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Biomedical subjects

H C Seftel

Publications and source records attributed to H C Seftel.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1992

Identification and properties of the proline664-leucine mutant LDL receptor in South Africans of Indian origin.

The incidence of familial hypercholesterolemia (FH) is high among South African Indians. The proline664-leucine low density lipoprotein (LDL)-receptor mutation was detected in four apparently unrelated Indian FH families in South Africa. This mutation was originally described in an FH subject (MM) of Indian (Gujerat province) origin (Soutar et al. 1989. Proc. Natl. Acad. Sci. 86: 4166-4170). All four South African families trace their origin to the vicinity of Surat in the Gujerat province of India. Haplotype analyses revealed that both LDL receptor genes in one of the homozygous patients are the same as those in the subject MM. The phenotype of the mutant protein was analyzed in skin fibroblasts of homozygous patients. [35S]methionine pulse-chase experiments revealed that the receptor precursors were slowly processed to mature receptors. Mature mutant receptors were degraded at faster than normal rates. This mutation, which is in the epidermal growth factor (EGF)-precursor-like domain of the LDL receptor, was previously reported to yield binding-defective receptors. Here we report that the affinity of the mutant LDL receptor for both LDL and beta-very low density lipoprotein (beta-VLDL) was normal and that the steady-state level of mutant receptors was about 20% of normal. Thus, the disease FH in these subjects is presumably due to the low steady-state level of receptor molecules that are functionally normal but exhibit accelerated turnover.

Adolescent↗
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↗
PubMed1991

A common Lithuanian mutation causing familial hypercholesterolemia in Ashkenazi Jews.

Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the low-density-lipoprotein (LDL) receptor. Here we characterize an LDL-receptor founder mutation that is associated with a distinct LDL-receptor haplotype and is responsible for FH in 35% of 71 Jewish-Ashkenazi FH families in Israel. Sixty four percent (16/25) of the Ashkenazi patients who carry this mutant allele were of Lithuanian origin. The mutation was not found in 47 non-Ashkenazi FH families. This mutation was prevalent (8/10 FH cases) in the Jewish community in South Africa, which originated mainly from Lithuania. The mutation, a 3-bp in-frame deletion that would result in the elimination of Gly197, has been previously designated FH-Piscataway. PCR amplification of a DNA fragment that includes the mutation in heterozygous individuals results in the formation of a heteroduplex that can be demonstrated by PAGE and used for molecular diagnosis.

Alleles↗
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

Initial hormonal and metabolic profile in critically ill patients with community-acquired lobar pneumonia.

A prospective study of 18 critically ill patients with community-acquired lobar pneumonia was undertaken at Hillbrow Hospital, Johannesburg, in order to document the initial plasma hormonal and substrate profile as part of the stress response to the infection. The results of these studies, carried out before therapy, were compared with the results in a group of healthy fasting adults. Highly significant (P less than or equal to 0.005) increases in the mean plasma levels of adrenaline, noradrenaline, human growth hormone, cortisol, glucose and free fatty acids were noted in the study group, with a lesser increase in the prolactin concentration (P less than or equal to 0.01). The levels of dopamine, glucagon, insulin and adrenocorticotrophin did not show any significant change. No significant differences were found in the hormonal profile when comparing survivors with non-survivors. The neuro-endocrine hormonal and metabolic responses in pneumonia appear to be similar to those seen in other stress situations and failure of the initial stress response does not appear to contribute to the mortality of critically ill patients with community-acquired lobar pneumonia.

Adult↗
PubMed1989

Prevalence of familial hypercholesterolemia in Johannesburg Jews.

The prevalence of heterozygous familial hypercholesterolemia was determined in a representative sample of 403 young Jewish men resident in Johannesburg, South Africa. Preliminary screening by measurement of serum total cholesterol demonstrated that 25 of them had levels greater than or equal to 7.5 mmol/l (290 mg/dl). On the basis of subsequent clinical, biochemical, and family studies, 6 men, or about 1 in 67 of the total sample, were considered to be heterozygotes. This very high prevalence, about 7 times greater than that found in other Caucasian populations, is probably related to founder effect. It may help to explain the high frequency of coronary heart disease in Johannesburg Jews.

Adult↗
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↗
PubMed1989

Haplotypes identified by 10 DNA restriction fragment length polymorphisms at the human low density lipoprotein receptor gene locus.

Ten useful two allele restriction fragment length polymorphisms of the low density lipoprotein receptor gene were used for haplotype analysis in 45 unrelated familial hypercholesterolaemic (FH) patients, 60 normal controls, and 32 FH homozygotes, all of whom were white Afrikaners. Pedigree analysis in 27 informative heterozygous FH and 23 normal families has shown the segregation of at least 17 haplotypes in the normal population (111 chromosomes) compared to a predominant association of two of these haplotypes with the disease in the FH subjects. This association was further confirmed in 32 FH homozygotes, indicating at least two 'founder' members for the disease in the Afrikaner population. Recombination events were not detected in any of the families studied and we thus conclude that the haplotypes associated with FH function as specific markers for the disease and will allow presymptomatic diagnosis in affected families.

Adolescent↗
PubMed1988

Action limits for serum total cholesterol. A statement for the medical profession by an ad hoc committee of the Heart Foundation of Southern Africa.

Hypercholesterolaemia is common in many segments of the South African population, both by virtue of high mean population serum total cholesterol (TC) values and of a high prevalence of familial hypercholesterolaemia (FH). Age-specific action limits for TC are proposed in order to remove the variation in 'normal values' used by different laboratories. The action limits are derived from epidemiological studies rather than purely statistical norms. They are used to designate individuals as falling into high, moderate and ideal TC ranges. The high-risk action limit has also proved to be useful for screening for FH. After an initial screening TC estimation, the further management of a patient will depend on the TC risk category and the presence or absence of other risk factors. Risk factors such as hypertension, a smoking habit, a low high-density lipoprotein cholesterol value, diabetes, evidence of existing coronary heart disease (CHD) or a family history of premature CHD multiply the risk conferred by elevated TC, and change the moderate-risk status of an individual with moderately elevated TC to a high-risk status. Intensity of investigation, treatment and follow-up depend on the overall risk status of an individual patient. Drug therapy is reserved for high-risk patients who have not responded to a reasonable trial of non-drug measures. Other reversible risk factors are treated in their own right. The guidelines embodied in this report are intended to facilitate and justify the clinical approach to individual patients with hypercholesterolaemia. They do not replace the need for a population strategy to reduce risk factors in the general population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Solubility changes on mixing short- and long-acting insulin preparations.

The loss of solubility of short-acting insulins when mixed in a ratio of 1:1 with intermediate-acting insulins in vitro was determined using high-performance liquid chromatography. Insulin preparations (porcine and human) from three different manufacturers were tested and various times of mixing (0-24 h) were investigated. The loss of solubility with mixtures of human insulins and with mixtures of porcine Velosulin (Nordisk) and Insulatard (Nordisk) was small at all the times used. A mixture of porcine Actrapid MC (Novo) and Monotard MC (Novo) led to a 60-95% loss of the soluble component, depending on the duration of mixing. The greater the time the greater the loss. These in vitro data indicate that short-acting insulins may lose solubility when mixed with long- or intermediate-acting ones. This phenomenon could be clinically relevant when patients are changed from mixtures of monocomponent to human insulins.

Drug Combinations↗