Search PubMed⌕ Search

Biomedical subjects

B I Joffe

Publications and source records attributed to B I Joffe.

At least 73 records · Page 4Linked to original sources

Metabolic and hormonal responses to salbutamol in asthma. Evidence of beta-adrenergic overactivity?

The possibility that beta-adrenergic hyposensitivity may be involved in the pathogenesis of bronchial asthma remains a controversial issue. The hormonal, metabolic and cardiovascular responses to selective beta 2-adrenergic stimulation with salbutamol were compared in 11 asthmatic and 11 non-asthmatic subjects. There was no consistent difference between the two groups in the plasma free fatty acid, glucose and potassium responses, or in the cardiovascular variables studied, but the asthmatic patients demonstrated a marked dose-dependent hyperinsulinaemic response to salbutamol. Although this phenomenon cannot be accounted for with certainty, it may be a manifestation of pancreatic beta-adrenergic overactivity which would not be in keeping with the concept of generalised hyposensitivity of beta-adrenergic mechanisms in asthma. The present results provide a clear demonstration of the difficulties involved in attempts to relate extrapulmonary autonomic phenomena to the pathogenesis of bronchial asthma.

Albuterol↗

The hormonal response to exercise in asthma.

The hormonal responses to exercise of 10 asthmatic patients and 12 normal subjects were compared by studying the changes in the plasma levels of growth hormone, prolactin, adrenocorticotropic hormone (ACTH) and cortisol induced by treadmill running. The asthmatic patients demonstrated absence of the plasma cortisol response to exercise (peak increment -15 +/- 21 (SEM) vs 108 +/- 34 nmol.l-1 p less than 0.02). None of these patients were being treated with systemic corticosteroids and there was no difference between the responses of users and non-users of beclomethasone dipropionate. The results suggest the presence of an impaired adrenocortical response to the stress of physical exercise in asthma and indicate the need for detailed evaluation of hypothalamic-pituitary-adrenal function in patients with the disease.

Adrenocorticotropic Hormone↗

Natural history and cardiac manifestations of homozygous familial hypercholesterolaemia.

Forty-nine patients with homozygous familial hypercholesterolaemia (diagnosed on the basis of family history, xanthomatosis, total serum cholesterol and low-density lipoprotein receptor status) were studied over a period of 13 years, and underwent cardiovascular assessment. Eleven died, nine of myocardial infarction. Seven underwent coronary artery bypass, and another five had surgery to relieve supravalvular and valvular aortic stenosis. A distinctive pattern of disease was noted. Coronary ostial stenosis (four patients) and aortic root stenosis (six patients), both consequences of aortic root cholesterol deposition, were the typical manifestations of heart disease in childhood and adolescence. Adults developed severe coronary artery disease with a high incidence of main stem lesions (four of five patients). Surgery provided effective treatment for coronary artery disease and aortic outflow tract stenosis. Overall survival appeared to be better than reported in other studies which may reflect the 'receptor-defective' status of this group of patients.

Adolescent↗

Clinical and biochemical responses to nadolol and clonidine in hyperthyroidism.

Some features of hyperthyroidism mimic sympathetic nervous system overactivity. We have compared the clinical (scored on the Wayne Therapeutic Index), hemodynamic (blood pressure and heart rate) and biochemical (plasma epinephrine, norepinephrine, glucose, free fatty acids, insulin, growth hormone and free thyroxine index) effects of clonidine (alpha 2-agonist, which reduces plasma catecholamine levels) with those of nadolol (non-selective beta adrenergic receptor antagonist) in ten female hyperthyroid patients. Each patient received nadolol for 1 week followed by clonidine for 1 week in a single-blind manner. All measurements were made before treatment and then repeated at the end of the nadolol and clonidine treatment periods. Thyroid function remained unaltered during the study. Both agents caused significant clinical improvement--the mean Wayne Index score was 18 pretreatment, 2 on nadolol and 6 on clonidine (P less than .003 for each). Heart rate was reduced by both drugs, but blood pressure was unchanged. Side effects occurred in eight out of ten patients while on clonidine. Nadolol increased plasma concentrations of epinephrine from 47 +/- 18 pg/mL to 87 +/- 24 pg/mL, and norepinephrine from 241 +/- 154 pg/mL to 338 +/- 224 pg/mL (P less than .001 for each). In contrast, clonidine depressed norepinephrine levels from 241 +/- 154 pg/mL to 110 +/- 49 pg/mL (P less than .001) without lowering plasma epinephrine significantly. Plasma free fatty acids tended to fall on both agents compared to pretreatment levels. The blood glucose, insulin and growth hormone concentrations were unaffected by either drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Treatment of hypercholesterolemia with the HMG CoA reductase inhibitor, simvastatin.

We report the results of a two center study on the use of the HMG Co A reductase inhibitor, simvastatin, in 44 patients suffering from familial hypercholesterolemia or from primary hypercholesterolemia of unknown etiology. The study included two separate phases: Phase I was part of a multicenter, 4-week, placebo-controlled trial; phase II was a 6-month, open extension trial, the object of which was to reduce low density lipoprotein (LDL) cholesterol levels to below the 50th percentile by increasing the dose of simvastatin, by the use of additional lipid-lowering medication, or both. Our phase I results were commensurate with those reported for the entire international cohort of 272 patients, indicating a clear dose-response relationship, with approximately 75% of the maximum reduction in LDL-C levels being achieved with 20 mg/day and over 90% of the maximum being achieved with 40 mg of simvastatin per day. In the open extension trial, the results from the 2 centers were essentially similar. Total cholesterol fell by 29% on the 20 mg/day dose and by 34% on the full dose of 40 mg/day. LDL-C levels were reduced by 40% on the 40 mg/day schedule, and triglycerides also fell to between 20% and 40% below baseline values. HDL-C concentration rose by 14% and 17.6%. The effects of simvastatin were uniform, both within and between the two cohorts. The addition of cholestyramine caused a further substantial reduction in LDL-cholesterol to below 55% of the initial value in four patients, whereas bezafibrate further enhanced the fall in triglycerides and the increase in high-density lipoprotein cholesterol, but had only a slight effect on LDL-C levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Determination of cholesterol and triglycerides in blood: a comparison between wet chemistry methods and a dry chemistry analyser.

Total cholesterol and triglyceride concentrations in 127 samples of capillary and venous blood were measured with the portable Reflotron 'dry chemistry' reflectometer and compared with serum levels measured in the laboratory using wet chemistry methods. Results were grouped into low, middle and high ranges. Levels measured with the Reflotron correlated closely with those measured by wet chemistry methods. Reflotron values for both lipid fractions were, however, consistently higher than wet chemistry levels but the differences were small except at high levels. It is concluded that the Reflotron is a satisfactory instrument for providing clinically useful measurements of cholesterol and triglyceride nearer to the patient.

Cholesterol↗

Nocturnal events related to "morning dipping" in bronchial asthma.

The mechanism of early morning bronchospasm in asthma was investigated by analyzing circadian variations in the plasma levels of cortisol, ACTH, epinephrine, and norepinephrine, as well as in the serum neutrophil chemotactic activity and heart rate in asthmatic patients with (n = 6) and without (n = 7) "morning dipping" and normal subjects. Findings suggested that an exaggerated nocturnal nadir in plasma cortisol levels may precipitate "morning dipping" in some patients with asthma.

Adrenocorticotropic Hormone↗

Plasma C-peptide and insulin responses to intravenous glucagon stimulation in idiopathic haemochromatosis.

Beta-cell reserve was investigated in 15 patients with proven idiopathic haemochromatosis (IHC) (7 normoglycaemic haemochromatotic patients, 4 non-insulin-requiring diabetics and 4 insulin-requiring diabetics) by measuring the response of plasma C-peptide, insulin and glucose to a 2 mg intravenous bolus of glucagon, and compared with that in 5 lean normal subjects. The corresponding C-peptide/insulin molar ratios were also calculated. Despite the significant fasting hyperglycaemia in the insulin-requiring haemochromatotic diabetics, mean fasting C-peptide concentrations were similar in all four groups. However, after glucagon stimulation the C-peptide response was significantly reduced in the insulin-requiring group over the whole period of observation. A trend in insulin response to glucagon was noted, with the highest values in the non-diabetic haemochromatotic patients, followed by the controls and then by the non-insulin-requiring diabetics, although there were no significant differences. In contrast, C-peptide/insulin molar ratios after glucagon were significantly reduced in the normoglycaemic IHC group. These results suggest the presence of at least two abnormalities of insulin metabolism in IHC--a progressive reduction in beta-cell function and a diminished rate of removal of insulin by the liver.

Adult↗

The early biochemical and hormonal profile of patients with long bone fractures at risk of fat embolism syndrome.

Free fatty acids (FFA) are believed to play a role in the genesis of the fat embolism syndrome (FES). Levels of plasma FFA, glucose, insulin, and the stress hormones cortisol, growth hormone, prolactin, glucagon, and catecholamines were measured on admission to hospital in: a) 14 patients with long bone fractures at risk of developing FES, b) 14 patients with soft-tissue injuries of comparable severity, and c) 20 healthy fasting subjects. The findings were similar in both groups of injured patients and in keeping with the hormonal and substrate responses to the stress of trauma; plasma FFA levels were raised but in neither group was the rise pronounced. Plasma FFA levels of the fracture patients were only moderately higher than the values of the healthy fasting subjects. These findings suggest that mobilized FFA from peripheral adipose tissue are not important in the genesis of the FES, but do not exclude a role for FFA derived mainly from hydrolysis of triglyceride emboli in the lung.

Adolescent↗

Clonidine and the hormonal responses to graded exercise in healthy subjects.

The aim of this study was to assess the acute effects of clonidine, an alpha 2-adrenergic agonist, on hormonal responses to graded exercise in 8 healthy young men. After fasting overnight, each subject was tested on 2 mornings, 1 week apart. On one occasion he was given 200 micrograms clonidine orally and on the other identical placebo tablets, the order being randomized in a double-blind fashion over the 2 days. Thereafter each subject performed 2 successive treadmill runs, equivalent to 60 and 100%, respectively, of maximal aerobic power. Clonidine pretreatment blunted the maximal increase in plasma catecholamines by more than 60% of the control response (p less than 0.01), without significantly altering the rise of plasma cortisol or ACTH. Furthermore, clonidine significantly reduced the exercise-induced maximal rise in plasma glucose, without modifying the slight decline in mean plasma insulin or increase in pancreatic glucagon levels. The drug did not affect the maximal increments in plasma growth hormone or prolactin occurring after exercise. It was concluded that a single dose of clonidine suppressed peripheral sympathetic responses, without altering central (pituitary) alpha-adrenergic-mediated hormonal responses, to short-term exercise in healthy men.

Adrenocorticotropic Hormone↗

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↗