MAP template controlling Crohn's disease?

Crohn's disease is stated to be an immune-mediated disease initiated by Mycobacterium avium subspecies paratuberculosis (MAP) infection within a period of host immunological vulnerability and induced by the widespread prevalence of that organism in the human food chain. For over two decades, steroids and biologics have, move often than not, been able to induce temporary remissions, but not cures. This thesis examines how the only two, very divergent, therapeutic approaches that have produced cures achieved this positive outcome.

Is ulcerative colitis a disease of a dysfunctional microbiota?

Using the gross pathology literature and the prior decoupling of Crohn's disease from inflammatory bowel disease, IDI's White Paper puts into question the current understanding of what ulcerative colitis is and how it can be therapeutically addressed. The pathology literature, when coupled with the ability of fecal enema therapy to achieve a remission rate significantly superior to those documented for biologics, puts focus on the dominant role of the gastrointestinal microbiota in both disease induction and its recovery. The concept of endogenous enterotoxogenesis is introduced.

Are the permanent sequelae of Crohn's disease a failure to treat the gastrointestinal microbiota?

Using parallel knowledge derived from gynecological infections, the thesis is advanced that late sequelae in Crohn's disease are the consequence of the failure to treat or the undertreating of the co-functioning infection by the gastrointestinal microbiota.

The myth of autoimmunity.

Within the more than one hundred disease entities for which autoimmunity causation have been alleged, two subgroups can be identified. The first group is characterized by ability of disruption of the effector arm of the immune response to temporarily reverse the signs and symptoms of disease. The second group is characterized by the presence of antibodies directed against the target organ's cellular or subcellular components. As long as therapeutic palliation of the signs and symptoms of disease can be achieved, attributing causation to autoimmunity has tended to arrest therapeutics focus on attaining cure. Data relevant to a prime disease entity within each of the two allegedly autoimmune disease, Crohn's disease and Type 1 diabetes mellitus, refute the claim of autoimmunity. In particular, the events that combine to produce Crohn's disease have identified a mechanism by which a dysfunctional immune-mediated response against a specific set of antigens/agent can produces disease. Identification of this mechanism opens to rethinking the pathogenesis of other classic autoimmune diseases within that 5 subgroup.

The Hruska postulate of Crohn's disease.

Crohn's disease is due to the loss of immunological tolerance within the gastrointestinal tract to the antigenic array of Mycobacterium avium subspecies paratuberculosis (MAP) and closely related polymorphic variants. The loss of immune tolerance results in an effector cytokine responsive upon re-exposure to MAP. For immune tolerance to MAP to be induced, infection must occur when acquired immunity is markedly underdeveloped.

Attachment of Mycobacterium avium subspecies paratuberculosis to bovine intestinal organ cultures: method development and strain differences.

Mycobacterium avium spp. paratuberculosis (MAP) causes chronic granulomatous inflammation of the intestinal tract in many species of animals, but the mechanisms of disease are poorly understood. Attachment of bacteria to epithelial cells is a critical step in pathogenesis of many mucosal diseases. The goal of these studies was to develop an in vitro method to study attachment of MAP to bovine intestinal epithelial cells. Short-term, bovine intestinal organ cultures were used to show a significant difference in the ability of radiolabelled MAP strains to attach to intestinal epithelium. We found significant differences in the ability of different strains of MAP to attach, but there were no differences in attachment among different regions of the intestinal tract. Examination of acid fast stained tissue sections of organ cultures demonstrated that organisms were located adjacent to mucosal epithelium or within goblet cells. Coating of the organisms with fibronectin, which has been shown to be involved in attachment of many mycobacteria, including MAP, affected the attachment of the MAP strains in different ways, but did not affect the overall attachment of the organisms to different regions of the gastrointestinal tract. This organ culture method should also prove useful for defining the molecular mechanisms of attachment and interactions of MAP with intestinal epithelium.

A growing concern: inability to diagnose vulvovaginal infections correctly.

The accurate diagnosis of vulvovaginitis should distinguish obstetrician-gynecologists from the vast majority of primary care physicians. Diagnostic accuracy is lost when physicians are unable to do a microscopic examination of vaginal secretions, as well as a "whiff" test and a pH determination. Structured instruction in the use of a microscope should be a required component of obstetrics and gynecology residency training. Physician compensation for this testing should be commensurate with the time and office expense required to provide this service.