HDL cholesterol in familial hypercholesterolemia.
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Animals↗
Biomedical subjects
H C Seftel
Publications and source records attributed to H C Seftel.
The 8-hour metabolic profile after drinking ethanol.
The acute metabolic changes after drinking ethanol have been studied in 11 fasting, healthy, nonobese, medical students, 6 of whom consumed 40 g ethanol diluted with 750 ml of a sugar-free soft drink over 1 h. The other 5 drank the same volume of soft drink alone. Blood levels of ethanol, glucose, immunoreactive insulin and growth hormone were measured over the ensuing 8 h, as well as the plasma concentrations of prolactin, cortisol and triiodothyronine. After ingesting ethanol, the mean plasma glucose concentration declined, but not to hypoglycemic levels (the nadir was 3.9 mmol/l at 6 h), insulin levels fell gradually and the mean growth hormone concentration showed a modest late rise. Other hormones did not change significantly. We conclude that, in the particular setting examined, the oral administration of ethanol does not cause hypoglycemia or other adverse effects on carbohydrate metabolism.
Adult↗
Hormonal profile after insulin-induced hypoglycemia in chronic calcific pancreatitis. Pancreatic, pituitary and adrenal responses.
The present investigation defined the pattern of pancreatic, pituitary and adrenal responses after insulin-induced hypoglycemia in chronic calcific pancreatitis (CCP) related to alcohol abuse, and assessed the role of some of these hormones in the counterregulation of blood glucose. We studied 6 Black men with recently diagnosed CCP, all showing radiological evidence of pancreatic calcification and normal glucose tolerance, as well as 7 matched nonobese male controls. After a standard iv insulin tolerance test inducing marked hypoglycemia, patients with CCP showed significantly impaired mean plasma pancreatic glucagon and pancreatic polypeptide responses compared to the controls. Mean basal plasma somatostatin levels tended to be higher in chronic pancreatitis and remained so throughout the test without altering consistently; in the controls somatostatin peaked significantly at 30 min. Concerning extrapancreatic hormonal changes, plasma growth hormone, prolactin and total catecholamines responded normally in CCP, but plasma cortisol rose to significantly higher levels than controls at 60 and 120 min after the injection of insulin. This, coupled with the brisk output of catecholamines, may have prevented the heightened sensitivity to insulin anticipated because of their hypoglucagonemia. We conclude that patients with CCP show impaired pancreatic hormone release after insulin hypoglycemia with the exception of somatostatin; there is also an excessive rise in plasma cortisol, possibly related to the long standing abuse of alcohol in the past.
Adrenal Glands↗
Hyperglycaemia in infantile gastroenteritis.
The prevalence and pathogenesis of hyperglycaemia were investigated in a consecutive series of 27 black infants admitted to hospital with gastroenteritis over a period of three months. Hyperglycaemia (plasma glucose concentration greater than 10 mmol/l) occurred in 15 (55%) of these patients. The pathogenesis was not clear but possible contributory factors included raised concentrations of the stress hormones pancreatic glucagon, growth hormone, and cortisol; hypokalaemia; and peripheral insulin resistance. Intravenous rehydration, without insulin, corrected the plasma glucose concentrations and restored the hormonal profile towards normal within 36 to 48 hours.
Child, Preschool↗
Familial hypercholesterolaemia: esterification of cholesterol in lymphocytes from homozygous and heterozygous subjects.
A comparative study of the rates of cholesterol esterification in lymphocytes from healthy subjects and patients with familial hypercholesterolaemia (25 heterozygotes and 10 homozygotes) was carried out. Freshly isolated lymphocytes were incubated at 37 degrees C in medium containing lipoprotein-deficient serum and [3H]oleate-albumin was extracted, isolated by thin layer chromatography and quantitated. Incorporation of [3H]oleate into cholesteryloleate was significantly higher in lymphocytes from both heterozygotes and homozygotes than in cells from normal subjects; there was no significant difference between the values for heterozygotes and homozygotes. For all three groups cholesteryloleate formation was dependent on the concentration of lipoprotein-deficient serum in the medium.
Adolescent↗
Alcohol-potentiated reactive hypoglycaemia depends on the nature of the carbohydrate ingested at the same time.
Alcohol may provoke reactive hypoglycaemia when drunk with a sucrose mixer (gin and tonic) but not in the form of a starch-based beverage. In the present study alcohol-potentiated reactive hypoglycaemia was shown to depend on the nature of the carbohydrate ingested together with the alcohol. When 14 men (9 normal weight and 5 obese) aged between 20 and 50 years consumed a 50 g glucose load together with 50 g ethanol over an hour, their early plasma insulin response was significantly higher and their later fall in plasma glucose significantly lower than after drinking the same amount of a starch solution (maize meal) and alcohol. In four subjects (3 of them non-obese) plasma glucose concentrations dropped below 2.8 mmol/l after drinking the glucose-alcohol solution. Obesity seemed to be associated with features of peripheral insulin resistance. We conclude that the common social custom of drinking alcohol together with a simple sugar mixer should probably be modified.
Adult↗
HLA antigens in White and Black South African diabetics.
The HLA A and B specificities in 72 Whites with type 1 or juvenile-onset diabetes mellitus (JOD), 53 Blacks with type 1 diabetes or JOD and 52 Blacks with type II or maturity-onset diabetes (MOD) were determined and compared with those in 278 Whites and 311 Blacks who were not diabetic. In Whites with JOD, frequencies of HLA A1 and B8 antigens were significantly increased, whereas those of the A3 and B17 antigens were reduced. Blacks with JOD had an increased frequency of HLA B8. By contrast, in Blacks with MOD the antigen frequencies were not significantly altered. The D-locus antigens Dw3 (DRw3) and Dw4 (DRw4), which bear the strongest associations with JOD in Whites, need to be examined in Black South African diabetics.
Adult↗
Plasma lipid and lipoprotein levels in obese black diabetics.
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Adult↗
Dosage of antituberculosis agents in tuberculosis meningitis.
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Adult↗
Familial hypercholesterolaemia : effect of low density lipoproteins on cholesterol synthesis in lymphocytes from homozygous and heterozygous subjects.
The effect of low density lipoproteins on cholesterol synthesis was studied in lymphocytes from patients with familial hypercholesterolaemia (10 homozygotes and 11 heterozygotes); results were compared with those obtained using cells from apparently normal individuals. Freshly isolated lymphocytes were maintained in lipoprotein deficient medium for 48 h and the rate of formation of [14C] cholesterol from [14C] acetate then determined in the presence or absence of low density lipoproteins. In the absence of low density lipoproteins, incorporation of [14C] acetate was lower in homozygote cells than in normal lymphocytes; differences between heterozygote and normal cells were not significant. When low density lipoproteins were included, incorporation was considerably reduced in normal cells; in lymphocytes from both homozygotes and heterozygotes results were variable with incorporation being markedly reduced in some cases, but not in others.
Adult↗
Effect of drinking bottled beer on plasma insulin and glucose responses in normal subjects.
Alcohol may provoke reactive hypoglycaemia when drunk with a sucrose mixer ('gin and tonic') but does not do so when taken in the form of a starch-based beverage like sorghum beer. We examined the hypoglycaemic potential of bottled beer (Lion Lager; South African Breweries), which differs from sorghum beer in that it contains less carbohydrate (polysaccharides and simple sugars) and has a higher alcohol content. After an overnight fast 5 Black men each drank 2 litres of Lion Lager over an hour. Over the ensuing 5 hours their plasma insulin, glucose and alcohol concentrations were compared with the responses previously documented before and after consuming the same volume of sorghum beer or a 100 g control carbohydrate solution. Bottled beer elicited a prompt but short-lived rise in plasma insulin (mean +/- SEM, 37 +/- 7 mU/l at 1 hour), which was significantly greater than that produced by sorghum beer but less sustained than after drinking the control carbohydrate solution. After drinking bottled beer plasma glucose levels fell to a mean nadir of 3,6 mmol/l at 2 hours (compared with 5,4 mmol/l for sorghum beer), thereafter slowly returning to the basal value, while a substantial rise in the blood alcohol concentration occurred. We conclude that the development of alcohol-induced reactive hypoglycaemia is largely determined by the nature of the carbohydrate ingested together with alcohol.
Adult↗
Treatment of homozygous familial hypercholesterolaemia with probucol.
Ten patients with homozygous familial hypercholesterolaemia were treated with the recently introduced drug probucol (Lurselle; Mer-National) for 15-21 months. Xanthomas regressed or disappeared in most patients, angina lessened in two-thirds of cases and the ECG improved in half of those with pretreatment abnormalities. The mean fall in serum total cholesterol levels after 18 months of therapy was 27%. High-density lipoprotein cholesterol levels fell transiently in the early months of therapy but then returned to the pretreatment range. Plasma probucol levels varied between 20 micrograms/ml and 90 micrograms/ml, indicating good compliance, but did not correlate with the clinical or hypocholesterolaemic responses. Probucol was well tolerated by child and adult patients. The effects of probucol in this therapeutically resistant disorder were better than expected. Considered in relation to efficacy, safety, tolerance and convenience probucol appears to be the most satisfactory treatment for homozygous familial hypercholesterolaemia currently available.
Adolescent↗
Platelet function in familial hypercholesterolaemia in South Africa and the effects of probucol.
Patients with Familial Hyperlipoproteinaemia Type II showed evidence of increased platelet aggregability when compared to normal controls. This abnormality was not influenced by oral therapy with probucol whether or not the serum cholesterol levels were lowered during the study period. Probucol assays indicated adequate compliance during the study period but did not demonstrate any uptake of the drug by platelets. In vitro studies also failed to demonstrate any inhibition of platelet function at therapeutic drug levels although higher levels were inhibitory.
Adolescent↗
Treatment of homozygous familial hypercholesterolaemia with portacaval shunt.
Thirteen patients with homozygous familial hypercholesterolaemia (HFH) were treated with portacaval shunt operations. One patient died postoperatively and the others were followed for 2-6 years. The main beneficial effects were regression of xanthomas and sustained falls in serum total and LDL cholesterol levels of about 18% in the majority of cases, sustained rises in HDL cholesterol values in most patients, and the long period of survival after the operation without further deaths or serious cardiac complications. Other favourable effects were improvement of angina pectoris, ejection systolic múrmurs or electrocardiograms in some cases. Growth and development of patients after the operation were normal and there were no clinical or biochemical signs of liver damage or portal systemic encephalopathy. Apart from the patient who died, negative or adverse effects of the operation included shunt closure causing portal hypertension and bleeding varices in 1 case, unsatisfactory clinical responses in half the patients, small or unsustained falls in serum total cholesterol in one third of cases, and failure of total cholesterol to fall below 12.0 mmol/l in any patient. Enlargement of the spleen appeared to be an invariable consequence of the operation and possible reasons for this are discussed. Finally the place of portacaval shunts in the management of HFH is reviewed.
Adolescent↗
Nonspecific blinding of insulin to gamma globulin in the serum of black patients with hepatocellular carcinoma and other forms of liver disease.
The study was prompted by the apparent detection of insulin antibodies in a black patient with HCC and recurrent hypoglycemia who had never received insulin. It consisted of two parts. Initially the sera of 30 individuals (six normoglycemic HCC patients, three with HCC and recurrent hypoglycemia, 11 patients with noncancerous liver diseases, and 10 healthy black controls) were analyzed for the presence of insulin (and glucagon) antibodies by precipitating the bound, labeled hormone with ethanol and also by the technique of radioimmunoelectrophoresis. In the nine HCC patients, binding of 125I-insulin averaged 13% by ethanol separation and 0.018 mU/ml with radioimmunoelectrophoresis, levels that were similar to those of patients with noncancerous liver disease and significantly higher than those of the healthy controls. Mean binding of 125I-glucagon was 11% in HCC sera. Serum binding of labeled hormones correlated significantly with IgG concentrations in the patients. The second part of the study attempted to define the nature of insulin binding in HCC and other forms of liver disease. After confirmation of the increased serum binding of labeled insulin by another method of precipitation, PEG, an attempt was made to compete with the labeled insulin for its serum binding sites by adding a large amount of unlabeled insulin. This binding was not displaceable, however, and was therefore considered nonspecific. When the same procedures were repeated using normal serum to which increasing amounts of gamma globulin were added, the nonspecific binding of insulin increased in a linear fashion. Furthermore, a similar degree of high nonspecific insulin binding occurred in six patients with multiple myeloma and raised serum IgG concentrations. We therefore conclude that in the many clinical situations where hypergammaglobulinemia exists, false positive tests for the detection of antibodies against insulin (and probably other peptide hormones) will emerge unless appropriate methods are used to check for nonspecific peptide binding.
Black People↗
Serum lipid, uric acid and glucose levels in urban black males doing manual or clerical work.
Serum lipid, uric acid and glucose levels were measured in four groups of Black male factory workers 1 hour after an oral glucose load. These groups comprised non-obese manual, obese manual, non-obese clerical and obese clerical workers. Obese men had significantly higher serum uric acid, total cholesterol and triglyceride levels and lower high=density lipoprotein (HDL) cholesterol levels than non-obese men. Serum glucose and low-density lipoprotein (LDL) cholesterol values were also higher in obese than in non-obese men, but the differences were not significant. Clerical workers had higher levels than manual workers for most of the biochemical variables measured, but only in the case of uric acid was the difference significant. Possible reasons for the fact that the effect of occupation on the variables was slight are briefly discussed.
Adult↗
Serum lipoproteins in diabetes secondary to chronic calcific pancreatitis.
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Blood Glucose↗
Failure to induce reactive hypoglycaemia by drinking a starch-based alcohol beverage (sorghum beer).
Alcohol is a well-recognised cause of fasting hypoglycaemia but may also provoked reactive hypoglycaemia when drunk together with a carbohydratee mixer. In this study the ability of sorghum beer (an 'in-built' alcohol-starch beverage widely enjoyed in Southern Africa) to induce reactive hypoglycaemia was compared with "gin and tonic' in eight non-obese health African men. After an overnight fast, each subject drank, in random sequence on their different occasions, 2 litres of sorghum beer (carbohydrat content approximately 5% and alcohol concentration 2.24 g/dl-2.8% v/v), the same volume of a control solution providing a similar carbohydrate load, or a gin and standard tonic water mixture. No evidence of reactive hypoglycaemia was apparent during the 5 hours after the beginning of the sorghum beer tolerance tests, despite a mean peak blood alcohol level reaching 80 mg/dl. both the peak and total plasma insulin responses were significantly reduced (p less than or equal to 0.05) when compared to the brisk responses elicited by the carbohydrate solution alone and the gin and tonic drinks, with consequent hypoglycaemia. These data suggest that African home-brews are not potent causes of reactive hypoglycaemia, although they may be implicated in the development of ethanol-induced hypoglycaemia in the fasting state.
Adult↗