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Biomedical subjects

D J Betteridge

Publications and source records attributed to D J Betteridge.

At least 127 records · Page 7Linked to original sources
PubMed1984

The neuromuscular features of acromegaly: a clinical and pathological study.

A study of the neuromuscular features of acromegaly was performed in six patients. Clinical assessment was supplemented by quadriceps force measurements, plasma creatine kinase (CK) activities, electromyography (EMG) and nerve conduction studies. Muscle mass was measured by urinary creatinine/height indices (CHI) and cross sectional area (CSA) of thighs and calves on computed tomography. Quadriceps force/unit cross sectional area was derived. Needle biopsies of vastus lateralis were studied by histochemical and ultrastructural methods. Mean fibre area (MFA) and fibre type proportions were measured. Most of the subjects studied had muscle pain and proximal muscle weakness confirmed by quadriceps force measurements. This occurred in the absence of muscle wasting, as shown by cross sectional area measurements and normal or raised creatinine/height indices. "Myopathic" features were demonstrated by needle biopsy in half the patients and occasionally by electromyography and raised plasma creatine kinase activity. Abnormalities on needle biopsy included variation in fibre size, type 2 fibre atrophy and large type 1 MFA relative to type 2 MFA. Electronmicroscopy showed the non-specific findings of increased glycogen accumulation, excess lipofuscin pigment and myofilament loss.

Acromegaly↗
PubMed1983

Differences in the stability of prostacyclin in human, rabbit and rat plasma.

Prostacyclin (PGI2) is a potent vasodilator and inhibitor of platelet aggregation, however, its half-life in aqueous solutions at neutral or acid pH is very short. In this study we have investigated the stability of PGI2 in plasma from different species and have demonstrated that the half-life of the anti-aggregatory and the hypotensive activity of PGI2 is considerably prolonged in human plasma. Interestingly the activity of PGI2 was not maintained on incubation in rat or rabbit plasma indicating that the stabilising factor may be confined to human plasma. Whether such stabilisation prolongs the half-life of PGI2 in the human circulation merits investigation.

Adult↗
PubMed1983

Effect of treatment of Cushing's syndrome on skeletal muscle structure and function.

The time course of recovery in the myopathy of Cushing's syndrome was studied before and after removal of a pituitary adenoma at hypophysectomy in three patients and an adrenal adenoma in another. Serial measurements were performed of quadriceps force, total muscle mass/body weight, individual fibre size on needle biopsies of the lateral muscle mass of the thigh and skeletal muscle cross-sectional area (CSA) and force/unit CSA on computed (CT) scans of thighs and calves. All patients were weak, and recovery was slow but substantial except in one patient who had persistent Cushing's syndrome. An accompanying increase in overall and type II mean fibre area (MFA) occurred after surgery in the patients with a pituitary adenoma, as did an increase in skeletal muscle CSA and force/unit CSA in both patients having CT scans. The only patient with pronounced muscle wasting showed severe type II fibre atrophy with a reduced total muscle mass/body weight, but muscle morphology and total muscle mass were normal in the other patients. Only in this patient was a significant increase in total muscle mass/body weight noted after surgery. These findings suggest that the increase in muscle mass which may follow hypophysectomy in Cushing's syndrome is due to an increase in individual cell size.

Adult↗
PubMed1982

Platelets from diabetic subjects show diminished sensitivity to prostacyclin.

Prostacyclin, an unstable metabolite of arachidonic acid metabolism, has been shown to have potent platelet antiaggregatory and vasodilator activity. Available evidence suggests that arterial prostacyclin production is diminished in the diabetic state. In this study we have examined the sensitivity of platelets from diabetic subjects to the antiaggregatory effects of prostacyclin in vitro and report that platelets from some diabetic patients show diminished sensitivity to the antiaggregatory effects of prostacyclin. Thus diabetic subjects may not only have diminished prostacyclin production but also their platelets may be less sensitive to its effects. These findings may help to explain the increase in vascular disease observed in diabetic patients.

Adenosine Diphosphate↗
PubMed1982

The effect of experimental diabetes on prostacyclin production by tissues from pregnant rats.

Prostacyclin (PGI2) the major product of arachidonic acid metabolism in blood vessels has potent platelet anti-aggregatory and vasodilator activities. Recently it has been shown that PGI2 production is depressed in arterial tissue from diabetic patients. We have studied the effect of experimental diabetes on PGI2 production in both arterial and myometrial tissue from pregnant rats to determine whether myometrial PI2 production is affected in a similar way to vascular synthesis. We confirm that vascular production of PGI2 is diminished in pregnant diabetic rats but this reduction appears to be related to the duration of diabetes. However no difference was seen in myometrial PGI2 production between diabetic and control pregnant rats. It therefore appears that the effect of the diabetic state on PGI2 synthesis in this study shows a degree of selectivity.

Animals↗
PubMed1981

Platelet function in diabetes mellitus in relationship to complications, glycosylated haemoglobin and serum lipoproteins.

Mean levels of beta-thromboglobulin and platelet factor 4 were highly significantly elevated in diabetes compared to controls (72.6 v. 36.3 ng/ml, P less than 0.0005; 48.5 v. 16.5 ng/ml, P less than 0.0005; respectively) as was malondialdehyde formation (12.4 v. 8.1 nmol/10(9) platelets, P less than 0.0005). Diabetes with retinopathy had significantly higher levels of beta-thromboglobulin than those without retinopathy (79 v. 70 ng/ml; P less than 0.042). However, those diabetics without clinical evidence of vascular disease had levels of beta-thromboglobulin and platelet factor 4 significantly higher than controls. beta-Thromboglobulin did not correlate with glycosylated haemoglobin but did correlate significantly with individual lipid and lipoprotein levels (beta-thromboglobulin v. total triglyceride, P less than 0.029; v. VLDL triglyceride, P less than 0.041; v. LDL cholesterol, P less than 0.042; v. HDL/total cholesterol ratio, P less than 0.02). Abnormal platelet function may contribute to the vascular complications of diabetes mellitus.

Beta-Globulins↗
PubMed1980

Regulation of sterol synthesis in human intestinal mucosa.

The effect of dietary factors and experimental manipulations designed to perturb the enterohepatic circulation on the rate of sterol synthesis were studied in freshly isolated human jejunal mucosa from normal subjects. Fasting significantly reduced the rate of sterol synthesis from [14C]acetate in jejunal mucosa obtained from normolipaemic obese subjects. A high cholesterol diet had no consistent effect on the synthesis in normal subjects. Administration of cholestyramine resulted in a marked rise in the incorporation of [14C]acetate into sterols, while the administration of chenodeoxycholic acid did not significantly reduce basal sterol synthesis in normal subjects. These results demonstrate that in man the rate of sterol synthesis in intestinal mucosa is altered in response to physiological variables. Although these findings indicate that sterol synthesis in this tissue is subject to regulation, no difference was observed in basal sterol synthesis between normal subjects and patients heterozygous for familial hypercholesterolaemia.

Administration, Oral↗
PubMed1979

Regulation of sterol synthesis in human lymphocytes: evidence for post-transcriptional control by low density lipoprotein.

The effect of cordycepin (3'-deoxyadenosine), an inhibitor of messenger RNA synthesis, on the induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase mediated by lipid-depleted serum was studied in isolated human lymphocytes. 50 micrograms/ml cordycepin, although inhibiting messenger RNA synthesis by more than 50%, had no inhibitory effect on the two and four-fold induction of hydroxymethylglutaryl-CoA reductase when cells were incubated in a medium containing lipid-depleted serum for 8 and 16 h, respectively. This result suggests that newly synthesises messenger RNA is not required for the effect of lipid-depleted serum on the induction of hydroxymethylglutaryl-CoA reductase in human lymphocytes.

Deoxyadenosines↗
PubMed1979

Regulation of sterol synthesis in leukaemic blast cells: a defect resembling familial hypercholesterolaemia.

Leucocytes from normal subjects and from patients with acute myeloblastic leukaemia incubated for 9 h in the absence of lipoproteins increased their rate of sterol biosynthesis from [2-14C]acetate threefold. Subsequent addition of complete serum, low density lipoprotein or cholesterol in a non-lipoprotein form suppressed sterol synthesis in leucocytes from normal subjects. In contrast, complete serum or low density lipoprotein totally failed to suppress sterol synthesis in leukaemic blast cells. However, when these cells were incubated with cholesterol in a non-lipoprotein form suppression of sterol synthesis occurred as in normal leucocytes. These results suggest that leukaemic blast cells behave like cells from patients with familial hypercholesterolaemia in showing failure of regulation of sterol synthesis by low density lipoprotein.

Humans↗
PubMed1979

Metformin and clofibrate in maturity onset diabetes mellitus: advantages of combined treatment.

Blood glucose, lipoproteins, non-esterified fatty acids, fibrinogen and intermediary metabolites were measured in twenty-two diet failed maturity onset diabetics during a double blind crossover study of metformin (1.7 g/day) or clofibrate (2 g/day) therapy. Patients received combined therapy for a final two month period. Four patients had 12 hour metabolic profiles performed during each treatment period. A more significant improvement in fasting blood glucose and glycosuria occured with metformin and combined therapy. However, clofibrate and combined therapy significantly decreased total and low density lipoprotein cholesterol, total and very low density lipoprotein triglyceride and fibrinogen. Metabolic profiles demonstrated significant elevations of blood lactate and alanine with metformin treatment but these parameters returned to normal with combined therapy. Non-esterified fatty acids and glycerol were significantly lower during combined therapy compared with metformin or clofibrate alone. Despite the recent adverse report on clofibrate, this study indicates that the addition of clofibrate to metformin therapy may have advantages in the management of maturity onset diabetics.

Alanine↗
PubMed1978

High-density and low-density lipoproteins and prevalence of vascular disease in diabetes mellitus.

The prevalence of vascular disease among 154 diabetic patients was analysed in relation to the serum concentrations of individual lipoproteins. Overal the presence of vascular disease (59 cases) was positively associated with serum cholesterol and low-density-lipoprotein cholesterol but negatively associated with high-density-lipoprotein (HDL) cholesterol. The negative relation between HDL and vascular disease was not observed in all subgroups of diabetics. We conclude that there may be no overriding association between HDL and vascular disease in diabetics as proposed for some non-diabetic populations.

Aged↗