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Biomedical subjects

R Shires

Publications and source records attributed to R Shires.

33 records · Page 2Linked to original sources

Effect of drinking bottled beer on plasma insulin and glucose responses in normal subjects.

Alcohol may provoke reactive hypoglycaemia when drunk with a sucrose mixer ('gin and tonic') but does not do so when taken in the form of a starch-based beverage like sorghum beer. We examined the hypoglycaemic potential of bottled beer (Lion Lager; South African Breweries), which differs from sorghum beer in that it contains less carbohydrate (polysaccharides and simple sugars) and has a higher alcohol content. After an overnight fast 5 Black men each drank 2 litres of Lion Lager over an hour. Over the ensuing 5 hours their plasma insulin, glucose and alcohol concentrations were compared with the responses previously documented before and after consuming the same volume of sorghum beer or a 100 g control carbohydrate solution. Bottled beer elicited a prompt but short-lived rise in plasma insulin (mean +/- SEM, 37 +/- 7 mU/l at 1 hour), which was significantly greater than that produced by sorghum beer but less sustained than after drinking the control carbohydrate solution. After drinking bottled beer plasma glucose levels fell to a mean nadir of 3,6 mmol/l at 2 hours (compared with 5,4 mmol/l for sorghum beer), thereafter slowly returning to the basal value, while a substantial rise in the blood alcohol concentration occurred. We conclude that the development of alcohol-induced reactive hypoglycaemia is largely determined by the nature of the carbohydrate ingested together with alcohol.

Adult↗

Failure to induce reactive hypoglycaemia by drinking a starch-based alcohol beverage (sorghum beer).

Alcohol is a well-recognised cause of fasting hypoglycaemia but may also provoked reactive hypoglycaemia when drunk together with a carbohydratee mixer. In this study the ability of sorghum beer (an 'in-built' alcohol-starch beverage widely enjoyed in Southern Africa) to induce reactive hypoglycaemia was compared with "gin and tonic' in eight non-obese health African men. After an overnight fast, each subject drank, in random sequence on their different occasions, 2 litres of sorghum beer (carbohydrat content approximately 5% and alcohol concentration 2.24 g/dl-2.8% v/v), the same volume of a control solution providing a similar carbohydrate load, or a gin and standard tonic water mixture. No evidence of reactive hypoglycaemia was apparent during the 5 hours after the beginning of the sorghum beer tolerance tests, despite a mean peak blood alcohol level reaching 80 mg/dl. both the peak and total plasma insulin responses were significantly reduced (p less than or equal to 0.05) when compared to the brisk responses elicited by the carbohydrate solution alone and the gin and tonic drinks, with consequent hypoglycaemia. These data suggest that African home-brews are not potent causes of reactive hypoglycaemia, although they may be implicated in the development of ethanol-induced hypoglycaemia in the fasting state.

Adult↗

The effect of streptozotocin-induced chronic diabetes mellitus on bone and mineral homeostasis in the rat.

Diabetes mellitus was induced in Lewis rats by streptozotocin, and these animals and control rats fed ad lib were studied after 7 weeks. At the time of sacrifice, nondecalcified histological sections of bone were prepared and subsequently quantitated by micromorphometric techniques. In addition, tibial alkaline phosphatase and mineral ash content were determined. The bones obtained from the diabetic animals are characterized by significant decrements in the quantities of osteoid and osteoclasts and by failure to acquire a tetracycline label. These histological features are attended by reduced quantities of urinary hydroxyproline and tibial alkaline phosphatase. As compared with control animals fed ad lib, diabetic rats are hyperphosphatemic and markedly hypercalciuric. Circulating alkaline phosphatase is also elevated and associated with a parallel increase in intestinal content of this enzyme. Although serum corticosterone levels are increased, diabetes is associated with decrements in both circulating immunoreactive parathyroid hormone and 1,25(OH)2D. We conclude that prolonged streptozotocin-induced diabetes mellitus in the rat results in reduced bone turnover. The relative roles that functional caloric deprivation, low circulating levels of 1,25(OH)2D, hypercalciuria, hypercortisolemia, and decreased blood parathyroid hormone levels play in the genesis of these skeletal abnormalities remain to be determined.

Alkaline Phosphatase↗

Effects of semistarvation on skeletal homeostasis.

Rats were semistarved over a 7-week period, resulting in a loss of 28.2 +/- 1.6% (SEM) of their initial body weights, while ad libitum fed controls gained 15.1 +/- 1.8% (SEM). Bone loss occurred and skeletal turnover was markedly reduced in the semistarved rats, as evidenced by a paucity of osteoid and osteoclasts, failure of the bone to assume a tetracycline label, and reduced urinary hydroxyproline excretion. Despite these changes, there were no alterations of serum or bone alkaline phosphatase activity with semistarvation, and analysis of tibial mineral content revealed reductions only in magnesium and sodium. The malnourished animals, however, were hypercalciuric and hypophosphatemic. Semistarvation had no effect on circulating levels of immunoreactive parathyroid hormone or 25-hydroxyvitamin D, but did result in reduced serum levels of corticosterone, insulin, and 1,25-dihydroxyvitamin D. Therefore, it appears that the effects of semistarvation on the rat skeleton are osteoporotic rather than osteomalacic, and that the defect is the consequence of reduced bone turnover. The contribution which the abnormalities of bone-regulating hormones play in the genesis of this skeletal lesion remains to be determined.

Animals↗

Metabolic studies in acute asthma before and after treatment.

We studied the metabolism and hormone profile of 9 patients with moderately severe acute asthma before treatment, and again 10 min after intravenous aminophylline (250 mg) or the selective beta-adrenergic stimulant hexoprenaline (5 microgram) intravenously. Compared with basal values in normal subjects the untreated asthmatics had statistically significant raised mean plasma pancreatic glucagon, free fatty acid (FFA) and glucose levels in the plasma and a significantly depressed mean plasma potassium level. Insulin, growth hormone, cortisol, thyrotropin and ketone body levels were normal. The only significant changes after therapy were a further fall in plasma potassium in the hexoprenaline-treated patients and a rise in the mean lactate concentration of the group as a whole. The clinical implications of these findings are briefly considered.

Acute Disease↗

Idiopathic hypothalamic hypogonadotropic hypogonadism with polyostotic fibrous dysplasia.

A 22-year-old woman had polyostotic fibrous dysplasia (POFD) and idiopathic hypothalamic hypogonadotropic hypogonadism (isolated gonadotropin deficiency). Recurrent fracture of dysplastic bone during childhood was associated with primary amenorrhea, clinical and laboratory evidence of estrogen deficiency, and subnormal circulating and urinary gonadotropin levels during adolescence. Gonadorelin (luteinizing hormone-releasing hormone) stimulation initially showed a luteinizing hormone (LH) response but absent follicle-stimulating hormone (FSH) response. After three months without estrogen and progesterone and after four days of gonadorelin "priming," a subsequent gonadorelin infusion produced an enhanced LH and FSH response. All other tests of peripheral and trophic hormone levels and pituitary trophic hormone reserves were normal. Whereas POFD is known to occur with sexual precocity and other endocrinopathies, to our knowledge this is the first report of its association with isolated gonadotropin deficiency.

Adult↗

Hormonal and metabolic responses to an oral glucose load in obese Black diabetics.

Plasma insulin responses to a 4-hour glucose tolerance (100 g) were studied in urbanized Black people. Persons of normal weight without diabetes (12) and obese persons without diabetes (18) were compared with obese diabetics (19). Fasting serum ketone levels were measured, and the plasma potassium, triglyceride and growth hormone responses during the glucose tolerance test were determined. Obese subjects without diabetes had a twofold greater total plasma insulin response (area under curve) than their counterparts of normal weight, but there was a progressive fall in total plasma insulin response from subjects with mild diabetes (with fasting normoglycaemia) to those with severe diabetes (with fasting hyperglycaemia). The early plasma insulin responses of the group with mild diabetes were significantly impaired, and the peak response was only reached at 120 minutes. The subjects with severe diabetes had a flat insulin response curve. Fasting serum ketone levels were highest in the group with severe diabetes. The growth hormone responses were similar in all the groups. Plasma potassium and tryglyceride levels fell less during the glucose tolerance test in the group with severe diabetes than in the other three groups. These data indicate that insulin secretion is reduced in obese Blacks with chemical evidence of diabetes and this reduction becomes severe in the symptomatic diabetic.

Adult↗

Intravenous fat tolerance in obese Africans with varying grades of carbohydrate tolerance.

An intravenous fat tolerance test (IVFTT) was performed and fasting plasma lipid values determined in 12 healthy normal weight, 18 obese non-diabetic, 9 obese chemical diabetic and 10 obese symptomatic diabetic African subjects. Their insulin responses to an oral glucose load were also determined. Mean plasma triglyceride levels were similar in the normal weight and obese non-diabetic groups but were significantly raised in the two diabetic groups, being highest in the symptomatic diabetics. The fractional removal-rate of an intravenous injection of the fat emulsion Intralipid was significantly less in each of the obese diabetic groups compared with the normal weight or obese non-diabetic group. There was a significant negative correlation in all but the symptomatic diabetic group between the fasting triglyceride level and the rate constants for the IVFTT. These results suggest that the rate of triglyceride clearance is an important determinant of the basal plasma triglyceride concentration in urban African subjects.

Adult↗

Choriocarcinoma presenting as Jacksonian epilepsy.

Cerebral deposits of choriocarcinoma tend to be multiple and usually result in a rapidly fatal course. Two patients presented with Jacksonian epilepsy due to metastatic choriocarcinoma in the brain. In the first patient, the diagnosis of metastatic choriocarcinoma was unsuspected, since curetted uterine material was normal, the haemagglutination inhibition test for pregnancy was negative and a chest radiograph was unremarkable. A diagnosis of choriocarcinoma was made by brain biopsy 2 days before death. The second patient had been previously treated with systemic chemotherapy (methotrexate and actinomycin D) for uterine and pulmonary choriocarcinoma associated with hyperthyroidism. Human chorionic gonadotrophin could not be detected in the urine when the patient presented with Jacksonian epilepsy. A brain scan showed multiple areas of increased uptake consistent with metastatic choriocarcinoma. She was treated with both systemic chemotherapy and intrathecal methotrexate and cranial irradiation. A complete remission was obtained. Intrathecal methotrexate and cranial irradiation appear to offer a hopeful new approach to the problem of metastatic cerebral choriocarcinoma.

Adult↗

Serum dihydroxyvitamin D metabolite concentrations in patients on chronic anticonvulsant drug therapy: response to pharmacologic doses of vitamin D2.

We examined the effects of chronic anticonvulsant drug administration on the serum concentrations of dihydroxyvitamin D metabolites and the response of these metabolite levels to short-term treatment with pharmacologic doses of vitamin D2. Twelve patients maintained on chronic combined diphenylhydantoin and phenobarbital therapy were studied before and after the administration of vitamin D2, 75,000 units/week for 6 weeks. Prior to vitamin D2 administration, the patient group demonstrated decreased serum calcium (P less than 0.01) and increased serum iPTH (P less than 0.02) concentrations relative to 18 matched controls. Serum 25OHD and 24,25(OH)2D concentrations in the patient group were reduced by 38% and 75% (P less than 0.001), while serum 1,25(OH)2D concentration was increased by 27% (P less than 0.05) relative to control values. After vitamin D administration serum calcium and iPTH concentrations in the patient group were restored to values that were not significantly different from control levels. Serum 25OHD and 24,25(OH)2D concentrations were increased by 4.6- and 6.3-fold, respectively, to supranormal levels. Serum 1,25(OH)2D concentration exhibited an unexpected further 30% increase over pretreatment values, resulting in a return of the serum 1,25(OH)2D/24,25(OH)2D concentration ratio to a normal value. These data indicate that in patients treated chronically with anticonvulsant drugs, serum 25OHD concentration responds appropriately to vitamin D2 administration, but regulation of renal dihydroxy metabolite formation may be altered.

25-Hydroxyvitamin D 2↗