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Biomedical subjects

A M Dawson

Publications and source records attributed to A M Dawson.

At least 19 recordsLinked to original sources

Cryptosporidium parvum: investigation of sporozoite excystation in vivo and the association of merozoites with intestinal mucus.

Enteric cryptosporidiosis was studied in the small intestine of five-day-old sucking mice after infection with 10(6) Cryptosporidium parvum oocysts. It was shown that excystation and the majority of subsequent endogenous stages occurred predominantly in the ileum. During the first three days of infection the number of merozoites collected in ileal washings increased over 100-fold to approximately 10(6) merozoites per mouse on the third day. In contrast to control mice, wash fluid from infected mice contained numerous strands of dislodged mucus. Estimates of mucus in the ileal washings of infected mice were similar to those made in controls until day 4 after infection when they increased and remained high throughout the remainder of the experiment. This study describes a method whereby ileal mucus washings from C parvum infected infant mice could be used as a rich source of merozoites.

Animals

Analysis of the kinetics, isotype and specificity of serum and coproantibody in lambs infected with Cryptosporidium parvum.

Enteric cryptosporidiosis was studied in colostrum-deprived lambs each infected at five days old with 10(6) oocysts. The prepatent period was three to five days and faecal oocyst concentration fell below detectable levels by day 16 after infection. Specific IgA, the only isotype detected by immunofluorescent assay in faecal extracts from infected lambs, was first evident on day 10 and titres continued to rise until day 16 of infection in association with declining oocyst output. Specific IgM and IgG antibodies were first detected in serum seven days after infection. No specific antibody was detected in uninfected control lambs. Immunoblotting methods showed that serum antibody and faecal IgA had similar profiles of antigen recognition. Antigens with approximate molecular weights of 180,000, 23,000 and 15,000 were consistent features on immunoblots performed with convalescent sera and faecal extracts. The results suggest that specific IgA in intestinal secretions has an important role in immunity to cryptosporidiosis.

Animals

Relationship between gastric acid and elevated plasma somatostatinlike immunoreactivity after a mixed meal.

The aim of this study was to examine whether hydrochloric acid plays a role mediating the post-prandial increase in plasma somatostatinlike immunoreactivity in normal subjects. Intravenous infusion of cimetidine was found to reduce by 45% the postprandial increment in plasma somatostatin-like immunoreactivity. This effect was reversed by concomitant intragastric administration of 0.1 N hydrochloric acid, which in previous studies in fasted subjects had not affected plasma somatostatinlike immunoreactivity. The effects of cimetidine on postprandial plasma gastrin were the inverse of those observed on postprandial somatostatin. There was a greatly enhanced increment in postprandial plasma gastrin during cimetidine infusion, which was reduced significantly toward control levels by concomitant intragastric infusion of hydrochloric acid. To exclude direct inhibition by cimetidine of nutrient-stimulated plasma somatostatinlike immunoreactivity we studied the effect of cimetidine on plasma somatostatinlike immunoreactivity stimulated by an intraduodenal infusion of fat. Cimetidine did not alter the incremental response of somatostatinlike immunoreactivity to intraduodenal fat infusion. These data show that cimetidine does not invariably reduce nutrient-stimulated plasma somatostatinlike immunoreactivity and are consistent with the hypothesis that the action of cimetidine in reducing the plasma somatostatin response to ingestion of a meal is a consequence of reduction of postprandial acid secretion. These data suggest that the postprandial elevation in plasma somatostatin observed in humans is mediated in part through postprandial secretion of gastric acid, which in turn acts to elevate plasma somatostatin.

Adult

Effect of bicarbonate, acetate, and citrate on water and sodium movement in normal and cholera toxin-treated rat small intestine.

Bicarbonate, citrate, or acetate are commonly included in oral rehydration solutions to correct acidosis and possibly because of their ability to promote water and sodium absorption. We have investigated the effect of these anions on water and sodium transport in normal and also in secreting (cholera toxin-treated) rat small intestine using a single-pass perfusion technique. In normal jejunum bicarbonate and acetate produced net absorption, and citrate net secretion of both water and sodium. In normal ileum all anions produced net absorption of water and sodium. In the secreting jejunum, however, bicarbonate had no effect on water and sodium secretion, whereas acetate and citrate actually enhanced the secretory state for both water and sodium. None of these anions had any effect on water and sodium secretion in the ileum. These observations suggest that normal and secreting intestine are qualitatively different with regard to handling of these organic anions. The addition, therefore, of bicarbonate, acetate, or citrate to oral rehydration solutions may have no beneficial effect with regard to the promotion of water and sodium absorption in the secreting intestine during acute diarrhoeal states and could actually be deleterious.

Acetates

Is bran efficacious in irritable bowel syndrome? A double blind placebo controlled crossover study.

Twenty eight patients with classical irritable bowel syndrome completed a double blind placebo controlled crossover trial in which they added to their normal diet a daily supplement of either 12 bran biscuits (1 = 1.3 g fibre) or 12 placebo biscuits (1 = 0.23 g fibre). Each biscuit was given for three months in random order with crossover to the alternative biscuit at three months. After the initial three months therapy, there was a significant symptomatic improvement compared with pretreatment in both the bran treated (p less than 0.01) and placebo treated groups (p less than 0.01), but there was no significant difference in symptom scores between these two groups. There was no further improvement in either group after the second three months treatment with the alternative therapy. When crossover data for all 28 subjects were combined, symptoms scores after three months bran therapy and after three months placebo therapy did not differ significantly. Twenty four patients completed three day stool collections in both treatment periods. When the symptomatic response to bran among 15 subjects in whom stool weights rose on bran was compared with that among nine subjects whose stool weights were static or fell on the bran, it was shown that symptomatic improvement was independent of an increase in stool weight. These data suggest that in irritable bowel syndrome, especially that associated with abdominal pain, the beneficial effects of bran are due to a placebo response which is independent of an increase in stool weight.

Adult

Comparative modes of action of lactitol and lactulose in the treatment of hepatic encephalopathy.

Lactitol, an unabsorbed sugar with defined laxative threshold and superior taste properties has been suggested as an alternative to lactulose in the treatment of hepatic encephalopathy. In the present study we have compared the colonic metabolism of the two sugars using an in vitro faecal incubation system. Both sugars were readily metabolised by faecal bacteria producing volatile fatty acids and the metabolism was inhibited by neomycin. The effect of lactitol and lactulose on terminal ileal and colonic pH was monitored in six normal subjects using a radiotelemetry technique. Both sugars significantly lowered right colonic pH (basal -6.51 +/- 0.48 vs lactitol -5.63 +/- 0.50; lactulose -5.18 +/- 0.82, p less than 0.05). The pH of rest of the colon and terminal ileum was unaffected. Neomycin given concurrently with lactulose abolished acidification of right colon. As lactitol and lactulose have similar effects within the colon, lactitol would appear to have a role in the treatment of hepatic encephalopathy. As neomycin antagonises the effect of lactulose in the colon, its concurrent use may be less effective in the treatment of hepatic encephalopathy.

Colon

Granular cells as a marker of early amiodarone hepatotoxicity: a pathological and analytical study.

Two contrasting cases of amiodarone hepatotoxicity are described. In one, perivenular collections of swollen cells, probably macrophages, with granular cytoplasm in an otherwise nearly normal liver were observed. Transmission electron microscopy showed that the cytoplasmic granularity was due to lysosomal bodies of various sizes. X-ray energy and wavelength spectroscopic analysis showed a high iodine content in these lysosomal bodies, good presumptive evidence of the presence of amiodarone or one of its metabolites. In the second case there was a micronodular cirrhosis, and similar granular cells also containing iodine were seen in the fibrous connective tissue. These cases seem to represent the very early and late stages of amiodarone hepatotoxicity. In a patient taking this drug aggregates of swollen granular cells may be a sensitive and histopathologically useful marker of early amiodarone toxicity.

Amiodarone

Assessment of an on-line computerized perinatal data collection and information system.

An on-line maternity data collection system has been designed to provide the information required for perinatal audit and to allow many of the letters and forms required for effective communication in pregnancy to be produced automatically. The system meets the requirements of the Korner Committee on Health Services Information and has been approved by the Computer Policy Committee. Pregnancy is followed prospectively from the first antenatal clinic visit until the file is closed 28 days after delivery. Data are entered by midwives and secretaries onto a network of microcomputers placed at convenient points in the maternity unit. The system has been fully operational with no significant problems since the beginning of 1984 and has led to improved communication between hospital and the community. Analysis of 253 consecutive case notes showed a high level of accuracy of the data recorded on computer. Reports and clinical audit are readily available both from the system locally, from standard programmes on the regional mainframe computer and via a mainframe computer at London University.

Computer Systems

Collagenous colitis.

Clinical and pathological aspects of six patients with collagenous colitis are presented. These patients have been observed for between four and 15 years and the evolution of the condition is documented in three (cases 1, 3 and 5). Management and possible pathogenetic mechanisms of this enigmatic condition are discussed.

Adult

Detection of hepatic encephalopathy.

The most sensitive index of hepatic encephalopathy in 29 patients following a porta-caval shunt appeared to be the assessment of a close relative who had known the patient pre-operatively. They noticed that 19 of the 20 patients were mentally slower; 11 were markedly aggressive and 8 had become placid and uncaring about family problems. Only 9 of these patients had clinical encephalopathy as judged by two independent observers, 14 had a prolonged trail test and 8 produced an abnormal five-pointed star. Eight patients were forced to retire prematurely after the operation due to ill health and 20 felt that their marriage had deteriorated. Eighteen of the 29 patients had a lie score on the Eysenck personality questionnaire (an index of 'social naïvety') which was more than one standard deviation above the mean value for a large control group (P less than 0.01). This did not correlate with other measurements of encephalopathy, but 8 out of the 11 patients who exhibited aggressive behaviour had an abnormal score.

Adult

Acetate and citrate stimulate water and sodium absorption in the human jejunum.

Using a standard perfusion technique, the organic anions acetate (50 mmol/l) and citrate (5 mmol/l) have been shown to stimulate absorption of water and sodium from the human jejunum. These observations may support further the rationale for including acetate or citrate in oral rehydration solutions for the treatment of acute diarrhoeal disease in humans.

Acetates

Relative nutritional value of whole protein, hydrolysed protein and free amino acids in man.

To compare their effects on nitrogen balance, diets containing either lactalbumin whole protein, its peptide-rich enzymic hydrolysate or an equivalent mixture of free amino acids as the sole source of dietary nitrogen were fed to two healthy subjects, each studied for 38 days on two separate occasions. The nitrogen intake (47 mg/kg body wt/day) induced a state of negative nitrogen balance, stimulating nitrogen conservation. Net daily nitrogen balance (mean +/- SD) in subject 1 was -0.23 +/- 0.72 g (amino acids) vs + 0.05 +/- 0.52 g (protein) and -0.21 +/- 0.58 g (amino acids) vs -0.05 +/- 0.57 g (hydrolysate), and in subject 2, -0.19 +/- 0.60 g (amino acids) vs -0.16 +/- 0.51 g (protein) and -0.42 +/- 0.35 g (amino acids) vs -0.62 +/- 0.34 g (hydrolysate). Analysis of these results by the cumulative sum technique showed no significant differences in the effect of the three nitrogen sources on nitrogen balance. This study indicates that there is no nutritional evidence to support the current practice of prescribing expensive enteral diets containing peptides or amino acids rather than the much cheaper whole protein to patients with normal gastrointestinal function.

Amino Acids

Origin of chronic right upper quadrant pain.

We have studied 22 consecutive patients referred for investigation of severe chronic right upper quadrant pain. The majority were women whose symptoms had been present for many years. All had undergone repeated investigations of the pancreatico-biliary, gastro-intestinal, urinary, and even gynaecological systems without a satisfactory diagnosis. Most had undergone at least one abdominal operation in an unsuccessful attempt to cure their pain. In 21 of 22 patients the customary pain was completely and reproducibly mimicked by balloon distension of the small or large intestine in at least one site. The trigger sites were jejunum (15), ileum (12), right colon (nine), and duodenum (six). In 12 more than one trigger site was found. Close questioning revealed features of the irritable bowel syndrome in the majority and depression in many though the symptoms were not spontaneously volunteered. Reproduction of pain has provided a convincing demonstration to this difficult group of patients that they have a sensitive gut and allows appropriate management.

Abdomen

Antigenic relationships between the serotypes of Pasteurella haemolytica demonstrable by enzyme-linked immunosorbent assay (ELISA).

Mice and rabbits were immunised with sodium salicylate extracts (SSE) prepared from each of 12 serotypes of Pasteurella haemolytica, and the antisera to each were used in cross-indirect haemagglutination (IHA) tests and cross-enzyme-linked immunosorbent assays (ELISA) to study antigenic relationships between the serotypes. An indirect micro-ELISA demonstrated common antigenic relationships which were not apparent by IHA. Antisera from both species revealed considerable shared antigenicity between all the serotypes. Rabbit antisera presented clearer differences between the A biotypes on one hand and the T biotypes on the other, the T biotypes exhibiting much less cross-relatedness than that shown between the A serotypes.

Antigens, Bacterial

Specificity of the enzyme-linked immunosorbent assay (ELISA) for antibodies in the sera of specific pathogen-free lambs vaccinated with Pasteurella haemolytica antigens.

Pooled serum from specific pathogen-free (SPF) lambs vaccinated with sodium salicylate extracted (SSE) antigens of Pasteurella haemolytica serotype A1 was shown to contain antibody to other A serotype SSE antigens when tested by the enzyme-linked immunosorbent assay (ELISA). Specific antibody to serotype A1 SSE antigens was demonstrated by absorption of the serum pool with heterologous serotype SSE antigens. The type-specific antigens of serotypes A1 and A9 were prepared by phenol--water extraction (PWE) of their respective SSE antigens. The PWE antigens were examined in a sandwich ELISA where rabbit IgG anti-P. haemolytica A1 cells or A9 cells was used as a coating layer to bind PWE antigens. The specificity of these antigens was demonstrated by marked reduction of reactivity between serum from SPF lambs vaccinated with SSE of serotypes A1 or A9.

Animals

Impaired semen quality in Crohn's disease--drugs, ill health, or undernutrition?

Even though abnormalities of semen quality in inflammatory bowel disease have been attributed to sulphasalazine therapy, oligospermia was found in 46% of men with Crohn's disease, none of whom were receiving this drug. Oligospermia occurred more commonly than in men with coeliac disease (6%, P less than 0.02), although disordered sperm motility and morphology were found commonly in both conditions. Our findings suggest that factors such as disease activity, nutritional status, and, possibly, other drugs must also be considered when investigating infertility in Crohn's disease.

Adult

Microscopic colitis-a cause of chronic watery diarrhoea.

Six patients with severe watery diarrhoea were found to have microscopic total colitis. None had any abnormality detectable by conventional tests used to diagnose inflammatory bowel disease-namely, barium radiology and endoscopy. The diagnosis could only be made by microscopic examination of biopsy specimens from the apparently normal colon. Anaemia, raised erythrocyte sedimentation rate, hypokalaemia, and hypoalbuminaemia were common findings. Small-bowel function was normal in all, though three patients had jejunal lesions of uncertain relevance but seemingly unrelated to the diarrhoea. The five patients given anti-inflammatory drugs showed a satisfactory response with improvement of the diarrhoea and colonic inflammation and return to normal of the abnormal laboratory findings. Microscopic colitis is responsible for a proportion of cases of intractable diarrhoea of obscure origin and rectal and colonic biopsies sould be undertaken in such cases.

Adult