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Biomedical subjects

L Lazarus

Publications and source records attributed to L Lazarus.

At least 73 records · Page 4Linked to original sources
PubMed1979

Development of a closed-loop artificial pancreas.

A closed-loop glucose controlled insulin infusion system was developed, consisting of elements for continuous blood glucose analysis, a computer control system, and infusion systems. Improvements include decreased size, cost reduction and better performance. The algorithm used was a piecewise linear representation of the sigmoidal curve commonly employed. The apparatus has been applied to simulation of the healthy beta cell and glucose clamp studies.

Artificial Organs↗
PubMed1978

Circulating thyroid hormone levels and adequacy of dialysis.

In vitro thyroid function tests were performed in three groups of patients with chronic renal failure who were receiving, on average, 15, 18 and 27 hours of maintenance hemodialysis per week. Total thyroxine levels were low and total triiodothyronine levels low to normal in those receiving the least dialysis (15 hours), and were significantly higher in those receiving longer dialysis. Free thyroxine levels, as measured by the effective thyroxine ratio, were normal and similar in all three groups, as were serum thyrotrophin levels. All patients were clinically euthyroid. As total hormone levels showed a significant inverse relationship to both urea and creatinine, this study suggests that there is a dialyzable metabolite retained in uremia which competes with thyroid hormones for protein-binding sites.

Adult↗
PubMed1977

Defective blood glucose counter-regulation in diabetics is a selective form of autonomic neuropathy.

Administration of a low-dose insulin infusion to normal subjects results in a mild drop in blood glucose concentration (1.1 mmol/1 (20 mg/100 ml)) and the resetting of the basal glucose at the lower concentration. Clinical hypoglycaemia does not develop, and there is a significant release of glucagon, growth hormone, and cortisol. A similar infusion in insulin-requiring diabetics results in hypoglycaemia accompanied by a release of growth hormone and cortisol but no significant release of glucagon. Subsequently giving arginine to these patients results in a significant release of glucagon, indicating that the alpha cell is intact and can respond to local, direct stimulation. In one patient the defect in glucagon response to impending hypoglycaemia developed after two years' insulin treatment. This type of dissociated response' of the alpha cell has been reported in animals after denervation of the pancreas, and insulin-requiring diabetics may develop a selective form of autonomic neuropathy affecting the vagal control of glucagon release.

Adult↗
PubMed1977

Depressed lymphocyte function after bereavement.

During 1975 twenty-six bereaved spouses took part in a detailed prospective investigation of the effects of severe stress on the immune system. T and B cell numbers and function, and hormone concentrations were studied approximately 2 weeks after bereavement and 6 weeks thereafter. The response to phytohaemagglutinin was significantly depressed in the bereaved group on the second occasion, as was the response to concanavalin A at 6 weeks. There was no difference in T and B cell numbers, protein concentrations, the presence of autoantibodies and delayed hypersensitivity, and in cortisol, prolactin, growth hormone, and thyroid hormone assays between the bereaved group and the controls. This is the first time severe psychological stress has been shown to produce a measurable abnormality in immune function which is not obviously caused by hormonal changes.

Adult↗
PubMed1977

Pituitary adenomas and dyspituitarism.

Recent studies of the structure and function of pituitary adenomas reveal that the majority are functional and that the commonest type is a prolactin secreting adenoma. Studies of hypothalamic-pituitary function provide evidence to suggest that the adenoma develops following prolonged hypothalamic stimulation of the pituitary gland, and that the clinical dyspituitarism is due to the hypothalamic-pituitary dysfunction and not to pituitary destruction by the adenoma. Pituitary adenomas may be classified into those due to a basic neuroendocrine dysfunction (prolactin secreting, acromegaly, Cushing's disease) and those arising secondary to end-organ failure (TSH and FSH secreting). The former group have APUD characteristics and may form part of a pluriglandular syndrome of apudomas. The persistence of a basic neuroendocrine dysfunction following the surgical removal of an adenoma explains the frequent recurrence of symptoms in patients and indicates a need for continued surveillance and long-term therapy.

Acromegaly↗
PubMed1977

Effects of triiodothyronine administration in patients with chronic renal failure.

Clinically euthyroid patients with severe, chronic, non-thyroidal illnesses usually have decreased serum total and absolute free T3 concentrations. Since T3 is the metabolically more active of the two thyroid hormones, it has been suggested that these patients may be hypothyroid and thus may benefit from T3 therapy. To test this hypothesis, five patients with chronic renal failure requiring maintenance haemodialysis were treated with 5 microgram T3 eight hourly, increasing at three weekly intervals to 10 microgram eight hourly, 20 microgram eight hourly and finally 30 microgram eight hourly. The mean +/- SD serum T3 level did not change over the 12 week period (1.42 +/- 0.17 vs. 1.41 +/- 0.26 nmoll-1 whilst the mean serum T4 and TSH levels fell from 87.0 +/- 15.2 to 47.5 +/- 18.8 nmoll-1 and 1.9 +/- 0.9 to 1.3 +/- 1.6 mUl-1 respectively. Only the change in T4 levels was significant (P less than 0.005). A significant decrease in mean serum T4 levels was apparent even after the treatment period with 5 microgram T3 eight hourly (87.0 +/- 15.2 vs. 51.2 +/- 15.7; P less than 0.005). The mean fasting serum triglyceride level fell from 1.16 +/- 0.74 to 0.94 +/- 0.74 mmoll-1 (P less than 0.05) and the mean fasting serum cholesterol level fell from 6.06 +/- 1.13 to 4.69 +/- 1.10 mmoll-1 (P less than 0.05). There were no subjective improvements in any of the patients. From the marked changes in serum T4 levels during the administration of T3, it is concluded that, prior to treatment, the patients were biochemically euthyroid and not hypothyroid and thus did not require T3 therapy.

Adult↗
PubMed1977

Control of blood glucose in diabetics using an artificial pancreas.

Studies have been performed using an on-line computer system programmed for blood gucose control of insulin and dextrose infusion (artificial pancreas). The aim of these studies was to test performance of the artificial pancreas and to suggest directions for future optimisation. Blood glucose stabilisation studies of diabetic volunteers were extended throughout the day and included three main meals and light exercise periods. Monitoring of blood glucose profiles of the same diabetics after depot insulin were performed on a separate occasion for comparison. The presence of insulin antibodies did not impair operation of the artificial pancreas. Most of the insulin infused by the artificial pancreas was to initially correct hyperglycaemia with relatively little required to subsequently maintian euglycaemia. The afternoon intra-meal average infusion rate was 0-9 U/hr. It is suggested that correction of fasting hyperglycaemia and maintenance of euglycaemia in diabetics be treated as separate control problems for the artificial pancreas. The overall ability of the artificial pancreas to control blood glucose to a degree not attainable by conventional insulin therapy is confirmed, in this case under conditions which include patient activity.

Adult↗
PubMed1976

Routine use of low-dose intravenous insulin infusion in severe hyperglycaemia.

A review if presented of the use of low-dose insulin infusion in the management of 58 episodes of severe diabetic hyperglycaemia. Neutral insulin in a dosage of 2-4 units per hour is infused via a paediatric giving set to achieve a sustained physiological elevation of insulin levels. This method is safe, simple and rapidly effective in lowering the blood glucose level, the mean rate of fall (62 mg/100 ml/hr, or 11% per hour) being unaffected by prior insulin therapy, acidosis or ketonuria. Classification of the hyperglycaemia as ketoacidotic or hyperosmolar is unnecessary before insulin therapy is instituted, as the relative decline in glucose level is the same in the hyperosmolar non-ketotic group as in the others. Proven infection significantly lowers the rate of fall of glucose level. Hypoglycaemia and hypokalaemia are rare during low-dose infusion. Early and adequate replacement with potassium phosphate is recommended, oral potassium supplements being continued for several days. Bicarbonate therapy is rarely indicated in the management of acidosis. No patient had cerebral oedema during treatment, and one elderly patient with extensive pneumonia and empyema died during the infusion. It is suggested that continuation of low-dose insulin infusion, together with 5% dextrose solution, after the plasma glucose level reaches 200 mg/100 ml, may hasten the clearance of ketones, preventing relapse.

Adolescent↗
PubMed1976

Hyperprolactinaemia: its physiology and investigation.

Since the establishment of a sensitive and specific radioimmunoassay for serum prolactin levels, very rapid progress has been made in the understanding of the physiology of prolactin and its role in human disease. Hyperprolactinaemia is now known to be a common finding in many conditions. Up to 20% of women with unexplained functional secondary amenorrhoea have an elevated serum prolactin level. Reduction of serum prolactin levels to normal, by removal of a prolactin-secreting tumour or by treatment with bromoergocryptine, results in a restoration of normal menstrual cycles and fertility. This paper outlines the control of prolactin secretion and discusses the mechanisms which result in secondary amenorrhoea. A new method of investigation of hyperprolactinaemia is proposed which localizes the site of abnormality which results in an elevation of serum prolactin levels.

Adenoma, Chromophobe↗
PubMed1976

Somatomedin production in the neonatal rat.

The hormonal stimulus to rat fetal and neonatal somatic and skeletal growth has been investigated by a study of ciruclating somatomedin (SM), growth hormone (GH) and insulin levels in rats from 21 days in utero to 40 days of post natal life. Somatomedin activity could not be detected in the serum of fetal rats in which circulating GH and insulin levels were high. In early post natal life GH and insulin levels remained high but gradually declined reaching normal adult levels at 19 days and 40 days respectively. Somatomedin activity was measurable only at low levels until 11 days after birth and thereafter remained steady throughout the time period studied. These studies suggest that somatomedin alone is not responsible for the rapid growth of the rat in early neonatal life and it is suggested that insulin may also be active as a growth factor in this period.

Age Factors↗
PubMed1976

Inhibition of conversion of thyroxine to triiodothyronine in patients with severe chronic illness.

Many clinically euthyroid patients with severe, chronic, non-throidal illnesses (i.e. sick euthyroid patients) have very low circulating concentrations of total and absolute free triiodothyronine (T3), low-normal concentrations of total thyroxine (T4), elevated concentrations of absolute free T4, and circulating concentrations of thyrotrophin (TSH) that are either normal or subnormal. This study was undertaken to elucidate the mechanism of the low circulating T3 concentrations. The disappearance rate of 125 I-T3 from the circulation of five representative sick euthyroid patients was studied and found to be slower, but not significantly so, compared with three control subjects, thus excluding an increased destruction rate as the cause of the low T3 levels. A selective decrease of T3 secretion from the thyroid gland of these patients was also excluded by the results of TSH stimulation tests. Inhibition of extra-thyroidal conversion of T4 to T3 was suggested by studies of the thyroid function in a hypothyroid woman with a Grade IV lymphoma on T4 replacement therapy. When the lymphoma was in remission, her circulating T3 concentration was 2-55 nmol/l but when it relapsed it fell to 0-55 nmol/l. The T4 concentrations were 124-7 nmol/l and 126 nmol/1 respectively. Decreased monodeiodination of T4 to T3 in sick euthyroid patients was confirmed by paper chromatography of extracted serum obtained 48 h after an i.v. injection of 125 I-T4 into two severely ill patients from the intensive therapy unit and a control subject. Peaks of radioactivity corresponding to 125 I-T4 and 125 I-T3 were detected in the control subject, but only a single peak corresponding to 125 I-T4 was detected in the ill patients.

Chronic Disease↗
PubMed1976

A combined test of anterior pituitary reserve.

Determination of the functional reserve of the anterior pituitary gland requires the serial measurement of hormones released from the pituitary by specific stimuli. Individually, insulin-induced hypoglycaemia, thyrotrophin releasing hormone (TRH) and gonadotrophin releasing hormone (GnRH) have proved to be reliable stimuli for the release of the various pituary hormones. The maximum incremental hormone response of growth hormone, cortisol, luteinising hormone, follicle stimulating hormone, thyrotrophin, triiodothyronine and prolactin has been assessed after the simultaneous administration of insulin, TRH and GnRH in six normal subjects. These responses have been compared to previously determined responses in a normal population when insulin, TRH or GnRH have been given separately. There were no significant differences in the peak response or the maximum incremental response of any hormone. The test has been used to assess the pituitary reserve of 54 patients with disorders of the hypothalamic-pituitary axis, and five patients have been assessed both before and after hypophysectomy. The test is found to be convenient, sensitive and reliable in the assessment of pituitary reserve.

Acromegaly↗
PubMed1976

Growth hormone in exercise: comparison of physiological and pharmacological stimuli.

This study was designed to compare the serum growth hormone (GH) response with quantified exercise to that obtained with other stimuli. In eight normal males, aged 21-24 yr, we studied the serum GH response to 20 min cycle ergometer exercise at 300, 600, and 900 kpm/min on three separate occasions and compared the results with those found during sleep, insulin hypoglycemia, arginine infusion, and L-DOPA. Exercise at 900 kpm/min and insulin hypoglycemia resulted in the greatest elevations in serum GH which were significantly greater than those found with sleep, arginine or L-DOPA. The 20-min exercise at 900 kpm/min represented 75-90% of the subjects' maximal oxygen uptake and is a suitable provocative test for GH secretion. As a screening test for pituitary GH reserve, exercise compares favorably with insulin hypoglycemia and is superior to sleep, arginine, and L-DOPA.

Adult↗
PubMed1976

Biogenic amine control of growth hormone secretion in the fetal and neonatal rat.

The development of the hypothalamic-pituitary axis for growth hormone (GH) secretion has been studied in the rat fetus and in the neonate 4, 24, 48 and 72 h after birth. Injections of the serotonin blocker cyproheptadine (Cypro) and a catecholamine, dopamine (DA), each led to reductions in the level of serum GH in 21 to 22 day fetuses and in neonates up to 3 days after birth. The O-methylated derivative of dopamine, dimethoxyphenylethylamine (DMPEA), did not alter serum GH levels from those seen in saline-treated control animals. These results indicate that biogenic amines exert control over GH secretion in the fetus, close to term, and in early neonatal period. They suggest that this control is similar to that seen in the adult rat and in man and that such control may operate through serotonin receptors.

Animals↗