Biomedical subjects
Publications and source records attributed to A M Dawson.
Disturbance of ammonia metabolism is an important but not the only factor in the genesis of hepatic coma. In this review mechanisms controlling the concentration of ammonia in the blood other than disturbed liver function have been discussed. The key function of ammonia in the pyridine nucleotide cyde has been outlined and it is suggested that the function of this cycle in patients with liver disease would repay further study.
An intestinal perfusion technique has been used to study absorption of glucose from free glucose and the disacchairde maltose in a patient with congenital glucose-galactose malabsorption. Minimal absorption of glucose occurred from high luminal concentrations of either free glucose (100 mmole/liter) or maltose (50 mmole/liter). Glucose diffused into the intestinal lumen during perfusion of a 2 mmole/liter glucose solution. These observations offer no support for nutritionally important glucose absorption in congenital glucose-galactose malabsorption by either passive diffusion or via a "disaccharidase-related" transport system.
18 454 men and 5471 women attending a screening centre had serum-bilirubin concentrations measured. 2.0% of men and 0.6% of women had concentrations of 25 micronmol/1 (1-5 MG/DL) or above. Both sexes showed skewed distributions for bilirubin concentration, but analysis of the data showed no evidence of bimodality for either sex. This suggests that people who are now diagnosed as having Gilbert's disease may constitute upper end of the normal range rather than a disease state. The term "constitutional hyperbilirubinaemia" is preferable, and its use can be coupled with reassurance to the patient that the condition causes no symptoms.
Plasma androgen and gonadotrophin concentrations have been measured before and during treatment of 23 men with gluten enteropathy. Before treatment, there was marked rise in total plasma-testosterone, free testosterone concentration (as assessed by the free testosterone index), and plasma-luteinising-hormone concentration. In contrast, 5 alpha-dihydrotestosterone concentrations were lower than normal. All these abnormalities reverted towards normal with successful treatment of the jejunal mucosal lesion. These data are consistent with a reversible tissue resistance to circulating plasma-testosterone in men with gluten enteropathy and subtotal villous atrophy.
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Salbutamol was administered intravenously to 14 patients in premature labour. Inhibition of uterine contractions occurred on 22 out of 23 occasions. The mean increase in maternal and fetal heart rate and blood pressure were within clinically acceptable limits but there were wide individual variations. The mean delay achieved when the intravenous regime was supplemented with oral salbutamol was greater than that achieved by intravenous salbutamol alone, but the difference was not statistically significant.
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.
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.
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.
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.
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.
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.
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.
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.
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