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L R Sutherland

Publications and source records attributed to L R Sutherland.

At least 73 records · Page 4Linked to original sources
PubMed1993

Sucrose: a novel permeability marker for gastroduodenal disease.

BACKGROUND: Nonsteroidal anti-inflammatory agents (NSAIDs) commonly cause asymptomatic gastroduodenal damage that may be clinically severe. At present the only method to determine the presence or absence of such damage is by invasive techniques such as endoscopy. Because distal small intestinal damage can be noninvasively detected with oral permeability tests, the hypothesis that gastroduodenal damage could be detected using similar methods was examined in the present study. RESULTS: Animal data are presented suggesting that sucrose represents an ideal probe molecule to detect increased gastroduodenal permeability in a site-specific manner. With gastroduodenal damage, caused by either ethanol or NSAIDs, sucrose permeability is increased. Furthermore, because sucrose is rapidly degraded within the small intestine, this probe does not detect small intestinal damage, making it specific for the upper gastrointestinal tract. Finally, a pilot study in humans is presented to show the use of this technique in evaluating human gastric permeability. CONCLUSIONS: Sucrose represents a novel permeability probe with specificity for damage of the upper gastrointestinal tract. In animals and humans it appears useful to noninvasively detect gastroduodenal injury caused by several agents.

Animals↗
PubMed1993

Is small intestinal permeability really increased in relatives of patients with Crohn's disease?

BACKGROUND: Patients with Crohn's disease have increased intestinal permeability, which may precede the development of clinical disease and be involved in disease pathogenesis. Subsequent studies have suggested that, as a group, first-degree relatives of patients with Crohn's disease do not have significantly increased small intestinal permeability rates. The present study proposes that conventional data analysis, used in these studies, may be inappropriate and has overlooked an important observation. METHODS: Lactulose and mannitol permeabilities were defined in healthy controls and in patients with Crohn's disease and their first-degree relatives. RESULTS: Intestinal permeability in relatives was similar to that in the control group, but a subpopulation had abnormally high permeability rates in the absence of clinical evidence for disease. Raw data from another investigator confirmed this finding in an additional study; consequently, it is concluded that the original hypothesis is still viable. A small proportion of individuals, at high risk of developing Crohn's disease, have increased intestinal permeability. CONCLUSIONS: Increased intestinal permeability may precede clinical manifestations of Crohn's disease.

Crohn Disease↗
PubMed1993

Erratic zidovudine bioavailability in HIV seropositive patients.

The bioavailability of zidovudine was evaluated in 16 HIV seropositive patients using a prospective standardized study. Symptomatology, D-xylose absorption and immune status were also measured to determine indicators of poor bioavailability. Zidovudine was rapidly absorbed (Tmax: 0.82 +/- 0.39 h) with a large variation in peak serum concentrations (Cmax: 1.21 +/- 0.64 mg/L). The mean elimination half-lives after intravenous and oral administration were 1.5 +/- 0.4 h and 1.3 +/- 0.2 h, respectively. Mean zidovudine bioavailability was 64.0 +/- 21.3% and was not associated with D-xylose absorption values. Five h urine D-xylose excretion was abnormal in seven patients but only three (43%) had zidovudine bioavailabilities below the mean for the group. Conversely, only five of nine patients (56%) with normal D-xylose absorption tests had zidovudine absorption values below the mean. The presence of a mild alteration in bowel habits, defined as up to four unformed or semi-solid stools per day, showed a highly significant relationship to low bioavailability (P < 0.0001, Student's t-test). Lower CD4 lymphocyte counts were also associated with a low bioavailability (R-squared, 0.36, P = 0.0143). Patients with lower CD4 lymphocyte counts or with mild diarrhoea may be at risk for erratic zidovudine absorption.

Adult↗
PubMed1993

Efficacy of bile acid therapy for gallstone dissolution: a meta-analysis of randomized trials.

To define better the efficacy of bile acid therapy for dissolution of radiolucent gallstones, we performed a meta-analysis of published trials from January 1966 to September 1992. Studies were identified using a MEDLINE computer search followed by an extensive manual search. The inclusion criteria used were: randomized trial, radiolucent gallstones in a visualizing gallbladder on oral cholecystography, and complete stone dissolution confirmed by oral cholecystography or ultrasound. Study results were pooled into 6 groups: placebo: high- and low-dose chenodeoxycholic acid (CDCA) (> or = 10 mg.kg/day and < 10 mg.kg/day); high- and low-dose ursodeoxycholic acid (UDCA) (> or = 7 mg.kg/day and < 7 mg.kg/day) and combined CDCA plus UDCA. Homogeneity calculations were performed and the percentage of complete stone dissolution calculated for each group with 95% confidence intervals. Of 66 trials identified, 23 comprising 1949 patients met the inclusion criteria. A total of 1062 patients were treated with CDCA, 819 with UDCA and 78 combination therapy. In studies > 6 months' duration, high-dose UDCA completely dissolved stones in 37.3% of patients (95% C.I. 33-42%), low-dose UDCA in 20.6%) and high-dose CDCA 18.2% (95% C.I. 15-21%). Based on only two studies, combination therapy achieved dissolution in 62.8% (95% C.I. 51-74%) of patients. Stones less than 10 mm dissolved significantly more frequently than stones larger than 10 mm. This analysis shows that UDCA in doses greater than 7 mg.kg/day taken for greater than 6 months will dissolve radiolucent gallstones in 38% of patients. The combination of UDCA and CDCA may be more efficacious but this observation is based upon only 78 patients and requires confirmation in further randomized trials.

Chenodeoxycholic Acid↗
PubMed1992

Effect of oral contraceptive use on reoperation following surgery for Crohn's disease.

The influence of oral contraceptive (OCP) use as a risk factor for the development of Crohn's disease is disputed. We wished to determine if OCP use affected the risk of recurrence (defined as need for a second surgery) in women who had already undergone a resection for Crohn's disease. We hypothesized that if contraceptive use was a risk factor for disease development, it could influence recurrence. Using a mail questionnaire, we surveyed 138 women regarding their OCP use following surgery for Crohn's disease. All participants were between ages 16 and 35 at the time of their initial surgery which occurred between 1966 and 1984. Ninety-seven women (70%) responded. Mean follow-up was 9.9 years (range 4-27). Forty-six women required a second surgery. The recurrence rate as determined by actuarial analysis, was 27.2% (95% confidence intervals (CI95 16.5-38.1) and 58.0% (CI95 37.8-78.2) at 5 and 10 years, respectively. Thirty-two women took OCP in the first year following surgery. Eleven OCP users (34.4%) required additional surgery compared to 34 (53.1%) of nonusers. Using life table analysis, the percentage requiring a second surgery was 25.0% (CI95 6.9-43.1) and 40.7% (CI95 1.5-80%) at 5 and 10 years, respectively, for users compared to 28.4% (CI95 6.9-43.1) and 64.0% (CI95 40.5-87.5) for nonusers (Lee Desu, P greater than 0.05). When surveyed about their reasons for using OCP, most women stated that their disease did not affect their decision to use contraceptives.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Neutrophil autoantibodies in ulcerative colitis: familial aggregation and genetic heterogeneity.

The possibility that the neutrophil autoantibodies associated with ulcerative colitis represent a genetic marker of susceptibility was investigated by determining their prevalence in unaffected relatives of patients. Neutrophil autoantibodies were detected using an enzyme-linked immunosorbent assay, and positive values were confirmed by indirect immunofluorescence. An increased prevalence of neutrophil antibodies was found not only in the probands (68%, 26/38) but also in their clinically unaffected family members (15.7%, 17/108) compared with controls (2.9%, 1/35) (P less than 0.0001 and P less than 0.05, respectively). These results were confirmed with sera from a second center, where 86.4% (19/22) of probands were positive and 20.9% (9/43) of their relatives were positive. The prevalence of neutrophil autoantibodies in the relatives of probands who were antibody positive (21.4%) was significantly greater than the prevalence in relatives of probands who were antibody negative (7%; P less than 0.05). The findings are consistent with these antibodies being a potential marker of genetic susceptibility to ulcerative colitis and suggest the possibility of genetic heterogeneity within this disease.

Adolescent↗
PubMed1992

Peptides in the gastrointestinal tract in human immunodeficiency virus infection. The GI/HIV Study Group of the University of Calgary.

The presence of immunoreactivity to the neuronal phosphoprotein B-50 and the peptides bombesin, calcitonin gene-related peptide, galanin, neurotensin, neuropeptide Y, somatostatin, substance P, and vasoactive intestinal polypeptide was examined in biopsy specimens from the duodenum and rectum of human immunodeficiency virus (HIV)-seropositive and HIV-seronegative male homosexual patients. The distribution of B-50 and the peptides was correlated with HIV serology, number of CD4+ lymphocytes, and the presence of HIV in biopsy culture. There was a very low incidence of enteric pathogens in both groups of patients. It was found that HIV-seropositive patients had a greater incidence of abnormal patterns of immunoreactivity (reduced intensity and/or density of innervation) in enteric nerves and enteroendocrine cells than HIV-seronegative patients. A reduction of substance P immunoreactivity was significantly correlated with reduced CD4+ lymphocyte count and HIV status; a similar trend was also seen for somatostatin and vasoactive intestinal polypeptide. Using B-50 as a marker, it was found that both groups of patients had altered patterns of immunoreactivity in rectal nerves. The findings of this study suggest that some of the clinical symptoms associated with HIV infection may be caused by a specific HIV enteropathy that influences enteric nerve and/or enteroendocrine cell function by altering the density of peptide immunoreactivity.

Adult↗
PubMed1992

Gastrointestinal tissue cultures for HIV in HIV-infected/AIDS patients. The University of Calgary Gastrointestinal/HIV Study Group.

OBJECTIVE: To determine the prevalence of HIV in endoscopic biopsies from the esophagus, stomach, duodenum, and rectum of homosexual and bisexual men at various stages of HIV infection as part of a comprehensive study of gastrointestinal dysfunction in HIV infection. METHODS: After repeated washings and mechanical disruption, biopsies obtained from 58 volunteers were individually cocultured with pooled peripheral blood lymphocytes from healthy HIV-seronegative blood donors. RESULTS: HIV was isolated from at least one site in 40 out of 49 patients. Esophageal biopsies were most frequently found positive (46%), followed by duodenal biopsies (44%), rectal biopsies (43%), and gastric biopsies (27%). Recovery of HIV was not related to any gastrointestinal signs or symptoms. HIV was recovered in the biopsies both from asymptomatic patients with CD4 lymphocyte counts greater than 500 x 10(6)/l and also from patients with more advanced disease receiving zidovudine therapy. CONCLUSIONS: The entire gastrointestinal tract appears to be a target site throughout the course of HIV infection in homosexual and bisexual men.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Absence of an association between enteric parasites in the manifestations and pathogenesis of HIV enteropathy in gay men. The GI/HIV Study Group.

49 gay men confirmed to be infected with the human immunodeficiency virus (HIV) and 9 HIV seronegative gay men participated in a pilot study comparing clinical status and enteric parasite load with gastrointestinal structure, function and symptomatology. Cases included 16/49 (33%) men who were CDC stage II, 7/49 (14%) who were CDC stage III, and 26/49 (53%) who were CDC stage IV. The mean CD4-lymphocyte count was 476 +/- 199 (SD)/microliter. The prevalence of enteric parasitic flora was similar in HIV seropositive patients and controls. Seven cases had enteric infection with pathogenic agents including 3 patients with Entamoeba histolytica, and 4 patients with Giardia lamblia, one of whom also had cryptosporidiosis. Other cases were most frequently colonized with Blastocystis hominis (44%) and Endolimax nana (41%) regardless of the HIV clinical status. HIV seropositive patients with enteric parasitic colonization tended to have lower mean levels of serum IgA than cases without parasites. Duodenal morphometric mucosal changes demonstrated a significant decrease in the mean villous height (p < 0.01) with no elongation of the crypt depth in HIV-infected patients with and without diarrhea compared to controls. Despite gastrointestinal symptoms including diarrhea and weight loss being more prevalent in HIV infected individuals than controls, no correlations were found between the presence of particular enteric parasites, gastrointestinal symptomatology, the clinical HIV status of the CD4-lymphocyte count, the malabsorption of D-xylose or morphometric changes in the duodenum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Nutritional status and food intake in human immunodeficiency virus infection. GI/HIV Study Group.

Nutritional status and food intake of HIV+ and HIV- homosexual men that were free from enteric pathogens were compared. Food intake (7-day weighed record), anthropometry, and D-xylose excretion were measured in 44 patients (9 HIV-, 35 HIV+). HIV+ patients were found to be thinner, based on anthropometric measurements of skinfold thickness (p < 0.05) and percentage body fat (p < 0.05), and they also tended to be lighter than the HIV- patients. No differences were observed in the arm muscle mass or the food intake of the two groups. In the HIV+ patients, regression analysis was used to correlate changes in nutritional status with progression of the disease, using CD4+ lymphocyte count as a measure of severity. A decrease in CD4 count positively correlated with a decrease in weight (r = 0.48, p < 0.01), body mass index (r = 0.41, p < 0.05), and arm muscle area (r = 0.42, p < 0.01). Energy intake (r = 0.67, p < 0.01), serum albumin (r = 0.52, p < 0.01), and D-xylose excretion (r = 0.57, p < 0.0001) also positively correlated with CD4 count. Multiple regression analysis revealed a relationship between CD4 count, weight, and energy intake, indicating that as the disease progresses, a decline in weight is seen parallel to a reduction in food intake. These data indicate that changes in body composition and nutritional status are present throughout the stages of HIV disease, though no causal relationships can be interpreted from this study. The initial changes appear to be due to loss of fat stores, as determined by anthropometry.(ABSTRACT TRUNCATED AT 250 WORDS)

Anthropometry↗
PubMed1991

Frequency of hereditary nonpolyposis colorectal cancer in southern Alberta.

The frequency of hereditary nonpolyposis colorectal cancer was evaluated in a group of colorectal cancer patients under age 50 diagnosed in southern Alberta between 1973 and 1987. Families were identified as positive for this syndrome if three first-degree relatives in the kindred had colorectal cancer. Of the 390 patients with adenocarcinoma, 318 patients participated. The frequency of hereditary nonpolyposis colorectal cancer was 3.1% (12 families) in this group (Ci95 1.6-5.3%). Clinical characteristics reported on from the index patients include tumor location, Dukes stage at presentation, frequency of synchronous and metachronous tumors, frequency of second primaries, and survival. The 5- and 10-year actuarial survival was 86% and 69%, respectively.

Adenocarcinoma↗
PubMed1991

Pilot study of sandostatin (octreotide) therapy of refractory HIV-associated diarrhea.

Seventeen AIDS patients were enrolled in a prospective open-label dose-finding study of octreotide (Sandostatin) therapy for refractory diarrhea. Five were nonevaluable due to progression of AIDS symptomatology, and one was excluded because of lack of confirmation of HIV infection. Five of 11 evaluable patients responded to therapy (45%); two each at 50 micrograms and 100 micrograms, and one at 250 micrograms thrice daily doses. A sixth patient demonstrated a moderate reduction in stool volume at 250 micrograms thrice daily, which, although deemed clinically relevant, did not meet the criteria for response. On discontinuation of therapy, diarrhea recurred in all patients within 1-12 days, and responded to reinitiation of octreotide in those five patients who resumed treatment. Only one of the three patients with concurrent cryptosporidial infection responded to treatment. The drug was well tolerated, with mild symptomatology in three patients. Long-term treatment at a stable dose was effective in three of five treated patients for periods for seven months in one (moderate responder) and one year in two. One patient required dose increases to control symptoms, but after one year of treatment developed severe nausea following injections, which required dose cessation. One patient had partial control of his diarrhea for only three months despite two dose increases. These data suggest that octreotide may be of useful therapeutic value in HIV-associated diarrhea and that further studies are indicated.

Adult↗
PubMed1991

Anti-neutrophil cytoplasmic antibodies in ulcerative colitis. Comparison with other colitides/diarrheal illnesses.

Previous studies from this laboratory showed that serum anti-neutrophil cytoplasmic antibodies, distinct from those associated with active Wegener's granulomatosis, are present in the majority of patients with ulcerative colitis. In this study, the specificity of anti-neutrophil cytoplasmic antibodies for ulcerative colitis as compared with other colitides and diarrheal illness was determined. In a blinded study, test samples of serum were screened for anti-neutrophil immunoglobulin G in a fixed neutrophil enzyme-linked immunosorbent assay. Levels of neutrophil binding by immunoglobulin G and titers of anti-neutrophil immunoglobulin G in sera from patients with ulcerative colitis and patients with ulcerative colitis post colectomy were each significantly greater than the levels and titers for normal controls and patients with a variety of other colitides and diarrheal illnesses. Levels of neutrophil binding for colonic Crohn's disease, bacterial/amoebic colitis, the irritable bowel syndrome with diarrhea, and other miscellaneous diarrheal illnesses were not significantly different than the levels for normal controls. Although the levels of binding for collagenous colitis were significantly less than the levels for ulcerative colitis, they were significantly greater than the levels for normal controls. Patterns of neutrophil binding by serum samples that were positive in the enzyme-linked immunosorbent assay were determined by indirect immunofluorescence. Perinuclear staining was the predominant pattern shown by sera from patients with ulcerative colitis. The combination of a positive value in the enzyme-linked immunosorbent assay and a perinuclear immunofluorescence pattern was 60% sensitive and 94% specific for ulcerative colitis. It is concluded that anti-neutrophil cytoplasmic antibodies in ulcerative colitis are not simply an epiphenomenon related to inflammation of the colon. Identification of the antigen(s) to which these autoantibodies are directed may facilitate understanding of the underlying immune response and may allow development of an assay that is more sensitive and specific for ulcerative colitis.

Adult↗
PubMed1990

Gastrointestinal function and structure in HIV-positive patients.

We examined 19 patients (17 men) with human immunodeficiency virus (HIV) infection and gastrointestinal symptoms to determine whether those symptoms were due to either a gastrointestinal tract infection or a defect in mucosal absorption because of an enteropathy. The erythrocyte folate and serum vitamin B12 levels were within normal limits in all of the patients. The serum ferritin level was elevated in 12. The xylose absorption test results were abnormal in 8 of the 13 patients able to complete the study. None of the duodenal aspirates yielded a pathogen. Light microscopy revealed nonspecific lymphocytic inflammation without infection in the stomach (in seven patients), the esophagus (in five), the duodenum (in two) and the rectum (in two). However, biopsy specimens were positive for Candida albicans in the esophagus (four patients), cytomegalovirus in the esophagus (one) and the rectum (two), Helicobacter pylori in the antrum (two), Treponema infection in the rectum (two) and Mycobacterium avium-intracellulare in the small intestine (one). Only three patients had a normal series of biopsy specimens. All of the patients had similar ultrastructural changes at the epithelial-stromal junction of the antral glands and in the intestinal crypts. We conclude that abnormal biochemical and endoscopic findings are common in HIV-positive patients with gastrointestinal symptoms. Defects in carbohydrate absorption and ultrastructural changes may be responsible for some aspects of HIV enteropathy.

Bacterial Infections↗
PubMed1990

Use of alternative medicine by patients attending a gastroenterology clinic.

We carried out a study to determine the proportion of patients attending a university-based gastroenterology outpatient clinic who sought alternative medical care for the same health problem that had prompted them to see a gastroenterologist. After the patients completed a self-administered questionnaire, the gastroenterologist gave a diagnosis and assigned a functional rating. Of the 395 patients 287 (73%) had not used alternative medicine, and 36 (9%) had sought alternative medical care for the problem that had prompted them to see a gastroenterologist. There were no significant differences between alternative medicine users and nonusers in sociodemographic characteristics, use of health care services or general health status. Patients with a functional disease were more likely to seek alternative medical care than those with organic disease (33% v. 7%) (p less than 0.0001). Fewer alternative medicine users (54%) than nonusers (85%) were satisfied with conventional medicine (p less than 0.001), and more alternative medicine users (49%) than nonusers (13%) were very sceptical of conventional medicine (p less than 0.0001).

Adolescent↗
PubMed1990

Outpatient health care utilization of patients with inflammatory bowel disease.

On the basis of the normal life expectancy of inflammatory bowel disease patients, the early onset of their disease, and the variety of symptoms, inflammatory bowel disease patients were anticipated to be frequent users of outpatients services. This study assesses (1) the characteristics, (2) outpatient health care utilization, and (3) the degree of satisfaction with health care of inflammatory bowel disease patients compared to patients with other gastrointestinal disease. The study method was a secondary analysis of data collected on 395 patients attending the University of Calgary Gastroenterology Outpatient Clinic in 1988. Inflammatory bowel disease patients were significantly younger (P less than 0.001) and better educated (P less than 0.05) than other patients. During the past year inflammatory bowel disease patients consulted significantly more often with their gastroenterologist (P less than 0.001) and spent more time in hospital (P less than 0.05) than other patients. Inflammatory bowel disease patients also consulted more frequently with herbalists and naturopaths. Lastly, inflammatory bowel disease patients were as satisfied with the health care they received as other patients. These results provide information useful for health care planners as well as for those dealing directly with inflammatory bowel disease patients.

Adolescent↗