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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the causes, events initiating and triggering inflammation, and the precise immunoregulatory defects of IBD are still not known, investigations have provided a better understanding of the mechanisms of perpetuation of inflammation, genetic susceptibility, tissue injury, and symptoms. Ulcerative colitis and Crohn's disease are related disorders that probably share susceptibility genes and have similar nonspecific inflammatory mediator profiles. These diseases, however, almost certainly have different causes and respond to different antigenic stimuli. It is probable that both ulcerative colitis and Crohn's disease represent heterogenic groups of diseases that share similar mechanisms of tissue damage but have different initiating events and immunoregulatory abnormalities. Rodent models demonstrate that a wide variety of initial injuries or perturbations of immunoregulatory pathways can lead to similar phenotypes of intestinal injury, and human studies show evidence of genetic heterogeneity. It is equally apparent from these models that initiating and perpetuating mechanisms are entirely distinct and that the intestine has a remarkable ability to heal. Chronicity of disease depends on continued exposure to toxic luminal components, most commonly of bacterial origin, and genetically determined host susceptibility. Precise mechanisms of differential genetic susceptibility remain unclear, but defective down-regulation of inflammation is consistent with clinical and experimental observations. The author proposes the following sequence of events (Fig. 9). Nonspecific intestinal inflammation can be induced by a wide variety of enteric infections or ingested toxins. Resultant increased mucosal permeability leads to enhanced uptake of toxic luminal bacterial products, which potentiate local injury. The vast majority of hosts respond to these injurious events by promptly down-regulating the inflammatory response and rapidly healing the mucosal damage without residual scarring. The genetically susceptible host, however, who lacks the ability to suppress the inflammatory response efficiently, has inappropriate amplification of the immune cascade. In response to constant exposure to phlogistic luminal constituents, these patients develop an unrestrained inflammatory response, leading to tissue destruction, chronic inflammation, and fibrosis. Thus, IBD is caused by a genetically determined defective down-regulation of inflammation driven by ubiquitous antigens. Luminal anaerobic bacterial antigens are the stimuli in Crohn's disease, but ulcerative colitis may be caused by functionally abnormal aerobic bacteria or primary defects in epithelial cell physiology. Spontaneous or therapy-induced remissions can be achieved, but the risk of reactivation of inflammation is high because of the frequent exposure to triggering episodes that can reignite the inflammatory cascade. [formula: see text] This theory suggests that the intestine is in a constant state of controlled inflammation, mediated by a balance between aggressive luminal forces and host protective mechanisms (Fig. 10). This delicate balance can be deranged by any number of environmental triggering events and is in dysequilibrium in IBD. Amplification of the inflammatory response activates effector cells and cascades of soluble inflammatory molecules, which mediate tissue injury and physiologic responses leading to symptoms of IBD. These relatively nonspecific events are the target of most current therapeutic agents, which can inhibit but not completely block intestinal inflammation because of the overwhelming number of parallel pathways involved. Specific inhibition of selected effector molecules is intellectually intriguing but is less likely to paralyze the inflammatory response during clinically apparent inflammation than is blockade of key immunoregulatory cells and molecules. Better understanding of initiating, perpetuating, and immunoregulatory mechanisms should provide more
Gastroenterol Clin North Am 1995 Sep
PMID:Current concepts of the etiology and pathogenesis of ulcerative colitis and Crohn's disease. 880 32

Clinicians have witnessed an evolution from sulfasalazine and hydrocortisone to alternative aminosalicylates and steroids. Revolutionary changes beyond these, however, and other "nonspecific" anti-immunoinflammatory compounds require clarification of the primary events either activating inflammatory cascades or preventing the down-regulation of homeopathic inflammation. The authors remain encouraged by advances in basic research pertaining to IBD and optimistic that novel empiric observations and therapeutic trials will focus bench-side investigation as clinicians strive to improve the quality of life for patients.
Gastroenterol Clin North Am 1995 Sep
PMID:New therapeutic approaches. 880 34

Although many foods have been suggested to play a role in the cause of IBD, there are not yet definitive data to support diet as a cause of either CD or UC. Malnutrition is a common occurrence in IBD, and this must be considered in the treatment of these diseases. Nutritional support in IBD has limited use as primary therapy (Table 2). Even though parenteral and enteral nutrition have been associated with remission, relapse frequently occurs when normal food intake is resumed. Likewise, fistulae may resolve with aggressive, nutritional therapy, but they frequently recur with reinstitution of food. In short bowel syndrome caused by extensive intestinal resection performed in CD, parenteral nutrition provides an important mode of therapy. In addition, perioperative use of nutritional support may decrease the incidence of postoperative complications in patients who are malnourished. Nutritional support in pediatric patients with CD who have growth failure has been effective in stimulating growth.
Gastroenterol Clin North Am 1995 Sep
PMID:Nutritional considerations in inflammatory bowel diseases. 880 38

If one reviews the literature with zeal, it is increasingly apparent that few organs escape recruitment when IBD is chronic or progressive. Insights into mucosal pathophysiology have helped with understanding the more frequent extraintestinal manifestations, but the mechanisms attendant to the development of less common events (e.g. acute pancreatitis, concurrent gluten sensitive enteropathy, or active pulmonary disease) remain either poorly studied or obscure. It is particularly interesting, however, to read reports of abnormal pulmonary function, generally of the obstructive type, correlated to measurements of abnormal intestinal permeability in patients with either active pulmonary sarcoid or pulmonary involvement in Crohn's disease. It has been further speculated that similarities in the mucosal immune system of the lung and intestine are responsible for evidence of bronchial hyperreactivity in patients with active IBD. Finally, it is important to recognize that extensions of the inflammatory process are not restricted to the development of organ-based events but may be responsible for some of the most frequent systemic abnormalities detected in IBD patients. It is now also well confirmed that the cytokine environment in IBD can support activated coagulation and, in some clinical situations, overt vascular thrombosis. The cerebrovascular complications of IBD are well recognized and range from peripheral venous thrombosis to central stroke syndromes and pseudotumor cerebri. Reports of focal white matter lesions in the brains of patients with IBD or an increased incidence of polyneuropathy may be other clinical examples of regional microvascular clotting. Microvascular injury appears to be more ubiquitously present, with reports ranging from a speculated primary causative role (e.g., granulomatous vasculitis in the mesenteric circulation) to the utility of nailbed vasospasm, in Crohn's disease, as a clinical marker for disease activity. It is also reported that IL-6 suppression of erythropoietin production is a major feature of the chronic anemia seen in active IBD. Moreover, the capacity of peripheral monocytes from active IBD patients to secrete TNF and IL-8 is reported predictive for the degree of therapeutic response from recombinant erythropoietin. These collected observations constitute another excellent example of the symmetry between basic science and clinical utility. It is from the context of applied basic science that many future therapies will arise. Empiricism will lose much of its appeal as clinical observations will be increasingly translated into cellular language. Already in animal models, elemental diets diminish IL-6-related acute inflammatory injury, and reductions in dietary lipid alter the antigenicity of bacteria. Provocatively, in humans, unconfirmed reports have even associated diet therapy with the resolution of uveitis and pyoderma gangrenosum. It is likely that efforts will also be made to induce oral tolerance if specific triggering proteins are discovered or to alter bowel flora if such an arcane area of investigation becomes resurgent.
Gastroenterol Clin North Am 1995 Sep
PMID:Extraintestinal considerations in inflammatory bowel disease. 880 40

PSC is the most common and most important hepatobiliary disease seen in association with IBD. Approximately 5% of all patients with CUC have PSC, and most patients with PSC ultimately develop IBD, usually CUC. PSC and CUC appear to be associated diseases-one does not cause the other, but common pathogenic mechanisms are likely involved. PSC alone does not differ from PSC with IBD with regard to clinical, biochemical, cholangiographic, and hepatic histologic features. There is an overlap syndrome of CAH and PSC in patients with CUC suggesting that patients with CAH and CUC should have a cholangiogram. Colectomy in patients with PSC and CUC does not influence the PSC and, if done for colitic indications, should be accompanied by an ileal pouch-anal anastomosis. Serologic markers are being identified, which are frequently found in PSC with or without CUC, including markers for the dreaded complication of cholangiocarcinoma. Unfortunately, patients with PSC and CUC are doubly at risk for malignancies of the colon and biliary system. Medical therapies are being assessed that may beneficially affect both PSC and CUC, and liver transplantation is life-saving for patients with advanced PSC. Although CAH and gallstones are also found in association with IBD, they are much less common and of considerably less clinical importance than PSC associated with IBD.
Gastroenterol Clin North Am 1995 Sep
PMID:Hepatobiliary disease in inflammatory bowel disease. 880 41

The IBD patient should be optimistic about a potential pregnancy. Inactive IBD is not associated with decreased fertility. Inactive IBD does not affect the course of pregnancy; however, IBD has been associated with increased preterm deliveries. Active IBD during pregnancy is associated with increased stillbirths and spontaneous abortions but not with increased congenital abnormalities. Pregnancy does not cause exacerbation of previously quiescent IBD. If the disease is active at conception, it remains active or worsens in approximately two thirds of patients. Corticosteroids, sulfasalazine, and 5-ASA drugs are safe and should be used to maintain or induce remission. Antimetabolites may possibly be proved safe in the future during pregnancy but cannot yet be recommended. Both enteral nutrition and total parenteral nutrition can and should be used safely and effectively during pregnancy. Radiographs are to be used in diagnosis if an emergent condition, such as perforation or toxic megacolon, is suspected. The chance of an offspring developing IBD is about 9% but rises to 34% if both parents have IBD.
Gastroenterol Clin North Am 1995 Sep
PMID:Pregnancy and nursing. 880 43

From the case example, it can be seen that when the physician considered the psychosocial aspects of the disease in the treatment of Ms. B, she was able to make a complete recovery, something the medications themselves had been unable to do. Although originally thought to be a purely psychosomatic illness, research in IBD in the past three decades has shown that psychosocial aspects are an important component of IBD, but they are not the cause of the disease. Several studies have indicated that stress can adversely affect the gastrointestinal tract directly, by altering inflammatory mediators and gastrointestinal neurotransmitters. To get a complete clinical assessment of how a patient is functioning with the disease, it is important to incorporate psychosocial information into daily patient care in addition to laboratory measurements of disease severity. How does one obtain the psychosocial information for an individual patient? An understanding of the positive and negative factors that may influence how a patient adapts to chronic illness is important, including the patient's social support system, the self-confidence of the patient, and the presence of any comorbid psychiatric disease. In addition, HRQOL can help the clinician identify areas that may be of concern to large groups of patients with the same disease. By incorporating information obtained through HRQOL and modifying it to the psychosocial situation of the individual patient, the treatment plan becomes a negotiated agreement between the physician and the patient. These steps may lead to increased compliance, decreased likelihood of misunderstanding between the physician and the patient, and improvement in the health status of patients with IBD.
Gastroenterol Clin North Am 1995 Sep
PMID:Psychosocial factors in inflammatory bowel disease. 880 44

1. An atypical non beta 1/beta 2-adrenoceptor (AR) subtype (beta 3-AR) has been identified which is selectively stimulated by a group of ligands which mediate lipolytic and thermic responses in brown and white adipose tissue. 2. Molecular studies have shown that beta 3-AR in man are mainly expressed in visceral adipocytes, and to a lesser extent in gall-bladder and colon. In vitro studies with beta 3-AR agonists have shown activity at other sites including skeletal muscle and myocardium. 3. Regulation of beta 3-AR may differ from beta 1/beta 2-AR subtypes in that continuous agonist exposure does not result in receptor down-regulation. 4. A polymorphism of the human beta 3-AR gene (Trp64Arg) has been identified which is associated with obesity, insulin resistance and an earlier onset of non-insulin-dependent diabetes mellitus (NIDDM). Studies are required to establish whether expression of the mutant gene results in altered metabolic responses to beta 3-AR stimulation in man. 5. There is accumulating evidence to support a therapeutic role of beta 3-AR agonists in NIDDM because of anti-obesity and anti-diabetic activity, as a consequence of thermogenic effects as well as increased insulin sensitivity and glucose tolerance. 6. Selectivity studies with BRL35135 and isoprenaline in humans have demonstrated a beta 3-AR mediated component to thermogenesis which is dissociated from beta 1/beta 2-mediated effects on carbohydrate and fat metabolism. Similar studies have suggested a functional beta 3-AR mediating cardiac but not airway responses in humans. An evaluation of beta 3-AR agonists in irritable bowel syndrome may be warranted in view of colonic antimotility properties in vitro.
Br J Clin Pharmacol 1996 Sep
PMID:Clinical pharmacology of beta 3-adrenoceptors. 887 18

IBS is a challenging, functional GI disorder that affects many individuals around the world. Early life experiences, the biologic nature of the condition, and the psychosocial milieu interact to affect the severity and outcome of symptoms. Most people do not seek medical attention for their GI symptoms, or they require intermittent, limited medical therapy and assurance from their physician. Fewer patients, but still a significant number, demand frequent interaction with their physician, who may select pharmacotherapy or psychological and behavioral treatments to control symptoms, depending on the severity. A biopsychosocial approach with attention to the patient-doctor relationship is recommended as the basis for treatment.
Prim Care 1996 Sep
PMID:Newer aspects of the irritable bowel syndrome. 888 39

Despite the progress made in understanding the mechanisms of allergic disease, the pathophysiology and clinical significance of intestinal allergic reactions is largely unclear. The intestinal mucosa is pre-destined for allergic reactions against food proteins and other antigens, and a number of studies indicate that allergic reactions occur in the GI tract. However, only a few epidemiological data are available, and the mechanisms are poorly understood. Intestinal allergic reactions may be different to classical IgE-mediated reactions because patients with intestinal allergy often have negative skin tests and low levels of serum IgE. There is increasing evidence that, as with the findings in the skin and lung, mast cells and eosinophils play a central role in mediating intestinal allergic reactions. Furthermore, both types of cell are found to be activated in a number of other GI inflammatory diseases such as inflammatory bowel disease, celiac disease and eosinophilic gastroenteritis. However, the relationship between these pathologies and intestinal allergy is largely unclear. A major clinical problem is the lack of appropriate means for confirming the diagnosis of intestinal allergy. However, new test systems have been developed--such as the measurement of eosinophil mediators in stool samples or endoscopic provocation tests performed locally at the intestinal mucosa, which may improve the possibility of identifying afflicted patients on an objective basis. Since symptoms of intestinal allergic reactions are variable and non-specific, the diagnosis requires the use of multiple tests and the exclusion of other pathologies such as infectious disease or non-immunological intolerance reactions. The preferred therapeutic option is avoidance of the allergens of relevance; however, this approach can be realized only in some patients, whereas others require additional treatment, for example, with oral cromoglycate or corticosteroids. Although we do not yet know to what extent intestinal allergic reactions may be an aetiological factor in GI diseases, such reactions should be considered in the differential diagnosis of unclear intestinal inflammation and irritable bowel syndrome.
Baillieres Clin Gastroenterol 1996 Sep
PMID:Mucosal allergy: role of mast cells and eosinophil granulocytes in the gut. 890 18


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