, David Geffen School of Medicine at UCLA, VAGLAHS, Bldg. 115, Room 223, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA. emayer###ucla.eduRecent reports have emphasized the possible role of mucosal immune activation and inflammation in neuropathic changes in the pathophysiology of irritable bowel syndrome (IBS). However, novel findings using functional brain imaging techniques have underlined the importance of altered perception of visceral stimuli to symptom generation in IBS. These new developments have rekindled an old debate on peripheral versus central mechanisms in the pathophysiology of IBS. In this review we discuss the latest findings in light of these two concepts. *In addition, we provide evidence for the hypothesis that, in the absence of alterations in endogenous pain modulation systems and changes in visceral perception, chronic inflammatory mucosal changes in the gut are not a plausible mechanism to explain the presence of chronic abdominal pain, a cardinal IBS symptom.* Publication Types: Review Review, Tutorial PMID: 12864964 It can contribute to pain, but with out "alterations in endogenous pain modulation systems and changes in visceral perception"Which they already find in IBS, it cannot explain chronic pain in IBS. Other systems are impaired in IBS and something else is going on.They also know when D IBSers eat there is an increase in serotonin in the gut. The increase causes d. IBS has three subgroups as we all know, d IBS and c IBS and alternating. They are connected to the same problem of those gut receptors that either cause d or c or alternating. They have known this for quite some time now.IN PI IBS there is an increase of those cells that conntain it and release it and they are no more or less important then mast cells. Its all connected.Dr Spiller is one of the world leaders in PI IBS."Distinctive clinical, psychological, and histological features of postinfective irritable bowel syndrome.Dunlop SP, Jenkins D, Spiller RC.Division of Divisions of Gastroenterology, University Hospital, Nottingham, United Kingdom.OBJECTIVE: Irritable bowel syndrome *after * gastroenteritis is well recognized. Our aim was to determine whether postinfective IBS (PI-IBS) has histological or clinical features that are distinct from those of IBS patients with no history of preceding infection. METHODS: A total of 75 consecutive IBS outpatients and 36 healthy control subjects completed a questionnaire detailing symptoms, mode of onset, and previous psychiatric history. All underwent a full diagnostic workup including rectal biopsy, which included immunostaining and quantification for lamina propria or intraepithelial T lymphocytes, serotonin-containing enterochromaffin (EC), and mast cells. Patients were divided according to onset of symptoms into PI-IBS (n = 23) or non-PI-IBS (n = 52) patients. RESULTS: Diarrhea predominance occurred more frequently in PI-IBS (70%) than in non-PI-IBS (42%) patients (p = 0.03). A history of previous treatment for anxiety or depression was present in 26% of PI-IBS patients compared to 54% of non-PI-IBS (p = 0.02). Biopsy results for all patients were normal using conventional criteria; however, quantification revealed that PI-IBS showed increased EC cells compared to those of non-PI-IBS patients (p = 0.017) and controls (p = 0.02). Lamina propria T lymphocytes were increased in PI-IBS (p = 0.026) and non-PI-IBS (p = 0.011) patients compared to controls. Mast cells were increased in non-PI-IBS patients (p = 0.054) compared to controls. *CONCLUSIONS: Individuals with PI-IBS are a clinically distinct subgroup characterized by diarrheal symptoms, less psychiatric illness, and increased serotonin-containing EC cells compared to those with non-PI-IBS.* PMID: 12873581Serotonin is also part of the anxiety issues in IBS.Also, when they pet scanned people on lotronex, they found it effected some of the same areas in IBS that were impaired in the brain.They can also give rats basically IBS.Am J Physiol Gastrointest Liver Physiol. 2001 Apr;280(4):G519-24. Related Articles, Links V. Stress and irritable bowel syndrome.Mayer EA, Naliboff BD, Chang L, Coutinho SV.UCLA/CURE Neuroenteric Disease Program, Departments of Medicine, Physiology, and Biobehavioral Sciences, UCLA School of Medicine, Los Angeles, California 90024, USA. emayer###ucla.eduDifferent types of stress play important roles in the onset and modulation of irritable bowel syndrome (IBS) symptoms. The physiological effects of psychological and physical stressors on gut function and brain-gut interactions are mediated by outputs of the emotional motor system in terms of autonomic, neuroendocrine, attentional, and pain modulatory responses. IBS patients show an enhanced responsiveness of this system manifesting in altered modulation of gastrointestinal motility and secretion and in alterations in the perception of visceral events. Functional brain imaging techniques are beginning to identify brain circuits involved in the perceptual alterations. Animal models have recently been proposed that mimic key features of the human syndrome.Publication Types: Review Review, Tutorial PMID: 11254476Its also important to understand gut permeability at the time of infection in PI IBS. Not all IBSers have intestinal permeability. People who have been infected by an enteric infection that leads to IBS have altered gut permeability at those stages do to the inflammtion of the INTIAL INFECTION.This was from 2001 and they actually know more now."Can J Gastroenterol. 2001 Oct;15 Suppl B:14B-16B. Related Articles, Links Peripheral mechanisms of symptom generation in irritable bowel syndrome.Collins SM.Division of Gastroenterology, McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada. scollins###mcmaster.caThere is considerable interest in the mechanisms that underlie symptom generation in irritable bowel syndrome (IBS) and particularly those mechanisms peripheral to higher centres in the nervous system. While the central nervous system is important in IBS, it is restricted largely to the role of behaviour in stress perception and symptom reporting. The gut and the autonomic nervous system are principal areas of research in identifying mechanisms underlying symptom generation and in the identification of new targets for drug development. While motility changes occur in IBS, they are neither specific nor predictable, and this is one reason why drugs aimed at influencing motility patterns have enjoyed limited success to date. This success has prompted interest in sensory physiology to explain pain and other discomforts expressed by patients with IBS. Patients with IBS exhibit intolerance to rectal distension and other manoeuvres of the gut, while exhibiting normal or raised thresholds for somatic pain. The mechanisms underlying the development of hyperalgesia or allodynia in the gut remain to be determined. In other systems and experimental models, low grade inflammation is a predictable inducer of these states, and recent evidence suggests that a subpopulation of patients with IBS develop chronic symptoms after acute gastroenteritis. This and other inflammatory stimuli may induce a hyperalgesic state and alter motor function in patients with IBS. Substances that mediate these changes are not fully understood, but there is growing recognition of the role of serotonin as a sensitizing agent.Publication Types: Review Review, Tutorial PMID: 11694910The brain can effect the gut and the gut effects the brain in IBS, both are operational to cause the symptoms.Dig Dis. 2001;19(3):212-8. Related Articles, Links Basic pathophysiologic mechanisms in irritable bowel syndrome.Mayer EA, Naliboff BD, Chang L.UCLA/CURE Neuroenteric Disease Program, Department of Medicine, Physiology and Biobehavioral Sciences, UCLA School of Medicine, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA. emayer###ucla.eduConverging evidence supports the concept that the irritable bowel syndrome (IBS) symptom complex results from altered regulation of gastrointestinal motility and epithelial function, as well as an altered perception of visceral events. Despite similar symptoms, there is likely heterogeneity of underlying dysfunction and pathogenesis in different subgroups of IBS patients: the syndrome may be produced by primary alterations in the central nervous system (CNS; top down model), or by primary alterations in the periphery (bottom up model), or by a combination of both. One plausible mechanism by which alterations in the CNS result in symptoms, is the enhanced responsiveness of central stress/emotion circuits. The physiological effects of psychological and physical stressors on gut function and brain-gut interactions are mediated by outputs of the emotional motor system in terms of autonomic, neuroendocrine, attentional and pain modulatory responses. IBS patients show an enhanced responsiveness of this system manifesting in altered modulation of gastrointestinal motility, secretion, immune function and in alterations in the perceptual and emotional response to visceral events. Copyright 2001 S. Karger AG, BaselPublication Types: Review Review, Tutorial PMID: 11752839 I have been saying this for years know, mast cells and EC cells (that store serotonin) are very problematic in IBS, not totally understood yet, but very much implicated one way or another, regardless. Stress on the psycophysiological level also seems to be very very important in both the condition itself and in treating it.There is a lot of threads and talk on altered gut permeability and there is a lot of research on IBS pointing to chronic stressors, both physical and mental leading to increased permeability, but not much on stress reduction to combat it, more on probiotics, which I am all for in IBS, although not quite as "Thrilled" with the results from studies which have not shown major impacts on IBS, more a prevention and over all gut health role, along with a possible decrease in Bloating and possibly pain, which of course is very helpful for sure.Many times I see this role blown out of purportion on the bb. I agree they need to be studied and they are being studied, but its is way to early to call IBS an altered gut flora "disease." They have a role as do the many neurotramsitters and gases and hormones and other chemicals and even systems, like the colonic pacemaker and many others and all kinds of other issues that need to be studied in IBS and added to the vast library of IBS infromation that has already been gathered in regards to the big picture of IBS. However, there is already quite a bit known now.For example, people here can implicate and post all kinds of studies on bacteria and IBS, but the ACC of the brain is impaired in IBS and the researchers have to find and learn how impairment of ACC and other brain regions can be effected and HOW that happens in IBS, due to gut flora, thay have already with other systems and chemicals done some major research. That is one example, another would be rectal sensitivity and many more.Tals post above shows how gut flora can altered gene expression for example. Probiotics are benefical bacteria for the most part, but that is why they are more cautious in there role in IBS, because they are not sure all of the roles and what each specific strain does, like many other things that are majorally complex in brain gut communications and IBS and all the things gut flora does do good or bad. Many of them have been shown to be benefical and harmless, however there have not been enough studies and enough long term studies for them to sort it all out yet. So its still basically we don't know, we think they help, these are possible ways they might help and this is what we have shown so far to help and you can try them if you want.Curr Treat Options Gastroenterol. 2003 Aug;6(4):283-288. Related Articles, Links Probiotics, Irritable Bowel Syndrome, and Inflammatory Bowel Disease.Floch MH.Department of Medicine, Yale University School of Medicine, 30 Stevens Street, Suite E, Norwalk, CT 06850, USA. martinfloch###snet.netProbiotics are live, microbial food supplements that benefit the host animal by improving intestinal microbial balance. Their major role in preventing and treating gastrointestinal disease appears to be from their effect on the immune process, protection against abnormal invasive bacteria, and in the production of short-chain fatty acids from starch and non-starch polysaccharides. Probiotic microorganisms are administered in food supplements and yogurts. They are also now sold in the form of capsules and powders. There is great variation in the microorganisms in the various supplements. It is important to understand that all probiotic products are different. Some contain a single organism and others contain multiple organisms. Therapeutic results have been achieved with various probiotics in different diseases. In the treatment of inflammatory bowel diseases (IBD), success has been reported with Escherichia coli Nissle strain in ulcerative colitis, and with a multiple organism product, VSL#3 (VSL Pharmaceuticals, Fort Lauderdale, FL), in Crohn's disease and pouchitis. Initial reports in irritable bowel syndrome (IBS) have resulted in encouraging results with the use of E. coli Nissle strain, and recently with multiple organism probiotic supplements. However, caution must still apply to the use of probiotics in IBD and IBS because the reports and the number of patients treated are limited.PMID: 12846937 This one in this study did not do anything."Dig Dis Sci. 2002 Nov;47(11):2615-20. Related Articles, Links Effect of Lactobacillus plantarum 299v on colonic fermentation and symptoms of irritable bowel syndrome.Sen S, Mullan MM, Parker TJ, Woolner JT, Tarry SA, Hunter JO.Department of Gastroenterology, Addenbrooke's Hospital, Cambridge, UK.A number of recent clinical trials have promoted the use of probiotic bacteria as a treatment for irritable bowel syndrome (IBS). The recent demonstration of abnormal colonic fermentation in some patients with this condition provides an opportunity for the objective assessment of the therapeutic value of these bacteria. This study was designed to investigate the effects of Lactobacillus plantarum 299V on colonic fermentation. We conducted a double-blind, placebo-controlled, cross-over, four-week trial of Lactobacillus plantarum 299V in 12 previously untreated patients with IBS. Symptoms were assessed daily by a validated composite score and fermentation by 24-hr indirect calorimetry in a 1.4-m3 canopy followed by breath hydrogen determination for 3 hr after 20 ml of lactulose. On placebo, the median symptom score was 8.5 6.25-11.25 interquartile range (IQR), the median maximum rate of gas production was 0.55 ml/min (0.4-1.1 IQR), and the median hydrogen production was 189.7 ml/24 hr (118.3-291.1 IQR). On Lactobacillus plantarum 299V the median symptom score was 8 (6.75-13.5 IQR), the median maximum rate of gas production 0.92 ml/min (0.45-1.5 IQR), and the median hydrogen production 208.2 ml/24 hr (146-350.9 IQR). There was no significant difference. Breath hydrogen excretion after lactulose was reduced by the probiotic (median at 120 min, 6 ppm; placebo, 17 ppm; P = 0.019). In conclusion, Lactobacillus plantarum 299V in this study did not appear to alter colonic fermentation or improve symptoms in patients with the irritable bowel syndrome.Publication Types: Clinical TrialPMID: 12452404 Br J Nutr. 2002 Sep;88 Suppl 1:S67-72. Related Articles, Links A review of the role of the gut microflora in irritable bowel syndrome and the effects of probiotics.Madden JA, Hunter JO.Gastroenterology Research Unit, Unit E7, Box 201 A, Addenbrookes NHS Trust, Hill's Road, CB2 2QQ, Cambridge, UK.Irritable bowel syndrome (IBS) is a multi-factorial gastrointestinal condition affecting 8-22 % of the population with a higher prevalence in women and accounting for 20-50 % of referrals to gastroenterology clinics. It is characterised by abdominal pain, excessive flatus, variable bowel habit and abdominal bloating for which there is no evidence of detectable organic disease. Suggested aetiologies include gut motility and psychological disorders, psychophysiological phenomena and colonic malfermentation. The faecal microflora in IBS has been shown to be abnormal with higher numbers of facultative organisms and low numbers of lactobacilli and bifidobacteria. Although there is no evidence of food allergy in IBS, food intolerance has been identified and exclusion diets are beneficial to many IBS patients. Food intolerance may be due to abnormal fermentation of food residues in the colon, as a result of disruption of the normal flora. The role of probiotics in IBS has not been clearly defined. *Some studies have shown improvements in pain and flatulence in response to probiotic administration, whilst others have shown no symptomatic improvement. It is possible that the future role of probiotics in IBS will lie in prevention, rather than cure.* Publication Types: Review Review, Tutorial PMID: 12215182


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## eric (Jul 8, 1999)

Eur J Gastroenterol Hepatol. 2001 Oct;13(10):1135-6. Related Articles, Links Comment on: Eur J Gastroenterol Hepatol. 2001 Oct;13(10):1143-7. Probiotics for irritable bowel syndrome: a light in the darkness?Thompson WG.Medicine, University of Ottawa, Canada. wgthompson###home.comProbiotics have been used with apparent success for several gut disorders, so it is not surprising they have been tried in the treatment of irritable bowel syndrome (IBS). However, the pathogenesis of this disease is unknown, and opinions about how probiotics might work are speculative. Nevertheless, two small trials suggest they might benefit patients with IBS, particularly those suffering from pain and bloating. *Nevertheless, two small trials suggest they might benefit patients with IBS, particularly those suffering from pain and bloating.* This possibility deserves further study. It is important though, that future trials employ criteria-identified subjects, be sufficiently powered and strictly double blind, and select a suitable outcome measure. Until state-of-the-art trials of probiotics are available, their use should remain in the experimental arena.Publication Types: Comment Editorial PMID: 11711765


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## eric (Jul 8, 1999)

Eur J Gastroenterol Hepatol. 2001 Oct;13(10):1135-6. Related Articles, Links Comment on: Eur J Gastroenterol Hepatol. 2001 Oct;13(10):1143-7. Probiotics for irritable bowel syndrome: a light in the darkness?Thompson WG.Medicine, University of Ottawa, Canada. wgthompson###home.comProbiotics have been used with apparent success for several gut disorders, so it is not surprising they have been tried in the treatment of irritable bowel syndrome (IBS). However, the pathogenesis of this disease is unknown, and opinions about how probiotics might work are speculative. Nevertheless, two small trials suggest they might benefit patients with IBS, particularly those suffering from pain and bloating. *Nevertheless, two small trials suggest they might benefit patients with IBS, particularly those suffering from pain and bloating.* This possibility deserves further study. It is important though, that future trials employ criteria-identified subjects, be sufficiently powered and strictly double blind, and select a suitable outcome measure. Until state-of-the-art trials of probiotics are available, their use should remain in the experimental arena.Publication Types: Comment Editorial PMID: 11711765


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## Guest (Aug 24, 2004)

is Asacol. I too question him, but this is what he gave me. It says right on the label that it could cause stomach upset. But i have no problem with stomach, so perhaps its ok for colon?i tried ibsacol and thought my head would burst and also got very constipated. atleast it did something.


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## Guest (Aug 24, 2004)

is Asacol. I too question him, but this is what he gave me. It says right on the label that it could cause stomach upset. But i have no problem with stomach, so perhaps its ok for colon?i tried ibsacol and thought my head would burst and also got very constipated. atleast it did something.


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## SpAsMaN* (May 11, 2002)

The anti-inflammatory drug is Asacol?It says it is tough on the stomack?Guess what,it will destroy the lining of the stomack and makes the bowel worst.NSAIDS are the WORST thing to drop.A specific anti-inflammatory drug should be designed for the G.I. tract but i don't think that will happen in a near future.And i took Vioxx this week,results:less pain in the lower bowel but high irritation of the stomack and the bowel.





















I'm still on Nexium to heal the lining.


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## SpAsMaN* (May 11, 2002)

The anti-inflammatory drug is Asacol?It says it is tough on the stomack?Guess what,it will destroy the lining of the stomack and makes the bowel worst.NSAIDS are the WORST thing to drop.A specific anti-inflammatory drug should be designed for the G.I. tract but i don't think that will happen in a near future.And i took Vioxx this week,results:less pain in the lower bowel but high irritation of the stomack and the bowel.





















I'm still on Nexium to heal the lining.


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## Talissa (Apr 10, 2004)

Joanofarc, that's amazingly reaffirming that your GI believes the inflammation is the cause of IBS symptoms. But I don't believe that taking a medical drug that can cause stomach upset is the way to go. For myself, I'd rather try the non-irritating "Aller-Max" or the Ibsacol.Scotty, I have ibsacol, but stopped taking it because, well it says not to drink alcohol. I couldn't drink socially for FOUR years, but now I don't react to it(thanx to DA-IBS) and each wkd, I have a beer or two. I fit in again with my friends & don't embarass my husband(who says peer pressure ends in high school?)!!! It's hard to give up. Do you not drink at all while on it? Do you think a beer or 2 would hurt?As far as what probiotics to take, these are ones that have helped me noticeably:-iFlora-Digestive Advatage IBS-Kyo DophilusBut they haven't taken me to 100%, only close. The new Metagenics brands' Lactoviden & Bifoviden have helped other people here get to 100%. Ultra Flora Plus has helped many others on other bb's recover completely. Metagenics can be bought at: http://www.ritecare.com/mtg_index.html (thanks tropigal)On the homefront, I've upped my intake of Kyo Dophilus from 4 billion or so per day to 14 billion, and it still probably isn't enough. Yesterday, I had more stomach rumbles as my body adjusted, and this am, I only went once, perfectly normal. But until I get off the metamucil, I won't feel free of this IBS.>>>>>>>>>>>>>>>>>Other than prebiotics, there's 2 other things you can take/eat that help the beneficial bacteria colonize: soluble fiber and fatty acids(maybe why ibsacol works?)"A very important effect of fiber results from its metabolism by bacteria within the intestinal tract. The intestines are normally home to hundreds of trillions of bacteria comprised of some 400 species. Some of these produce more favorable metabolites for human health than do others. The "good" bacteria feed upon soluble fiber and produce compounds called short chain fatty acids, which have anti-tumor activity. Butyrate is the most important of the short chain fatty acids. The benefits of soluble fiber are minimized if there are not enough "good" bacteria to metabolize it. " http://www.drdebe.com/COLOCANC.htm (maybe this is why some people have no luck with fiber, because the beneficial bacteria is low, which can happen from stress overload, poor diet, etc)And re: fatty acids~(2004)"Results suggest that a deficiency of n-3 fatty acid can lead to increased cell proliferation, inflammation and microbe overgrowth in the normal intestinal tract. An association was identified between the structural changes and microbe population present in the ileum due to n-3 fatty acid deficiency." http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=15294580 I also have something on how micorflora affects serotonin levels, "I'll be back"







Talissa


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## Talissa (Apr 10, 2004)

Joanofarc, that's amazingly reaffirming that your GI believes the inflammation is the cause of IBS symptoms. But I don't believe that taking a medical drug that can cause stomach upset is the way to go. For myself, I'd rather try the non-irritating "Aller-Max" or the Ibsacol.Scotty, I have ibsacol, but stopped taking it because, well it says not to drink alcohol. I couldn't drink socially for FOUR years, but now I don't react to it(thanx to DA-IBS) and each wkd, I have a beer or two. I fit in again with my friends & don't embarass my husband(who says peer pressure ends in high school?)!!! It's hard to give up. Do you not drink at all while on it? Do you think a beer or 2 would hurt?As far as what probiotics to take, these are ones that have helped me noticeably:-iFlora-Digestive Advatage IBS-Kyo DophilusBut they haven't taken me to 100%, only close. The new Metagenics brands' Lactoviden & Bifoviden have helped other people here get to 100%. Ultra Flora Plus has helped many others on other bb's recover completely. Metagenics can be bought at: http://www.ritecare.com/mtg_index.html (thanks tropigal)On the homefront, I've upped my intake of Kyo Dophilus from 4 billion or so per day to 14 billion, and it still probably isn't enough. Yesterday, I had more stomach rumbles as my body adjusted, and this am, I only went once, perfectly normal. But until I get off the metamucil, I won't feel free of this IBS.>>>>>>>>>>>>>>>>>Other than prebiotics, there's 2 other things you can take/eat that help the beneficial bacteria colonize: soluble fiber and fatty acids(maybe why ibsacol works?)"A very important effect of fiber results from its metabolism by bacteria within the intestinal tract. The intestines are normally home to hundreds of trillions of bacteria comprised of some 400 species. Some of these produce more favorable metabolites for human health than do others. The "good" bacteria feed upon soluble fiber and produce compounds called short chain fatty acids, which have anti-tumor activity. Butyrate is the most important of the short chain fatty acids. The benefits of soluble fiber are minimized if there are not enough "good" bacteria to metabolize it. " http://www.drdebe.com/COLOCANC.htm (maybe this is why some people have no luck with fiber, because the beneficial bacteria is low, which can happen from stress overload, poor diet, etc)And re: fatty acids~(2004)"Results suggest that a deficiency of n-3 fatty acid can lead to increased cell proliferation, inflammation and microbe overgrowth in the normal intestinal tract. An association was identified between the structural changes and microbe population present in the ileum due to n-3 fatty acid deficiency." http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=15294580 I also have something on how micorflora affects serotonin levels, "I'll be back"







Talissa


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## SpAsMaN* (May 11, 2002)

Joan,don't ever drink coffe with NSaids,i was "fine" with Vioxx untill i drank coffee then my stomack became irritated very bad.


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## SpAsMaN* (May 11, 2002)

Joan,don't ever drink coffe with NSaids,i was "fine" with Vioxx untill i drank coffee then my stomack became irritated very bad.


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## SpAsMaN* (May 11, 2002)

What this mean Talissa? http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=15294580 To drop megadose of omega 3 and 6?I think i can tolerate megadose of Omega.


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## SpAsMaN* (May 11, 2002)

What this mean Talissa? http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=15294580 To drop megadose of omega 3 and 6?I think i can tolerate megadose of Omega.


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## Talissa (Apr 10, 2004)

RE: Flora & serotonin~Colonic bacteria modify the contents such that biogenic amines like histamine or serotonin may be formedï¿½ Bacteria also make vitamin K and some B-complex vitamins that are absorbed in the colon. The bacterial flora vary with individuals and can change with diet, medication, or environmental changes. Such changes may cause diarrhea, gas or constipation. http://www.e-gastrointestinal.com/ RE: inflammation & serotonin~ï¿½Serotonin is released by gastrointestinal enteroendocrine cells after mucosal stimulation ( inflammation), diffuses to the nerve endings, and stimulates peristalsis by binding to serotonin-3 and serotonin-4 receptors located on enteric nerves.75 ï¿½ http://www.medical-journals.com/r031128b.htm This is most interestingï¿½RE: differences btn PI IBS-D, IBS-D, IBS-C~ï¿½ï¿½They subdivided their patients into 3 groups, those with: (1) postinfectious IBS; (2) constipation-predominant IBS; and, (3) nonconstipated, non-postinfectious IBS. These investigators found that cell counts in constipation-predominant IBS were not significantly different from that of controls.In contrast, patients with diarrhea, but without a postinfectious history, showed increased CD3 and lamina propria lymphocytes, in addition to mast cells, whereas patients with postinfectious IBS had increased enteroendocrine cells, CD3, and lamina propria lymphocytes. http://www.medscape.com/viewarticle/434526 Does this mean that only diarrhea-predominant IBS has low grade inflammation/increased mucosal lining cells?______________________Spasman, the fatty acid esters of ibsacol may be enough for you? Just take them long enough to know, scotty's suggestion of 2 months sounds good. Eating fish without mercury. Flax sseds freshly ground and added to water are another option(1 TBSP daily in 8 oz water).


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## Talissa (Apr 10, 2004)

RE: Flora & serotonin~Colonic bacteria modify the contents such that biogenic amines like histamine or serotonin may be formedï¿½ Bacteria also make vitamin K and some B-complex vitamins that are absorbed in the colon. The bacterial flora vary with individuals and can change with diet, medication, or environmental changes. Such changes may cause diarrhea, gas or constipation. http://www.e-gastrointestinal.com/ RE: inflammation & serotonin~ï¿½Serotonin is released by gastrointestinal enteroendocrine cells after mucosal stimulation ( inflammation), diffuses to the nerve endings, and stimulates peristalsis by binding to serotonin-3 and serotonin-4 receptors located on enteric nerves.75 ï¿½ http://www.medical-journals.com/r031128b.htm This is most interestingï¿½RE: differences btn PI IBS-D, IBS-D, IBS-C~ï¿½ï¿½They subdivided their patients into 3 groups, those with: (1) postinfectious IBS; (2) constipation-predominant IBS; and, (3) nonconstipated, non-postinfectious IBS. These investigators found that cell counts in constipation-predominant IBS were not significantly different from that of controls.In contrast, patients with diarrhea, but without a postinfectious history, showed increased CD3 and lamina propria lymphocytes, in addition to mast cells, whereas patients with postinfectious IBS had increased enteroendocrine cells, CD3, and lamina propria lymphocytes. http://www.medscape.com/viewarticle/434526 Does this mean that only diarrhea-predominant IBS has low grade inflammation/increased mucosal lining cells?______________________Spasman, the fatty acid esters of ibsacol may be enough for you? Just take them long enough to know, scotty's suggestion of 2 months sounds good. Eating fish without mercury. Flax sseds freshly ground and added to water are another option(1 TBSP daily in 8 oz water).


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## eric (Jul 8, 1999)

From the author of"Inflammatory Bowel Disease and Irritable Bowel Syndrome: Separate or Unified?" http://www.ibsgroup.org/cgi-local/ubbcgi/u...c;f=10;t=000777 Center for Neuroviceral Sciences and Womens health. From fall of 99. A lot of research has been done on this and PI IBS and IBS.Does stress cause IBS or similar disorders in other parts of the gi tract.Does stress exacerbate symptoms in people who already have these disorders.What kind of stress is worse and will the problems go away if stress is decreased.These questions and many more like them are often asked by patients with GI disorders. They are also asked by physicians who are confronted with a confusing set of symptoms and few ï¿½objectiveï¿½ physiological markers for disease (like infections or blockage). As you might expect there are no simple answers, but new research has begun to point the way to a better picture of how stress and GI problems might be linked and even ways to address the role of stress in treatment. *The first thing to remember is that stress has a strong impact on the GI tract in everyone.* *It is well known that patients with IBS often report that stressful events precede the onset or exacerbation of IBS symptoms. In one survey study for example 73% of IBS patients reported that stress altered their stool pattern, and 84% reported that stress led to abdominal pain. Interestingly in the same study 54% of persons without IBS also reported stress altered stool patterns and 68% reported stress caused abdominal pain.* *While affecting everyone, stress does seem to more strongly impact GI function in persons with IBS or similar disorders, such as dyspepsia, or chronic heartburn. * *In a recent study examining IBS patients over a several year period, up to 90% of the fluctuations in symptoms could be predicted by chronic stressors during the several preceding months. Another recent study examined patients who developed an acute GI infection (often after traveling in a foreign country). Most of the subjects recovered over a period of a few weeks with treatment but a significant percentage seemed to develop chronic symptoms similar to IBS.* *Level of stress during the three months prior to the infection was a strong predictor of who did and did not develop these chronic symptoms. Thus while stress is not the sole cause of IBS some stress clearly play a significant role in generating and prolonging symptoms in susceptible individuals, especially those with some GI symptoms. * What kinds of stress are most important? It is interesting that a variety of early studies did not find very strong relationships between daily ups and downs and symptom fluctuations. This is consistent with patientsï¿½ reports that even on relaxing days symptoms can be severe. *Newer studies like those described above have taken a different point of view and this has led to a much better understanding of the kinds of stress which may be important in GI disorders.* For example, the long-term study of IBS patients that successfully connected symptom fluctuations with stress used a ï¿½life stressï¿½ approach. *In this approach major events in ones life such as; changes in a job, family tension, moving to a new city, or loss of a friend are monitored and rated as to the amount of threat they pose to the individual. The chronic (over a month or more) and most threatening stressors were those associated with increases in IBS symptoms. Those with none of these stressors over a several month period had very few exacerbation of symptoms. Those with multiple chronic and threatening stressors had a very high probability of symptom exacerbation. To the extent possible the investigators demonstrated that it was the stress and not changes in diet, exercise or medications which led to symptom differences. * *Similarly, in the post-infection study the life stress method was also used. Subjects who developed chronic symptoms reported having experienced a life event that most often involved some disruption of personal relationships in the three months prior to the infection. * *In addition, the post-infectious symptom group also experienced an excess of life events in the three months following the acute gastroenteritis. So the newest evidence points to significant and especially longer lasting, and threatening stressors as the most important in influencing GI symptoms. One or two good or bad days may not be that important, but one's response to major life events may be critical for managing IBS symptoms. * *This new data is consistent with the developmental model of IBS which indicates that a history of major traumatic events (i.e. physical and/or sexual abuse) or major losses (i.e. the loss of a parent) during childhood are present more frequently in patients with IBS than healthy controls. In addition to daily stressors, a history of severe emotional trauma such as physical and sexual abuse especially when incurred during childhood also appears to be associated with an increased risk to become an IBS patient.* In a study of women at the University of North Carolina, 53% of women with IBS had a history of abuse, while 37% of women with structural GI diagnoses gave such a history. Not surprisingly, patients who have experienced life threatening resulting in post-traumatic stress disorder (PTSD) also have a high incidence of IBS. *How might these kinds of stressors lead to increased symptoms in IBS or other GI disorders? * *It does not appear to be true that under stress patients just worry or complain more about symptoms (although in some cases this may be important). Instead we believe that stress may disrupt the function of nerve and even immune cells in the GI tract and in the brain. * *For example, in the study of the patients with gastroenteritis discussed earlier, the study found that stressful life events preceding the infection and 3 months after the infection appeared to have the greatest predictive value for the development of postinfectious IBS symptoms.* *In addition to the differences in psychological parameters however, patients with post-infectious IBS had persistence of chronic inflammatory changes in rectal mucosa (a layer of tissue inside the colon) while the mucosa in those patients without persistent symptoms returned to normal at 3 months post infection.* *These kinds of changes in the mucosa have been previously linked to certain types of bowel symptoms. * *The findings suggest that, in predisposed individuals, enteric infections and presumably other causes of mucosal irritation can precipitate on-going IBS symptoms and mucosal changes which may persist long after the infection or inflammation has resolved.* *Stress can also increase GI symptoms by changing how the brain controls unwanted and painful sensation. Our own built in pain control system is constantly active, allowing painful information from any part of the body to be noticed (in fact it overrides almost all other information to gain our attention).* *The system also can suppress pain and other sensations when the information is old or unnecessary for action. Stress can disrupt this pain control system allowing more attention to certain physical sensations to predominate, especially those from areas we are concerned about or have had problems with.* *It is also well known that the same parts of the nervous system that respond to stress, the autonomic nervous system, is the primary control system for the GI tract, influencing muscle contractions, biochemical changes and digestion* http://www.ibs.med.ucla.edu/Articles/Patie...l99StressGI.htm Mast Cells and Stressï¿½A PsychoneuroimmunologicalPerspectiveTHEOHARISC. THEOHARIDES, PHD, MD Tufts University School of Medicine, Boston, Massachusetts http://66.218.71.225/search/cache?p=mast+c...84813F509&icp=1 Inflammation, Infection, and Irritable Bowel Syndrome: An UpdateYehuda Ringel, MD Douglas A. Drossman, MDThe growing interest of clinicians and researchers in the pathogenesis of functional gastrointestinal disorders led to several research presentations during this year's Digestive Disease Week meeting. Although these presentations addressed various factors implicated in the pathogenesis of these disorders (ie, behavioral/psychosocial, central and peripheral contributors), this article focuses on some new insights into the possible contribution of gut infection and inflammation in the development of symptoms and other potential clinical consequences."Infection and Inflammation Stephen M. Collins2 provided a comprehensive review of the evidence suggesting *the need to consider infection and inflammation in the pathogenesis of some patients with IBS.* *He presented data from clinical studies showing the development of IBS symptoms following acute gastroenteritis (ie, postinfectious PI IBS) and a higher than expected prevalence of IBS symptoms among patients with inflammatory bowel disease that was in remission.* *Additionally, data from animal studies demonstrated that altered gut physiology can persist even after the infection and associated inflammation have resolved.* *Furthermore, studies of mucosal biopsies, from both human and animal models, have shown increased inflammatory cells and inflammatory mediators in patients with IBS and in previously sensitized/stressed animals. Finally, some recent studies have shown proximity between nerve trunks and the inflammatory cells, suggesting a local neuroimmune interaction that may contribute to the pathogenesis of IBS.* With respect to the latter, several key studies presented during these meeting proceedings provided some supportive evidence relating the role of infection and inflammation to IBS. Wheatcroft and colleagues3 *have shown a significant increase in serotonin-containing entero-endocrine cells (EC) following Trichinella spiralis infection in mice. This finding suggests that the increased EC numbers that have previously been reported in humans after Campylobacter enteritis are likely not specific to bacterial infections.* *These events may also occur after protozoan and other parasitic infections, and thus may contribute to postinfectious bowel dysfunction. * Dunlop and colleagues4 compared the numbers of rectal mucosal lymphocytes, EC, and mast cells from IBS patients (n = 76) and healthy controls (n = 40). * Although all biopsies were normal using conventional histology, immunohistochemical studies showed differences in patterns of mucosal pathology between several distinct subgroups of IBS.* Patients with PI-IBS showed increased EC and CD3+ lamina propria lymphocytes (LPL),confirming previous findings. *However, patients with constipation-predominant IBS were not significantly different from controls, and nonconstipated, non-PI-IBS patients showed increased CD3+, LPLs, and mast cells. These findings suggest that within the broad clinical grouping of IBS, there may be several distinct groups with different patterns of mucosal pathology. The clinical relevance of these findings needs further investigation. * The growing interest and the emerging evidence supporting the role of infection and inflammation in the pathogenesis of at least a subset of IBS patients was also manifest in some key studies presented in the American Gastroenterological Association Research Forum on the "Medical Treatment of Functional GI Disorders." As discussed below, these studies explored possible new approaches in the treatment of IBS, while focusing on modulating and reversing infections and/or inflammation. " http://www.medscape.com/viewarticle/434527 Chapter 12: The Mast Cell As A Neuroimmuneondocrine Effector In Interstitial CystitisThere are also a number of Neuroimmunoendocrine disorders that are noticed mostly in woman with IC. They may Include: IBS Multiple Sclerosis Scleroderma Migraines Neurofibromatosis A possible connection could possibly be related to the activation of the mast cell. Many mast cells release various cytokines and are found to be found in *neuroinflammatory disorders* . Mast Cell Biology Mast cells originate from the bone marrow and under micro environmental factors they grow and enter the tissues. The two mast cell subtypes are: Typical, connective tissue mast cells, located in the lungs and/or skin (CTMC) *Atypical, located in the bladder and/or the GI tract. (MMC) mucosal mast cell * *Some* of the triggers of Mast Cells are: Bacteria (E-coli) Chemicals (detergents-food additives/preservatives, and xenoestrogines) Drugs (local anesthetics; neuromuscular blockers and opiods) Hormones (adrenocorticotropic hormone, estradiol) Physical conditions (cold, exercise, and pressure) Etc. Mast Cell Activation in IC There have been numerous studies done, reference to mast cells and there relationship to IC. Many of the studies have shown that mast cells are increased in bladders of patients with IC. However, conflicting reports have also been demonstrated which indicate that mast cells are not uniformly increased in the lamina propria (a highly vascular layer of connective tissue under the basement membrane lining of the epithelium) and/or detrusor (outer musculature) layer. The deviations in the studies suggest that the possibility of subgroups is prevalent. Nevertheless, IC patients with nonulcerative IC showed mast cells to be highly activated. 'The increase in bladder mast cells was recently related to possible high local *levels of corticotrophin- releasing factor* .... Thus, it appears that the mast cell has a pathogenic role in at least a subset of patients with interstitial cystitis.Mast Cell-Neuron Interactions Functional interactions have been suggested to have association with the central and peripheral nervous system. It is currently being invoked in the pathophysiology of certain inflammatory diseases. Studies have shown by using Electron Microscopic methods that the mast cells can be related to sensory nerve fibers, moreover, direct nerve stimulation results in mast cell activation, and the histamines as we know can stimulate the peripheral nerves. (whats released under chronic stressors histimine for one.)60% of IC patients have reported that their IC symptoms are exacerbated by stress. This is interesting because it has also been documented that immobilization stress causes mast cell activation in both the bladder and the intestinal areas. It has been noticed that the increased number of mast cells are reported in both IC patients and patients with Irritable Bowel Syndrome. *IBS is similar to IC, as it occurs more in women than in men. The symptoms are , abdominal pain and can be associated with urinary frequency, dyspareunia and fatigue. IBS is also exacerbated by stress and shows hypersensitivity to visceral stimuli,' a process that is also selectively activated by the sympathetic nervous system. Stress is known to affect the development of inflammation, and the contribution of the nervous system to the regulation of immune and inflammatory processes is now accepted.' * Many things can degranulate mast cells and cause macroscopic inflammation in the gi tract. http://www.ic-network.com/sant/sant12.html a little convergenge there with bladder problems and IBS as well.


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## eric (Jul 8, 1999)

From the author of"Inflammatory Bowel Disease and Irritable Bowel Syndrome: Separate or Unified?" http://www.ibsgroup.org/cgi-local/ubbcgi/u...c;f=10;t=000777 Center for Neuroviceral Sciences and Womens health. From fall of 99. A lot of research has been done on this and PI IBS and IBS.Does stress cause IBS or similar disorders in other parts of the gi tract.Does stress exacerbate symptoms in people who already have these disorders.What kind of stress is worse and will the problems go away if stress is decreased.These questions and many more like them are often asked by patients with GI disorders. They are also asked by physicians who are confronted with a confusing set of symptoms and few ï¿½objectiveï¿½ physiological markers for disease (like infections or blockage). As you might expect there are no simple answers, but new research has begun to point the way to a better picture of how stress and GI problems might be linked and even ways to address the role of stress in treatment. *The first thing to remember is that stress has a strong impact on the GI tract in everyone.* *It is well known that patients with IBS often report that stressful events precede the onset or exacerbation of IBS symptoms. In one survey study for example 73% of IBS patients reported that stress altered their stool pattern, and 84% reported that stress led to abdominal pain. Interestingly in the same study 54% of persons without IBS also reported stress altered stool patterns and 68% reported stress caused abdominal pain.* *While affecting everyone, stress does seem to more strongly impact GI function in persons with IBS or similar disorders, such as dyspepsia, or chronic heartburn. * *In a recent study examining IBS patients over a several year period, up to 90% of the fluctuations in symptoms could be predicted by chronic stressors during the several preceding months. Another recent study examined patients who developed an acute GI infection (often after traveling in a foreign country). Most of the subjects recovered over a period of a few weeks with treatment but a significant percentage seemed to develop chronic symptoms similar to IBS.* *Level of stress during the three months prior to the infection was a strong predictor of who did and did not develop these chronic symptoms. Thus while stress is not the sole cause of IBS some stress clearly play a significant role in generating and prolonging symptoms in susceptible individuals, especially those with some GI symptoms. * What kinds of stress are most important? It is interesting that a variety of early studies did not find very strong relationships between daily ups and downs and symptom fluctuations. This is consistent with patientsï¿½ reports that even on relaxing days symptoms can be severe. *Newer studies like those described above have taken a different point of view and this has led to a much better understanding of the kinds of stress which may be important in GI disorders.* For example, the long-term study of IBS patients that successfully connected symptom fluctuations with stress used a ï¿½life stressï¿½ approach. *In this approach major events in ones life such as; changes in a job, family tension, moving to a new city, or loss of a friend are monitored and rated as to the amount of threat they pose to the individual. The chronic (over a month or more) and most threatening stressors were those associated with increases in IBS symptoms. Those with none of these stressors over a several month period had very few exacerbation of symptoms. Those with multiple chronic and threatening stressors had a very high probability of symptom exacerbation. To the extent possible the investigators demonstrated that it was the stress and not changes in diet, exercise or medications which led to symptom differences. * *Similarly, in the post-infection study the life stress method was also used. Subjects who developed chronic symptoms reported having experienced a life event that most often involved some disruption of personal relationships in the three months prior to the infection. * *In addition, the post-infectious symptom group also experienced an excess of life events in the three months following the acute gastroenteritis. So the newest evidence points to significant and especially longer lasting, and threatening stressors as the most important in influencing GI symptoms. One or two good or bad days may not be that important, but one's response to major life events may be critical for managing IBS symptoms. * *This new data is consistent with the developmental model of IBS which indicates that a history of major traumatic events (i.e. physical and/or sexual abuse) or major losses (i.e. the loss of a parent) during childhood are present more frequently in patients with IBS than healthy controls. In addition to daily stressors, a history of severe emotional trauma such as physical and sexual abuse especially when incurred during childhood also appears to be associated with an increased risk to become an IBS patient.* In a study of women at the University of North Carolina, 53% of women with IBS had a history of abuse, while 37% of women with structural GI diagnoses gave such a history. Not surprisingly, patients who have experienced life threatening resulting in post-traumatic stress disorder (PTSD) also have a high incidence of IBS. *How might these kinds of stressors lead to increased symptoms in IBS or other GI disorders? * *It does not appear to be true that under stress patients just worry or complain more about symptoms (although in some cases this may be important). Instead we believe that stress may disrupt the function of nerve and even immune cells in the GI tract and in the brain. * *For example, in the study of the patients with gastroenteritis discussed earlier, the study found that stressful life events preceding the infection and 3 months after the infection appeared to have the greatest predictive value for the development of postinfectious IBS symptoms.* *In addition to the differences in psychological parameters however, patients with post-infectious IBS had persistence of chronic inflammatory changes in rectal mucosa (a layer of tissue inside the colon) while the mucosa in those patients without persistent symptoms returned to normal at 3 months post infection.* *These kinds of changes in the mucosa have been previously linked to certain types of bowel symptoms. * *The findings suggest that, in predisposed individuals, enteric infections and presumably other causes of mucosal irritation can precipitate on-going IBS symptoms and mucosal changes which may persist long after the infection or inflammation has resolved.* *Stress can also increase GI symptoms by changing how the brain controls unwanted and painful sensation. Our own built in pain control system is constantly active, allowing painful information from any part of the body to be noticed (in fact it overrides almost all other information to gain our attention).* *The system also can suppress pain and other sensations when the information is old or unnecessary for action. Stress can disrupt this pain control system allowing more attention to certain physical sensations to predominate, especially those from areas we are concerned about or have had problems with.* *It is also well known that the same parts of the nervous system that respond to stress, the autonomic nervous system, is the primary control system for the GI tract, influencing muscle contractions, biochemical changes and digestion* http://www.ibs.med.ucla.edu/Articles/Patie...l99StressGI.htm Mast Cells and Stressï¿½A PsychoneuroimmunologicalPerspectiveTHEOHARISC. THEOHARIDES, PHD, MD Tufts University School of Medicine, Boston, Massachusetts http://66.218.71.225/search/cache?p=mast+c...84813F509&icp=1 Inflammation, Infection, and Irritable Bowel Syndrome: An UpdateYehuda Ringel, MD Douglas A. Drossman, MDThe growing interest of clinicians and researchers in the pathogenesis of functional gastrointestinal disorders led to several research presentations during this year's Digestive Disease Week meeting. Although these presentations addressed various factors implicated in the pathogenesis of these disorders (ie, behavioral/psychosocial, central and peripheral contributors), this article focuses on some new insights into the possible contribution of gut infection and inflammation in the development of symptoms and other potential clinical consequences."Infection and Inflammation Stephen M. Collins2 provided a comprehensive review of the evidence suggesting *the need to consider infection and inflammation in the pathogenesis of some patients with IBS.* *He presented data from clinical studies showing the development of IBS symptoms following acute gastroenteritis (ie, postinfectious PI IBS) and a higher than expected prevalence of IBS symptoms among patients with inflammatory bowel disease that was in remission.* *Additionally, data from animal studies demonstrated that altered gut physiology can persist even after the infection and associated inflammation have resolved.* *Furthermore, studies of mucosal biopsies, from both human and animal models, have shown increased inflammatory cells and inflammatory mediators in patients with IBS and in previously sensitized/stressed animals. Finally, some recent studies have shown proximity between nerve trunks and the inflammatory cells, suggesting a local neuroimmune interaction that may contribute to the pathogenesis of IBS.* With respect to the latter, several key studies presented during these meeting proceedings provided some supportive evidence relating the role of infection and inflammation to IBS. Wheatcroft and colleagues3 *have shown a significant increase in serotonin-containing entero-endocrine cells (EC) following Trichinella spiralis infection in mice. This finding suggests that the increased EC numbers that have previously been reported in humans after Campylobacter enteritis are likely not specific to bacterial infections.* *These events may also occur after protozoan and other parasitic infections, and thus may contribute to postinfectious bowel dysfunction. * Dunlop and colleagues4 compared the numbers of rectal mucosal lymphocytes, EC, and mast cells from IBS patients (n = 76) and healthy controls (n = 40). * Although all biopsies were normal using conventional histology, immunohistochemical studies showed differences in patterns of mucosal pathology between several distinct subgroups of IBS.* Patients with PI-IBS showed increased EC and CD3+ lamina propria lymphocytes (LPL),confirming previous findings. *However, patients with constipation-predominant IBS were not significantly different from controls, and nonconstipated, non-PI-IBS patients showed increased CD3+, LPLs, and mast cells. These findings suggest that within the broad clinical grouping of IBS, there may be several distinct groups with different patterns of mucosal pathology. The clinical relevance of these findings needs further investigation. * The growing interest and the emerging evidence supporting the role of infection and inflammation in the pathogenesis of at least a subset of IBS patients was also manifest in some key studies presented in the American Gastroenterological Association Research Forum on the "Medical Treatment of Functional GI Disorders." As discussed below, these studies explored possible new approaches in the treatment of IBS, while focusing on modulating and reversing infections and/or inflammation. " http://www.medscape.com/viewarticle/434527 Chapter 12: The Mast Cell As A Neuroimmuneondocrine Effector In Interstitial CystitisThere are also a number of Neuroimmunoendocrine disorders that are noticed mostly in woman with IC. They may Include: IBS Multiple Sclerosis Scleroderma Migraines Neurofibromatosis A possible connection could possibly be related to the activation of the mast cell. Many mast cells release various cytokines and are found to be found in *neuroinflammatory disorders* . Mast Cell Biology Mast cells originate from the bone marrow and under micro environmental factors they grow and enter the tissues. The two mast cell subtypes are: Typical, connective tissue mast cells, located in the lungs and/or skin (CTMC) *Atypical, located in the bladder and/or the GI tract. (MMC) mucosal mast cell * *Some* of the triggers of Mast Cells are: Bacteria (E-coli) Chemicals (detergents-food additives/preservatives, and xenoestrogines) Drugs (local anesthetics; neuromuscular blockers and opiods) Hormones (adrenocorticotropic hormone, estradiol) Physical conditions (cold, exercise, and pressure) Etc. Mast Cell Activation in IC There have been numerous studies done, reference to mast cells and there relationship to IC. Many of the studies have shown that mast cells are increased in bladders of patients with IC. However, conflicting reports have also been demonstrated which indicate that mast cells are not uniformly increased in the lamina propria (a highly vascular layer of connective tissue under the basement membrane lining of the epithelium) and/or detrusor (outer musculature) layer. The deviations in the studies suggest that the possibility of subgroups is prevalent. Nevertheless, IC patients with nonulcerative IC showed mast cells to be highly activated. 'The increase in bladder mast cells was recently related to possible high local *levels of corticotrophin- releasing factor* .... Thus, it appears that the mast cell has a pathogenic role in at least a subset of patients with interstitial cystitis.Mast Cell-Neuron Interactions Functional interactions have been suggested to have association with the central and peripheral nervous system. It is currently being invoked in the pathophysiology of certain inflammatory diseases. Studies have shown by using Electron Microscopic methods that the mast cells can be related to sensory nerve fibers, moreover, direct nerve stimulation results in mast cell activation, and the histamines as we know can stimulate the peripheral nerves. (whats released under chronic stressors histimine for one.)60% of IC patients have reported that their IC symptoms are exacerbated by stress. This is interesting because it has also been documented that immobilization stress causes mast cell activation in both the bladder and the intestinal areas. It has been noticed that the increased number of mast cells are reported in both IC patients and patients with Irritable Bowel Syndrome. *IBS is similar to IC, as it occurs more in women than in men. The symptoms are , abdominal pain and can be associated with urinary frequency, dyspareunia and fatigue. IBS is also exacerbated by stress and shows hypersensitivity to visceral stimuli,' a process that is also selectively activated by the sympathetic nervous system. Stress is known to affect the development of inflammation, and the contribution of the nervous system to the regulation of immune and inflammatory processes is now accepted.' * Many things can degranulate mast cells and cause macroscopic inflammation in the gi tract. http://www.ic-network.com/sant/sant12.html a little convergenge there with bladder problems and IBS as well.


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## Guest (Aug 24, 2004)

What these articles don't explain though is what makes ibs so HARD to get rid of. Lets say there is inflammation, lets say its somewhat stress induced etc. What about the many many patients who have had symptoms every day for the last 10 years despite massive fluctuations in stress levels. I can't think of any other chronic health problem that is so predictable and long term. Can any of these doctors/researchers explain why ibs is so resilient? Seems like there should be a large subset of folks where, like depression, it just completely resolves, however this is not true, once you get ibs, doctos will tell you...well, you now have this for life. That does not make sense to me. But makes me think there IS some kind of bacterial basis for ibs. Or some other change that occurs that feeds upon itself - perhaps an immune response.the asacol made my gut hurt, but i'm doing a little better than normal now. will see.did hypno for over a year but it didnt do anything for my GI symptoms.


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## Guest (Aug 24, 2004)

What these articles don't explain though is what makes ibs so HARD to get rid of. Lets say there is inflammation, lets say its somewhat stress induced etc. What about the many many patients who have had symptoms every day for the last 10 years despite massive fluctuations in stress levels. I can't think of any other chronic health problem that is so predictable and long term. Can any of these doctors/researchers explain why ibs is so resilient? Seems like there should be a large subset of folks where, like depression, it just completely resolves, however this is not true, once you get ibs, doctos will tell you...well, you now have this for life. That does not make sense to me. But makes me think there IS some kind of bacterial basis for ibs. Or some other change that occurs that feeds upon itself - perhaps an immune response.the asacol made my gut hurt, but i'm doing a little better than normal now. will see.did hypno for over a year but it didnt do anything for my GI symptoms.


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## SpAsMaN* (May 11, 2002)

Joan,maybe you should drop it with Losec or Nexium.You said your gut hurt and you feel better.The definition of this is contradiction.(But it's cut LOL.)I think i have been there last week.You feel less pressure in your gut but it hurt because the sensitivity have increase.But then your stomack will not take it anymore and you will be left with stomack and bowel irritation.But that was just me.


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## SpAsMaN* (May 11, 2002)

Joan,maybe you should drop it with Losec or Nexium.You said your gut hurt and you feel better.The definition of this is contradiction.(But it's cut LOL.)I think i have been there last week.You feel less pressure in your gut but it hurt because the sensitivity have increase.But then your stomack will not take it anymore and you will be left with stomack and bowel irritation.But that was just me.


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## SpAsMaN* (May 11, 2002)

Joan,i take extra here for you.I think your doc is crazy personnally.Everyone knows anti-inflammatory drug are bad for the stomack and the bowel as well.Why someone with a bad gut would take that?Do a research and call the pharmacist about this drug.I'm concerned that it will makes you worst in a very short time.







Is there any C.trial on this drug for IBS?Look my signature and check if i'm like you.


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## SpAsMaN* (May 11, 2002)

Joan,i take extra here for you.I think your doc is crazy personnally.Everyone knows anti-inflammatory drug are bad for the stomack and the bowel as well.Why someone with a bad gut would take that?Do a research and call the pharmacist about this drug.I'm concerned that it will makes you worst in a very short time.







Is there any C.trial on this drug for IBS?Look my signature and check if i'm like you.


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## Talissa (Apr 10, 2004)

Joan, you make a good point. This might make more clear(it did for me) the relationship btn flora/bacteria and stress, at least for "chronic stress":Gastroenterology. 2002 Oct"Chronic psychological stress is an important factor in relapses of intestinal disorders, but it remains unclear if stress can induce primary gut inflammation in a previously healthy host...CONCLUSIONS: These findings suggest that chronic psychological stress can be an initiating factor in intestinal inflammation _by impairing mucosal defenses against luminal bacteria _ and highlight the importance of mast cells in this process. http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=12360472 But like you said, what if we aren't having chronic stress? I think we're the ones just low on the good bugs that normally keep low grade inflammation in check. Then when we DO have something very stressful happen, it "exascerbates" our IBS.Also~"...Recent evidence also suggest that bacterial flora can modulate the function of the intestinal mucosal cells. These observations support the role of the intestinal bacterial flora in the induction of an uncontrolled inflammation in the human gut, leading to tissue damage. Probiotics, defined as living micro-organisms which, _when taken in appropriate amounts_ , improve the health status, have been proposed in the treatment of inflammatory bowel disease, but their mechanisms of action still remain to be fully elucidated.' http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=12408438 (this was from 2002, they know more today)


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## Talissa (Apr 10, 2004)

Joan, you make a good point. This might make more clear(it did for me) the relationship btn flora/bacteria and stress, at least for "chronic stress":Gastroenterology. 2002 Oct"Chronic psychological stress is an important factor in relapses of intestinal disorders, but it remains unclear if stress can induce primary gut inflammation in a previously healthy host...CONCLUSIONS: These findings suggest that chronic psychological stress can be an initiating factor in intestinal inflammation _by impairing mucosal defenses against luminal bacteria _ and highlight the importance of mast cells in this process. http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=12360472 But like you said, what if we aren't having chronic stress? I think we're the ones just low on the good bugs that normally keep low grade inflammation in check. Then when we DO have something very stressful happen, it "exascerbates" our IBS.Also~"...Recent evidence also suggest that bacterial flora can modulate the function of the intestinal mucosal cells. These observations support the role of the intestinal bacterial flora in the induction of an uncontrolled inflammation in the human gut, leading to tissue damage. Probiotics, defined as living micro-organisms which, _when taken in appropriate amounts_ , improve the health status, have been proposed in the treatment of inflammatory bowel disease, but their mechanisms of action still remain to be fully elucidated.' http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=12408438 (this was from 2002, they know more today)


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## LDanna (Apr 13, 1999)

In my personal experience (IBS-D predominant with gas, bloating, and spasms for 20+ years), I've pretty much come to the conclusion that IBS requires a combination approach. I have had very good success with the following:*L-Glutamine for D and intestinal healing*Kyodophilus for bloating*Digestive Advantage (original formula) for dairy sensitivity*Omega/Fish Oil supplements for generally calming the digestive tract*Hypnotherapy and Yoga for related stress and anxiety*Fiber -- both soluble and insoluble in balance on a daily basis*Restriction of dietary fats, dairy, fructose, and processed foodsI know it seems like a lot of things to take/do but the ability to eat fairly normally and to function (i.e., go to work, travel, etc.) nearly every day like a normal, happy person is more than worth the minimal trouble and expense.


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## LDanna (Apr 13, 1999)

In my personal experience (IBS-D predominant with gas, bloating, and spasms for 20+ years), I've pretty much come to the conclusion that IBS requires a combination approach. I have had very good success with the following:*L-Glutamine for D and intestinal healing*Kyodophilus for bloating*Digestive Advantage (original formula) for dairy sensitivity*Omega/Fish Oil supplements for generally calming the digestive tract*Hypnotherapy and Yoga for related stress and anxiety*Fiber -- both soluble and insoluble in balance on a daily basis*Restriction of dietary fats, dairy, fructose, and processed foodsI know it seems like a lot of things to take/do but the ability to eat fairly normally and to function (i.e., go to work, travel, etc.) nearly every day like a normal, happy person is more than worth the minimal trouble and expense.


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## scottyswotty (Jun 29, 2000)

Hi Tal







Yes you can drink alcohol on it. I think for the first 1 or 2 months its best not to but after that you can get as boozed as you want. All my friends are still in that heavy drinking phase (25ish) and I drank 2/3rds a 40oz of Jim Beam last weekend without any problems (except putting my neck severely out of alignment...).


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## scottyswotty (Jun 29, 2000)

Hi Tal







Yes you can drink alcohol on it. I think for the first 1 or 2 months its best not to but after that you can get as boozed as you want. All my friends are still in that heavy drinking phase (25ish) and I drank 2/3rds a 40oz of Jim Beam last weekend without any problems (except putting my neck severely out of alignment...).


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## eric (Jul 8, 1999)

Because stress does not cause IBS, it is a percipating factor in getting it, it can reactivate infammation after it has resolved and it can majorally exassperate symptoms. It can also contribute greatly to pain. Were also in part talking about emotions here.In order to understand all that, its important to understand homeostasis and what stress really is an the fight or flight mechansims. This is not stress that is always conciously perceived either.There is also lot of research that there is a molecular defect in the cells that control gut function also. But serotonin is also connected to sleep, appetite, anxiety and other problems they see associated with IBS. And IBSers effectively demonstrate serotonin dysregulation.There are biological reasons for IBS at the gut level. This is why they call IBS a brain gut axis dysfunction. There are problems in the brain and the gut and the brain is not regulating pain right. That process is part of the issues of pain and IBS and inflammation cannot explain pain in IBS fully without that problem in the brain and pain. So there trying to figure out that problem in the brain and why that is happening. Why is the digestive system, specifically the sigmoid colon extra sesnitve to ALL stimuli.Also every time you eat a left over out of your fridge, it may have a pathogenic bacteria on it that could trigger the gut, because it is sensitive to all stimuli, even invaders, that come and go.Bacteria is not the only thing that can go wrong here.From the above people can get IBS from other infections besides bacteria.They don't know what causes IBS fully and hence it is a chronic condition, but it does go into remission on its own for a small amount of people, no matter what they do. There is also and this is very important, mild, moderate and severe IBS. Its also very important that more women then men get it and why.It is easy to pin bacteria or altered gut flora on IBS as the "cause" or mecahanism, but that might or might not be the case and at the moment there is little to support this, as I have said before and once again, infllamtion does not always produce pain, so something else important is going on. There are tons of neurotransmitters and substance that need to be studied, not just bacteria. To date no single bacteria has been found in IBS, and many different kinds can lead to IBS, including protozoas as mentioned above and a recent study on viruses. It is more the damage these things to to the operation of the digestive system. If it is a bacteria, it doesn't ever progress or harm tissue severly. I have had it thirty years and there has been no progression and many others I know have had it all there life and it has never on its own lead to anything serious. It does not for example lead to IBD conditions. But IBD conditions might lead to IBS because of the damage they can cause.Its how the system functions or malfunctions as opposed to diasease in the sence of the word that staf infection progresses for example and leads to a serious tissue damage. That does not happen in IBS. The inflammation in IBS has been studied quite a bit now, most experts believe it is a neuroimmune problem, with a major focus on chronic stress activating mast cells to degranulate without a pathogen. Some people say with d, have a high antispatory anxiety level about there symptoms coming on everyday, will I be in pain, will I be close enough to the bathroom ect, there are many more and those thoughts trigger the hpa axis and the fight or flight which in turn triggers the mast cells in the gut and inflamme them, a neuroimmune responce. But inflmmation is NOT the only problems.It is well know however that stressors are the mechanisms behind what you hear in the terms, Vicious cycle.symptoms =stress and anxiety=symptoms...I have said this also, the HPA axis is the bodies stress system, but its also used to fight infections.So there is a lot of convergence there."What does this have to do with IBS Converging evidence from different laboratories and research groups are consistent with the concept of an "enhanced stress responsiveness" as a major vulnerability factor in many IBS patients. As outlined above, such an enhanced stress responsiveness may not be obvious to the affected individual, until he or she is exposed to a period of sustained threatening stressors (financial or employment problems, divorce, aftermath of a major disaster with consequences on daily life), repeated mild to moderate stressors, or a one time severe (life threatening) type stressor (robbery or physical assault). Under these circumstances the mechanisms that normally turn off the stress response are overwhelmed, and attempts of the nervous system at adaptation or habituation fail. Many of the vulnerability factors for such enhanced stress responsiveness have been identified and many of them occur in a particular vulnerable period of the developing brain (before age 10). Some of the best-studied factors include loss of the primary care giver, distant mother-child relationship, emotional neglect, and physical and verbal or sexual abuse. In order to understand how a chronically enhanced stress response can produce the cardinal symptoms of IBS (abdominal pain and discomfort associated with altered bowel habits) we have to go back to the earlier section on the emotional motor system: activation of the stress system will stimulate contractions and secretion in the sigmoid colon and rectum. Depending on the specific emotional context (fear vs. anger), the upper GI tract will be either inhibited (fear) or stimulated (anger). In addition, recent research in animals has demonstrated a phenomenon referred to as stress-induced visceral hyperalgesia. What this means is that in vulnerable animals, exposure to an acute moderate stressor will make the colon more sensitive to distension (and the perception of discomfort or pain). "Perceptions of pain, muscle tensions, and other somatic symptoms can cause stress levels to spiral upward. Self-regulation strategies that reduce unpleasant symptoms offer both physical and psychological relief." ï¿½R. Sovik Why do the symptoms go away after one stressful situation has resolved and persist in another? Amongst many factors, anxiety and fear generated by IBSsymptoms themselves are sufficient in many patients to maintain the stress responsiveness in a chronically enhanced state. Some of the more common symptom related anxieties include: Am I close enough to a bathroom when my symptoms come on? Will I be OK for the rest of the day, unless I completely empty my colon in the morning before leaving the house? What can IBS patients do to guard against the detrimental effects of allostatic load and enhanced stress responsiveness Based on our current state of knowledge, little can be done in the affected patients to reverse vulnerability factors that have been programmed into our genes or have been hardwired into our nervous system during the first few years in life. Nevertheless, a variety of cognitive and behavioral approaches may be useful in protecting ourselves against the effects of allostatic load, or the wear and tear, of stress. These include: 1) Developing effective coping styles towards life stress and IBS symptoms; 2) Learning to activate mechanisms in the body that oppose the stress response and induce what has been referred to as the "relaxation response" through various relaxation techniques (e.g., breathing exercises, progressive relaxation, hypnosis, meditation); and 3) Moderate but sustained exercise. "Most people do get better with stress reduction of some kind and understanding stressors and that emotions can trigger symptoms, anger can and does effect the colon, worry does effect the colon, worry about a pathogen constantly can effect the colon, anxiety they missed something can and does effect the colon, in IBS this is much more pronounced.Dr Spiller is a world authority on PI IBS.New approaches in the management and treatment of irritable bowel syndromeProfessor Robin SpillerDivision of GastroentereologyUniversity HospitalNottinghamNG7 2UHTel 0115 9709352Fax 0115 9422232E-mail robin.spiller###nottingham.ac.ukThe last few years have seen some important advances in our understanding of theirritable bowel syndrome (IBS). The new Rome II Criteria are simpler than Rome I (seeFig 1), and have undoubtedly improved the comparability of clinical trail populationsthough care is needed to avoid these criteria acting as blinkers and inhibiting progress inunderstanding pathogenesis.Epidemiological studies suggest that symptom clusters define three sub-types of IBS. 1:characterised by loose stools passed with urgency with minimal straining, onecharacterised by hard stools and straining and incomplete evacuation but also someurgency and notably a similar bowel frequency. Finally there is a group of patients withminimal disturbance of stooling and a normal stool frequency whose main complaint ispain and bloating 1. It is apparent therefore that stool frequency is an unreliable guide tosub typing since it depends on social and psychological factors. It is probably moreuseful to define IBS subtypes based on the stool consistency, which is closely related tocolonic transit 2Sub-typing IBS patients is important since lumping them altogether may miss beneficialeffects if the treatment help one group but hinder another. Thus Loperamide improvespatients with diarrhoea but worsens symptoms in those with constipation 3.All clinicians are well aware that patients with a considerable psychological burdenrespond poorly to treatments. This was clearly shown by Bennett and colleagues 4whoshowed that those suffering from life stresses of greater than six months duration wereless likely to improve than those who lacked such features.When seeing a patient for the first time it is important to try and fit them into the multi-dimensional symptom space whose major axes are anxiety, colonic transit times andunderlying pathology (Figure 2). The third dimension is poorly defined, apart from postinfectious IBS (PI-IBS). These dimensions have important prognostic significance as canbe seen in Fig 35. PI-IBS is characterised by abdominal cramps, lose and urgent stoolsand accounts for between 6 and 17% of IBS patients attending GI clinics 6. Physiologicalchanges which affect nearly all individuals following GI infections include shortening ofwhole gut transit and lowering of discomfort threshold for rectal distension, the severityof the abnormality being increased in those who meet the criteria for IBS. Associatedwith these changes there is also evidence of low grade inflammation and elevatedenteroendocrine cells which resolves in most patients, but persists in those with persistentsymptoms7. These cells which are responsive to both luminal and neural signals are foundthroughout the GI tract. More than 50% of these cells contain 5HT, in the upper gut CCKand in the lower gut PYY account for most of the remainder. 5HT is released in responseto pressure, luminal nutrients and bacterial toxins including cholera toxins. It acts on arange of receptors the most important of which in the GI tract are 1a, 1p, 2, 3 and 4.Currently the most important ones therapeutically are 3 and 4. 5HT3 receptor is foundonly on nerves and produces a short duration depolarisation, stimulating sensory nervesincluding the vagus, thereby indirectly stimulating gastric and pancreatic secretions. Italso activates enteric cholinergic and VIPergic nerves, which stimulate enterocytesecretion. 5HT4 receptors are found on both nerves and enterocytes. The receptor is Gprotein-linked and when stimulated elevates cyclic AMP. This produces a slower onsetof action, inhibiting the delayed rectifier potassium channel and producing a prolongedincrease in the excitability of nerves, stimulating peristalsis and enterocyte chloridesecretion.Peristalsis involves the action of a bolus distending the lumen exciting descendinginhibition and ascending contraction of the circular muscles. It is believed that the bolusactivates the enteroendocrine cells to release 5HT, which stimulates peristalsis (seeFigure 4). Enteroendocrine cell numbers have been reported as increased in patients withchronic IBS seen in GI outpatients and a pilot study has reported an increased release of5HT after a meal in diarrhoea predominate IBS 8. Postprandially 5HT appears tostimulate both colonic tone and motility, effects which can be blocked by the intravenous5HT3 antagonist, granisetron. Alosetron is a more specific 5HT3 antagonist which hasbeen shown to improve stool consistency in diarrhoea-predominant IBS and increase theportion of patients experiencing adequate relief of symptoms 9. Its rather prematurewithdrawal was unfortunately due to rare adverse events which were both expected(severe constipation 70 / 435,000, 3 deaths) and unexpected (ischaemic colitis40/435,000, no deaths). Tegaserod is a highly selective 5HT4 agonist which acceleratesGI transit and accelerates gastric emptying and small bowel transit and increases theproportion of patients with relief of symptoms 10. It also increases stool frequency withinthe first week. Both Alosetron and Tegaserod represent exiting new opportunities fortreatment in a field where there have been no new drugs for many years. However, weshould not become too over enthusiastic based on novelty alone. When assessingefficacy it should be remembered that one needs to treat 8 ï¿½ 9 patients with Alosetron orTegaserod to get one extra patient responding compared with placebo alone. Thechallenge in the future is to better identify who will respond best to these treatments thusimproving the efficacy.In summary, there are no panaceas! Individual patients require individual treatments. Weshould always remember that as yet only psychological and dietary measures have beenshown to provide long-term improvement of symptoms. Not withstanding that drugs,which have reliable benefit, may well be useful in providing a sense of control over thesesymptoms which these patients so often lack. http://66.218.71.225/search/cache?p=ea+may...4A45D3B63&icp=1 There has also been enough people taking a variety of antibiotics to kill any pathogens and that has not panned out over the years.andVISCERAL PERCEPTION A role for inflammation in irritable bowel syndrome? http://gut.bmjjournals.com/cgi/content/full/51/suppl_1/i41 again from the author of""Inflammatory Bowel Disease and Irritable Bowel Syndrome: Separate or Unified?""and also from Dr Collins which some of you maybe starting to recgonize.Brain Imaging: CNS Abnormalities in Patients with IBSThe lack of a clearcut pathophysiology and an often noted association between physical and psychological symptoms has led some clinicians to dismiss irritable bowel syndrome (IBS) as a condition that is "all in their head." However recent findings showing CNS abnormalities in patients with IBS may offer a new perspective on the etiology of this debilitating condition, characterized by abdominal discomfort and pain and altered bowel habits. Until recently, the presence and severity of IBS were measured only by gut function and the subjective perceptions of the patient. "Now, the use of functional brain imaging techniques is contributing to an increased under- standing of the pathophysiology of this disease and new target areas for treatment," said Emeran A. Mayer, MD, Professor of Medicine, Physiology, and Biobehavioral Sciences, and Director of the CURE Neuroenteric Disease Program at the University of California, Los Angeles.Pathophysiology of IBSIBS is a disease that develops as the result of an abnormally altered brain-gut interaction (Table 1). One manifestation of this alteration consists of aberrant output patterns of the emotional motor system, a part of the limbic system in the brain, in response to external (psychosocial) or internal (immune, nutrient) stressors. Outputs from the limbic system in the form of autonomic, pain modulatory, and neuroendocrine responses can be modu- lated by cognitive factors, such as the beliefs, thoughts, and emotions of the patient. Aberrant output of the emotional motor system in large part accounts for the constellation of symptoms that makes up IBS. "A hyperresponsiveness of circuits in the brain may be one common link to both the abnormal responses to internal inflammatory stressors and external psychosocial stressors," Dr. Mayer explained. Treatment is chosen with consideration of altered motility, visceral hypersensitivity, and the brain's role in modulating these factors. The autonomic regulatory systems affect not only muscle cells in the gut, but also other cell types, such as mast cells, enterochromaffin cells, and nerve cells of the enteric nervous system. Responses of some of these cells to autonomic modulation, for example in the form of tryptase secretion by mast cells or serotonin secretion by enterochromaffin cells, may play a role in the modulation of visceral afferent sensitivity. According to Dr. Mayer, such mechanisms may play a role in the development of stress-induced visceral hyperalgesia. Another form of visceral hypersensitivity may be related to altered arousal or hypervigilance toward visceral sensations. Such hypervigilance can result in decreased tolerance to balloon distension and lower discomfort thresholds. A cognitive factor involved in the development of hypervigilance is an increased threat appraisal of visceral sensations.Functional Brain Imaging TechniquesRecently, functional brain imaging techniques have been used to assess directly the activation of certain regions of the brain in response to visceral stimulation. Today, these techniques, particularly functional magnetic resonance imaging, are being used to assess activation of brain circuits that process visceral afferent information from the gut. Dr. Mayer noted that there are distinct but overlapping brain circuits that relate to subjective perception of gut sensations, autonomic responses, and pain modulatory responses. Even in terms of subjective gut sensations, different overlapping circuits are present for intensity coding of the stimulus; threat appraisal of the stimulus; and attribution of primary affect, or "unpleasantness". Both serial and parallel pathways are involved in the processing of visceral sensory information and the control of descending modulatory systems. Input from the gut is derived from multiple channels, such as spinothalamic, vagal, and dorsal column pathways; different regions of the brain then code for intensity, appraise the threat of the stimulus, and determine the level of attention the brain attributes to the stimulus and the unpleasantness the patient experiences. These processes are modulated both by the stress- or arousal- activated system and by recollection of past experiences.Intensity Coding, Threat Appraisal, and UnpleasantnessIntensity coding. As visceral sensory information is delivered via the spinal cord, it is encoded for intensity in the anterior aspects of the insula, or visceral sensory cortex. PET scan studies of somatic and visceral experimental pain have shown that the insula most objectively and reliably encodes information. Interestingly, studies have also demonstrated a greater activation of the insula in male IBS patients, compared with female patients, when exposed to the same stimulus intensity. Threat appraisal and unpleasantness. The information that reaches the insula is "appraised" in the dorsal aspects of the anterior cingulate cortex. Blood flow changes in this part of the brain may also correlate with attentional processes and the subjective unpleasantness ratings in response to a somatic stimulus. The ventral (perigenual) cingulate cortex, which is rich in muopioid receptors, functions to encode the affective quality of the stimulus. In a study by Mayer and colleagues, rectal and sigmoid distension resulted in a lower activation of the ventral anterior cingulate cortex in patients with IBS compared with healthy controls, but an increased activation of the dorsal aspects of the anterior cingulate. Increased activation of an unspecified region of the anterior cingulate was also reported by Mertz and colleagues, in a functional MRI study. Modulatory factors. Finally, the CNS processing of sensory experience may be simultaneously modulated by two parallel pathways: memory-based modulation and stress- or arousal-induced modulation. The posterior parietal cortex, or sensory association cortex, forms a network with the hippocampus and the amygdala (the brain's memory centers) as well as with the lateral prefrontal cortex. Somatic pain studies have shown that, in response to a stimulus, the recall of a similar past event, along with subsequent interpretation of this memory in the lateral prefrontal cortex, plays a major role in the threat appraisal of a sensory experience. The second modulatory effect is the stress- or arousal-induced response. The pontine locus ceruleus is activated in response to potentially threatening experiences. This region then projects to nearly all other regions of the brain that receive visceral input, causing secretions of norepinephrine and arousal of these sections of the brain. When the secretion of norepinephrine is excessive, these target regions are inhibited. It is of interest that descending projections from the locus coeruleus complex to the sacral spinal cord appear to play a major role in the modulation of distal colonic motor and secretory function.Conclusion *Brain imaging and other studies of IBS pathophysiology indicate that the perception of gut stimuli and altered autonomic responses to these stimuli are affected by activation of various parts of the brain, resulting in increased attention to these stimuli, greater unpleasantness of the subjective experience, greater threat appraisal, and greater arousal in response to visceral sensations. Further study may lead to new developments in treatment for persons with IBS. * --------------------------------------------------------------------------------Table 1. Clinical Relevance of Altered Brain-Gut InteractionAltered attentional mechanisms o Greater awareness of normally subliminal visceral afferent stimuliAltered affective stimulus processing o Greater unpleasantness of visceral sensations, including heartburn, bloating, fullness, abdominal pain, incomplete rectal evacuationAltered threat appraisal o Leads to fears such as not being close enough to a bathroom anything eaten may trigger abdominal painEnhanced arousal o Shared by clinical conditions frequently overlapping IBS, such as anxiety, panic disorder and PTSD o Arousal reduced by sedatives, anxiolytics, low-dose tricyclics o May respond to relaxation exercises--------------------------------------------------------------------------------Post-Infective Irritable Bowel SyndromeAmong many postulated causes of irritable bowel syndrome (IBS), one of the most intriguing is that the syndrome represents sequelae of an acute enteric infection. In fact, such an association is not just an interesting theory. According to Stephen M. Collins, MBBS, FRCP, FRCPC, Professor of Medicine and Director of Gastroenterology at McMaster University in Hamilton, Ontario, Canada, "Acute enteric infection appears to be a significant contributing cause to the development of irritable bowel syndrome." The changes associated with such enteric infection appear to be reversible, introducing the opportunity for new treatment strategies for persons at high risk for irritable bowel syndrome (IBS).Clinical observations have suggested that transient infection in the gut can lead to persistent neuromotor dysfunction, and possible symptom generation in persons with IBS. In a large review, Chaudhary and Truelove found that 33% of persons with IBS reported an acute onset to their symptoms. Indeed, a recent controlled study showed that enteric infection was a strong risk factor for developing IBS.Animal Studies: Neuromuscular Dysfunction Post-InfectionIn one animal study by Tougas, Collins and colleagues infected mice with Trichinella spiralis. The results showed that the infection was accompanied by inflammation, reaching its peak in week 2. By week 3, the parasite had been expelled and inflammation had subsided. However, accompanying muscle hypercontractility persisted for up to 6 weeks' post-infection.In a second study by Tougas, the colons of the infected mice were distended using a small balloon and there was evidence of increased afferent nerve activity not only during the infection, but also 4 to 6 weeks' post-infection. Together, these results suggest that transient infection and subsequent inflammation in the gut can alter muscle contraction and increase sensory activity in the colon, suggesting a possible basis for dysmotility and hyperalgesia that occurs in post-infective IBS. But are these effects reversible?In a third study, animals were infected and allowed to recover. After 3 weeks, a short course of dexamethasone was administered. In the animals treated with steroids, muscle hypercontractility was prevented or reversed by day 28 post-infection. "Post-infective changes appear to be reversible and thus provide a basis for designing new experimental approaches in patients," said Dr. Collins.Clinical Association Between Infection and IBSFive recent studies showed that 7% to 31% of persons having food poisoning-associated bacterial gastroenteritis developed IBS, 3 to 12 months' post-infection. This phenomenon has also been observed with parasitic infection; however, the role of viral gastroenteritis is not yet known. The development of IBS appears to be due to a convergence of infection, inflammatory stimuli, central nervous system stimuli, and psychological factors. "The response to inflammatory stimuli is enhanced under stress, with the timing of the stress in relation tostimuli being important," Dr. Collins explained. Psychological factors, however, do not appear to be the sole determinants of whether someone develops IBS post-infection and other human studies suggest that local alterations in response to inflammatory stimuli may be important; this may be, in part, genetically determined.One study showed that 32% of persons with Salmonella-related gastroenteritis developed IBS symptoms within 2 years' post-infection. Biopsies showed no overt inflammatory presence; however, a semiquantitative approach showed an increase in inflammatory cells in those with IBS. Indeed, there was an increased number of lymphocytes and hyperplasia of the serotonin-containing enterochromaffin cells, a major source of 5-HT in the gut. "It is likely that 5-HT measurements would be increased in this subgroup, affording new therapeutic opportunities for these patients," Dr. Collins said. In addition, other studies have shown a potential role for lumenal factors and for cholestyramine-type factors, especially for diarrhea-dominant disease.ConclusionIn closing, Dr. Collins noted that post-infection effects associated with IBS appear to be reversible, warranting further clinical investigation of anti-inflammatory agents and other innovative therapies for persons at risk for IBS. Treatment Options in Irritable Bowel SyndromePrimary care physicians often refer patients with irritable bowel syndrome (IBS) to gastroenterologists because of difficulty finding an effective treatment. IBS is a condition characterized by abdominal pain, as well as diarrhea, constipation, or an alternating of the two. Treatment options for IBS are targeted to relieve either diarrhea, constipation, or pain, depending on the patient's predominant symptom (Table 1). For many patients, available therapies have not been successful in relieving their IBS, making further study and development of new products essential, said Anthony J. Lembo, MD, Instructor at Harvard Medical School and Director of the GI Motility Center at Beth Israel Deaconess Medical Center, in Boston. Focusing on pain-predominant IBS, Dr. Lembo profiled current and emerging new therapies. Recent studies suggest that the new smooth muscle relaxants can be effective against pain-predominant IBS and that antidepressants can be beneficial in treating functional gastrointestinal disorders. According to Dr. Lembo, these agents, together with newer 5-HT4 agonists, may offer promise for persons with pain-predominant IBS.Antispasmodic AgentsAntispasmodic agents are beneficial to some patients with IBS because they interfere with the exaggerated gastrocolic response that occurs with IBS, thereby reducing postprandial motor activity. The three main classes of antispasmodics include anticholinergics, peppermint oil, and the newer direct smooth muscle relaxants. Of four randomized double-blind studies of anticholinergics in IBS, only one showed a significant global symptom improvement over placebo. In this study, more than 50% of patients developed anticholinergic side effects. Of five randomized, double-blind studies of peppermint oil products, three showed significant global symptom improvement over placebo. However, significant side effects occurred with treatment, and the studies consisted of small sample sizes and short duration of followup. Constipation is one potentially significant side effect of antispasmodic agents. In a recent meta-analysis of all antispasmodic agents, Poynard and colleagues found that antispasmodics did benefit patients in terms of global symptom improvement in general, and pain, in particular. The antispasmodics that were most effective were the newer smooth muscle relaxants not currently available in the United States.Antidepressant AgentsAntidepressant agents, including tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors, are used in persons with IBS (particularly pain-predominant) because they are effective against chronic pain (especially TCAs); pain reduction is independent of effects on mood; and they are effective against conditions that often overlap with IBS. Side effects with these agents might include sedation, agitation, anticholinergic effects, and constipation.5-HT3 Antagonists and 5-HT4 AgonistsThere are four main types of 5-HT receptors, of which 5-HT3 and 5-HT4 are most relevant to the treatment of IBS. 5-HT3 receptors are associated with the provocation and perception of pain, the emesis reflex, and gut motility and secretion; while 5-HT4 receptors are associated with emesis reflex, visceral sensation, secretion, and activation of neurotransmitter release and gut motility. 5-HT3 antagonists have been shown to increase colonic compliance, reduce postprandial rectal sensitivity and motility, enhance jejunal water and sodium absorption, and prolong left colon transit time. Alosetron has been the only U.S. Food and Drug Administration (FDA)-approved 5-HT3 antagonist for the treatment of IBS (in women); however, Glaxo Wellcome has since voluntarily withdrawn this drug from the market after some reports of ischemic colitis and severe constipation. "Studies have shown 5-HT4 agonists to decrease small bowel transit time in persons with constipation-predominant IBS; to dose dependently inhibit afferent nerve activity to rectal distention in cats; and to inhibit visceral discomfort in rats," said Dr. Lembo. When serotonin is released from enterochromaffin cells in the gut, it stimulates 5-HT4 receptors on primary intrinsic afferent nerves, which in turn stimulate both ascending excitation and descending inhibition of motor neurons, resulting in peristaltic contraction in the gastrointestinal tract. 5-HT4 receptor agonists, such as tegaserod maleate, directly stimulate the peristaltic reflex and accelerate gastrointestinal transit. In a study of tegaserod, 881 persons having IBS-associated constipation and abdominal pain, were treated. Those taking tegaserod showed significant symptom improvement over placebo. In addition, tegaserod was associated with a significant increase in number of stools, improvement in stool consistency, and decrease in bloating. A significant response was achieved in women; small sample sizes of men studied thus far make these data difficult to interpret. Side effects included transient diarrhea (12% vs 5% in placebo), but there were no effects on QTc intervals. Tegaserod is currently under review by the FDA. In closing, Dr. Lembo emphasized that, "promising new agents-such as new muscle relaxants and 5-HT4 agonists-may soon mean more treatment options and greater relief for persons with IBS." --------------------------------------------------------------------------------Table 1. Treatment Options for IBSDiarrhea-Predominant IBS o Antidiarrheal agents (loperamide, diphenoxylate, cholestyramine) o Alosetron, a 5-HT3 receptor antagonist*Constipation-Predominant IBS o Fiber o Osmotic cathartics (sorbitol, lactulose) o Nonosmotic cathartics (polyethylene glycol) o Tegaserod, a 5-HT4 partial agonist that may be available in future**Pain-Predominant IBS o Antispasmodics (anticholinergics, peppermint oil, smooth muscle relaxantsï¿½) o Antidepressants (tricyclic antidepressants or selective serotonin reuptake inhibitors) o Alosetron for diarrhea-related pain* o Tegaserod for constipation-related pain, perhaps in near future** http://www.cmecorner.com/macmcm/pcp/pcp2000_01.htm


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## eric (Jul 8, 1999)

Because stress does not cause IBS, it is a percipating factor in getting it, it can reactivate infammation after it has resolved and it can majorally exassperate symptoms. It can also contribute greatly to pain. Were also in part talking about emotions here.In order to understand all that, its important to understand homeostasis and what stress really is an the fight or flight mechansims. This is not stress that is always conciously perceived either.There is also lot of research that there is a molecular defect in the cells that control gut function also. But serotonin is also connected to sleep, appetite, anxiety and other problems they see associated with IBS. And IBSers effectively demonstrate serotonin dysregulation.There are biological reasons for IBS at the gut level. This is why they call IBS a brain gut axis dysfunction. There are problems in the brain and the gut and the brain is not regulating pain right. That process is part of the issues of pain and IBS and inflammation cannot explain pain in IBS fully without that problem in the brain and pain. So there trying to figure out that problem in the brain and why that is happening. Why is the digestive system, specifically the sigmoid colon extra sesnitve to ALL stimuli.Also every time you eat a left over out of your fridge, it may have a pathogenic bacteria on it that could trigger the gut, because it is sensitive to all stimuli, even invaders, that come and go.Bacteria is not the only thing that can go wrong here.From the above people can get IBS from other infections besides bacteria.They don't know what causes IBS fully and hence it is a chronic condition, but it does go into remission on its own for a small amount of people, no matter what they do. There is also and this is very important, mild, moderate and severe IBS. Its also very important that more women then men get it and why.It is easy to pin bacteria or altered gut flora on IBS as the "cause" or mecahanism, but that might or might not be the case and at the moment there is little to support this, as I have said before and once again, infllamtion does not always produce pain, so something else important is going on. There are tons of neurotransmitters and substance that need to be studied, not just bacteria. To date no single bacteria has been found in IBS, and many different kinds can lead to IBS, including protozoas as mentioned above and a recent study on viruses. It is more the damage these things to to the operation of the digestive system. If it is a bacteria, it doesn't ever progress or harm tissue severly. I have had it thirty years and there has been no progression and many others I know have had it all there life and it has never on its own lead to anything serious. It does not for example lead to IBD conditions. But IBD conditions might lead to IBS because of the damage they can cause.Its how the system functions or malfunctions as opposed to diasease in the sence of the word that staf infection progresses for example and leads to a serious tissue damage. That does not happen in IBS. The inflammation in IBS has been studied quite a bit now, most experts believe it is a neuroimmune problem, with a major focus on chronic stress activating mast cells to degranulate without a pathogen. Some people say with d, have a high antispatory anxiety level about there symptoms coming on everyday, will I be in pain, will I be close enough to the bathroom ect, there are many more and those thoughts trigger the hpa axis and the fight or flight which in turn triggers the mast cells in the gut and inflamme them, a neuroimmune responce. But inflmmation is NOT the only problems.It is well know however that stressors are the mechanisms behind what you hear in the terms, Vicious cycle.symptoms =stress and anxiety=symptoms...I have said this also, the HPA axis is the bodies stress system, but its also used to fight infections.So there is a lot of convergence there."What does this have to do with IBS Converging evidence from different laboratories and research groups are consistent with the concept of an "enhanced stress responsiveness" as a major vulnerability factor in many IBS patients. As outlined above, such an enhanced stress responsiveness may not be obvious to the affected individual, until he or she is exposed to a period of sustained threatening stressors (financial or employment problems, divorce, aftermath of a major disaster with consequences on daily life), repeated mild to moderate stressors, or a one time severe (life threatening) type stressor (robbery or physical assault). Under these circumstances the mechanisms that normally turn off the stress response are overwhelmed, and attempts of the nervous system at adaptation or habituation fail. Many of the vulnerability factors for such enhanced stress responsiveness have been identified and many of them occur in a particular vulnerable period of the developing brain (before age 10). Some of the best-studied factors include loss of the primary care giver, distant mother-child relationship, emotional neglect, and physical and verbal or sexual abuse. In order to understand how a chronically enhanced stress response can produce the cardinal symptoms of IBS (abdominal pain and discomfort associated with altered bowel habits) we have to go back to the earlier section on the emotional motor system: activation of the stress system will stimulate contractions and secretion in the sigmoid colon and rectum. Depending on the specific emotional context (fear vs. anger), the upper GI tract will be either inhibited (fear) or stimulated (anger). In addition, recent research in animals has demonstrated a phenomenon referred to as stress-induced visceral hyperalgesia. What this means is that in vulnerable animals, exposure to an acute moderate stressor will make the colon more sensitive to distension (and the perception of discomfort or pain). "Perceptions of pain, muscle tensions, and other somatic symptoms can cause stress levels to spiral upward. Self-regulation strategies that reduce unpleasant symptoms offer both physical and psychological relief." ï¿½R. Sovik Why do the symptoms go away after one stressful situation has resolved and persist in another? Amongst many factors, anxiety and fear generated by IBSsymptoms themselves are sufficient in many patients to maintain the stress responsiveness in a chronically enhanced state. Some of the more common symptom related anxieties include: Am I close enough to a bathroom when my symptoms come on? Will I be OK for the rest of the day, unless I completely empty my colon in the morning before leaving the house? What can IBS patients do to guard against the detrimental effects of allostatic load and enhanced stress responsiveness Based on our current state of knowledge, little can be done in the affected patients to reverse vulnerability factors that have been programmed into our genes or have been hardwired into our nervous system during the first few years in life. Nevertheless, a variety of cognitive and behavioral approaches may be useful in protecting ourselves against the effects of allostatic load, or the wear and tear, of stress. These include: 1) Developing effective coping styles towards life stress and IBS symptoms; 2) Learning to activate mechanisms in the body that oppose the stress response and induce what has been referred to as the "relaxation response" through various relaxation techniques (e.g., breathing exercises, progressive relaxation, hypnosis, meditation); and 3) Moderate but sustained exercise. "Most people do get better with stress reduction of some kind and understanding stressors and that emotions can trigger symptoms, anger can and does effect the colon, worry does effect the colon, worry about a pathogen constantly can effect the colon, anxiety they missed something can and does effect the colon, in IBS this is much more pronounced.Dr Spiller is a world authority on PI IBS.New approaches in the management and treatment of irritable bowel syndromeProfessor Robin SpillerDivision of GastroentereologyUniversity HospitalNottinghamNG7 2UHTel 0115 9709352Fax 0115 9422232E-mail robin.spiller###nottingham.ac.ukThe last few years have seen some important advances in our understanding of theirritable bowel syndrome (IBS). The new Rome II Criteria are simpler than Rome I (seeFig 1), and have undoubtedly improved the comparability of clinical trail populationsthough care is needed to avoid these criteria acting as blinkers and inhibiting progress inunderstanding pathogenesis.Epidemiological studies suggest that symptom clusters define three sub-types of IBS. 1:characterised by loose stools passed with urgency with minimal straining, onecharacterised by hard stools and straining and incomplete evacuation but also someurgency and notably a similar bowel frequency. Finally there is a group of patients withminimal disturbance of stooling and a normal stool frequency whose main complaint ispain and bloating 1. It is apparent therefore that stool frequency is an unreliable guide tosub typing since it depends on social and psychological factors. It is probably moreuseful to define IBS subtypes based on the stool consistency, which is closely related tocolonic transit 2Sub-typing IBS patients is important since lumping them altogether may miss beneficialeffects if the treatment help one group but hinder another. Thus Loperamide improvespatients with diarrhoea but worsens symptoms in those with constipation 3.All clinicians are well aware that patients with a considerable psychological burdenrespond poorly to treatments. This was clearly shown by Bennett and colleagues 4whoshowed that those suffering from life stresses of greater than six months duration wereless likely to improve than those who lacked such features.When seeing a patient for the first time it is important to try and fit them into the multi-dimensional symptom space whose major axes are anxiety, colonic transit times andunderlying pathology (Figure 2). The third dimension is poorly defined, apart from postinfectious IBS (PI-IBS). These dimensions have important prognostic significance as canbe seen in Fig 35. PI-IBS is characterised by abdominal cramps, lose and urgent stoolsand accounts for between 6 and 17% of IBS patients attending GI clinics 6. Physiologicalchanges which affect nearly all individuals following GI infections include shortening ofwhole gut transit and lowering of discomfort threshold for rectal distension, the severityof the abnormality being increased in those who meet the criteria for IBS. Associatedwith these changes there is also evidence of low grade inflammation and elevatedenteroendocrine cells which resolves in most patients, but persists in those with persistentsymptoms7. These cells which are responsive to both luminal and neural signals are foundthroughout the GI tract. More than 50% of these cells contain 5HT, in the upper gut CCKand in the lower gut PYY account for most of the remainder. 5HT is released in responseto pressure, luminal nutrients and bacterial toxins including cholera toxins. It acts on arange of receptors the most important of which in the GI tract are 1a, 1p, 2, 3 and 4.Currently the most important ones therapeutically are 3 and 4. 5HT3 receptor is foundonly on nerves and produces a short duration depolarisation, stimulating sensory nervesincluding the vagus, thereby indirectly stimulating gastric and pancreatic secretions. Italso activates enteric cholinergic and VIPergic nerves, which stimulate enterocytesecretion. 5HT4 receptors are found on both nerves and enterocytes. The receptor is Gprotein-linked and when stimulated elevates cyclic AMP. This produces a slower onsetof action, inhibiting the delayed rectifier potassium channel and producing a prolongedincrease in the excitability of nerves, stimulating peristalsis and enterocyte chloridesecretion.Peristalsis involves the action of a bolus distending the lumen exciting descendinginhibition and ascending contraction of the circular muscles. It is believed that the bolusactivates the enteroendocrine cells to release 5HT, which stimulates peristalsis (seeFigure 4). Enteroendocrine cell numbers have been reported as increased in patients withchronic IBS seen in GI outpatients and a pilot study has reported an increased release of5HT after a meal in diarrhoea predominate IBS 8. Postprandially 5HT appears tostimulate both colonic tone and motility, effects which can be blocked by the intravenous5HT3 antagonist, granisetron. Alosetron is a more specific 5HT3 antagonist which hasbeen shown to improve stool consistency in diarrhoea-predominant IBS and increase theportion of patients experiencing adequate relief of symptoms 9. Its rather prematurewithdrawal was unfortunately due to rare adverse events which were both expected(severe constipation 70 / 435,000, 3 deaths) and unexpected (ischaemic colitis40/435,000, no deaths). Tegaserod is a highly selective 5HT4 agonist which acceleratesGI transit and accelerates gastric emptying and small bowel transit and increases theproportion of patients with relief of symptoms 10. It also increases stool frequency withinthe first week. Both Alosetron and Tegaserod represent exiting new opportunities fortreatment in a field where there have been no new drugs for many years. However, weshould not become too over enthusiastic based on novelty alone. When assessingefficacy it should be remembered that one needs to treat 8 ï¿½ 9 patients with Alosetron orTegaserod to get one extra patient responding compared with placebo alone. Thechallenge in the future is to better identify who will respond best to these treatments thusimproving the efficacy.In summary, there are no panaceas! Individual patients require individual treatments. Weshould always remember that as yet only psychological and dietary measures have beenshown to provide long-term improvement of symptoms. Not withstanding that drugs,which have reliable benefit, may well be useful in providing a sense of control over thesesymptoms which these patients so often lack. http://66.218.71.225/search/cache?p=ea+may...4A45D3B63&icp=1 There has also been enough people taking a variety of antibiotics to kill any pathogens and that has not panned out over the years.andVISCERAL PERCEPTION A role for inflammation in irritable bowel syndrome? http://gut.bmjjournals.com/cgi/content/full/51/suppl_1/i41 again from the author of""Inflammatory Bowel Disease and Irritable Bowel Syndrome: Separate or Unified?""and also from Dr Collins which some of you maybe starting to recgonize.Brain Imaging: CNS Abnormalities in Patients with IBSThe lack of a clearcut pathophysiology and an often noted association between physical and psychological symptoms has led some clinicians to dismiss irritable bowel syndrome (IBS) as a condition that is "all in their head." However recent findings showing CNS abnormalities in patients with IBS may offer a new perspective on the etiology of this debilitating condition, characterized by abdominal discomfort and pain and altered bowel habits. Until recently, the presence and severity of IBS were measured only by gut function and the subjective perceptions of the patient. "Now, the use of functional brain imaging techniques is contributing to an increased under- standing of the pathophysiology of this disease and new target areas for treatment," said Emeran A. Mayer, MD, Professor of Medicine, Physiology, and Biobehavioral Sciences, and Director of the CURE Neuroenteric Disease Program at the University of California, Los Angeles.Pathophysiology of IBSIBS is a disease that develops as the result of an abnormally altered brain-gut interaction (Table 1). One manifestation of this alteration consists of aberrant output patterns of the emotional motor system, a part of the limbic system in the brain, in response to external (psychosocial) or internal (immune, nutrient) stressors. Outputs from the limbic system in the form of autonomic, pain modulatory, and neuroendocrine responses can be modu- lated by cognitive factors, such as the beliefs, thoughts, and emotions of the patient. Aberrant output of the emotional motor system in large part accounts for the constellation of symptoms that makes up IBS. "A hyperresponsiveness of circuits in the brain may be one common link to both the abnormal responses to internal inflammatory stressors and external psychosocial stressors," Dr. Mayer explained. Treatment is chosen with consideration of altered motility, visceral hypersensitivity, and the brain's role in modulating these factors. The autonomic regulatory systems affect not only muscle cells in the gut, but also other cell types, such as mast cells, enterochromaffin cells, and nerve cells of the enteric nervous system. Responses of some of these cells to autonomic modulation, for example in the form of tryptase secretion by mast cells or serotonin secretion by enterochromaffin cells, may play a role in the modulation of visceral afferent sensitivity. According to Dr. Mayer, such mechanisms may play a role in the development of stress-induced visceral hyperalgesia. Another form of visceral hypersensitivity may be related to altered arousal or hypervigilance toward visceral sensations. Such hypervigilance can result in decreased tolerance to balloon distension and lower discomfort thresholds. A cognitive factor involved in the development of hypervigilance is an increased threat appraisal of visceral sensations.Functional Brain Imaging TechniquesRecently, functional brain imaging techniques have been used to assess directly the activation of certain regions of the brain in response to visceral stimulation. Today, these techniques, particularly functional magnetic resonance imaging, are being used to assess activation of brain circuits that process visceral afferent information from the gut. Dr. Mayer noted that there are distinct but overlapping brain circuits that relate to subjective perception of gut sensations, autonomic responses, and pain modulatory responses. Even in terms of subjective gut sensations, different overlapping circuits are present for intensity coding of the stimulus; threat appraisal of the stimulus; and attribution of primary affect, or "unpleasantness". Both serial and parallel pathways are involved in the processing of visceral sensory information and the control of descending modulatory systems. Input from the gut is derived from multiple channels, such as spinothalamic, vagal, and dorsal column pathways; different regions of the brain then code for intensity, appraise the threat of the stimulus, and determine the level of attention the brain attributes to the stimulus and the unpleasantness the patient experiences. These processes are modulated both by the stress- or arousal- activated system and by recollection of past experiences.Intensity Coding, Threat Appraisal, and UnpleasantnessIntensity coding. As visceral sensory information is delivered via the spinal cord, it is encoded for intensity in the anterior aspects of the insula, or visceral sensory cortex. PET scan studies of somatic and visceral experimental pain have shown that the insula most objectively and reliably encodes information. Interestingly, studies have also demonstrated a greater activation of the insula in male IBS patients, compared with female patients, when exposed to the same stimulus intensity. Threat appraisal and unpleasantness. The information that reaches the insula is "appraised" in the dorsal aspects of the anterior cingulate cortex. Blood flow changes in this part of the brain may also correlate with attentional processes and the subjective unpleasantness ratings in response to a somatic stimulus. The ventral (perigenual) cingulate cortex, which is rich in muopioid receptors, functions to encode the affective quality of the stimulus. In a study by Mayer and colleagues, rectal and sigmoid distension resulted in a lower activation of the ventral anterior cingulate cortex in patients with IBS compared with healthy controls, but an increased activation of the dorsal aspects of the anterior cingulate. Increased activation of an unspecified region of the anterior cingulate was also reported by Mertz and colleagues, in a functional MRI study. Modulatory factors. Finally, the CNS processing of sensory experience may be simultaneously modulated by two parallel pathways: memory-based modulation and stress- or arousal-induced modulation. The posterior parietal cortex, or sensory association cortex, forms a network with the hippocampus and the amygdala (the brain's memory centers) as well as with the lateral prefrontal cortex. Somatic pain studies have shown that, in response to a stimulus, the recall of a similar past event, along with subsequent interpretation of this memory in the lateral prefrontal cortex, plays a major role in the threat appraisal of a sensory experience. The second modulatory effect is the stress- or arousal-induced response. The pontine locus ceruleus is activated in response to potentially threatening experiences. This region then projects to nearly all other regions of the brain that receive visceral input, causing secretions of norepinephrine and arousal of these sections of the brain. When the secretion of norepinephrine is excessive, these target regions are inhibited. It is of interest that descending projections from the locus coeruleus complex to the sacral spinal cord appear to play a major role in the modulation of distal colonic motor and secretory function.Conclusion *Brain imaging and other studies of IBS pathophysiology indicate that the perception of gut stimuli and altered autonomic responses to these stimuli are affected by activation of various parts of the brain, resulting in increased attention to these stimuli, greater unpleasantness of the subjective experience, greater threat appraisal, and greater arousal in response to visceral sensations. Further study may lead to new developments in treatment for persons with IBS. * --------------------------------------------------------------------------------Table 1. Clinical Relevance of Altered Brain-Gut InteractionAltered attentional mechanisms o Greater awareness of normally subliminal visceral afferent stimuliAltered affective stimulus processing o Greater unpleasantness of visceral sensations, including heartburn, bloating, fullness, abdominal pain, incomplete rectal evacuationAltered threat appraisal o Leads to fears such as not being close enough to a bathroom anything eaten may trigger abdominal painEnhanced arousal o Shared by clinical conditions frequently overlapping IBS, such as anxiety, panic disorder and PTSD o Arousal reduced by sedatives, anxiolytics, low-dose tricyclics o May respond to relaxation exercises--------------------------------------------------------------------------------Post-Infective Irritable Bowel SyndromeAmong many postulated causes of irritable bowel syndrome (IBS), one of the most intriguing is that the syndrome represents sequelae of an acute enteric infection. In fact, such an association is not just an interesting theory. According to Stephen M. Collins, MBBS, FRCP, FRCPC, Professor of Medicine and Director of Gastroenterology at McMaster University in Hamilton, Ontario, Canada, "Acute enteric infection appears to be a significant contributing cause to the development of irritable bowel syndrome." The changes associated with such enteric infection appear to be reversible, introducing the opportunity for new treatment strategies for persons at high risk for irritable bowel syndrome (IBS).Clinical observations have suggested that transient infection in the gut can lead to persistent neuromotor dysfunction, and possible symptom generation in persons with IBS. In a large review, Chaudhary and Truelove found that 33% of persons with IBS reported an acute onset to their symptoms. Indeed, a recent controlled study showed that enteric infection was a strong risk factor for developing IBS.Animal Studies: Neuromuscular Dysfunction Post-InfectionIn one animal study by Tougas, Collins and colleagues infected mice with Trichinella spiralis. The results showed that the infection was accompanied by inflammation, reaching its peak in week 2. By week 3, the parasite had been expelled and inflammation had subsided. However, accompanying muscle hypercontractility persisted for up to 6 weeks' post-infection.In a second study by Tougas, the colons of the infected mice were distended using a small balloon and there was evidence of increased afferent nerve activity not only during the infection, but also 4 to 6 weeks' post-infection. Together, these results suggest that transient infection and subsequent inflammation in the gut can alter muscle contraction and increase sensory activity in the colon, suggesting a possible basis for dysmotility and hyperalgesia that occurs in post-infective IBS. But are these effects reversible?In a third study, animals were infected and allowed to recover. After 3 weeks, a short course of dexamethasone was administered. In the animals treated with steroids, muscle hypercontractility was prevented or reversed by day 28 post-infection. "Post-infective changes appear to be reversible and thus provide a basis for designing new experimental approaches in patients," said Dr. Collins.Clinical Association Between Infection and IBSFive recent studies showed that 7% to 31% of persons having food poisoning-associated bacterial gastroenteritis developed IBS, 3 to 12 months' post-infection. This phenomenon has also been observed with parasitic infection; however, the role of viral gastroenteritis is not yet known. The development of IBS appears to be due to a convergence of infection, inflammatory stimuli, central nervous system stimuli, and psychological factors. "The response to inflammatory stimuli is enhanced under stress, with the timing of the stress in relation tostimuli being important," Dr. Collins explained. Psychological factors, however, do not appear to be the sole determinants of whether someone develops IBS post-infection and other human studies suggest that local alterations in response to inflammatory stimuli may be important; this may be, in part, genetically determined.One study showed that 32% of persons with Salmonella-related gastroenteritis developed IBS symptoms within 2 years' post-infection. Biopsies showed no overt inflammatory presence; however, a semiquantitative approach showed an increase in inflammatory cells in those with IBS. Indeed, there was an increased number of lymphocytes and hyperplasia of the serotonin-containing enterochromaffin cells, a major source of 5-HT in the gut. "It is likely that 5-HT measurements would be increased in this subgroup, affording new therapeutic opportunities for these patients," Dr. Collins said. In addition, other studies have shown a potential role for lumenal factors and for cholestyramine-type factors, especially for diarrhea-dominant disease.ConclusionIn closing, Dr. Collins noted that post-infection effects associated with IBS appear to be reversible, warranting further clinical investigation of anti-inflammatory agents and other innovative therapies for persons at risk for IBS. Treatment Options in Irritable Bowel SyndromePrimary care physicians often refer patients with irritable bowel syndrome (IBS) to gastroenterologists because of difficulty finding an effective treatment. IBS is a condition characterized by abdominal pain, as well as diarrhea, constipation, or an alternating of the two. Treatment options for IBS are targeted to relieve either diarrhea, constipation, or pain, depending on the patient's predominant symptom (Table 1). For many patients, available therapies have not been successful in relieving their IBS, making further study and development of new products essential, said Anthony J. Lembo, MD, Instructor at Harvard Medical School and Director of the GI Motility Center at Beth Israel Deaconess Medical Center, in Boston. Focusing on pain-predominant IBS, Dr. Lembo profiled current and emerging new therapies. Recent studies suggest that the new smooth muscle relaxants can be effective against pain-predominant IBS and that antidepressants can be beneficial in treating functional gastrointestinal disorders. According to Dr. Lembo, these agents, together with newer 5-HT4 agonists, may offer promise for persons with pain-predominant IBS.Antispasmodic AgentsAntispasmodic agents are beneficial to some patients with IBS because they interfere with the exaggerated gastrocolic response that occurs with IBS, thereby reducing postprandial motor activity. The three main classes of antispasmodics include anticholinergics, peppermint oil, and the newer direct smooth muscle relaxants. Of four randomized double-blind studies of anticholinergics in IBS, only one showed a significant global symptom improvement over placebo. In this study, more than 50% of patients developed anticholinergic side effects. Of five randomized, double-blind studies of peppermint oil products, three showed significant global symptom improvement over placebo. However, significant side effects occurred with treatment, and the studies consisted of small sample sizes and short duration of followup. Constipation is one potentially significant side effect of antispasmodic agents. In a recent meta-analysis of all antispasmodic agents, Poynard and colleagues found that antispasmodics did benefit patients in terms of global symptom improvement in general, and pain, in particular. The antispasmodics that were most effective were the newer smooth muscle relaxants not currently available in the United States.Antidepressant AgentsAntidepressant agents, including tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors, are used in persons with IBS (particularly pain-predominant) because they are effective against chronic pain (especially TCAs); pain reduction is independent of effects on mood; and they are effective against conditions that often overlap with IBS. Side effects with these agents might include sedation, agitation, anticholinergic effects, and constipation.5-HT3 Antagonists and 5-HT4 AgonistsThere are four main types of 5-HT receptors, of which 5-HT3 and 5-HT4 are most relevant to the treatment of IBS. 5-HT3 receptors are associated with the provocation and perception of pain, the emesis reflex, and gut motility and secretion; while 5-HT4 receptors are associated with emesis reflex, visceral sensation, secretion, and activation of neurotransmitter release and gut motility. 5-HT3 antagonists have been shown to increase colonic compliance, reduce postprandial rectal sensitivity and motility, enhance jejunal water and sodium absorption, and prolong left colon transit time. Alosetron has been the only U.S. Food and Drug Administration (FDA)-approved 5-HT3 antagonist for the treatment of IBS (in women); however, Glaxo Wellcome has since voluntarily withdrawn this drug from the market after some reports of ischemic colitis and severe constipation. "Studies have shown 5-HT4 agonists to decrease small bowel transit time in persons with constipation-predominant IBS; to dose dependently inhibit afferent nerve activity to rectal distention in cats; and to inhibit visceral discomfort in rats," said Dr. Lembo. When serotonin is released from enterochromaffin cells in the gut, it stimulates 5-HT4 receptors on primary intrinsic afferent nerves, which in turn stimulate both ascending excitation and descending inhibition of motor neurons, resulting in peristaltic contraction in the gastrointestinal tract. 5-HT4 receptor agonists, such as tegaserod maleate, directly stimulate the peristaltic reflex and accelerate gastrointestinal transit. In a study of tegaserod, 881 persons having IBS-associated constipation and abdominal pain, were treated. Those taking tegaserod showed significant symptom improvement over placebo. In addition, tegaserod was associated with a significant increase in number of stools, improvement in stool consistency, and decrease in bloating. A significant response was achieved in women; small sample sizes of men studied thus far make these data difficult to interpret. Side effects included transient diarrhea (12% vs 5% in placebo), but there were no effects on QTc intervals. Tegaserod is currently under review by the FDA. In closing, Dr. Lembo emphasized that, "promising new agents-such as new muscle relaxants and 5-HT4 agonists-may soon mean more treatment options and greater relief for persons with IBS." --------------------------------------------------------------------------------Table 1. Treatment Options for IBSDiarrhea-Predominant IBS o Antidiarrheal agents (loperamide, diphenoxylate, cholestyramine) o Alosetron, a 5-HT3 receptor antagonist*Constipation-Predominant IBS o Fiber o Osmotic cathartics (sorbitol, lactulose) o Nonosmotic cathartics (polyethylene glycol) o Tegaserod, a 5-HT4 partial agonist that may be available in future**Pain-Predominant IBS o Antispasmodics (anticholinergics, peppermint oil, smooth muscle relaxantsï¿½) o Antidepressants (tricyclic antidepressants or selective serotonin reuptake inhibitors) o Alosetron for diarrhea-related pain* o Tegaserod for constipation-related pain, perhaps in near future** http://www.cmecorner.com/macmcm/pcp/pcp2000_01.htm


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## Talissa (Apr 10, 2004)

Thanks former bad-a** gangsta rapper.







You've got some wild friends btw, glad you lived thru last wkd. That would kill me I'm sure. Then again, I'm 35ish. (but of course, I look 25ish. I do! I swear...) I'm going to try the ibsacol, limit myself to one beer a week for 2 months & if it doesn't help, I'll blame the beer.LDanna, that's some good advice, with a few tweaks, we manage our IBS-D similarly(except for the hypno, which I don't think is bad, it's good, but when I was IBS sick, I was helped by simply meditating with music therapy. Now its just yoga & pilates, other exercise, & jamming to music).


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## Talissa (Apr 10, 2004)

Thanks former bad-a** gangsta rapper.







You've got some wild friends btw, glad you lived thru last wkd. That would kill me I'm sure. Then again, I'm 35ish. (but of course, I look 25ish. I do! I swear...) I'm going to try the ibsacol, limit myself to one beer a week for 2 months & if it doesn't help, I'll blame the beer.LDanna, that's some good advice, with a few tweaks, we manage our IBS-D similarly(except for the hypno, which I don't think is bad, it's good, but when I was IBS sick, I was helped by simply meditating with music therapy. Now its just yoga & pilates, other exercise, & jamming to music).


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## SpAsMaN* (May 11, 2002)

Rapper quote:...Jim Beam last weekend without any problems (except putting my neck severely out of alignment...). I think you makes a Flux-target of yourself.


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## SpAsMaN* (May 11, 2002)

Rapper quote:...Jim Beam last weekend without any problems (except putting my neck severely out of alignment...). I think you makes a Flux-target of yourself.


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## stinky too (May 21, 1999)

I drank 2/3rds a 40oz of Jim Beam last weekend without any problems (except putting my neck severely out of alignment...).


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## stinky too (May 21, 1999)

I drank 2/3rds a 40oz of Jim Beam last weekend without any problems (except putting my neck severely out of alignment...).


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## eric (Jul 8, 1999)

Dig Dis Sci. 2004 Jun;49(6):1046-53. Related Articles, Links Patients and nonconsulters with irritable bowel syndrome reporting a parental history of bowel problems have more impaired psychological distress.Kanazawa M, Endo Y, Whitehead WE, Kano M, Hongo M, Fukudo S.Center for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, North Carolina 27599-7080, USA. mkanazw###med.unc.eduLittle is known about the prevalence and risk factors for development of irritable bowel syndrome (IBS) in Japan. In the United States, it is reported that heredity and social learning contribute to the development of IBS. Our aims were (1) to estimate the prevalence of IBS, (2) to confirm that subjects with IBS are more likely to have parents with a history of bowel problems, (3) to confirm that gastroenteritis is a risk factor for IBS, and (4) to determine whether these two risk factors interact with psychological distress. Prevalence was estimated from a sample of 417 young adults seen for annual health screening examinations. To evaluate risk factors related to consulting physicians, the 46 subjects who fulfilled Rome II diagnostic criteria for IBS but denied ever having seen a physician about these symptoms (IBS non-consulters) were compared to the 317 subjects who did not meet the criteria for IBS (controls) and to a group of 56 patients diagnosed with IBS by gastroenterologists (IBS patients). All subjects completed the Gastrointestinal Symptoms Rating Scale, the State-Trait Anxiety Inventory, the Self-Rating Depression Scale, the Perceived Stress Scale, and the SF-36 quality of life scale. Fourteen and two-tenths percent (15.5% of females and 12.9% of males) of the community sample met the criteria for IBS diagnosis, of whom 22% consulted physicians. IBS patients and IBS nonconsulters were more likely than controls to have a parental history (33.9 vs. 12.6%, P 0.001, for patients and 26.1 vs. 12.6%, P 0.01, for nonconsulters) and were more likely to report an infective history compared to controls (44.6 vs. 16.1%, P 0.001, for patients and 32.6 vs. 16.1%, P 0.01, for nonconsulters). Two-way analysis of variance showed that the parental history was associated with a significantly greater impact on symptoms of indigestion, diarrhea, constipation, state and trait anxiety, and the SF-36 scales for social functioning and role emotional and that an infective history was associated with a greater impact on bodily pain. Both a parental history of bowel problems and a history of acute gastroenteritis are significant risk factors for development of IBS in Japan, as reported for the United States. Moreover, patients with such a family history show more psychological distress than other patients.PMID: 15309899 Med Sci Monit. 2004 Apr;10(4):RA55-62. Related Articles, Links Irritable bowel syndrome: a model of the brain-gut interactions.Mulak A, Bonaz B.Department of Gastroenterology and Hepatology, Wroclaw Medical University, Wroclaw, Poland. agata.mulak###wp.plBrain-gut interactions are increasingly recognized as underlying pathomechanisms of functional gastrointestinal disorders. Bi-directional communication between the central nervous system (CNS) and the enteric nervous system (ENS) occurs both in health and disease. Various CNS- and gut-directed stressors stimulate the brain-gut axis. Processes modulating responsiveness to stressors along the brain-gut axis involve neural pathways, the immunological, and endocrinological mechanisms. Disturbances at every level of neural control of the gastrointestinal tract can affect modulation of gastrointestinal motility, secretion, immune functions as well as perception and emotional response to visceral events. ENS function, central processing, and autonomic regulation play an important role in the brain-gut dialogue. Stress and emotions may trigger neuroimmune and neuroendocrine reactions via the brain-gut axis. Various non-site specific neurotransmitters influence gastrointestinal, endocrine and immune function, as well as human behavior and emotional state, depending on their location. The physiology of the digestive tract, the subjective experience of symptom, health behavior, and treatment outcome are strongly affected by psychosocial factors. Recently, a biopsychosocial model of IBS containing physiological, emotional, cognitive and behavioral components has been proposed. Rapid progress in neurogastroenterology, using new brain imaging techniques, should bring better understanding of the brain-gut axis and open new therapeutic perspectives.Publication Types: Review Review, Tutorial PMID: 15260348


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## eric (Jul 8, 1999)

Dig Dis Sci. 2004 Jun;49(6):1046-53. Related Articles, Links Patients and nonconsulters with irritable bowel syndrome reporting a parental history of bowel problems have more impaired psychological distress.Kanazawa M, Endo Y, Whitehead WE, Kano M, Hongo M, Fukudo S.Center for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, North Carolina 27599-7080, USA. mkanazw###med.unc.eduLittle is known about the prevalence and risk factors for development of irritable bowel syndrome (IBS) in Japan. In the United States, it is reported that heredity and social learning contribute to the development of IBS. Our aims were (1) to estimate the prevalence of IBS, (2) to confirm that subjects with IBS are more likely to have parents with a history of bowel problems, (3) to confirm that gastroenteritis is a risk factor for IBS, and (4) to determine whether these two risk factors interact with psychological distress. Prevalence was estimated from a sample of 417 young adults seen for annual health screening examinations. To evaluate risk factors related to consulting physicians, the 46 subjects who fulfilled Rome II diagnostic criteria for IBS but denied ever having seen a physician about these symptoms (IBS non-consulters) were compared to the 317 subjects who did not meet the criteria for IBS (controls) and to a group of 56 patients diagnosed with IBS by gastroenterologists (IBS patients). All subjects completed the Gastrointestinal Symptoms Rating Scale, the State-Trait Anxiety Inventory, the Self-Rating Depression Scale, the Perceived Stress Scale, and the SF-36 quality of life scale. Fourteen and two-tenths percent (15.5% of females and 12.9% of males) of the community sample met the criteria for IBS diagnosis, of whom 22% consulted physicians. IBS patients and IBS nonconsulters were more likely than controls to have a parental history (33.9 vs. 12.6%, P 0.001, for patients and 26.1 vs. 12.6%, P 0.01, for nonconsulters) and were more likely to report an infective history compared to controls (44.6 vs. 16.1%, P 0.001, for patients and 32.6 vs. 16.1%, P 0.01, for nonconsulters). Two-way analysis of variance showed that the parental history was associated with a significantly greater impact on symptoms of indigestion, diarrhea, constipation, state and trait anxiety, and the SF-36 scales for social functioning and role emotional and that an infective history was associated with a greater impact on bodily pain. Both a parental history of bowel problems and a history of acute gastroenteritis are significant risk factors for development of IBS in Japan, as reported for the United States. Moreover, patients with such a family history show more psychological distress than other patients.PMID: 15309899 Med Sci Monit. 2004 Apr;10(4):RA55-62. Related Articles, Links Irritable bowel syndrome: a model of the brain-gut interactions.Mulak A, Bonaz B.Department of Gastroenterology and Hepatology, Wroclaw Medical University, Wroclaw, Poland. agata.mulak###wp.plBrain-gut interactions are increasingly recognized as underlying pathomechanisms of functional gastrointestinal disorders. Bi-directional communication between the central nervous system (CNS) and the enteric nervous system (ENS) occurs both in health and disease. Various CNS- and gut-directed stressors stimulate the brain-gut axis. Processes modulating responsiveness to stressors along the brain-gut axis involve neural pathways, the immunological, and endocrinological mechanisms. Disturbances at every level of neural control of the gastrointestinal tract can affect modulation of gastrointestinal motility, secretion, immune functions as well as perception and emotional response to visceral events. ENS function, central processing, and autonomic regulation play an important role in the brain-gut dialogue. Stress and emotions may trigger neuroimmune and neuroendocrine reactions via the brain-gut axis. Various non-site specific neurotransmitters influence gastrointestinal, endocrine and immune function, as well as human behavior and emotional state, depending on their location. The physiology of the digestive tract, the subjective experience of symptom, health behavior, and treatment outcome are strongly affected by psychosocial factors. Recently, a biopsychosocial model of IBS containing physiological, emotional, cognitive and behavioral components has been proposed. Rapid progress in neurogastroenterology, using new brain imaging techniques, should bring better understanding of the brain-gut axis and open new therapeutic perspectives.Publication Types: Review Review, Tutorial PMID: 15260348


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## scottyswotty (Jun 29, 2000)

> quote:I think you makes a Flux-target of yourself.


I ain't too worried.


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## scottyswotty (Jun 29, 2000)

> quote:I think you makes a Flux-target of yourself.


I ain't too worried.


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## Talissa (Apr 10, 2004)

Just got this from Heather's IBS newsletter~"Dead or Alive, Probiotics can relieve gut disease""...The irradiated probiotics were given to mice with experimentally induced colitis, which is similar to human IBD. The irradiated probiotics effectively improved the colitis symptoms, as did the administration of viable, ï¿½liveï¿½ bacteria to another group of mice with colitis. This indicated that inactivated probiotics were as effective as live probiotics. The scientists say that the beneficial, anti-inflammatory activities seen with the inactivated probiotics could be the product of the innate immune system, the bodyï¿½s instant response to invasion by pathogens..." http://www.nutraingredients.com/news/news.asp?id=8601 So it seems the probiotics being alive to be viable(living through the stomach acid & bile) isn't necessarily necessary?


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## Talissa (Apr 10, 2004)

Just got this from Heather's IBS newsletter~"Dead or Alive, Probiotics can relieve gut disease""...The irradiated probiotics were given to mice with experimentally induced colitis, which is similar to human IBD. The irradiated probiotics effectively improved the colitis symptoms, as did the administration of viable, ï¿½liveï¿½ bacteria to another group of mice with colitis. This indicated that inactivated probiotics were as effective as live probiotics. The scientists say that the beneficial, anti-inflammatory activities seen with the inactivated probiotics could be the product of the innate immune system, the bodyï¿½s instant response to invasion by pathogens..." http://www.nutraingredients.com/news/news.asp?id=8601 So it seems the probiotics being alive to be viable(living through the stomach acid & bile) isn't necessarily necessary?


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## eric (Jul 8, 1999)

So there is no confusion, some probiotics have shown to help some symptoms of IBS. This is well known.Probiotics Claims, Benefits: Cures cancer, Crohnï¿½s disease, irritable bowel syndrome, yeast infections, heart disease, counteracts ï¿½poisonsï¿½ in our ï¿½modern life-style.ï¿½ Also strengthens your immune system, counteracts the side effects of antibiotics, wards off travelerï¿½s diarrhea.Bottom Line: Consume probiotic cultures in yogurt. But donï¿½t look to probiotic supplements as a cure for anything. Some day these bacteria will one day be harnessed as a treatment for diseaseï¿½but a lot of scientific work still needs to be done. Full article, Wellness Letter, September 2003: Going By Your Gut Probiotic supplementsï¿½that is, pills, capsules, powders, and beverages containing Lactobacillus acidophilus and other live bacteria, as well as some fungiï¿½can do a lot for you, or so their promoters claim. According to the website of one brand, a capsule a day will strengthen your immune system, counteract the side effects of antibiotics, ward off travelerï¿½s diarrhea, and generally make your tummy feel better. In addition, these supplements are said to be not only safe but necessary for infants, as well as pregnant and nursing women. Should you believe this? First, a little background on friendly intestinal bugs, now termed ï¿½probiotics,ï¿½ meaning ï¿½for life.ï¿½ The human digestive tract houses a huge variety of bacteriaï¿½creatures who live in us but are not us, strictly speaking, and whose populations actually outnumber our own cells. They live on wastes from our digestive processes, and they thrive on fiber from foods derived from plants. We get essential services from these invisible boarders, though some of our bacteria can be troublemakers, tooï¿½the stomach bacteria Helicobacter pylori that cause ulcers, for example. Some strains of beneficial bacteria cause gas, bloating, and cramping when their human hosts eat too many beans, for example. Infants are born with sterile intestines, but their digestive tracts are quickly colonized as they emerge from the womb and begin taking nourishment. The good bacteria that we all acquire perform such tasks as synthesizing certain vitamins (K, plus very small amounts of B12, folate, and thiamin) from the foods we eat. They make it harder for Salmonella and other harmful bacteria to get a foothold. In addition, they may play a role in neutralizing cancer-causing substances, and in other ways help keep us well. They may indeed play some role in immunity. Large bacterial populations in the human gut are essential for health and longevity. Foreign aid How can you help your invisible guests? If you eat a good diet with plenty of fruits, grains, and vegetables, they can take care of them-selvesï¿½you donï¿½t need to send foreign aid. Yogurt, kefir, and other products may contain live cultures of Lactobacillus (which help digest milk) and other bacteria. You can get similar cultures in soy milk now, as well as a range of other products. Itï¿½s not certain, however, that they arenï¿½t killed by stomach acids before they can join the ranks in the large intestine. And according to Dr. Gerald Tannock, a New Zealand expert on probiotics, the notion that ingested bacteriaï¿½assuming stomach acids have not killed themï¿½stick to the lining of the intestines and multiply is far from certain. The bacteria that are naturally present in our digestive systems may be highly competitiveï¿½they may not want help from aliens. Thus, any that you consume may make a pretty fast trip through, rather than settling down to serious jobs on the production line. As to the range of cultures in supplementsï¿½including Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, Bifidobacterium longum, and the yeast Saccharomycesï¿½there is little reason to think you need to swallow them. Since supplements are unregulated, you have no guarantee that they contain what the labels sayï¿½or that live bacteria could survive in such forms. In fact, a recent Belgian study found that many of the powdered or pill-form supplements contain little or no live bacteria, and that none contain enough to have any effect in the intestines. The wild claims made by some manufacturers should be enough to scare off anybody: probiotics will cure cancer, Crohnï¿½s disease, irritable bowel syndrome, yeast infections, heart disease, you-name-it, or will counteract alleged ï¿½poisonsï¿½ in our ï¿½modern life-style.ï¿½ Everybody, they say, from newborns to centenarians, should be taking them daily. People who make up such stories have only their own best interests at heart. How probiotics in food might help you ï¿½ Yogurt is an excellent food, particularly if you stick to the plain low-fat or nonfat varieties. Thereï¿½s no harm, but no proven benefit, to eating the kinds with live cultures. If you have trouble digesting the lactose in milk, you can still eat yogurt, since the bacteria in it help digest the lactose.ï¿½ If you are taking antibiotics, there is no harm in eating yogurt to try to restore the good bacteria. But ask your doctor or pharmacist about possible interactions.ï¿½ The evidence that eating yogurt or douching with it can ward off or cure vaginal yeast infections is very scant. Donï¿½t count on it.As Dr. Tannock points out, itï¿½s fine to consume probiotic cultures in yogurt. Just donï¿½t look to probiotics as a cure for anything. And people with certain bowel diseases such as ulcerative colitis should talk to a doctor before consuming them at all. Maybe these bacteria will one day be harnessed as a treatment for diseaseï¿½but a lot of scientific work still needs to be done. UC Berkeley Wellness Letter, September 2003 http://www.berkeleywellness.com/html/ds/dsProbiotics.php


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## eric (Jul 8, 1999)

So there is no confusion, some probiotics have shown to help some symptoms of IBS. This is well known.Probiotics Claims, Benefits: Cures cancer, Crohnï¿½s disease, irritable bowel syndrome, yeast infections, heart disease, counteracts ï¿½poisonsï¿½ in our ï¿½modern life-style.ï¿½ Also strengthens your immune system, counteracts the side effects of antibiotics, wards off travelerï¿½s diarrhea.Bottom Line: Consume probiotic cultures in yogurt. But donï¿½t look to probiotic supplements as a cure for anything. Some day these bacteria will one day be harnessed as a treatment for diseaseï¿½but a lot of scientific work still needs to be done. Full article, Wellness Letter, September 2003: Going By Your Gut Probiotic supplementsï¿½that is, pills, capsules, powders, and beverages containing Lactobacillus acidophilus and other live bacteria, as well as some fungiï¿½can do a lot for you, or so their promoters claim. According to the website of one brand, a capsule a day will strengthen your immune system, counteract the side effects of antibiotics, ward off travelerï¿½s diarrhea, and generally make your tummy feel better. In addition, these supplements are said to be not only safe but necessary for infants, as well as pregnant and nursing women. Should you believe this? First, a little background on friendly intestinal bugs, now termed ï¿½probiotics,ï¿½ meaning ï¿½for life.ï¿½ The human digestive tract houses a huge variety of bacteriaï¿½creatures who live in us but are not us, strictly speaking, and whose populations actually outnumber our own cells. They live on wastes from our digestive processes, and they thrive on fiber from foods derived from plants. We get essential services from these invisible boarders, though some of our bacteria can be troublemakers, tooï¿½the stomach bacteria Helicobacter pylori that cause ulcers, for example. Some strains of beneficial bacteria cause gas, bloating, and cramping when their human hosts eat too many beans, for example. Infants are born with sterile intestines, but their digestive tracts are quickly colonized as they emerge from the womb and begin taking nourishment. The good bacteria that we all acquire perform such tasks as synthesizing certain vitamins (K, plus very small amounts of B12, folate, and thiamin) from the foods we eat. They make it harder for Salmonella and other harmful bacteria to get a foothold. In addition, they may play a role in neutralizing cancer-causing substances, and in other ways help keep us well. They may indeed play some role in immunity. Large bacterial populations in the human gut are essential for health and longevity. Foreign aid How can you help your invisible guests? If you eat a good diet with plenty of fruits, grains, and vegetables, they can take care of them-selvesï¿½you donï¿½t need to send foreign aid. Yogurt, kefir, and other products may contain live cultures of Lactobacillus (which help digest milk) and other bacteria. You can get similar cultures in soy milk now, as well as a range of other products. Itï¿½s not certain, however, that they arenï¿½t killed by stomach acids before they can join the ranks in the large intestine. And according to Dr. Gerald Tannock, a New Zealand expert on probiotics, the notion that ingested bacteriaï¿½assuming stomach acids have not killed themï¿½stick to the lining of the intestines and multiply is far from certain. The bacteria that are naturally present in our digestive systems may be highly competitiveï¿½they may not want help from aliens. Thus, any that you consume may make a pretty fast trip through, rather than settling down to serious jobs on the production line. As to the range of cultures in supplementsï¿½including Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, Bifidobacterium longum, and the yeast Saccharomycesï¿½there is little reason to think you need to swallow them. Since supplements are unregulated, you have no guarantee that they contain what the labels sayï¿½or that live bacteria could survive in such forms. In fact, a recent Belgian study found that many of the powdered or pill-form supplements contain little or no live bacteria, and that none contain enough to have any effect in the intestines. The wild claims made by some manufacturers should be enough to scare off anybody: probiotics will cure cancer, Crohnï¿½s disease, irritable bowel syndrome, yeast infections, heart disease, you-name-it, or will counteract alleged ï¿½poisonsï¿½ in our ï¿½modern life-style.ï¿½ Everybody, they say, from newborns to centenarians, should be taking them daily. People who make up such stories have only their own best interests at heart. How probiotics in food might help you ï¿½ Yogurt is an excellent food, particularly if you stick to the plain low-fat or nonfat varieties. Thereï¿½s no harm, but no proven benefit, to eating the kinds with live cultures. If you have trouble digesting the lactose in milk, you can still eat yogurt, since the bacteria in it help digest the lactose.ï¿½ If you are taking antibiotics, there is no harm in eating yogurt to try to restore the good bacteria. But ask your doctor or pharmacist about possible interactions.ï¿½ The evidence that eating yogurt or douching with it can ward off or cure vaginal yeast infections is very scant. Donï¿½t count on it.As Dr. Tannock points out, itï¿½s fine to consume probiotic cultures in yogurt. Just donï¿½t look to probiotics as a cure for anything. And people with certain bowel diseases such as ulcerative colitis should talk to a doctor before consuming them at all. Maybe these bacteria will one day be harnessed as a treatment for diseaseï¿½but a lot of scientific work still needs to be done. UC Berkeley Wellness Letter, September 2003 http://www.berkeleywellness.com/html/ds/dsProbiotics.php


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## Talissa (Apr 10, 2004)

Here's another one that says probiotics work, dead or alive~"Probiotics reduce inflammation through toll-like receptor 9 signalling A study published in the February issue of Gastroenterology investigated the mechanism by which live probiotic bacteria attenuate experimental colitis. Dr Rachmilewitz and colleagues isolated methylated and unmethylated genomic DNA from probiotics (VSL-3), DNAse-treated probiotics and from E.coli. They then administered the DNA intragastrically (i.g.) or subcutaneously (sc) to mice, before inducing colitis. The researchers also administered viable gamma-irradiated probiotcs i.g. to wild-type mice and to mice deficient in different types of toll-like receptors (TLR) or in the adaptor protein MyD88. The probiotics were given 10 days before adding DSS to the drinking water, and for 7 days afterwards. Both i.g. and sc administration of probiotic and E.coli DNA ameliorated the severity of the colitis, whereas methylated probiotic DNA, DNAse-treated probiotic DNA and calf thymus DNA had no effect. The delivery of viable and non-viable probiotics had the same effect on colitis in wild-type mice. However, mice deficient in MyD88 did not respond to the non-viable probiotics. The severity of colitis in TLR2 and TLR4 deficient mice was significantly attenuated by the non-viable probiotics, but in the TLR9-deficient mice, the non-viable probiotics had no effect. These findings indicated that the protective effects of probiotics are medicated by their own DNA, rather than by their metabolites or their ability to colonise the colon. The authors concluded, "TLR9 signaling is essential in mediating the anti-inflammatory effect of probiotics, and live microorganisms are not required to attenuate experimental colitis because non-viable probiotics are equally effective." Source: Gastroenterology Citation: Rachmilewitz D et al., Gastroenterology. 2004 Feb;126(2):520-8.


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## Talissa (Apr 10, 2004)

Here's another one that says probiotics work, dead or alive~"Probiotics reduce inflammation through toll-like receptor 9 signalling A study published in the February issue of Gastroenterology investigated the mechanism by which live probiotic bacteria attenuate experimental colitis. Dr Rachmilewitz and colleagues isolated methylated and unmethylated genomic DNA from probiotics (VSL-3), DNAse-treated probiotics and from E.coli. They then administered the DNA intragastrically (i.g.) or subcutaneously (sc) to mice, before inducing colitis. The researchers also administered viable gamma-irradiated probiotcs i.g. to wild-type mice and to mice deficient in different types of toll-like receptors (TLR) or in the adaptor protein MyD88. The probiotics were given 10 days before adding DSS to the drinking water, and for 7 days afterwards. Both i.g. and sc administration of probiotic and E.coli DNA ameliorated the severity of the colitis, whereas methylated probiotic DNA, DNAse-treated probiotic DNA and calf thymus DNA had no effect. The delivery of viable and non-viable probiotics had the same effect on colitis in wild-type mice. However, mice deficient in MyD88 did not respond to the non-viable probiotics. The severity of colitis in TLR2 and TLR4 deficient mice was significantly attenuated by the non-viable probiotics, but in the TLR9-deficient mice, the non-viable probiotics had no effect. These findings indicated that the protective effects of probiotics are medicated by their own DNA, rather than by their metabolites or their ability to colonise the colon. The authors concluded, "TLR9 signaling is essential in mediating the anti-inflammatory effect of probiotics, and live microorganisms are not required to attenuate experimental colitis because non-viable probiotics are equally effective." Source: Gastroenterology Citation: Rachmilewitz D et al., Gastroenterology. 2004 Feb;126(2):520-8.


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