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Biomedical subjects

W J Vermaak

Publications and source records attributed to W J Vermaak.

At least 19 recordsLinked to original sources
PubMed1992

The effect of blood sample aging and food consumption on plasma total homocysteine levels.

The stability of homocysteine in whole blood and plasma was investigated. Total homocysteine concentrations in whole blood increased rapidly to values in excess of 180% of the basal concentration if whole blood was left at ambient temperature. Sodium fluoride partially inhibited homocysteine accumulation, while refrigeration inhibited homocysteine accumulation for at least 4 h. Since intracellular concentrations of homocysteine were low, the results indicate continued metabolism of L-methionine to homocysteine after the blood sample had been obtained. In contrast to whole blood, homocysteine was stable in plasma, even at room temperature. Food consumption (normal breakfast) resulted in significantly lower plasma homocysteine concentrations, which returned to pre-prandial concentrations 8 h later. The results indicate that both blood sampling and food intake should be rigorously standardized in epidemiological studies to elucidate the possible role of elevated circulating homocysteine concentrations in premature vascular disease.

Adult↗
PubMed1992

Quantification of erythrocyte S-adenosyl-L-methionine levels and its application in enzyme studies.

A highly selective high-performance liquid chromatographic method for the quantification of human erythrocyte S-adenosyl-L-methionine levels is described. A strong cation-exchange sorbent with propylsulphonic acid functional groups was used to extract S-adenosyl-L-methionine and S-adenosylethionine (internal standard) from erythrocytes. Quantification of erythrocyte S-adenosyl-L-methionine levels was achieved by using reversed-phase high-performance liquid chromatography and ultraviolet detection at 254 nm. This method was adapted to measure methionine-adenosyltransferase activity in erythrocytes, which enables us to study the possible role of altered methylation in different diseases.

Chromatography, High Pressure Liquid↗
PubMed1992

Experience with a provocative test of calcitonin release as a prospective screening for preclinical medullary thyroid carcinoma in MEN type 2A family members.

We report our experience with a provocative test of calcitonin (CT) release using a combined stimulus of intravenous 10% CaCl2 solution and pentagastrin on 34 normal adults (15 females: age 41 +/- 12.3 years and range 22-65 years; and 19 males: age 43 +/- 9.1 years and range 23-60 years) and in 44 family members of three proven multiple endocrine neoplasia type 2A syndrome (MEN 2A) patients. A commercial radioimmunoassay was used to determine the serum CT levels. Peak CT levels were reached within 2 to 5 minutes after administration of the stimulus in all subjects tested. In the group of normal subjects there was no significant difference in the mean basal CT levels between males (54.8 +/- 21.7 pg/ml) and females (56.5 +/- 34.8 pg/ml), whilst the mean peak response values for males was 146.3 +/- 120.6 pg/ml, which was significantly different from the mean value of females, namely 71.6 +/- 39.0 pg/ml. We did not find significant correlations between the basal CT level, peak CT response, and age. Of the 44 family members tested, 9 showed an exaggerated CT response to the combined stimulus and subsequently had a total thyroidectomy. Histological examination confirmed C-cell hyperplasia (CCH) in one and medullary thyroid carcinoma (MTC) in the other 8. Three of the 9 had high basal plasma CT levels. The 9 patients were retested postoperatively and all showed a flat response to the combined stimulus. Those family members with histological proof of MTC or CCH were screened for genetic linkage to the disease gene for MEN 2A using probe MCK2, and showed correlation in each instance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Using changes in attributable risk to predict long-term efficacy of simvastatin treatment.

It is a common perception that coronary heart disease (CHD) deaths will decline by 2% for every 1% decrease in serum total cholesterol (TC). We investigated the changes in serum TC concentrations obtained with simvastatin, an inhibitor of hydroxymethylglutaryl-CoA reductase, in 70 hypercholesterolemic subjects. Although simvastatin reduced serum TC concentrations by 30% after 6 months, calculations from age- and risk-related TC quintiles show that the absolute difference in attributable CHD deaths would be just > 1%. These results are reminiscent of the experience from several large prospective primary drug trials that demonstrated impressive relative benefit ratios but much smaller absolute differences (< 2%) in CHD endpoints between the treated and untreated groups. This epidemiologically based approach of assessing efficacy and potential long-term benefit of a lipid-lowering drug may be more appropriate and potentially less misleading than just the percentage change of TC (or other lipoproteins) so frequently reported in short-term drug trials.

Adult↗
PubMed1992

Simvastatin in non-insulin-dependent diabetic patients with hypercholesterolaemia.

The objective of this study was to evaluate the lipid-lowering effect of simvastatin in non-insulin-dependent diabetes mellitus (NIDDM) patients with hypercholesterolaemia while possible clinical and biochemical adverse effects were monitored for. Forty-three NIDDM patients with hypercholesterolaemia (total cholesterol > 6.5 mmol/l) used simvastatin after a detailed clinical laboratory evaluation as well as a 4-week wash-out period and a 4-week placebo baseline period. Simvastatin treatment was initiated with a 10 mg dose for 6 weeks; this was increased to 20 mg and 40 mg at 12 and 18 weeks of follow-up respectively if the total cholesterol level had not decreased to below 5.17 mmol/l. Patients were placed on a lipid-lowering diet and continued to take any regular non-lipid-lowering medication throughout the trial; side-effects were monitored at 6-week intervals until patients had taken simvastatin for 24 weeks. The mean total cholesterol level was reduced by 22.2% at the first follow-up visit, and by 24.2%, 23.3%, and 28.5% at the second, third and fourth follow-up visits respectively compared with base-line levels. A dose of 10 mg simvastatin brought about a reduction in total cholesterol similar to those found with higher doses. The mean triglyceride level was reduced by 20.9% with 20 mg simvastatin. The high-density lipoprotein cholesterol level was not altered significantly and neither was the control of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Serum adenosine deaminase: isoenzymes and diagnostic application.

Human adenosine deaminase (ADA; EC 3.5.4.4) consists of three isoenzymes: ADA1, ADA1+CP, and ADA2. We developed an electrophoretic technique to distinguish between these three isoenzymes. The isoenzyme pattern was studied in tissue and cell homogenates, as well as in serum from normal subjects and from patients with increased serum ADA who had either hepatitis, infectious mononucleosis, tuberculosis, pneumonia, rheumatoid arthritis, or acute lymphoblastic leukemia (ALL). The highest ADA activity was found in lymphocytes and monocytes. ADA2 could be detected only in monocytes (18% of total ADA activity). It was also the predominant isoenzyme in the sera of controls and all disease groups, except for ALL--the only condition evaluated that is not of an inflammatory nature. We conclude that serum ADA reflects monocyte/macrophage activity or turnover in most diseases studied. The exception is ALL, where serum ADA most probably originates from lymphocyte precursors.

Adenosine Deaminase↗
PubMed1991

The prevalence of homocysteinemia and hypercholesterolemia in angiographically defined coronary heart disease.

Total serum homocysteine and cholesterol levels were determined in 163 male patients with typical angina who were subjected to coronary angiography. The prevalence of homocysteinemia in coronary heart disease (CHD) was 41.9%. Serum homocysteine levels were significantly elevated (p less than 0.05) in patients with major occlusion in two or three coronary arteries. Furthermore, the prevalence of homocysteinemia correlated positively (p less than 0.05) with the number of coronary vessels that were occluded. The prevalence of hypercholesterolemia was 34.9%, but, in contrast to homocysteinemia, no graded strength of association with the number of stenotic coronary arteries could be demonstrated. The results suggest that homocysteinemia may contribute significantly to the development of coronary heart disease.

Adult↗
PubMed1991

Multiple endocrine neoplasia type 2A (MEN 2A) syndrome in a South African family. Biochemistry and molecular genetics.

Multiple endocrine neoplasia type 2A (MEN 2A), an uncommon heritable disease, was investigated in an Afrikaner kindred. Serum calcitonin levels after combined pentagastrin and calcium chloride stimulation were measured to determine thyroid involvement, as were urinary metadrenalin levels to determine adrenal gland involvement. MEN 2A genotype status was determined using the DNA probe MCK2 (D10S15). The index patient, who showed both thyroid and adrenal gland involvement, died of phaeochromocytoma complications. Thirty-four of his 114 family members, in 4 generations, were investigated. Nine had positive histological and calcitonin tests and were predicted to be MEN 2A genotypes by DNA analysis. One asymptomatic individual had a positive calcitonin test after being predicted to be a MEN 2A genotype with the probe MCK2. In 3 DNA-positive cases calcitonin stimulation tests were negative. Preclinical detection of the heritable form of MEN 2A will be facilitated by utilising the DNA probe MCK2 to determine carrier status in this large South African family. It is also the first South African family in which biochemical and molecular genetic techniques were used to facilitate diagnosis.

Adolescent↗
PubMed1991

A 6-month trial of simvastatin (HMG-CoA reductase inhibitor) in the treatment of hypercholesterolaemia.

The aim of this study was to evaluate the long-term efficacy and tolerability of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor simvastatin, over a 24-week period. Patients (108) with primary hypercholesterolaemia were clinically, haematologically and biochemically evaluated and established on a cholesterol-lowering diet. After a wash-out period free from other lipid-lowering drugs and a baseline period on placebo of 1 month each, 10 mg simvastatin was introduced at night. The dose was increased to 20 mg and 40 mg at 6 and 12 weeks' follow-up respectively if the total cholesterol (TC) level was still above 5.17 mmol/l. Follow-up took place every 6 weeks and included lipid, haematological, biochemical and clinical evaluation. A full ophthalmological evaluation was conducted at baseline and at 24 weeks' follow-up. Overall the TC level was reduced below the baseline level by 34.3% at week 18 of follow-up and 32.5% at week 24. Patients with higher initial TC levels showed greater TC lowering in response to simvastatin than did those with lower initial TC levels. A group of 45 patients was followed up for an additional 12 weeks after the end of the trial and maintained TC reductions similar to those at the end of the trial. Fourteen patients experienced adverse effects which were thought to be drug-related. One patient was withdrawn from the trial after developing conjunctivitis that proved to be related to the use of simvastatin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

High-performance liquid chromatographic assay of human lymphocyte kynureninase activity levels.

Human lymphocyte kynureninase activity was assessed in homogenized cells by determination of 3-hydroxyanthranilic acid production as a function of time after addition of the substrate, 3-hydroxykynurenine. The product, 3-hydroxyanthranilic acid, was determined by isocratic high-performance liquid chromatography and fluorescence detection. Mean (+/- S.D.) lymphocyte kynureninase activity in a group (n = 12) of vitamin B6-deficient men was 5.04 +/- 0.81 pmol 3-hydroxyanthranilic acid formed per mg protein per min, which was significantly (p = 0.005) lower than the 6.69 +/- 1.70 pmol 3-hydroxyanthranilic acid formed per mg protein per min in men with a normal vitamin B6 status. This indicates that lymphocyte kynureninase activity is depressed during a vitamin B6 deficiency.

3-Hydroxyanthranilic Acid↗
PubMed1991

Epidemiological reference ranges for low-density lipoprotein cholesterol and apolipoprotein B for identification of increased risk of ischaemic heart disease.

Although there is widespread acceptance that total cholesterol (TC) value reference ranges should be based on epidemiological rather than statistical considerations, the epidemiological action limits for low-density lipoprotein cholesterol (LDL-C) are still incomplete and only statistical reference ranges for apolipoprotein B (Apo-B) levels are available. The combined use of epidemiological reference ranges for TC and incomplete or statistical reference ranges for LDL-C and Apo-B is illogical, since these parameters may fall into discordant risk categories that will hamper and complicate the management of hypercholesterolaemia. Based on a study of lipograms obtained from +/- 3,000 inhabitants of two industrialised Transvaal towns, the age-related epidemiological reference ranges for LDL-C and Apo-B were established. A comparison with published observational studies of other populations, in which comparable lipid, lipoprotein and apolipoprotein methodologies were used, reflected the severity of these lipid-related abnormalities in white South Africans, especially after the age of 30 years. In addition, the serum TC values found in this survey were not significantly different from those obtained 10 years ago.

Adolescent↗
PubMed1991

Ethnic immunity to coronary heart disease?

Dietary fat intake is often regarded as a major determinant of coronary heart disease (CHD) rate and it has been deemed unnecessary to invoke racial or other factors to explain the differences in CHD rates among different ethnic groups. Despite a high prevalence of CHD risk factors such as hypertension, obesity, and smoking, CHD remains a rarity in westernized black Africans. Cord blood total cholesterol (TC), low density lipoprotein cholesterol (LDLC) and apolipoprotein B (apo B) levels were measured and found to be respectively 12.1%, 18.3% and 22.4% lower in black neonates when compared to white neonates. These differences were again studied in a group of young black African males and a comparable group of age-matched whites who had been exposed to the same environment and western diet for at least 2 years. Although the body mass indices and serum albumin concentrations in the adult males were not significantly different, serum levels of TC, LDLC and apo B were 10.7%, 18.7% and 39.7% lower in the blacks, respectively. Furthermore, high density lipoprotein cholesterol (HDLC) and Apolipoprotein AI were 20.2% and 9.5% higher, homocysteine 45.6% lower and coagulation factor VII 26.6% lower in the adult black Africans. It is concluded that blacks are biochemically less responsive to an atherogenic diet than whites and these differences are already present at birth.

Adult↗
PubMed1990

Biochemical reference values in elderly black subjects.

Biochemical reference values for the black age group of greater than or equal to 65 years were determined from the black urban population of the Orange Free State. Biochemical investigations performed were those included in the Sequential Multiple Analyser Computer profile because it includes the 20 most requested clinical chemistry investigations. Most of the reference values corresponded to values for the same age groups in the Western world. There was no age-related rise in the alkaline phosphatase values, which suggested absence of occult Paget's disease. Reference values for serum total protein and globulin were found to be higher than values derived from elderly white groups.

Age Factors↗
PubMed1990

Vitamin B-6 nutrition status and cigarette smoking.

We investigated the vitamin B-6 status in smokers, nonsmokers, and exsmokers by measuring both B-6 aldehyde vitamers, pyridoxal-5'-phosphate (PLP) and pyridoxal (PL), in the plasma as well as in the erythrocyte compartment. Two hundred eighty-six healthy, sedentary male workers from a middle-income group were investigated. There were 159 smokers, 59 exsmokers, and 68 nonsmokers. Plasma PLP and PL concentrations were significantly lower in smokers than in the nonsmokers and exsmokers whereas erythrocyte PLP and PL did not differ significantly between groups. Because PLP mainly functions as an intracellular coenzyme, the clinical significance of a depressed plasma PLP concentration alone is uncertain. It is concluded that circulating plasma PLP is labile and not necessarily indicative of intracellular PLP concentrations. The measurement of erythrocyte PLP and/or PL may be more informative about vitamin B-6 status than is plasma PLP alone.

Adult↗
PubMed1990

Relationship between vitamin B-6 status and elevated pyridoxal kinase levels induced by theophylline therapy in humans.

Theophylline administration to seven healthy male volunteers resulted in a rapid and significant decline in both plasma and erythrocyte pyridoxal-5'-phosphate levels. Total erythrocyte pyridoxal kinase levels increased during 15 wk of theophylline treatment from a mean initial activity of 19.23 +/- 5.03 (mean +/- SD) to 62.64 +/- 11.59 nmol pyridoxal-5'-phosphate formed/(g hemoglobin.h). Although plasma pyridoxal levels remained normal, the threefold increase in total erythrocyte pyridoxal kinase activity levels did not normalize plasma and erythrocyte pyridoxal-5'-phosphate levels. Pyridoxal-5'-phosphate hydrolysis was not affected by theophylline therapy. Increased pyridoxal oxidation was confirmed by elevated urinary 4-pyridoxic acid excretion after 15 wk of theophylline treatment. Mean erythrocyte alanine aminotransferase activity declined by 70%, and aspartate aminotransferase activity declined by 50%, indicating that decreased availability of pyridoxal-5'-phosphate can have widespread metabolic consequences. We conclude that the effect of theophylline on vitamin B-6 metabolism is not transitory and cannot be overcome by elevated intracellular levels of pyridoxal kinase. However, pyridoxine supplementation (10 mg/d for 1 wk) normalized indices of vitamin B-6 status and reversed the downward trend in both alanine aminotransferase and aspartate aminotransferase activity levels.

Adult↗
PubMed1990

Inhibition of pyridoxal kinase by methylxanthines.

In the presence of saturating concentrations of adenosine triphosphate (ATP) and rate-limiting amounts of pyridoxal, theophylline was found to inhibit sheep brain pyridoxal kinase (EC 2.7.1.35) competitively. The apparent inhibition constant (Ki) of theophylline for pyridoxal kinase was determined as 8.7 mumol/l. Theophylline concentrations of up to 60 mumol/l did not affect pyridoxal phosphorylation in the presence of saturating amounts of pyridoxal and rate-limiting concentrations of ATP. Caffeine was less potent to inhibit pyridoxal kinase (Ki = 45 mumol/l) due to the presence of a methyl group on the 7 position of the xanthine ring structure. Theobromine showed only a weak inhibition of pyridoxal kinase (Ki = 453 mumol/l). The presence of a hydroxyethyl, hydroxypropyl or dihydroxypropyl group on the N7 position of theophylline completely abolished inhibition of pyridoxal kinase. Enprofylline (3-propylxanthine), a recently described bronchodilator, was also able to inhibit pyridoxal kinase with a Ki of 256 mumol/l.

Animals↗