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Biomedical subjects

B F Clarke

Publications and source records attributed to B F Clarke.

At least 73 records · Page 4Linked to original sources
PubMed1986

Platelet-density analysis and intraplatelet granule content in young insulin-dependent diabetics.

This study was designed to assess the density characteristics of platelets from controls (N = 10) and three groups of diabetics (N = 32) exhibiting various degrees of glycemic control. With continuous gradients of Percoll, platelets from controls and diabetics (N = 8) with an HbA1 less than or equal to 9% formed a band extending from 1.0625 g/ml to 1.0925 g/ml with a mean platelet density of 1.0775 g/ml. In the two groups of diabetics with HbA1 greater than or equal to 10%, there was an increase in the proportion of low-density platelets recovered on the gradients and the mean platelet density was reduced to 1.0750 g/ml (HbA1 = 10-13%) and 1.070 g/ml (HbA1 greater than or equal to 14%). All three groups of diabetics had normal levels of intraplatelet ATP/ADP and beta-thromboglobulin. It is unlikely that in vivo degranulation of platelets after activation was responsible for the altered density profiles. We propose that abnormal platelet subpopulations with low density but normal intraplatelet granule content were responsible for the changed density profiles.

Adult↗
PubMed1986

Variable relationship between peripheral somatic and autonomic neuropathy in patients with different syndromes of diabetic polyneuropathy.

The relationship between abnormal peripheral nerve electrophysiology and abnormal cardiovascular autonomic function has been studied in four groups of diabetic subjects, comparable with regard to age, duration, and type of diabetes. Thirty-three had no symptoms of neuropathy, 28 had newly developed painful neuropathy, 24 had chronic painful neuropathy, and 21 had painless neuropathy with associated recurrent foot ulcers. In all three symptomatic groups, electrophysiology and autonomic function were more abnormal than in asymptomatic diabetic subjects. There was a significant overall relationship between peripheral nerve (electrophysiologic) and autonomic (cardiovascular reflex) dysfunction. However, when considered by groups, the degree of cardiovascular reflex abnormality was similar in the three symptomatic groups, whereas electrophysiology was appreciably worse in the foot ulcer group than in patients with painful neuropathy. Thus, patients with painful neuropathy had a higher ratio of autonomic (small fiber) abnormality to electrophysiologic (large fiber) abnormality. By contrast, foot ulceration was associated with the worst electrophysiologic (large fiber) abnormality. Heavier alcohol consumption and more severe retinopathy were also related to foot ulceration. In diabetic subjects with symmetrical sensory neuropathy, the relationship between large fiber and small fiber damage is not uniform. We conclude that there may be different etiologic influences on large and small fiber neuropathy in diabetic subjects and that the predominant type of fiber damage may determine the form of the presenting clinical syndrome.

Adult↗
PubMed1986

The relationship of soluble immune complexes, insulin antibodies and insulin-anti-insulin complexes to platelet and coagulation factors in type 1 diabetic patients with and without proliferative retinopathy.

The possible correlation between soluble immune factors and platelet and coagulation factors has been evaluated in Type 1 diabetic patients with and without proliferative retinopathy, and in non-diabetic controls. Soluble immune complexes, platelet factor IV (PF4), beta-thromboglobulin, fibrinogen, factor VIII related antigen and anti-thrombin III were significantly increased in Type 1 diabetic patients with retinopathy as compared to non-diabetic controls. Fibrinogen and anti-thrombin III were also higher in those patients with retinopathy compared to those without retinopathy. A significant correlation was found between positive values of soluble immune complexes and increased levels of PF4 and beta-thromboglobulin in diabetic patients with retinopathy. The presence of soluble immune complexes and insulin-anti-insulin complexes was associated with a significantly greater number of elevated haemostatic factors in retinopathic patients. Our findings suggest that the interaction of platelets and soluble immune complexes or insulin-anti-insulin complexes may be pathologically relevant to the development of diabetic retinopathy.

Adult↗
PubMed1986

The effect of captopril on blood pressure and glucose tolerance in hypertensive non-insulin dependent diabetics.

Thirteen hypetensive non-insulin dependent diabetics (9 male, 4 female, mean age 61.6 +/- 6 years) were given 6 weeks treatment with captopril in a dose range 75-150 mg/day. Each patient underwent a standard glucose tolerance test and had blood pressure profiles recorded before and after captopril. Supine systolic blood pressure (mmHg) improved from 181 (+/- 16) to 162 (+/- 17) and diastolic blood pressure from 103 (+/- 11) to 89 (+/- 9). A similar improvement was seen in erect systolic (174 +/- 19 to 156 +/- 19) and diastolic (103 +/- 14 to 87 +/- 11) blood pressures. Following treatment there was no significant change in glucose tolerance although the 120 minute plasma glucose value improved from 15.3 +/- 4.2 to 13.9 +/- 3.4 mmol/l (P less than 0.05). The drug was well tolerated and free of adverse effects. Captopril would therefore appear to be an effective and safe anti-hypertensive agent in non-insulin dependent diabetes and did not result in any deterioration of glucose tolerance.

Aged↗
PubMed1985

Influence of insulin antibodies on pharmacokinetics and bioavailability of recombinant human and highly purified beef insulins in insulin dependent diabetics.

Sixteen insulin dependent diabetics of long standing, with undetectable fasting plasma C peptide concentrations, and eight non-diabetic controls were each infused intravenously with biosynthetic human and highly purified beef insulin (1 mU/kg/min) while euglycaemia was maintained by a Biostator. No difference was observed between the two insulins in respect of insulin pharmacokinetics or biological action. The diabetics showed appreciable insulin resistance, manifested by a 40% reduction in the rate of insulin mediated glucose disposal, which was unrelated to the presence of insulin antibodies. Insulin binding antibodies, however, increased insulin's clearance rate and distribution space and prolonged its pharmacological and biological half lives. The rate at which insulin action was lost, after an intravenous infusion, was more rapid in diabetics without insulin antibody binding than in controls. In respect of their influence on insulin pharmacokinetics, moderate concentrations of insulin antibodies may be of positive advantage to all diabetics without endogenous insulin secretion and are not responsible for the insulin resistance of type 1 diabetes.

Adult↗
PubMed1985

Assessment of erectile function in diabetic and non-diabetic impotence by simultaneous recording of penile diameter and penile arterial pulse.

Simultaneous monitoring of penile diameter and penile arterial pulse during laboratory-based erotic stimulation with film and fantasy, has been used to compare diabetic and non-diabetic impotent men with non-impotent controls. The degree of erection to erotic film distinguished between organic and psychogenic aetiologies. The diabetic group showed smaller penile pulse amplitude changes than the other two groups. Amongst the diabetics, severe autonomic neuropathy was associated with impaired erectile and penile pulse amplitude responses. Severe retinopathy was associated with smaller baseline penile pulse amplitude as well as smaller amplitude response. Blood pressure response to erotic stimuli did not differ between the three groups. An analysis of the temporal relationship between penile diameter change and pulse amplitude change revealed differences between the groups that may prove to have diagnostic as well as theoretical implications.

Adult↗
PubMed1985

Pain relief in diabetic neuropathy: the effectiveness of imipramine and related drugs.

Experience of treating 80 consecutive patients with painful diabetic neuropathy and a double-blind study of imipramine in acute painful neuropathy are reported. A standard stepwise protocol was used, based on imipramine as the drug of first choice, substitution of amitriptyline or mianserin as second choice, and, thirdly, addition of phenothiazine or clonazepam if necessary. Sixty per cent were satisfied with imipramine alone and all but 3 (5%) were improved by the stepwise scheme. Paradoxically, the most effective analgesia was obtained in those with the most severe and unpleasant pain. Often 150 mg of imipramine or amitriptyline was necessary. The onset of analgesia and relapse after withdrawal of treatment were rapid, facilitating clinical use, and suggesting a peripheral rather than central drug action.

Adult↗
PubMed1984

Alcohol: another risk factor for diabetic retinopathy?

In a five year prospective study clinical features associated with the development and progress of retinopathy were sought in 296 randomly selected diabetic men aged 20-59. None had ophthalmoscopically detectable retinopathy initially, but during follow up 66 developed the condition (47 background, 10 exudative, 9 proliferative). Linear logistic analyses (two tailed tests) showed that the initial features independently predictive of retinopathy were duration of diabetes, poor glycaemic control, impotence, and--unexpectedly--heavy alcohol consumption. Poor glycaemic control in the interim and proteinuria at review were also associated with the development of retinopathy. No relation was found with smoking or obesity. Glycaemic control and alcohol consumption were therefore the only aetiologically relevant associations identified. The development of severe retinopathy (exudative and proliferative) showed a particular association with heavy alcohol consumption, occurring in nine of the 70 heavy drinkers (13%) compared with 10 (4.4%) of the rest. Alcohol consumption may be an important independent factor associated predictively with sight threatening diabetic retinopathy.

Adult↗
PubMed1984

The natural history of impotence in diabetic men.

The natural history of erectile impotence in diabetic men has been defined in a 5-year prospective study of 466 patients initially aged 20-59 years. Of the 275 who were originally potent, 78 (28%) have become impotent. Five features present at first interview were found to be independently predictive of the subsequent development of impotence; age (p less than 0.0001), alcohol intake (p less than 0.0001), initial glycaemic control (p = 0.03), intermittent claudication (p = 0.04) and retinopathy (p = 0.05). The development of impotence was also significantly associated with the appearance of neuropathic symptoms (p = 0.003) and poor glycaemic control in the intervening 5 years (p = 0.01). Only 11 out of 128 (9%) of those originally impotent regained potency; they were young, had short duration of diabetes, and often features of psychogenic impotence. Those with impotence originally but no clinically apparent micro/macrovascular or neuropathic diabetic complications developed retinopathy (p = 0.001) and neuropathy (p = 0.01) more frequently than their comparable potent counterparts. It is concluded that diabetic impotence rarely reverses, that it is strongly associated with neuropathic and vascular complications of diabetes, and that moderation of alcohol consumption and improvement of glycaemic control are possible preventative factors.

Adult↗
PubMed1984

Insulin action and pharmacokinetics in insulin treated diabetics during the third trimester of pregnancy.

Insulin action and pharmacokinetics were compared, using the euglycaemic insulin clamp technique, in seven insulin-treated diabetics during the third trimester of pregnancy and one to three weeks post-partum. At an insulin infusion rate of 1 mU/kg/min, insulin mediated glucose disposal was significantly greater (p less than 0.02) following delivery (1.194 +/- 0.138 mmol/m2/min) than in pregnancy (0.761 +/- 0.072 mmol/m2/min) and the rate of decline in insulin mediated glucose disposal, at the end of the insulin infusion, was significantly greater (p less than 0.02) following delivery (24.78 +/- 4.22 mumol/m2/min2) than in pregnancy (15.17 +/- 2.00 mumol/m2/min2). The metabolic clearance rate, distribution space and pharmacological half-life of insulin were not significantly altered by pregnancy. These findings show that the third trimester of pregnancy is associated with steady state insulin resistance accompanied by a reduced rate of insulin deactivation, but normal insulin pharmacokinetics.

Adult↗
PubMed1984

Platelet and coagulation factors in proliferative diabetic retinopathy.

Plasma beta-thromboglobulin, platelet factor 4, fibrinogen, fibrinopeptide A, antithrombin III, factor VIII related antigen, alpha 2-macroglobulin, platelet count, and total glycosylated haemoglobin were measured in three well matched groups of subjects: non-diabetic controls, diabetics without retinopathy, and diabetics with proliferative retinopathy. beta-thromboglobulin and platelet factor 4 concentrations were significantly higher in the diabetics with retinopathy than in the controls and platelet factor 4 was also increased in the diabetics without retinopathy compared with controls. Fibrinogen concentration was raised in diabetics without retinopathy compared with controls, diabetics with retinopathy compared with controls, and diabetics with retinopathy compared with those without. Fibrinopeptide A concentration did not differ significantly between groups. Antithrombin III levels were increased in diabetics with retinopathy compared with controls, and in diabetics with retinopathy compared with those without. Factor VIII related antigen values were higher in both the diabetic groups when compared with the controls. Fibrinopeptide A concentration correlated with both beta-thromboglobulin and platelet factor 4 in each of the three groups. Haemostatic abnormalities in diabetes have been shown, although a hypercoagulable state has not been confirmed. These changes in platelet and coagulation function may be secondary to the development of microvascular disease and their role in the pathogenesis of retinopathy remains uncertain.

Adult↗
PubMed1984

Glycosylated haemoglobin and serum insulin antibodies in type I diabetes.

Type 1 diabetics receiving once (Group 1, n = 72) and twice (Group 2, n = 48) daily subcutaneous injections of conventional beef insulin were compared, on a cross-sectional basis, in respect of insulin antibody binding by serum and total glycosylated haemoglobin (HbA1). Patients in Group 1 had higher insulin antibody binding (25.2 +/- 15.8% vs 17.0 +/- 13.9%; p less than 0.01) and higher HbA1 levels (12.5 +/- 2.0% vs 11.0 +/- 1.8%; p less than 0.001) than patients in Group 2. An inverse correlation (tau = -0.28, p less than 0.01) was observed between HbA1 and insulin antibody binding in C-peptide non-secretors of Group 1 but not in Group 1 C-peptide secretors, nor in C-peptide secretors and/or non-secretors of Group 2. It is suggested that in Type 1 diabetics who receive a single daily insulin injection and who have no endogenous insulin secretion, insulin antibodies may aid glycaemic control by prolonging insulin action.

Adult↗
PubMed1984

Breathing, sleep, and diabetic autonomic neuropathy.

Sudden, unexplained deaths are relatively common in diabetic autonomic neuropathy. As disturbed autonomic function has been associated with sleep apnea, and sleep apnea with sudden death, we recorded breathing patterns, arterial oxygen saturation, and EEG during sleep in 8 male diabetic subjects with severe autonomic neuropathy and 8 age-matched, male diabetic subjects without autonomic neuropathy. None of the patients with autonomic neuropathy had more than 11 apneic episodes per night, and there were no significant differences between the two groups in the number of sleep apneas, the duration of individual apneic episodes, the total duration of irregular breathing during sleep, or the duration and quality of sleep. The arterial oxygen saturation when awake and the lowest arterial oxygen saturation during sleep were also similar in both groups. Thus, diabetic patients with severe autonomic neuropathy have normal breathing patterns and oxygenation during sleep, and it is unlikely that sleep apnea causes these unexpected deaths.

Adult↗
PubMed1984

A comparison of the biological actions and pharmacokinetics of intravenously infused highly purified beef and biosynthetic human insulins in normal man.

By means of the euglycaemic insulin clamp technique the rate of insulin-mediated peripheral glucose disposal (GDR) was compared in response to intravenous infusions of highly purified beef insulin (BI) and biosynthetic human insulin (BHI), infused at 1 and 6 mU/kg/min, in healthy volunteers. The metabolic clearance rates of BI and BHI were similar at the lower insulin infusion rate and were both greater than those observed at the higher insulin infusion rate, which were also similar, implying the process of insulin clearance to be saturable. The GDRs were similar in response to infusions of BI and BHI at each insulin infusion rate. The rates of insulin deactivation were similar, having discontinued BI and BHI infusions at 1 mU/kg/min.

Animals↗
PubMed1983

Sexual responsiveness in diabetic women.

Sexual responsiveness in 82 Type 1 (insulin-dependent) diabetic women was compared with that of 47 normal control subjects, using an interview method for rating various aspects of sexual response, and attitude questionnaires. The diabetic women were questioned about symptoms of autonomic neuropathy, and cardiovascular autonomic nerve function tests were performed. There were differences between the two groups in the reports of vaginal lubrication, but in most other respects the groups were similar. The diabetic women were not less orgasmic, and reported significantly fewer unpleasant feelings during sexual intercourse. They saw themselves and their husbands as less 'potent' than did the normal subjects. The possible enhancing effect of diabetes on the marriage of some diabetic women possibly counteracted the relatively mild physiological deficits involved. There was very little difference in sexual response between women with and without symptomatic autonomic neuropathy.

Adult↗
PubMed1983

Natural history of thyroid function in diabetics with impaired thyroid reserve: a four year controlled study.

An attempt was made to compare the natural history of thyroid function in 80 diabetics having raised serum TSH concentrations (median 8.9 mU/l, range 5.8-46.3 mU/l) but serum T4 concentrations within the normal range (Group 1), and in 59 diabetics having normal serum TSH (median 1.9 mU/l, range 0.8-4.7 mU/l) and T4 concentrations (Group 2). Thyroid microsomal antibodies were present initially in 65% of patients in Group 1 and 15% of patients in Group 2. By 1981, 59 patients (74%) in Group 1 and 47 patients (80%) in Group 2 had been followed for a mean +/- SD duration of 4.2 +/- 1.8 and 4.2 +/- 1.5 years, respectively. Hypothyroidism developed in 9 patients in Group 1, but none from Group 2. Of patients in Group 1, hypothyroidism developed at a rate of 5% per annum in those with thyroid microsomal antibodies, but only 1% per annum in those without antibodies. Therefore, the risk of development of hypothyroidism is greatest in diabetics having both elevated serum TSH concentrations and thyroid microsomal antibodies and such patients should have regular review of thyroid function. Either risk factor alone appears to be a poor predictor of development of hypothyroidism.

Antibodies↗