# Eric, question about cromolyn sodium for IBS?



## chelsea (Jun 26, 2000)

I think it was you who cited a study for patients with IBS and asthma that were able to take cromolyn sodium orally and achieved some relief from their IBS symptoms. This is the same thing as brand name, Gastrocrom, I believe. I was reading about Gastrocrom and what it is used for here in the US, which is Systemic Mastocytosis, a rare condition where the body produces an excessive number of mast cells in the GI tract, liver, and a few other organs. This in turn causes inflammation when an allergen is introduced into the body, and can produce symptoms of nausea, vomiting, diarrhea, headache and a few other symptoms. I, myself, have asthma which flares up my IBS, causing cramping in my stomach and intestine, and sometimes constipation. But, I don't think I have the extreme of Systemic Mastocystitis. Do you think that some people with IBS and asthma could have a moderate form of this condition, where the GI tract becomes inflammed just like the respiratory tract, just to a lesser extent?My immunology doctor is willing to prescribe the oral cromolyn sodium at my request to me to see if that helps. I'm just not sure if it will help me or not. Have you heard of anyone with IBS and asthma having this medication prescribed for them? Thanks.


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## eric (Jul 8, 1999)

It maybe worth a try, but many, many things activate mast cells including stress which releases a chemical from the brain that stimulates the mast cells. There are also other very important mechanisms going on in IBS.You may try this if your d symptoms and it may help you. I would discuss this with your doctor in more depth.The majority of serotonin a very important chemical neurotransmitter implicated in IBS though is released from a different cell in the gut, although also released from mast cells.Histamine can flare up the symptoms of IBS.


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## eric (Jul 8, 1999)

It maybe worth a try, but many, many things activate mast cells including stress which releases a chemical from the brain that stimulates the mast cells. There are also other very important mechanisms going on in IBS.You may try this if your d symptoms and it may help you. I would discuss this with your doctor in more depth.The majority of serotonin a very important chemical neurotransmitter implicated in IBS though is released from a different cell in the gut, although also released from mast cells.Histamine can flare up the symptoms of IBS.


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## ohnometo (Sep 20, 2001)

> quote:


Histamine can flare up the symptoms of IBS.Eric,Could you please explain alittle more about Histamine and IBS. What causes the Histamine to flare up IBS ?


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## ohnometo (Sep 20, 2001)

> quote:


Histamine can flare up the symptoms of IBS.Eric,Could you please explain alittle more about Histamine and IBS. What causes the Histamine to flare up IBS ?


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## Kathleen M. (Nov 16, 1999)

Histamine is one of the chemicals released by the mast cells in response to thing, particularly allergens. (And your brain uses it as a signal to stay awake--which is why antihistamines can make you drowsy--and the stomach uses it as a signal to release acid....like most things it has many roles)People with a disorder called Mastocytosis have too many mast cells, high levels of circulating histamine and diarrhea and abdominal pain in addition to many other symptoms.When the mast cells in the gut release histamine the gut responds by dumping in water and mucus into the GI tract and causing the muscles to push every thing out.Mast cells in the gut are also enervated from the brain so stress and possibly eating something you are conditioned to responding to could set things off (this may explain why some people react to some foods only when the know they ate them--if the brain knows it is there it "releases the hounds" and runs the bad food out. If you eat it and the brain doesn't know it is there then you do not react).K.


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## Kathleen M. (Nov 16, 1999)

Histamine is one of the chemicals released by the mast cells in response to thing, particularly allergens. (And your brain uses it as a signal to stay awake--which is why antihistamines can make you drowsy--and the stomach uses it as a signal to release acid....like most things it has many roles)People with a disorder called Mastocytosis have too many mast cells, high levels of circulating histamine and diarrhea and abdominal pain in addition to many other symptoms.When the mast cells in the gut release histamine the gut responds by dumping in water and mucus into the GI tract and causing the muscles to push every thing out.Mast cells in the gut are also enervated from the brain so stress and possibly eating something you are conditioned to responding to could set things off (this may explain why some people react to some foods only when the know they ate them--if the brain knows it is there it "releases the hounds" and runs the bad food out. If you eat it and the brain doesn't know it is there then you do not react).K.


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## eric (Jul 8, 1999)

There is a lot to the mechanisms behind this really.But,"For instance certain white blood cells known as ï¿½Mastï¿½ cellsfight the unfriendly elements by releasing a substance called ï¿½histamineï¿½. Histamine when released causesinflammation. Thus the bodyï¿½s defence system might go to work against unfriendly elements in the colon andinflammation there might cause the colon to malfunction." The release of histamine and also of mast cell degranulation is very much multifactoral.


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## eric (Jul 8, 1999)

There is a lot to the mechanisms behind this really.But,"For instance certain white blood cells known as ï¿½Mastï¿½ cellsfight the unfriendly elements by releasing a substance called ï¿½histamineï¿½. Histamine when released causesinflammation. Thus the bodyï¿½s defence system might go to work against unfriendly elements in the colon andinflammation there might cause the colon to malfunction." The release of histamine and also of mast cell degranulation is very much multifactoral.


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## eric (Jul 8, 1999)

FYIThis book by an IBS expert and international Immunology expert will help you learn some very important aspects of this and mast cell release and inflammation and how they apply to IBS. http://www.esthersternberg.com/


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## eric (Jul 8, 1999)

FYIThis book by an IBS expert and international Immunology expert will help you learn some very important aspects of this and mast cell release and inflammation and how they apply to IBS. http://www.esthersternberg.com/


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## Mike NoLomotil (Jun 6, 2000)

The mast cell is one type of immunocyte (the "tissue" immunocyte...it sits still in mucosa or cionnective tissue ionce it takes up residence) involved in the abnormal inflammatory response in the small bowel isolated from (so far) IBS d-types and cyclics.The primary function of the mast cell is immunologic and the primary mechanism of mast cell degranulation is IgE. As weith any portion of the integrated gastro-neuro-immuno-endo-exocrine "system" all the compnenents are interractive and can be influenced by other parts of the system, and can infleucne those parts themselves.So right now, a lot of people are acting as if the mast cell involvement is some big DISCOVERY> Not. The issue is a chicken-or-egg issue: which is the mechanism of activation or is it multiple means or different mechanisms at different times. ALL of the above are probably correct.As far back as the 1980s people have been suspicious of, and investigated indirectly, the mechanisms of why foods, even those with no pseudoallergy or chemical-mediating substances within, could provoke both the GI and extraintestinal symptoms of IBS and other conditions.Cromolyn sodium was found long ago to reduce both the GI and extraintestinal symptoms of patients with IBS by various people. Here area just a couple examples: __________________________________Minerva Dietol Gastroenterol 1989 Oct-Dec;35(4):219-24	[Irritable colon syndrome in intolerance to food additives].[Article in Italian]Antico A, Soana R, Clivio L, Baioni RThe rate of the irritable bowel syndrome (IBS) and the follow-up of its symptoms on diet and in therapy with disodium cromoglycate have been studied in a group of patients suffering from mainly extra-digestive symptoms related to food intolerance. Following our observation, we can draw the conclusion that food additives intolerance may be a major factor in the pathogenesis of IBS.PMID: 2516298, UI: 90159202 __________________________________Clin Exp Allergy 1991 Sep;21(5):569-72	Related Articles, Books, LinkOut Double-blind cross-over trial of oral sodium cromoglycate in patients with irritable bowel syndrome due to food intolerance.Lunardi C, Bambara LM, Biasi D, Cortina P, Peroli P, Nicolis F, Favari F, Pacor MLIstituto Clinica Medica, Policlinico Borgo Roma, University of Verona, Italy.Twenty patients with irritable bowel syndrome due to food intolerance were randomized to either oral sodium cromoglycate or placebo in a double-blind cross-over trial. The study consisted of treatment with either sodium cromoglycate or placebo for 8 weeks, followed by the cross-over treatment for 8 further weeks. Patients were allowed to eat the offending foods during the study. Eighteen patients completed the study. Analysis of patients' diary card scores showed a statistically significant difference in favour of sodium cromoglycate. There was a long carry-over effect in the active-placebo order group. Therefore oral sodium cromoglycate seems to be a useful treatment in patients with irritable bowel syndrome and proven food intolerance.Publication Types: ï¿½	Clinical trial ï¿½	Randomized controlled trial PMID: 1742648, UI: 92076294 _____________________________________ Minerva Pediatr 1993 Jun;45(6):253-8[Food intolerance and irritable bowel syndrome of childhood: clinical efficacy of oral sodium cromoglycate and elimination diet][Article in Italian]Grazioli I, Melzi G, Balsamo V, Castellucci G, Castro M, Catassi C, Ratsch JM, Scotta S.Schiapparelli Searle, Torino.Irritable bowel syndrome (IBS) is recognized to be a common cause of chronic diarrhea without failure to thrive in childhood. Several studies stressed the role of food intolerance as a major factor in the pathogenesis of IBS. The aim of this multicenter study was to investigate the offending role of food in IBS and to compare the therapeutic role of oral sodium cromoglycate versus elimination diet. 153 patients (mean age 4 years) with diarrhea (> 3 stools per day for four days in a week) and abdominal pain for about 10 months were enrolled in this trial. About half of the patients had a family history positive for atopy and 70% of the cases complained of intestinal symptoms after food ingestion. In 17% of the patients Skin Prick test (SPT) resulted positive to at least one food allergen and 87% of positive reactions to SPT was provoked by common foodstuffs. 87% of patients treated with elimination diet (rice, lamb, turkey, lettuce, carrots, sweet potatoes, pears, oil, tea, salt, mineral water, brown sugar) and 97% of patients treated with SCG (mean 63 mg/kg/day) for one month showed a significant improvement of intestinal symptoms. An elimination diet for several weeks can produce, beside a bad compliance (23% of patients admitted to our study didn't strictly follow diet regimen) also a nutritional deprivation. The results of this trial suggest that it's correct to investigate the role of food in children with diarrhea not due to organic diseases and diagnosed such as IBS and to use oral SCG to obtain the improvement of these symptoms.Publication Types: ï¿½	Clinical Trial ï¿½	Multicenter Study _______________________________________Scand J Gastroenterol 1995 Jun;30(6):535-41	Oral cromolyn sodium in comparison with elimination diet in the irritable bowel syndrome, diarrheic type. Multicenter study of 428 patients.Stefanini GF, Saggioro A, Alvisi V, Angelini G, Capurso L, di Lorenzo G, Dobrilla G, Dodero M, Galimberti M, Gasbarrini G, et alSant'Orsola Policlinic, University of Bologna, Italy.BACKGROUND: In a significant number of patients affected by the irritable bowel syndrome, an adverse reaction to food is proposed to be a causative factor. A diet that eliminates the offending foods is the obvious treatment for such adverse reactions. Compliance with a dietetic regimen is often poor and sometimes not completely free from risks. METHODS: Since the diarrheic type of irritable bowel syndrome seems mainly affected by food intolerance, and previous observations suggested that oral cromolyn sodium is effective in such patients, a multicenter therapeutic trial in the diarrheic type of irritable bowel syndrome was carried out in 346 of 409 patients with this disease, to evaluate the effects of oral cromolyn sodium and compare its efficacy with that of an elimination diet. RESULTS: Symptoms related to the irritable bowel syndrome improved in 60% of patients treated with elimination diet and in 67% of those treated with oral cromolyn sodium (1500 mg/day) for 1 month. Moreover, in both groups clinical results were significantly better in the patients positive to the skin prick test than in the negative ones. CONCLUSIONS: These results confirm the high prevalence of adverse reactions to foods in diarrheic irritable bowel syndrome and the usefulness of cromolyn sodium treatment in these patients.Publication Types: ï¿½	Clinical trial ï¿½	Multicenter study ï¿½	Randomized controlled trial _____________________________________...and so forth.Now their are (2) aspects of the mast cell issue in IBS that keep getting overlooked in the rush to isolate some possible CNS etiology: IgE.This is to some extent understandable, because for many years the patients with IBS symptoms were confirmed food allergy negative prior to study (IgE positive subjects excluded) by the known methods of detecting IgE (Type I Gel & Coombs reactions) food allergy. These methods would isolate and remove from study any patient who was test-positive in any way for the presence of circulating IgE antibodies specific to the food or foods which provoked the symptoms.So when mast cell degranulation is observed, and confirmed reversible by sodium cromoglycate administration, other mechanisms of mast cell destabilization have been assumed, and theorized, but not demonstrated quantitatively. All that was quantifiable is that mast cells in the gut do degranulate and release dozens of proinflammatory mediators (includinf but not limited to the histamine and serotonin of interest) which efect gut nerves, smooth muscle, vasculature, etc and thus can provide a mechanism of the observed upregulation.Several times in the last few years, though, by using an innovative technique of jejunal isolation and direct challenge, it was not only confirmed that mast cell degranulation occurs in the small bowel and is provoked by various foodstuffs depending upon the person(and by the way there is recruitment to the ileocecal junstion as well which is significant) BUT IgE was isolated from both the jejunal washings and by biopsy. As Gomer Pyle would say..surprise surprise surprise.This was wholly unexpected by even the immunologists and allergists and their GI pals doing the studies...they just expected the usual IgA and a bunch of inflammatory mediators. which they do get also.The presence of specific IgE signifies that at least one known PRIMARY immunologic mechanism for arming and degranulating mast cells independent of any neurologic influence has been isolated.To what degree it is participative vs other mechanisms needs to be quanitified. But the old rule book on "food allelrgy" is bound to be rewritten by such findings. Some feel it already has been. It is of particular note that some subjects ABSENT IBS symptoms also showed IgE arming of but mast cells...making this all the more reason to suspect a heretofore unseen and thus unobserved and unstudied local immunoprotective mechanism regulated by LOCAL IgE, since it is NOT detectable in circulation.One thing is for sure, though, is that one can isolate foods and chemicals which when eaten provoke degranulation, and lymphocyte activation as well as granulocyte activation, remove them from the diet and the symptoms subside.You can also use a mast cell stabilizer like Gastrocrom and stabilize the cell membrane thus reducing reactivity to provocation....BUT only for a while apparently.The main reason that this has not caught on as a treatment is tachyphylaxis....the patient, unless you isolate and remove the agents which provoke repsonse, needs more and more CS to achieve the same benefit. Apparently some of the dosing becomes massive accorindg to the doctors who have used it. So it is not considered as practical as was once thought.Other classes of cytoprotective drugs have been looked at over the years in these populatins with varying degrees of efficacy sugested. But This tachyphylaxis is why more focused diet therapy has persisted as a primary modality in this population instead of pharmacologic therapy for the gut mast cells...and why other forms of immunomodulation are being looked at....there are other substances which will stabilize immunocytes and which may not suffer from this problem. One is being sold commercially now (IBSACOL) and we are working with that and another from elsewhere which is very promising but it is early.if you obtain this book you can learn alot about this subject food allelrgy mechanisms vs food intolerance mechanisms from an authoritative viewpoint:"FOOD ALLERGIES AND FOOD INTOLERANCE: THE COMPLETE GUIDE TO THEIR IDENTIFICTION AND TREATMENT", Professor Jonathan Brostoff (M.D.. Allergy, Immunology and Environmental Medicine, Kings' College, London)http://www.amazon.com/exec/obidos/ASIN/089...r=2-1/102-64875 08-3420903[/URL]Books by: brostoff jonathan http://www.greenleaves.com/bookcat/by_brostoff_jonathan.html CURRICULUM VITAErofessor Jonothan Brostoff, MA, MD, DSc. FRCP, FRCPath. CURRENT APPOINTMENTSrofessor and Chairman, Immunology, Allergy and Environmental Medicine, Kings College, London. (New Appointment 2000) (Immediate Prior Appointment







rofessor of Immunology, Allergy & PathologyUniversity College London Medical SchoolDirector of Clinical Immunology and AllergyUniversity College London Hospitals, (Middlesex and Associated Hospitals)Director, Diagnostic Laboratory: Autoimmunology, Immunology, and AllergyGraduated Oxford University and St. Marys Medical SchoolPast President, Clinical Immunology and Allergy Section, Royal Society of Medicine EDITORIAL BOARDS:Clinical reviews in AllergyClinics in Immunology and AllergyPerspectives in ENT-AllergyAllergologia et ImmunopathologiaClinical Immunotherapeutics SCIENTIFIC SOCIETIES:Member of every conceivable European and American Society related to Immunology and Allergy MEDICAL ADVISORIES:Chief Advisor To the United Kingdom Minister of Agriculture, Food and Fisheries (Food and Chemical Sensitivity)To The National Eczema SocietyTo The Myalgic Encephalomyelitis AssociationChairman to the Allergy research Foundation Chief Consultant, Immunology and Allergy, Signet Diagnostic CorporationEat well. Think well. Be well. Don't aggravate your immune cells.MNL


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## Mike NoLomotil (Jun 6, 2000)

The mast cell is one type of immunocyte (the "tissue" immunocyte...it sits still in mucosa or cionnective tissue ionce it takes up residence) involved in the abnormal inflammatory response in the small bowel isolated from (so far) IBS d-types and cyclics.The primary function of the mast cell is immunologic and the primary mechanism of mast cell degranulation is IgE. As weith any portion of the integrated gastro-neuro-immuno-endo-exocrine "system" all the compnenents are interractive and can be influenced by other parts of the system, and can infleucne those parts themselves.So right now, a lot of people are acting as if the mast cell involvement is some big DISCOVERY> Not. The issue is a chicken-or-egg issue: which is the mechanism of activation or is it multiple means or different mechanisms at different times. ALL of the above are probably correct.As far back as the 1980s people have been suspicious of, and investigated indirectly, the mechanisms of why foods, even those with no pseudoallergy or chemical-mediating substances within, could provoke both the GI and extraintestinal symptoms of IBS and other conditions.Cromolyn sodium was found long ago to reduce both the GI and extraintestinal symptoms of patients with IBS by various people. Here area just a couple examples: __________________________________Minerva Dietol Gastroenterol 1989 Oct-Dec;35(4):219-24	[Irritable colon syndrome in intolerance to food additives].[Article in Italian]Antico A, Soana R, Clivio L, Baioni RThe rate of the irritable bowel syndrome (IBS) and the follow-up of its symptoms on diet and in therapy with disodium cromoglycate have been studied in a group of patients suffering from mainly extra-digestive symptoms related to food intolerance. Following our observation, we can draw the conclusion that food additives intolerance may be a major factor in the pathogenesis of IBS.PMID: 2516298, UI: 90159202 __________________________________Clin Exp Allergy 1991 Sep;21(5):569-72	Related Articles, Books, LinkOut Double-blind cross-over trial of oral sodium cromoglycate in patients with irritable bowel syndrome due to food intolerance.Lunardi C, Bambara LM, Biasi D, Cortina P, Peroli P, Nicolis F, Favari F, Pacor MLIstituto Clinica Medica, Policlinico Borgo Roma, University of Verona, Italy.Twenty patients with irritable bowel syndrome due to food intolerance were randomized to either oral sodium cromoglycate or placebo in a double-blind cross-over trial. The study consisted of treatment with either sodium cromoglycate or placebo for 8 weeks, followed by the cross-over treatment for 8 further weeks. Patients were allowed to eat the offending foods during the study. Eighteen patients completed the study. Analysis of patients' diary card scores showed a statistically significant difference in favour of sodium cromoglycate. There was a long carry-over effect in the active-placebo order group. Therefore oral sodium cromoglycate seems to be a useful treatment in patients with irritable bowel syndrome and proven food intolerance.Publication Types: ï¿½	Clinical trial ï¿½	Randomized controlled trial PMID: 1742648, UI: 92076294 _____________________________________ Minerva Pediatr 1993 Jun;45(6):253-8[Food intolerance and irritable bowel syndrome of childhood: clinical efficacy of oral sodium cromoglycate and elimination diet][Article in Italian]Grazioli I, Melzi G, Balsamo V, Castellucci G, Castro M, Catassi C, Ratsch JM, Scotta S.Schiapparelli Searle, Torino.Irritable bowel syndrome (IBS) is recognized to be a common cause of chronic diarrhea without failure to thrive in childhood. Several studies stressed the role of food intolerance as a major factor in the pathogenesis of IBS. The aim of this multicenter study was to investigate the offending role of food in IBS and to compare the therapeutic role of oral sodium cromoglycate versus elimination diet. 153 patients (mean age 4 years) with diarrhea (> 3 stools per day for four days in a week) and abdominal pain for about 10 months were enrolled in this trial. About half of the patients had a family history positive for atopy and 70% of the cases complained of intestinal symptoms after food ingestion. In 17% of the patients Skin Prick test (SPT) resulted positive to at least one food allergen and 87% of positive reactions to SPT was provoked by common foodstuffs. 87% of patients treated with elimination diet (rice, lamb, turkey, lettuce, carrots, sweet potatoes, pears, oil, tea, salt, mineral water, brown sugar) and 97% of patients treated with SCG (mean 63 mg/kg/day) for one month showed a significant improvement of intestinal symptoms. An elimination diet for several weeks can produce, beside a bad compliance (23% of patients admitted to our study didn't strictly follow diet regimen) also a nutritional deprivation. The results of this trial suggest that it's correct to investigate the role of food in children with diarrhea not due to organic diseases and diagnosed such as IBS and to use oral SCG to obtain the improvement of these symptoms.Publication Types: ï¿½	Clinical Trial ï¿½	Multicenter Study _______________________________________Scand J Gastroenterol 1995 Jun;30(6):535-41	Oral cromolyn sodium in comparison with elimination diet in the irritable bowel syndrome, diarrheic type. Multicenter study of 428 patients.Stefanini GF, Saggioro A, Alvisi V, Angelini G, Capurso L, di Lorenzo G, Dobrilla G, Dodero M, Galimberti M, Gasbarrini G, et alSant'Orsola Policlinic, University of Bologna, Italy.BACKGROUND: In a significant number of patients affected by the irritable bowel syndrome, an adverse reaction to food is proposed to be a causative factor. A diet that eliminates the offending foods is the obvious treatment for such adverse reactions. Compliance with a dietetic regimen is often poor and sometimes not completely free from risks. METHODS: Since the diarrheic type of irritable bowel syndrome seems mainly affected by food intolerance, and previous observations suggested that oral cromolyn sodium is effective in such patients, a multicenter therapeutic trial in the diarrheic type of irritable bowel syndrome was carried out in 346 of 409 patients with this disease, to evaluate the effects of oral cromolyn sodium and compare its efficacy with that of an elimination diet. RESULTS: Symptoms related to the irritable bowel syndrome improved in 60% of patients treated with elimination diet and in 67% of those treated with oral cromolyn sodium (1500 mg/day) for 1 month. Moreover, in both groups clinical results were significantly better in the patients positive to the skin prick test than in the negative ones. CONCLUSIONS: These results confirm the high prevalence of adverse reactions to foods in diarrheic irritable bowel syndrome and the usefulness of cromolyn sodium treatment in these patients.Publication Types: ï¿½	Clinical trial ï¿½	Multicenter study ï¿½	Randomized controlled trial _____________________________________...and so forth.Now their are (2) aspects of the mast cell issue in IBS that keep getting overlooked in the rush to isolate some possible CNS etiology: IgE.This is to some extent understandable, because for many years the patients with IBS symptoms were confirmed food allergy negative prior to study (IgE positive subjects excluded) by the known methods of detecting IgE (Type I Gel & Coombs reactions) food allergy. These methods would isolate and remove from study any patient who was test-positive in any way for the presence of circulating IgE antibodies specific to the food or foods which provoked the symptoms.So when mast cell degranulation is observed, and confirmed reversible by sodium cromoglycate administration, other mechanisms of mast cell destabilization have been assumed, and theorized, but not demonstrated quantitatively. All that was quantifiable is that mast cells in the gut do degranulate and release dozens of proinflammatory mediators (includinf but not limited to the histamine and serotonin of interest) which efect gut nerves, smooth muscle, vasculature, etc and thus can provide a mechanism of the observed upregulation.Several times in the last few years, though, by using an innovative technique of jejunal isolation and direct challenge, it was not only confirmed that mast cell degranulation occurs in the small bowel and is provoked by various foodstuffs depending upon the person(and by the way there is recruitment to the ileocecal junstion as well which is significant) BUT IgE was isolated from both the jejunal washings and by biopsy. As Gomer Pyle would say..surprise surprise surprise.This was wholly unexpected by even the immunologists and allergists and their GI pals doing the studies...they just expected the usual IgA and a bunch of inflammatory mediators. which they do get also.The presence of specific IgE signifies that at least one known PRIMARY immunologic mechanism for arming and degranulating mast cells independent of any neurologic influence has been isolated.To what degree it is participative vs other mechanisms needs to be quanitified. But the old rule book on "food allelrgy" is bound to be rewritten by such findings. Some feel it already has been. It is of particular note that some subjects ABSENT IBS symptoms also showed IgE arming of but mast cells...making this all the more reason to suspect a heretofore unseen and thus unobserved and unstudied local immunoprotective mechanism regulated by LOCAL IgE, since it is NOT detectable in circulation.One thing is for sure, though, is that one can isolate foods and chemicals which when eaten provoke degranulation, and lymphocyte activation as well as granulocyte activation, remove them from the diet and the symptoms subside.You can also use a mast cell stabilizer like Gastrocrom and stabilize the cell membrane thus reducing reactivity to provocation....BUT only for a while apparently.The main reason that this has not caught on as a treatment is tachyphylaxis....the patient, unless you isolate and remove the agents which provoke repsonse, needs more and more CS to achieve the same benefit. Apparently some of the dosing becomes massive accorindg to the doctors who have used it. So it is not considered as practical as was once thought.Other classes of cytoprotective drugs have been looked at over the years in these populatins with varying degrees of efficacy sugested. But This tachyphylaxis is why more focused diet therapy has persisted as a primary modality in this population instead of pharmacologic therapy for the gut mast cells...and why other forms of immunomodulation are being looked at....there are other substances which will stabilize immunocytes and which may not suffer from this problem. One is being sold commercially now (IBSACOL) and we are working with that and another from elsewhere which is very promising but it is early.if you obtain this book you can learn alot about this subject food allelrgy mechanisms vs food intolerance mechanisms from an authoritative viewpoint:"FOOD ALLERGIES AND FOOD INTOLERANCE: THE COMPLETE GUIDE TO THEIR IDENTIFICTION AND TREATMENT", Professor Jonathan Brostoff (M.D.. Allergy, Immunology and Environmental Medicine, Kings' College, London)http://www.amazon.com/exec/obidos/ASIN/089...r=2-1/102-64875 08-3420903[/URL]Books by: brostoff jonathan http://www.greenleaves.com/bookcat/by_brostoff_jonathan.html CURRICULUM VITAErofessor Jonothan Brostoff, MA, MD, DSc. FRCP, FRCPath. CURRENT APPOINTMENTSrofessor and Chairman, Immunology, Allergy and Environmental Medicine, Kings College, London. (New Appointment 2000) (Immediate Prior Appointment







rofessor of Immunology, Allergy & PathologyUniversity College London Medical SchoolDirector of Clinical Immunology and AllergyUniversity College London Hospitals, (Middlesex and Associated Hospitals)Director, Diagnostic Laboratory: Autoimmunology, Immunology, and AllergyGraduated Oxford University and St. Marys Medical SchoolPast President, Clinical Immunology and Allergy Section, Royal Society of Medicine EDITORIAL BOARDS:Clinical reviews in AllergyClinics in Immunology and AllergyPerspectives in ENT-AllergyAllergologia et ImmunopathologiaClinical Immunotherapeutics SCIENTIFIC SOCIETIES:Member of every conceivable European and American Society related to Immunology and Allergy MEDICAL ADVISORIES:Chief Advisor To the United Kingdom Minister of Agriculture, Food and Fisheries (Food and Chemical Sensitivity)To The National Eczema SocietyTo The Myalgic Encephalomyelitis AssociationChairman to the Allergy research Foundation Chief Consultant, Immunology and Allergy, Signet Diagnostic CorporationEat well. Think well. Be well. Don't aggravate your immune cells.MNL


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## chelsea (Jun 26, 2000)

Mike, Thank you so much for all the information you have provided regarding cromolyn sodium. This is very interesting and brings to mind some questions I have about the various antibodies our bodies produce. From what you stated above, it sounds like your saying that just because our gut may produce IgE antibodies against certain things we ingest, they don't necessarily show up in skin prick tests or serum tests? So, would the only way to determine if our GI tract is producing IgE antibodies to certain things would be to actually take a biopsy of the mucosal lining, or is it not this simple? My reason for asking this is that my immuologist (who, by the way, is a professor at Stanford University Medical School)took serum antibody tests, which consisted of a food and mold panel for the protective antibody, IgG, and another panel for IgE antibodies against environmental, as well as potential food antigens. The IgE tests were negative to all the foods, molds, animals, grasses, trees, etc. (I previously as a child had produced high IgE antibodies to many of these things, but was given a series of allergy shots over 12 years.)However, the IgG antibodies were very high positive to many molds and candida, and moderately positive to egg whites. As a result, he has suggested removing all foods that are processed with, or have aspergillus in them, as well as some of the other molds - he gave me a list of the foods. What I'm wondering though is whether there may actually be other foods that really do produce IgE antibodies in my gut but do not show positive on this test. Also, maybe the foods that ARE producing the IgG antibodies aren't even the ones that I should be eliminating if IgG is just the protective antibody. I'm sure it's not that simple. Nothing seems to be with this DARN IBS. Anyway, you seem to be very knowledgeable in this area, and I was hoping you might have some insight on this. Again, I really appreciate all your time and effort you put into helping educate us on these topics.


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## chelsea (Jun 26, 2000)

Mike, Thank you so much for all the information you have provided regarding cromolyn sodium. This is very interesting and brings to mind some questions I have about the various antibodies our bodies produce. From what you stated above, it sounds like your saying that just because our gut may produce IgE antibodies against certain things we ingest, they don't necessarily show up in skin prick tests or serum tests? So, would the only way to determine if our GI tract is producing IgE antibodies to certain things would be to actually take a biopsy of the mucosal lining, or is it not this simple? My reason for asking this is that my immuologist (who, by the way, is a professor at Stanford University Medical School)took serum antibody tests, which consisted of a food and mold panel for the protective antibody, IgG, and another panel for IgE antibodies against environmental, as well as potential food antigens. The IgE tests were negative to all the foods, molds, animals, grasses, trees, etc. (I previously as a child had produced high IgE antibodies to many of these things, but was given a series of allergy shots over 12 years.)However, the IgG antibodies were very high positive to many molds and candida, and moderately positive to egg whites. As a result, he has suggested removing all foods that are processed with, or have aspergillus in them, as well as some of the other molds - he gave me a list of the foods. What I'm wondering though is whether there may actually be other foods that really do produce IgE antibodies in my gut but do not show positive on this test. Also, maybe the foods that ARE producing the IgG antibodies aren't even the ones that I should be eliminating if IgG is just the protective antibody. I'm sure it's not that simple. Nothing seems to be with this DARN IBS. Anyway, you seem to be very knowledgeable in this area, and I was hoping you might have some insight on this. Again, I really appreciate all your time and effort you put into helping educate us on these topics.


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## Mike NoLomotil (Jun 6, 2000)

CHELSEA:Yes in a nutshell that is what the point is. It can be very difficult for people (practitioners and patients alike) to establish an understanding of the interraction between the CNS and the gut immune system in IBS when taken from the viewpoint of "traditional allergy-think" and/or the strict "brain-gut axis-think". These are not independent mechanisms and "systems" as regards gut function and IBS symptomology.So many studies which purported to rule out "allergy" to food or other hypersensitivity were performed on the assumption that the gut immune system, including the methods of circulating and tissue immunocyte activation, follow the same model as inflammatory response in other body organ systems. They do not, and it is misleading to refer to other inflammatory conditions as models for the guts' various local and systemic inflammatory reactions. It's a little like saying toes and fingers, both being digits, behave the same or perform the same functions. Similar but each has unique properties. So equivocal results with nonsensical methods of skin prick testing, oral challenges, RAST et al were classically interpreted as excluding the phenomena even though clinically to do so did not make sense based on the presentation of the patients, only by the limited nature of 'the numbers" and how they were derived.People first got suspicious when things like cromolyn sodium affectd symptoms equal to or greater than guesswork diet protocols. The findings of fragmentary IgE in the feces raised eyebrows, at least tothose who bothered to look, especially in patients who were RAST and SPT negative, and no history of atopy. COLAP testing found signs of food provoked inflammatory response in the colon and this also raised some eyebrows, but it was also clear that the colon was not the primary shock organ.But it was not until very recently, and the best and most definitive findings are not yet published, that investigators removed the variable of "placebo" CNS mediated response by direct-jejunal challenge via jejunal isolation and the quantification studies.The patient has no idea if you are pumping potato starch or water down the tube. So correlations can be established the possible influence of conditioned-response which can occur with oral challenge the conventional way, as well as being able to get a real provoking dose into the patient.While doing so IgE was sucked out of the jejunal washings and retrieved from biopsy. This is significant and fills a gap in the CNS-Immunologic model of food sensitivity in IBS.This link is to an article for you that covers pros and cons, soup to nuts, in an evolutionary fashion, and includes an immuno-neural model of the interractive brain-gut-immunologic mechanisms of food intolerance in IBS. It was completed before Bengtsson pumped the IgE out last year, but was written in such fashion that this finding was not unexpected since ssuch things as Tornblooms findings of lympocyte activation in the lamina propria of the small bowel had been disclosed prior to this tutorial.When you read it (this is the text model, you can get the PDF copy as well with the tables imbedded) be sure to click and print this model: "Figure 1 . Pathogenesis of food hypersensitivity induced irritable bowel syndrome. You will no doubt find it interesting, and an easy way of visualizing some of the interactive elements of the psychoneuroimmunoendocexocrine mechnanisms in IBS.Here is the link, I think you will find it an interesting tutorial on the subject: http://www.blackwell-synergy.com/servlet/u...36.2001.00951.x Gotta run, but if you look at the diagram you will see the point being made poorly by the written word of how the CNS and immune system can interact, independently and otherwise, to elicit the IRS (Inlfammatory response system) to diet components in IBS subpopulations. If one really knows the subject the model makes a lot of sense. It is incomplete but evolving.MNL


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## Mike NoLomotil (Jun 6, 2000)

CHELSEA:Yes in a nutshell that is what the point is. It can be very difficult for people (practitioners and patients alike) to establish an understanding of the interraction between the CNS and the gut immune system in IBS when taken from the viewpoint of "traditional allergy-think" and/or the strict "brain-gut axis-think". These are not independent mechanisms and "systems" as regards gut function and IBS symptomology.So many studies which purported to rule out "allergy" to food or other hypersensitivity were performed on the assumption that the gut immune system, including the methods of circulating and tissue immunocyte activation, follow the same model as inflammatory response in other body organ systems. They do not, and it is misleading to refer to other inflammatory conditions as models for the guts' various local and systemic inflammatory reactions. It's a little like saying toes and fingers, both being digits, behave the same or perform the same functions. Similar but each has unique properties. So equivocal results with nonsensical methods of skin prick testing, oral challenges, RAST et al were classically interpreted as excluding the phenomena even though clinically to do so did not make sense based on the presentation of the patients, only by the limited nature of 'the numbers" and how they were derived.People first got suspicious when things like cromolyn sodium affectd symptoms equal to or greater than guesswork diet protocols. The findings of fragmentary IgE in the feces raised eyebrows, at least tothose who bothered to look, especially in patients who were RAST and SPT negative, and no history of atopy. COLAP testing found signs of food provoked inflammatory response in the colon and this also raised some eyebrows, but it was also clear that the colon was not the primary shock organ.But it was not until very recently, and the best and most definitive findings are not yet published, that investigators removed the variable of "placebo" CNS mediated response by direct-jejunal challenge via jejunal isolation and the quantification studies.The patient has no idea if you are pumping potato starch or water down the tube. So correlations can be established the possible influence of conditioned-response which can occur with oral challenge the conventional way, as well as being able to get a real provoking dose into the patient.While doing so IgE was sucked out of the jejunal washings and retrieved from biopsy. This is significant and fills a gap in the CNS-Immunologic model of food sensitivity in IBS.This link is to an article for you that covers pros and cons, soup to nuts, in an evolutionary fashion, and includes an immuno-neural model of the interractive brain-gut-immunologic mechanisms of food intolerance in IBS. It was completed before Bengtsson pumped the IgE out last year, but was written in such fashion that this finding was not unexpected since ssuch things as Tornblooms findings of lympocyte activation in the lamina propria of the small bowel had been disclosed prior to this tutorial.When you read it (this is the text model, you can get the PDF copy as well with the tables imbedded) be sure to click and print this model: "Figure 1 . Pathogenesis of food hypersensitivity induced irritable bowel syndrome. You will no doubt find it interesting, and an easy way of visualizing some of the interactive elements of the psychoneuroimmunoendocexocrine mechnanisms in IBS.Here is the link, I think you will find it an interesting tutorial on the subject: http://www.blackwell-synergy.com/servlet/u...36.2001.00951.x Gotta run, but if you look at the diagram you will see the point being made poorly by the written word of how the CNS and immune system can interact, independently and otherwise, to elicit the IRS (Inlfammatory response system) to diet components in IBS subpopulations. If one really knows the subject the model makes a lot of sense. It is incomplete but evolving.MNL


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## chelsea (Jun 26, 2000)

Wow!! Very interesting. You just have so much helpful information. I was away for a bit, but had a chance to read this article last night.So how does one go about having a test like the COLAP test or a test that directly challenges the gut mucosal lining for antibodies? Are there any studies like this being done that one can enter? It also sounds like cromolyn sodium can be used as a general diagnostic tool in determining if a food intolerance or allergy, in general, may be contributing to the IBS based on the fact of whether symptoms improve while on it. That could be a start of at least seeing if there is an antibody mediated food hypersensitivity that is causing some or most of these symptoms...correct?I am very interested in any knowledge or articles to which you may refer me. This research sounds very promising. Do you think that this will become part of the testing procedures on those of us with IBS anytime soon?Thank you, once again.


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## chelsea (Jun 26, 2000)

Wow!! Very interesting. You just have so much helpful information. I was away for a bit, but had a chance to read this article last night.So how does one go about having a test like the COLAP test or a test that directly challenges the gut mucosal lining for antibodies? Are there any studies like this being done that one can enter? It also sounds like cromolyn sodium can be used as a general diagnostic tool in determining if a food intolerance or allergy, in general, may be contributing to the IBS based on the fact of whether symptoms improve while on it. That could be a start of at least seeing if there is an antibody mediated food hypersensitivity that is causing some or most of these symptoms...correct?I am very interested in any knowledge or articles to which you may refer me. This research sounds very promising. Do you think that this will become part of the testing procedures on those of us with IBS anytime soon?Thank you, once again.


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## Mike NoLomotil (Jun 6, 2000)

CHELSEA:First thing is to get that diagram in front of you. print out a copy.Got it?Now take a writing utensil (they let me have crayons here so I choose the red one) and see the box "other non-IgE mediated"? That box is illustrative of the role of all the mechanisms which can provoke a proinflammatory response in the small bowel and vasuclature that are not IgE (allergy) mediated. Suffice to say there are multiple mechanisms.First draw a line connecting the IgM box to the OTHER Box. Then draw a line down from the OTHER box PAST the mast cell box and over to the RELEASE OF MEDIATORS box.NOW the model is more complete. Those missing lines represent the part, the biggest part, of the food sensitivity equation in IBS that has been impossible to sort out. Thus causing the typical closing statements made by this author and all others including our chief consulting immunologist Brostoff when he worte the last book a few years ago, that since there is no way they know of (no "marker" that can be easily checked) to assess this part of the picture then the subject has to be approached with reservations clinically. How do you accurately and quickly isolate the offending foods or additives???? Until you can how do you apply the knowledge that it occurs to the patient before you?This is due to the characteristics of these reactions (non IgE mediated) of being DOSE DEPENDENT and DELAYED ONSET.SINCE the foods which provoke the mediator release from those mechanisms do not cause specific IgE antibodies to be formed which can be detected with existing technology (exception is the IgG for example)AND ORAL CHALLENGE cannot be relied upon much either since you CANNOT OFTEN GET A PROVOKING DOSE into the person double-blinded, it has been for years excrutiating work to try to isolate even 4-5 sensitive foods or chemicals clinically. Extensive dietary intake and symptom log analysis must be conducted to isolate evn a few of the non-allergic reactive foods. BUT if you do, nd remove them, even those limited numbers of 3-4 always result in success in anywhere from 60%-80% of the patients with symptoms...2/3 is pretty damn good having no tool other than a log to isolate the most obviosu non alleregenic reactions.henmce the years of clinical success by doctors who do work with food sensitivity patients. They are the only ones to take the time and effort and discipline to do it manually to at least this degree.COLAP is invaive and still not particularly specific overall, since you are working on the colon and the shock organ is the proximal small intestine, where the immune system is first exposed to the food or chemical and begins to respond. You can isolate some of the reactions via the colon, but the interface and immune fucntion and interraction dynamic between ingestants, the immune sytem, and the nervosu system is wholly different in the colon than the proximal small bowel where digestion begins and antigenicity is first manifest.THis is the reaction range you have to detect and what provokes it. It involves mast cells and circulating immunocytes which are there inside and outside the tiny blood vessels. The other immunocytes are recruited within the blood vessels or from a direct toxic effect of chemicals in foods upon the immunocytes. (leaving the CNS and ENS part of possible provocation out of this discussion since we already KNOW about that part of the equation and how the immune systen and bnervous sytem corss-talk with each other neurichemically and hormonally. The part that is hard to quantify is the immunologic or chemotoxic parts that occur inedependent of whether there is an additional ENS or CNS effect....it works in BOTH directions and both contribute to the symptom manifestations to differing degrees at different times.So until the invention of the Mediator Release Test (because it is the basis for the LEAP Lifetyle Plan diet part of the program it is sometimes just called LEAP test by people) the nearest thing that could isolate the offending foods was the old form of cellular immunocyte exam invented back in the 1980's by the same immunologist who perfected the MRT. His first-generation work using 1980's knowledge and technology.The difference is the new MRT (which is not widely known yet as I said but will be within 2 years) is what is called a common-end point quantitative assay for mediator release. Were the older test was basically an automoted form of cytotoxic test (which detected qualitative changes in the various leukocyte classes in vitro in response to foods or additives) because it is/was qualitative even when it was automated to remove human error in reproducibility it was always just that....viewed and used with some reluctance since it was linked to the old and unreliable manual Cytotoxic test of Dr. Braynt from back in the 1950's and 1960's. It is hilariosu at times to see how to this day peole who do not understand the subject must less the technology, keep referencing the old Cytotoxic test as if it has something to do with anything now in existence (outside what I beleive is called the Nutron test in the UK which, as I recall, is basically a a cyto using a ig expansive hematology analyzer to get the cell counts and sizings and then is interpreted manually...so the machine is used instead of the microsocope....maybe that is now gone though I don't know. It does not reproduce well).The new MRT (finished and patented in final form 2001) detects the quantitative shift (plasma volume differential) of the actual fluid containing and transporting chemical proinflammatory mediators from inside to outside (intrcellular to extracellular release)in response to exposure to a food or a chemical NO MATTER WHAT the Non IgE mediated mechanism is. Nor does it much matter clinically what the absolute array is, since any mediator release in response to the benign like food is NOT SUPPOSED TO OCCUR, only in response to a pathogenic threat! So symptoms will be provoked if enough of a response occurs. This does not happen in asymptomatic people. It happens in symptomatic people. So the method isolates which foods or chemicals or additives resulted in any reaction no matter what the non IgE mechanism which causes the non-tissue immunocyte reactions (or if you will, the non IgE stuff in that box). So when combined with the existing allergy assesssment methods which can detect anything which provokes allergic reaction,you can have the whole picture from the food allergy and intolerance side and contrive the best possible dietary regiment to achiev the avoidance of what is in that box below the immune system boxes: mediator release (it only says histamine but the etc. re[presnets up to 100 different ones).The one thing that no in vitro assay can do is detetc such things as the direct-lectin response in the gut of a mst cell since this is not duplicatable in vitro except with live tissue culture challenge. So you still have to check intake-resposne of such things as lectin-foods even if all tests are negative. This, however, is suaully what turns up once a person is on a rotation-elimination diet for all allelrgy and non-allergy food provocation. A peristent symptom from pseudoallaergy can then be easily isolated, and it reproduces readily on oral challenge so ttha is usually the lsat thing to go if the person is one of those susceptible to pseudoallergy response. Anyway starting to stary far afield if I don't reel myself in here....So drawing a line from the Non IgE box down to the mediator release box completes the integrative model of food sensitivity in IBS (or several other symptom sets for that matter). Now you could have your jejunum cannulated and isolated, then allow many days under those conditions to conduct serial direct-food-challenges to the small bowel with mediator recovery to check for which ones are provocative (do do this for, say, 100 foods might required, oh, 3-4 months with the catheter in, or putting it in and out every 3 days. that would do it. That will also, as you can see, be impractical hence the univeral references to an inability to do this (mark the food sesnitivity reaction) clinically. My guess is Professor Bengtsson at Sahlgrens in Goteborg, Sweden would be glad to have you living there







to this one you.That is why the team that worked on this project did so for so many years to conceive, develop and patent such a test. Now that it is done, the next step, which will take a couple years, will be getting it out there, using it, reporting on it by those who use it, and then widespread acceptance as the confirmatory data if effectiveness accumulates and is set forth in public places by third parties..Since it (the method) is not backed by a large public corporation like a drug company or major DME manufacturer, nor is the pet project at a big university medical center where a staff immunologist or allegrist or GI team and engineers conceived, designed, constructed, tested, modified, ran trials, and then were satisfied that it worked and then set forth to do what was necessary to get it into widespread use, there is no huge bank account to draw on so it will take longer as it has been done and will continue to be done with private funding. If that were not the case it could have been finished years earlier (the whole damn project).But it is indeed moving along. The first American independent study of the use of the LEAP tetsing and diet has started, but it was not for IBS where an interest funded something. It was fior dietetic manipulation in Autistics. It is being conducted at the Texas Center for Autistic Research and Treatment (Dr's Knicker and James). They were the first to have both interest and access to study-money after they tried it on some patients and found improvements in cognitive scoring. So I guess that will be the first US study, not IBS, and we will see if the immunocyte reactionms have an effect on autisitics or not. We will have to dig for more (the work progresses of doing so). The rest will come over the next 18-24 months.Speaking of that gotta run as the plane is landing soon bearing some people for training who are flying in this weekend. Gotta Go!MNL


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## Mike NoLomotil (Jun 6, 2000)

CHELSEA:First thing is to get that diagram in front of you. print out a copy.Got it?Now take a writing utensil (they let me have crayons here so I choose the red one) and see the box "other non-IgE mediated"? That box is illustrative of the role of all the mechanisms which can provoke a proinflammatory response in the small bowel and vasuclature that are not IgE (allergy) mediated. Suffice to say there are multiple mechanisms.First draw a line connecting the IgM box to the OTHER Box. Then draw a line down from the OTHER box PAST the mast cell box and over to the RELEASE OF MEDIATORS box.NOW the model is more complete. Those missing lines represent the part, the biggest part, of the food sensitivity equation in IBS that has been impossible to sort out. Thus causing the typical closing statements made by this author and all others including our chief consulting immunologist Brostoff when he worte the last book a few years ago, that since there is no way they know of (no "marker" that can be easily checked) to assess this part of the picture then the subject has to be approached with reservations clinically. How do you accurately and quickly isolate the offending foods or additives???? Until you can how do you apply the knowledge that it occurs to the patient before you?This is due to the characteristics of these reactions (non IgE mediated) of being DOSE DEPENDENT and DELAYED ONSET.SINCE the foods which provoke the mediator release from those mechanisms do not cause specific IgE antibodies to be formed which can be detected with existing technology (exception is the IgG for example)AND ORAL CHALLENGE cannot be relied upon much either since you CANNOT OFTEN GET A PROVOKING DOSE into the person double-blinded, it has been for years excrutiating work to try to isolate even 4-5 sensitive foods or chemicals clinically. Extensive dietary intake and symptom log analysis must be conducted to isolate evn a few of the non-allergic reactive foods. BUT if you do, nd remove them, even those limited numbers of 3-4 always result in success in anywhere from 60%-80% of the patients with symptoms...2/3 is pretty damn good having no tool other than a log to isolate the most obviosu non alleregenic reactions.henmce the years of clinical success by doctors who do work with food sensitivity patients. They are the only ones to take the time and effort and discipline to do it manually to at least this degree.COLAP is invaive and still not particularly specific overall, since you are working on the colon and the shock organ is the proximal small intestine, where the immune system is first exposed to the food or chemical and begins to respond. You can isolate some of the reactions via the colon, but the interface and immune fucntion and interraction dynamic between ingestants, the immune sytem, and the nervosu system is wholly different in the colon than the proximal small bowel where digestion begins and antigenicity is first manifest.THis is the reaction range you have to detect and what provokes it. It involves mast cells and circulating immunocytes which are there inside and outside the tiny blood vessels. The other immunocytes are recruited within the blood vessels or from a direct toxic effect of chemicals in foods upon the immunocytes. (leaving the CNS and ENS part of possible provocation out of this discussion since we already KNOW about that part of the equation and how the immune systen and bnervous sytem corss-talk with each other neurichemically and hormonally. The part that is hard to quantify is the immunologic or chemotoxic parts that occur inedependent of whether there is an additional ENS or CNS effect....it works in BOTH directions and both contribute to the symptom manifestations to differing degrees at different times.So until the invention of the Mediator Release Test (because it is the basis for the LEAP Lifetyle Plan diet part of the program it is sometimes just called LEAP test by people) the nearest thing that could isolate the offending foods was the old form of cellular immunocyte exam invented back in the 1980's by the same immunologist who perfected the MRT. His first-generation work using 1980's knowledge and technology.The difference is the new MRT (which is not widely known yet as I said but will be within 2 years) is what is called a common-end point quantitative assay for mediator release. Were the older test was basically an automoted form of cytotoxic test (which detected qualitative changes in the various leukocyte classes in vitro in response to foods or additives) because it is/was qualitative even when it was automated to remove human error in reproducibility it was always just that....viewed and used with some reluctance since it was linked to the old and unreliable manual Cytotoxic test of Dr. Braynt from back in the 1950's and 1960's. It is hilariosu at times to see how to this day peole who do not understand the subject must less the technology, keep referencing the old Cytotoxic test as if it has something to do with anything now in existence (outside what I beleive is called the Nutron test in the UK which, as I recall, is basically a a cyto using a ig expansive hematology analyzer to get the cell counts and sizings and then is interpreted manually...so the machine is used instead of the microsocope....maybe that is now gone though I don't know. It does not reproduce well).The new MRT (finished and patented in final form 2001) detects the quantitative shift (plasma volume differential) of the actual fluid containing and transporting chemical proinflammatory mediators from inside to outside (intrcellular to extracellular release)in response to exposure to a food or a chemical NO MATTER WHAT the Non IgE mediated mechanism is. Nor does it much matter clinically what the absolute array is, since any mediator release in response to the benign like food is NOT SUPPOSED TO OCCUR, only in response to a pathogenic threat! So symptoms will be provoked if enough of a response occurs. This does not happen in asymptomatic people. It happens in symptomatic people. So the method isolates which foods or chemicals or additives resulted in any reaction no matter what the non IgE mechanism which causes the non-tissue immunocyte reactions (or if you will, the non IgE stuff in that box). So when combined with the existing allergy assesssment methods which can detect anything which provokes allergic reaction,you can have the whole picture from the food allergy and intolerance side and contrive the best possible dietary regiment to achiev the avoidance of what is in that box below the immune system boxes: mediator release (it only says histamine but the etc. re[presnets up to 100 different ones).The one thing that no in vitro assay can do is detetc such things as the direct-lectin response in the gut of a mst cell since this is not duplicatable in vitro except with live tissue culture challenge. So you still have to check intake-resposne of such things as lectin-foods even if all tests are negative. This, however, is suaully what turns up once a person is on a rotation-elimination diet for all allelrgy and non-allergy food provocation. A peristent symptom from pseudoallaergy can then be easily isolated, and it reproduces readily on oral challenge so ttha is usually the lsat thing to go if the person is one of those susceptible to pseudoallergy response. Anyway starting to stary far afield if I don't reel myself in here....So drawing a line from the Non IgE box down to the mediator release box completes the integrative model of food sensitivity in IBS (or several other symptom sets for that matter). Now you could have your jejunum cannulated and isolated, then allow many days under those conditions to conduct serial direct-food-challenges to the small bowel with mediator recovery to check for which ones are provocative (do do this for, say, 100 foods might required, oh, 3-4 months with the catheter in, or putting it in and out every 3 days. that would do it. That will also, as you can see, be impractical hence the univeral references to an inability to do this (mark the food sesnitivity reaction) clinically. My guess is Professor Bengtsson at Sahlgrens in Goteborg, Sweden would be glad to have you living there







to this one you.That is why the team that worked on this project did so for so many years to conceive, develop and patent such a test. Now that it is done, the next step, which will take a couple years, will be getting it out there, using it, reporting on it by those who use it, and then widespread acceptance as the confirmatory data if effectiveness accumulates and is set forth in public places by third parties..Since it (the method) is not backed by a large public corporation like a drug company or major DME manufacturer, nor is the pet project at a big university medical center where a staff immunologist or allegrist or GI team and engineers conceived, designed, constructed, tested, modified, ran trials, and then were satisfied that it worked and then set forth to do what was necessary to get it into widespread use, there is no huge bank account to draw on so it will take longer as it has been done and will continue to be done with private funding. If that were not the case it could have been finished years earlier (the whole damn project).But it is indeed moving along. The first American independent study of the use of the LEAP tetsing and diet has started, but it was not for IBS where an interest funded something. It was fior dietetic manipulation in Autistics. It is being conducted at the Texas Center for Autistic Research and Treatment (Dr's Knicker and James). They were the first to have both interest and access to study-money after they tried it on some patients and found improvements in cognitive scoring. So I guess that will be the first US study, not IBS, and we will see if the immunocyte reactionms have an effect on autisitics or not. We will have to dig for more (the work progresses of doing so). The rest will come over the next 18-24 months.Speaking of that gotta run as the plane is landing soon bearing some people for training who are flying in this weekend. Gotta Go!MNL


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## Mike NoLomotil (Jun 6, 2000)

PS.....There are so many articles to refer you to I need time to compile a lost for you. Shoot me an email Monday to remind me of this request and I will rememeber to find time to put tothere a list of some references for you. I also suggest this book which will save a lot of time since it contains all thatw as known on that subject up through the last edition: (published in 200, so info up to about 1999 allowing for editing and printin lag)"FOOD ALLERGIES AND FOOD INTOLERANCE: THE COMPLETE GUIDE TO THEIR IDENTIFICTION AND TREATMENT", Professor Jonathan Brostoff (M.D.. Allergy, Immunology and Environmental Medicine, Kings' College, London) http://www.amazon.com/exec/obidos/ASIN/089...6487508-3420903 Have a nice W/E....







MNL


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## Mike NoLomotil (Jun 6, 2000)

PS.....There are so many articles to refer you to I need time to compile a lost for you. Shoot me an email Monday to remind me of this request and I will rememeber to find time to put tothere a list of some references for you. I also suggest this book which will save a lot of time since it contains all thatw as known on that subject up through the last edition: (published in 200, so info up to about 1999 allowing for editing and printin lag)"FOOD ALLERGIES AND FOOD INTOLERANCE: THE COMPLETE GUIDE TO THEIR IDENTIFICTION AND TREATMENT", Professor Jonathan Brostoff (M.D.. Allergy, Immunology and Environmental Medicine, Kings' College, London) http://www.amazon.com/exec/obidos/ASIN/089...6487508-3420903 Have a nice W/E....







MNL


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