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Biomedical subjects

William D Chey

Publications and source records attributed to William D Chey.

33 records · Page 2Linked to original sources
PubMed2004

Tegaserod does not alter fasting or meal-induced biliary tract motility.

OBJECTIVE: Tegaserod is a 5-HT(4) receptor partial agonist that increases peristaltic activity of the intestinal tract. It is approved for the treatment of patients with irritable bowel syndrome with constipation (IBS-C). IBS is a chronic gastrointestinal disorder of function that is reported to be associated with an increased incidence of abdominal surgery including cholecystectomy. The effect of tegaserod on nongut digestive organs, such as the gallbladder and biliary tract, has not been previously investigated. Therefore, this study aimed to evaluate the effects of tegaserod on gallbladder contractility and on functional status of the sphincter of Oddi during both the interdigestive and the digestive periods in healthy female subjects and in female patients with IBS-C. METHODS: During a 6-wk, double-blind, placebo-controlled crossover study, gallbladder contractility and concomitant change in luminal diameter of the common hepatic duct (CHD) and the common bile duct (CBD, both proximal and distal) in response to a standard liquid meal were quantified using real-time ultrasonography. Changes in luminal diameter of the CHD and the CBD were used as a surrogate marker for sphincter of Oddi function. Ultrasound measurements were conducted every 15 min from 45 min before, to 60 min after the test meal to observe the impact of tegaserod on gallbladder volume and any concomitant change in the diameters of the CHD and the CBD that developed in response to gallbladder contraction. The ultrasound measurements of gallbladder contractility, along with the CHD and the CBD diameters, were repeated after each of the two 2-wk periods of treatment with tegaserod or placebo. The recommended dose of tegaserod (6 mg b.i.d.) for IBS-C patients was used in healthy female subjects (n = 13) and female patients with IBS-C (n = 20). Twice this dose (12 mg b.i.d.) was also evaluated in an additional 20 female patients with IBS-C. Statistical evaluations were conducted using a two-sided analysis of variance (ANOVA). RESULTS: Gallbladder contractility variables including ejection fraction, ejection rate and ejection period, fasting and residual volume, and maximal emptying, were similar after 2 wk of treatment with tegaserod 6 mg b.i.d. and placebo in healthy female subjects and female patients with IBS-C. There were no significant changes in the luminal diameters of the CHD or the CBD after tegaserod compared to placebo in any cohort. Additionally, no significant dilation (> or =7 mm in diameter) of the CHD or CBD was observed during maximal gallbladder emptying. Similar results were also observed when tegaserod was given at 12 mg b.i.d. in patients with IBS-C. Tegaserod treatment had no significant effect on plasma CCK concentration in response to the test meal. No significant abdominal pain or unexpected adverse events were reported during the study. CONCLUSIONS: This study showed no significant pharmacodynamic effect of tegaserod on gallbladder contractility or on CBD and CHD diameters as a surrogate marker of sphincter of Oddi function during both the interdigestive (fasting) and the digestive (postprandial) periods in healthy female subjects and female patients with IBS-C.

Biliary Tract↗
PubMed2004

Long-term safety and efficacy of alosetron in women with severe diarrhea-predominant irritable bowel syndrome.

OBJECTIVES: To assess long-term safety and efficacy of alosetron in women with severe, chronic diarrhea-predominant IBS and in a subset having more frequent urgency (i.e., bowel urgency at least 10 of 14 days during screening). METHODS: Randomized patients received either alosetron 1 mg (n = 351) or placebo (n = 363) twice daily during a 48-wk, double-blind study. The primary endpoint was the 48-wk average rate of adequate relief of IBS pain and discomfort. Secondary endpoints included 48-wk average satisfactory control rates of urgency, stool frequency, stool consistency, and bloating. Other efficacy endpoints were average monthly adequate relief and urgency control rates and impact of provided rescue medication. RESULTS: Alosetron-treated patients had significantly greater 48-wk average adequate relief (p= 0.01) and urgency control (p < 0.001) rates, regardless of rescue medication use, compared with placebo. Results in subjects with more frequent urgency were more robust than those in the overall population (p= 0.005). In weeks without rescue medication use, satisfactory control rates for stool frequency and stool consistency were significantly greater in alosetron-treated patients than placebo. Alosetron-treated patients had significantly greater adequate relief than placebo-treated patients (p < 0.05) in 9 of 12 months and significantly greater urgency control (p < 0.001) in all months. Adequate relief and urgency control were maintained throughout the treatment. Adverse events and serious adverse events were similar between treatment groups, except for constipation. Neither ischemic colitis nor serious events related to bowel motor dysfunction was reported. CONCLUSIONS: Long-term use of alosetron is effective and well-tolerated in women with chronic, diarrhea-predominant IBS, including those with more frequent urgency.

Abdominal Pain↗
PubMed2003

Advances in the management of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a commonly encountered condition seen in multiple medical specialties. Recent research has brought dramatic advances in our understanding of the epidemiology, burden of illness, diagnosis, and management of IBS. It is now widely accepted that the prevalence of IBS is between 10% and 20% of the US population and that the direct and indirect costs associated with IBS are significant. The processes required for diagnosis of IBS remain controversial. Scant evidence exists to support exhaustive diagnostic evaluations, and IBS is no longer considered a diagnosis of exclusion. The use of standardized symptom-based criteria remains to be perfected, and the diagnosis is often arrived at only after multiple laboratory, endoscopic, and radiologic examinations. The effects of treatment for IBS mirror the heterogeneous nature of the condition. No single medication has proven to be universally effective, and multiple therapeutic approaches exist. Greater understanding of gastrointestinal neurophysiology has led to promising advances in medical and nonmedical approaches to IBS.

Antidepressive Agents, Tricyclic↗
PubMed2003

Intrasphincteric botulinum toxin versus pneumatic balloon dilation for treatment of primary achalasia.

GOALS: Despite a high success rate, pneumatic dilatation for achalasia is accompanied by a significant risk of esophageal perforation. Injection of botulinum toxin (botox) into the lower esophageal sphincter (LES) can lead to improvement in symptoms with reduced risk of complications. Direct comparisons of the two techniques are needed to define their role in clinical management. STUDY: We compared pneumatic dilatation to botox for patients with achalasia using a double blind, randomized study design. Patients underwent clinical, manometric, radiographic and endoscopic evaluation to confirm primary achalasia. They were randomized to receive either 80 units of botox into the LES or Witzel balloon dilatation. Patients also received sham dilatation or injection, respectively. The patients and investigators assessing symptom response were blinded to therapy. Symptoms and esophageal function were assessed at 3 weeks, 3 months and 1 year after therapy. Treatment failure was defined as the lack of decrease in symptom grade more than 1 or recurrence of symptoms. Patients with treatment failure crossed over to the alternative treatment. RESULTS: Thirty four patients were studied, and 31 completed the trial. Of the 18 patients randomized to Witzel dilatation, 16 (89%) of 18 remained in clinical remission. Of the two patients with treatment failure, one responded to botox injection. Of the 16 patients randomized to botox, (38%) 6 of 16 remained in clinical remission. Four patients had initial failure, and 6 relapsed at a mean of 4 months after therapy. Of the nine patients who crossed over to dilatation, seven responded well, but two required surgical management of perforation. Although both treatments had excellent initial clinical improvement, patients randomized to Witzel dilatation had superior long-term success ( < 0.01). CONCLUSION: Initial therapy with Witzel dilatation is associated with better long-term outcome than a single injection of botox. Because of the risk of endoscopic perforation, botox remains a viable alternative to dilatation.

Anti-Dyskinesia Agents↗
PubMed2003

Number of responses on a review of systems questionnaire predicts the diagnosis of functional gastrointestinal disorders.

GOALS: We evaluated whether the number of positive responses on a review of systems questionnaire predicted the diagnosis of functional gastrointestinal (GI) disorders. STUDY: New patients to the University of Michigan GI clinics fill out a standardized questionnaire that includes a comprehensive review of systems which lists 87 items under 11 headings. We determined the number of items circled on the review of systems from the first 100 new patients seen in GI clinic in the year 2000. After a mean of 14 months follow-up, the final diagnoses in these patients were compared with the number of items circled on the review of systems. RESULTS: Completed questionnaires were available for review in 82/100 patients. Twenty-six patients were diagnosed with a functional GI disorder, 53 patients had a nonfunctional diagnosis, and 3 patients had no diagnosis determined. The mean number of items circled on the review of systems was 15.9 (SD = 11.2) for the functional GI group, compared with 5.9 (SD = 6.9) for the nonfunctional GI diagnosis group ( < 0.005). When the symptom headings were analyzed individually, the differences in general, gastroenterological, cardiovascular, urinary, neurological, eye, ear, nose and throat, and psychiatric symptoms were statistically significant. CONCLUSIONS: Patients with functional GI disorders have a significantly greater number of GI and non-GI symptoms on review of systems. If seven positive symptoms is used as a threshold, the standardized review of systems questionnaire had a sensitivity of 92% and specificity of 80% in detecting patients with functional GI disorders.

Adult↗
PubMed2003

Gastroesophageal reflux disease.

Heartburn on 2 or more days a week warrants medical attention, as patients are likely to suffer from gastroesophageal reflux disease (GERD). Chronic GERD can lead to the development of complications including erosive esophagitis, stricture formation, and Barrett's esophagus, which increases the risk of esophageal adenocarcinoma. A trial with a proton pump inhibitor (PPI) is the quickest and most cost-effective way to diagnose GERD, and is at least as sensitive as 24-hour intra-esophageal pH monitoring. As PPIs only bind to actively secreting proton pumps, they should be dosed 30 to 60 minutes before a meal. Despite these recommendations, a recent survey of over 1000 US primary care physicians found that 36% instructed their patients to take a PPI with or after a meal or did not specify the timing of dosing. The patients who will have the best response to surgical therapy for GERD are those who had clearly documented acid reflux with typical symptoms, and who have responded to PPI treatment. Unfortunately, the same survey found that most physicians recommend antireflux surgery for patients in whom medical therapy has failed.

Clinical Trials as Topic↗
PubMed2003

Tegaserod and other serotonergic agents: what is the evidence?

Through effects on gastrointestinal motor and secretory function as well as visceral sensation, serotonin (5-HT) plays a key role in the pathogenesis of irritable bowel syndrome (IBS). In particular, 5-HT3 and 5-HT4 receptors appear to be very important in IBS. This article critically appraises the evidence supporting the use of the 5-HT3 receptor antagonist alosetron in the treatment of women with diarrhea-predominant IBS. The safety profile and restricted-use program for alosetron is also reviewed. This discussion is followed by a comprehensive review of the efficacy and safety data in support of tegaserod for women with constipation-predominant IBS.

Carbolines↗
PubMed2002

Bile duct crystals do not contribute to sphincter of Oddi dysfunction.

BACKGROUND: Microlithiasis has been proposed as a cause of both occult gallbladder disease and of idiopathic pancreatitis. Theoretically, microlithiasis could also cause postcholecystectomy pain by causing temporary biliary obstruction and may be more common in patients with sphincter of Oddi dysfunction. The frequency of crystals in bile duct aspirates was assessed from patients with symptoms after cholecystectomy with and without elevated baseline sphincter of Oddi pressures. METHODS: A prospective analysis was performed on all patients with recurrent biliary pain after cholecystectomy who presented for ERCP and manometry between January 1998 and June 2000. All patients had aspirates obtained from the common bile duct for crystal analysis by using the aspirating port of the manometry catheter before the injection of contrast. Four to 20 mL of bile was examined by microscopy for both cholesterol and bilirubinate crystals. RESULTS: Sixty patients (83% women, mean age 44 years) were studied. Thirty-five had normal baseline biliary sphincter pressures and 25 elevated biliary baseline sphincter pressures (>40 mm Hg). Two patients in the normal pressure group and 1 in the elevated pressure group had cholesterol crystals present in their aspirate. No patient had bilirubinate crystals present. A 5% frequency of microlithiasis was identified overall. CONCLUSIONS: Bile duct crystals occur infrequently in patients with symptoms after cholecystectomy and are found in patients with normal and abnormal biliary sphincter manometry. This study suggests that the presence of bile duct crystals, or microlithiasis, does not play a role in sphincter of Oddi dysfunction.

Adult↗
PubMed2002

Utility of the Rome I and Rome II criteria for irritable bowel syndrome in U.S. women.

OBJECTIVES: Using interview data from a large, community-based sample of American women, we assessed the lifetime prevalence of irritable bowel syndrome (IBS) using questions consistent with the Rome II criteria, determined the sensitivity of Rome I and II in women diagnosed with IBS by their community physician, and identified whether there are differences in the patients identified by Rome I versus II. METHODS: A geographically diverse national probability sample of women diagnosed with IBS was identified and interviewed by telephone screening of a national, random digit dialing sample of households. A parallel national survey of adult females was conducted to determine the lifetime prevalence of IBS in U.S. women. Screening and interviews were conducted by experienced, female interviewers. IBS was defined by variations on the Rome I/II criteria. RESULTS: In the national community sample, lifetime IBS prevalence was 5.4% using Rome II. Full interviews were completed in 1,014 IBS patients. In the IBS sample, Rome I was significantly more sensitive than Rome II (84% vs 49%, p < 0.001). There was 47% agreement between Rome I and II. Of patients with IBS by Rome I, 58% met Rome II. Only 17.7% did not meet either Rome I or II. CONCLUSIONS: Rome I was more sensitive than Rome II in this community sample of female IBS patients. Rome I/II do not necessarily identify the same IBS patients. These findings have important implications for clinical research in IBS patients and raise questions about whether the Rome II criteria are sensitive enough to be useful in clinical practice.

Adult↗
PubMed2002

The utility of diagnostic tests in irritable bowel syndrome patients: a systematic review.

OBJECTIVE: The aim of this study was to determine the pretest probability of organic GI disease and the accuracy of diagnostic tests for organic GI disease in patients who meet symptom-based criteria for irritable bowel syndrome (IBS). METHODS: After a comprehensive literature search for studies examining the accuracy of diagnostic tests for organic GI disease among patients who meet symptom-based criteria for IBS, two independent observers qualitatively assessed the methodology of selected studies and extracted data. Data on the pretest probability of organic GI disease in this population and the accuracy of currently recommended diagnostic tests were converted to descriptive tables. RESULTS: Among patients meeting symptom-based criteria for IBS, the pretest probability of inflammatory bowel disease, colorectal cancer, or infectious diarrhea is less than 1%. Currently recommended diagnostic tests rarely identify organic GI disease in patients fulfilling symptom-based criteria for IBS. However, the pretest probability of celiac disease in patients meeting symptom-based criteria for IBS was 10 times higher than the prevalence of celiac disease in the general population. CONCLUSIONS: There is insufficient evidence to recommend the routine performance of a standardized battery of diagnostic tests in patients who meet symptom-based criteria for IBS. Based upon the increased pretest probability of celiac disease, routine performance of serological tests for celiac disease may be useful in this patient population, though additional study is needed in this area.

Autoantibodies↗
PubMed2002

Impaired gastrocolonic response and peristaltic reflex in slow-transit constipation: role of 5-HT(3) pathways.

Colonic motility is modulated by the 5-hydroxytryptamine (5-HT)(3)-dependent gastrocolonic response and 5-HT(3)-independent peristaltic reflex. We compared descending colon tone responses to antral distension, duodenal lipid perfusion, and colonic distension after double-blind placebo or granisetron in 13 healthy volunteers and nine slow-transit constipated patients. Antral distension (100-300 ml) and duodenal lipids (3 kcal/min) evoked increases in colon tone in volunteers, which were blunted in constipated patients (P < 0.05). Granisetron (10 microg/kg) reduced responses to antral distension and lipids in volunteers and to lipids in constipated patients (P < 0.05). The ascending contraction of the peristaltic reflex was blunted in constipated patients (P < 0.05), whereas descending responses were similar. Granisetron did not modify the peristaltic reflex. Colonic responses to bethanechol were similar in patients and volunteers. In conclusion, antral distension- and duodenal lipid-activated gastrocolonic responses and ascending contractions of the peristaltic reflex are impaired with slow-transit constipation with loss of both 5-HT(3)-dependent and -independent function. Thus abnormalities of neural reflex modulation of colonic motor function may play pathophysiological roles in slow-transit constipation.

Adult↗