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

Distension of the gastrointestinal tract elicits abdominal pain, as well as sensations such as discomfort or fullness. Many patients with irritable bowel syndrome have been reported to show a reduced threshold to the pain or discomfort due to experimental rectal distension. This hypersensitivity of the gut may be characteristics of the irritable bowel, as well as other functional gastrointestinal disorders. Intestinal distension in animals induces a range of responses which have been used as indexes of visceral nociception. This paper reviews a recently introduced canine model used to assess the antinociceptive properties of a novel 5-HT3 receptor antagonist, alosetron.
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PMID:Review article: evaluation of drugs in experimental gut distension models. 1042 41

Irritable bowel syndrome (IBS) is a common chronic functional bowel disorder characterized by abdominal pain or discomfort and alterations in bowel habits. In clinical practice, diagnosis is based on positive symptoms known as the Rome criteria and limited diagnostic screen, taking into account warning features suggestive of organic disease. Minimal diagnostic tests are warranted to rule out structural lesions in a cost-effective manner and to convince the patient of the diagnosis of IBS. An initial diagnosis of IBS is safe and rarely needs revision over time. Persistence of symptoms is to be expected and does not justify suspicion of other diagnoses. Only change in the clinical pattern over time justifies additional investigations. Other diagnostic evaluations depend on predominant symptoms, namely constipation, diarrhea, and pain or discomfort. It should be emphasized that although an initial "positive diagnosis" is safe to exclude other diseases with similar symptoms, a common disorder such as IBS may often coexist with other asymptomatic disorders.
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PMID:Diagnostic approach to the patient with irritable bowel syndrome. 1058 69

Irritable bowel syndrome (IBS) is a chronic disorder with symptoms that range in intensity from mild and infrequent to severe and continuous. A variety of approaches to symptom assessment are used in IBS, although there is little literature directly comparing or validating them. Determining the presence or absence of specific symptoms is the primary focus of diagnostic evaluation and categorization. In contrast, outcome assessment usually entails assessment of symptom severity. Symptom severity scales can themselves vary on a wide range of factors, including specificity (pain, discomfort, gastrointestinal problem), scaling properties (numerical, analogue, or descriptor), range (usual, highest, lowest), time frame (now, past week), response category (intensity, unpleasantness, change, relief), and use of modifying variables (frequency, impact, location). The measurement properties of similar symptom scales have been investigated more extensively in the context of somatic pain, and these studies will be reviewed in suggesting some guidelines for IBS symptom assessment in clinical trials.
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PMID:Measurement of symptoms in irritable bowel syndrome clinical trials. 1058 77

Alosetron is a potent and highly selective serotonin 5-HT3 receptor antagonist which has been evaluated for the management of irritable bowel syndrome (IBS). It blocked the fast 5HT3-mediated depolarisation of guinea-pig myenteric and submucosal neurons in vitro, with half-maximal inhibition at approximately 55 nmol/L. Alosetron attenuated the visceral nociceptive effect of rectal distension in conscious or anaesthetised dogs. It increased the compliance of the colon to distension in patients with IBS and delayed colonic transit in patients with IBS or carcinoid diarrhoea and in healthy volunteers. A single dose of alosetron 4 mg increased in vivo fluid absorption in normal human small intestine. In clinical trials in patients with IBS, alosetron 1 mg twice daily was effective in relieving abdominal pain and discomfort. Alosetron was most effective in female patients and particularly in those with diarrhoea-predominant IBS. In patients with IBS and healthy volunteers who received alosetron, the most common adverse event was constipation.
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PMID:Alosetron. 1077 33

Alterations in activation of pain modulation systems may play a role in the pathophysiology of irritable bowel syndrome (IBS). However, little is known about the effects of exogenous opioids on the perceptual and autonomic responses to aversive visceral stimulation. The aim of the study was to evaluate the effect of the mu opioid-preferring analgesic fentanyl (FEN), given intravenously, on perceptual and autonomic responses to rectal distension. Ten IBS patients and ten normal subjects received, on separate days, either high dose (HD) fentanyl (112 microg bolus followed by 0.04 microg/kg per min infusion), low dose (LD) fentanyl (56 microg bolus followed by 0.02 microg/kg per min) or normal saline (SAL) (50 cc bolus followed by 45 cc/h infusion). Perception thresholds for discomfort and pain during rectal distension were assessed using a tracking paradigm. Intensity and unpleasantness ratings of the distensions, and cardiac autonomic parameters were assessed during randomly delivered rectal stimuli. Effects of FEN on rectal compliance and tone as well as mental status were also assessed. IBS patients had lower perceptual thresholds for discomfort and pain under control conditions. FEN dose-dependently increased the perception thresholds in both healthy control subjects and in IBS patients with a greater relative efficacy in IBS patients than in normal subjects. IBS patients used significantly higher unpleasantness ratings of rectal stimuli compared to healthy controls, but showed no difference in the sensory intensity rating of the stimulus. FEN decreased both intensity and unpleasantness ratings for IBS and normals. FEN lowered cardiosympathetic tone in normal subjects but had no effect on IBS patients. FEN had no effect on rectal tone or compliance. FEN dose-dependently attenuates the perception of phasic rectal distension and affects unpleasantness ratings during random fixed rectal distension, with a greater relative efficacy for this antinociceptive effect in IBS patients. These findings support the hypothesis that IBS patients may have an altered central release of endogenous opioids in response to visceral stimulation.
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PMID:Irritable bowel syndrome patients show altered sensitivity to exogenous opioids. 1092 7

In two experiments including a total of 30 irritable bowel syndrome patients, symptom-mimicking rectal pressure stimuli elicited changes in regional neural activation as measured by positron electron tomography (PET) cerebral blood flow images. Although most stimuli were not rated as painful, rectal pressure increased regional cerebral blood flow (rCBF) in areas commonly associated with somatic pain, including the anterior cingulate, insula, prefrontal cortex, thalamus, and cerebellum. Despite similar stimulus ratings in male and female patients, regional activations were much stronger for males. In both experiments, rectal pressure activated the insula bilaterally in males but not in females. Insula activation was associated most strongly with objective visceral pressure, whereas anterior cingulate activation was associated more with correlated ratings of subjective discomfort. The insula is discussed as a visceral sensory cortex. Several possible reasons for the insula gender effect are proposed.
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PMID:Gender differences in regional brain response to visceral pressure in IBS patients. 1095 97

Alosetron (Lotronex) is a potent, highly selective 5-HT(3) antagonist. Animal models have shown it to be active in anxiety, psychosis, cognitive impairment, emesis and drug withdrawal, though its application in humans has been almost entirely restricted to irritable bowel syndrome (IBS). Alosetron does not cause adverse pharmacodynamic effects, is absorbed rapidly after oral administration and is widely distributed throughout tissues after oral or iv. dosing in animals. Its metabolism is rapid and extensive with N-demethylation, hydroxylation and oxidation. The drug, or its two principal metabolites, is equally excreted through the biliary tract and kidneys. Alosetron has proved safe in a range of toxicity studies; at high repeated dosing, clinical signs were transient and repeated administration produced no significant adverse effects on fertility, reproductive performance or fetal development. In pharmacokinetic studies, bioavailability of alosetron in healthy volunteers is approximately 60% and the plasma half-life is about 1.5 h. There are some gender differences in the pharmacokinetic profile, with 30 - 50% higher alosetron concentrations in females. No consistent differences in alosetron serum concentrations between the young and elderly were observed. The pharmacokinetics of single, oral doses of alosetron are linear up to 8 mg. In human pharmacodynamic studies, alosetron increased basal jejunal water and electrolyte absorption, increased colonic transit time and, consequently, whole gut transit time. Alosetron has been evaluated in two large Phase II trials (randomised, double-blinded, placebo-controlled) and in Phase III trials which included a four-week observation period after cessation. Dose response studies suggested that the effective dosages could be between 1 and 2 mg, twice-daily. In Phase II trials, alosetron, 1 mg b.i.d., resulted in a greater proportion of non-constipated IBS patients reporting adequate relief of pain and discomfort, as well as improvement of bowel symptoms, frequency, urgency and stool consistency when compared with placebo. However, this beneficial effect was seen exclusively among females. Phase III studies evaluated exclusively females with non-constipated IBS and confirmed the results of the Phase II studies. Alosetron was well-tolerated in all studies, with the most frequently recorded adverse event being constipation. Thus, alosetron appears promising in the treatment of abdominal pain and discomfort and normalising of bowel function in patients with non-constipated IBS. It also improves quality of life, has a high degree of tolerability and has an excellent safety profile to date.
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PMID:Pharmacology and clinical experience with alosetron. 1106 Jun 67

The irritable bowel syndrome (IBS) is a functional gastrointestinal disorder whose hallmark is abdominal pain or discomfort associated with a change in the consistency or frequency of stools. In the western world, 8% to 23% of adults have IBS and its socioeconomic cost is substantial. Research-generated insights have led to the understanding of IBS as a disorder of brain-gut regulation. The experience of symptoms derives from dysregulation of the bidirectional communication system between the gastrointestinal tract and the brain, mediated by neuroendocrine and immunological factors and modulated by psychosocial factors. The biopsychosocial model integrates the various physical and psychosocial factors that contribute to the patient's illness. This model and the recently revised symptom-based criteria (i.e. the "Rome II criteria") form the basis for establishing a comprehensive and effective approach for the diagnosis and management of the disorder.
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PMID:Irritable bowel syndrome. 1116 Jul 82

Dyspepsia refers to pain or discomfort centered in the upper abdomen. This symptom is remarkably common, with 1-year prevalence rates averaging 25% in the community. Symptoms suggestive of the irritable bowel syndrome and reflux disease frequently overlap but do not form part of the definition of dyspepsia. Electrical and other stimuli can cause similar or different symptoms in various patients, and even the site to which symptoms are referred varies considerably. Dyspeptic symptoms are therefore a relatively poor guide to the origin or nature of any "disturbances" in the gut. Identification of patients who require further investigation to rule out serious structural disease, such as peptic ulcer disease or cancer, is a key issue because unaided clinical diagnosis is unreliable. The use of an age threshold (typically 45 years) and the identification of alarm features, including weight loss, repeated vomiting, and signs of bleeding, seem to be valid on the basis of the limited evidence available. Dyspeptic symptoms fall into distinct subgroups resembling the perceived clinical entities of ulcer-like and dysmotility-like dyspepsia. Unfortunately, because of overlap with reflux symptoms and between the subgroups, the clinical significance of these groups remains highly questionable. A focus on symptom predominance may be more rewarding. Lack of validated outcome measures has hampered clinical studies and has led to the development of complex outcome measures that integrate and weigh different symptoms or other indirect indicators of outcome into a general score. Further testing and validation are in progress.
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PMID:Dyspepsia. 1134 16

Irritable bowel syndrome is one of the most commonly encountered functional gastrointestinal disorders, affecting an estimated one in five adult Americans. It is characterized by a symptom complex that includes chronic abdominal pain and discomfort that is relieved with defecation, abnormal stool frequency, and a change in stool form. Although the etiology of this disorder continues to remain elusive, this article reviews the current theory of the pathophysiologic mechanisms and reports on diagnostic and management principles for the primary care provider.
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PMID:Irritable bowel syndrome. 1139 10


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