Intensity of hemodialysis and response to erythropoietin.
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Anemia, Iron-Deficiency↗
Biomedical subjects
M J Farthing
Publications and source records attributed to M J Farthing.
Increased energy expenditure in growing adolescents with Crohn's disease.
Undernutrition is considered to have a central role in the pathogenesis of growth retardation in Crohn's disease. This may occur as a consequence of inadequate food intake, increased energy expenditure, or both. Ten growing adolescents with inactive Crohn's disease were assessed with respect to anthropometric parameters and resting energy expenditure, measured by indirect calorimetry during remission, repeated in relapse (N = 5), and compared to that predicted from the Harris-Benedict formula. Mean energy intake was assessed with seven-day diaries in five patients and compared to recommended intake for age, sex, weight, and physical activity. Ten healthy, growing, age- and sex-matched adolescents served as controls. Nine patients with inactive Crohn's disease, who had ceased growing, were matched for disease site and duration and acted as disease controls. Patients and disease controls had lower body mass index (19.2 +/- 0.6; 20.9 +/- 0.7) than healthy controls (23.7 +/- 0.6; P < 0.001). Percent body fat was lower in patients (13.2 +/- 1.9%) compared to healthy controls (20.5 +/- 2.4%; P < 0.05) but not to disease controls (17.0 +/- 2.6%). Patients had higher resting energy expenditure per kilogram of fat-free mass than disease or healthy controls (36.9 +/- 5.1; 32.9 +/- 2.6; 30.9 +/- 2.1 kcal; P < 0.02). Measured resting energy expenditure in patients, but not in disease or healthy controls, was higher than the predicted (measured: predicted 1.15, 1.03, 0.9, respectively; P < 0.03). Energy intake in patients was 97% of recommended intake but the measured ratio of energy intake/resting energy expenditure was lower than the predicted ratio (1.49 vs 1.71; P < 0.05). During subsequent relapse in five patients resting energy expenditure was unchanged. In growing adolescents with inactive Crohn's disease, there is increased energy expenditure that is not accompanied by an increase in energy intake. Relapse of disease does not appear to increase resting energy expenditure further but may "divert" energy from growth to disease activity. This suggests that nutritional therapy should be directed towards increasing caloric intake to maximize growth potential.
Adolescent↗
Jejunal water and electrolyte transport in human cryptosporidiosis.
Cryptosporidiosis may have severe clinical consequences in both immunocompromised and immunocompetent individuals. However, pathophysiological mechanisms that are responsible for diarrhea are poorly understood. We performed jejunal perfusion studies in patients with human immunodeficiency virus-related cryptosporidial diarrhea to measure water and electrolyte transport in vivo. Five patients with human immunodeficiency virus-related cryptosporidiosis and nine healthy volunteers were studied using a triple-lumen steady-state jejunal perfusion technique. Stool volume measurement and distal duodenal biopsy showed that the patients had diarrhea (600-1500 ml/24 hr) and morphological abnormalities of small intestinal mucosa. Net water, sodium, and chloride movement in the jejunum was not significantly different from healthy controls. In these patients with watery diarrhea and morphological mucosal abnormalities, we found no evidence that cryptosporidial diarrhea was due to a secretory state in the proximal small intestine. We conclude that diarrhea may be due to secretion of electrolytes and water efflux more distally or to other abnormalities of gastrointestinal function.
AIDS-Related Opportunistic Infections↗
The prevalence and aetiology of persistent diarrhoea in adults in urban Zambia.
As the AIDS pandemic has spread, diarrhoea in adults has become a major burden on health care institutions in central Africa and on the families of sufferers. In order to assess the magnitude of the problem, we carried out a survey of households in a high population density township of Lusaka to determine the prevalence of persistent diarrhoea in adults. We also carried out a study of the causes of persistent diarrhoea in patients attending the University Teaching Hospital, Lusaka. The community survey assessed 460 households, representing a sample of 1440 adults. 94 adults were reported as having had diarrhoea in the 2 weeks prior to the survey, implying an attack rate of 1.74 per adult per year. Of these 94 cases, six had diarrhoea of between 2 and 4 weeks duration, and ten had diarrhoea of over 4 weeks duration. In the hospital study, 75 (97%) out of 77 patients with diarrhoea of over 1 months' duration were HIV seropositive; potentially pathogenic parasites were found in 61/75 (81%) of seropositives. This information indicates that persistent diarrhoea in adults, mostly related to HIV infection, is likely to be an important and growing reservoir of enteric pathogens and represents a significant burden on hospitals and relatives. This emerging problem in sub-Saharan Africa may foreshadow developments in other continents.
Adult↗
Giardiasis.
Despite rapid progress in understanding the biology of Giardia, several questions remain unanswered. First, there is no adequate explanation for the diverse clinical spectrum of giardiasis. Second, the mechanisms by which Giardia produces diarrhea and malabsorption are poorly understood, although some progress has been made. Finally, despite extensive studies in animal models and human infections, the key immunologic determinants for clearance of acute infection and development of protective immunity remain ill defined. This article discusses the epidemiology, pathology, diagnosis, treatment, and prevention of giardiasis.
Animals↗
Codon usage in Cryptosporidium parvum differs from that in other Eimeriorina.
Codon usage of Crytosporidium parvum was compared with those of other Eimeriorina Toxoplasma gondii and Eimeria tenella and revealed a biased use of synonymous codons with a preference for NNU (40.0%) and NNA (33.4%). There was no close resemblance of the codon usage of C. parvum to T. gondii (correlation coefficient, r = 0.14) or E. tenella (r = 0.14) but it was similar to Entamoeba histolytica (r = 0.75) and Plasmodium falciparum (r = 0.5). Analysis of the codon usage in homologous gene sequences (actin, beta-tubulin) also failed to reveal a close relationship between C. parvum and T. gondii or E. tenella. The low usage codons in C. parvum were most frequently used codons in T. gondii and E. tenella. These observations are consistent with 18S rRNA sequence analysis which shows no close relationship of Cryptosporidium with other Eimeriorina (Sarcocystis, Toxoplasma and Eimeria) and questions the validity of the current classification of C. parvum.
Actins↗
A double-blind randomized trial of low-dose versus high-dose topical anaesthesia in unsedated upper gastrointestinal endoscopy.
BACKGROUND: Upper gastrointestinal endoscopy is frequently performed on unsedated subjects. Pharyngeal anaesthesia is thought to improve patient tolerance to the procedure but the optimum dose of anaesthesia is not known. The aim of this study was to assess the benefits of low-dose vs. high-dose topical anaesthesia in unsedated gastroscopy. METHODS: One hundred and fourteen subjects attending for diagnostic gastroscopy were studied. Patients were randomized to receive either 30 mg or 100 mg of topical pharyngeal lidocaine spray prior to endoscopy in a double-blind fashion. Subjects completed a questionnaire before and after endoscopy. RESULTS: A similar proportion of patients in each group required intravenous sedation because of discomfort or anxiety during the procedure (P = 0.48). The high-dose group experienced less discomfort during endoscope insertion (P = 0.002) and throughout the examination (P = 0.01). Overall satisfaction was almost identical in the two groups (P = 0.85) and a similar percentage of the high-dose and low-dose groups stated that they would request sedation prior to future endoscopy (37 vs. 44%; P = 0.48). Further analysis showed that apprehensive patients and younger patients reported relatively high levels of discomfort, and that female subjects were more likely to express a preference for sedation at any future gastroscopy. CONCLUSION: High-dose pharyngeal anaesthesia reduces patient discomfort during unsedated upper gastrointestinal endoscopy. However, patient tolerance is also influenced by clinical features, which might be useful in deciding which patients are suitable for this procedure.
Administration, Topical↗
Recently recognised microbial enteropathies and HIV infection.
Persistent diarrhoea and small bowel enteropathy are important features of HIV infection. At least 80% of cases of persistent diarrhoea in patients with HIV/AIDS can be attributed to a specific enteropathogen. The coccidian parasites Cryptosporidium parvum, Isospora belli and Cyclospora and the Microsporidia account for at least 50% of cases of persistent diarrhoea in the industrialised and developing world with major contributions from Mycobacterium avium complex and other bacteria and cytomeglovirus. The intracellular protozoa can be detected on faecal microscopy although confirmation may be required by intestinal mucosal biopsies. Although up to 20% of cases of persistent diarrhoea can not be attributed to a specific infection, the question as to whether HIV infection itself can produce enteropathy remains uncertain. Recent developments in the treatment of persistent diarrhoea in HIV include the use of albendazole for microsporidial diarrhoea and co-trimoxazole for the treatment and eradication of Cyclospora.
HIV Enteropathy↗
Systemic immune activation as a potential determinant of wasting in Zambians with HIV-related diarrhoea.
Wasting in African AIDS patients is severe, and its aetiology is probably multifactorial: persistent diarrhoea, poverty and tuberculosis may all contribute. We report a cross-sectional study of body composition measured anthropometrically in 75 adult patients with HIV-related persistent diarrhoea in Lusaka, and its relationship to gastrointestinal infection and systemic immune activation assessed using serum neopterin and soluble tumour necrosis factor receptor (sTNF-R55) concentrations. Patients as a group were generally severely wasted (mean body mass index (BMI) 15.8 kg/m2, range 11-22), but the severity of wasting was related neither to oesophageal candidiasis nor to intestinal infection. In men but not women, all measures of nutritional status were negatively related to serum sTNF-R55 concentration (fat-free mass in men, r = -0.64; 95% CI: -0.80, -0.41; p < 0.0001). Some wasted patients had cutaneous features of malnutrition, again associated with higher sTNF55 concentrations, and two had peripheral oedema. The diarrhoea-wasting syndrome in this part of Africa seems to be associated with evidence of high cytokine activity in men, rather than oesophageal candidiasis or any particular intestinal opportunistic infection. This immune activation requires further investigation in the context of the sex difference we have observed.
Adolescent↗
Improving the palatability of oral rehydration solutions has implications for salt and water transport: a study in animal models.
It is believed that improving the taste of oral rehydration solutions (ORSs) might lead to greater patient acceptability. A pilot trial showed that replacing glucose with sucrose and increasing the citrate concentration at the expense of chloride improves palatability. However, the transport implications of such modifications are not known. Three hypotonic experimental ORSs (Suc/cit-ORS, 211 mosmol/kg; Suc/Cl-ORS, 224 mosmol/kg; and Glu-ORS, 224 mosmol/kg) were compared with a standard European ORS (Euro-ORS, 265 mosmol/kg) by in vivo perfusion of entire rat small intestine in normal adult rats and rotavirus-infected neonates. All ORSs were of identical sodium, potassium, chloride, and citrate content except that in the Suc/cit-ORS, chloride was removed in favor of increased citrate, and the chloride concentration in Euro-ORS was higher than in the others. Suc/cit-ORS and Suc/Cl-ORS had glucose partially replaced by sucrose while Glu-ORS and Euro-ORS contained only glucose. In normal small intestine, water absorption was greater from Glu-ORS than Suc/cit-ORS or Euro-ORS, although water absorption was similar from Suc/cit-ORS and Suc/Cl-ORS. In the rotavirus model, Glu-ORS produced more water absorption than Euro-ORS or either sucrose ORS. In both models, Suc/cit-ORS caused sodium and chloride secretion. Glucose absorption was similar from all ORSs. These findings indicate that attempts to improve ORS palatability by adding sucrose or increasing citrate at the expense of chloride would incur a significant penalty in terms of salt and water absorption.
Animals↗
A national training programme for gastroenterology and hepatology.
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Curriculum↗
5-hydroxytryptamine release into human jejunum by cholera toxin.
BACKGROUND: Cholera toxin produces intestinal secretion by activation of the adenylate cyclase complex. However animal studies have shown 5-hydroxytryptamine may be released after exposure to cholera toxin, and thereby contribute to the secretory state. AIM: To determine whether cholera toxin releases 5-hydroxytryptamine in human jejunum. SUBJECTS: Seven male subjects were given a subclinical dose of cholera toxin in a paired, controlled, randomised, double blind study. METHODS: A closed 10 cm segment of upper jejunum was exposed to 15 micrograms of cholera toxin for two hours prior to closed segment perfusion with plasma electrolyte solution containing a non-absorbable volume marker, [14C]-polyethylene glycol. 5-Hydroxytryptamine in jejunal effluent and 5-hydroxyindoleacetic acid in urine (up to seven hours after cholera toxin) were measured by high performance liquid chromatography with fluorimetric detection. RESULTS: In contrast with controls, all subjects secreted fluid in response to cholera toxin, median-2.1 ml/cm/h (interquartile range-4.1 to -0.1). During seven hours following cholera toxin, 5-hydroxytryptamine was secreted into the lumen (range 31 to 395 nmol/l) but not in control experiments. After exposure to cholera toxin median urinary 5-hydroxyindoleacetic acid was 5.7 (4.1 to 6.3), which was similar to controls 4.9 (4.1 to 6.3), which was similar to controls 4.9 (4.1 to 6.2). CONCLUSION: Thus, cholera toxin induced a secretory state and promoted the release of 5-hydroxytryptamine into the intestinal lumen, but quantitative changes in urinary 5-hydroxyindoleacetic acid were not detectable. As an intestinal secretagogue, these findings suggest that 5-hydroxytryptamine may play a part in mediating cholera toxin induced secretion in humans.
Adult↗
L-Arginine, nitric oxide, and intestinal secretion: studies in rat jejunum in vivo.
BACKGROUND: L-Arginine has been shown to induce fluid secretion in human jejunum. Nitric oxide, a derivative of L-arginine is thought to have an important role as an intestinal secretagogue. AIM: To determine the effect of L-arginine and the nitric oxide synthase inhibitor, nitro L-arginine methyl ester (L-NAME), on fluid and electrolyte movement in rat jejunum. METHODS: A 25 cm segment of rat jejunum was perfused in situ with iso-osmotic solutions containing either (1) saline, (2) D-arginine 20, (3) L-arginine 20, (4) L-NAME 0.1, 1, or 20 mmol/l, or (5) a combination of L-arginine 20 and L-NAME 0.1, 1, or 20 mmol/l. In further groups the effect of a subcutaneous injection of L-NAME 100 mg/kg was examined in rats pretreated with either D-or L-arginine 500 mg/kg. RESULTS: L-Arginine, unlike D-arginine, induced fluid secretion despite being better absorbed (mean -7.3 v 17.0 microliters/min/g; p < 0.01). L-NAME at 0.1 mmol/l had no effect on basal fluid movement but reversed L-arginine induced secretion (7.8; p < 0.05). L-NAME at 1 and 20 mmol/l induced fluid secretion (-15.4 and -28.4, respectively), which was enhanced by the addition of L-arginine (-30.0 and -41.0, respectively; both p < 0.05). A subcutaneous injection of L-NAME resulted in marked fluid secretion (-39.9) and histological evidence of intestinal ischaemia. These changes were attenuated or reversed by pretreatment with subcutaneous L- but not D-arginine. CONCLUSIONS: L-arginine induces intestinal fluid secretion through production of nitric oxide. There is a delicate balance between the effect of nitric oxide as a secretagogue and its effect on maintaining blood flow and thus preventing intestinal ischaemia.
Animals↗
Intestinal transit in anxiety and depression.
BACKGROUND: Patients with anxiety and depression often have bowel symptoms. Until now, studies investigating a link between altered bowel habit and psychological illness have focused on patients with disturbed defecation presenting to gastroenterologists. AIMS: To determine whether patients with anxiety and depression have objective evidence of abnormal intestinal transit irrespective of any bowel symptoms. METHODS: 21 psychiatric outpatients fulfilling research criteria for generalised anxiety disorder and/or major depression, and 21 healthy volunteers were studied. Orocaecal transit time (OCTT) was measured by lactulose hydrogen breath test. Whole gut transit time (WGTT) was measured by abdominal radiography after ingestion of radio-opaque markers. RESULTS: Median (range) WGTT was shorter in patients with anxiety (14 (6-29) hours) than in patients with depression (49 (35-71) hours) (p < 0.001), and controls (42 (10-68) hours) (p < 0.001). In patients with anxiety, orocaecal transit time was shorter (60 (10-70) minutes) than in patients with depression (110 (60-180) minutes) (p < 0.01), and shorter than in controls (75 (50-140)) minutes (p < 0.05). The prolongation of transit times in depression compared with controls was not significant. However, WGTT correlated with both the Beck Depression Inventory score (r = 0.59, p < 0.01) and the depression score of the Hospital Anxiety and Depression scale (r = 0.66, p < 0.001). CONCLUSIONS: These objective measurements of intestinal transit in affective disorders are consistent with clinical impressions that anxiety is associated with increased bowel frequency, and depressed patients tend to be constipated; mood has an effect on intestinal motor function.
Adolescent↗
Ornithine decarboxylase activity is a marker of premalignancy in longstanding Helicobacter pylori infection.
BACKGROUND: Longstanding Helicobacter pylori infection may increase the risk of developing gastric adenocarcinoma. The sequence of chronic active gastritis leading to gastritis with atrophy and subsequent intestinal metaplasia is thought to be a key step in gastric carcinogenesis. Ornithine decarboxylase (ODC) activity is increased in some pre-malignant gastrointestinal conditions and is essential for malignant transformation in vitro. AIMS: To measure ODC activity in the antrum of H pylori infected and non-infected subjects and to relate this to histological abnormalities associated with recent and longstanding H pylori infection. METHODS: Six antral mucosal biopsy specimens were obtained from 75 patients for detailed histological assessment and measurement of ODC activity. Samples were measured in duplicate and results expressed as median, interquartile range in pmol/mg protein/h. RESULTS: ODC activity was significantly higher in H pylori positive (164, 88-259 pmol/mg/h) than H pylori negative subjects (99.8, 55-158 pmol/mg/h, p = 0.003). However the presence of gastritis, irrespective of the severity of inflammation or activity had no influence on ODC activity. Gastritis with atrophy was associated with increased ODC activity, which was closely related to the severity of the atrophy (p = 0.01). Similarly, ODC activity was significantly increased in subjects with intestinal metaplasia (196, 83-25) compared with those without intestinal metaplasia (111.7, 65-175, p < 0.04). CONCLUSIONS: These results indicate that the histological changes associated with longstanding H pylori infection rather than inflammation alone are associated with increased polyamine biosynthetic activity. This may be relevant to H pylori associated gastric carcinogenesis.
Adolescent↗
The role of somatostatin analogues in the treatment of refractory diarrhoea.
Octreotide inhibits intestinal motility and secretions of the gastro-intestinal tract and pancreas and mediators of diarrhoea and so is very useful in managing refractory diarrhoea. It is safe and effective in 75-80% of the 10-20% of cancer chemotherapy patients who develop severe diarrhoea, and is useful in the management of persistent diarrhoea associated with neuroendocrine tumours, particularly VIPoma and carcinoid tumours, congenital microvillus atrophy, some patients with the short bowel syndrome (giving them a reduced need for intravenous fluids), and AIDS-related diarrhoea that does not respond to antibiotics or conventional anti-diarrhoeal drugs. Some studies suggest a 50% effectiveness in graft-versus-host disease. Preliminary studies suggest that octreotide is also of value in persistent diarrhoea caused by neuromuscular disorders of the gut, particularly diabetes mellitus and systemic sclerosis, suggesting that it may have wider application in the future. Octreotide may prove useful as a tool for studying the pathogenesis of diarrhoea of diverse aetiologies, particularly those associated with disturbances of intestinal motility, such as irritable bowel syndrome.
Animals↗
Chronic Diarrhoea: current concepts on mechanisms and management.
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Chronic Disease↗
Minisatellites corresponding to the human polycore probes 33.6 and 33.15 in the genome of the most 'primitive' known eukaryote Giardia lamblia.
DNA fingerprinting has been widely used for genetic characterization and individual recognition in a range of species, from man and other mammals down the evolutionary scale to some lower eukaryotic parasites. These techniques utilise repetitive elements first characterised in the human genome, known as minisatellites, which display extensive allelic variability. Few biological or biochemical characteristics have been found that distinguish isolates of Giardia lamblia (Gl), or their apparent variations in virulence. We have characterized 21 Gl isolates in axenic culture using DNA fingerprinting with the human minisatellite probes, 33.6 and 33.15. Up to 12 variable bands per isolate were recognized in the size range of 2.5 to 15 kb by Southern blot hybridization of restriction endonuclease-digested Gl DNA. Most isolates demonstrated a distinct banding pattern or DNA fingerprint. The results suggest that this method may provide a basis for the detailed genotypic characterization of Gl which will be amenable to computer and statistical analysis for use in studies of virulence and epidemiology. Also, as Gl occupies a unique phylogenetic position as a member of the earliest known divergence from the eukaryotic line of descent, this study may provide a useful model for the study of other important eukaryotic pathogens, as it is rapidly becoming apparent that minisatellites are ubiquitous components of eukaryotic genomes.
Animals↗