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Biomedical subjects

B I Joffe

Publications and source records attributed to B I Joffe.

At least 19 recordsLinked to original sources
PubMed1992

Pathogenesis of non-insulin-dependent diabetes mellitus in the black population of southern Africa.

Non-insulin-dependent diabetes mellitus (NIDDM) is an important health problem in the black population of southern Africa. Whether the primary cause of NIDDM is insulin secretory dysfunction or peripheral insulin resistance is unknown. In westernised populations it is believed that insulin resistance and hyperinsulinaemia occur in the early stages of disease, followed later by progressive impairment of insulin secretion. However, we suggest that in the southern African black population a decrease in the mass of functioning beta cells is an important event, making these people vulnerable to the deleterious effects of insulin resistance induced by obesity and other factors. These abnormalities are, in turn, associated with insulin receptor down-regulation. An accelerated decline in beta-cell function then follows in susceptible individuals, ultimately producing striking insulinopenia. Insulinopenic NIDDM in black southern Africans may partly explain why this population has a comparatively low incidence of macrovascular complications and also predicts a short-lived therapeutic response to oral sulphonylureas in most patients.

Black or African American↗
PubMed1992

Autonomic dysfunction in systemic sclerosis: sympathetic overactivity and instability.

PURPOSE: This study was designed to assess the prevalence and nature of autonomic dysfunction (AD) in 34 patients with systemic sclerosis (SSc). PATIENTS AND METHODS: Patients were questioned for current symptoms possibly related to AD. Five noninvasive cardiovascular autonomic function tests and sequential plasma catecholamine estimations at rest, during standing, and during sustained handgrip were performed. Seven patients with manometrically documented esophageal involvement and high resting plasma adrenaline levels were treated with clonidine (75 to 375 micrograms/d). One month later, resting plasma catecholamine estimations and esophageal motility studies were repeated. RESULTS: Autonomic testing revealed AD in each patient, while symptoms were experienced by 33 of them. Findings on two of the three heart rate tests and both blood pressure tests were significantly impaired as compared with those in 25 matched control subjects. Mean resting plasma adrenaline levels were 18 times higher than in 10 matched controls (p less than 0.001). Plasma catecholamine (adrenaline, noradrenaline, and dopamine) concentrations and mean arterial blood pressures fluctuated inappropriately during standing and sustained handgrip in 28 (82%) of the patients. The presence of headaches correlated significantly with sympathetic overactivity and instability (p less than 0.05). Resting plasma adrenaline concentrations correlated inversely with disease duration (p less than 0.05). Significant suppression of sympathetic overactivity and increases in resting lower esophageal sphincter pressures were observed in the seven patients treated with clonidine. CONCLUSION: AD is extremely common in SSc. It is characterized by parasympathetic impairment and marked sympathetic overactivity, particularly in early disease. The potential role of AD in the pathogenesis of SSc deserves further study.

Adult↗
PubMed1992

Insulin-receptor activity in nondiabetic and diabetic urbanized South African black women.

OBJECTIVE: To evaluate insulin receptor binding characteristics of urbanized South African black women with normal glucose tolerance and of patients with newly diagnosed untreated non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Four groups of 10 subjects each were selected by the following criteria: group A, young (20-39 yr) nonobese (body mass index [BMI] 19.0-24.9 kg/m2) nondiabetic women; group B, middle-aged (40-60 yr) nonobese nondiabetic women; group C, middle-aged obese (BMI greater than 30.0 kg/m2) nondiabetic women; and group D, middle-aged obese newly diagnosed but untreated female patients with NIDDM. Insulin binding to monocyte receptors was determined by radioreceptor assay. Fasting plasma samples were analyzed for glucose, insulin, C-peptide, and nonesterified fatty acids. RESULTS: In the four groups studied, maximum specific binding and receptor concentration were highest in group A, with a progressive and significant decrease in values through groups B and C to group D. Significant inverse correlations were obtained between maximum specific binding, 50% inhibition dose, and total receptor concentration on the one hand and glucose, insulin, and NEFA on the other. CONCLUSIONS: Our study of urban South African black women showed decreasing insulin-receptor activity with obesity and glucose intolerance. In patients with NIDDM, hyperglycemia and beta-cell dysfunction were associated with a reduction in receptor concentration. In this regard, our findings in South African blacks are consistent with results of similar studies of NIDDM in other communities.

Adult↗
PubMed1992

Relationship between plasma insulin and blood pressure in South African black women in Johannesburg.

OBJECTIVE: To examine the relationship between fasting plasma insulin and blood pressure (BP) in 40 urbanized normotensive South African black women aged 24-60 yr, and to assess the effects of body mass index (BMI) and fasting plasma glucose on BP. RESEARCH DESIGN AND METHODS: The women comprised equal numbers of young nonobese nondiabetic subjects, middle-aged nonobese nondiabetic subjects, middle-aged obese nondiabetic subjects, and middle-aged obese newly diagnosed non-insulin-dependent diabetic subjects. Systolic and diastolic BPs were recorded (in duplicate) after 15 min of recumbency, and fasting plasma glucose and insulin levels were determined thereafter. The data were analyzed by simple and multivariate regression. RESULTS: There was a wide distribution of individual physical and biochemical features. With simple correlations, systolic BP correlated significantly with age, BMI, and fasting glucose but not with insulin. Diastolic BP correlated significantly with all four variables (r = 0.37, P less than 0.05). When adjusted for age, BMI, and glucose, however, the significant correlation between diastolic BP and insulin diminished (r = -0.04). CONCLUSIONS: As in other nonwhite communities, plasma insulin does not appear to play a major role in regulating the BP of South African black women.

Adult↗
PubMed1991

Glycaemic responses to different carbohydrate foods in healthy and diabetic blacks in Soweto.

Diabetes mellitus is uncommon in rural southern African blacks. With urbanisation and lifestyle changes, incidence rises to that in western populations. To assess associated changes in carbohydrate metabolism, glycaemic responses to glucose, refined maize, refined rice and bread were studied in 8 healthy and 8 non-insulin-dependent diabetic urban blacks. Additionally, in the healthy group serum insulin responses were measured. In the healthy, maize (the staple food of blacks) elicited the highest glucose response (207 mmol/l/min) and bread the lowest (107 mmol/l/min). The glycaemic indices of maize and glucose were similar. Serum insulin responses to maize were significantly lower than that of bread at 90 minutes (maize 66 muU/ml; bread 93 muU/ml; P = 0.02). In diabetics, maize and glucose elicited similar glycaemia (928 mmol/l/min and 921 mmol/l/min respectively). The high glucose response to maize could relate to its processing and physical form. The low insulin secretion could be due to inadequate stimulation by the 'entero-insular' axis. Moreover, variability in glucose insulin responses could stem from ethnic or genetic reasons. In the dietary management of black diabetics, refined maize should be replaced by other cereals.

Adult↗
PubMed1991

Hypoglycemia in hepatocellular carcinoma: failure of short-term growth hormone administration to reduce enhanced glucose requirements.

The mechanism of tumor-associated hypoglycemia was investigated in 10 (six hypoglycemic and four normoglycemic) southern African blacks with hepatocellular carcinoma. The mean basal blood glucose concentration was significantly lower (2.4 +/- 0.1 v 3.6 +/- 0.2 mmol/L; P less than .01) and steady-state exogenous glucose requirements were increased fourfold (3.6 +/- 0.6 v 0.97 +/- 0.2 mg/kg/min; P less than .01) in the hypoglycemic compared with the normoglycemic patients. Plasma insulin and C-peptide levels were suppressed to the lower limit of sensitivity of each of the assays in both groups of patients. The concentrations of insulin-like growth factors (IGF) I and II were lower (19 +/- 1.6 v 25 +/- 4.6 insulin-like growth factors (IGF) I and II were lower (19 +/- 1.6 v 25 +/- 4.6 ng/L) and higher (230 +/- 42 v 173 +/- 40 ng/L), respectively, in the hypoglycemic patients, although the differences were not statistically significant. Of the counterregulatory hormones measured, only the growth hormone (GH) concentration was significantly lower in the hypoglycemic patients (0.9 +/- 0.2 v 18.6 +/- 5.6 micrograms/L; P less than .01). Correction of the plasma GH level into the high-normal physiological range in two hypoglycemic patients failed to reduce steady-state exogenous glucose requirements. However, the glucose requirements were reduced from 2.6 to 1.1 mg/kg/min in the same two patients when "acromegalic" plasma concentrations of GH were achieved. We conclude that steady-state glucose requirements are increased in black patients with hypoglycemia complicating hepatocellular carcinoma, and that short-term correction of the associated hyposomatotropism fails to reduce the enhanced requirements.

Blood Glucose↗
PubMed1990

The effect of magnesium sulphate infusion on circulating catecholamine levels in severe gestational proteinuric hypertension. A report of 8 cases.

The effect of magnesium sulphate (MgSO4) infusion on blood pressure and circulating venous catecholamine levels in 8 patients with severe gestational proteinuric hypertension is described. A significant fall in blood pressure was noted after MgSO4 infusion; the maximal fall in diastolic blood pressure correlated with the greatest rise in serum magnesium levels (P less than 0.04). No significant change was observed in mean venous plasma adrenaline or noradrenaline levels after MgSO4 infusion, although the mean dopamine concentration declined significantly. It is concluded that the decrease in systemic vascular resistance after MgSO4 infusion in gestational proteinuric hypertension is mediated predominantly by mechanisms other than a change in circulating catecholamine levels.

Adult↗
PubMed1990

Methaemoglobinaemia due to accidental sodium nitrite poisoning. Report of 10 cases.

Nitrates and nitrites are widely used in the food and chemical industry. Poisoning with these agents may be potentially life-threatening as a result of the production of methaemoglobin. A group of 10 patients suffering from moderate to severe methaemoglobinaemia after accidental intoxication with a sodium nitrite salt is described. One patient died but the other 9 recovered rapidly. The low mortality rate was attributed to prompt diagnosis and institution of appropriate therapy with methylene blue and ascorbic acid.

Adult↗
PubMed1990

Growth hormone response to exercise in asthmatic and normal children.

Maximal growth hormone (GH) increments following exercise were compared in asthmatic (n = 14) and normal (n = 8) children. Exercise, which consisted of 6 min ergometer cycling while breathing cold dry (CD) air, induced asthma in all asthmatic patients but not in normal subjects. Baseline plasma GH levels were similar in both groups. Following exercise, however, asthmatic patients had significantly higher mean GH increments than normal subjects (14.8 vs 4.9 ng/ml, P less than 0.025). To evaluate the possible role of bronchoconstriction in the GH response all subjects exercised again, this time while breathing warm humid (WH) air. Despite the absence of exercise-induced asthma (EIA) while breathing WH air, asthmatic patients still had significantly higher mean GH increments than normal subjects (9.2 vs 2.3 ng/ml, P less than 0.05). We conclude that some asthmatic children show excessive GH secretion after exercise regardless of inspired air conditions or the development of EIA.

Adolescent↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1979

Recurrent hypoglycemia associated with glutaric aciduria type II in an adult.

Repeated episodes of hypoglycemia accompanied by elevated serum concentrations of free fatty acid without ketosis, fatty infiltration of the liver, hepatic dysfunction, and proximal myopathy in a 19-year-old woman, prompted us to analyze her urine for organic acids. Greatly increased quantities of glutaric acid, ethylmalonic acid, dicarboxylic acids with six to 10 carbons, and isovalerylglycine were consistently found in her urine. The ability of cultured skin fibroblasts from the patient to oxidize [1(-14)C]butyrate and [2(-14)C]lysine was reduced. These urinary and in vitro findings indicated defective activity of several acyl coenzyme A dehydrogenases, including glutaryl, isovaleryl, and butyryl coenzyme A dehydrogenases -- establishing a diagnosis of glutaric aciduria Type II. Carnitine concentrations in the skeletal muscle and liver were moderately reduced, but carnitine deficiency was considered a secondary biochemical abnormality. Although glutaric aciduria Type II has previously been described only in a neonate, the disease must be considered in the differential diagnosis of hypoglycemia in adults.

Adult↗
PubMed1979

Haemostatic factors in Black and White diabetics.

Haemostatic factors in 33 Black and 32 White maturity-onset diabetics were analysed and compared with those in 19 normal Black and 19 White subjects. The Black-White diabetic group comparisons revealed depressed antithrombin (AT) III functional activity, a raised factor VII level and a raised factor V level in females in the White diabetic group. On comparing the White diabetics with their respective controls a rise in factor VIII and fibrinogen activity was demonstrated. These changes are suggestive of a hypercoagulable state in the White maturity-onset diabetic. In contrast, Black diabetics have higher functional AT III levels than their respective controls. This may indicate a protective reaction which would explain in part the reported lower incidence of occlusive vascular disease in this group. Platelet hyperactivity was not demonstrated in the majority of White and Black diabetics. Black diabetics and controls demonstrated higher factor VIII levels than the corresponding White groups, confirming previous observations of raised factor VIII levels among Blacks and suggesting that this feature is a racial characteristic.

Adult↗
PubMed1979

Treatment of familial hypercholesterolaemia by partial ileal bypass.

Ten patients with heterozygous familial hypercholesterolaemia (Fredrickson type II) were treated by the operation of partial ileal bypass. Postoperatively, serum cholesterol levels fell by an average of 34% (P less than 0.005), and the decrease was satisfactorily sustained over a period of 12-30 months. Angina and xanthomas also improved in some patients. Postoperatively all patients experienced considerable diarrhoea, which lessened with time. Other complications of surgery included abdominal distension and cramps, colonic dilatation, sepsis and intestinal obstruction. It is concluded that partial ileal bypass significantly lowers serum cholesterol levels, but that in view of the complications the operation should be offered only to carefully selected patients who are intolerant of or unresponsive to conservative measures.

Adult↗