Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0392326 (discomfort)
 22,423 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of granisetron, a specific 5-hydroxytryptamine 3-receptor antagonist, on the anorectal responses to rectal distension and a 1000-calorie meal was assessed in 12 patients with irritable bowel syndrome. Each patient was studied on three occasions, receiving intravenously either 40 mcg/kg granisetron, 160 mcg/kg granisetron or normal saline. Granisetron caused a dose-dependent reduction in rectal sensitivity, manifested by an increase in the threshold volumes at which the sensations of gas, desire to defecate, urgency and discomfort were perceived. This reached significance for all sensations at the higher dose level (P < 0.01). No significant changes in anal pressures, rectal compliance or distension-induced motor activity occurred following drug administration. A dose-dependent reduction in post-prandial motility was observed following intravenous granisetron and this was highly significant at 160 mcg/kg (P = 0.005). These results suggest that the 5 hydroxytryptamine receptor antagonists may have a therapeutic role in patients with irritable bowel syndrome.
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PMID:Reduction of rectal sensitivity and post-prandial motility by granisetron, a 5 HT3-receptor antagonist, in patients with irritable bowel syndrome. 838 53

Pressure pain over the abdominal aorta is a clinical sign of undetermined significance. Ultrasonographic criteria were used to define and further evaluate this variety of epigastric tenderness. The incidence of aortic pressure pain, aortic characteristics, and gastrointestinal symptoms were scored in 250 consecutive patients. The incidence was approximately 7%. All the patients with aortic pressure pain had gastrointestinal symptoms, with a significantly higher mean symptom score. The occurrence of pressure pain was independent of any of the examined aortic characteristics, age, or body mass index. We further compared the incidence of aortic pressure pain between 25 patients with irritable bowel syndrome and 25 patients without apparent functional gastrointestinal disease. It was present in approximately 50% of the patients with irritable bowel syndrome. We found pressure pain over the abdominal aorta to be associated with significant gastrointestinal discomfort. A causal relationship is possible but not proven. Aortic pressure pain can be provoked in a significant subgroup of patients with the irritable bowel syndrome.
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PMID:Aortic pressure pain: clinical significance. Any relationship to the irritable bowel syndrome? 874 48

Chronic symptoms of abdominal pain and discomfort are reported by patients with inflammatory bowel disease (IBD) and functional disorders of the gut, such as Irritable Bowel Syndrome (IBS). It has recently been suggested that transient inflammatory mucosal events may result in long-lasting sensitization of visceral afferent pathways. To determine the effect of recurring intestinal tissue irritation on lumbosacral afferent pathways, and to identify a plausible mechanism that could account for the overlap in symptomatology between IBD and IBS, we compared rectal afferent mechanisms in patients with Crohn's disease (inflammation limited to the ileum) with those observed in patients with diarrhea-predominant IBS. Continuous volume ramp and phasic pressure step distension of a rectal balloon were performed in 9 healthy male control subjects, 12 male patients with isolated ileal Crohn's disease and 9 male patients with diarrhea-predominant IBS using an electronic visceral stimulation device. The response of rectal afferents to distension was evaluated by measuring thresholds for the perception of physiological (stool) and aversive (discomfort) sensations, viscerosomatic referral patterns, skin conductance responses, receptive relaxation, and rectoanal reflex responses. In response to slow ramp distension, thresholds for aversive sensations were significantly higher in Crohn's disease patients, but similar between the two other groups. In response to rapid phasic distension, IBS patients reported discomfort at lower distension pressures, while all other thresholds were similar between groups. Skin conductance responses to aversive distension were greatly reduced in Crohn's disease patients while IBS patients had greater responses when compared to normals. Changes in viscerosomatic referral patterns and receptive relaxation rate were similar in Crohn's disease and IBS patients. These findings demonstrate that chronic ileal inflammation is associated with increased thresholds for discomfort and greatly diminished systemic autonomic reflex responses. In contrast, IBS patients show lowered thresholds for discomfort associated with increased autonomic responses. The findings in Crohn's patients may result from descending bulbospinal inhibition of sacral dorsal horn neurons in response to chronic intestinal tissue irritation.
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PMID:Rectal afferent function in patients with inflammatory and functional intestinal disorders. 888 Aug 36

The possibility that 5-hydroxytryptamine (5-HT) acts as a key sensitising agent in the aetiology of irritable bowel syndrome (IBS) is reviewed. The strategic locations of 5-HT and its receptors are described, the most dominant being the 5-HT3 and 5-HT4 type. 5-HT, acting mostly at 5-HT3 or 5-HT3-like receptors, enhances the sensitivity of visceral neurones projecting between the gut and the central nervous systems. 5-HT, acting at 5-HT4 receptors promotes the sensitivity of enteric neurones that react to luminal stimuli. 5-HT4 and 5-HT3 receptors also mediate, respectively, sensitising and physiological actions of 5-HT on gastro-intestinal motor and secretory functions. This distribution implies that some 5-HT3 receptor antagonists might reduce certain symptoms of IBS, such as pain, by reducing the reactivity of the visceral afferent neurones linking the gut with the brain and spinal cord. However, such antagonists are not likely to find widespread clinical acceptance because they can also affect normal lower bowel function and promote constipation. 5-HT4 receptor antagonists, by contrast, reduce 5-HT-induced enteric nerve hypersensitivity without notably affecting the function of the normal bowel. Accordingly, these agents may reduce the symptoms of IBS directly, by reducing the incidence of defecation and diarrhoea and indirectly, by reducing both 'rebound' constipation and the post-prandial discomfort and pain associated with gastrointestinal hyper-reactivity.
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PMID:5-Hydroxytryptamine and functional bowel disorders. 895 36

Up to 60% of patients with IBS have lowered perception thresholds in the rectum to balloon distension. The current study sought to test the hypothesis that IBS patients with normal perception thresholds in the rectum show hypersensitivity of afferent pathways in the sigmoid colon. Eleven healthy normal subjects and eight IBS patients with normal rectal perception thresholds underwent a balloon distension protocol in the sigmoid and rectum. Discomfort thresholds, receptive relaxation, compliance, and referral patterns were measured. Although IBS patients had significantly lower discomfort thresholds in the sigmoid when measured as volume, pressure, and wall tension, thresholds were similar to normals. Receptive relaxation and dynamic compliance were significantly decreased in IBS patients in the sigmoid. Referral patterns were similar during sigmoid distention in IBS patients in comparison to normals. Despite normal perception thresholds in rectum and sigmoid, IBS patients show evidence for alterations in rectosigmoid afferent mechanisms. In the sigmoid, this is seen in the form of reduced reflex relaxation and compliance and in the rectum in the form of altered viscerosomatic referral.
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PMID:Sigmoid afferent mechanisms in patients with irritable bowel syndrome. 920 Oct 70

Irritable bowel syndrome is characterized by recurrent abdominal pain and altered bowel function. In designing studies to evaluate new treatments for this disease, however, it is difficult to select appropriate endpoints to reflect improvement in the range of symptoms of the syndrome. In the present study we evaluated the parameter of adequate relief of abdominal pain and discomfort, as perceived by the patients, as a key endpoint for efficacy in the treatment of patients with irritable bowel syndrome. Abdominal pain and bowel function data were collected daily from 370 patients with the disease during treatment with placebo or a novel potent 5HT3 receptor antagonist. Once every 7 days adequate relief of pain and discomfort was assessed. Quality-of-life data were collected using self-administered questionnaires. The endpoint of adequate relief was significantly (P < 0.05) correlated with improvement in pain severity scores, percentage of pain-free days, percentage of days with urgency, improvement in stool frequency and consistency, and quality-of-life parameters. Adequate relief of pain and discomfort is significantly correlated with changes in multiple parameters associated with irritable bowel syndrome and can be used as an endpoint for assessing response to therapy in these patients.
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PMID:Adequate relief as an endpoint in clinical trials in irritable bowel syndrome. 960 85

We examined symptom frequency, duration, and severity, as well as episode patterns, in 122 adult patients with irritable bowel syndrome in a 12-week study conducted in the United States, the United Kingdom, and The Netherlands. Patients used an interactive telephone data entry system daily to report symptoms. Data from 59 of the patients meeting inclusion criteria are presented, the remainder having been excluded for failing to complete at least 70 days of symptom reporting. The majority of patients experienced at least one symptom on over 50% of the reported days; however, individual symptoms were reported on less than 50% of the days, indicating that symptoms sometimes occurred sequentially rather than always simultaneously. On average, patients reported pain/discomfort on 33% of days, bloating on 28% of the days, altered stool form or stool passage on 25% and 18% of the days, respectively, and mucus on 7% of the days. The duration of symptoms was relatively short, with pain/discomfort and bloating lasting the longest, an average of five days each per episode. All symptoms but one (mucus) were moderately severe on the majority of reported days. Patients experienced an "episode" (defined as a period of days with symptoms bounded by one or more symptom-free days) on an average of 12.4 times during the study, but the duration of these episodes varied greatly among patients. These results further establish the chronic nature of irritable bowel syndrome and the burden that this condition imposes on patients.
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PMID:Irritable bowel syndrome symptom patterns: frequency, duration, and severity. 988 4

Irritable bowel syndrome (IBS) represents one of the most common gastrointestinal-related diagnoses. Although the precise etiologic basis of IBS is not known, a common presenting symptom is abdominal pain or discomfort that is thought to develop, at least in part, from a heightened awareness of visceral nociceptive input. Agents capable of reducing this heightened visceral nociception would, therefore, have utility in the treatment of IBS. In this study we evaluated the effects of intravenous and intracerebroventricular administration of a 5-HT3 receptor antagonist, alosetron, on blood pressure changes associated with rectal distension in anesthetized and awake dogs. This vasoactive reflex serves as a model for visceral nociception. For intracerebroventricular studies, the cerebroventricular guides were placed over the lateral ventricle. In anesthetized studies, blood pressure was measured by femoral artery cannulation. In awake studies, blood pressure was monitored by noninvasive measurement. A rectal balloon was placed in the rectum of each dog and maintained throughout the experiments. Each dose of alosetron was given to the dogs as an intravenous or intracerebroventricular bolus, and every 30 min the rectal balloon was inflated and blood pressure responses observed. In both anesthetized and awake dogs alosetron produced a significant inhibition of the vasoactive reflex. In particular, alosetron showed high potency when administered intracerebroventricularly. Alosetron, administered either centrally or peripherally, appears to modulate the visceral nociceptive effect of rectal distension in dogs.
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PMID:Central modulation of rectal distension-induced blood pressure changes by alosetron, a 5-HT3 receptor antagonist. 995 18

While many definitions exist, dyspepsia is best considered a symptom complex (not a diagnosis) thought to arise in the upper gastrointestinal tract, unrelated to defecation. The symptom complex includes: upper abdominal/epigastric pain or discomfort, postprandial fullness, bloating, belching, early satiety, anorexia, nausea, retching, vomiting, heartburn and regurgitation. Patients with typical gastroesophageal reflux, biliary colic and irritable bowel syndrome should not be considered to have dyspepsia. After investigations, if a cause of dyspepsia is found, this is 'organic or structural' dyspepsia. If no structural cause is found, this is best called 'functional dyspepsia', subclassified into a) ulcer-like b) dysmotility-like c) reflux-like and d) unspecified dyspepsia. This symptom guided classification should be shifted to the first presentation with uninvestigated dyspepsia, prior to any investigations, to define a clinically useful guide to patient care. As there is considerable symptom overlap, it may be useful to combine together the ulcer and reflux-like groups into an acid-related dyspepsia group. In 1998, another approach would be to screen dyspeptic patients with an H. pylori test and classify them as H. pylori positive and negative dyspepsia.
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PMID:Definitions of dyspepsia: time for a reappraisal. 1002 67

Functional gastrointestinal disorders are best understood by applying a bio-psycho-social model. The diseases are strongly associated with psychological factors, and in functional dyspepsia, low vagal activity might be a mediating mechanism by which psychological factors (like neuroticism and stress) influence gastrointestinal physiology and cause epigastric discomfort. Low vagal activity may be a manifestation of stress and a cause of impaired gastric accommodation to meals. Epigastric discomfort is elicited when the stomach is distended without prior (vagal) reflex relaxation. Conventional therapy for acid-related dyspepsia does not improve accommodation and hence, is ineffective. The beneficial effect of experimental therapy, like glyceryl trinitrate and sumatriptan, which improve gastric accommodation, gives very good prospects for further development. For patients with irritable bowel syndrome, today's therapy seems similarly inefficacious, but several new potentially effective drugs are at present undergoing clinical trials.
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PMID:Today's therapy of functional gastrointestinal disorders--does it help? 1002 81


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