Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 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

Feeding problems, anorexia and vomiting are common in infants and children with chronic renal failure (CRF), and play a major role in the growth failure often found in this condition. However, the gastroenterological and nutritional aspects of CRF in children have received little attention, hence therapeutic interventions are usually empirical and often ineffective. Gastritis, duodenitis and peptic ulcer are often found in adults with CRF on regular haemodialysis and following renal transplantation. Despite persistent hypergastrinaemia, gastric acid secretion is decreased rather than increased in most of these patients, and active peptic disease appears to be promoted by the removal of the acid output inhibition (neutralisation of gastric acid by ammonia) that follows active treatment. Helicobacter pylori, on the other hand, does not seem to play a significant role in the pathogenesis of peptic disease in CRF. Gastro-oesophageal reflux has been found in about 70% of infants and children with CRF suffering from vomiting and feeding problems, and thus appears to be a major problem in these patients. In a number of symptomatic patients with CRF, gastric dysrhythmias and delayed gastric emptying have also been found; hence there appears to be a complex disorder of gastrointestinal motility in CRF. Serum levels of several polypeptide hormones involved in the modulation of gastrointestinal motility [e.g. gastrin, cholecystokinin (CCK), neurotensin] and the regulation of hunger and satiety (e.g. glucagon, CCK) are significantly raised as a consequence of renal insufficiency, and can be reverted to normal by renal transplantation. Furthermore, several other humoral abnormalities (e.g. hypercalcaemia, hypokalaemia, acidosis, etc.) are not uncommon in CRF. By directly affecting the smooth muscle of the gut or stimulating particular areas within the central nervous system, all these humoral alterations may well play a major role in the gastrointestinal dysmotility, anorexia, nausea and vomiting in patients with CRF. Specific pharmacological and nutritional interventions should thus be considered for the treatment of vomiting and feeding problems in CRF.
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PMID:Gastrointestinal function in chronic renal failure. 874 22

To investigate changes in motility of the extrahepatic biliary system associated with emesis, we measured the volume of the gallbladder and flow resistance through the sphincter of Oddi, as well as antral and duodenal contractilities before and during retching in decerebrate paralyzed dogs. Motilities of the gallbladder, sphincter of Oddi, duodenum and antrum were enhanced with most episodes of fictive retching elicited by stimulation of the central part of the severed dorsal, as well as the ventral trunk of the thoracic vagus nerve. These enhanced motilities persisted until the end of retching. Motilities of the sphincter of Oddi and duodenum were sometimes transiently depressed at the beginning of retching. This depression in the sphincter continued for only 13 +/- 1.0 s, while the gallbladder contraction continued for 65 +/- 3.4 s. Motilities were rarely enhanced by vagal stimulation when retching was not elicited. These changes in motilities were abolished by bilateral vagotomy. The serum gastrin level was increased just after and 10 min after retching only when the ventral vagal trunk remained intact, while the plasma cholecystokinin level was not changed with retching. These results suggest that bile evacuation is interrupted with emesis despite contraction of the gallbladder during retching, since the sphincter of Oddi also contracts simultaneously.
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PMID:Changes in extrahepatic biliary motilities with emesis in dogs. 878 85

The pharmacological characteristics of DQ-2511, a substituted benzamide (3-[[[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl]methyl] amino-N-methylbenzamide), as a prokinetic agent were studied. Cholecystokinin-octapeptide, dopamine, and alpha-calcitonin gene-related peptide, all suppressed gastric emptying in mice. Reversal of the depressed emptying occurred when DQ-2511 was administered by the oral or intraperitoneal route. When the action of eight proposed metabolites of DQ-2511 on the mouse cholecystokinin-octapeptide model was investigated, the main metabolite in plasma, MA-2, showed no effect, although two minor metabolites ameliorated or aggravated the delayed gastric emptying. This finding implies that DQ-2511, as the parent compound itself, exerts the ameliorative action. In dogs treated with cisplatin or copper sulfate, DQ-2511 had no antiemetic activity, as assessed by the number of vomiting episodes. The concern that the mechanism of action of DQ-2511 was blockade of receptors for cholecystokinin-octapeptide, dopamine, serotonin, alpha-calcitonin gene-related peptide, nicotine or muscarine, was resolved by results of radioligand binding studies showing the absence of a DQ-2511 binding to any of these receptor types. Evidence is accumulating that the mechanism of the prokinetic action of DQ-2511 involves the intrinsic and extrinsic autonomic innervation.
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PMID:Pharmacological characteristics of DQ-2511 as a prokinetic agent. 883 52

The relative contributions of several gut-derived peptides as enterogastrones known to be released in response to a fatty meal and to inhibit acid secretion have not previously been compared directly. We determined the acid-inhibitory activities of increasing intravenous doses of several peptides before and after highly selective vagotomy (HSV) during intragastric titration of a peptone meal in dogs. Before HSV, threshold inhibitory doses of peptide YY (PYY), cholecystokinin (CCK), and secretin were 5, 7, and 10 pmol.kg-1.h-1, respectively, whereas neurotensin, glucagon-like peptide-1 (GLP-1), and oxyntomodulin failed to inhibit acid secretion at doses up to 1,000 pmol.kg-1.h-1. The calculated dose producing 50% acid inhibition (ID50) of secretin (62 pmol.kg-1.h-1) was one-half that of PYY (128 pmol.kg-1.h-1). Maximal (90%) acid inhibition was produced by 100 pmol.kg-1.h-1 secretin and 500 pmol.kg-1.h-1 PYY. The highest dose of CCK that did not cause vomiting (100 pmol.kg-1.h-1) inhibited peptone-stimulated acid output by only 60%. After HSV, 500 pmol.kg-1.h-1. PYY and 200 pmol.kg-1.h-1 CCK failed to inhibit acid output by more than 50%. Threshold doses for inhibition by PYY and CCK were 200 and 100 pmol.kg-1.h-1, respectively. Secretin remained a potent inhibitor after HSV, with an ID50 of 80 pmol.kg-1.h-1 and a threshold dose of 10 pmol.kg-1.h-1. HSV also failed to affect inhibition caused by somatostatin. This study has shown that PYY and secretin are somewhat more potent and efficacious inhibitors of acid secretion than CCK but that all three peptides are far more active than GLP-1, neurotensin, and oxyntomodulin. PYY and CCK inhibit acid secretion in large part through vagal innervation of the gastric fundus, but the inhibitory effects of secretin are independent of fundic vagal innervation.
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PMID:Candidate canine enterogastrones: acid inhibition before and after vagotomy. 917 35

Cholecystokinin octapeptide (CCK-8) and the peptide analog ARL 14294, formerly FPL 14294, [Hpa(SO3H)-Met-Gly-Trp-Met-Asp-N(Me)Phe-NH2], have been reported to induce satiety by interaction with the CCK-A receptor subtype. ARL 15849 [Hpa(SO3H)-Nle-Gly-Trp-Nle-N(Me)-Asp-Phe-NH2] is an improved ARL 14294 analog with enhanced CCK-A receptor selectivity, greater stability, and a longer duration of action. The affinity of ARL 15849 for the CCK-A receptor (Ki = 0.034 nM) is 6,600 fold greater than for the CCK-B receptor (Ki = 224 nM), whereas CCK-8 and ARL 14294 are nonselective. Although comparable in potency to contract isolated gallbladder and induce pancreatic phosphatidylinositol hydrolysis, ARL 15849 is 3- and 100-fold more potent than ARL 14294 and CCK-8, respectively, to inhibit 3-h feeding in rats. The duration of feeding inhibition was significantly longer for ARL 15849 (>5 h), compared to equipotent doses of ARL 14294 (3 h), and CCK-8 (1 h). Intranasal administration of ARL 15849 inhibits feeding in beagle dogs with a greater separation between doses that induce emesis and those that inhibit feeding. Therefore, ARL 15849 is a potent, selective, intranasally active anorectic agent which may be useful in the treatment of eating disorders.
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PMID:ARL 15849: a selective CCK-A agonist with anorectic activity in the rat and dog. 947 93

Bulimia nervosa is an eating disorder characterised by recurrent episodes of binge eating and associated efforts to purge the ingested calories through self-induced vomiting, laxative or diuretic abuse, fasting or intensive exercise. The aetiopathogenesis and pathophysiology of the disorder are currently unclear. Biological bases have been proposed repeatedly, based on several lines of evidence: hunger, satiety and food choice are regulated by neurotransmitters and neuropeptides, and impairment of eating habits may be related to alterations in the secretion of these chemicals; genetic studies suggest that these neurotransmitter systems are dysfunctional in individuals with bulimia nervosa; and the frequent comorbidity of bulimia nervosa with major depressive and obsessive-compulsive disorders, conditions in which multiple alterations of brain biochemical functions have been demonstrated. Data in the literature suggest that levels of noradrenaline (norepinephrine) and serotonin (5-hydroxytryptamine; 5-HT) are lower in individuals with bulimia nervosa than in healthy controls. Levels of dopamine are similar to, or lower than, those in controls. After remission of the disorder, noradrenergic function returns to that seen in controls, whereas dopaminergic and serotonergic function rebound to levels higher than in controls. Among the neuropeptides, alterations in the levels of neuropeptide Y, peptide YY, beta-endorphin, corticotrophin-releasing hormone, somatostatin, cholecystokinin and vasopressin have been found in the symptomatic phase of bulimia nervosa, with a return to levels seen in controls after remission. Pharmacological treatment of bulimia nervosa that is directed at correction of the neurochemical alterations observed is difficult because of the complexity of the impairments. However, such treatment is necessary and should be continued long after symptomatic remission to ensure reinstitution of cerebral biochemical homeostasis.
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PMID:Aetiopathogenesis and pathophysiology of bulimia nervosa: biological bases and implications for treatment. 1146 Aug 90

The pharmacological profile of AS-9705 ((R)-N-(1-ethyl-1H-hexahydroazepin-3- yl)-6- methoxy-1H-benzotriazole-5-carboxamide fumarate monohydrate, CAS 219622-61-4), a novel gastroprokinetic agent with potent anti-emetic activity, was investigated in the present study. AS-9705 inhibited [3H]spiperone binding to human dopamine D2.long receptors, and [3H]R(+)-7-OH-DPAT binding to human dopamine D3 receptors (IC50 values of 58.5 +/- 14.0 and 60.8 +/- 7.8 (nmol/l), respectively) and had negligible affinity (IC50 > 10 mumol/l) for other neurotransmitter recognition sites examined. Moreover, in ferrets or dogs, AS-9705 dose-dependently inhibited emesis induced by R(+)-7-OH-DPAT and apomorphine with ID50 values of 0.05 mg/kg p.o. and 0.04 mg/kg p.o., respectively. AS-9705 dose-dependently enhanced normal gastric emptying and potently inhibited the delay in gastric empting induced by apomorphine, morphine, cisplatin, clonidine and cholecystokinin in rats. Furthermore, in conscious fasting dogs, AS-9705 dose-dependently stimulated gastric motility. In conclusion, AS-9705 is a novel gastroprokinetic agent with potent antiemetic activity and minimal CNS adverse effects and is, therefore, worthy of clinical investigation.
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PMID:Pharmacological profile of AS-9705, a novel benzotriazolecarboxamide derivative, as a gastroprokinetic agent with potent anti-emetic activity. 1264 65

Functional dyspepsia is a clinical syndrome defined by chronic or recurrent pain or discomfort in the upper abdomen of unknown origin. Although generally accepted, investigators differently interpret this definition and clinical trials are often biased by inhomogeneous inclusion criteria. The poorly defined multifactorial pathogenesis of dyspeptic symptoms has hampered efforts to develop effective treatments. A general agreement exists on the irrelevant role played by Helicobacter pylori in the pathophysiology of functional dyspepsia. Gastric acid secretion is within normal limits in patients with functional dyspepsia but acid related symptoms may arise in a subgroup of them. Proton pump inhibitors appear to be effective in this subset of patients with dyspepsia. Non-painful dyspeptic symptoms are suggestive of underlying gastrointestinal motor disorders and such abnormalities can be demonstrated in a substantial proportion of patients. Postprandial fullness and vomiting have been associated with delayed gastric emptying of solids, and early satiety and weight loss to postcibal impaired accommodation of the gastric fundus. Prokinetics have been shown to exert beneficial effects, at least in some patients with dyspepsia. In contrast, drugs enhancing gastric fundus relaxation have been reported to improve symptoms, although conflicting results have also been published. An overdistended antrum may also generate symptoms, but its potential pathogenetic role and the effects of drugs on this abnormality have never been investigated formally. Visceral hypersensitivity plays a role in some dyspeptic patients and this abnormality is also a potential target for treatment. Both chemo- and mechanoreceptors can trigger hyperalgesic responses. Psychosocial abnormalities have been consistently found in functional digestive syndromes, including dyspepsia. Although useful in patients with irritable bowel syndromes (IBS), antidepressants have been only marginally explored in functional dyspepsia. Among the new potentially useful agents for the treatment of functional dyspepsia, serotonin 5-HT(4) receptor agonists have been shown to exert a prokinetic effect. Unlike motilides, 5-HT(4) receptor agonists do not appear to increase the gastric fundus tone and this may contribute to improve symptoms. 5-HT(3) receptor antagonists have been investigated mainly in the IBS and the few studies performed in functional dyspepsia have provided conflicting results. Also, kappa-opioid receptor agonists might be useful for functional digestive syndromes because of their antinociceptive effects, but available results in functional dyspepsia are scanty and inconclusive. Other receptors that represent potential clinical targets for antagonists include purinoceptors (i. e., P2X2/3 receptors), NMDA receptors (NR2B subtype), protease-activated receptor-2, the vanilloid receptor-1, tachykinin receptors (NK(1)/NK(2)) and cholecystokinin (CCK)(1) receptors.
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PMID:New developments in the treatment of functional dyspepsia. 1267 73

Patients with biliary dyskinesia have biliary colic, a normal gallbladder ultrasound, and a gallbladder ejection fraction typically less than 35%. We report a retrospective review of 70 patients with biliary dyskinesia who underwent cholecystectomy. Seventy-seven percent of the patients were women. Average age was 40. The most common symptoms were right upper quadrant pain, nausea, vomiting, and fatty food intolerance. All patients underwent a cholecystokinin-hepatobiliary scan or cholecystokinin-oral cholecystogram. Average ejection fractions were 20.2% and 28.4% respectively. Average post-operation follow-up was 10.9 months. Eighty-four percent of patients (59 of 70) reported improvement at follow-up. Eight patients had ejection fractions greater than 35%; seven of them reported improvement after cholecystectomy. Eleven patients did not improve after cholecystectomy; their average ejection fraction was 25%. These patients also had atypical symptoms (mid-epigastric pain and reflux symptoms). We believe cholecystectomy is effective therapy for biliary dyskinesia. Surgical outcomes could be improved by careful histories distinguishing biliary colic from other complaints. Less reliance should be placed on the ejection fraction when the patient has biliary colic without another etiology of abdominal pain.
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PMID:Outcomes of surgical therapy for biliary dyskinesia. 1450 24


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