DOWNLOAD PDF IS CROHNS DISEASE A MYCOBACTERIAL DISEASE?

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1 Chapter 1 : Crohn's MAP Vaccine A controversial theory is that paratuberculosis can also cause Crohn's disease in humans. In, unclassified Mycobacterium strains were isolated from 3 different Crohn's patients. In it became possible to positively identify these three strains as all belonging to M paratuberculosis. Associated with Th17 [] Vaguely associated with Th2 During a colonoscopy, biopsies of the colon are often taken to confirm the diagnosis. There is usually an abrupt transition between unaffected tissue and the ulcerâ a characteristic sign known as skip lesions. Under a microscope, biopsies of the affected colon may show mucosal inflammation, characterized by focal infiltration of neutrophils, a type of inflammatory cell, into the epithelium. This typically occurs in the area overlying lymphoid aggregates. These neutrophils, along with mononuclear cells, may infiltrate the crypts, leading to inflammation crypititis or abscess crypt abscess. Biopsies may also show chronic mucosal damage, as evidenced by blunting of the intestinal villi, atypical branching of the crypts, and a change in the tissue type metaplasia. One example of such metaplasia, Paneth cell metaplasia, involves development of Paneth cells typically found in the small intestine and a key regulator of intestinal microbiota in other parts of the gastrointestinal system. Disease in the small bowel is particularly difficult to diagnose, as a traditional colonoscopy allows access to only the colon and lower portions of the small intestines; introduction of the capsule endoscopy [] aids in endoscopic diagnosis. It typically manifests in the gastrointestinal tract and can be categorized by the specific tract region affected. Jejunoileitis causes spotty patches of inflammation in the top half of the small intestine, called the jejunum. However, individuals affected by the disease rarely fall outside these three classifications, with presentations in other areas. These categorizations formalized in the Vienna classification of the disease. Stricturing disease causes narrowing of the bowel that may lead to bowel obstruction or changes in the caliber of the feces. Penetrating disease creates abnormal passageways fistulae between the bowel and other structures, such as the skin. Inflammatory disease or nonstricturing, nonpenetrating disease causes inflammation without causing strictures or fistulae. On occasion, the colonoscopy can travel past the terminal ileum, but it varies from person to person. During the procedure, the gastroenterologist can also perform a biopsy, taking small samples of tissue for laboratory analysis, which may help confirm a diagnosis. Because colonoscopy and gastroscopy allow direct visualization of only the terminal ileum and beginning of the duodenum, they cannot be used to evaluate the remainder of the small intestine. As a result, a barium follow-through X-ray, wherein barium sulfate suspension is ingested and fluoroscopic images of the bowel are taken over time, is useful for looking for inflammation and narrowing of the small bowel. They remain useful for identifying anatomical abnormalities when strictures of the colon are too small for a colonoscope to pass through, or in the detection of colonic fistulae in this case contrast should be performed with iodate substances. Rarely autoimmune hemolysis may occur. Erythrocyte sedimentation rate ESR and C-reactive protein help assess the degree of inflammation, which is important as ferritin can also be raised in inflammation. Anemia of chronic disease results in a normocytic anemia. Other causes of anemia include medication used in treatment of inflammatory bowel disease, like azathioprine, which can lead to cytopenia, and sulfasalazine, which can also result in folate deficiency. It is important to differentiate these diseases, since the course of the diseases and treatments may be different. In some cases, however, it may not be possible to tell the difference, in which case the disease is classified as indeterminate colitis. Page 1

2 Chapter 2 : ParaTB pages:- Does Mycobacterium paratuberculosis cause Crohn's disease? Mycobacterium avium, subspecies paratuberculosis (MAP) causes a chronic disease of the intestines in dairy cows and a wide range of other animals, including nonhuman primates, called Johne's ("Yo-knee's") disease. MAP has been consistently identified by a variety of techniques in humans with Crohn's. Is it the Crohns disease cause? How to interpret Crohns disease research? I was doing Crohns disease research about causes of Crohns disease and got to my first article about Mycobacteria. When I first learned that this Mycobacteria is being associated as one of the possible causes of Crohns disease, I was thrilled! I was happy because, if that was the case, it would be so simple to eradicate Mycobacterium with a strong antimicrobial and finally cure Crohns disease. So what do we know about this? For years there were debates on this subject. This was investigated in many different countries. What is the connection? In order to investigate it we have to go back all the way to when Dr. Dalziel recognized Crohns disease before Dr. Crohn presented it to the medical world in Dalziel recognized that what is now called Crohns disease was different from then known disease called intestinal tuberculosis. Intestinal tuberculosis can be caused by Mycobacterium paratuberculosis. But this doctor believed that disease was similar enough to intestinal tuberculosis and probably also was caused by Mycobacteria. He could not prove it because when he analyzed tissues samples this bacteria was not showing up. Crohns classified Crohns disease with no mycobacterium origin because it was not possible to demonstrate visible bacteria. Mycobacterium is a genus of bacteria. There are many different species of this bacteria. Mycobacteria avium subspecies paratuberculosis MAP is an obligate pathogenic mycobacteria. It means that this bad bacteria will need a host like a human or an animal to multiply. It can live for a long time outside the host. MAP causes Johnes disease, an intestinal illness disease in animals. Johnes disease in animals is very similar to Crohns disease in humans. Recently, scientists at the University of Liverpool found that a type of carbohydrate, called mannose, comes from MAP. And this mannose molecule does not allow the white blood cells, which are macrophages, kill E-coli in the abdomen. In other words, the natural protectors could not fight the E-coli in the gut and E-coli can cause a fierce gastro-intestinal infection. The studies were mostly inconclusive. I realized that until this hypothesis is proven the only thing that I can do is try to keep my immune system working at its best so it would be able to fight off bad bacteria. Maintaining a well balanced immune system is very important. Some natural products and supplements can keep the immune system in harmony. But be careful in choosing an immune system booster because some of the boosters could possibly trigger an autoimmune reaction in the over-reactive immune system of a Crohns patient. The key here is to let our immune system balance itself with the help of a natural or herbal supplement that works like a modifier rather than a stimulant. Maintain great oral health. See your dentist regularly. Use sea salt with warm water as a mouth rinse every night. Exercise and try breathing techniques for relaxation. Every single slice of cake, white bread or carbonated, sugary drink can make a difference between flare-up or symptom-free life. I wish you great health! Page 2

3 Chapter 3 : ACG Dismisses Mycobacteria in Crohn's Human Para Foundation For a comparison of the symptoms of known mycobacterial diseases and Crohn's disease, and discussion of the known commonalities between the two diseases in terms of diagnosis and treatment, see the page "Similarities between Crohn's disease and mycobacterial disease.". We regret that we cannot answer questions or offer any recommendations related to treatment. The information offered on this site is for educational purposes only and should not be used as a basis for diagnosing or treating any illness. It should be noted that there is considerable overlapping subject matter in terms of research. Therefore, we would urge you to visit the Research section of this website for additional information. Early treatment regimes were composed of antibiotics chosen for their activity against Mycobacterium tuberculosis MTB, although both in-vitro and in-vivo data for these antibiotics showed that they had little effect against Mycobacterium paratuberculosis, as Mycobacterium avium subspecies paratuberculosis MAP was known at that time. For a full review of this early work, please read Chiodini Clinicians attempted to treat these MAC infections with the only anti-mycobacterial drugs available, namely drugs active against Mycobacterium tuberculosis. Successes with these early regimes were rare, since MAC bacteria were either resistant to anti-mtb drugs, or quickly developed resistance. Two of these macrolides, Clarithromycin and Azithromycin, were highly effective against MAC bacteria, and revolutionized the treatment of MAC infections. However, development of macrolide resistance is a common problem, and there are still no antibiotics regimes available which are guaranteed to eradicate a MAC infection. For a thorough review of antibiotic treatment for MAC disease, please read Heifets Clarithromycin against Mycobacterium avium complex infections. The results of their work are discussed below. Work to date To date, three groups of investigators have published results of open trials of anti-map treatment which includes macrolide antibiotics. Of the 9 patients not in remission, 6 patients withdrew because of the severity of side effects, and 3 patients experienced no improvement. Borody et al published in Digest Liver Dis ; After three months of treatment, the investigators found that 8 of the 29 patients were in clinical remission, 9 of the 29 patients experienced marked improvement, 8 of the 29 patients experienced minor improvement, and 4 of the 29 patients had to be taken off the medication, due to intolerance of side-effects. We would encourage you to visit Dr. To see a portion of that report and the accompanying photographs click here. Thomas Borody has also graciously provided "before" and "after" endoscopic photographs of intestinal condition of patients treated with antimycobacterial therapy. To see those photographs, click here. Trial structures Open trials, regardless of the results obtained, do not provide sufficient evidence to recommend the treatment which is being tested. In order for the treatment in question to be proven to be an effective treatment, it must be subjected to a double-blind, placebo-controlled, and preferably multi-center clinical trial, for the following reasons. When the patients in the trial are unaware whether they are in the active or placebo arm of the trial, the trial is said to be blind. In a trial where the doctors administering the trial are also not aware which arm the patient is in, the trial is said to be double-blind. A double-blind trial greatly reduces the possibility of investigator bias during the trial. In order to obtain objective data on the effectiveness of the treatment under trial, patients in the trial are divided into two groups. One group receives the treatment under trial, and is said to be in the active arm of the trial. The other group receives treatment which they are told is the active drug, but is in fact an ineffective substitute which is known not to have activity in the disease condition being treated. To increase diversity and eliminate regional bias of the study, a multi-center trial is conducted by several independent groups of investigators at several locations. Existing clinical trials A double-blind, multi-center, controlled clinical trial of combination anti-map treatment is underway in Australia. For full details see the report on the Antibiotic Clinical Trial section of this site. Known side effects of treatment Among the side effects noted with existing anti-map treatment regimes are: Some patients experienced a narrowing of the intestines which seemed to be caused by a build-up of fibrotic tissue fibrostenosis. The probability of such stricturing may be related to the length of disease involvement in the patient. A shortage of white blood cells occurred in some patients who were treated with Rifabutin. The level of white blood cells in many patients treated with anti-map treatment Page 3

4 fell during treatment, as a natural consequence of the reduction of inflammation in the body. However, in some patients the levels of such white blood cells was sufficient to be classified as a severe deficiency, and warranted modification of the treatment regime or even withdrawal from treatment. This is thought to be an immune-mediated phenomenon, since similar symptoms do not occur in immuno-compromised AIDS patients who are being treated for mycobacterial infections with Rifabutin. A flu-like syndrome appeared in some patients after one week of anti-map treatment, and lasted for between 3 and 8 weeks. Their results are largely unpublished. The reasons for such failures may include Multiple diseases. Therefore, not all patients treated with anti-map treatment would experience improvement. Insufficient activity of antibiotics. Infections by all species of Mycobacterium avium, including Mycobacterium avium subspecies paratuberculosis, are extremely difficult to eradicate with antibiotic treatment. Treatment failure of Mycobacterium avium infections is frequent, for a variety of reasons, including the ability of these bacteria to rapidly develop resistance to antibiotics. Existence of antibiotic resistance prior to treatment. Before anti-map treatment begins, some patients may have been treated with macrolide antibiotics, which are an essential element of all existing anti-map treatment regimes. Experience with Mycobacterium avium infections has shown that treatment of such infections with a single macrolide antibiotic, administered alone, results in a high risk that macrolide-resistance will develop. The mathematical probability of resistance is a function of how long monotherapy lasted, the number of separate treatment periods, and the number of infecting mycobacteria. Page 4

5 Chapter 4 : Crohn's disease RHB (GI/Inflammation) Development Pipeline Products RedHill known for a best download is crohns disease a mycobacterial disease transmission in the victory' Genetic Algorithms'. neighbors of the Genetic and Evolutionary Computation Conference(GECCO ). ACM download is crohns disease a mycobacterial disease, years Received Dec 9; Accepted Dec This article has been cited by other articles in PMC. The word "idiopathic" means "of unknown cause," but the currently accepted theory of the cause of these diseases postulates a nebulous combination of immune dysfunction, "dysbiosis," [ 1 ] and otherwise normal constituents of the commensal extracellular luminal gut bacteria [ 2 ] leaking through an abnormally permeable mucosal layer [ 3 ] in genetically predisposed individuals [ 4 ]. MAP causes a chronic disease of the intestines [ 9, 10 ] in a variety of animals [ ], including nonhuman primates [ 17 ], that shares some histologic i. This commentary proposes that ulcerative colitis is also caused by MAP. Fecal-oral transmission means that a microorganism present in the feces of an animal contaminates the food or water that a person swallows. The uniformity of ileal and cecal disease in family 1 is akin to that which might be expected had a uniform dose of an enteric pathogen been given to a genetically uniform group of experimental subjects, e. In one of these nonfamilial or sporadic clusters, Aisenberg and Janowitz [ 42 ] describe 3 friends who shared living quarters in college. For a pathologist such as the author, the most convincing evidence of causation is direct visualization: MAP can be directly visualized in patients with both diseases [ 60, 61 ]. The usual influences of dose, route, age, sex and genes on the clinical expression of an infection Like any other pathogenic disease-causing microorganism, a variety of factors influences the phenotype, the clinical expression of MAP infection; whether an individual develops one disease caused by MAP or another. Not everyone infected by a pathogenic microorganism develops a disease caused by that organism. The two routes of infection that potentially concentrate MAP are aerosolized water from rivers and other bodies of water contaminated with MAP, and MAP present in hyperosmolar milk rather than hypoosmolar water. The interactive influences of age and dose: This family had been living in a section of Germany with water that "was poorly controlled hygienically. As societies become more "westernized" or industrialized Studies from Japan recapitulate the US experience, with a predominance of UC cases early and a rise in CD approximately 1 decade later [ 67 ]. At the macroscopic level, however, a small number of organisms, a small "bacterial burden" or a small "dose" of MAP refers to numbers of organisms on the order of, 10 million organisms or less, while a large bacterial burden refers to doses on the order of or million organisms or more. Most acute infections originate from a small number of inoculating organisms, which even the dampened immunity in CD appears able to control. Our findings of the relationship between bacterial dose and clearance are important in this respect because they demonstrate that CD patients can deal efficiently with small numbers of organisms in the tissues, but that the clearance mechanisms are overwhelmed by a large bolus of bacteria [ 73 ]. Normal water treatment processes such as filtration and chlorination amplify rather than eliminate MAC organisms by killing off their competitors [ 75, 76 ]. In addition, MAC organisms grow on tap water pipes [ 77 ], in biofilms [ 78 ] and on plastic water bottles [ 79 ]. MAP has been identified in drinking water in the United States [ 80, 81 ] and elsewhere [ 82 ]. If an individual drinks 2 liters of water a day, it will take just over 2 months to ingest or "massive numbers" of MAP organisms. As the level of MAP organisms increases in the environment, including drinking water, a child has a greater chance of getting infected with a large dose. In the study above [ 73 ], ulcerative colitis patients were able to clear large doses of E. So patients develop ulcerative colitis even when infected with small doses of MAP. The two routes of MAP infection: There are, therefore, 2 different routes of infecting humans with MAP: The first route of transmission of MAP to humans is fecal-oral transmission. Direct contact with dairy cattle feces has also been associated with an increased risk of ulcerative colitis in adult male farm workers [ 90 ]. The second route of MAP transmission to humans is through contaminated milk. The ATG16L1 and IRGM proteins are involved in the process of autophagy, which is one of the ways cells process and eliminate intracellular bacteria [ ]. The influence of sex: While purely speculative, this difference might be due to the differing effects of testosterone [ ] versus estrogen [ ] on Page 5

6 blood and lymphatic vessels, to the greater effects of smoking on females than males [ ], or to the increase in oral contraceptive use, with its known vascular complications [ ]. An excellent review article by Lakatos and colleagues [ ] helps elucidate the reasons for the different effects of smoking on these diseases. If they started smoking before age 15, they were over three times more likely to develop both diseases. The explanation of the apparent "protective" effect of smoking on sporadic UC may be that the form of IBD that develops in a proportion of smokers is not UC but CD [ ]. But smokers with ulcerative colitis do have a more benign clinical course than nonsmokers. If MAP causes ulcerative colitis, what in the smoke is good for ulcerative colitis? First, nicotine reduces tone and muscular activity in the colon; it slows the colon down [ ]. Secondly, nicotine increases small bowel inflammation but decreases colonic inflammation [, ]. A rapid, focused effort to determine and implement the most efficacious treatments of already infected individuals [,, - ], and methods of preventing initial infection by vaccination [ ] and the effective removal of MAP organisms from drinking water [ ] will become top priorities. Dedicated to Cyrus E. Competing interests The author declares that no competing interests exist. No funding was received for the preparation of this commentary. Commensal bacteria, traditional and opportunistic pathogens, dysbiosis and bacterial killing in inflammatory bowel diseases. Curr Opin Infect Dis. Interplay of commensal and pathogenic bacteria, genetic mutations, and immunoregulatory defects in the pathogenesis of inflammatory bowel diseases. Intestinal barrier dysfunction in inflammatory bowel diseases. Susceptibility genes and overall pathogenesis of inflammatory bowel disease: The pathology and pathogenesis of paratuberculosis in ruminants and other species. Pathological evaluation of paratuberculosis in naturally infected cattle. The pathological study of paratuberculosis in goats, centered around the formation of remote lesions. Jpn J Vet Res. Description and classification of different types of lesion associated with natural paratuberculosis infection in sheep. J Vet Intern Med. Experimental infection by oral administration of Mycobacterium paratuberculosis. Mycobacterium paratuberculosis infection in a colony of stumptail macaques Macaca arctoides J Infect Dis. The Canadian Journal of Gastroenterology. Are there any differences in phenotype or disease course between familial and sporadic cases of inflammatory bowel disease? Results of a population-based follow-up study. Inflammatory bowel disease in 67 families each with three or more affected first-degree relatives. Analysis of the contribution of HLA genes to genetic predisposition in inflammatory bowel disease. Am J Hum Genet. Familial occurrence of inflammatory bowel disease. N Engl J Med. Clinical patterns of familial inflammatory bowel disease. Prevalence and incidence of inflammatory bowel disease in family members. Inflammatory bowel disease in married couples. Inflammatory bowel disease in married couples: Inflammatory bowel disease in spouses and their offspring. Frequency of inflammatory bowel disease in offspring of couples both presenting with inflammatory bowel disease. Chapter 5 : Crohn's disease - Symptoms and causes - Mayo Clinic Later, Dr. Crohns classified Crohns disease with no mycobacterium origin because it was not possible to demonstrate visible bacteria. Mycobacterium is a genus of bacteria. There are many different species of this bacteria. Chapter 6 : Anti-MAP treatment for Crohn's Disease ACG Turns a Blind Eye to Mycobacterial Therapy in Crohn's Disease. The American College of Gastroenterology (ACG) recently released the Guidelines for the treatment of Crohn's Disease (CD). Such guidelines can profoundly influence how practitioners treat CD and how younger physicians. Chapter 7 : Does Mycobacterium Really Cause Crohns Disease? Is It The Crohns Disease Cause? IS CROHN'S disorder A MYCOBACTERIAL DISEASE'! the truth that the differential analysis of inflammatory bowel illness comprises intestinal infections has been a resource of a lot curiosity and medical challenge for a few years. because the popularity of ulcerative colitis and Crohn's sickness as scientific entities, quite a few makes an attempt. Page 6

7 Chapter 8 : Download Is Crohns Disease A Mycobacterial Disease Crohn's disease causes inflammation in part of your digestive system. Crohn's can affect any part of it, but most often it affects your small intestine and colon.. Crohn's and another disease. Chapter 9 : Crohn's disease - Wikipedia Crohn's disease (sometimes called Crohn disease) is a chronic inflammatory disease of the blog.quintoapp.com primarily causes ulcerations (breaks in the mucosal lining) of the small and large intestines, but can affect the digestive system anywhere from the mouth to the anus. Page 7