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Biomedical subjects

R Shires

Publications and source records attributed to R Shires.

At least 19 recordsLinked to original sources

Fewer bone histomorphometric abnormalities with intermittent than with continuous slow-release sodium fluoride therapy.

To help resolve the uncertainty whether sodium fluoride (NaF) therapy should be given intermittently or continuously, we examined iliac crest bone biopsies (before and after treatment) and fragility fracture rates in 35 intermittently treated (group I) and 69 continuously treated (group C) patients; all received calcium. The following statistically significant results were obtained. Reduction in vertebral fracture rate was similar in the two groups. Trabecular thickness and the structurally more important mineralized thickness increased only in group I. Group I also accumulated less excess osteoid (surface, volume). Mean osteoid thickness did not change in either group because of a bimodal distribution of wide seams with osteoblasts and double tetracycline labels, and thin seams without osteoblasts or labels. Osteoid was lamellar. Osteoid in abnormal sites (within bone marrow or bone, or around osteocytes) was found less frequently in group I. Adjusted apposition rate declined and mineralization lag time increased in both groups because of extended unlabelled osteoid seams. Erosion surface increased only in group C. Hook and/or tunnel erosion was seen less frequently in group I; it was closely associated with osteoid in abnormal sites and correlated with osteoid surface. Extended osteoid surface may have forced osteoclasts to hollow out trabeculae, leaving the empty osteoid shell in marrow. Excess osteoid volume and eroded surface and osteoid and erosion in abnormal sites correlated with bone fragility in group C. We conclude that intermittent therapy is to be preferred because it (1) increased mineralized trabecular thickness, (2) did not cause excessive osteoid accumulation and erosion, (3) showed less osteoid and erosion in abnormal sites and (4) led to a similar reduction in the vertebral fracture rate as did continuous treatment. The question of whether intermittency of therapy has some other effect independent of the cumulative dose of fluoride administered cannot be answered by this study.

Adult↗

Osteoporosis in African hemosiderosis: role of alcohol and iron.

This paper aims to examine the relative contributions made by alcohol and iron overload and hypovitaminosis C to the osteoporosis associated with African hemosiderosis. To characterize this bone disorder, we examined double-tetracycline-labeled iliac crest bone biopsies and serum biochemistry in 53 black male drinkers, 38 with (Fe+) and 15 without (Fe-) iron overload, and in controls. We reasoned that abnormalities found in both patient groups were likely to be caused by alcohol abuse and those found only in the Fe+ group to be caused by iron overload and hypovitaminosis C (iron/C-). The patient groups differed only with respect to greater erosion depth (p < 0.05) and abnormal markers of iron overload in the Fe+ group. Ascorbic acid levels were lower in the Fe+ group than in controls (p < 0.001). Bone volume and trabecular thickness were significantly lower in both patient groups compared with controls and therefore likely caused by alcohol. There were no positive correlations between formation and erosion variables in either patient group, which suggests uncoupling of formation from erosion, possibly as a result of alcohol abuse. Prolonged mineralization lag time associated with thin osteoid seams was found in 32% of patients, affecting both groups. This rules out osteomalacia and suggests osteoblast dysfunction, probably caused by alcohol. The number of iron granules in the marrow correlated with erosion depth (r = 0.373, p < 0.01), trabecular number (r = -0.295, p < 0.05), and trabecular separation (r = 0.347, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The effect of magnesium sulphate infusion on circulating catecholamine levels in severe gestational proteinuric hypertension. A report of 8 cases.

The effect of magnesium sulphate (MgSO4) infusion on blood pressure and circulating venous catecholamine levels in 8 patients with severe gestational proteinuric hypertension is described. A significant fall in blood pressure was noted after MgSO4 infusion; the maximal fall in diastolic blood pressure correlated with the greatest rise in serum magnesium levels (P less than 0.04). No significant change was observed in mean venous plasma adrenaline or noradrenaline levels after MgSO4 infusion, although the mean dopamine concentration declined significantly. It is concluded that the decrease in systemic vascular resistance after MgSO4 infusion in gestational proteinuric hypertension is mediated predominantly by mechanisms other than a change in circulating catecholamine levels.

Adult↗

The absorption of tricalcium phosphate and its acute metabolic effects.

The use of calcium (Ca) supplements by postmenopausal women is growing rapidly. A commercial preparation of tricalcium phosphate (TCP) is available in the USA. Depending on the relative absorption of Ca versus phosphate, a rise in serum phosphorus (P) could stimulate parathyroid hormone (iPTH) secretion. We therefore compared Ca absorption and the metabolic responses following TCP to that of Ca carbonate (CC) on separate occasions in each of 10 women, aged 22-40 years. The subjects were fasted overnight for 12 hours while good hydration was maintained. Following a 2-hour baseline-urine collection, 1200 mg calcium (as CC or TCP) was ingested and two 2-hour postload urine collections were made. Blood was drawn at 1, 2, and 4 hours after the Ca load. Serum (S) and urine (U) Ca, P, and creatinine, and U cyclic AMP (cAMP) were determined. iPTH levels following TCP were also measured. Ca absorption was determined by the postload rise in Uca above baseline. Uca excretion increased significantly and was accompanied by significant rises in Sca after both preparations. Following TCP, S and U phosphorus increased. Urinary cAMP did not change after either preparation, and iPTH levels fell after oral TCP. We conclude that Ca taken as TCP is absorbed adequately and, thus, despite a rise in the S phosphorus level does not stimulate parathyroid activity.

Administration, Oral↗

Primary hyperparathyroidism. A study of 100 patients in Johannesburg.

This study comprised 100 white patients with primary hyperparathyroidism treated between 1975 and 1984. Of these, 75 attended Johannesburg Hospital and 25 were managed by private practitioners. The mean age was 56.4 +/- 1.4 years at the time of diagnosis. There were almost twice as many women as men. In patients attending Johannesburg Hospital there was a progressive increase in the detection rate after 1979, which corresponded with the introduction of automated multichannel serum analysis. The commonest major complications were renal stones (54%), renal insufficiency (27%), a history of skeletal fractures (12%), radiographic evidence of osteopenia (38%) and peptic ulcers (20%). Bone disease was particularly common in postmenopausal women (64%). Other notable features were the frequency of weakness and fatigue (40%) and hypertension (45%). Coincidental thyroid abnormalities were frequent (18%). Ninety-three patients were treated surgically; 76 (81.7%) had a single adenoma. Our findings are compared with those of other large series. This study indicates the need for a greater awareness of this condition and earlier diagnosis to forestall the development of its harmful complications, and for the collection of additional information from a prospective study.

Adolescent↗

Maximal pancreatic beta-cell stimulation and the counter-regulatory hormonal responses in South African black and white obese subjects.

We evaluated beta-cell secretory capacity over 60 minutes in response to oral glucose (75 g) followed 30 minutes later by the intravenous injection of tolbutamide 0,5 g and glucagon 1 mg (combined) in 10 black and 8 white obese non-diabetic female volunteers. Thirty minutes after oral glucose administration both insulin and C-peptide levels were significantly higher in the white group. The levels of both substances after tolbutamide-glucagon stimulation were likewise higher in the white group at all times, being significantly so 30 minutes after the injection. Hepatic extraction of insulin, calculated as the C-peptide: insulin molar ratio, was similar in both groups. These results indicate that the beta-cell secretory capacity of black obese subjects is less than that of whites. In response to insulin-induced hypoglycaemia in 6 of the black and 5 of the white subjects, the pancreatic glucagon rise was lower in the black group, despite greater falls in plasma glucose levels. In view of this finding it is possible that blacks may be at risk of slower recovery from insulin-induced hypoglycaemia.

Adult↗

Hormonal and biochemical responses to transcendental meditation.

This study was designed to assess whether transcendental meditation (TM) could influence various endocrine responses in 10 experienced male meditators. Nine matched subjects, uninformed of the TM procedure, acted as controls. Meditators successfully practised their technique for 40 min in the morning while controls relaxed for this period. No significant differences emerged between these 2 groups with respect to carbohydrate metabolism (plasma glucose, insulin and pancreatic glucagon concentrations), pituitary hormones (growth hormone and prolactin) or the 'stress' hormones, cortisol and total catecholamines-although meditators tended to have higher mean catecholamine levels. Plasma free fatty acids were significantly elevated in meditators 40 min after completing the period of TM. No clear evidence was thus obtained that any of the stress, or stress-related, hormones were suppressed during or after meditation in the particular setting examined.

Adult↗

Nifedipine does not impair the hormonal responses to graded exercise in healthy subjects.

The aim of this study was to assess whether the potent calcium antagonist nifedipine was capable of modifying the hormonal response to graded exercise in 7 healthy young men. After fasting overnight, each subject came to the laboratory on 2 consecutive mornings. On one day he was given 10 mg of nifedipine sublingually and on the other an identical placebo capsule; the order was randomised in a double-blind fashion over the 2 days. Thereafter each subject performed 2 successive short treadmill runs, equivalent to 60 and 100%, respectively, of maximal aerobic power. While significantly blunting the rise in mean systolic blood pressure and inducing a greater fall in diastolic blood pressure during and after exercise compared with the placebo, nifedipine did not impair the brisk response to pituitary-adrenal hormones (ACTH, cortisol and total catecholamines). Nifedipine also did not modify the effects of short-term exercise in raising mean plasma glucose levels, stimulating pancreatic glucagon secretion and producing a delayed increase in plasma insulin concentrations. Nor did the drug blunt the significant rise of growth hormone and prolactin levels occurring during and after the treadmill run. It was concluded that, apart from inducing significant changes in blood pressure, a single dose of nifedipine does not appear to suppress the counterregulatory hormonal responses to short-term physical activity in healthy men.

Adrenal Cortex Hormones↗

The 8-hour metabolic profile after drinking ethanol.

The acute metabolic changes after drinking ethanol have been studied in 11 fasting, healthy, nonobese, medical students, 6 of whom consumed 40 g ethanol diluted with 750 ml of a sugar-free soft drink over 1 h. The other 5 drank the same volume of soft drink alone. Blood levels of ethanol, glucose, immunoreactive insulin and growth hormone were measured over the ensuing 8 h, as well as the plasma concentrations of prolactin, cortisol and triiodothyronine. After ingesting ethanol, the mean plasma glucose concentration declined, but not to hypoglycemic levels (the nadir was 3.9 mmol/l at 6 h), insulin levels fell gradually and the mean growth hormone concentration showed a modest late rise. Other hormones did not change significantly. We conclude that, in the particular setting examined, the oral administration of ethanol does not cause hypoglycemia or other adverse effects on carbohydrate metabolism.

Adult↗

Hormonal profile after insulin-induced hypoglycemia in chronic calcific pancreatitis. Pancreatic, pituitary and adrenal responses.

The present investigation defined the pattern of pancreatic, pituitary and adrenal responses after insulin-induced hypoglycemia in chronic calcific pancreatitis (CCP) related to alcohol abuse, and assessed the role of some of these hormones in the counterregulation of blood glucose. We studied 6 Black men with recently diagnosed CCP, all showing radiological evidence of pancreatic calcification and normal glucose tolerance, as well as 7 matched nonobese male controls. After a standard iv insulin tolerance test inducing marked hypoglycemia, patients with CCP showed significantly impaired mean plasma pancreatic glucagon and pancreatic polypeptide responses compared to the controls. Mean basal plasma somatostatin levels tended to be higher in chronic pancreatitis and remained so throughout the test without altering consistently; in the controls somatostatin peaked significantly at 30 min. Concerning extrapancreatic hormonal changes, plasma growth hormone, prolactin and total catecholamines responded normally in CCP, but plasma cortisol rose to significantly higher levels than controls at 60 and 120 min after the injection of insulin. This, coupled with the brisk output of catecholamines, may have prevented the heightened sensitivity to insulin anticipated because of their hypoglucagonemia. We conclude that patients with CCP show impaired pancreatic hormone release after insulin hypoglycemia with the exception of somatostatin; there is also an excessive rise in plasma cortisol, possibly related to the long standing abuse of alcohol in the past.

Adrenal Glands↗

Hyperglycaemia in infantile gastroenteritis.

The prevalence and pathogenesis of hyperglycaemia were investigated in a consecutive series of 27 black infants admitted to hospital with gastroenteritis over a period of three months. Hyperglycaemia (plasma glucose concentration greater than 10 mmol/l) occurred in 15 (55%) of these patients. The pathogenesis was not clear but possible contributory factors included raised concentrations of the stress hormones pancreatic glucagon, growth hormone, and cortisol; hypokalaemia; and peripheral insulin resistance. Intravenous rehydration, without insulin, corrected the plasma glucose concentrations and restored the hormonal profile towards normal within 36 to 48 hours.

Child, Preschool↗

Alcohol-potentiated reactive hypoglycaemia depends on the nature of the carbohydrate ingested at the same time.

Alcohol may provoke reactive hypoglycaemia when drunk with a sucrose mixer (gin and tonic) but not in the form of a starch-based beverage. In the present study alcohol-potentiated reactive hypoglycaemia was shown to depend on the nature of the carbohydrate ingested together with the alcohol. When 14 men (9 normal weight and 5 obese) aged between 20 and 50 years consumed a 50 g glucose load together with 50 g ethanol over an hour, their early plasma insulin response was significantly higher and their later fall in plasma glucose significantly lower than after drinking the same amount of a starch solution (maize meal) and alcohol. In four subjects (3 of them non-obese) plasma glucose concentrations dropped below 2.8 mmol/l after drinking the glucose-alcohol solution. Obesity seemed to be associated with features of peripheral insulin resistance. We conclude that the common social custom of drinking alcohol together with a simple sugar mixer should probably be modified.

Adult↗

HLA antigens in White and Black South African diabetics.

The HLA A and B specificities in 72 Whites with type 1 or juvenile-onset diabetes mellitus (JOD), 53 Blacks with type 1 diabetes or JOD and 52 Blacks with type II or maturity-onset diabetes (MOD) were determined and compared with those in 278 Whites and 311 Blacks who were not diabetic. In Whites with JOD, frequencies of HLA A1 and B8 antigens were significantly increased, whereas those of the A3 and B17 antigens were reduced. Blacks with JOD had an increased frequency of HLA B8. By contrast, in Blacks with MOD the antigen frequencies were not significantly altered. The D-locus antigens Dw3 (DRw3) and Dw4 (DRw4), which bear the strongest associations with JOD in Whites, need to be examined in Black South African diabetics.

Adult↗

The effect of low-dose aspirin and platelet aggregation in familial hypercholesterolaemia.

Since the platelets of patients with familial hypercholesterolaemia (FH) are hyperaggregable, the inhibitory effect of low-dose aspirin on platelet aggregation in response to adenosine diphosphate, collagen, adrenaline and arachidonic acid was tested in 9 young adult patients with FH and compared with that in 9 normal subjects. After a single oral dose (150 mg) of aspirin the degree of inhibition of platelet aggregation was the same in the two groups, as was the recovery time (in days) for full restoration of platelet aggregation . In a second experiment in which 162 mg aspirin was administered daily for 28 days, inhibition of platelet aggregation was sustainable in both the patient and the control groups. These results suggest that despite the recognized hyperaggregability of platelets from patients with FH, daily low-dose aspirin ingestion effectively inhibits their in vitro aggregation and may therefore prove beneficial as supplemental therapy to reduce the rate of myocardial infarction in this high-risk group.

Adult↗