[Show abstract][Hide abstract] ABSTRACT: Adults with acquired immune deficiency syndrome and persistent diarrhoea in Zambia have intestinal infection, predominantly protozoa.
To search for treatment which can be offered with minimal investigation, we carried out a double-blind, randomized-controlled trial of nitazoxanide (a drug with a range of activity against parasites and bacteria).
Patients with diarrhoea of 1 month duration or longer were randomized to receive nitazoxanide (1000 mg twice daily) or placebo for 2 weeks. End-points were clinical response, parasitological clearance and mortality.
Two hundred and seven adults were randomized; 42 died during the study. The primary assessment of efficacy was made after 17 days. Clinical response was observed in 56 (75%) of 75 patients receiving nitazoxanide and 45 (58%) of 77 patients receiving placebo (P = 0.03). The rate of improvement was markedly higher in patients with CD4 counts under 50 cells/microL receiving nitazoxanide (P = 0.007). The benefit was largely restricted to the period when the drug was being administered. No difference was seen in parasitological clearance between the two groups. Mortality was 19% by 4 weeks of follow-up and did not differ with treatment allocation.
Nitazoxanide given orally for 14 days was associated with clinical improvement in Zambian acquired immune deficiency syndrome patients with diarrhoea, especially those with very low CD4 counts.
[Show abstract][Hide abstract] ABSTRACT: To determine the response of the small intestinal mucosa to environmental conditions, we studied changes in mucosal architecture and function in a longitudinal cohort study in African adults. Over three consecutive years, 238 adults submitted monthly stool samples for parasitologic and bacteriologic analysis and underwent an annual endoscopic jejunal biopsy for mucosal morphometry. Absorption and permeability assays were performed on the same day as the enteroscopy. Variation in mucosal architecture and function was correlated with environmental factors and stool microbiology. The whole cohort had structural and functional evidence of tropical enteropathy, but structure and function were only weakly correlated. There were marked changes over time, and seasonal variation was observed in villous height (16%), xylose recovery (16%), and permeability (28%). Asymptomatic intestinal infections were common. Enteropathy was more severe in participants with Citrobacter rodentium or hookworm ova in the stool sample taken one month before the investigations were performed.
The American journal of tropical medicine and hygiene 05/2004; 70(4):412-9. · 2.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Identification of patients likely to experience high levels of discomfort during unsedated gastroscopy would be useful as these patients could be prospectively targeted for sedation. We prospectively assessed patient and endoscopic variables in subjects attending for endoscopy in order to identify factors associated with patients' experience of the unsedated examination.
We studied 508 patients attending for routine diagnostic gastroscopy. Clinical and endoscopic data were collected and patients completed a two-part questionnaire assessing their anxiety with, and experience of, the procedure.
Thirty-nine subjects failed to complete the initial unsedated endoscopy. Failure to tolerate endoscopy was associated with younger age (P = 0.002) and examination with a standard-bore (> or = 9.0 mm) endoscope (P = 0.004). High levels of patient discomfort during the procedure were associated with younger age (P < 0.001), high levels of pre-endoscopic anxiety (P < 0.001), high levels of pre-endoscopic discomfort due to throat spray (P = 0.02) and examination with a standard-bore endoscope (P < 0.001). Preference for sedation during future examinations was related to female gender (P = 0.02), young age (P = 0.02), high levels of apprehension (P < 0.001), the examining doctor (P = 0.002) and use of a standard-bore endoscope (P < 0.001).
Discrete clinical characteristics and endoscopic variables are associated with patients' experience of unsedated endoscopy. Further work might result in an algorithm for identifying patients who would benefit from sedation prior to gastroscopy.
Scandinavian Journal of Gastroenterology 01/2002; 36(12):1352-7. · 2.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The role of mucosal T-cell activation in HIV-associated enteropathy is uncertain. Twenty Zambian patients with AIDS and chronic diarrhea were studied, as were nine controls. Distal duodenal biopsies were taken at endoscopy. Morphometric analysis and dual color immunofluorescence staining were performed. Villous height was reduced [177 (118-228) vs 305 (244-358) microm P = 0.002] and crypt depth increased [220 (164-202) vs 194 (164-202) microm P = 0.008] in AIDS patients compared to controls. CD3+CD4+ T cells were reduced in AIDS patients compared to controls [12.9 (5.7-25.2) vs 47.6 (33.4-65.5)% P = 0.04]. There was no significant difference in expression of CD8, CD25, CD69, HML-1, or HLA-DR on T cells between the AIDS patients and controls, with the exception of CD3+HML-1+ cells, which were increased in AIDS patients (P = 0.05). Small intestinal T-cell activation was similar between AIDS patients and controls. We conclude, therefore, that this mechanism is not likely to be important in the pathogenesis of HIV-associated enteropathy.
[Show abstract][Hide abstract] ABSTRACT: Upper gastrointestinal endoscopy is performed without sedation in many countries. Unsedated patients experience more discomfort during endoscopy than sedated patients, but few studies have examined factors which could be modified to minimize discomfort during the procedure. We assessed the effect of endoscope diameter on patient discomfort during unsedated transoral gastroscopy.
A total of 322 patients attending for unsedated endoscopy were examined using an endoscope of diameter either 6.0 mm or 9.8 mm. Patients completed a two-part questionnaire assessing tolerance of the procedure and discomfort during it.
There was failure to complete the initial unsedated endoscopy in three of 163 patients in the 6.0 mm group and 14 of 159 in the 9.8 mm group (P = 0.009). Patients in the 6.0 mm group reported less discomfort both during endoscope insertion (P < 0.0001) and during the remainder of the procedure (P < 0.0001). 14% of patients in the 6.0 mm group indicated that they would request sedation if a further endoscopy were necessary, compared with 31% in the 9.8 mm group (P = 0.0005).
Ultrathin endoscopes may have a role in clinical practice if randomized comparative studies with standard-bore instruments confirm that they do not compromise diagnostic quality.
[Show abstract][Hide abstract] ABSTRACT: Nonsteroidal antiinflammatory drugs, inhibitors of prostaglandin synthesis, have different effects on gallbladder contractility in normal and diseased human gallbladders in vivo. We investigated this differential effect by comparing the effects of prostaglandins PGE2 and PGF2alpha, the thromboxane A2 mimetic U46619, and PGI2 on in vitro contractility in gallstone-free and gallstone-containing human gallbladders. Isometric tension was measured in gallbladder muscle strips mounted in organ baths. EC50 was calculated for each agonist. The rank order of potency in gallstone-free gallbladders was PGE2 > CCK > U46619 > PGF2alpha and in gallstone-containing gallbladders was U46619 > PGE2 > CCK > PGF2alpha. PGI2 produced contraction of gallstone-free gallbladder and relaxation of gallstone-containing gallbladder in the basal state. Further, PGI2 produced no relaxation in gallstone-free muscle strips precontracted with CCK, but significant relaxation in CCK precontracted gallstone-containing strips. PGE2, PGF2alpha, and U46619 are potent contractors of gallstone-free and gallstone-containing gallbladders, whereas PGI2 relaxes only gallstone-containing gallbladders. Since gallbladders containing cholesterol-supersaturated bile produce increased PGI2, this PGI2-induced relaxation may be a determinant of the impaired gallbladder motility of gallstone disease.
[Show abstract][Hide abstract] ABSTRACT: We report two cases of factitious diarrhoea caused by stool dilution. In the first report stools from a patient with chronic diarrhoea were found to have been diluted with urine, and the diarrhoea further compounded by surreptitious laxative misuse. In the second report, after prolonged investigation of high output ileostomy, the patient's ileal effluent was found to have been diluted with water. We conclude that factitious diarrhoea, in particular dilutional diarrhoea, is over-investigated and underdiagnosed. Stool weights, complete input/output measurement, analysis of stool osmolality and electrolytes, and laxative screening are essential in the investigation of chronic watery diarrhoea.
European Journal of Gastroenterology & Hepatology 07/2000; 12(6):609-11. DOI:10.1097/00042737-200012060-00005 · 2.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effects of Helicobacter pylori infection and its associated gastric histology on alpha-tocopherol and beta-carotene concentrations in serum, gastric juice and antral mucosa were investigated in patients undergoing routine gastroscopy for investigation of dyspepsia.
Eighty-six patients were studied. High-performance liquid chromatography was used to measure alpha-tocopherol and beta-carotene concentrations. H. pylori infection was assessed by histology, bacterial culture, rapid urease test and serology.
No obvious association was found between age, sex, smoking or endoscopic diagnosis and alpha-tocopherol or beta-carotene concentrations in serum, gastric juice and antral mucosa. However, alcohol drinkers had significantly lower antral mucosal and gastric juice beta-carotene concentrations compared to non-drinkers. Gastric juice beta-carotene concentration was markedly lower in patients infected with H. pylori than uninfected controls (2.9 nmol/l (interquartile range 0.3-4.3) versus 4.6 nmol/l (interquartile range 3.5-7.6), P = 0.01), but there was no significant difference in serum or gastric mucosal beta-carotene concentrations between the two patient groups. The presence of gastric atrophy and intestinal metaplasia was significantly associated with reduced mucosal alpha-tocopherol and beta-carotene concentrations. Furthermore, antral mucosal alpha-tocopherol concentrations decreased progressively as antral mucosal histology changed from normal to chronic gastritis alone and finally to atrophy and intestinal metaplasia.
Gastric alpha-tocopherol and beta-carotene concentrations are affected by H. pylori-associated gastric histological changes, and these findings suggest that H. pylori infection may not only impair the protective role of vitamin C, but also of alpha-tocopherol and beta-carotene in the stomach.
European Journal of Gastroenterology & Hepatology 06/2000; 12(5):497-503. · 2.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent reports have suggested that intrasphincteric injection of botulinum toxin is effective and long-lasting in the treatment of achalasia.
To report our experience of botulinum toxin injection in a prospective series of consecutive patients with achalasia.
Eleven consecutive patients with achalasia (eight male, mean age 55 years, range 20-87) were treated with 60 units of botulinum toxin (Dysport; Speywood Pharmaceuticals Ltd, UK) into each of four quadrants at the lower oesophageal sphincter. Patients were assessed pre-treatment and 1 month after treatment using a symptom score and oesophageal manometry. Median follow-up was 12 months (range 6-28).
The injection procedure was simple to perform and free of adverse effects. Although treatment had a beneficial effect on dysphagia (median pre-treatment score 3 [interquartile range 3-3]; post-treatment score 2 [0-3]: P=0.03) 1 month following therapy, there was no significant improvement in chest pain or regurgitation scores. Similarly, no significant reduction in median lower oesophageal sphincter pressure was observed (29.5 mmHg [21-42] pre-treatment, 28.5 [17.5-55.5] post-treatment P=0.67). Four patients (36%) required further therapy within 3 months and the overall relapse rate was 73% (eight of 11) within 2 years.
Although botulinum toxin injection was well tolerated, these results using Dysport at a dose of 240 mouse units question its efficacy as a treatment for achalasia.
[Show abstract][Hide abstract] ABSTRACT: One hundred years ago, apart from the treatment of war injuries, the prevention and treatment of diarrhoea was the dominant preoccupation of the deployed military doctor. Since, then our understanding of the pathogenesis and pathophysiology of enteric disease has developed exponentially and our armamentarium for the treatment of enteric diseases has expanded considerably. However, diarrhoea continues to be the dominant military medical concern in deployed units. Here, we examine the evidence for this, discuss the reasons why and critically evaluate current modes of prevention and treatment that are now available to the military medical officer.
Journal of the Royal Army Medical Corps 07/1999; 145(2):95-101. DOI:10.1136/jramc-145-02-11 · 0.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: As HIV has spread through sub-Saharan Africa, persistent diarrhoea has emerged as a major problem in hospitals and in the community in severely affected areas. We have previously demonstrated that antiprotozoal therapy with albendazole reduces diarrhoea in AIDS patients in urban Zambia. This trial was designed to test the hypothesis that the clinical response to albendazole might be improved by oral micronutrient supplementation.
Randomized, placebo-controlled trial.
Home care service of Ndola Central Hospital, Zambia.
HIV-seropositive patients with persistent diarrhoea.
Patients were randomized to albendazole plus vitamins A, C and E, selenium and zinc orally or albendazole plus placebo, for 2 weeks.
Time with diarrhoea following completion of treatment; mortality; adverse events.
Serum vitamin A and E concentrations before treatment were powerful predictors of early mortality, but supplementation did not reduce time with diarrhoea or mortality during the first month, even after taking into account initial vitamin A or E concentrations, CD4 cell count or clinical markers of illness severity. Serum concentrations of vitamins A and E did not increase significantly in supplemented patients compared with those given placebo, and there were no changes in CD4 cell count or haematological parameters. No adverse events were detected except those attributable to underlying disease.
Although micronutrient deficiency is predictive of early death in Zambian patients with the diarrhoea-wasting syndrome, short-term oral supplementation does not overcome it nor influence morbidity or mortality.
AIDS 04/1999; 13(4):495-500. DOI:10.1097/00002030-199903110-00008 · 5.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Investigation of anti-colon antibodies may be simplified if a sensitive method and homogeneous source of antigen were available.
To examine the anti-colon antibody response using human colonic carcinoma cell lines as antigen. Subjects: Patients with inflammatory bowel disease and other gastrointestinal disorders and healthy controls were studied.
Comparative enzyme linked immunosorbent assays (ELISAs) were performed to assess the value of whole Caco-2, HT-29, and LS-180 cells as antigen. The antigenic determinants of the immune response were characterised by western blot analysis.
Sera demonstrated immunoreactivity against each of the cell lines, but different epitopes were recognised. Applying whole Caco-2 cells as antigen in an ELISA, the prevalence of anti-colon antibodies was significantly greater in patients with ulcerative colitis (36%) than Crohn's disease (13%), other gastrointestinal disorders (13%) and healthy controls (0) (p<0. 05). The immune response was not associated with one predominant antigen.
Fixed whole cell ELISA is a simple and feasible method for studying the anti-colon antibody response. This response is non-specific, being directed against multiple antigens, and is likely to be an epiphenomenon of inflammatory bowel disease, more so for ulcerative colitis than Crohn's disease.
Gut 02/1999; 44(2):196-202. DOI:10.1136/gut.44.2.196 · 14.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In four crowded townships of Lusaka, Zambia, the prevalence of cryptosporidiosis in 222 children with diarrhea was 18%, with marked temporal and geographic variation over the course of one rainy season. Using data on the finding of oocysts of Cryptosporidium parvum in urban water supplies, the areas under study were categorized as high or low risk. Prevalence of cryptosporidiosis in children with diarrhea was higher in high risk areas after stratification by early/late stage of the rains (Mantel-Haenszel odds ratio [OR] = 2.9, 95% confidence interval [CI] = 1.3, 6.7; P = 0.008). Cryptosporidiosis was not associated with keeping animals, nutritional status, or parental education, but was apparently more common in breast fed children (OR = 2.7, 95% CI = 1.1, 6.9; P = 0.01), although the proportion of exclusively breast fed children was not measured. Since most of these infections were of short duration, we conclude that transmission of C. parvum can vary dynamically within one city and over short periods of time, and that water-borne contamination may be a substantial influence.
The American journal of tropical medicine and hygiene 10/1998; 59(3):435-7. · 2.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An audit was carried out on the activities of a one stop clinic where patients referred by GPs for endoscopy are first interviewed by a gastroenterologist, directly before the procedure. Such a barrier to open access endoscopy did not seem to reduce the workload or the rate of normal examinations.
British Journal of General Practice 05/1998; 48(429):1165-6. · 2.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 1. Leptin inhibits food intake and is an important regulator of long-term energy balance. In rodents, plasma concentrations of leptin are increased by administration of interleukin-1 and tumour necrosis factor. Hyperleptinaemia may mediate the anorexia and weight loss which is observed in chronic infections and inflammatory conditions. 2. Plasma leptin and soluble tumour necrosis factor receptor (sTNF-r55) concentrations were measured in patients with inflammatory bowel disease and acquired immunodeficiency syndrome (AIDS), and healthy controls. 3. The patients with AIDS were severely wasted [% body fat 12 (9-16); median (interquartile range)] compared with those with inflammatory bowel disease [25.1 (19-31.5)] and control subjects [29.4 (23.6-37.8)]. Leptin concentrations were highly correlated with percentage body fat in controls (r = 0.74, P < 0.001) and patients with IBD (r = 0.73, P < 0.001) but not in the patients with AIDS (r = -0.024). Leptin concentrations were similar in the inflammatory bowel disease [4.8 (2.6-10.1) ng/ml] and control groups [8.0 (3.1-14.1) ng/ml] but were significantly lower (P < 0.05) in patients with AIDS [1.8 (1.5-2.3) ng/ml] after 23 patients were matched for sex and percentage body fat in patients with inflammatory bowel disease [2.4 (1.8-4.1) ng/ml]. Plasma concentrations of sTNF-r55 were higher in both the patients with inflammatory bowel disease [0.19 (0.16-0.23) ng/ml] and those with AIDS [4.8 (2.8-7.3) ng/ml] compared with controls [0.14 (0.09-0.16) ng/ml] but were not correlated with either percentage body fat or plasma leptin concentrations. 4. Hyperleptinaemia does not appear to mediate the anorexia and weight loss associated with inflammatory bowel disease and AIDS. In patients with AIDS with extreme wasting there was no relationship between body fat and leptin and this may be related to the rapid weight loss which occurs in these patients.