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Biomedical subjects

A M Dawson

Publications and source records attributed to A M Dawson.

34 records · Page 2Linked to original sources

A case of apparent hypopituitarism complicating chronic inflammatory bowel disease in childhood and adolescence.

There is conflicting evidence regarding the adequacy of hypothalamic-pituitary function in children and adolescents with chronic inflammatory bowel disease complicated by growth retardation and delayed sexual maturation. A child with Crohn's disease, who has never received corticosteroid therapy, had delay of both growth and sexual maturation and has been investigated over the course of his disease. In addition to a skull X-ray (normal) and thyroid function tests (normal), a standard insulin tolerance test (insulin 0.15 u/kg) and a standard gonadotropin-releasing hormone (Gn-RH) test (100 microgram Gn-RH i/v) were performed when the bowel disease was in relapse and again during a remission of the bowel disease, achieved by surgery. When the bowel disease was in relapse (coincident with growth arrest) results showed an inadequate release of gonadotrophins and of growth hormone (even after pre-treatment with stilboestrol) but normal release of cortisol and prolactin. During a remission of the bowel disease coinciding with a period of rapid "catch-up" growth, release of growth hormone was normal and that of gonadotrophins supranormal. The demonstration of a reversible apparent partial hypopituitarism in this boy not only re-questions the adequacy of hypothalamic-pituitary function in inflammatory bowel disease but also indicates a potential diagnostic pitfall in the routine investigation of growth retardation if gastrointestinal symptoms are not prominent at presentation.

Adolescent

Crohn's disease in childhood.

In 32 patients with Crohn's disease which started in childhood, abdominal pain, diarrhoea, and weight loss were the common presenting symptoms, but unexplained fever and failure to grow were also prominent. Stunted growth was the most frequent physical abnormality when first seen in hospital. The mean delay in diagnosis was almost 3 years and the principal contributing factor here was failure to consider the diagnosis and thus perform a barium follow-through examination. The cumulative relapse rate after medical therapy or surgical resection was disappointingly high, but because the median relapse time is much longer for surgically treated patients, surgery is recommended at an early stage, especially in those patients who are growth-retarded or whose education is suffering because of time lost from school.

Abdomen

The transfer of circulating 131I IgG1 and 125I IgG2 to the nasal secretions of sheep.

Ovine IgG1 and IgG2 labelled with 131I and 125I respectively were injected intravenously into four sheep. Serum and nasal secretion samples were collected and fractionated by gel filtration on columns of Sephadex G100. Results showed that in serum more than 95 per cent of the radioactivity was associated with intact IgG molecules whereas in nasal secretion samples the percentage varied from five to 47. It was found that the concentrations of IgG1 and IgG2 in the nasal secretions were similar and were approximately 2 per cent of the serum concentrations. This finding indicates a lack of selective transfer of either IgG1 or IgG2 from blood to nasal secretions in sheep.

Animals

The role of the colon in urea metabolism in man.

1. The urea content of ileostomy effluent has been measured by the urease method as an indirect estimate of the urea concentration in the lumen of the normal ileum. 2. The plasma disappearance of intravenously administered[14C]urea was used to study intestinal urea breakdown. Normal subjects on high and low protein diets and patients with either excised (i.e. with ileostomies) or excluded colons were studied. 3. The 24 h intestinal urea breakdown was considerably greater than the quantity of urea estimated to be entering the colon from the ileum and across the colonic mucosa. 4. Intestinal urea breakdown increased with increase in dietary protein and decreased with, but was not abolished by, exclusion or excision of the colon. 5. Our results suggest that the colonic lumen is not the only site of intestinal ureolysis and that significant quantities of urea must be broken down either at a juxtamucosal site or in the ileum.

Body Weight

Protein absorption and ammonia production: the effects of dietary protein and removal of the colon.

1. The effect of increasing dietary protein content on the amount of faecal nitrogen was measured in six normal subjects and five subjects without functioning colons (three with ileostomy and two with ileo-rectal anastomosis). 2. There was a significant inontent in the subjects without functioning colons. 3. In normal subjects with intact colons, faceal N content was found to be lower than that in subjects without colons, and furthermore there was no significant variation with diet. 4. The source of the increase in faecal N with increased dietary protein content in subjects without functioning colons is discussed and the significance of these findings in relation to the efficiency of protein absorption is considered.

Ammonia

Hypothalamic-pituitary-gonadal function in men with cirrhosis of the liver.

Hypothalamic-pituitary-gonadal function was studied in 37 cirrhotic males, 25 of whom were alcoholic. Irrespective of aetiology, cirrhotic patients had significantly reduced free testosterone concentrations. Despite low free testosterone concentrations and reduced or absent spermatogenesis, basal levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were normal in nearly all patients, suggesting impaired function of the hypothalamic-pituitary-gonadal axis. In 14 cirrhotic men, seven of whom had gynaecomastia, the ability of the pituitary to secrete LH and FSH in response to exogenous gonadotrophin releasing-hormone (LH/FSH-RH) was asssessed. A normal LH response to LH/FSH-RH was obtained in patients without gynaecomastia. An exaggerated LH response was found in four of seven with gynaecomastia, suggesting Leydig cell failure. The Leydig cell response to exogenous gonadotrophin in eight consecutive cirrhotic patients was probably abnormal but difficult to interpret as all but one were within conventionally accepted limits of normality. The patients without gynaecomastia gave a normal or minimally exaggerated FSH response to LH/FSH-RH. Six of seven with gynaecomastia gave a markedly exaggerated response suggesting failure of spermatogenesis, and all tested were either azoospermic of oligospermic. The single patient with a normal FSH response had a normal sperm count. The pituitary cells can therefore respond to LH/RSH-RH and the Leydig cells of the testes show some response to exogenous gonadotrophin. Similar abnormalities in hypothalamic-pituitary-gonadal function have recently been described in patients with normal liver function on chronic oestrogen therapy.

Adult

Maternal immunoglobulins and parainfluenza 3 virus inhibitors in the nasal and lachrymal secretions and serum of newborn lambs.

Concentrations of IgG, IgM and IgA were measured in the serum, nasal secretions and lachrymal secretions of suckled newborn lambs. The major immunoglobulin constituent of precolostral serum was IgM. Maternal immunoglobulins, of which IgG was predominant, reached peak values on day 1 of life and then declined over the next 3 weeks. Half lives were calculated as: IgG, 13-7 days; IgM, 4-1 days; and IgA 1-8 days. No immunoglobulin was detectable in nasal or lachrymal secretions prior to sucking but IgG was present in all samples of these secretions obtained approximately 24 hr after first sucking. IgG was present in nasal washings from suckled lambs, reared either naturally or on immunoglobulin-free milk substitute and levels declined as the lambs grew older. IgM and IgA did not appear consistently in the secretions until lambs were 2-3 weeks old. It was concluded, therefore, that colostral IgG reaches the nasal and lachrymal secretions of the newborn lamb. However, because the ewes in this experiment had only low serum titres, no maternal antibody to parainfluenza 3 virus (PI3) was detected in the nasal secretions of the lambs, although non-specific inhibitors were present. It is suggested, however, that low levels of maternal antibody in the secretions may play a valuable role in preventing respiratory virus infections of young ruminants before active local production of IgA and IgM begins at 2 to 3 weeks of age.

Animals

Immunoglobulins in the serum and nasal secretions of lambs following vaccination and aerosol challenge with parainfluenza 3 virus.

Serial changes in the concentrations of IgM, IgG and IgA were compared in specific pathogen free (SPF) lambs which had been vaccinated with live or inactivated parainfluenza 3 virus (PI 3) by either intramuscular (IM) or intranasal (IN) routes followed by aerosol challenge with PI 3. In the serum, an increase in IgM was associated with the primary antibody response to the aerosol challenge, whereas increased IgG was associated with the secondary antibody response. No changes in immunoglobulin concentrations were observed in the nasal secretions of lambs administered live or inactivated virus IM or IN without adjuvant. Marked increases in IgG were found in the serum and nasal secretions of lambs vaccinated IM with inactivated virus in Freund's complete adjuvant (FCA) and fractionation by gel filtration confirmed that the antibody was associated with IgG in both these fluids.

Administration, Intranasal

Immunoglobulins, antibodies and inhibitors of parainfluenza 3 virus in respiratory secretions of sheep.

Virus neutralising and haemagglutination inhibiting (HI) activities were monitored in the serum, nasal secretions and tracheo-bronchial secretions of lambs infected with Parainfluenza virus type 3 (PI3). HI activity was found in the secretions of both control and infected lambs, whereas neutralising antibody was found only in nasal secretions from infected lambs. Fractionation revealed that most of the HI activity in the secretions was due to a large molecular weight protein which also inhibited the haemagglutination (HA) of Parainfluenza virus type 1 (PI1) and type 2 (PI2) and Newcastle disease virus (NDV). This inhibitory activity was partially sensitive to receptor destroying enzyme (RDE). IgA antibodies specific for PI3 were also found in the respiratory secretions. However no increase in IgA levels was detected in the nasal secretions of the infected lambs. It is suggested that in certain reports non-specific inhibitors present in the nasal secretions of calves, may have been confused with PI3 specific IgA antibody.

Animals

A study of relations between the absorption of amino acids, dipeptides, water and electrolytes in the normal human jejunum.

1. A double-lumen perfusion technique was used to study the effect of a wide range of concentrations of the dipeptide glycyl-L-alanine and its constituent amino acids on water and electrolyte absorption from iso-osmotic solutions in the upper jejunum of normal human subjects. 2. There was no significant absorption of water and electrolytes from sodium chloride solution (150 mmol/l) but the presence of the dipeptide or its constituent amino acids stimulated water and electrolyte absorption. 3. Water absorption reached a peak at increasing amino acid and dipeptide concentrations and then tailed off. Our data suggest that the tailing off is not solely due to the diminished sodium content of the solutions. 4. During perfusion of the dipeptide-sodium chloride and amino acid-sodium chloride solutions solute and water were absorbed as an iso-osmotic solution. Analysis of the results indicates that this could occur at high dipeptide concentrations only if the majority of the dipeptide enters the cell intact.

Adult

Ileal function in patients with untreated adult coeliac disease.

A double-lumen perfusion technique has been used to investigate jejunal and ileal absorption of glucose, water, and electrolytes in a group of patients with untreated adult coeliac disease. Correct positioning of the tube was confirmed by measuring the differential jejunal and ileal handling of bicarbonate. Eight control subjects and eight patients with coeliac disease were perfused with an isotonic electrolyte solution containing 50 mM glucose and 25 mM bicarbonate. The group of coeliac patients had impaired jejunal absorption of glucose (P less than 0.001), water (P less than 0.01), sodium (P less than 0.02), and chloride (P greater than 0.05) compared with the control group. In contrast the group of coeliac patients had normal ileal glucose and water absorption and increased ileal sodium (P greater than 0.01) and chloride (P greater than 0.05) absorption compared with the controls. Evidence for ileal adaptation was found in three individual patients who had absorptive values outside 2SD of the normal mean. The results indicate that the distal small intestine in coeliac disease has the ability to adopt to the damage and loss of absorptive capacity in the proximal small intestine.

Adolescent

The cellular infiltrate of the jejunum in adult coeliac disease and dermatitis herpetiformis following the reintroduction of dietary gluten.

The cellular infiltrate of the jejunal mucosa has been studied in patients with both treated and untreated adult coeliac disease and dermatitis herpetiformis and serially in treated patients before and after the reintroduction of gluten to the diet. In adult coeliac disease and dermatitis herpetiformis the jejunal mucosa showed similar abnormalities of the cellular infiltrate which was characterized by an increase in intraepithelial lymphocytes and lamina propria plasma cells and eosinophils, with the greatest numbers of cells occurring in untreated patients. At 24-48 hours following a single 25-g gluten challenge there was an increase in lamina propria plasma cells, lymphocytes and eosinophils and intraepithelial lymphocytes. This rise was sustained after seven days on a gluten-containing diet for all of these cell groups except lamina propria lymphocytes. These responses were essentially similar in both adult coeliac disease and in those dermatitis herpetiformis patients who had jejunal lesions before treatment. In dermatitis herpetiformis patients with normal jejunal morphology on a normal diet there was an upward trend in lamina propria plasma cells and intraepithelial lymphocytes within one to three weeks of taking extra dietary gluten. These results are compatible with the view that more than one immunological mechanism may be responsible for the pathogenesis of the jejunal lesion of coeliac disease and dermatitis herpetiformis.

Adult

Immunoglobulin concentrations in ovine body fluids.

Ovine IgG, IgM and IgA and antisera specific for these immunoglobulins were prepared. The specific antisera were used to estimate the immunoglobulin concentrations in certain sheep body fluids. IgA was shown to be the major immunoglobulin in saliva, lung and lachrymal fluid, tracheobronchial and nasal secretions while IgG was the predominant immunoglobulin in colostrum, milk, bile and serum.

Animals