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Biomedical subjects

A M Dawson

Publications and source records attributed to A M Dawson.

At least 37 records · Page 2Linked to original sources

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↗

Male gonadal function in coeliac disease: III. Pituitary regulation.

Pituitary regulation of gonadal function was investigated in 39 consecutive men with treated and untreated coeliac disease and in an intestinal disease control group of 19 men with Crohn's disease of similar age and general nutritional status. Basal serum FSH concentration was increased in 10 of the coeliacs (26%) compared to only two of 19 men with Crohn's disease (11%). This abnormality was observed with equal frequency in both treated and untreated coeliacs, and was not associated with oligospermia. Serum LH concentration was increased in eight of 15 untreated coeliacs (53%) with sub-total villous atrophy, an abnormality which unlike the elevation of serum FSH, appears to return towards normal after gluten withdrawal. Serum LH was high in coeliacs despite marked elevation of the free testosterone index. Exaggerated responses of FSH and LH to LHRH were found in 89% and 45% respectively, of coeliacs with sub-total villous atrophy. However, exaggerated responses of LH alone were found more frequently in coeliacs than in men with Crohn's disease (P less than 0.02) and unlike the exaggerated FSH responses, LH responses were closely related to jejunal morphology. Exaggerated responses of FSH and LH in coeliacs were commonly found when basal gonadotrophin concentrations were normal. The occurrence of exaggerated gonadotrophin responses could not be related to plasma concentration of testosterone, dihydrotestosterone, oestradiol or the free testosterone index. Serum prolactin was modestly raised in 25% of untreated and partially treated coeliacs and in the same proportion of men with Crohn's disease. Elevated serum prolactin concentrations never exceeded 809 mU/l and were not associated with impotence or infertility. This study provides further evidence that in men with coeliac disease there is a derangement of pituitary regulation of gonadal function. This would seem to be part of a wider disturbance of central regulatory mechanisms of endocrine function in coeliac disease.

Adolescent↗

Selection of an obstetric data base for a microcomputer and its use for on-line production of birth notification forms, discharge summaries and perinatal audit.

A microcomputer system is described which stores data for perinatal audit and produces 'on-line' the statutory birth notification form and mother and baby discharge summary. The derivation of a minimum data-base and the methods used to obtain reliable data are outlined. The results of a trial of the production of the birth notification form for 195 deliveries are reported together with those of a further trial of 86 deliveries in which the system was used to produce both the notification form and the discharge summary. A study of the accuracy of the handwritten birth notification forms revealed a high error rate which was markedly reduced by the use of the microcomputer system. The system is now in routine use and further developments are outlined.

Computers↗

Male gonadal function in coeliac disease: 2. Sex hormones.

Hypogonadism, infertility, and sexual dysfunction occur in some men with coeliac disease. We have measured plasma testosterone, dihydrotestosterone, sex-hormone binding globulin, oestradiol, and serum luteinising hormone in 41 men with coeliac disease and have related these findings to jejunal morphology, fertility, semen quality, and sexual function. To determine the specificity of these observations in coeliacs we also studied 19 nutritionally-matched men with Crohn's disease, and men with chronic ill-health due to rheumatoid arthritis and Hodgkin's disease. The most striking endocrine findings in untreated coeliacs were increased plasma testosterone and free testosterone index, reduced dihydrotestosterone (testosterone's potent peripheral metabolite), and raised serum luteinising hormone, a pattern of abnormalities indicative of androgen resistance. As jejunal morphology improved hormone levels appeared to return to normal. This specific combination of abnormalities was not present in any of the disease control groups and, to our knowledge, androgen resistance has not been described previously in any other non-endocrine disorder. Plasma oestradiol concentration was modestly raised in 10% of coeliacs and 11% of patients with Crohn's disease. Unlike plasma androgens and serum luteinising hormone in coeliacs, plasma oestradiol was not clearly related to jejunal morphology. Androgen resistance and associated hypothalamic-pituitary dysfunction appear to be relatively specific to coeliac disease and cannot be explained merely in terms of malnutrition or chronic ill-health. In addition, our findings suggest that this endocrine disturbance may be related to sexual dysfunction in coeliac disease but its relationship to disordered spermatogenesis in this condition has not been clearly established.

Adolescent↗

What is indigestion?

Ninety patients and 30 senior hospital doctors were questioned about indigestion and dyspepsia. There were marked discrepancies between the views of patients and doctors. Most doctors considered indigestion to be synonymous with dyspepsia and associated it with peptic ulcer. Patients, however, were not generally conversant with the term dyspepsia and linked indigestion with psychological factors, feeding patterns and bowel function rather than physical illness. The patients' concept of indigestion corresponded closely with medically-accepted features of irritable bowel syndrome. Uncritical use of these terms may lead to misinterpretation of the patient's complaint and inappropriate management.

Colonic Diseases, Functional↗

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↗

Serum protein changes in grass sickness.

Polyacrylamide gel electrophoresis was used to compare serum taken from ponies before and during clinical illness confirmed as grass sickness. A consistent rise in the level of haptoglobin was seen in serum from animals which had shown symptoms for more than two days. Serum albumin was also shown to have altered mobility at the onset of clinical disease. Estimation of the haemoglobin-binding capacity confirmed the haptoglobin increase. This haptoglobin has been purified and some of its properties determined. In contrast to the situation in acute inflammatory conditions no other acute-phase proteins increased to a significant extent in grass sickness. It is concluded that the neurotoxin known to be present in sera of animals experiencing acute grass sickness cannot itself be detected by polyacrylamide gel electrophoresis but may be bound to serum albumin.

Animals↗

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↗

Functional abdominal pain: further evidence that whole gut is affected.

The distribution and referral of abdominal pain in 21 patients with functional abdominal pain were investigated by performing balloon distension of the ileum, proximal jejunum, second part of the duodenum, and distal oesophagus. Pain was perceived not just in classically described sites but throughout the abdomen and was referred to several unusual extra-abdominal sites. The presenting pain was reproduced by this technique in 14 patients, in three of whom it was also reproduced by colonoscopic distension. This study emphasises the protean presentation of functional abdominal pain and demonstrates the existence of potentially tender "trigger" areas for the production of abdominal pain in the proximal as well as the distal gut.

Abdomen↗

Colonoscopic diagnosis of minimal change colitis in patients with a normal sigmoidoscopy and normal air-contrast barium enema.

8 patients with normal sigmoidoscopic appearances and normal results by high-quality air contrast barium enema had substantial or total colitis diagnosed for the first time at colonoscopy performed within a month of the radiological examination. Colitis was confirmed in all 8 patients by histological examination of biopsy specimens. Barium enema radiographs were independently reviewed by three experienced observers who also reviewed other normal and abnormal radiographs. One observer regarded all 8 sets of radiographs from the patients with colitis as being of normal appearance, and 4 patients were reported as having normal radiographs by all three observers. All 7 of the rectal biopsy specimens taken showed histological features of inflammatory bowel disease. This emphasises the importance of performing a rectal biopsy in patients with gastrointestinal symptoms of unknown cause.

Adult↗

Slow cirrhosis--or no cirrhosis? a lesion causing benign intrahepatic portal hypertension.

We report the histological findings in livers from a group of 60 patients with benign intrahepatic portal hypertension. The lesion is benign in comparison with true cirrhosis in the sense that most of the patients survive many years from the time of diagnosis. The histological changes, in our view, differ from those of any variant of cirrhosis and generally do not progress even after many years. The essential features are: (1) irregular capsular thickening; (2) thickening of some portal tracts with fine fibrous septa radiating out from some of them; and (3) distortion of lobular architecture with hyperplastic expansion of some areas and compression of others and irregularly distributed central veins. We suggest that this is the lesion responsible for at least some cases of so-called idiopathic non-cirrhotic portal hypertension.

Follow-Up Studies↗

Relationship between plasma testosterone and dihydrotestosterone concentrations and male facial hair growth.

Linear facial hair growth and the density of facial hair were measured by a photographic method and their relationship to plasma testosterone (T) and dihydrotestosterone (DHT) concentrations was examined in twelve healthy men. In addition, we investigated eight men with coeliac disease in whom we have previously demonstrated reversible androgen resistance. The divergence of plasma T (increased) and DHT (decreased) concentrations in this condition enabled examination of possible independent actions of these androgens on facial hair growth. Linear facial hair growth was significantly reduced in coeliac patients compared with controls and correlated with plasma DHT but not with plasma T concentration. Conversely, hair density was significantly greater in coeliacs than controls and correlated only with plasma T concentration. These abnormalities of facial hair growth and hair density appeared more marked in treated patients receiving a gluten-free diet. These findings suggest that T and DHT may have independent roles in the control of male facial hair growth, i.e. T for hair follicle priming and DHT for promotion of linear growth. The relationship between hair growth abnormalities in coeliac disease and withdrawal of dietary gluten requires further investigation.

Adult↗

Testosterone metabolism by the rat gastrointestinal tract, in vitro and in vivo.

We have shown previously that the capacity of the jejunal mucosa to oxidise testosterone to the weaker androgen, androstenedione, by the enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD), is considerable. The present study extends these earlier observations by measuring 17 beta-HSD activity in different regions of the gastrointestinal tract, by investigating the potential for testosterone metabolism by slices and everted sacs of rat jejunum, and estimating the contribution of intestinal testosterone metabolites to circulating levels of plasma androgens, by portal vein sampling in the rat, in vivo. 17 beta-HSD activity in homogenates of gastric and duodenal mucosa was significantly higher than that in jejunum, and was also present in ileum and colon. In addition to androstenedione, slices and everted sacs of rat jejunum produced various metabolites, one of which was probably dihydrotestosterone. It was not, however, a major metabolite in vivo. It is suggested that 5 alpha-reduction may be favoured in vitro by a lower oxidation-reduction potential resulting from tissue anoxia. The major portal vein metabolite was androstenedione, the same major metabolite produced by mucosal homogenates. We conclude that oxidation of testosterone is the major metabolic pathway in intestinal mucosa and the capacity of the gastrointestinal tract to reduce the potency of testosterone is considerable. Our findings suggest that the gut, rather than the liver, is responsible for the failure of oral testosterone to provide effective androgen replacement therapy. The qualitative difference in testosterone metabolism between in vitro and in vivo preparations emphasises the need for caution in the interpretation of similar in vitro experiments.

17-Hydroxysteroid Dehydrogenases↗

Progesterone, prolactin, and gynaecomastia in men with liver disease.

Plasma progesterone was raised in 36 of 50 (72%) men with liver disease compared with 20 healthy male control subjects. Plasma progesterone was significantly higher in men with non-alcoholic cirrhosis with gynaecomastia than those without, but no similar relationship was found in men with alcoholic fatty change and alcoholic cirrhosis. Hyperprolactinaemia was found in 14% of men with liver disease but levels were unrelated to the presence of gynaecomastia. Increased circulating levels of progesterone and prolactin alone do not explain the development of gynaecomastia in patients with liver disease, but progesterone may be an additional factor acting in association with the known disturbances of other sex steroids.

Adult↗

Male gonadal function in coeliac disease: 1. Sexual dysfunction, infertility, and semen quality.

The prevalence of hypogonadism, sexual dysfunction and abnormalities of semen quality was determined in 28 consecutive males with coeliac disease. These observations were related to jejunal morphology and nutritional status, and were compared with findings in 19 men with Crohn's disease of similar age and nutritional status. Two of the 28 coeliacs (7%) had clinical evidence of hypogonadism but impotence and decreased sexual activity occurred more commonly, the latter apparently improving after gluten withdrawal. Of the married coeliacs, 19% had infertile marriages, a value greater than expected in the general population. Hypogonadism and sexual dysfunction were not detected in our patients with Crohn's disease. Seminal analysis in coeliacs revealed marked abnormalities of sperm morphology and motility, but only the former appeared to improve after gluten withdrawal. Similar abnormalities, however, were also detected in patients with Crohn's disease, although, unlike the coeliacs, 46% also had reduced concentrations of spermatozoa. Semen quality in coeliac disease could not be clearly related to general or specific (serum vitamin B(12) and red cell folate) nutritional deficiencies or to fertility, although sperm motility was markedly reduced in two of the three coeliacs with infertile marriages. The presence of antisperm antibodies did not appear to be an important aetiological factor in male infertility in coeliac disease. The pathogenesis of infertility and sexual dysfunction in coeliac disease remains unclear, suggesting that factors such as endocrine dysfunction or other specific nutritional deficiency may be involved.

Adolescent↗

Comparison of plasma and intraluminal amino acid profiles in man after meals containing a protein hydrolysate and equivalent amino acid mixture.

Plasma and intraluminal amino acid profiles were compared in normal subjects 30, 60, 120, 180 minutes after meals containing either a peptide-rich protein hydrolysate (H) or an equivalent free amino acid mixture (AA) as the nitrogen source. Except for asparagine (30 minutes) and glutamine (30 and 60 minutes), which were absorbed to a significantly (p less than 0.05) greater extent from the peptide mixture, there were no significant differences in the plasma increments of the remaining 13 amino acids at any time interval after the meals. Positive correlations (p less than 0.01 or less) between the amino acid composition of the hydrolysate and amino acid meals and both (1) the post-prandial increments in the individual plasma amino acids and (2) the residual intraluminal amino acid content suggested that the amino acid composition of ingested protein, rather than specialised free amino acid and peptide transport systems, dictated the pattern of amino acid absorption. The studies provide no evidence that peptides rather than free amino acids are the ideal nitrogen source in elemental diets.

Adult↗