Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1291077 (bloating)
 1,674 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From 1990 through 1993, we treated 36 patients with recurrent typical biliary colic but who showed no ultrasonic evidence of cholelithiasis by laparoscopic cholecystectomy. Associated symptoms included nausea (75%), bloating (56%), fatty-food intolerance (53%), vomiting (17%), weight loss (31%), bowel irregularity (28%), reflux or dyspepsia (25%), and fever (17%). Diagnostic evaluation included ultrasound (100%), upper gastrointestinal series (36%), oral cholecystogram (14%), computed tomographic scan (39%), endoscopic retrograde cholangiopancreatography (17%), upper gastrointestinal endoscopy (14%), and hepatobiliary scan (92%). Quantitative hepatobiliary scans in 33 patients revealed a low gallbladder ejection fraction (EF) of less than 35% in 29 patients (88%; mean EF = 9%), and 13 patients experienced reproducible pain after cholecystokinin provocation. All patients underwent attempted laparoscopic cholecystectomy; one case of unsuspected acute acalculous cholecystitis was converted to open laparotomy because of unclear anatomy. Gross and histological examination of the gallbladders revealed chronic inflammation (83%), cholesterolosis (31%), cholesterol crystals or small stones (17%), acute inflammation (8%), polyps (6%), and normal histology (6%); however, blind retrospective scoring of gallbladders revealed significant chronic inflammation in only 38%. In the 2 to 40 months (mean, 14 months) since operation, there have been no deaths (97% follow-up). Laparoscopic cholecystectomy relieved pain in 93% of patients with a low preoperative EF compared with 75% of patients with a normal EF (nonsignificant p value). Persistent abdominal or gastrointestinal complaints included flatulence (31%), loose stools or fecal urgency (29%), belching (29%), indigestion (20%), nausea (11%), and "typical" gallbladder pain (9%). We conclude that many patients with symptoms of biliary colic and scintigraphic evidence of biliary dyskinesia have histologic findings of chronic cholecystitis. Although laparoscopic cholecystectomy usually eliminates biliary colic, persistent nonbiliary complaints are frequent.
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PMID:Chronic acalculous cholecystitis: laparoscopic treatment. 868 Jun 33

Irritable bowel syndrome (IBS) continues to provide a major therapeutic challenge to clinicians and those involved in drug development. It seems unlikely from the data before us that this multisymptom syndrome with peripheral and central components is likely to respond reliably in all patients to the same single agent. There is still a lack of well designed, appropriately powered, randomised clinical trials and the problems of dealing with the high placebo response rate in this group of patients remains a dilemma for trial designers. There are, however, some new ideas, particularly those relating to the role of hyperalgesia in IBS. For many patients, abdominal pain and bloating are the most distressing symptoms of this disease and the new drugs targeted at pain control, such as kappa agonists and serotonin antagonists (5-HT3) and possibly 5-HT4), may eventually find a place in the clinical management of this syndrome. Other candidates include somatostatin analogues and antidepressants, the latter predominantly for their effects on increasing pain threshold. More speculative new drugs for IBS include cholecystokinin antagonists such as loxiglumide and the gonadotrophin-releasing hormone analogue, leuprorelin (leuprolide). The results of on-going randomised clinical trials are still awaited for some of these newer agents. The irritable bowel syndrome (IBS) is the most common gastrointestinal condition encountered by general practitioners and is reported to account for up to 50% of the work of gastroenterologists in secondary care. However, most people with the symptoms of IBS (60 to 75%) do not consult a doctor. Its cause is unknown, its development is poorly understand and, perhaps not surprisingly, no universally agreed approach to treatment exists.
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PMID:New drugs in the management of the irritable bowel syndrome. 966 95

Abdominal pain/discomfort, bloating, need to rush to the toilet, straining, feeling of incomplete bowel emptying and alternating periods of diarrhea and constipation is the clinical definition of the irritable bowel syndrome. The internationally used syndrome definition is based on expert opinions and answers to patient questionnaires. When symptoms are registered prospectively, abdominal pain starts or worsens after meals and is not relieved by defecation. As in the general population patients with the syndrome define diarrhea as loose stools and constipation as hard stools regardless of stool frequencies. Variation in defecatory symptoms and discrepancies between these symptoms and stool consistency are the hallmarks of the syndrome, and the degree of variation per fortnight is relatively stable in the individual patient. Fermentation of carbohydrates by colonic bacteria, increased sensitivity to bowel distention by gas, gas-producing food, increased secretion of cholecystokinin after fatty meals and/or increased sympathetic nerve tone at stress can give rise to symptoms. Symptoms can start after a single period of bacterial gastroenteritis. Although patients seeking medical care for the syndrome are more often anxious, the syndrome itself is not psychosomatic. Symptoms are possibly mediated through partial degranulation of mast cells in bowel mucosa, but this does not make it an allergic disease. If bowel dysmotility can be measured, early stage or a mild case of intestinal pseudoobstruction should be considered. Hyperreactivity in the enteric nervous system and/or in the brain is the likely main cause of the symptoms. More widespread activity in the brain after exposure to stimuli originating from bowel nerves or less inhibition of this stimulation in the brain are possible mechanisms.
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PMID:[Irritable bowel syndrome. Survey of definitions, differential diagnosis and pathogenesis]. 1147 55

The main factors involved in the pathophysiology of fat induced dyspepsia were investigated by reviewing a series of controlled double blind randomised studies which sought to determine the role of nutrient fat and the postprandial release of cholecystokinin (CCK) in the development of dyspeptic symptoms in healthy volunteers and in patients with functional dyspepsia. The studies showed that during distension of the stomach, lipids are a major trigger of dyspeptic symptoms such as nausea, bloating, pain, and fullness, and that they modulate upper gastrointestinal sensations and symptoms in a dose related fashion. CCK is a major mediator of the sensitisation of gastric perception by lipids in patients with functional dyspepsia as the CCK-A receptor antagonist dexloxiglumide markedly diminishes this effect. The studies provide important insights into the mechanisms underlying gastrointestinal perception in response to fat and the role of CCK in patients with functional dyspepsia.
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PMID:The role of fat and cholecystokinin in functional dyspepsia. 1207 66

Anticholinergics and prokinetics are mainstays of therapy for Irritable Bowel Syndrome (IBS) patients despite their limited efficacy and troublesome side-effect profile. The clinical limitations of these drugs are a result of their relative broad and nonspecific pharmacologic interaction with various receptors. Recent advances in gut physiology have led to the identification of various receptor targets that may play a pivotal role in the pathogenesis of IBS. Medicinal chemists searching for safe and effective IBS therapies are now developing compounds targeting many of these specific receptors. The latest generation of anticholinergics, such as zamifenacin, darifenacin, and YM-905, provide selective antagonism of the muscarinic type-3 receptor. Tegaserod, a selective 5-HT4 partial agonist, tested in multiple clinical trials, is effective in reducing the symptoms of abdominal pain, bloating, and constipation. Ezlopitant and nepadudant, selective antagonists for neurokinin receptors type 1 and type 2, respectively, show promise in reducing gut motility and pain. Loperamide, a mu (mu) opioid receptor agonist, is safe and effective for IBS patients with diarrhea (IBS-D) as the predominant bowel syndrome. Fedotozine, a kappa (kappa) opioid receptor agonist, has been tried as a visccral analgesic in various clinical trials with conflicting results. Alosetron, a 5-HT3 receptor antagonist, has demonstrated efficacy in IBS-D patients but incidents of ischemic colitis seen in post-marketing follow-up resulted its removal from the market. Compounds that target cholecystokinin. A, N-methyl-D-aspartate, alpha 2-adrenergic, and corticotropin-releasing factor receptors are also examined in this review.
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PMID:Irritable bowel syndrome neuropharmacology. A review of approved and investigational compounds. 1218 41

The management of the irritable bowel syndrome (IBS) remains unsatisfactory. For abdominal pain, antispasmodics are, at best, of only modest efficacy. Tricyclic antidepressants in low dose are useful (with the number needed to treat being three), but side effects and patient concerns regarding use of a centrally acting agent for depression remain limitations. Selective serotonin reuptake inhibitors are of uncertain efficacy in IBS. Opioid agonists, especially loperamide, are useful for diarrhea but not for pain in IBS; rebound constipation also remains a problem. Bile salt sequestering agents are not of established value in IBS but seem to be useful clinically in a small group of IBS patients with diarrhea. Aloestron, a 5HT(3) antagonist, should be reserved, if available, for women with severe diarrhea predominant IBS who have failed to respond to conventional therapy, and started at a low dose. Fiber and bulking agents may help constipation in some trials, but the evidence that they are efficacious in IBS is equivocal; they are frequently prescribed as first-line drugs for IBS regardless of the primary bowel disturbance but often increase bloating, gas, and pain. Laxatives are not of established value in IBS but are often taken by patients with constipation predominant IBS. Tegaserod, a partial 5HT(4) agonist, is now available in the United States and other countries for use in women with IBS whose primary bowel symptom is constipation; its efficacy in men and in those with alternating bowel habits is unknown. Probiotics are of uncertain efficacy. Chinese herbal medicine data are insufficient. Other new drugs in development include the cholecystokinin antagonists and novel visceral analgesics. Both current and potential therapies for IBS are reviewed in this article.
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PMID:Pharmacologic therapy for the irritable bowel syndrome. 1273 51

Irritable bowel syndrome (IBS) is an extremely common cause of consultation, and at present is diagnosed on the basis of symptoms and a few simple exclusion tests. Exclusion diets can be successful, but many patients have already attempted and failed such treatments before consulting. Anxiety and somatization may be an important driver of consultation. Patients' concerns should be understood and addressed. Those with prominent psychiatric disease may benefit from psychotherapy. Hypnotherapy benefits symptoms in those without psychologic disturbance, but its availability is limited. Antidepressants are effective in improving both mood and IBS symptoms globally, and the evidence is particularly good for tricyclic antidepressants. Although antispasmodics are currently the most commonly prescribed drugs, most responses (75%) are due to the placebo effect and not specific to the drug. Bulk laxatives such as ispaghula can increase stool frequency and help pain, but bloating may be aggravated. Loperamide is effective treatment for urgency and loose stools, but less effective for bloating and pain. 5-HT(3) antagonists such as alosetron improve urgency, stool consistency, and pain in diarrhea-predominant-IBS. The 5-HT(4) agonist tegaserod shows modest benefit in constipation-predominant IBS, improving stool frequency, consistency, and bloating as well as global improvement. There are many new drugs, such as cholecystokinin, neurokinin, and corticotropin receptor antagonists, in development.
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PMID:Treatment of Irritable Bowel Syndrome. 1284 42

Cholecystokinin (CCK) is a brain-gut peptide; it functions both as a neuropeptide and as a gut hormone. Although the pancreas and the gallbladder were long thought to be the principal peripheral targets of CCK, CCK receptors are found throughout the gut. It is likely that CCK has a physiological role not only in the stimulation of pancreatic and biliary secretions but also in the regulation of gastrointestinal motility. The motor effects of CCK include postprandial inhibition of gastric emptying and inhibition of colonic transit. It is now evident that at least two different receptors, CCK(1) and CCK(2) (formerly CCK-A and CCK-B, respectively), mediate the actions of CCK. Both localization and functional studies suggest that the motor effects of CCK are mediated by CCK(1) receptors in humans. Since CCK is involved in sensory and motor responses to distension in the intestinal tract, it may contribute to the symptoms of constipation, bloating and abdominal pain that are often characteristic of functional gastrointestinal disorders in general and irritable bowel syndrome (IBS), in particular. CCK(1) receptor antagonists are therefore currently under development for the treatment of constipation-predominant IBS. Clinical studies suggest that CCK(1) receptor antagonists are effective facilitators of gastric emptying and inhibitors of gallbladder contraction and can accelerate colonic transit time in healthy volunteers and patients with IBS. These drugs are therefore potentially of great value in the treatment of motility disorders such as constipation and constipation-predominant IBS.
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PMID:Involvement of endogenous CCK and CCK1 receptors in colonic motor function. 1510 Jan 63

Symptoms of functional dyspepsia are characterized by upper abdominal discomfort or pain, early satiety, postprandial fullness,bloating, nausea and vomiting. It is a chronic disorder, with symptoms more than 3 mo per year,and no evidence of organic diseases. Dysfunctional motility, altered visceral sensation, and psychosocial factors have all been identified as major pathophysiological mechanisms. It is believed that these pathophysiological mechanisms interact to produce the observed symptoms. Dyspepsia has been categorized into three subgroups based on dominant symptoms. Dysmotility-like dyspepsia describes a subgroup of patients whose symptom complex is usually related to a gastric sensorimotor dysfunction. The brain-gut peptide cholecystokinin (CCK) and serotonin (5-HT) share certain physiological effects. Both have been shown to decrease gastric emptying and affect satiety. Furthermore the CCK induced anorexia depended on serotonergic functions probably acting via central pathways. We believe that abnormalities of central serotonergic receptors functioning together with a hyper responsiveness to CCK or their interactions may be responsible for the genesis of symptoms in functional dyspepsia (FD).
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PMID:Role of cholecystokinin and central serotonergic receptors in functional dyspepsia. 1655 97

Women often complain gut symptoms during pregnancy and the luteal phase of the menstrual cycle. To investigate the relationship between ovarian steroids and the abnormal gut motility and sensitivity, the expressions of cholecystokinin (CCK), calcitonin gene-related peptide (CGRP) and their receptors in stomach were studied in ovariectomized rats. Blood samples were collected for estradiol (E(2)), progesterone (P(4)), CCK and CGRP radioimmunoassay. Expression of CCK(A) receptor in fundus was assessed by Western blot and CGRP receptor was determined by (125)I-CGRP radioligand binding assay (RBA). The replacement therapy with estradiol benzoate (EB) could dose-dependently increase the plasma CCK level and the expression of gastric CCK(A) receptor (P<0.05 respectively). P(4) replacement therapy could stimulate the release of CGRP and increase the binding sites of CGRP receptors in stomach (P<0.05 respectively). The combined effect of EB and P(4) was to stimulate the release of CCK and CGRP, and to increase the expressions of gastric CCK(A) and CGRP receptors. These results indicate that EB could inhibit gastric emptying by increasing CCK secretion and CCK(A) receptor expression in ovariectomized rats. P(4) could increase gut sensitivity by up-regulating the release of CGRP and the activity of CGRP receptor. It could be deduced from these observations that CCK(A) and CGRP receptor antagonists could be used for female patients who suffer from gastrointestinal dysfunction closely related with the menstrual cycle, such as distension, satiety, bloating and abdominal pain.
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PMID:Regulative effects of ovarian steroids on rat gastric motility and sensitivity. 1678 13


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