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Biomedical subjects

P H Wise

Publications and source records attributed to P H Wise.

16 recordsLinked to original sources

Mode of action of carbimazole in Graves' disease.

In a series of hyperthyroid subjects treated with a high dose 'block-replace' regime, mean thyroidal technetium uptake was shown to fall progressively over an 18 month period. Furthermore, sub-total inhibition of hormone biosynthesis could be demonstrated, without evidence of proportionate inhibition of organification, the regression of radio-iodine on technetium thyroid uptake showing similar slopes in euthyroid, treated and untreated hyperthyroid subjects. Together with the reported differential in remission rates between propranolol and anti-thyroid drugs, it is concluded that carbimazole does not act solely by inhibiting intrathyroid hormono-genesis, but more definitively by affecting thyroid hyperstimulation at a pre-biosynthetic level. The inability to demonstrate normal suppressibility of trapping in any subject in the present series despite extended therapy with a 'block-replace' regime, further suggests that current concepts of 'suppressibility' are invalid, the progressive fall in technetium uptake being unlikely to represent spontaneous restoration of a normal pituitary-thyroid axis, but rather a direct influence or prolonged therapy with anti-thyroid drugs on the natural history of the disease.

Adolescent

Prolactin suppression in the treatment of premenstrual syndrome.

Abnormal secretion of prolactin is amongst the many disorders of hormone secretion which have been proposed as potential causes for the common syndrome of premenstrual tension. Eight women suffering from this disorder participated in a five-month double-blind crossover trial of bromocriptine (5 mg per day) given in the luteal phase of the cycle. Significant improvement in most symptoms occurred during active as opposed to placebo therapy, together with objective evidence of a decrease in premenstrual weight gain and breast enlargement. This corresponds with the results of other studies which used bromocriptine in this dosage. The effect may be mediated by suppression of prolactin secretion, but could equally be a direct effect of bromocriptine.

Adult

Effects of therapy on plasma-high-density-lipoprotein-cholesterol concentration in diabetes mellitus.

In 122 diabetic patients there was a signnificant inverse correlation between plasma-high-density-lipoprotein (H.D.L.)-Cholesterol concentrations and glycosylated haemoglobin concentrations. In an insulin-treated subgroup improvement in diabetic control, confirmed by a decrease in glycosylated haemoglobin concentrations, was accompanied by a significant rise in plasma-H.D.L.-cholesterol concentration. This result suggests that improved diabetic control may diminish the risk of premature ischaemic heart-disease. When three groups of patients on different treatments were matched for age, sex, weight, and diabetic control, diabetic patients receiving sulphonylureas had significantly lower plasma-H.D.L.-cholesterol concentrations than those receiving insulin or on diet alone, or non-diabetic controls. This association suggests that sulphonyl-urea administration may constitute a positive risk factor for ischaemic heart-disease in diabetic patients.

Adolescent

DDAVP in the treatment of diabetes insipidus: a clinical study.

In three cases of established cranial diabetes insipidus, the effectiveness of the new vasopressin analogue 1-desamino-8-D-arginine vasopressin (DDAVP) in controlling diabetes insipidus is demonstrated. A single dose of 20 micrograms of DDAVP given intranasally had an antidiuretic action from 16 to 24 hours in the three cases, and 10 micrograms given twice daily intranasally was effective in controlling the diabetes insipidus with no side effects. All the patients preferred this form of therapy to their previous treatment.

Adult

Successful intra-splenic transplantation of syngeneic and allogeneic isolated pancreatic islets.

Adult rat islets harvested by the collagenase digestion/Ficoll separation technique were injected into the splenic pulp in 9 syngeneic (Lewis-leads to Lewis and WaG leads to WaG) and 13 allogeneic [(DA X Lewis) F1 leads to Lewis] experiments. Normal serum glucose levels and 24 hour urine volumes were restored in all 9 syngeneic recipients and in 11 out of the 13 allogeneic recipients in a mean of 3.3 days. Splenectomy performed on 3 of the 9 syngeneic recipients 110-178 days after transplantation resulted in a prompt return to the diabetic state. In all the remaining syngeneic recipients, normal values have persisted for the current period of observation of 6 months. In 5 untreated allogeneic recipients, rejection occurred in a mean of 5.2 days. The administration of a short course of ALS (1 ml I.P. days-1, 1, 3 and 5) to the remaining 6 animals greatly prolonged graft survival with all animals remaining normoglycaemic for at lest 4 weeks. These results were not significantly different from those recorded in comparable groups of intra-portal allogeneic islet recipients.

Animals

Significance of anomalous thermoregulation in the pre-diabetic spiny mouse (Acomys cahirinus): oxygen consumption and temperature regulation.

In keeping with studies of other desert rodents, the potentially diabetic spiny mouse has been demonstrated to have a very low basal metabolic rate, disproportionate to its body weight. The maintenance of a lower body temperature in response to high environmental temperatures and a lack of increase in metabolic rate in response to cooling have also been demonstrated. Assessments of "mechanical efficiency" have shown that spiny mice carry a potential selective advantage under fasting conditions. The findings, some of which are similar to those noted in other desert rodents, and in other species showing either spontaneous or induced hyperglycaemia, suggest that the low metabolic rate is at least partly based on ineffective glucose utilization. This phenomenon may be the common denominator of the survival advantage which has allowed both the successful evolution of species inhabiting warm, arid climes, and the persistence of the diabetic genotype in animal and human populations.

Animals

Significance of anomalous thermoregulation in the pre-diabetic spiny mouse (Acomys cahirinus): cold tolerance: blood glucose and food consumption responses to environmental heat.

Decreased cold tolerance, reduced food requirement for body weight maintenance and comparative resistance to the hypoglycaemic effect of fasting in high ambient temperatures have been demonstrated in the spiny mouse. These phenomena could be related to anomalous spiny mouse thermoregulation, a phenomenon which is common in desert rodents and is simulated by mutant and artificially diabetic rodent species. The data can be interpreted as showing evidence for a survival advantage of genotypes with potential diabetic expression, and may provide an explanation of the geographic distribution of certain species.

Animals

Phenformin and lactic acidosis.

Thirty-eight patients who presented with diabetes and a changed state of consciousness satisfied the criteria for lactic acidosis. Sixteen patients were non-ketotic, and 15 of these were receiving phenformin on admission. In all but one of these 15 patients, however, additional renal or cardiovascular abnormalities, or both, could be identified, which supported a multifactorial aetiology for lactic acidosis. Advanced age and cardiovascular and renal disease are absolute contraindications to the use of phenformin in diabetics.

Adolescent

Intentional radioiodine ablation in Graves' disease.

In a series of 50 cases of Graves' disease qualifying for therapy with radioiodine, "ablative" doses of radioiodine resulted in hypothyroidism in 92% of cases at six months. Hypothyroidism was treated by thyroxine or tri-iodothyronine replacement therapy. Rapid responses and predictable outcome were regarded as important advantages. Intentional ablation is particularly convenient in situations where clinical and biochemical follow-up may be difficult. Further follow-up studies are needed to determine whether ablative therapy is the treatment of choice in all cases of Graves' disease.

Administration, Oral