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mast cells

6K views 138 replies 10 participants last post by  Blair 
Man, I could pound out info and references on this one all day....and have you and other readers reading and puzzling all day on how it all fits together. Instea lets cut to the chase with a very breif and simplified answer to your posted question.The bottom line is that for decades various investigators have been looking at the links between IBS symptom sets (primarily d-types and cyclic types of the population so far, which is about 70% of all the people diagnosed with IBS) and inflammatory responses to provocation in the small bowel as the most plausible explanation for these symptoms sets since it is the only scenarios which consistently fits all the pieces of the puzzel together biochemically.Some of the most obvious observations which have always pointed to this:They (the symptoms) fit perfectly what happens when the immunocytes associated with the bowels' immunoprotective functions are activated. Various types of inflammatory reactions can occur which result in shortened transit time, increased sensory perception, pain, increased secretion of fluid and reduced absorption, reduced response threshold of gut smooth muscle, non-gut symptoms related to activation of other neurons in the body besides those of the gut up to and including (depending upn which reaction occurs) very specific and general CNS ("brain tissue") activation.For many years now experiments have shown that in this subpopulation that some form of abnormal immune reaction occurs in the small bowel, and that it can be provoked by food or additives in foods and aggravated and perpatuated by behavioral responses both autonomous and learned.Symptoms can be reduced or eliminated by isolating and removing provoking dietery components, and can be attenuated to varying degrees with therapies that alter perception and stress response (ie CBT and HT for example). And when combined properly a greater degree of relief can be obtained than with single mode therapy since the involved gastroneuroimmunoendoexocrine systems are fully integrated and codependent.It has also been shown that the majority of the response of the immune system of the gut is not allergic in origin, but it appears about 8% of the IBS patients have comorbid true food allergies in addition to food and chemical provoked reactions of the small bowel. These predominating multi-pathway reactions are not mediated by the specific circulating immunoglobulins you can isolate with conventional allergy tests(the patients for example come back oral challenge positive, positive to provocation of circulating immunocytes like granulocytes, lyphocytes and platelets but negative by skin testing and such things as radioimmunoassaysa for specific immunoglobulins, exept for those with allergy comorbdity). This has been for decades a 'fascinoma'.Also, while the colon appears normal except for increased mast cell tissue density in some patients at the ileaocecal junction, there are irrefutable and clear confirmations of immunocyte involvemement in the gut. This first came in the form of consistent response to cell wall stabilizers like cromolyn sodium when taken by IBS patients of the d and cyclic type. if the immunocytes, esp. mast cells, were not involved then they would have no effect.These are substances used in asthmatics to stabilize the mast cells, to keep them from a process called "degranulaton". Their classic use has been in asthma, and in some cases IBD. The mucosa of the respiratory tract and small bowel are very similar in function and immune structure. The front line of defense is the "tissue" immune system dominated by the mast cells. They contain a storehouse of numerous preformed chemicals (including histamine and serotonin among many others) which are released when the mast cell is trigered to release them. This promotes a cascade of reactions of the immune system which are protective in intent. Also, once activated, there are other mediators that are synthesized from pieces-parts and added to the mix of preformed mast cell mediators.The circulating immunocytes (lymphocyte types, granulocyte types, platelets and macrophages) may also be invoked to act via various mechanisms. Their mediators are also released...they are "cytoprotective" proinflammatory mediators as well. The idea is to discriminate between danger (pathogens) and safe (food and drink) and respond to danger with attack and evacuation (removal) and to remain silent when safe things are present.So for many years it has been shown over and over again that the mast cells of the small bowel are being activated in these IBS patients, and that they can be and are being abnormally provoked by dietary components. Though nobody knows yet all the possible reasons WHY they start to misbehave, the markers of mast cell and circulating immunocyte reaction can be and have been recovered from the fluids within the small bowel and the markers of circulating immunocytes reactions, including accumulations of the cells themselves at the root ganglia even, can be seen on biopsy.Again, this all happens even in IBS patients who are allergy-negative. So the mucosal reaction (mast cells are at the root of it) is King so to speak and the circulating immunocytes are subjects (vasals) in a way, BUT they are also summoned independently of the King (they do not rely upon mast cell degranulation to react...this can be demonstarted any day of the week in vitro...healthy peoples immunocytes do not react to to non-chemotoxic foods or additives in vitro and patients with symptoms of such conditions as IBS and migraine and asthma and FMS DO react to safe things both in vivo and in vitro).The symptoms experienced are collateral damage...side effects of the mediators either intentional as part of the protective mechanisms being invoked specifically, or as untoward effects...consequences of releasing that chemical to activate Process A causes Tissue B to respond in the desired way but Tissue C is also effected as a consequence and this is an undesireable but temporary effect. And even when Tissue B responds positively an untoward efect usually accompanies the esired effect. It's like Joker said "If you want to make an omelet you have got to crack some eggs!". If you want to contain and kill and remove pathogens you are going to offend some normal tissue or processes when you act.This is a good book to read to try to get a picture of the myriad immune mechanisms and mediators (including mast cells) and interractive functions, as least as much as is known so far (there is much that is not understood you will see the more you read):The Immune System by Peter Parham http://www.amazon.com/exec/obidos/ASIN/081...4326764-6290107 and this is a good book to read to understand the role of the immune system structures in disease:"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 So is this, if you can find one. It is a medical reference text for physicians which is out of print now, but a new edition is in editing at this time with updated info. These are sometimes locatable in the medical library or used:Food Allergy and Intolerance- by Jonathan Brostoff, Stephen J. Challacombe http://www.amazon.com/exec/obidos/ASIN/070...2580864-1502269 The mast cell is so effective as a protective structure, and so dangerous, because of where it sits in the gut wall...if you look at the gut wall structures you will see those babaies an the enterocromafin cells sitting right there with the gut nerves and smooth muscle and vasculature. They have to be as they must act directly upon them when provoked to do so.Now interestingly, it has been very difficult to understand why the mast cells begin to misidentify safe things like foods or safe additives as dangerous and degranulate without the specific immunoglobnulins to the substance cirulating around (except in the case of pseudoallergic response where the chemical reaction is direct, like from lectin which can plug right into the cell and trigger it to go BOOM). Also, why the circulating immunocytes down there in the microvasculature of the bowel are also responding...independently. Now those are easier to explain when you look at things like the alternate complement pathway and cytotoxic reactions and several other pathways and how permeability is altered in response to mast cell mediators (to let more immonytes get to the apparant site of danger OUTSIDE the capillaries)thus how this can lead to the wrong kind of immune complexes being formed ad nauseum, but why the mast cells misidentify things absent detectible immunoglobulins to things has been puzzling.However, in Sweden they have recently discovered (among the many mediators that can be recovered from the small bowel washings in the IBS patients studied by jejunal isolation) was....IgE?. So these allergists are now pondering if the whole thing is some kind of localized IgE mediated reaction...that is, there actaully are specific immunoglobulins involved but they do not circulate around so that is why SPT and RAST and ELISA do not show any signs of them.Trouble that complicates it is that they found some of the same thing in non-symptomatic patients...so the mast cells may be naturally prearmed, or prearmed under certain conditions and the preconditions, and something else discriminates the ones that remain stable from those which do not...reactive patients which show off with IBS and those that do not. It is very unclear, though, at this time. This stage of investigation has just finally been reached, as this is not exactly a benign thing to do to someone (jejunal and duodenal isolation and challenge). Not to mention wh funds such things? So far just certain Swedish medical centers, nd maybe the Italians will jump on it now too. These are hotbeds of investigation into preventive or prophylactic medicine.But what is clear as a bell is that these bad boys are a major player in at least so far the subpopulation (70%)of the d's and cyclics, and what can trigger them to go off can be isolated and thus avoided. Also that things which stabilize mast cells and other immunocytes reduce symptoms proportionate to the array of cells they are effective on (cromolyn soidum works alot better on mast cells than granulocytes, so they can stop the mast cell response but only blunt the granulocyte response...this was seena s far back as 1988 where it was discussed at the 47th annual conference of the American College of Allergy and Immunology [everybody knew that CS worked on mast cells but it was first shown that it could blunt granulocyte response some also when the patients suffered non IgE food reactivity]. Oh before you jump up and aay 'Why don't we just give everyone CS...let me answer: tachyphylaxis.
Bummer.Another interesting thing about mast cells is that they localize...that is if there is a site of the body of chronic danger, chronic provocation, the number of mast cells in the tissue will increase. Conversely if the number of mast cells increases inappropriately and they are unstable then that site paradoxically becomes a site of chronic inflammation.A number of times (I cannot remember the count I would ahve to go back anf look) it has been noted that many IBS victims show increased tissue mast cell density at the ileocecal junction...the place in the large bowel where the small bowel empties into the large bowel. This signifies a sight of chronic provocation of some sort.
Anyway we can go on and on and on...I hope that puts some of Mr. mast cell into fairly plain english. He is largely responsible for IBS being referred to by some as "asthma of the gut" due to the similarities seen between the two immune responses. And as we know one is sometimes a comorbidity of the other. editorially, it's funny how so many of the comorbidities of IBS are conditions which are linked by the common thread of aberrant immune response. Yet there are those who persist in citing immunologists and allergists who wave the smoking guns as nothing but cowboys, so to speak. Or just totally ignore it as it does not fit their own line of thought or theories or line of funded investigation.But the consept is so simple...if an aberrant immune rsponse was not implicated in the symptoms of the 70% of IBS victoms with diaarheic and cyclic diarrhea and constipation, then thse apteints would NOT respond to variosu immunomodulators NOR would there be proinflammatory mediators in the small bowel washings NOR would there be clear tissue signs of chronic immunocyte activaton on small bowel biopsy NOR would their circualting immunocytes discharge mediators in vitro when exposed to safe substances as opposed to normal peoples immunocytes which do not.As Grouch Said, "It's so simple a child of five would understand this. Send someone to fetch a child of five."
Eat well. Think well. be well. (Don't degranulate)MNL
 
Man, I could pound out info and references on this one all day....and have you and other readers reading and puzzling all day on how it all fits together. Instea lets cut to the chase with a very breif and simplified answer to your posted question.The bottom line is that for decades various investigators have been looking at the links between IBS symptom sets (primarily d-types and cyclic types of the population so far, which is about 70% of all the people diagnosed with IBS) and inflammatory responses to provocation in the small bowel as the most plausible explanation for these symptoms sets since it is the only scenarios which consistently fits all the pieces of the puzzel together biochemically.Some of the most obvious observations which have always pointed to this:They (the symptoms) fit perfectly what happens when the immunocytes associated with the bowels' immunoprotective functions are activated. Various types of inflammatory reactions can occur which result in shortened transit time, increased sensory perception, pain, increased secretion of fluid and reduced absorption, reduced response threshold of gut smooth muscle, non-gut symptoms related to activation of other neurons in the body besides those of the gut up to and including (depending upn which reaction occurs) very specific and general CNS ("brain tissue") activation.For many years now experiments have shown that in this subpopulation that some form of abnormal immune reaction occurs in the small bowel, and that it can be provoked by food or additives in foods and aggravated and perpatuated by behavioral responses both autonomous and learned.Symptoms can be reduced or eliminated by isolating and removing provoking dietery components, and can be attenuated to varying degrees with therapies that alter perception and stress response (ie CBT and HT for example). And when combined properly a greater degree of relief can be obtained than with single mode therapy since the involved gastroneuroimmunoendoexocrine systems are fully integrated and codependent.It has also been shown that the majority of the response of the immune system of the gut is not allergic in origin, but it appears about 8% of the IBS patients have comorbid true food allergies in addition to food and chemical provoked reactions of the small bowel. These predominating multi-pathway reactions are not mediated by the specific circulating immunoglobulins you can isolate with conventional allergy tests(the patients for example come back oral challenge positive, positive to provocation of circulating immunocytes like granulocytes, lyphocytes and platelets but negative by skin testing and such things as radioimmunoassaysa for specific immunoglobulins, exept for those with allergy comorbdity). This has been for decades a 'fascinoma'.Also, while the colon appears normal except for increased mast cell tissue density in some patients at the ileaocecal junction, there are irrefutable and clear confirmations of immunocyte involvemement in the gut. This first came in the form of consistent response to cell wall stabilizers like cromolyn sodium when taken by IBS patients of the d and cyclic type. if the immunocytes, esp. mast cells, were not involved then they would have no effect.These are substances used in asthmatics to stabilize the mast cells, to keep them from a process called "degranulaton". Their classic use has been in asthma, and in some cases IBD. The mucosa of the respiratory tract and small bowel are very similar in function and immune structure. The front line of defense is the "tissue" immune system dominated by the mast cells. They contain a storehouse of numerous preformed chemicals (including histamine and serotonin among many others) which are released when the mast cell is trigered to release them. This promotes a cascade of reactions of the immune system which are protective in intent. Also, once activated, there are other mediators that are synthesized from pieces-parts and added to the mix of preformed mast cell mediators.The circulating immunocytes (lymphocyte types, granulocyte types, platelets and macrophages) may also be invoked to act via various mechanisms. Their mediators are also released...they are "cytoprotective" proinflammatory mediators as well. The idea is to discriminate between danger (pathogens) and safe (food and drink) and respond to danger with attack and evacuation (removal) and to remain silent when safe things are present.So for many years it has been shown over and over again that the mast cells of the small bowel are being activated in these IBS patients, and that they can be and are being abnormally provoked by dietary components. Though nobody knows yet all the possible reasons WHY they start to misbehave, the markers of mast cell and circulating immunocyte reaction can be and have been recovered from the fluids within the small bowel and the markers of circulating immunocytes reactions, including accumulations of the cells themselves at the root ganglia even, can be seen on biopsy.Again, this all happens even in IBS patients who are allergy-negative. So the mucosal reaction (mast cells are at the root of it) is King so to speak and the circulating immunocytes are subjects (vasals) in a way, BUT they are also summoned independently of the King (they do not rely upon mast cell degranulation to react...this can be demonstarted any day of the week in vitro...healthy peoples immunocytes do not react to to non-chemotoxic foods or additives in vitro and patients with symptoms of such conditions as IBS and migraine and asthma and FMS DO react to safe things both in vivo and in vitro).The symptoms experienced are collateral damage...side effects of the mediators either intentional as part of the protective mechanisms being invoked specifically, or as untoward effects...consequences of releasing that chemical to activate Process A causes Tissue B to respond in the desired way but Tissue C is also effected as a consequence and this is an undesireable but temporary effect. And even when Tissue B responds positively an untoward efect usually accompanies the esired effect. It's like Joker said "If you want to make an omelet you have got to crack some eggs!". If you want to contain and kill and remove pathogens you are going to offend some normal tissue or processes when you act.This is a good book to read to try to get a picture of the myriad immune mechanisms and mediators (including mast cells) and interractive functions, as least as much as is known so far (there is much that is not understood you will see the more you read):The Immune System by Peter Parham http://www.amazon.com/exec/obidos/ASIN/081...4326764-6290107 and this is a good book to read to understand the role of the immune system structures in disease:"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 So is this, if you can find one. It is a medical reference text for physicians which is out of print now, but a new edition is in editing at this time with updated info. These are sometimes locatable in the medical library or used:Food Allergy and Intolerance- by Jonathan Brostoff, Stephen J. Challacombe http://www.amazon.com/exec/obidos/ASIN/070...2580864-1502269 The mast cell is so effective as a protective structure, and so dangerous, because of where it sits in the gut wall...if you look at the gut wall structures you will see those babaies an the enterocromafin cells sitting right there with the gut nerves and smooth muscle and vasculature. They have to be as they must act directly upon them when provoked to do so.Now interestingly, it has been very difficult to understand why the mast cells begin to misidentify safe things like foods or safe additives as dangerous and degranulate without the specific immunoglobnulins to the substance cirulating around (except in the case of pseudoallergic response where the chemical reaction is direct, like from lectin which can plug right into the cell and trigger it to go BOOM). Also, why the circulating immunocytes down there in the microvasculature of the bowel are also responding...independently. Now those are easier to explain when you look at things like the alternate complement pathway and cytotoxic reactions and several other pathways and how permeability is altered in response to mast cell mediators (to let more immonytes get to the apparant site of danger OUTSIDE the capillaries)thus how this can lead to the wrong kind of immune complexes being formed ad nauseum, but why the mast cells misidentify things absent detectible immunoglobulins to things has been puzzling.However, in Sweden they have recently discovered (among the many mediators that can be recovered from the small bowel washings in the IBS patients studied by jejunal isolation) was....IgE?. So these allergists are now pondering if the whole thing is some kind of localized IgE mediated reaction...that is, there actaully are specific immunoglobulins involved but they do not circulate around so that is why SPT and RAST and ELISA do not show any signs of them.Trouble that complicates it is that they found some of the same thing in non-symptomatic patients...so the mast cells may be naturally prearmed, or prearmed under certain conditions and the preconditions, and something else discriminates the ones that remain stable from those which do not...reactive patients which show off with IBS and those that do not. It is very unclear, though, at this time. This stage of investigation has just finally been reached, as this is not exactly a benign thing to do to someone (jejunal and duodenal isolation and challenge). Not to mention wh funds such things? So far just certain Swedish medical centers, nd maybe the Italians will jump on it now too. These are hotbeds of investigation into preventive or prophylactic medicine.But what is clear as a bell is that these bad boys are a major player in at least so far the subpopulation (70%)of the d's and cyclics, and what can trigger them to go off can be isolated and thus avoided. Also that things which stabilize mast cells and other immunocytes reduce symptoms proportionate to the array of cells they are effective on (cromolyn soidum works alot better on mast cells than granulocytes, so they can stop the mast cell response but only blunt the granulocyte response...this was seena s far back as 1988 where it was discussed at the 47th annual conference of the American College of Allergy and Immunology [everybody knew that CS worked on mast cells but it was first shown that it could blunt granulocyte response some also when the patients suffered non IgE food reactivity]. Oh before you jump up and aay 'Why don't we just give everyone CS...let me answer: tachyphylaxis.
Bummer.Another interesting thing about mast cells is that they localize...that is if there is a site of the body of chronic danger, chronic provocation, the number of mast cells in the tissue will increase. Conversely if the number of mast cells increases inappropriately and they are unstable then that site paradoxically becomes a site of chronic inflammation.A number of times (I cannot remember the count I would ahve to go back anf look) it has been noted that many IBS victims show increased tissue mast cell density at the ileocecal junction...the place in the large bowel where the small bowel empties into the large bowel. This signifies a sight of chronic provocation of some sort.
Anyway we can go on and on and on...I hope that puts some of Mr. mast cell into fairly plain english. He is largely responsible for IBS being referred to by some as "asthma of the gut" due to the similarities seen between the two immune responses. And as we know one is sometimes a comorbidity of the other. editorially, it's funny how so many of the comorbidities of IBS are conditions which are linked by the common thread of aberrant immune response. Yet there are those who persist in citing immunologists and allergists who wave the smoking guns as nothing but cowboys, so to speak. Or just totally ignore it as it does not fit their own line of thought or theories or line of funded investigation.But the consept is so simple...if an aberrant immune rsponse was not implicated in the symptoms of the 70% of IBS victoms with diaarheic and cyclic diarrhea and constipation, then thse apteints would NOT respond to variosu immunomodulators NOR would there be proinflammatory mediators in the small bowel washings NOR would there be clear tissue signs of chronic immunocyte activaton on small bowel biopsy NOR would their circualting immunocytes discharge mediators in vitro when exposed to safe substances as opposed to normal peoples immunocytes which do not.As Grouch Said, "It's so simple a child of five would understand this. Send someone to fetch a child of five."
Eat well. Think well. be well. (Don't degranulate)MNL
 
Oh..the rhetorical question: _____________________________________"...maybe no big drug company has figured out a way to make alot of money from it?" _____________________________________Actually this is true...if the cell wall stabiLizers worked without tachyphylaxis it would be marketed like crazy. i HAVE BEEN TOLD OF PATIENTS WHO HAD WORKED UP TO TAKING AS MANY AS 80 CAPSULES A DAY...thats a bit much. Now in pediatric IBS patients it seems to take a while longer For effectiveness to be lost, but so far itr has been easier to find a nerve which reagulates something and the mediator associated with that nerve and either chemically block it, block reuptake, or engance or augment mediator generation depending upon if you want to activate or stop the nerve(s). This seems easier than stabilizing immunocytes.However, there is a very quiet effort going on within our side of the industry (the non pharmaceutical side which is focuse more on preventive and integartive therapies) assessing other types of immunomodulators which may be effective at altering immunocyte response in one way or another and which may not produce tachyphylaxis. Combined with the proven benefits of antigen-identification-and-elimination dieting while establishing a therapeutic blood level of the immunomodulator (it is a lot easier to stabilize an immunocyte if you remove the provocation just like it is easier to put out a fire if you stop throwing gasoline and wood on it while spraying it with water...you need less water and less time) the very real possibility of regaining some or all of a persons oral tolerance clearly exists. Once the right combination and protocol is isolated this will provide a very attractive alternative to long term pharmacotherapy or long-term rotation-elimination dieting. Imagine if you could know what is provoking the reaction, thus the sympotms, stop exposure for awhile while you bathe the various tissue and circulating immunocytes in a natural food extract which makes the immunocytes less reactive, or even are able (in those whose dysfunction is clearly linked to dysbiosis) restore the flora and soon regain the ability to return partially or fully to a normal diet of eating whatever you wanted??? That would be pretty cool I'll bet. Well, it is being worked on, beleive me.
MNL
 
Oh..the rhetorical question: _____________________________________"...maybe no big drug company has figured out a way to make alot of money from it?" _____________________________________Actually this is true...if the cell wall stabiLizers worked without tachyphylaxis it would be marketed like crazy. i HAVE BEEN TOLD OF PATIENTS WHO HAD WORKED UP TO TAKING AS MANY AS 80 CAPSULES A DAY...thats a bit much. Now in pediatric IBS patients it seems to take a while longer For effectiveness to be lost, but so far itr has been easier to find a nerve which reagulates something and the mediator associated with that nerve and either chemically block it, block reuptake, or engance or augment mediator generation depending upon if you want to activate or stop the nerve(s). This seems easier than stabilizing immunocytes.However, there is a very quiet effort going on within our side of the industry (the non pharmaceutical side which is focuse more on preventive and integartive therapies) assessing other types of immunomodulators which may be effective at altering immunocyte response in one way or another and which may not produce tachyphylaxis. Combined with the proven benefits of antigen-identification-and-elimination dieting while establishing a therapeutic blood level of the immunomodulator (it is a lot easier to stabilize an immunocyte if you remove the provocation just like it is easier to put out a fire if you stop throwing gasoline and wood on it while spraying it with water...you need less water and less time) the very real possibility of regaining some or all of a persons oral tolerance clearly exists. Once the right combination and protocol is isolated this will provide a very attractive alternative to long term pharmacotherapy or long-term rotation-elimination dieting. Imagine if you could know what is provoking the reaction, thus the sympotms, stop exposure for awhile while you bathe the various tissue and circulating immunocytes in a natural food extract which makes the immunocytes less reactive, or even are able (in those whose dysfunction is clearly linked to dysbiosis) restore the flora and soon regain the ability to return partially or fully to a normal diet of eating whatever you wanted??? That would be pretty cool I'll bet. Well, it is being worked on, beleive me.
MNL
 
Comment: ___________________________________"...Food appears to have nothing to do with this despite detailed pseudo-claims that it does." ____________________________________This is one of the most ill-informed pronouncements I have ever read on this Board or anywhere else the subject is discussed. It reflects a Total lack of familiarity with the topic and any of the actual research related to it.
Statements to this effect should be disregarded, as they are intentionally misleading and result in victims of food sensitivity conditions such as IBS-d, for example, failing to find permanent prophylactic means of controlling their symptoms. This reflects 1970's understanding. _____________________________________"They contain and can release histamine. Histamine can apparently lead to diarrhea. So if the brain gets a wrong signal (from the gut) or sends a wrong signal itself, it can turn this mechanism in motion." _____________________________________Simplifcation is desireable when talking with patients, but This statement is too oversimplified and misleading since mast cell control is not primarily vested in the CNS, which can and does have afferent and efferent communication with various immunocyte classes including mast cells and can and does particpate in mediating mast cell response, but is ONE factor which influences mast cell behavior.Mast cells role in humoral immunity is one of being a sentinel-cell so to speak. They are inserted in various places in the body tissue throughout the body particularly in the connective tissues lying in the mucosa of the respirtatory tract and the GI tract.They are also found in abundance in the connective tissue along blood vesels especially those in the dermal skin layer. The inflammatory mediator array of mast cells performs nay functions by the design of humoral immunity....primarily when activated some of the mediators are supposed to increase the permeability of local blood vessels, which will enable other immune cells and immune-molecules to move out of the bloodstream into the surrounding tissue fluid. This also causes a local accumulation of fluid (basophils and activated eosinophils are also triggered along with mast cells with the same immune mechanism...see below). This response is supposed to occur as a primary response to pathogen invasion as it recruits the host cells and proteins required for host defense at the site of infection. The primary natural targets of the immunoglobulin which activates this reaction is thought to be parasites, and inadvertant activation of this cell class is called Type I Hypersensitivity: allergy.Anyway besides facilitating recruitment of other cells to the site (as has been seen in the gut biopsies recently of IBS patients....increased lymphocyte accumulation at the root ganglia in the small bowel wall for example) indeed one function of mast cell mediators besides altered vessel permeabilioty is to increase contraction of the smooth muscle in the gut wall or airway wall. In the gut the violent contractions which are part of diarrhea response (or vomiting response) are designed to aid in propelling the pathogen out of the GI tract by all means and with dispatch. So the primary natural function of mast cells is supposed to be parasite protection.The primary mast cell activating mechanism is crosslinking of the high-affinity IgE receptor FCERI on the mast cell surface. Crosslinking by antigen and IgE is the primary cause of mast cell activation and degranulation. This receptor is also found on on basophils and eosinophils. When specific IgE is formed to a normally safe substance, be it a food or an inhalant, the mast cells can be rapidly degranulated when the antigen is introduced into the body via one of these portals of entry (lung or gut). This is also how skin prick testing works. If there is specific IgE present the characteristic "wheal and flare" appears when the antigen is stuck into the skin. This does not mean actual allergy is guaranteed, only that the IgE is present to that substance and allergy is possible (you have to confirm it esp. with food becasue the correlation between the two is often less than 50%).Pseudoallergy can also occur in some cases wherein the site is directlty crosslinked by a food-specific molecule class called lectins.These are found in many foods including such common foods as wheat and legumes.To understand what mast cells effect when degranulation occurs, be it within the bowel, the lung, or other tissue sites, one must study the mast cell mediators in total that are prepackaged and released (proteases, histamine, heparin, TNF-alpha, etc) and the post-activation synthesized meditors to comprehend what mast cell activation results in physiologically....some other main mast cell mediators include tryptase, chymase, cathespin G, carboxypeptidase, heparin, IL-3, IL-4, IL-5, IL-13, GM CSF, TNF alpha, MIP 1 alpha, leukotrienes C4 and D4, and platelet activating factor (among the platelet mediators released on activation by PAF is serotonin). Of interest is the fact that this type of immune response was apparently evolved for protection against parasites. There is little parasite exposure in the modern western world, and the incidence of allergy in the western world where parasite infection is rare, is much higher than in underdeveloped areas. Funny how certain immune functions which go unstimulated seem to find a way to activate through other means (just a musing of some immunologists).IBS d-types have over and over been shown to have symptoms provocable with specific dietary components, and the symptoms ablate when mast cell stabilizers are used....and mast cell mediators can be and have been retrieved from the isolated and food challenged small bowel. There were no parasites present and there was no detecible IgE allergy by conventional gel & Coombs definition and associated standard alelrgy tests...as the patients with negative testing for specific IgE are preidentified and either accounted for or removed.In the most recent investigation by one of the worlds most respected teams in a highly regarded institution in Sweden, IgE was also recovered from the small bowel to their great surpise along with the mast cell and non-mast cell mediators.Some elements of the medical community can go on forever ignoring this....it is sort of like the Islamic extremist response to yesterdays Bin laden tape: "It's a fabrication!!! It's fake! American Devils!" etc.
yeah yeah yeah rag on, rag on.My personal sympathies go out to those patients unfortunate enough to be guided by such myopic views of their symptoms.This statement falls into the RES IPSA LOQUITUR category.... _____________________________________"There is a histamine 3 receptor and some people are looking into blocking it. If that works pans out, it may lead to a drug. Drug development takes a lot of time and a lot of luck. " _______________________________________...and it takes spending twice as much on marketing as on research: 39% of revenues, or $14 billion per year, on marketing and sales costs to support 70,000 sales reps averaging $140,000 per year income each so as to maintain your position as the most profitable industry in the world, and to be sure to maintain the lobbyists and PACS who will help you retain your pork-barrel tax package which allows your industry to write off all the advertising and sales dollars unlike every other industry in the USA which much EAT those costs as opertaing costs, so you can finish FY 2000 with an overall pretax profit rate of 18.6% which is even higher than banks with 15.8%....on $99.6 BILLION in sales. [NOTE that most of the money pharmaceutical firms spend on research is for "me-too" drug development not new drugs sunce, as this post states flaty, they might not pan out. Too much risk. Instead we end up with such things as FIVE different branded statins on the market with more in the pipe which all work about the same...or a dozen different NSIADS...etc.]If the line of investigation is driven solely by drug development as the end-game then the information gleaned is gathered and interpreted solely in that selective context. Thus the context of the entire post. This is reflective of all that is wrong about IBS research in the United States. The only parts we get right are the parts that focus on how to find bodily functions which can be modified by commercially viable pharmacotherspies. All else is dismissed as it detracts from this specific end-game. --------------------------KMOTTUS makes an interesting observation: ___________________________________"The drug companies have been there done that. As far as I know there is nothing preventing wider usage of these drugs." ____________________________________The use of GATSROCROM I belive for IBS therapy would be an off-label use indeed. But the real thing that stands in the way of use of sodium cromoglycate for IBS isa) The studies on its effectiveness have been done in large part overseas, mostly Italy, and have not been widely read among the physician who manage IBS patients in the USA.
Even if they were, and patients with IBS -d and cyclics were placed on Gastrocrom in many cases tachyphylaxis becomes a problem...and once that sets in the protocol is worse than nothing at all as the patient is trapped by higher and higher dosing to get the same degree of relief and then, if no work has been done to isolate the provoking foods and chemicals before the therapy started, there is no prophylaxis to fallback to (no effective elimination diet specific to the patient)This is why people are looking to other natural substances with known immunomodulating qualities seeking better solutions. __________________________________"there must be more to it than getting rid of mast cells, otherwise it wouldhave been tried before?" ___________________________________By "getting rid" I asume you men attenuating mast cell response. Now there is more to it, and I pointed to part of it, as the mast cell is not the only immunocyte involved in the aberrant immune response in IBS and migraine and the like...lymphocytes, granulocyte classes, and platelets are also involved in the raction. Think of the mast cells as one of the bigger players though.And it has been done before...several times...mostly in Italy. In one study (I am doing this from memeory I will have to go look it up) on IBS-d type kids (it was a pretty good sized sample as I recall)they found that about 8% of them had actual confirmed comorbid IgE allergy (the SPT rate was about 17% and its only 40% positive predictive of allergy so that makes the actual comorbidity maybe 8%) and the rest did not yet they were positive to oral challenge on certain staple foods they tested as the kids responded with symptom reduction to one of the "statistical probability based" elimination diets, almost 90%.They also responded short term (30 days) to cromolyn sodium at a very high rate, over 90% I recall HEY I REMEMBER WHERE I PUT THE ABSRACT HOLD ON...
[elevator music interlude} _____________________________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: � Clinical Trial � Multicenter Study _________________________________At the risk of being repetitious, this was done a number of times and always with the same results..short term. It was then, in Europe, practitioners started using CS that the problem with tachyphylaxis cropped up. Brostoff has said to me that this is why the therapy ultimately was not efficacious, but it pointed the way to more investigation of immunomodulation therapy that has been going on with alternatives which might be as effective but not produce tachyphylaxis. ______________________________"trbell, I'm not so sure suppressing the immune system cells for any length of time is a good idea. Mast cells in the digestion are the defense against any bugs we swallow - suppressing them could lead to massive infections. Personally I'd rather have IBS or even allergies. " ______________________________This is a good point, Julia, and one that the people experimenting with immunomodulation have to take into account. Ther is a fine line between IMMUNOMODULATION (attenuating the aberrant immunocyte response or damping the excessive reactivity without interfering with normal humoral and cellular immune response to pathogens). It is possible to overdo it. In the west, however, the chance of damping the mast cell response so much that the parasite protection is blocked is less likely than overattenuating the cellular immune responses which protect against the more common pathogens (bacteria and virus).This area of investigation, except for CS which is well documented, is not new but this application is new. But it is one of the areas of promise among non-drug related therapies. _______________________________OHNOYOUTOO:
I am SOOOOO glad to hear that you are making progress so soon, as you, Like WashoeLisa who posted her whole case in thread on this board last year, were quite quite ill as you have posted before. Be prepared, however, to possibly be dismissed and insulted as Lisa was by certain elements of the community whose motivations lie elsewhere. Lisa, who is also the Digestive Disease Community Moderator in AmericasDoctor.com (and her father is the Chairman of the Board of one of the most prominent private hospital groups in California, so her case was under very close scrutiny) had severe IBS and Fibromyalgia and achieved 100% remission and drug freedom within 60 days on her LEAP lifetyle plan). So did her daughter with refractory eczema.You may even be called a SHILL and a FAKER that MNL PLANTED here...or that you are experiencing the (now debunked) magical placebo effect.
However, you will also find MORE support and confirmation from many lucky people here that isolation and elimination of dietary provoking agents has brought alot of help to many people here, regardless of how they arrived at their beneficial dietary changes.Stick 100% to the plan to get the best results. Cannot take ANY of the forbidden foods (sigh) as it is unclear exactly what the provoking dose is of each except in realtive terms to each other within your body. But I know you will!! Keep on keeping on...and OUT of the ER!!!
I am proud of your will power so far!!!!Eat well. Think well. Be well. Type well. Or at least better than:MNL
 
Comment: ___________________________________"...Food appears to have nothing to do with this despite detailed pseudo-claims that it does." ____________________________________This is one of the most ill-informed pronouncements I have ever read on this Board or anywhere else the subject is discussed. It reflects a Total lack of familiarity with the topic and any of the actual research related to it.
Statements to this effect should be disregarded, as they are intentionally misleading and result in victims of food sensitivity conditions such as IBS-d, for example, failing to find permanent prophylactic means of controlling their symptoms. This reflects 1970's understanding. _____________________________________"They contain and can release histamine. Histamine can apparently lead to diarrhea. So if the brain gets a wrong signal (from the gut) or sends a wrong signal itself, it can turn this mechanism in motion." _____________________________________Simplifcation is desireable when talking with patients, but This statement is too oversimplified and misleading since mast cell control is not primarily vested in the CNS, which can and does have afferent and efferent communication with various immunocyte classes including mast cells and can and does particpate in mediating mast cell response, but is ONE factor which influences mast cell behavior.Mast cells role in humoral immunity is one of being a sentinel-cell so to speak. They are inserted in various places in the body tissue throughout the body particularly in the connective tissues lying in the mucosa of the respirtatory tract and the GI tract.They are also found in abundance in the connective tissue along blood vesels especially those in the dermal skin layer. The inflammatory mediator array of mast cells performs nay functions by the design of humoral immunity....primarily when activated some of the mediators are supposed to increase the permeability of local blood vessels, which will enable other immune cells and immune-molecules to move out of the bloodstream into the surrounding tissue fluid. This also causes a local accumulation of fluid (basophils and activated eosinophils are also triggered along with mast cells with the same immune mechanism...see below). This response is supposed to occur as a primary response to pathogen invasion as it recruits the host cells and proteins required for host defense at the site of infection. The primary natural targets of the immunoglobulin which activates this reaction is thought to be parasites, and inadvertant activation of this cell class is called Type I Hypersensitivity: allergy.Anyway besides facilitating recruitment of other cells to the site (as has been seen in the gut biopsies recently of IBS patients....increased lymphocyte accumulation at the root ganglia in the small bowel wall for example) indeed one function of mast cell mediators besides altered vessel permeabilioty is to increase contraction of the smooth muscle in the gut wall or airway wall. In the gut the violent contractions which are part of diarrhea response (or vomiting response) are designed to aid in propelling the pathogen out of the GI tract by all means and with dispatch. So the primary natural function of mast cells is supposed to be parasite protection.The primary mast cell activating mechanism is crosslinking of the high-affinity IgE receptor FCERI on the mast cell surface. Crosslinking by antigen and IgE is the primary cause of mast cell activation and degranulation. This receptor is also found on on basophils and eosinophils. When specific IgE is formed to a normally safe substance, be it a food or an inhalant, the mast cells can be rapidly degranulated when the antigen is introduced into the body via one of these portals of entry (lung or gut). This is also how skin prick testing works. If there is specific IgE present the characteristic "wheal and flare" appears when the antigen is stuck into the skin. This does not mean actual allergy is guaranteed, only that the IgE is present to that substance and allergy is possible (you have to confirm it esp. with food becasue the correlation between the two is often less than 50%).Pseudoallergy can also occur in some cases wherein the site is directlty crosslinked by a food-specific molecule class called lectins.These are found in many foods including such common foods as wheat and legumes.To understand what mast cells effect when degranulation occurs, be it within the bowel, the lung, or other tissue sites, one must study the mast cell mediators in total that are prepackaged and released (proteases, histamine, heparin, TNF-alpha, etc) and the post-activation synthesized meditors to comprehend what mast cell activation results in physiologically....some other main mast cell mediators include tryptase, chymase, cathespin G, carboxypeptidase, heparin, IL-3, IL-4, IL-5, IL-13, GM CSF, TNF alpha, MIP 1 alpha, leukotrienes C4 and D4, and platelet activating factor (among the platelet mediators released on activation by PAF is serotonin). Of interest is the fact that this type of immune response was apparently evolved for protection against parasites. There is little parasite exposure in the modern western world, and the incidence of allergy in the western world where parasite infection is rare, is much higher than in underdeveloped areas. Funny how certain immune functions which go unstimulated seem to find a way to activate through other means (just a musing of some immunologists).IBS d-types have over and over been shown to have symptoms provocable with specific dietary components, and the symptoms ablate when mast cell stabilizers are used....and mast cell mediators can be and have been retrieved from the isolated and food challenged small bowel. There were no parasites present and there was no detecible IgE allergy by conventional gel & Coombs definition and associated standard alelrgy tests...as the patients with negative testing for specific IgE are preidentified and either accounted for or removed.In the most recent investigation by one of the worlds most respected teams in a highly regarded institution in Sweden, IgE was also recovered from the small bowel to their great surpise along with the mast cell and non-mast cell mediators.Some elements of the medical community can go on forever ignoring this....it is sort of like the Islamic extremist response to yesterdays Bin laden tape: "It's a fabrication!!! It's fake! American Devils!" etc.
yeah yeah yeah rag on, rag on.My personal sympathies go out to those patients unfortunate enough to be guided by such myopic views of their symptoms.This statement falls into the RES IPSA LOQUITUR category.... _____________________________________"There is a histamine 3 receptor and some people are looking into blocking it. If that works pans out, it may lead to a drug. Drug development takes a lot of time and a lot of luck. " _______________________________________...and it takes spending twice as much on marketing as on research: 39% of revenues, or $14 billion per year, on marketing and sales costs to support 70,000 sales reps averaging $140,000 per year income each so as to maintain your position as the most profitable industry in the world, and to be sure to maintain the lobbyists and PACS who will help you retain your pork-barrel tax package which allows your industry to write off all the advertising and sales dollars unlike every other industry in the USA which much EAT those costs as opertaing costs, so you can finish FY 2000 with an overall pretax profit rate of 18.6% which is even higher than banks with 15.8%....on $99.6 BILLION in sales. [NOTE that most of the money pharmaceutical firms spend on research is for "me-too" drug development not new drugs sunce, as this post states flaty, they might not pan out. Too much risk. Instead we end up with such things as FIVE different branded statins on the market with more in the pipe which all work about the same...or a dozen different NSIADS...etc.]If the line of investigation is driven solely by drug development as the end-game then the information gleaned is gathered and interpreted solely in that selective context. Thus the context of the entire post. This is reflective of all that is wrong about IBS research in the United States. The only parts we get right are the parts that focus on how to find bodily functions which can be modified by commercially viable pharmacotherspies. All else is dismissed as it detracts from this specific end-game. --------------------------KMOTTUS makes an interesting observation: ___________________________________"The drug companies have been there done that. As far as I know there is nothing preventing wider usage of these drugs." ____________________________________The use of GATSROCROM I belive for IBS therapy would be an off-label use indeed. But the real thing that stands in the way of use of sodium cromoglycate for IBS isa) The studies on its effectiveness have been done in large part overseas, mostly Italy, and have not been widely read among the physician who manage IBS patients in the USA.
Even if they were, and patients with IBS -d and cyclics were placed on Gastrocrom in many cases tachyphylaxis becomes a problem...and once that sets in the protocol is worse than nothing at all as the patient is trapped by higher and higher dosing to get the same degree of relief and then, if no work has been done to isolate the provoking foods and chemicals before the therapy started, there is no prophylaxis to fallback to (no effective elimination diet specific to the patient)This is why people are looking to other natural substances with known immunomodulating qualities seeking better solutions. __________________________________"there must be more to it than getting rid of mast cells, otherwise it wouldhave been tried before?" ___________________________________By "getting rid" I asume you men attenuating mast cell response. Now there is more to it, and I pointed to part of it, as the mast cell is not the only immunocyte involved in the aberrant immune response in IBS and migraine and the like...lymphocytes, granulocyte classes, and platelets are also involved in the raction. Think of the mast cells as one of the bigger players though.And it has been done before...several times...mostly in Italy. In one study (I am doing this from memeory I will have to go look it up) on IBS-d type kids (it was a pretty good sized sample as I recall)they found that about 8% of them had actual confirmed comorbid IgE allergy (the SPT rate was about 17% and its only 40% positive predictive of allergy so that makes the actual comorbidity maybe 8%) and the rest did not yet they were positive to oral challenge on certain staple foods they tested as the kids responded with symptom reduction to one of the "statistical probability based" elimination diets, almost 90%.They also responded short term (30 days) to cromolyn sodium at a very high rate, over 90% I recall HEY I REMEMBER WHERE I PUT THE ABSRACT HOLD ON...
[elevator music interlude} _____________________________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: � Clinical Trial � Multicenter Study _________________________________At the risk of being repetitious, this was done a number of times and always with the same results..short term. It was then, in Europe, practitioners started using CS that the problem with tachyphylaxis cropped up. Brostoff has said to me that this is why the therapy ultimately was not efficacious, but it pointed the way to more investigation of immunomodulation therapy that has been going on with alternatives which might be as effective but not produce tachyphylaxis. ______________________________"trbell, I'm not so sure suppressing the immune system cells for any length of time is a good idea. Mast cells in the digestion are the defense against any bugs we swallow - suppressing them could lead to massive infections. Personally I'd rather have IBS or even allergies. " ______________________________This is a good point, Julia, and one that the people experimenting with immunomodulation have to take into account. Ther is a fine line between IMMUNOMODULATION (attenuating the aberrant immunocyte response or damping the excessive reactivity without interfering with normal humoral and cellular immune response to pathogens). It is possible to overdo it. In the west, however, the chance of damping the mast cell response so much that the parasite protection is blocked is less likely than overattenuating the cellular immune responses which protect against the more common pathogens (bacteria and virus).This area of investigation, except for CS which is well documented, is not new but this application is new. But it is one of the areas of promise among non-drug related therapies. _______________________________OHNOYOUTOO:
I am SOOOOO glad to hear that you are making progress so soon, as you, Like WashoeLisa who posted her whole case in thread on this board last year, were quite quite ill as you have posted before. Be prepared, however, to possibly be dismissed and insulted as Lisa was by certain elements of the community whose motivations lie elsewhere. Lisa, who is also the Digestive Disease Community Moderator in AmericasDoctor.com (and her father is the Chairman of the Board of one of the most prominent private hospital groups in California, so her case was under very close scrutiny) had severe IBS and Fibromyalgia and achieved 100% remission and drug freedom within 60 days on her LEAP lifetyle plan). So did her daughter with refractory eczema.You may even be called a SHILL and a FAKER that MNL PLANTED here...or that you are experiencing the (now debunked) magical placebo effect.
However, you will also find MORE support and confirmation from many lucky people here that isolation and elimination of dietary provoking agents has brought alot of help to many people here, regardless of how they arrived at their beneficial dietary changes.Stick 100% to the plan to get the best results. Cannot take ANY of the forbidden foods (sigh) as it is unclear exactly what the provoking dose is of each except in realtive terms to each other within your body. But I know you will!! Keep on keeping on...and OUT of the ER!!!
I am proud of your will power so far!!!!Eat well. Think well. Be well. Type well. Or at least better than:MNL
 
Julia....sorry I made it sound a might more definitive than it is vis a vis mast cells parasites et al. To be more specific most immunology texts base the supposition of primary function as protection against parasites based upon the degree of understanding, so far, of what they respond to immunologically. This is just usually classified as what they BELEIVE their PRIMARY function was evolved to be.
Oh, here are a couple of the things other people made up about mast cells, then a very list of some papers about the the integrative neuroimmune side of mast cell regulation vs. the immunologic mast cell function (which, by the way, is not made up, if you read any textbook on immunology the immunologic mechanisms for mast cell dgeranulation are described in a far more complicated and thorough fashion than I disclosed). ________________________________First lets go back and look again for a second at the reults of adminstering a drug which stabilizes mast cells in kids with IBS...somehow that got missed since it is claimed that I make things up: ________________________________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: � Clinical Trial � Multicenter Study _____________________________________BRIEF DISCUSSION: Half the kids had a family history of atopy, but only 17% came of SPT positive for any of the comon foodstiffs tested. SPT is about 40% to 50% positivively predictive (JAMA) so that means the comorbdity rate in the subjects of possible actual food allergy was 6-8%. 87% experienced symptom reduction with an elimination diet based solely on the statistical probabilities of low reactivity, as no in vitro assay was available at that time to the investigators which could detect non-Ig[x] mediated reactions. This reflects a well thought out diet, that eliminated enough of the reactive foods that almost 9 out of 10 experienced significant symptom reduction.Of the group treated with cromolyn sodium, a substance developed for asthma because it stabilizes mast cells [at LEAST as far back as I can remember first using it on asthmatics at the Cleveland Clinic where I was supervisor of pulmonary care in their med/surg intensive care units and their staff instructor in pulmonary care: 1973] was 97%. When only 8% had a high probability of detectible circulating specific immunoglobulin to foods.Duh....again....ignoring this is akin to the folks who said "Osama was not talking about the Twin Towers. You lie! You deceive! The tape was made 2 years ago and he and the Sheik of Arabi are talking about his sons wedding!!!" Double duh. _______________________________________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: � Clinical trial � Multicenter study � Randomized controlled trial _______________________________________In this case two intersting observations, when one has the whole paper, is that the elimionation diet the Stefanini used was not as well matched to the reaction profile of the patients, and his compliance measures were not as strict as the ped's study where the childrens compliance could be strictly controlled. Yet they still achieved a rate of 60% of the patients responded in spite of the looser dietary controls.Interstingly, 67% again responded to cromolyn sodium. At the time the study was reported there was some debate as to whether this reflected that IBS in kids and IBS in adults (D-type) suggested different mechanisms...less mast cell immunocyte involvement since CS is very effective on mast cells but only moderately effective on granulocytes (one study found a reduction in granulcyte response of about 17%). Actually, Stefanini used a different dosing protocol...he did not give them enough CS at 1500mg/day when the kids got 63mg/kg/day. A 60 pound kid is, what?, 60/2.2 = 27 kg. x 63mg = 1700 mg/day dose. So many of the patients received a sub-therapeutic dose and even the lighter wright patients were dosed to a degree that produced less mast cell stabilizaton.The lesson here was...crank it up.
________________________________: Neurogastroenterol Motil 2000 Oct;12(5):449-57 Increased mast cells in the irritable bowel syndrome.O'Sullivan M, Clayton N, Breslin NP, Harman I, Bountra C, McLaren A, O'Morain CAAdelaide & Meath Hospitals, Trinity College Dublin, Ireland; GlaxoWellcome Medicines Research Centre, Stevenage, UK.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 COLON OF] 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. ____________________________There are two types of mast cells (the mucosal mast cell and the connective tissue mast cell)tiswhich arise from the same common progenitor cell (myeloid) in the bone marrow as the other granulocytes (neutrophils, eosinophils, basophils). They "migrate" depending upon the stimuli, and take up residence at specific sites. When you find increased mast cell density in the mucosa of the upper colon (cecum) this is a smoking-gun for this being a site of chronic provocation....so something coming out of the small intestine chronically in these IBS patients is provoking reactions at the place where the two join often enough and long enough that the tissue density of mast cells has increased.In addition to the mediator effects previously discussed from mast cell degranulation, the combined effects of the chemical mediators released by mast cells is to attract circulating leukocytes to the site of mast-cell activation. This is not happening in the lower colon as again is confirmed since there is no sign of this activity found as always in the colon. But up where the colon meets the small bowel there is sign of a problem coming from upstream. So what happened when investigators started looking upstream recently in patients with IBS symptoms provoked by food which is complementary to the fact that mast cells are being degranulated by foods in the absence of detectible specific circulating IgE and it is clearly reversible if you avoid the right foods and the more cromolyn sodium (mast cell stabilizer) you give people... ____________________________Tornblom H, Lindberg G, Nyberg B, Veress B.Histopathological findings in jejunum of patients with severe irritable bowel syndrome. Program and abstracts of Digestive Disease Week; May 21-24, 2000; San Diego, California. Abstract 3840. "Dr. Hans Tornblom and colleagues[8] from the University of Lund in Malmo, Sweden, reported direct evidence of inflammation in IBS. They examined 6 patients with documented, severe IBS. These patients fulfilled the Rome criteria and had normal antro-duodenal manometry, implying they were not misdiagnosed cases of chronic idiopathic intestinal pseudo-obstruction. At laparoscopy, full-thickness biopsies from the proximal jejunum were obtained. In all 6 patients, inflammatory infiltration of lymphocytes in the myenteric plexus was observed. These lymphocytes were situated in peri- and intraganglionic locations. The authors also noted hypertrophy of the longitudinal muscle layer in 4 patients and abnormalities in the interstitial cells of the Cajal (the pacemakers of the gut) in 5 patients. These results are provocative. The major concern remains misdiagnosis of pseudo-obstruction. Furthermore, it is unclear whether these results can be generalized to all IBS patients." [comments on presentation made by Nicholas Talley, MD] ____________________________In answer to the query, at least in D-types and cyclics the findings can be generalized, as Bengtssons work at Sahlgrens Medical Univerisity is confirming, as we finally have in vivo findings of the aberant immune response in IBS to accompany eyars of in vitro findings and clinical observation. Again, WHY is far from clear but what the several mechanisms are which provokes it are abundantly clear.When Professor Bengtsson first began using jejunal isolation and washings analysis techniques back in the mid-90's he began by comparing patients who would get IBS-diarrheic symptoms provoked by various types of foods he etsted them with against those patients with known inflammatory diseases. Note that Bengtsoon, like Brostoff, Fell, Kaczmarski and many others in Europe that work with food alelrgy and intolerance, have the persitent predisposition to consider d-type IBS symptoms to not be an unexplainable phenomenon and label it "IBS": often they rather relate to IBS-d-type symptoms as food intolerance becasue that is what they find provokes it, and to what it responds preventively.This is the biggest of why some people are ignorant of work in this area, either by chance or by choice. They choose an opposing side in the war of words. A disservice to patients.Many of the practitioners in Europe who study and publish on this patient group, which comprises the bulk of what we call the "IBS population" (70% of it), are viewed from the perspective that they are suffering food intolerance symptoms, or sensitivity or whatever the wOrd du jour is, since they have ben successfully isolating and treating it that way all their profesional adult lives. *There were some American immunlogists and allergists who collaborated with this group as well, but they are older and in "emeritus" roles for the most part (Sandgerg, Bellanti) and some do not work with IBS food intolerancE patients, rather have focused on autism or ADD for personal reasons (Kniker, James).So some people do not read a paper unles the word "IBS" is in it, and the work they miss becomes analagous to the tree which falls in the forest but they are not there to hear it. And their answer to that riddle is, of course, it makes no sound, it does not exist.So this line of investigation does not exist in that persons world, and MNL makes it all up. Their nomenclature is different (by choice) even though the patient selection is the same and thus words rather than symptoms are used to apply selective thinking. Not very good clinical thinking.Now what Bengtsson et al found in the beginning was surprising, as inflammtory mediators were consiStently recovered from the small bowel of BOTH patient groups. This is an abstract of a tutorial about his work where he briefly describes his initial surprising findings: ____________________________Lakartidningen 1994 May 11;91(19):1941-6 Segmental intestinal perfusion. A "new" technique for human studies.[Article in Swedish]Knutson L, Hallgren R, Ahrenstedt O, Bengtsson U, Lavo B, Lennernas H, Wilhelmsson-Knutson TKirurgiska kliniken, Akademiska sjukhuset, Uppsala.Intestinal release of inflammatory mediators and permeation of macromolecules were studied in patients suffering from Crohn's disease, celiac disease and food intolerance with the use of a system for segmental intestinal perfusion. Drug absorption and ion and bicarbonate transport were also studied in healthy subjects. Patients with Crohn's disease of the distal ileum revealed an increased release of inflammatory agents into the lumen of the proximal jejunum. Luminal provocation with different antigens in cases of celiac disease and food intolerance not only activated cells in the intestinal mucosa but also increased the leakage from plasma and lymph. Studies of drug absorption elucidated the kinetics of drug transport from intestine to plasma, and basal neurologic effects on ion and bicarbonate transport were determined.Tutorial Review ____________________________res ipsa loquitur.In this NEXT study, Bengtson takes people whose symptoms of diarrhea, gas, bloating etc. are provoked my cow milk, and assesses the small bowel. first he confirms they do not test allergy positive for milk so that he is not investigating milk allergy. Since we know perhaps a few IBS patients have problems with cow milk and milk products, have no detectible milk allergy, and have no lactose intolerance (and if they did they could correct it with Lactaid)...what did he "imagine" finding in the milk provoked patients? Let's peek.... __________________________J Allergy Clin Immunol 1997 Aug;100(2):216-21 Eosinophil cationic protein and histamine after intestinal challenge in patients with cow's milk intolerance.Bengtsson U, Knutson TW, Knutson L, Dannaeus A, Hallgren R, Ahlstedt SAsthma and Allergy Research Center, Sahlgrens' Hospital, Goteborg, Sweden.BACKGROUND: Mast cells and eosinophils are key cells in the development of active symptoms in allergic diseases and other inflammatory conditions, and they mediate their action through the release of very potent granule constituents. METHODS: Five patients with milk-related gastrointestinal symptoms diagnosed by double-blind placebo-controlled milk challenges, but with negative responses to skin prick tests and RASTs with milk, and eight healthy control subjects were investigated. Repeated perfusion studies were performed with a two-balloon, six-channel tube by using milk, casein, and whey as antigens. Luminal eosinophil cationic protein, histamine, and albumin were measured by radioimmunoassay. RESULTS: Luminal cow's milk induced a pronounced increase in intestinal secretion of histamine and eosinophil cationic protein in patients, but not control subjects, during the first 20 minutes after challenge (histamine from 123 +/- 12 to 543 +/- 175 ng/cm, hr; eosinophil cationic protein from 80 +/- 23 to 686 +/- 262 ng/cm, hr). Albumin, as a marker of plasma leakage, was also significantly increased. CONCLUSION: These data indicate that mast cells and eosinophils are effector cells not only in patients with allergic disease but also in patients intolerant to foods and lacking circulating antibodies. The underlying mechanisms may be a reaction mediated by locally appearing antibodies or an immunologic activation resembling that found in intestinal disorders such as celiac disease. ___________________________________So if you are among the milk sensitive but are test negative for milk allergy and lactose intolerance, one should consider these findings as significant.
The increase in intraluminal albumin is significant. Thats a big damn molecule and links well with some of Brostoffs discussions concerning altered permeability in rsponse to proinflammatory mediators in the bowel and thje formation of immune complexes which can precipitate and additional set of alternate pathways in food reactivity.Oh there's lots more but trying to stay close to the core of the subject and my time is past run out. This is an excerpt from an email I received from Professor Bengtsson while communicating with him to keep up with his present work. waiting for publication puts one way out of sync so we try to keep in touch as you know with allergists and immunologists doing parallel work.The letter reads in part: _______________________________"...I think you have seen my papers from 1996and 1997 when we studied allergy-like inflammation in a closed segment in jejunum. When challenged with different staple foods [we] could show high levels of inflammatory mediators suggesting allergy-like inflammation. Most of these adult patients had IBS-likesymptoms with negative skin prick test and RAST but DBPCFC were positive. However, the method was time-consuming and expensive so we went on with immunohistocheminstry methods with Biopsies from duodenum before and during challenges. In a near future we hope to publish our results. Even here we can show an allergy-like inflammation during challenges, with parameters like Il-4, IFN-gamma, CD3, CD4, CD8 and IgE....I hope we can keep contact and later on discuss how to develop better methods to investige patients with food problems. Looking for your comments.Sincerely YoursUlf BengtssonMD, PhD ______________________________Now one should go and study up on these mediators, where they come from, what they do, etc. and one can maybe perhaps start to get an inkling of what it is we are talking about.
Once this material is famliar territory, one then needs to venture into the studies on abnormal peptides in the small bowel of IBS patients, then study what regulates that componenet and its role in gut management, then link that with any of several turorials on neuroimmune interractivity so as to have the ability to keep that part of the equation in perspective.Some good papers to read on neurimmune and mediator interconnectvity in the gut are:1. Z Gastroenterol 1995 Apr;33(4):219-24Neuroimmune interactions in the gastrointestinal tract. [Article in German]Frieling T, Strohmeyer GAbteilung fur Gastroenterologie, Heinrich-Heine-Universitat Dusseldorf.2.Vet Res 1996;27(4-5):427-42 Integrative neuroimmunology of the digestive tract. Theodorou V, Fioramonti J, Bueno L Ecole superieure d'agriculture de Purpan, Toulouse, France.3. Reprod Nutr Dev 1994;34(6):513-25Neurohormonal control of intestinal transit.Bueno L, Fioramonti J.INRA, Department of Pharmacology, Toulouse, France.4.Nippon Rinsho 1998 Sep;56(9):2228-34 Related Articles, Books Mucosal immune system of the intestine.Miura S, Fujimori H, Koseki S, Hokari R.Second Department of Internal Medicine, National Defense Medical College.5.1: Can J Gastroenterol 1999 Mar;13 Suppl A:42A-46aEffects of inflammatory mediators on gut sensitivity. Bueno L, Fioramonti J Department of Pharmacology, INRA, Toulouse, France. ________________________________________Oy, if only we had the time to go on trhere is so much more ....it's better to get the books I recommend since those are written by immunologists who actually know all this stuff, or maybe they make it up as they go along.
THIS IS FOR YOU OHNOYOKOONO: ________________________________Adv Pediatr 2000;47:11Cyclic vomiting syndrome: evolution in our understanding of a brain-gut disorder.Li BU, Balint JP.Ohio State University, USA.Cyclic vomiting syndrome (CVS) remains a mysterious disorder despite our increasing knowledge since its classic description by Gee in 1882. Its hallmark feature of recurrent, explosive bouts of vomiting punctuating periods of normal health causes substantial medical morbidity (50% of patients require intravenous therapy), as well as significant time lost from school (20 school absences per year) and work. Limited epidemiologic data indicate that CVS may occur more commonly than previously thought, affecting as many as 1.9% of school-aged children. Besides the relentless vomiting, the child usually has pallor (87%), lethargy (91%), anorexia (74%), nausea (72%), and abdominal pain (80%). There is evidence of clinical and physiologic overlap among CVS, abdominal migraine, and migraine headaches. We propose revised criteria for abdominal migraine that include pain as the predominant and consistent symptom, lack of abnormal screening tests, and in retrospect, either subsequent development of migraines or positive response to antimigraine medication. Besides migraines, other etiologic possibilities include mitochondrial DNA mutations, ion channelopathies, excessive hypothalamic-pituitary-adrenal axis activation, and heightened autonomic reactivity. The differential diagnosis includes idiopathic CVS (88%); gastrointestinal disorders (7%), including serious surgical disorders (e.g., malrotation); and extraintestinal disorders (5%), including serious surgical (brain stem neoplasm) and metabolic disorders (e.g., fatty acid oxidation disorder). Within the idiopathic group, there may be migraine, Sato's neuroendocrine, mitochondrial, and other subgroups. Treatment includes avoidance of triggers [YOU ARE ON YOUR WAY], prophylactic medication, supportive care, abortive medication, and family support. In the future, investigation into mitochondrial DNA mutations, ion channel defects, corticotropin-releasing factor, and serotonin and tachykinin receptor physiology and pharmacology may help discover the etiology and pathogenesis of this disorder. __________________________________Hey guess what? One of the first and most chalLenginG cases we had when we first developed this test and diet was a poor kid from Boca Raton who had Cyclic Vomiting Syndrome. He was so sick he made the papers. No one could help him. He took an early version of the new MRT and was one of the first trial LEAP subjects. He was reactive to a number of things in his diet, esp. certain food additives. His cycle wAs broken within 30 days of starting the diet. When he reintroduced the forbidden stuff when mom was not looking his symptoms would return.
But of course I made that up toO. Damn I am good at this lying thing!!! So MANY PEOPLe we have LIED right out of their symptoms!!!
Gotta run....Eat well. Think Well. Be well. Type well.Fib well.
MNL
 
Julia....sorry I made it sound a might more definitive than it is vis a vis mast cells parasites et al. To be more specific most immunology texts base the supposition of primary function as protection against parasites based upon the degree of understanding, so far, of what they respond to immunologically. This is just usually classified as what they BELEIVE their PRIMARY function was evolved to be.
Oh, here are a couple of the things other people made up about mast cells, then a very list of some papers about the the integrative neuroimmune side of mast cell regulation vs. the immunologic mast cell function (which, by the way, is not made up, if you read any textbook on immunology the immunologic mechanisms for mast cell dgeranulation are described in a far more complicated and thorough fashion than I disclosed). ________________________________First lets go back and look again for a second at the reults of adminstering a drug which stabilizes mast cells in kids with IBS...somehow that got missed since it is claimed that I make things up: ________________________________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: � Clinical Trial � Multicenter Study _____________________________________BRIEF DISCUSSION: Half the kids had a family history of atopy, but only 17% came of SPT positive for any of the comon foodstiffs tested. SPT is about 40% to 50% positivively predictive (JAMA) so that means the comorbdity rate in the subjects of possible actual food allergy was 6-8%. 87% experienced symptom reduction with an elimination diet based solely on the statistical probabilities of low reactivity, as no in vitro assay was available at that time to the investigators which could detect non-Ig[x] mediated reactions. This reflects a well thought out diet, that eliminated enough of the reactive foods that almost 9 out of 10 experienced significant symptom reduction.Of the group treated with cromolyn sodium, a substance developed for asthma because it stabilizes mast cells [at LEAST as far back as I can remember first using it on asthmatics at the Cleveland Clinic where I was supervisor of pulmonary care in their med/surg intensive care units and their staff instructor in pulmonary care: 1973] was 97%. When only 8% had a high probability of detectible circulating specific immunoglobulin to foods.Duh....again....ignoring this is akin to the folks who said "Osama was not talking about the Twin Towers. You lie! You deceive! The tape was made 2 years ago and he and the Sheik of Arabi are talking about his sons wedding!!!" Double duh. _______________________________________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: � Clinical trial � Multicenter study � Randomized controlled trial _______________________________________In this case two intersting observations, when one has the whole paper, is that the elimionation diet the Stefanini used was not as well matched to the reaction profile of the patients, and his compliance measures were not as strict as the ped's study where the childrens compliance could be strictly controlled. Yet they still achieved a rate of 60% of the patients responded in spite of the looser dietary controls.Interstingly, 67% again responded to cromolyn sodium. At the time the study was reported there was some debate as to whether this reflected that IBS in kids and IBS in adults (D-type) suggested different mechanisms...less mast cell immunocyte involvement since CS is very effective on mast cells but only moderately effective on granulocytes (one study found a reduction in granulcyte response of about 17%). Actually, Stefanini used a different dosing protocol...he did not give them enough CS at 1500mg/day when the kids got 63mg/kg/day. A 60 pound kid is, what?, 60/2.2 = 27 kg. x 63mg = 1700 mg/day dose. So many of the patients received a sub-therapeutic dose and even the lighter wright patients were dosed to a degree that produced less mast cell stabilizaton.The lesson here was...crank it up.
________________________________: Neurogastroenterol Motil 2000 Oct;12(5):449-57 Increased mast cells in the irritable bowel syndrome.O'Sullivan M, Clayton N, Breslin NP, Harman I, Bountra C, McLaren A, O'Morain CAAdelaide & Meath Hospitals, Trinity College Dublin, Ireland; GlaxoWellcome Medicines Research Centre, Stevenage, UK.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 COLON OF] 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. ____________________________There are two types of mast cells (the mucosal mast cell and the connective tissue mast cell)tiswhich arise from the same common progenitor cell (myeloid) in the bone marrow as the other granulocytes (neutrophils, eosinophils, basophils). They "migrate" depending upon the stimuli, and take up residence at specific sites. When you find increased mast cell density in the mucosa of the upper colon (cecum) this is a smoking-gun for this being a site of chronic provocation....so something coming out of the small intestine chronically in these IBS patients is provoking reactions at the place where the two join often enough and long enough that the tissue density of mast cells has increased.In addition to the mediator effects previously discussed from mast cell degranulation, the combined effects of the chemical mediators released by mast cells is to attract circulating leukocytes to the site of mast-cell activation. This is not happening in the lower colon as again is confirmed since there is no sign of this activity found as always in the colon. But up where the colon meets the small bowel there is sign of a problem coming from upstream. So what happened when investigators started looking upstream recently in patients with IBS symptoms provoked by food which is complementary to the fact that mast cells are being degranulated by foods in the absence of detectible specific circulating IgE and it is clearly reversible if you avoid the right foods and the more cromolyn sodium (mast cell stabilizer) you give people... ____________________________Tornblom H, Lindberg G, Nyberg B, Veress B.Histopathological findings in jejunum of patients with severe irritable bowel syndrome. Program and abstracts of Digestive Disease Week; May 21-24, 2000; San Diego, California. Abstract 3840. "Dr. Hans Tornblom and colleagues[8] from the University of Lund in Malmo, Sweden, reported direct evidence of inflammation in IBS. They examined 6 patients with documented, severe IBS. These patients fulfilled the Rome criteria and had normal antro-duodenal manometry, implying they were not misdiagnosed cases of chronic idiopathic intestinal pseudo-obstruction. At laparoscopy, full-thickness biopsies from the proximal jejunum were obtained. In all 6 patients, inflammatory infiltration of lymphocytes in the myenteric plexus was observed. These lymphocytes were situated in peri- and intraganglionic locations. The authors also noted hypertrophy of the longitudinal muscle layer in 4 patients and abnormalities in the interstitial cells of the Cajal (the pacemakers of the gut) in 5 patients. These results are provocative. The major concern remains misdiagnosis of pseudo-obstruction. Furthermore, it is unclear whether these results can be generalized to all IBS patients." [comments on presentation made by Nicholas Talley, MD] ____________________________In answer to the query, at least in D-types and cyclics the findings can be generalized, as Bengtssons work at Sahlgrens Medical Univerisity is confirming, as we finally have in vivo findings of the aberant immune response in IBS to accompany eyars of in vitro findings and clinical observation. Again, WHY is far from clear but what the several mechanisms are which provokes it are abundantly clear.When Professor Bengtsson first began using jejunal isolation and washings analysis techniques back in the mid-90's he began by comparing patients who would get IBS-diarrheic symptoms provoked by various types of foods he etsted them with against those patients with known inflammatory diseases. Note that Bengtsoon, like Brostoff, Fell, Kaczmarski and many others in Europe that work with food alelrgy and intolerance, have the persitent predisposition to consider d-type IBS symptoms to not be an unexplainable phenomenon and label it "IBS": often they rather relate to IBS-d-type symptoms as food intolerance becasue that is what they find provokes it, and to what it responds preventively.This is the biggest of why some people are ignorant of work in this area, either by chance or by choice. They choose an opposing side in the war of words. A disservice to patients.Many of the practitioners in Europe who study and publish on this patient group, which comprises the bulk of what we call the "IBS population" (70% of it), are viewed from the perspective that they are suffering food intolerance symptoms, or sensitivity or whatever the wOrd du jour is, since they have ben successfully isolating and treating it that way all their profesional adult lives. *There were some American immunlogists and allergists who collaborated with this group as well, but they are older and in "emeritus" roles for the most part (Sandgerg, Bellanti) and some do not work with IBS food intolerancE patients, rather have focused on autism or ADD for personal reasons (Kniker, James).So some people do not read a paper unles the word "IBS" is in it, and the work they miss becomes analagous to the tree which falls in the forest but they are not there to hear it. And their answer to that riddle is, of course, it makes no sound, it does not exist.So this line of investigation does not exist in that persons world, and MNL makes it all up. Their nomenclature is different (by choice) even though the patient selection is the same and thus words rather than symptoms are used to apply selective thinking. Not very good clinical thinking.Now what Bengtsson et al found in the beginning was surprising, as inflammtory mediators were consiStently recovered from the small bowel of BOTH patient groups. This is an abstract of a tutorial about his work where he briefly describes his initial surprising findings: ____________________________Lakartidningen 1994 May 11;91(19):1941-6 Segmental intestinal perfusion. A "new" technique for human studies.[Article in Swedish]Knutson L, Hallgren R, Ahrenstedt O, Bengtsson U, Lavo B, Lennernas H, Wilhelmsson-Knutson TKirurgiska kliniken, Akademiska sjukhuset, Uppsala.Intestinal release of inflammatory mediators and permeation of macromolecules were studied in patients suffering from Crohn's disease, celiac disease and food intolerance with the use of a system for segmental intestinal perfusion. Drug absorption and ion and bicarbonate transport were also studied in healthy subjects. Patients with Crohn's disease of the distal ileum revealed an increased release of inflammatory agents into the lumen of the proximal jejunum. Luminal provocation with different antigens in cases of celiac disease and food intolerance not only activated cells in the intestinal mucosa but also increased the leakage from plasma and lymph. Studies of drug absorption elucidated the kinetics of drug transport from intestine to plasma, and basal neurologic effects on ion and bicarbonate transport were determined.Tutorial Review ____________________________res ipsa loquitur.In this NEXT study, Bengtson takes people whose symptoms of diarrhea, gas, bloating etc. are provoked my cow milk, and assesses the small bowel. first he confirms they do not test allergy positive for milk so that he is not investigating milk allergy. Since we know perhaps a few IBS patients have problems with cow milk and milk products, have no detectible milk allergy, and have no lactose intolerance (and if they did they could correct it with Lactaid)...what did he "imagine" finding in the milk provoked patients? Let's peek.... __________________________J Allergy Clin Immunol 1997 Aug;100(2):216-21 Eosinophil cationic protein and histamine after intestinal challenge in patients with cow's milk intolerance.Bengtsson U, Knutson TW, Knutson L, Dannaeus A, Hallgren R, Ahlstedt SAsthma and Allergy Research Center, Sahlgrens' Hospital, Goteborg, Sweden.BACKGROUND: Mast cells and eosinophils are key cells in the development of active symptoms in allergic diseases and other inflammatory conditions, and they mediate their action through the release of very potent granule constituents. METHODS: Five patients with milk-related gastrointestinal symptoms diagnosed by double-blind placebo-controlled milk challenges, but with negative responses to skin prick tests and RASTs with milk, and eight healthy control subjects were investigated. Repeated perfusion studies were performed with a two-balloon, six-channel tube by using milk, casein, and whey as antigens. Luminal eosinophil cationic protein, histamine, and albumin were measured by radioimmunoassay. RESULTS: Luminal cow's milk induced a pronounced increase in intestinal secretion of histamine and eosinophil cationic protein in patients, but not control subjects, during the first 20 minutes after challenge (histamine from 123 +/- 12 to 543 +/- 175 ng/cm, hr; eosinophil cationic protein from 80 +/- 23 to 686 +/- 262 ng/cm, hr). Albumin, as a marker of plasma leakage, was also significantly increased. CONCLUSION: These data indicate that mast cells and eosinophils are effector cells not only in patients with allergic disease but also in patients intolerant to foods and lacking circulating antibodies. The underlying mechanisms may be a reaction mediated by locally appearing antibodies or an immunologic activation resembling that found in intestinal disorders such as celiac disease. ___________________________________So if you are among the milk sensitive but are test negative for milk allergy and lactose intolerance, one should consider these findings as significant.
The increase in intraluminal albumin is significant. Thats a big damn molecule and links well with some of Brostoffs discussions concerning altered permeability in rsponse to proinflammatory mediators in the bowel and thje formation of immune complexes which can precipitate and additional set of alternate pathways in food reactivity.Oh there's lots more but trying to stay close to the core of the subject and my time is past run out. This is an excerpt from an email I received from Professor Bengtsson while communicating with him to keep up with his present work. waiting for publication puts one way out of sync so we try to keep in touch as you know with allergists and immunologists doing parallel work.The letter reads in part: _______________________________"...I think you have seen my papers from 1996and 1997 when we studied allergy-like inflammation in a closed segment in jejunum. When challenged with different staple foods [we] could show high levels of inflammatory mediators suggesting allergy-like inflammation. Most of these adult patients had IBS-likesymptoms with negative skin prick test and RAST but DBPCFC were positive. However, the method was time-consuming and expensive so we went on with immunohistocheminstry methods with Biopsies from duodenum before and during challenges. In a near future we hope to publish our results. Even here we can show an allergy-like inflammation during challenges, with parameters like Il-4, IFN-gamma, CD3, CD4, CD8 and IgE....I hope we can keep contact and later on discuss how to develop better methods to investige patients with food problems. Looking for your comments.Sincerely YoursUlf BengtssonMD, PhD ______________________________Now one should go and study up on these mediators, where they come from, what they do, etc. and one can maybe perhaps start to get an inkling of what it is we are talking about.
Once this material is famliar territory, one then needs to venture into the studies on abnormal peptides in the small bowel of IBS patients, then study what regulates that componenet and its role in gut management, then link that with any of several turorials on neuroimmune interractivity so as to have the ability to keep that part of the equation in perspective.Some good papers to read on neurimmune and mediator interconnectvity in the gut are:1. Z Gastroenterol 1995 Apr;33(4):219-24Neuroimmune interactions in the gastrointestinal tract. [Article in German]Frieling T, Strohmeyer GAbteilung fur Gastroenterologie, Heinrich-Heine-Universitat Dusseldorf.2.Vet Res 1996;27(4-5):427-42 Integrative neuroimmunology of the digestive tract. Theodorou V, Fioramonti J, Bueno L Ecole superieure d'agriculture de Purpan, Toulouse, France.3. Reprod Nutr Dev 1994;34(6):513-25Neurohormonal control of intestinal transit.Bueno L, Fioramonti J.INRA, Department of Pharmacology, Toulouse, France.4.Nippon Rinsho 1998 Sep;56(9):2228-34 Related Articles, Books Mucosal immune system of the intestine.Miura S, Fujimori H, Koseki S, Hokari R.Second Department of Internal Medicine, National Defense Medical College.5.1: Can J Gastroenterol 1999 Mar;13 Suppl A:42A-46aEffects of inflammatory mediators on gut sensitivity. Bueno L, Fioramonti J Department of Pharmacology, INRA, Toulouse, France. ________________________________________Oy, if only we had the time to go on trhere is so much more ....it's better to get the books I recommend since those are written by immunologists who actually know all this stuff, or maybe they make it up as they go along.
THIS IS FOR YOU OHNOYOKOONO: ________________________________Adv Pediatr 2000;47:11Cyclic vomiting syndrome: evolution in our understanding of a brain-gut disorder.Li BU, Balint JP.Ohio State University, USA.Cyclic vomiting syndrome (CVS) remains a mysterious disorder despite our increasing knowledge since its classic description by Gee in 1882. Its hallmark feature of recurrent, explosive bouts of vomiting punctuating periods of normal health causes substantial medical morbidity (50% of patients require intravenous therapy), as well as significant time lost from school (20 school absences per year) and work. Limited epidemiologic data indicate that CVS may occur more commonly than previously thought, affecting as many as 1.9% of school-aged children. Besides the relentless vomiting, the child usually has pallor (87%), lethargy (91%), anorexia (74%), nausea (72%), and abdominal pain (80%). There is evidence of clinical and physiologic overlap among CVS, abdominal migraine, and migraine headaches. We propose revised criteria for abdominal migraine that include pain as the predominant and consistent symptom, lack of abnormal screening tests, and in retrospect, either subsequent development of migraines or positive response to antimigraine medication. Besides migraines, other etiologic possibilities include mitochondrial DNA mutations, ion channelopathies, excessive hypothalamic-pituitary-adrenal axis activation, and heightened autonomic reactivity. The differential diagnosis includes idiopathic CVS (88%); gastrointestinal disorders (7%), including serious surgical disorders (e.g., malrotation); and extraintestinal disorders (5%), including serious surgical (brain stem neoplasm) and metabolic disorders (e.g., fatty acid oxidation disorder). Within the idiopathic group, there may be migraine, Sato's neuroendocrine, mitochondrial, and other subgroups. Treatment includes avoidance of triggers [YOU ARE ON YOUR WAY], prophylactic medication, supportive care, abortive medication, and family support. In the future, investigation into mitochondrial DNA mutations, ion channel defects, corticotropin-releasing factor, and serotonin and tachykinin receptor physiology and pharmacology may help discover the etiology and pathogenesis of this disorder. __________________________________Hey guess what? One of the first and most chalLenginG cases we had when we first developed this test and diet was a poor kid from Boca Raton who had Cyclic Vomiting Syndrome. He was so sick he made the papers. No one could help him. He took an early version of the new MRT and was one of the first trial LEAP subjects. He was reactive to a number of things in his diet, esp. certain food additives. His cycle wAs broken within 30 days of starting the diet. When he reintroduced the forbidden stuff when mom was not looking his symptoms would return.
But of course I made that up toO. Damn I am good at this lying thing!!! So MANY PEOPLe we have LIED right out of their symptoms!!!
Gotta run....Eat well. Think Well. Be well. Type well.Fib well.
MNL
 
Assertion: __________________________________"...the first notion something that has been an underpinning in IBS reseearch? " __________________________________Correction: An underpinning of all IBS research that is funded directly or indirectly by the pharmaceutical industry.The rest is pointless to engage in further discourse upon for reasons suggested by Tom's perceptions.... __________________________________"I really can't tell if you just don't understand or just pretend not to understand so you can argue with someone. " ___________________________________TR, Sometimes it's (a) and sometimes its (
neither of which are acceptable from persons who are healthcare professionals at any level. Since we are not addressing a healthcare profesional in some cases, sometimes such people consider themselves exempt from the rules that govern the behavior of healthcare professionals when interracting with sick people seeking help. This will not change, I assure you, regardless of the content of the exchanges with persons of that ilk.So this thread, like many others, confirms again the question is moot. The argument is perpetuated in this case by a person who admittedly has never read even one of the books I am talkign about, even the most simple book on the subject, much less the standard medical texts on the subject from authoritative sources vis a vis highly qualified allergists and immunologists who have studied the subject for decades. If a patient read [first] the (2) books I often refer to, the patient would gain a better understanding of the subject than I personally can convey within the time available to me and within this medium. there are quite a few around here who have done so and know this to be a fact from thier own personal experience. Yet they are deridied when they express that exprience. What folly to do so.
ALSO the good news is that finally the only physician-directed medical text on the subject ever published, which was produced and edited by Brostoff and Challacombe which was written in the first edition by perhaps 50+ allergists and immunlogists all over the world who are actually familiar with the subject "FOOD ALLERGY AND FOOD INTOLERANCE", which has been out of print, has a new edition nearly completed. It has been updated as much as was possible through the final edit (which is presently going on) and should be republished this year. This will be an excellent reference on the subject which it is hoped will thus provide a more reliable source of information from the worlds leaders in the field.Hmmmm....hey, wait, something posted leads me to beleive that the correct answer is
a consious choice has been made NOT to understand. The information conflicts with the presuppositions of his own, and the drug-company funded so called "IBS research" he relies upon as if it is the sole-source of information concerning the SYNDROME (which is not a disease....it is a group of overlapping etiologies like COPD which have not all been elucidated yet and as long as the majority of the research is funded by drug companies never will...all that will be understood is a portion of the physiology...that portion which can be intervened with pharmaceutically or by attenuative therapies which only address certain aspects of the phsyiology, therefore usually require pharmacotherpy to be provided as an adjunct thus perpetuating the realizable revenue stream which results from the clinical application of said drug-compny funded research). So welcome, my friend, welcome to the machine...AND to the worlds longest run-on sentence.
There is precise validity, however, in references to "people with other conditions". The whole field of so-called IBS research reflects the horrific error in thinking of the entire symptom-based approach to diagnosis and treatment. A HUGE population of people suffering from avoidable, reversible, aberrant immune response (the origins of which renain to be wholly understood) which can be provoked by dietary componenets are "diagnosed" as having a "functional condition" by primary care practitoners and specialists alike solely on the basis that everything they read int their respective journals drives diagnostics and treatment to that realm and perpetuates the mythology of "IBS".Its like the lost map...its not lost, it just has not been found yet, ecept by some, and their patients benefit from the finding of the map to preventive therapies. That does not make it Ponce deLeon's fairy tale, it makes it analagous to what COPD was 50 years ago: not yet fully understood. BUT avoidable from a symptom-provocation perspective.Work done from the phsychoneuro perspective begins to elucidate part of the physiology which is involved, and work done from the neuorimmune side elucidates another part. It is because they are treated as mutually exclusive we end up in the situation we are in: debating facts as if they are not facts, and confusing what is fact with what is theory based upon the objectives of who funded the particular information source. Since the work doen by those investigating the aberant immune response to dietary provocation in the small bowel runs afoul of the objectives of research funded by the drug industry it must be ignored regardless of how obvious it maybe. This is sort of like saying that I-75 does not really exist because you did not post the mile markers that all highways must have. Therefore, even though there are people driving up and down it successfully as we speak by the thousands, I will not acknoweldge its existence until the mile markers are added. TR, this foolishness has gone on as long as I can rememeber....and that is a long time.This debate over the undebatable is illustrative of what Hobbes wrote: "True and False are attributes of SPEECH not THINGS. Where speech is not there is neither truth for falsehood." This is "speech", albeit written word, but that which is debated is not imbued with the character of true or false since the phsyiology exists and is real.I have been in healthcare for over 30 years, and this whole 'Debate" which surrounds so called "IBS" is very far from the first such stupidly polarized debate over a syndrome that I have witnessed. The present situation is also far from the first time I have been involved on one side of such an issue or the other. The diference here is THIS debacle of IBS is highly personal.I was a victim of this foolishness my WHOLE life, from a child on into my 40's. That's a lotta damn suffering and alotta damn "experts" treating me from the same "learned sources" which contained not a 'nit' of information helpful to my condition. Not a morsel outside of more and more prescriptions or more and more "therapy" recommended for my "stress". USELESS. I got SO MUCH WORSE from this apprioach that by 40 the only solution offered to me was an interventional PARTIAL BOWEL RESECTION and PERMANENT COLOSTOMY. NO WAY JOSE.I was and remain (since I have yet to disapear from the planet) a walking talking venom-spewing testament to this. A victim of how research and teaching on the diagnosis and treatment of this condition has been conducted by the medical industry in the United States. I BECAME a beneficiary of knowledge which is COMPLEMENTARY to that which is promulgated by the drug-company-funded work preeminent in the US..BUT such information is treated, to the great disservice of millions of Amercan victims of IBS, as mutually exclusive...or "imaginary" or "made up".My REMISSION is not made up. My EXTREME-D EPISODES provoked by specific oral challenges is not a FAIRY TALE. MY degranulating leukocytes are not a FABRICATION. NOR are the thousands of others who have experienced the exact same thing as myself. And they will NOT be waved-away by ignorance.In the past, while I was actively involved in patient care, hospital managment, clinical research, product development, and teaching, since I had NO personal physical health "stake" in the situations, it was easy to be amused and aloof about how the "industry driven" machine works in healthcare in the USA. [Don't misunderstand the pharmaceutical industry is not the only driving wheel of the mechine, it is just the biggest, the same thing happens on the "hardware side" of healthcare technology].However, since I was a victim of this and have either observed or participated in the recovery of many many victims since I met doctors aproaching so called IBS and other "elusive" symptom sets from the caasal approach, I am unable to remain aloof about matters which I know are detrimental to the lives of fellow victims and patients when they occur in such a large forum of such victims and these are people who need HELP.While I apprecaite the suggestion I not allow myself to be drawn in to a rhetorical exchange with someone, please be assured I am not being "drawn" into anything by anyone or otherwise manipulated into responding...I am proactively compelled to address what I beleive is a disservice to the sick when I see it being perpetrated. It is a matter of personal ethics.And there is a lot of that going around. That being said, I am also fully aware that such people, whomever they are from practitioners to wannabes, are wholly unable to see themselves committing the disservice they do to those sick people who could be helped with some very simple methods...or maybe they are and they do it anyway, which is worse.
Seen that more times than I care to recall as well.Eat well. THINK well. Be well.MNL
 
Assertion: __________________________________"...the first notion something that has been an underpinning in IBS reseearch? " __________________________________Correction: An underpinning of all IBS research that is funded directly or indirectly by the pharmaceutical industry.The rest is pointless to engage in further discourse upon for reasons suggested by Tom's perceptions.... __________________________________"I really can't tell if you just don't understand or just pretend not to understand so you can argue with someone. " ___________________________________TR, Sometimes it's (a) and sometimes its (
neither of which are acceptable from persons who are healthcare professionals at any level. Since we are not addressing a healthcare profesional in some cases, sometimes such people consider themselves exempt from the rules that govern the behavior of healthcare professionals when interracting with sick people seeking help. This will not change, I assure you, regardless of the content of the exchanges with persons of that ilk.So this thread, like many others, confirms again the question is moot. The argument is perpetuated in this case by a person who admittedly has never read even one of the books I am talkign about, even the most simple book on the subject, much less the standard medical texts on the subject from authoritative sources vis a vis highly qualified allergists and immunologists who have studied the subject for decades. If a patient read [first] the (2) books I often refer to, the patient would gain a better understanding of the subject than I personally can convey within the time available to me and within this medium. there are quite a few around here who have done so and know this to be a fact from thier own personal experience. Yet they are deridied when they express that exprience. What folly to do so.
ALSO the good news is that finally the only physician-directed medical text on the subject ever published, which was produced and edited by Brostoff and Challacombe which was written in the first edition by perhaps 50+ allergists and immunlogists all over the world who are actually familiar with the subject "FOOD ALLERGY AND FOOD INTOLERANCE", which has been out of print, has a new edition nearly completed. It has been updated as much as was possible through the final edit (which is presently going on) and should be republished this year. This will be an excellent reference on the subject which it is hoped will thus provide a more reliable source of information from the worlds leaders in the field.Hmmmm....hey, wait, something posted leads me to beleive that the correct answer is
a consious choice has been made NOT to understand. The information conflicts with the presuppositions of his own, and the drug-company funded so called "IBS research" he relies upon as if it is the sole-source of information concerning the SYNDROME (which is not a disease....it is a group of overlapping etiologies like COPD which have not all been elucidated yet and as long as the majority of the research is funded by drug companies never will...all that will be understood is a portion of the physiology...that portion which can be intervened with pharmaceutically or by attenuative therapies which only address certain aspects of the phsyiology, therefore usually require pharmacotherpy to be provided as an adjunct thus perpetuating the realizable revenue stream which results from the clinical application of said drug-compny funded research). So welcome, my friend, welcome to the machine...AND to the worlds longest run-on sentence.
There is precise validity, however, in references to "people with other conditions". The whole field of so-called IBS research reflects the horrific error in thinking of the entire symptom-based approach to diagnosis and treatment. A HUGE population of people suffering from avoidable, reversible, aberrant immune response (the origins of which renain to be wholly understood) which can be provoked by dietary componenets are "diagnosed" as having a "functional condition" by primary care practitoners and specialists alike solely on the basis that everything they read int their respective journals drives diagnostics and treatment to that realm and perpetuates the mythology of "IBS".Its like the lost map...its not lost, it just has not been found yet, ecept by some, and their patients benefit from the finding of the map to preventive therapies. That does not make it Ponce deLeon's fairy tale, it makes it analagous to what COPD was 50 years ago: not yet fully understood. BUT avoidable from a symptom-provocation perspective.Work done from the phsychoneuro perspective begins to elucidate part of the physiology which is involved, and work done from the neuorimmune side elucidates another part. It is because they are treated as mutually exclusive we end up in the situation we are in: debating facts as if they are not facts, and confusing what is fact with what is theory based upon the objectives of who funded the particular information source. Since the work doen by those investigating the aberant immune response to dietary provocation in the small bowel runs afoul of the objectives of research funded by the drug industry it must be ignored regardless of how obvious it maybe. This is sort of like saying that I-75 does not really exist because you did not post the mile markers that all highways must have. Therefore, even though there are people driving up and down it successfully as we speak by the thousands, I will not acknoweldge its existence until the mile markers are added. TR, this foolishness has gone on as long as I can rememeber....and that is a long time.This debate over the undebatable is illustrative of what Hobbes wrote: "True and False are attributes of SPEECH not THINGS. Where speech is not there is neither truth for falsehood." This is "speech", albeit written word, but that which is debated is not imbued with the character of true or false since the phsyiology exists and is real.I have been in healthcare for over 30 years, and this whole 'Debate" which surrounds so called "IBS" is very far from the first such stupidly polarized debate over a syndrome that I have witnessed. The present situation is also far from the first time I have been involved on one side of such an issue or the other. The diference here is THIS debacle of IBS is highly personal.I was a victim of this foolishness my WHOLE life, from a child on into my 40's. That's a lotta damn suffering and alotta damn "experts" treating me from the same "learned sources" which contained not a 'nit' of information helpful to my condition. Not a morsel outside of more and more prescriptions or more and more "therapy" recommended for my "stress". USELESS. I got SO MUCH WORSE from this apprioach that by 40 the only solution offered to me was an interventional PARTIAL BOWEL RESECTION and PERMANENT COLOSTOMY. NO WAY JOSE.I was and remain (since I have yet to disapear from the planet) a walking talking venom-spewing testament to this. A victim of how research and teaching on the diagnosis and treatment of this condition has been conducted by the medical industry in the United States. I BECAME a beneficiary of knowledge which is COMPLEMENTARY to that which is promulgated by the drug-company-funded work preeminent in the US..BUT such information is treated, to the great disservice of millions of Amercan victims of IBS, as mutually exclusive...or "imaginary" or "made up".My REMISSION is not made up. My EXTREME-D EPISODES provoked by specific oral challenges is not a FAIRY TALE. MY degranulating leukocytes are not a FABRICATION. NOR are the thousands of others who have experienced the exact same thing as myself. And they will NOT be waved-away by ignorance.In the past, while I was actively involved in patient care, hospital managment, clinical research, product development, and teaching, since I had NO personal physical health "stake" in the situations, it was easy to be amused and aloof about how the "industry driven" machine works in healthcare in the USA. [Don't misunderstand the pharmaceutical industry is not the only driving wheel of the mechine, it is just the biggest, the same thing happens on the "hardware side" of healthcare technology].However, since I was a victim of this and have either observed or participated in the recovery of many many victims since I met doctors aproaching so called IBS and other "elusive" symptom sets from the caasal approach, I am unable to remain aloof about matters which I know are detrimental to the lives of fellow victims and patients when they occur in such a large forum of such victims and these are people who need HELP.While I apprecaite the suggestion I not allow myself to be drawn in to a rhetorical exchange with someone, please be assured I am not being "drawn" into anything by anyone or otherwise manipulated into responding...I am proactively compelled to address what I beleive is a disservice to the sick when I see it being perpetrated. It is a matter of personal ethics.And there is a lot of that going around. That being said, I am also fully aware that such people, whomever they are from practitioners to wannabes, are wholly unable to see themselves committing the disservice they do to those sick people who could be helped with some very simple methods...or maybe they are and they do it anyway, which is worse.
Seen that more times than I care to recall as well.Eat well. THINK well. Be well.MNL
 
OHNO!U-2: ________________________________"I was drinking at the hospital to get some sips of fluid "Apple Juice" " _______________________________See what the hell I mean? Did you see the movie NETWORK? See why I am mad as hell and I am not going to take it anymore!!! Oh but wait, where is your "control" taking no diet therapy?
Your fellow CVS members whose symptoms are not subsiding while yours are. Hang in there as the longer you stick to it the farther apart the episodes become and the milder the symptoms are if they do come...and do not forget to rotate the foods as there is the possibility of losong tolerance to a new one if you consume too much or too regularly. My, my I sound like "Dr. Mom".
sorryMNL
 
OHNO!U-2: ________________________________"I was drinking at the hospital to get some sips of fluid "Apple Juice" " _______________________________See what the hell I mean? Did you see the movie NETWORK? See why I am mad as hell and I am not going to take it anymore!!! Oh but wait, where is your "control" taking no diet therapy?
Your fellow CVS members whose symptoms are not subsiding while yours are. Hang in there as the longer you stick to it the farther apart the episodes become and the milder the symptoms are if they do come...and do not forget to rotate the foods as there is the possibility of losong tolerance to a new one if you consume too much or too regularly. My, my I sound like "Dr. Mom".
sorryMNL
 
JULIA:I just noticed the reference to Chicago. I would be pleased to meet you if I come that way. There is a good chance that I may be coming to the Chicago are in january...better bring my mittens...we have a vigorous schedule of nationwide travel for training sessions for the new group of lab service representatives I have retained. There are 100 of them all over the USA now and we have to add 50 more. Their training meetings are being set up in key cities for the whole month of 1/02.
I am sure gonna miss BabyNL while I am on the road! (Baby? StephanieNL is 3.5 yrs now, I guess she qualifies as ChildNL now
)If I am going to be in ChiTown I will let you know in advance when. I am not sure if we will do the central US meetings there or up in minneapolis/St.Paul...OWWW no way no Florida Boy wants to go there in january BRRR...Hey, we can have a plate of allergens together!
Eat well, think well, be well.MNL
 
JULIA:I just noticed the reference to Chicago. I would be pleased to meet you if I come that way. There is a good chance that I may be coming to the Chicago are in january...better bring my mittens...we have a vigorous schedule of nationwide travel for training sessions for the new group of lab service representatives I have retained. There are 100 of them all over the USA now and we have to add 50 more. Their training meetings are being set up in key cities for the whole month of 1/02.
I am sure gonna miss BabyNL while I am on the road! (Baby? StephanieNL is 3.5 yrs now, I guess she qualifies as ChildNL now
)If I am going to be in ChiTown I will let you know in advance when. I am not sure if we will do the central US meetings there or up in minneapolis/St.Paul...OWWW no way no Florida Boy wants to go there in january BRRR...Hey, we can have a plate of allergens together!
Eat well, think well, be well.MNL
 
Hi Julia...a couple quickies then gotta run...it's Monday and that means the phone starts ringing again. No time waste. You lay out make a couple of interesting tidbits.....or cheese bites.Dairy products. What a nightmare to sort out. Why? The substance from which they are derived is an immunologic nightmare of multiple base dairy fractions PLUS an immunoglobulin profile from momma cow for baby cows' temporary immunity which varies from place to place depending upon where the cows live, and what they are fed.So the only thing about milk tolerance that is simple is figuring out if you have trouble digesting lactose or not, and that has become pretty well understood what and how to do, and its fixable anyway with lactaid.But if milk still provokes symptoms WITH lactaid then one has to start looking for allergy or intolerance. In theory it would be ideal to be able to acquire and prepare antigen titrations of each of the main dairy fractions to test against, then one could see which processed dairy products (at keast in theory) contain which main dairy fractions after processing and then tell which might be safe.There are two main problems with this. Part of the problem is that even though processing milk into another product involves in many cases a process which removes one or more of the fractions, the way the processes (like butter processing) ar enow done to speed mas production does not always result in the degree of purity from antigen that the old fashined way would. I mean in theory, and if you did it all by hand, butter would end up technically not a dairy product, rather a big glob of fatty acids and all the milk fractions would be gone. But the way it is made now its not that perfect. An unpredictable amount and type of the potential allergen remains behind as a "contaminant", so if you have a non-dose dependent reactivity or allergy especially to one of the milk fractions, some butter might set you off and some butter might not.Ditto with cheese........it ain't 100% casein, otherwsie all cheese would be the same...a big block of casein. Kinda bland. I think depending upon the kind of cheese and how it is made it can contain over 100 potentially antigenic substances I am told.
The even if you are lucky enough to somehow sort it out, am also told that the allergenic properties of the various milk fractions and immunoglobulins can be altered when the products are heated during processing...and by which means they are pasteurized (slow and hot or real fast and real hot for a short period for example).Because there is so much variability from "lot to lot" of the extracts one must acquire from FDA approved preparers of food extracts to prepare the extracts for use in allergy or sensitivity testing, over the years it has been seen that rather than trying to isolate out the variosu fractions and test for them, esp. when dose-sensitivity is also in the freakin equation, you try to just test for whole milk to check general tolerance and try to buy cow milk antigen in big "lots" so when you do your production quality controls you are doing them on a big batch so you will have standardized with that milk antigen for a long time before you have to adjust to a new batch, and then do basic tolerance tests for the basic dairy by productas like American cheese and swiss cheese and yogurt which are the staples of most diets.Once one knows at least if one is tolerant of the base product at the fractional concentrations of each antigen that is in it (the main fractions) at least the patient knows if she has to monitor orally the possibility of dairy sensitivity product by product, or if in general dairy should be safe.Cows milk and products are the very hardest dietary components to assess and manage. takes work. ______________________________________"The only things I could eat were hot water and jello. For some reason I haven't figured out yet, as soon as I ate the jello my pain went away and didn't come back. I wonder if it was made with pure glucose instead of sugar." _______________________________________Well that's a standard "do it by the procedure manual" hospital outome story. The infrastructure is not known for being flexible due to the inter dependent policies and procedures which overlapped on you between the various services. If criterian A are not met then Action B does not take place and Examination C on patient A is cancelled and pateint B is plugged in immediatley to prevent down time. Managing special diets? Let's see we have 'soft", lo salt, diabetic, low cholesterol...do you fit any of those formulae which will appear on the options list in the computer system? I don't know how it is now I have been out of the loop in-hospital for some years but it sounds like allergyconsiderations, unless specifically written into the orders by the attending physician, still cannot be connected from the patient to the dietary dept.As far as the pain stopping when you ate the jello, this is hard to assess the way the eating pattern is described. Did you eat any of the poson they kept putting on your tray or were you fasting? An allergen withdrawl will produce a cessation of sympotms in tiem, after the second or Late phase reaction passes if it is a true allergy. If you have GERD or gastritis in yo lil belly for example and keep fasting while they give you nothing but poison, then pain will persist due to the fasting conditions. Whwn you break the fast and the food contains no allergen the rest of the pain may pass immediatley and as long as what you eat is allergen free can remain gone as no further provocation occurs.Think of it like when they ask the patient they atre assessing for specific ulcerative conditions is asked to determine if the pain ceases with food or not ro gets worse. tells you different things.I guess that articially flavored cow toe-jam was non-allergenic in any event!
And you are right....being a Cleveland boy groing up across the lake from Canada I know about them Chicago winter deals.....I am really trying to find a way to meet in a less hostile climate in that neck of the woods. But then again the winter has been very mild this year maybe it will hold up?
yeah when pigs fly right?
take care there!MNL
 
Hi Julia...a couple quickies then gotta run...it's Monday and that means the phone starts ringing again. No time waste. You lay out make a couple of interesting tidbits.....or cheese bites.Dairy products. What a nightmare to sort out. Why? The substance from which they are derived is an immunologic nightmare of multiple base dairy fractions PLUS an immunoglobulin profile from momma cow for baby cows' temporary immunity which varies from place to place depending upon where the cows live, and what they are fed.So the only thing about milk tolerance that is simple is figuring out if you have trouble digesting lactose or not, and that has become pretty well understood what and how to do, and its fixable anyway with lactaid.But if milk still provokes symptoms WITH lactaid then one has to start looking for allergy or intolerance. In theory it would be ideal to be able to acquire and prepare antigen titrations of each of the main dairy fractions to test against, then one could see which processed dairy products (at keast in theory) contain which main dairy fractions after processing and then tell which might be safe.There are two main problems with this. Part of the problem is that even though processing milk into another product involves in many cases a process which removes one or more of the fractions, the way the processes (like butter processing) ar enow done to speed mas production does not always result in the degree of purity from antigen that the old fashined way would. I mean in theory, and if you did it all by hand, butter would end up technically not a dairy product, rather a big glob of fatty acids and all the milk fractions would be gone. But the way it is made now its not that perfect. An unpredictable amount and type of the potential allergen remains behind as a "contaminant", so if you have a non-dose dependent reactivity or allergy especially to one of the milk fractions, some butter might set you off and some butter might not.Ditto with cheese........it ain't 100% casein, otherwsie all cheese would be the same...a big block of casein. Kinda bland. I think depending upon the kind of cheese and how it is made it can contain over 100 potentially antigenic substances I am told.
The even if you are lucky enough to somehow sort it out, am also told that the allergenic properties of the various milk fractions and immunoglobulins can be altered when the products are heated during processing...and by which means they are pasteurized (slow and hot or real fast and real hot for a short period for example).Because there is so much variability from "lot to lot" of the extracts one must acquire from FDA approved preparers of food extracts to prepare the extracts for use in allergy or sensitivity testing, over the years it has been seen that rather than trying to isolate out the variosu fractions and test for them, esp. when dose-sensitivity is also in the freakin equation, you try to just test for whole milk to check general tolerance and try to buy cow milk antigen in big "lots" so when you do your production quality controls you are doing them on a big batch so you will have standardized with that milk antigen for a long time before you have to adjust to a new batch, and then do basic tolerance tests for the basic dairy by productas like American cheese and swiss cheese and yogurt which are the staples of most diets.Once one knows at least if one is tolerant of the base product at the fractional concentrations of each antigen that is in it (the main fractions) at least the patient knows if she has to monitor orally the possibility of dairy sensitivity product by product, or if in general dairy should be safe.Cows milk and products are the very hardest dietary components to assess and manage. takes work. ______________________________________"The only things I could eat were hot water and jello. For some reason I haven't figured out yet, as soon as I ate the jello my pain went away and didn't come back. I wonder if it was made with pure glucose instead of sugar." _______________________________________Well that's a standard "do it by the procedure manual" hospital outome story. The infrastructure is not known for being flexible due to the inter dependent policies and procedures which overlapped on you between the various services. If criterian A are not met then Action B does not take place and Examination C on patient A is cancelled and pateint B is plugged in immediatley to prevent down time. Managing special diets? Let's see we have 'soft", lo salt, diabetic, low cholesterol...do you fit any of those formulae which will appear on the options list in the computer system? I don't know how it is now I have been out of the loop in-hospital for some years but it sounds like allergyconsiderations, unless specifically written into the orders by the attending physician, still cannot be connected from the patient to the dietary dept.As far as the pain stopping when you ate the jello, this is hard to assess the way the eating pattern is described. Did you eat any of the poson they kept putting on your tray or were you fasting? An allergen withdrawl will produce a cessation of sympotms in tiem, after the second or Late phase reaction passes if it is a true allergy. If you have GERD or gastritis in yo lil belly for example and keep fasting while they give you nothing but poison, then pain will persist due to the fasting conditions. Whwn you break the fast and the food contains no allergen the rest of the pain may pass immediatley and as long as what you eat is allergen free can remain gone as no further provocation occurs.Think of it like when they ask the patient they atre assessing for specific ulcerative conditions is asked to determine if the pain ceases with food or not ro gets worse. tells you different things.I guess that articially flavored cow toe-jam was non-allergenic in any event!
And you are right....being a Cleveland boy groing up across the lake from Canada I know about them Chicago winter deals.....I am really trying to find a way to meet in a less hostile climate in that neck of the woods. But then again the winter has been very mild this year maybe it will hold up?
yeah when pigs fly right?
take care there!MNL
 
Yo, U2:I know what you meant...I did not think you would drink any since you had your test. Don't worry
I was commenting on how many times over the years I have seen such a scenario where staff never puts 2+2 together...its like the forest is invisible because there are so many big trees
[Patient has been throwing up for 36 hours. She is NPO except for apple juice, Cannot keep anything in her. OK but keep trying until she can keep some juice down or we will have to start an IV so she does not dehydrate. Tell dietary to hold her trays just send up lotsa little cups of apple juice and keep trying to get her to drink some.]Hmmmm I see Church Lady dressed as charge nurse at report: "Patient NPO 36 hours except apple juice...constant vomiting....could it be...
APPLE JUICE????
Naw.Case closed.
U-ee,
relax I did not think you were drinking the test-positive stuff since you found out. NO spanking to day!! read your email and keep up the goof work, er , good work
MNL
 
Yo, U2:I know what you meant...I did not think you would drink any since you had your test. Don't worry
I was commenting on how many times over the years I have seen such a scenario where staff never puts 2+2 together...its like the forest is invisible because there are so many big trees
[Patient has been throwing up for 36 hours. She is NPO except for apple juice, Cannot keep anything in her. OK but keep trying until she can keep some juice down or we will have to start an IV so she does not dehydrate. Tell dietary to hold her trays just send up lotsa little cups of apple juice and keep trying to get her to drink some.]Hmmmm I see Church Lady dressed as charge nurse at report: "Patient NPO 36 hours except apple juice...constant vomiting....could it be...
APPLE JUICE????
Naw.Case closed.
U-ee,
relax I did not think you were drinking the test-positive stuff since you found out. NO spanking to day!! read your email and keep up the goof work, er , good work
MNL
 
Hi J....gotta run to one of those infernal meetings but this is intriguing...a couplle quick questions in case I missed it ____________________________________"They did put allergens on my tray, but I didn't eat any - didn't even try the tea since in the past it had upset my tummy, I just drank the hot water. " _____________________________________Q:1. What would you say the elpased time was from when you last ingested any "food" other than the hot water until you ingested the Medicinal jello? I mean I know that you had 8 hours of asting basically, but what was the last thing you took beofre the fast and then if it was not a meal per se when was your last real meal and what was it? What prep did they give you to use (there are differing protocols) as the contents of the prep can have a bearing on this to...2. What was your last supper so to speak before you stopped eating and fasted until the Jumpin Jello arrived? ____________________________________"I'm catching a cold ..." ____________________________________
Hope it runs faster before you catch it. Just go to bed and leave the poor cold alone. Once you catch him you will not want him anayway, then it is too late to give the little sucker back!
Guten tagMNLPSI'm from Cleveland anyway so, Chicago is my kind of town, Chicago is..etc. Da Bears!!!
MNoSinatra
 
Hi J....gotta run to one of those infernal meetings but this is intriguing...a couplle quick questions in case I missed it ____________________________________"They did put allergens on my tray, but I didn't eat any - didn't even try the tea since in the past it had upset my tummy, I just drank the hot water. " _____________________________________Q:1. What would you say the elpased time was from when you last ingested any "food" other than the hot water until you ingested the Medicinal jello? I mean I know that you had 8 hours of asting basically, but what was the last thing you took beofre the fast and then if it was not a meal per se when was your last real meal and what was it? What prep did they give you to use (there are differing protocols) as the contents of the prep can have a bearing on this to...2. What was your last supper so to speak before you stopped eating and fasted until the Jumpin Jello arrived? ____________________________________"I'm catching a cold ..." ____________________________________
Hope it runs faster before you catch it. Just go to bed and leave the poor cold alone. Once you catch him you will not want him anayway, then it is too late to give the little sucker back!
Guten tagMNLPSI'm from Cleveland anyway so, Chicago is my kind of town, Chicago is..etc. Da Bears!!!
MNoSinatra
 
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