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Biomedical subjects

L R Sutherland

Publications and source records attributed to L R Sutherland.

At least 55 records · Page 3Linked to original sources
PubMed1996

Oral budesonide as maintenance treatment for Crohn's disease: a placebo-controlled, dose-ranging study. Canadian Inflammatory Bowel Disease Study Group.

BACKGROUND & AIMS: Budesonide is a corticosteroid with high topical anti-inflammatory activity and low systemic activity due to rapid hepatic metabolism. The efficacy and safety of an oral controlled-release preparation of budesonide for maintenance of remission was evaluated in patients with ileal or ileocecal Crohn's disease. METHODS: In a double-blind, multicenter trial, 105 patients were randomly assigned to receive placebo or budesonide at doses of 3 or 6 mg daily for 1 year. The primary outcome measure was relapse defined by a Crohn's Disease Activity Index score of > 150 and a minimum increase of 60 points. RESULTS: Patients receiving 6 mg of budesonide had a median time to relapse or discontinuation of therapy of 178 days compared with 124 days in those receiving 3 mg of budesonide and 39 days in those receiving placebo. However, at 1 year, the rate of relapse in the group receiving 6 mg of budesonide was similar to the rates in the 3-mg and placebo groups. Basal plasma cortisol levels and incidence of corticosteroid-associated effects were similar in the three groups. CONCLUSIONS: Oral controlled-release budesonide (6 mg/day) was well tolerated and prolonged remission in Crohn's disease of the ileum and proximal colon, but this effect was not sustained at 1-year follow-up.

Administration, Oral↗
PubMed1996

Intestinal permeability changes in response to acetylsalicylic acid in relatives of patients with Crohn's disease.

BACKGROUND & AIMS: Presence of a familial intestinal permeability defect in Crohn's disease remains controversial despite numerous studies. The purpose of this study was to determine whether detection of a permeability defect in first-degree relatives of patients with Crohn's disease can be enhanced using an acetylsalicylic acid provocation test. METHODS: Lactulose-mannitol ratio, a measure of intestinal permeability, and total sucrose excretion, a measure of gastroduodenal permeability, were determined before and after ingestion of acetylsalicylic acid in healthy controls, in patients with Crohn's disease, and in the first-degree relatives of patients with Crohn's disease. Subjects were classified as hyperresponders if their results were above the mean of + 2SD of the controls. RESULTS: First-degree relatives had a 110% increase in intestinal permeability after acetylsalicylic acid compared with an increase of 57% in controls (P = 0.001). Thirty-five percent of relatives were classified as hyperresponders. There was no significant difference in the change in sucrose excretion between relatives and controls (259% vs 198%; P < 0.05). CONCLUSIONS: First-degree relatives of patients with Crohn's disease have an exaggerated increase in intestinal but not gastroduodenal permeability in response to acetylsalicylic acid. This study supports a familial permeability defect in Crohn's disease, which may not be present in all families.

Adult↗
PubMed1996

Zidovudine absorption and small intestinal function in HIV seropositive patients.

Zidovudine absorption was evaluated in HIV seropositive patients with (n = 15) and without diarrhoea (n = 20) in a standardised prospective pharmacokinetic study using single oral 200 mg doses. Zidovudine was rapidly absorbed with large peak variation (Cmax: 1.10 +/- 0.43 mg/L). There were no significant associations between pharmacokinetic parameters and presence of diarrhoea, CD4 counts, red blood cell folate concentrations, stool cultures/leucocytes or the lactulose/mannitol absorption test. Mean diarrhoea AUC (mg/L.h) was 1.13 +/- 0.30 and 1.07 +/- 0.36 in non-diarrhoeal patients. Antidiarrhoeals increased AUC and Cmax values in a small, non statistically significant subset of diarrhoea patients. Although zidovudine absorption varies significantly, our data do not support dosage individualisation based on any of the above parameters.

Administration, Oral↗
PubMed1996

HIV-associated non-Hodgkin's lymphoma of the gastrointestinal tract.

OBJECTIVE: To determine the number of HIV-associated non-Hodgkin's lymphoma (NHL) of the gastrointestinal tract (GI) in a population of HIV-infected patients from a distinct geographic region (southern Alberta, Canada), from 1983 to 1995. The type and location of NHL within the GI tract as well it's affect on survival was examined. Patients with GI HIV-associated NHL were compared to patients with extraintestinal HIV-associated NHL. METHODS: The Southern Alberta HIV Clinic in Calgary (SAC) serves all of southern Alberta which has an estimated population of one million. SAC provided primary care for 1086 patients from January 1983 to August 1995. Data were obtained by reviewing the clinic's data base and patient's charts. RESULTS: Over a 12-yr period, 13 cases of NHL of the GI tract and 26 cases of extraintestinal NHL were diagnosed in the 1086 HIV-infected patients. HIV-associated GI NHL occurred in individuals of similar age, sex, HIV risk factors, incidence of preceding AIDS-defining illnesses and CD4 count compared to those with extraintestinal NHL. The most common presentations of GI NHL were; abdominal pain (77%), abdominal tenderness (77%), weight loss (77%), and GI bleeding (38%). The most common sites of GI involvement were the large bowel (46%), ileum (39%), and stomach (23%). Those with GI NHL survived longer (1.96 +/- 0.50 yr vs 0.95 +/- 0.20 yr, p < 0.05) and were more likely to respond to therapy (72.7% vs 33.3%, p < 0.03) than those with extraintestinal NHL. CONCLUSIONS: This study suggests that; 1) the GI tract is common site of involvement in HIV-associated NHL, 2) HIV-associated GI NHL occurs in similar individuals as HIV-associated extraintestinal NHL, 3) those with HIV-associated GI NHL survive longer and are more likely to respond therapy than those with extraintestinal HIV-associated NHL.

Adult↗
PubMed1995

Azathioprine and 6-mercaptopurine in Crohn disease. A meta-analysis.

PURPOSE: To assess the effectiveness of azathioprine and 6-mercaptopurine in inducing remission of active Crohn disease and the effectiveness of azathioprine in maintaining remission of quiescent disease. DATA SOURCES: Pertinent studies were selected from the MEDLINE database (1966 to May 1994), abstracts from major gastrointestinal meetings, and references from published articles and reviews. STUDY SELECTION: Nine randomized, placebo-controlled trials of azathioprine or 6-mercaptopurine therapy were identified: Four addressed active disease, two addressed quiescent disease, and three had multiple therapeutic arms. DATA EXTRACTION: Data were extracted by three independent observers on the basis of the intention-to-treat principle and were analyzed with logistic regression. Each study was given a quality score on the basis of predetermined criteria. DATA SYNTHESIS: Compared with placebo, azathioprine or 6-mercaptopurine therapy had an odds ratio of response of 3.09 (95% CI, 2.45 to 3.91) in patients with active Crohn disease. When the single trial that used 6-mercaptopurine in active disease was excluded from the analysis, the odds ratio of response was 1.45 (CI, 1.12 to 1.87). No trials of quiescent disease used 6-mercaptopurine; the odds ratio of response in these trials of quiescent disease was 2.27 (CI, 1.76 to 2.93). For active disease, continuation of therapy for at least 17 weeks improved response (P = 0.03). For quiescent disease, a higher dose improved response (P = 0.008). Increased cumulative dose improved response in both groups (P < 0.001 for active disease and P = 0.01 for quiescent disease). A steroid-sparing effect was seen in active disease (odds ratio, 3.69 (CI, 2.12 to 6.42) and in quiescent disease (odds ratio, 4.64 [CI, 1.00 to 21.54]). Fistulae improved with therapy (odds ratio, 4.44 [CI, 1.50 to 13.20]). Adverse events requiring withdrawal from a trial, primarily allergy, leukopenia, pancreatitis, and nausea, were increased with therapy (odds ratio, 5.26 [CI, 2.20 to 12.60]). CONCLUSIONS: Azathioprine and 6-mercaptopurine are effective in treating active Crohn disease and in maintaining remission. Cumulative dose was an important factor in predicting response. Adverse effects were more common among patients receiving therapy.

Azathioprine↗
PubMed1995

Meta-analysis of enteral nutrition as a primary treatment of active Crohn's disease.

BACKGROUND/AIMS: The efficacy of enteral nutrition as primary therapy of active Crohn's disease is controversial. The aim of the study was to compare by meta-analysis the likelihood of clinical response to liquid diet therapy vs. corticosteroids and to assess the importance of formula composition to efficacy. METHODS: Randomized controlled trials comparing exclusive enteral nutrition with corticosteroids and elemental with nonelemental formulas were identified through a combination of computerized and hand-searching techniques. Rates of clinical remission of active Crohn's disease, based on the intention-to-treat principle, were extracted from the studies by two independent reviewers. Odds ratios for likelihood of clinical response were calculated. RESULTS: In eight trials comprising 413 patients, enteral nutrition was inferior to corticosteroids (pooled odds ratio, 0.35; 95% confidence interval, 0.23-0.53). In five trials comprising 134 patients, there was no difference in the efficacy of elemental versus nonelemental formulas (pooled odds ratio, 0.87; 95% confidence interval, 0.41-1.83). CONCLUSIONS: Corticosteroids are more effective than enteral nutrition in the treatment of active Crohn's disease. Limited sample size precludes definitive conclusions about the importance of formula composition in the efficacy of enteral nutrition; however, data analyzed in this study do not support an advantage to elemental feedings compared with a polymeric formulation.

Adrenal Cortex Hormones↗
PubMed1995

General practitioners' assessment of and interest in alternative medicine in Canada.

Canadian physicians' opinions about alternative medicine have, as yet, not been assessed. The objectives of this pilot study were to assess general practitioners': (1) desired involvement in alternative medicine; (2) perceived demand for alternative medicine; and (3) beliefs about the efficacy of different alternative approaches. The study design was a cross-sectional survey of 400 randomly selected Alberta and Ontario general practitioners. Of the 384 eligible physicians, 200 (52%) completed the questionnaire. Seventy-three percent of physicians felt that they should have some knowledge about the most important alternative treatments. However, with respect to other issues, physicians desired less involvement with alternative medicine. Sixty-five percent perceived a demand for alternative medicine from their patients, in particular chiropractic. Alternative medicine was perceived to be needed most for musculoskeletal problems and chronic pain or illness. Chiropractic, hypnosis and acupuncture (for chronic pain) were believed to be most efficacious, while homeopathy and reflexology were considered to be least efficacious. Undergraduate, graduate clinical and continuing medical education will need to address alternative treatments in order to provide physicians with up-to-date and relevant information.

Attitude of Health Personnel↗
PubMed1995

Perioperative blood transfusion does not prevent recurrence in Crohn's disease. A pooled analysis.

The effect of perioperative blood transfusion on the recurrence of Crohn's disease is controversial. Various studies have suggested that perioperative blood transfusions reduce the risk of recurrence; others have failed to find a protective effect. Since all the studies are based on relatively small numbers, we performed a pooled analysis. We contacted the senior authors of seven previously published studies and asked for the original data. Four authors provided their data. The pooled database included 622 patients with a primary and complete resection of macroscopic disease. Recurrence was defined as the need for repeat surgery for disease control. Kaplan-Meier life table analysis was performed. Of the study sample, 366 cases (59%) were female. Disease distribution was as follows: small bowel (47%), small/large bowel (35%), and large bowel only (18%). Three hundred thirty-one patients (53%) received blood in the perioperative period. Mean follow-up was 72.8 months. For the overall sample, the 5-year recurrence rates were 26.9% for the transfused group and 25.2% for the nontransfused (p = 0.456). When the data were stratified by age, gender, disease location, and length of resection, no difference in 5-year recurrence rates between transfused and nontransfused cases could be detected. In this pooled analysis of four retrospective studies on the effect of blood transfusions on the risk of recurrence in Crohn's disease, we were unable to document a protective effect.

Adolescent↗
PubMed1995

Meta-analysis of the role of oral contraceptive agents in inflammatory bowel disease.

Numerous epidemiological studies have been performed to determine factors that might contribute to the development of inflammatory bowel disease. Although the role of oral contraceptive agents in Crohn's disease (CD) and ulcerative colitis (UC) have been assessed, most studies were of small sample size and characterised by low statistical precision. A meta-analysis was performed to increase the statistical power and to investigate the association between the use of oral contraceptives and the development of CD and UC. The study was based on a search of a Medline database from 1975 to October 1993 and a review of reference lists from published articles, reviews, symposia proceedings, and abstracts from major gastrointestinal meetings. All studies specifically designed to evaluate this association were selected. The combined results of nine studies--two cohort studies (30,379 unexposed and 30,673 exposed patients) and seven case-control studies (482 CD, 237 UC, and 3198 controls)--which satisfied our selection criteria were evaluated. The pooled relative risk (adjusted for smoking) associated with oral contraceptive use was 1.44 (1.12, 1.86) for CD and 1.29 (0.94, 1.77) for UC. These results suggest modest associations between the use of oral contraceptives and the development of CD and UC. As these associations are weak, non-causal explanations for the findings cannot be eliminated.

Case-Control Studies↗
PubMed1995

Alternative medicine and general practitioners. Opinions and behaviour.

OBJECTIVE: To describe general practitioners' opinions and behaviour regarding alternative medicine. DESIGN: Cross-sectional survey of a random sample of Ontario and Alberta general practitioners. SETTING: General practices in Ontario and Alberta. PARTICIPANTS: A questionnaire was mailed to 400 general practitioners. Of the 384 eligible physicians, 200 completed the questionnaire. MAIN OUTCOME MEASURES: Reported beliefs and practices concerning alternative medicine. RESULTS: Acupuncture, chiropractic, and hypnosis were considered most useful and reflexology, naturopathy, and homeopathy least useful. Results showed 56% of general practitioners believed that alternative medicine has ideas and methods from which conventional medicine could benefit, 54% referred to alternative practitioners, and 16% practised some form of alternative medicine. Province of practice, place of graduation, training in alternative approaches, number of alternative approaches perceived useful, and attitude toward alternative medicine were clearly related to referring to alternative practitioners. Sex, age, type of practice, training in alternative medicine, referring to alternative practitioners, number of alternative approaches perceived useful, and attitude toward alternative medicine were related to practicing alternative medicine. CONCLUSION: Although acceptance and integration of alternative medicine extend only to certain approaches, alternative medicine cannot be discounted in general practice. A study encompassing all Canadian provinces could help in planning medical education and developing policies to guide physician behaviour.

Adult↗
PubMed1994

Oral budesonide for active Crohn's disease. Canadian Inflammatory Bowel Disease Study Group.

BACKGROUND: Corticosteroids are the most efficacious drugs for inducing remission in active Crohn's disease, but their benefits are frequently offset by serious side effects. Budesonide is a corticosteroid with high topical antiinflammatory activity but low systemic activity because of extensive hepatic metabolism. We investigated the efficacy and safety of an oral controlled-ileal-release preparation of budesonide in patients with active Crohn's disease involving the ileum or ileum and proximal colon. METHODS: In a double-blind, multicenter trial, 258 patients were randomly assigned to receive placebo or one of three doses of budesonide--3, 9, or 15 mg daily. The primary outcome measure was clinical remission, as defined by a score of 150 or less on the Crohn's disease activity index. RESULTS: After eight weeks of treatment, remission occurred in 51 percent of the patients in the group receiving 9 mg of budesonide (95 percent confidence interval, 39 to 63 percent), 43 percent of those receiving 15 mg (95 percent confidence interval, 31 to 55 percent), and 33 percent of those receiving 3 mg (95 percent confidence interval, 21 to 44 percent), as compared with 20 percent of those receiving placebo (P < 0.001, P = 0.009, and P = 0.13, respectively). Improvements in the quality of life, as measured by the patients' responses to the inflammatory bowel disease questionnaire, paralleled these remission rates. Location of disease, prior surgical resection, and previous use of corticosteroids did not affect the outcome. A total of 119 patients (46 percent) were withdrawn from the study before the trial ended, 96 because of insufficient therapeutic effects, 13 because of adverse reactions, and 10 because of noncompliance. Budesonide caused a dose-related reduction in basal and corticotropin-stimulated plasma cortisol concentrations but was not associated with clinically important corticosteroid-related symptoms or other toxic effects. CONCLUSIONS: In an eight-week trial, an oral controlled-release preparation of budesonide at an optimal daily dose of 9 mg was well tolerated and effective against active Crohn's disease of the ileum and proximal colon.

Administration, Oral↗
PubMed1994

A simple, non-invasive marker of gastric damage: sucrose permeability.

Disaccharides do not cross intact gastrointestinal mucosa to any appreciable extent unless there is damage to the epithelium. Furthermore, since sucrose is rapidly broken down in the small intestine, the absorption of intact sucrose implies damage to proximal epithelium. We have reported that measurement of sucrose permeability detects gastric damage in animals. Whilst such a non-specific test could not replace endoscopy, it might represent a clinically useful technique to identify patients who would benefit from endoscopy. 189 patients underwent endoscopy and assessment of sucrose permeability to evaluate the effectiveness of increased sucrose permeability in the prediction of endoscopic findings. The endoscopist was blinded to results of the sucrose assay. Gastric damage, particularly ulcers and severe gastritis, was successfully detected with this technique. Increased sucrose permeability, however, did not reliably detect mild gastritis, oesophagitis, or duodenal disease. The sensitivity of the test for gastric ulceration was 84% and specificity in predicting an abnormal endoscopy was 96%. Measurement of sucrose permeability is a simple way of screening for gastric damage. It has a sensitivity similar to that for upper gastrointestinal radiology and provides a new way to effectively screen large populations at risk of gastric damage.

Duodenal Ulcer↗
PubMed1994

Why do patients seek a second opinion or alternative medicine?

The objectives of the study were (a) to determine psychosocial determinants of two measures of health care use: seeking a second opinion and alternative medicine use, and (b) to assess whether changes in these two measures of health care use had taken place during the past 4 to 5 years. All patients attending a university-based gastroenterology clinic were asked to complete a self-administered questionnaire. The response rate was 83% (N = 341). Health locus of control, scepticism toward medicine, satisfaction with health care, and perceived health status were included as potential determinants. Sixteen percent (21) of the new patients (95% confidence interval, 10.0-22.8) sought a second opinion compared to 7.5% (95% confidence interval, 4.3-10.7) 5 years ago. Seeking a second opinion was negatively related to internal locus of control, perceived health status, and demanding to know all details of treatment. Eight percent (28) of all patients (95% confidence interval, 5.3-11.1) saw an alternative practitioner for the same problem for which they saw the gastroenterologist compared to 9% (95% confidence interval, 6.2-12.8) 4 years ago. Using alternative medical care was positively related to scepticism toward conventional medicine and negatively related to perceived health status and satisfaction with clinic physicians. Knowledge about the incidence and determinants of these behaviors provides valuable information for clinicians in communicating with their patients and may eventually result in cost containment.

Adolescent↗
PubMed1994

Time course of nitric oxide production and epithelial dysfunction during ischemia/reperfusion of the feline small intestine.

The objective of this study was to correlate nitric oxide production with time of reperfusion of the post-ischemic feline small intestine. Epithelial permeability, quantitated as blood-to-lumen clearance of 51Cr-EDTA, following 1 hr of ischemia and 4 hr of reperfusion of the small intestine, increased approximately 10-fold. This increase was further augmented by L-NAME infusion between 60 and 120 min but not at 240 min. Ca(2+)-dependent nitric oxide synthase activity was reduced by approximately 50% at 3 and 4 hr of reperfusion, whereas Ca(2+)-independent nitric oxide synthase activity was undetectable throughout the experiment. Administration of L-arginine at the start of reperfusion attenuated the reperfusion-induced epithelial barrier dysfunction for the first 120 min but not at 180 or 240 min. Continuous infusion of a nitric oxide donor (CAS 754) following 1 hr of reperfusion reduced epithelial permeability at 4 hr of reperfusion. In conclusion, a reduction in nitric oxide production was observed with time of reperfusion, possibly due to reduced nitric oxide synthase levels.

Animals↗
PubMed1993

Sulfasalazine revisited: a meta-analysis of 5-aminosalicylic acid in the treatment of ulcerative colitis.

PURPOSE: To assess the effectiveness of the newer 5-aminosalicylic acid (5-ASA) delivery systems compared with placebo or sulfasalazine for the treatment of active ulcerative colitis and for the maintenance of remission. DATA SOURCES: Pertinent studies were selected using the MEDLINE and BIOS (1981 to 1992) data bases, reference lists from published articles, reviews, symposia proceedings, and abstracts from major gastrointestinal meetings. STUDY SELECTION: Randomized controlled trials of 5-ASA compared with placebo or sulfasalazine of a minimum of 4 weeks duration for active disease and a minimum of 6 months for maintenance of disease remission. Sixteen trials of 5-ASA for active disease, published either in abstract or full manuscript, were available. Eleven trials of 5-ASA for maintenance of remission were also reviewed. DATA EXTRACTION: Crude rates for either induction of remission (active disease studies) or maintenance of remission (relapse-prevention trials) based on the intention-to-treat principle were extracted from the studies by two independent observers. Each study was given a quality score, based on predetermined criteria. RESULTS: Studies were placed in three groups: 5-ASA compared with placebo, 5-ASA compared with sulfasalazine for active disease, and 5-ASA compared with sulfasalazine for maintenance of remission. 5-Aminosalicylic acid was superior to placebo in the treatment of active ulcerative colitis (pooled odds ratio, 2.02; 95% CI, 1.50 to 2.72). A dose-response effect for 5-ASA existed (P < 0.001). For active disease, the pooled odds ratio for 5-ASA compared with sulfasalazine was 1.15 (CI, 0.83 to 1.61). When 5-ASA was compared with sulfasalazine for maintenance of disease remission, the pooled odds ratio was 0.85 (CI, 0.64 to 1.15). Withdrawal rates and reported side effects were similar for 5-ASA compared with placebo- or sulfasalazine-treated patients. CONCLUSIONS: Although the newer 5-ASA preparations in a dose of at least 2 g/d are more effective than placebo in the treatment of ulcerative colitis, insufficient evidence exists to suggest that they are superior to sulfasalazine. Although they offer a benefit to the sulfasalazine-sensitive patient, use of 5-ASA preparations instead of sulfasalazine in the treatment of ulcerative colitis cannot yet be substantiated.

Aminosalicylic Acids↗
PubMed1993

Gastrointestinal symptoms in ambulatory HIV-infected patients.

Gastrointestinal symptoms are commonly seen in patients with established AIDS. We examined the charts of 258 HIV-infected patients attending our HIV outpatient clinic to determine: (1) the frequency of gastrointestinal symptoms in unselected HIV-infected patients and (2) if there are any predictors of the development of symptoms in initially asymptomatic patients. We found the overall frequency of gastrointestinal symptoms at initial presentation in our ambulatory, predominantly homosexual population of HIV-infected patients was 35% (95% CI 30-40%) with 19% having anorexia, 15% weight loss, 14% diarrhea, and 5% dysphagia. There was no association between the presence of symptoms and stool parasites, which were found in 51% of patients. In 165 patients who were initially asymptomatic, 72% subsequently developed symptoms over 36 months of actuarial follow-up. Patients with initial T4 counts < 500 were more likely to develop symptoms. Patients with a greater degree of immunosuppression as indicated by a lower T4 count, are more likely to develop gastrointestinal symptoms.

Ambulatory Care↗
PubMed1993

Biochemical models as early predictors of the etiology of acute pancreatitis.

In this study we observed the discriminative ability of five commonly measured laboratory tests to distinguish between gallstone- and non-gallstone-associated pancreatitis. We also assessed the ability of the lipase-amylase ratio to discriminate between alcohol- and non-alcohol-induced pancreatitis. One hundred sixty-two patients with acute pancreatitis were included in the study. Group A consisted of patients presenting to our hospital in 1988 and 1989. Group B consisted of patients presenting in 1992. Models developed using group A patients were validated using group B patients. For gallstone pancreatitis, AST (threshold value 80 IU/liter) alone and a three-factor model, AST, ALP and bilirubin (threshold values of 80 IU/liter, 115 IU/liter, and 15 mumol/liter, respectively) were the best predictors, correctly classifying at least 80% of cases in group A and B. A lipase-amylase ratio of two correctly classified only 48% of cases in group A and 54% in group B. We conclude that biochemical models are useful in predicting the presence of gallstone pancreatitis but not alcoholic pancreatitis.

Acute Disease↗