Biomedical subjects
Publications and source records attributed to R R Davies.
A vertebral fracture occurred in a 51-year-old man with previously undiagnosed osteoporosis. The underlying cause of the osteoporosis was primary hypogonadism. Back pain was the presenting symptom in this case of primary hypogonadism.
The growth hormone (GH) response to iv injection of GH releasing hormone 1-44 (GHRH 1-44) has been examined in 10 hyperthyroid and 6 hypothyroid patients. Both groups of patients were studied at presentation and when euthyroid (mean 5 months for hyperthyroid, 8 months for hypothyroid). Hyperthyroid subjects demonstrated a peak mean (+/- SE) level of 17.7 +/- 3.8 mU/l, with an integrated GH 29.3 +/- 6.4 mU/l.h. When euthyroid the peak mean level was 17.0 +/- 5.0 mU/l and the integrated GH 22.8 +/- 4.2 mU/l.h. Neither change was statistically significant. Hypothyroid subjects had a peak mean level of 5.0 +/- 2.7 mU/l and integrated GH of 5.9 +/- 1.7 mU/l.h and when euthyroid a peak mean level of 7.1 +/- 4.8 mU/l and integrated GH of 8.1 +/- 3.6 mU/l.h. Body weight did not change significantly in this group of hypothyroid subjects with prolonged treatment. The increase in GH response to GHRH previously reported following replacement therapy may reflect a treatment-induced decrease in body weight, or may be a short term effect.
Growth hormone (GH) has long been considered to have importance in diabetes. With poor control in Type 1 diabetes GH levels are high and may aggravate poor metabolic control. Pharmacological suppression of GH release at this stage might reverse the metabolic changes, with the possible added benefit of lower plasma insulin concentrations. Diabetic patients with life-long GH deficiency rarely develop retinopathy, while pituitary ablation in patients with retinopathy often leads to improvement. Growth hormone release inhibiting factor, somatostatin, has a short plasma half-life, and multiple effects on the endocrine system and on the gastrointestinal tract, making it unsuitable for clinical use as a GH suppressant. Long-acting analogues have a long half-life, but remain non-specific in their effects. In Type 2 diabetes the analogue Octreotide suppresses insulin and glucagon release, leaving glucose levels either unchanged or somewhat elevated. Gastrointestinal side-effects have been common, but may diminish with long-term treatment. In Type 1 diabetes insulin requirement is decreased by Octreotide, but as in Type 2 diabetes GH suppression has been observed consistently only when the drug was given at bed-time. The decrease in insulin requirement may reflect suppression of glucagon release and/or gut effects. Amelioration of the 'dawn phenomenon' has not proved possible, and hypoglycaemia has proved a particular problem with Octreotide given subcutaneously at night. The lack of effective GH suppression (particularly in patients with proliferative retinopathy), lack of specificity, and the gut and hypoglycaemic side-effects, argue strongly against a clinical role for the current somatostatin analogues in diabetes mellitus.
We describe a case of amiodarone-induced thyrotoxicosis following heart valve replacement in a patient with a multinodular goitre. He responded to medical therapy with carbimazole and potassium perchlorate. Subsequent therapy with radio-iodine was followed 30 weeks later by the development of anaplastic thyroid carcinoma. It is possible that amiodarone caused a low uptake of radio-iodine by the thyroid. It is not known whether this possible low dose exposure to ionising radiation played a part in the development of the anaplastic carcinoma.
Explore the source record for details and available documents.
Three 'pen'-administered multiple injection regimens have been compared with twice daily insulin injection regimens by means of 24-h profiles of plasma glucose and free insulin concentrations. Ten Type 1 diabetic patients received their usual twice daily insulin regimen and were then randomized to receive the same total daily insulin dose in four divided doses using (1) 50:50 premixed soluble and isophane, (2) 30:70 premixed soluble and isophane, and (3) preprandial soluble and evening crystalline-zinc insulins. Profiles were performed after 1 week on each regimen. Plasma glucose concentrations were similar during the twice daily regimen and the two premixed regimens, rising during the early hours of the morning to a peak between 0900 and 0930 h of 13.8 +/- 2.8 (+/- SD) mmol l-1 on the twice daily regimen, 13.6 +/- 5.3 mmol l-1 on the premixed 50:50 regimen, and 13.5 +/- 4.2 mmol-1 on the premixed 30:70 regimen. With the basal and prandial regimen, overnight plasma glucose concentrations were higher than with the other regimens between 2400 and 0300 h (p less than 0.05). Concentrations then fell until breakfast, and rose after this meal to a peak of 9.5 +/- 4.3 mmol l-1 (p less than 0.01). Mean plasma glucose concentrations were significantly lower than on the other three regimens between 0830 and 1100 h (p less than 0.05). Less variability was observed in 24-h mean plasma glucose concentrations during the basal and prandial regimen than during the other three regimens.
Explore the source record for details and available documents.
The hormonal and metabolic effects of the somatostatin analogue SMS 201-995 have been examined in normal and diabetic humans. When 50 micrograms of analogue was administered subcutaneously at 8 A.M. and 5:30 P.M., growth hormone secretion over 24 hours was not significantly affected, and the nocturnal growth hormone surge persisted in normal subjects and in type II diabetic patients. Insulin secretion was suppressed in both groups, but glucose tolerance deteriorated only in the normal subjects. Gastrointestinal side effects developed in both groups. Subcutaneous administration of 50 micrograms of SMS 201-995 at 11 P.M. decreased nocturnal growth hormone secretion (peak, 5 +/- 2 milliunits/liter versus 23 +/- 6 milliunits/liter; p less than 0.01) in normal subjects. Postprandial circulating glucose and insulin levels the following day were unaffected by SMS 201-995, and no side effects were observed. In type I diabetic patients receiving a variable rate insulin infusion overnight to maintain normoglycemia, SMS 201-995 (50 micrograms) administered at 11 P.M. decreased insulin requirements for two to three hours after injection. Insulin sensitivity thereafter was unaffected despite suppression of growth hormone secretion. Alternative dosage regimens are necessary to suppress growth hormone release over 24 hours and to minimize side effects in type II diabetes. Administration of the analogue in the late evening suppresses growth hormone secretion overnight, but the "dawn phenomenon" persists in type I diabetic patients.
Long-acting somatostatin analogues may be of benefit in certain hypersecretory endocrine and gastrointestinal disorders. The 24 h hormonal and metabolic profiles of six normal male subjects receiving a twice daily subcutaneous injection of one such analogue SMS 201-995, 50 micrograms, has been compared to that obtained following placebo injection. Spontaneous daytime peaks of GH secretion were delayed until 1400 h following SMS 201-995 but nocturnal and total 24 h GH secretion were unaffected. The nocturnal rise in thyrotrophin was abolished by SMS 201-995 but thyroid function was unaffected. Insulin levels were suppressed following SMS 201-995 and the response to meals was inhibited. Glucose intolerance followed main meals. Glucagon levels were suppressed for up to 6 h. Circulating alanine levels were raised between 1200 h and 0600 h and there were intermittent elevations in lactate, pyruvate, glycerol and 3-hydroxybutyrate. Amino acid levels, including branched chain amino acids, were also increased. All six subjects suffered gastrointestinal side-effects. SMS 201-995, 50 micrograms, given twice daily shortly before meals does not suppress 24 h GH secretion, but demonstrates significant effects on metabolism and causes side effects in normal subjects.
The 24-h hormonal and metabolic profiles obtained in five non-insulin-dependent diabetics receiving twice daily s.c. injections of the long-acting somatostatin analogue SMS 201-995 (50 micrograms) have been compared with those obtained following placebo injection. Injections were given 30 min before breakfast and the evening meal. GH secretion was not suppressed by the analogue administered in this manner. Despite suppression of serum insulin levels following breakfast and the evening meal, blood glucose levels were similar during the two study periods with no evidence of worsening in diabetic control. Prolonged suppression of plasma glucagon levels was observed and the nocturnal elevation in serum TSH levels was abolished. Free T4 levels fell significantly following the analogue but total T3 levels were unaffected. Blood alanine levels were elevated throughout the study period following SMS 201-995 but changes in lactate, pyruvate, glycerol and 3-hydroxybutyrate were minor. All five subjects suffered gastrointestinal side-effects. SMS 201-995 (50 micrograms) given twice daily before meals does not cause a deterioration in metabolic control, does not suppress 24-h GH secretion and causes significant side-effects in patients with non-insulin-dependent diabetes mellitus.
Growth hormone (GH) is important in diabetes in view of its anti-insulin actions and its relation to the long-term complications of the disease. The suppression of GH secretion in diabetics has theoretical and possible therapeutic interest. Native somatostatin has multiple actions, including inhibition of the secretion of insulin, glucagon, thyroid-stimulating hormone (TSH), and various gut hormones. It also has inhibitory effects on gastrointestinal motility, exocrine secretion, nutrient absorption, and splanchnic blood flow. Its therapeutic use is limited by a duration of effect of several minutes only. SMS 201-995 holds more potential than native somatostatin in view of its longer duration of action. Preliminary data suggest that 50 micrograms SMS 201-995 subcutaneously at night inhibits the nocturnal rise in GH secretion in normal man, but no effect on 24-h GH secretion is observed when SMS 201-995 is injected twice daily before meals. SMS 201-995 inhibits secretion of insulin, glucagon, and TSH in addition to growth hormone and induces carbohydrate intolerance when administered before food in normal subjects. Gastrointestinal side effects suggest additional effects on nutrient disposal, which are important when it is administered before food. Further studies are required to elucidate these effects of SMS 201-995 on endocrine and gastro-intestinal function in normal and diabetic man.
Investigations on the chemotaxis of polymorphonuclear neutrophils (PMNs) towards a cytoplasmic extract of Trichophyton rubrum in the presence and absence of antifungal drugs are described. It is shown that with griseofulvin, clotrimazole, econazole, ketoconazole, miconazole and natamycin at 1 mg l(-1), the number of PMNs migrating was significantly reduced. After 3 h of exposure to 10 mg l(-1), not one of the drugs tested had any discernable effect on the viability of the PMNs, or the complement. The anti-inflammatory activity of the drugs is discussed and whilst the chemosuppression of PMN chemotaxis may be an undesirable feature in a drug used to treat systemic mycoses, it is unlikely to have any adverse effect in the therapy of the dermatophytoses.
The interaction between the stimulatory effects of hpGRF 1-44 and the inhibitory effects of somatostatin on GH release have been investigated in six normal male subjects receiving continuous 4 h infusions of these peptides alone and in combination. hpGRF 1-44 0.3 microgram/kg/h alone produced a peak GH response of 27.0 +/- 7.6 mU/l (mean +/- SEM). Somatostatin 1.0 microgram/kg/h markedly inhibited the GH response to hpGRF 1-44 with mean levels less than 4.0 mU/l during the infusion, though a rebound rise in GH levels to 26.1 +/- 9.0 mU/l was observed at the end of the infusion period. Somatostatin 0.2 microgram/kg/h inhibited the GH response to hpGRF 1-44 to a lesser degree (peak GH during the infusion 11.7 +/- 2.5 mU/l) and the rebound rise in GH levels (maximum 13.2 +/- 4.3 mU/l) was less than that observed with high dose somatostatin. During somatostatin 1.0 microgram/kg/h alone GH levels were suppressed less than 1.0 mU/l followed by a rebound at the end of the infusion in only two subjects. These data demonstrate a dose-dependent inhibition of hpGRF 1-44 by somatostatin in vivo in man.
The growth hormone (GH) response of seven obese subjects to a 4 h continuous infusion of human pancreatic GH-releasing factor, 0.3 micrograms/kg/h, has been compared with that obtained in seven sex and age matched controls. The pattern of response was normal in the obese but peak GH levels (mean +/- SEM: 13.8 +/- 1.9 compared to 30.9 +/- 4.7 mU/l, P less than 0.01) and integrated GH levels (mean +/- SEM: 27.1 +/- 3.6 compared to 62.0 +/- 9.7 mU/l/h, P less than 0.01) were reduced in obese subjects. There was a negative correlation between the integrated GH response and the percentage ideal body weight (r = -0.80, P less than 0.05), but no significant correlation with somatomedin-C levels (r = +0.72; P = 0.07). Obese subjects have an impaired GH response to infusion of GH-releasing factor which is not related to negative feedback by somatomedins.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The GH response to a prolonged continuous infusion of human pancreatic growth hormone releasing factor (hpGRF 1-44), 0.3 microgram/kg/h was evaluated in seven patients with severe idiopathic GH deficiency, one patient with partial deficiency and in seven normal controls. Normal controls had a multiphasic response with a first peak between 15 and 90 min of 13.6 to 88.5, mean 45.6 mU/l and a second peak between 105 and 195 min of 8.8 to 73.1, mean 33.8 mU/l. However, the magnitude and pattern of response were highly variable. Six of the seven patients with severe GH deficiency had a response with a maximum level between 30 and 90 min of 3.3 to 7.5, mean 4.8 mU/l. Mean levels remained greater than 2.0 mU/l throughout the infusion but further peaks were absent or minimal. The patient with partial GH deficiency responded in a normal manner. hpGRF 1-44 by continuous infusion thus induced GH release in seven of eight patients with idiopathic GH deficiency though the response was impaired and the pattern of secretion abnormal in severely deficient patients.