Biomedical subjects
Publications and source records attributed to R S Gray.
An infant with persistent hyperinsulinism had hypertrophic cardiomyopathy that progressed until near-total pancreatectomy was performed. After pancreatectomy the condition resolved. Hyperinsulinism may be a cause of treatable cardiomyopathy.
Serotonin (5-hydroxytryptamine, 5-HT) and dopamine (DA) are endogenous components of the central nervous and endocrine systems of the chicken. To determine the effects of these monoamines on antibody-mediated immunity. New Hampshire chickens of Line UNH 105 were injected intravenously with 5-HT (100 micrograms/kg of body weight) and DA (1 mg/kg of body weight). One milliliter of a 5% SRBC suspension was injected intravenously 30 min later. Both IgM and IgG splenic plaque-forming cells were assayed 5 days after antigen injection. For in vitro studies, spleen lymphocytes from SRBC-primed chicks were incubated with DA and 5-HT followed by quantitation of IgM and IgG plaque-forming cells. The in vivo incubation of splenic lymphocytes with specific antagonists was used to ascertain the presence of monoamine receptors on lymphocytes. The 5-HT significantly enhanced IgM plaque-forming cells compared with controls following in vivo [550 +/- 85 (SE) cells/10(6) splenic lymphocytes versus 359 +/- 44] but not in vitro exposure. The IgG plaque-forming cells were not affected by 5-HT. The DA significantly suppressed IgM plaque-forming cells responses following in vivo (284 +/- 46 versus 499 +/- 66) and in vitro (254 +/- 57 versus 451 +/- 51) exposure. Significant suppression of IgG plaque-forming cells was found in vivo (287 +/- 40 versus 462 +/- 75) and in vitro (153 +/- 36 versus 371 +/- 81) following treatment. Specific DA antagonists, apomorphine and metoclopramide, did not alleviate the in vitro suppressive effect of DA.
Twelve non-obese non insulin dependent diabetics whose mean +/- SE fasting blood glucose was 12.9 +/- 0.9 mmol/l despite maximal doses of sulphonylureas, received 8 weeks of guar (5 g tid before meals) and 8 weeks of metformin (0.5 g tid) following a six week washout period, in a cross-over design. Guar significantly lowered fasting cholesterol and triglyceride concentrations but did not alter glucose concentrations. Conversely, metformin significantly reduced fasting and post-prandial glucose concentrations but had no influence on plasma lipids.
A case of steroid-responsive malignant lymphoma of the optic chiasm is reported in a 58-year-old woman presenting with subacute vision loss, headaches, and decreased hearing. The exquisite sensitivity of magnetic resonance imaging (MRI) of the parasellar area and the usefulness of MR-directed stereotactic biopsy in identifying a chiasmatic lesion are shown. Primary CNS lymphomas are briefly reviewed. Ophthalmologists will be asked to evaluate patients with malignant lymphoma of the optic chiasm with increased frequency in the future, as CNS lymphomas are expected to be the most common neurological neoplasm by 1991.
A single-blind comparison of the effectiveness of miglitol (BAY-m-1099) and placebo in controlling postprandial hyperglycaemia was performed in 13 insulin dependent diabetics. Each subject received placebo and miglitol for four weeks, with an intervening two week placebo (washout) period, and underwent a 9.5 hr glycaemic profile after each four week treatment period. The area under the glucose curve was significantly (p less than 0.01) reduced by miglitol although no reduction in fasting blood glucose, HbA1, plasma lipids, insulin dosage or weight was observed. Side effects were not appreciably more common when patients received miglitol than when receiving placebo.
The effect of acarbose, an alpha-glucosidase inhibitor, on glycaemic control, was compared with placebo in a double-blind, randomised, group comparison study during 16 weeks in 20 non-obese non-insulin dependent diabetic patients in whom sulphonylurea treatment had been withdrawn. There was significant deterioration in glycaemic control as assessed by HbA1 following withdrawal of the sulphonylurea. There was no significant improvement in HbA1 between weeks 0 and 16 in either the acarbose (11.3% and 12.4% respectively) or the placebo group (10.6% and 12.2% respectively). In both the acarbose and placebo treated groups fasting glucose and insulin concentrations were unaltered. This study also suggests that acarbose was not an effective substitute for sulphonylureas in non-obese Type 2 diabetes uncontrolled by diet alone.
The biological action and pharmacokinetics of insulin were assessed in nine type 1 (insulin-dependent) diabetic patients before and after 3 months conventional insulin treatment, and in seven age and weight-matched non-diabetic controls, by means of the euglycaemic insulin clamp technique. The mean (+/- S.E.) metabolic clearance rate of insulin, when infused at 1 mU/kg/min, was similar in untreated and treated diabetic patients and in controls (22.7 +/- 2.0, 19.3 +/- 3.8, and 22.9 +/- 3.3 ml/kg/min) but, when infused at 6 mU/kg/min, was greater (p less than 0.01 and less than 0.01) in untreated patients (18.0 +/- 2.5 ml/kg/min) than in treated patients (11.5 +/- 1.4 ml/kg/min) and controls (12.7 +/- 1.3 ml/kg/min). Insulin-mediated glucose disposal was reduced (p less than 0.01 and less than 0.01) at insulin infusion rates 1 and 6 mU/kg/min in untreated patients (18.5 +/- 1.9 and 33.8 +/- 4.5 mumol/kg/min) when compared with controls (35.8 +/- 3.4 and 62.0 +/- 4.7 mumol/kg/min) and was improved (p less than 0.01 and less than 0.01) following insulin treatment (36.1 +/- 4.6 and 64.8 +/- 4.2 mumol/kg/min). Daily insulin requirement fell by 33% following 3 months insulin treatment with improvement in mean HbA1 from 16.3 +/- 0.7 to 8.2 +/- 0.4%, but without significant increase in endogenous insulin secretion. The 'honeymoon phenomenon', which has traditionally been attributed exclusively to resurrection of endogenous insulin release, may also be related to normalization of insulin action following institution of insulin treatment.
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The birth weights of infants born to patients with insulin-dependent diabetes (IDD) and insulin-independent diabetes (IID) before the disease was diagnosed were compared. An appreciable excess of infants above the 90th centile for weight was found, the proportions being 27% of infants born to mothers with IDD and 30% of those born to mothers with IID. These findings suggest that many patients with both types of diabetes have a prolonged period of metabolic abnormality before overt symptoms of diabetes arise and that the apparent acute onset of the disease in patients who are insulin dependent is illusory.
Concentrations of total glycosylated haemoglobins (Hb A1) were measured in 40 diabetics at diagnosis and at monthly intervals after treatment with chlorpropamide, insulin, or diet alone was begun. The mean Hb A1 concentration at presentation in 16 patients treated with chlorpropamide was significantly higher than that in 12 patients treated with insulin, and the duration of glycaemic symptoms was much longer in the chlorpropamide-treated group. In contrast, the mean plasma glucose concentration was similar in both groups. The mean concentrations of Hb A1 and plasma glucose at diagnosis in the 12 patients treated by diet alone were lower than those in the other two groups, and most of these patients were free of symptoms. Treatment quickly relieved symptoms and lowered plasma glucose in all patients. The Hb A1 concentration fell significantly with treatment such that after two months there was no significant difference between the three groups, although results remained above the normal range. These findings support the theory that the Hb A1 concentration reflects the blood glucose control over the previous one to two months and suggest that the duration of hyperglycaemia may be important in determining the Hb A1 concentration as well as the absolute blood glucose concentration.
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All newly diagnosed insulin dependent diabetics presenting consecutively to the Diabetic Department of the Royal Infirmary from the City of Edinburgh or its environs, between the years 1964 and 1977, were analysed for sex (297 males, 205 females), age at diagnosis (range 10--75 years), month of diagnosis, duration of symptoms and month of symptomatic onset. Males aged 10--19 years showed a significant seasonal variation in diagnosis (p less than 0.025) with an increase in autumn and winter months which was not seen in females aged 10--19 years nor in patients of either sex aged more than 19 years at diagnosis. The duration of diabetic symptoms increased with increasing age at diagnosis in both males and females and was consistently greater in females than in males for each age group at diagnosis. When the month of symptomatic onset was considered in relation to sex and age at diagnosis, having excluded patients with duration of symptoms of more than three months, only males aged 10--19 years at diagnosis showed a significant seasonal variation in incidence (p less than 0.005).
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In an attempt to assess the predictive value of the TRH test in patients in remission after stopping antithyroid drugs for thyrotoxicosis, 11 euthyroid patients with a subnormal (group I) and 23 euthyroid patients with a normal serum TSH response to TRH (group II) were followed-up for one year. The mean +/- SE intervals since the withdrawal of drug therapy were 23.2 +/- 1.6 and 20.4 +/- 0.7 months, respectively, at the outset of the study. Five patients (45%) from group I and 7 patients (30%) from group II relapsed during the period of observation. In addition, a change from a subnormal TSH response to TRH and vice versa occurred in some patients. It is not possible to predict by means of the TRH test the subsequent clinical course of patients in remission following antithyroid drug therapy.
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Soluble immune complexes (AgAb) and islet cell antibodies (ICAb) were studied in 110 insulin dependent diabetics (IDD) within a week of diagnosis and in about a third of the patients after 1, 3, 6 and 12 months. AgAb were studied by the solid phase Clq binding test in all the patients and also by the Raji cell radioimmunoassay in 52 sera at diagnosis. Diabetics at diagnosis showed a significantly higher incidence of AgAb in comparison with the control population. AgAb positivity declined with increasing time from diagnosis to reach the normal range within 3 months. Both the Clq and the Raji methods revealed a significant correlation at diagnosis between the occurrence at AgAb and the presence of ICAb. The possibility exists that AgAb, perhaps comprised of pancreatic antigen and ICAb, may be involved in the pathogenesis of type I diabetes.
The prevalence of HLA-B8 was found to be significantly increased in patients with primary atrophic (no goitre) hypothyroidism, but not in goitrous patients with Hashimoto thyroiditis, whether euthroid or hypothroid. There was no correlation between the occurrence of HLA-B8 and the presence of titres of thyroid antibodies at diagnosis or their persistence for at least three years after diagnosis.
The prevalence of HLA-B8 in thyrotoxic (Graves' disease) patients who relapsed after withdrawal of antithyroid drugs was high (69%) compared with that in patients who remained in remission (40%) and in healthy controls (28%). B8-positive patients were 1-8 times more likely to relapse after withdrawal of drug therapy than B8-negative patients. The persistence of thyroid microsomal antibodies after withdrawal of therapy correlated significantly with the presence of HLA-B8. This association was more pronounced in patients who remained in remission. From this it might be assumed that B8 is also associated with the persistence of thyroid T.S.H. (thyroid-stimulating hormone) receptor stimulating antibodies. In view of these findings, it is suggested that patients who are thyrotoxic might be typed for HLA, and those who are B8-negative could be given a trial of long-term antithyroid drug therapy.