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Biomedical subjects

K Steyn

Publications and source records attributed to K Steyn.

At least 55 records · Page 3Linked to original sources

FH Afrikaner-3 LDL receptor mutation results in defective LDL receptors and causes a mild form of familial hypercholesterolemia.

Three founder-related gene mutations (FH Afrikaner-1, -2, and -3) that affect the LDL receptor are responsible for 90% of the familial hypercholesterolemia (FH) in South African Afrikaners. Patients heterozygous for the FH Afrikaner-1 (FH1) mutation, which results in receptors having approximately 20% of normal receptor activity, have significantly lower plasma cholesterol levels and milder clinical symptoms than heterozygotes with the FH Afrikaner-2 mutation, which completely abolishes LDL receptor activity. In this study we re-created the FH3 mutation (Asp154-->Asn) in exon 4 by site-directed mutagenesis and analyzed the expression of the mutant receptors in Chinese hamster ovary cells. The mutation resulted in the formation of LDL receptors that are markedly defective in their ability to bind LDL, whereas binding of apoE-containing beta-VLDL is less affected. The mutant receptors are poorly expressed on the cell surface as a result of significant degradation of receptor precursors. The plasma cholesterol levels of 31 FH3 heterozygotes were similar to FH1 heterozygotes but significantly lower than FH2 heterozygotes. The FH1 and FH3 heterozygotes also tended to be less severely affected clinically (by coronary heart disease and xanthomata) than FH2 patients. This study demonstrates that mutational heterogeneity in the LDL receptor gene influences the phenotypic expression of heterozygous FH and that severity of expression correlates with the activity of the LDL receptor measured in vitro. The results further indicate that knowledge of the specific mutation underlying FH in heterozygotes is valuable in determining the potential risk of premature atherosclerosis and should influence the clinical management of FH patients.

Adult↗

Coronary heart disease risk factors in a rural and urban Orange Free State black population.

OBJECTIVE: To determine and compare the prevalence of ischaemic heart disease (IHD) risk factors in a rural and an urban black population. DESIGN: A survey to determine the prevalence of hypertension, diabetes mellitus, smoking, obesity, central obesity and dyslipidaemia in black subjects 25 years and older. SETTING: The indigenous black populations of QwaQwa and Mangaung. PARTICIPANTS: A random sample of 950 households was selected from each area. From each household an unrelated male and/or female subject was selected in a standardised way. From QwaQwa 853 subjects (279 men and 574 women) and from Mangaung 758 subjects (290 men and 468 women) participated in the study. The response rate was 68% and 62% respectively for QwaQwa and Mangaung. MAIN OUTCOME MEASURES: Few urban-rural differences in the prevalence of IHD risk factors were found in this study. A low prevalence of clustering of major IHD risk factors was noted. RESULTS: The age- and sex-adjusted prevalences of hypertension were 29% in QwaQwa and 30.3% in Mangaung. Diabetes was present in 4.8% of the QwaQwa sample and 6% of the Mangaung sample. The prevalence of heavy smoking in the Mangaung sample was almost double that of the QwaQwa sample and mostly confined to men. High-risk hypercholesterolaemia was present in 12.5% of QwaQwa and 6% of Mangaung men in the 25-34-year age group. The corresponding figures for moderate-risk hypercholesterolaemia were 34% and 44.8% and both levels of risk declined with increasing age. The mean body mass index of women in both samples exceeded 25 kg/m2. CONCLUSION: All the elements for a potential epidemic of atherosclerotic cardiovascular disease are present in the study populations. The similarity of findings in the two samples may be indicative of the advanced stage of urbanisation and westernisation of the rural group. It is alarming that subjects in the younger age groups tended to have the highest prevalences of moderate and even high-risk hypercholesterolaemia.

Adult↗

The haematological profile of urban black Africans aged 15-64 years in the Cape Peninsula.

A stratified probability sample (n = 986) with quotas was drawn from black residential areas in the Cape Peninsula, South Africa. Subjects (n = 819) aged 15-64 years, participated in a coronary heart disease (CHD) risk factor survey, the BRISK Study. Nutritional status and prevalence of CHD was determined in this population undergoing rapid urbanization. Full blood and differential white blood cell counts provided data to calculate population reference values based on the 95% reference limits of the haematological parameter. Mean haemoglobin concentrations (Hb) in men (14.0 g/dl) and women (12.4 g/dl) were +/- 1.5 g/dl lower than previous South African reports. Mean BRISK Hb values were very similar to the World Health Organization's Hb cutoff criteria (< 13 g/dl men; < 12 g/dl women), indicating a possible high prevalence of anaemia. Significantly higher (P < 0.05) mean values for red cell indices were confirmed in men, which also reflected equally higher red blood cell counts (RBC), haematocrit (HCT) and mean corpuscular haemoglobin (MCH) values. Mean Hb values were significantly lower in the younger (15-24 years) and older (55-64 years) men compared with 25-54 year-olds (P < 0.05). Hypochromic microcytic anaemia was more prevalent in women, possibly due to iron deficiency (ID), while macrocytic anaemia was more prevalent in men. No significant differences were noted in mean total and differential white blood cell counts (WBC) between men and women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Rationale for the hypertension guidelines for primary care in South Africa.

New South African guidelines are proposed by the Hypertension Society of Southern Africa for the management of hypertension by primary health care services in South Africa. Specific South African guidelines are appropriate for hypertension, which is now recognised as one of the five major diseases that must be given priority by the new Government. Furthermore, patient participation and empowerment in blood pressure (BP) control become feasible through the new concept of lifestyle modification. This article gives the rationale underpinning these guidelines. The correct methods to measure blood pressure (BP), with patients sitting for 5 minutes, correct cuff-size and repeated readings, are emphasised to eliminate the 'white coat' effect and ensure accurate BP readings. The rationale for the overall management of all atherosclerosis-related risk factors is given, as are the principles of non-drug hypertension treatment and patient education. We emphasise that patients must understand hypertension to be a risk factor and not a disease. Patients should also be empowered to contribute to effective BP control. The justification for the chosen BP levels at which specific action is required by the primary health care team is given. The BP levels span the range from mild hypertension, requiring conservative treatment schedules, to possible malignant hypertension, which requires urgent management and referral to the appropriate level of care. The motivation for cost-effective antihypertensive drug therapy is provided. The recommended initiation of drug therapy is with effective, safe low-cost drugs. Suggested first-line therapy comprises lifestyle management and low-dose diuretics. The second-line drugs, in order of increasing price, are low-dose reserpine, or a beta-blocker, or a calcium blocker, or an ACE inhibitor. For third-line therapy hydralazine is chosen, or other second-line drugs could be added. Where possible, the examples of specific drugs given are those for which a generic is available, to ensure cost-containment. The motivation for drug choices for hypertension in special cases such as pregnancy, the elderly, blacks and patients with diabetes and renal disease is given. The management of malignant hypertension receives special attention.

Antihypertensive Agents↗

Smoking in the black community of the Cape Peninsula, South Africa.

The purpose of this study was to determine tobacco-use and related factors in the black population of the Cape Peninsula. About 52% of the men, but only 8% of the women used tobacco regularly. Men and women who smoked cigarettes, smoked 9.6 and 4.3 cigarettes on average per day, respectively. Although many men smoked, 80% perceived smoking to be harmful to health as did 92% of the women. For women, smoking was inversely related to their level of education, while for men it was directly related to being employed. Smoking was also related to the use of alcohol in both genders. Women below 45 years who had spent less than a third of their lives in the city had lower smoking rates than those who had spent more than a third of their lives in the city. Smoking is one of the most important public health issues facing the black community of the Cape Peninsula.

Adolescent↗

Nutritional status of 3-6 year-old African children in the Cape Peninsula.

A survey was conducted in the Cape Town metropolitan area in 1990 to determine the dietary intake and anthropometric status of 3-6 year-old African children (N = 163). Dietary data obtained from 24-hour recalls revealed that mean energy intake (5200 kJ) was low and that mean intakes of most nutrients fell considerably below the recommended dietary allowances (RDAs). The average diet included an adequate number of portions from the meat and cereal groups, but was inadequate with respect to the milk and fruit/vegetable groups when compared with the recommendations of the Department of Health Services and Welfare. The macronutrient energy distribution was within prudent dietary guidelines, with 28.1% of energy (E) being obtained from total fat, 63.7% from carbohydrate and 13.2% from protein. Anthropometric profiles expressed in terms of the National Centre for Health Statistics' (NCHS) standards, revealed evidence of growth retardation and wasting in this population, coexisting with emergent obesity. The development of a nutrition and health policy to address the problems of both deficit and excess represents a pressing challenge.

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Level of physical activity and CHD risk factors in black South African men.

Coronary heart disease (CHD) is uncommonly low among black South Africans. Although dietary and genetic influences probably contribute to their favorable serum lipid profile, other cardioprotective factors may also play a significant role in explaining the low incidence of CHD. From a socioeconomic perspective, it appears that the black community engages in regular physical activity (PA) more so than other populations. Since data are lacking, our aim was to provide preliminary data on the association between PA and the traditional CHD risk factors. The sample consisted of 212 working, middle-aged men drawn from an epidemiological database on the African population of metropolitan Cape Town. Analysis of responses to basic questions on PA behavior indicated i) 43% of the sample were employed in jobs requiring moderate to strenuous PA, and ii) the most favorable blood pressure and serum lipid profiles were associated with low to moderate levels of habitual exercise. As this community becomes more urbanized, job-related PA as well as PA of daily living will decline. The need for sports and leisure-time PA programs will become more important and should be considered as part of a public health strategic plan.

Adult↗

The food and meal pattern in the urban African population of the Cape Peninsula, South Africa: the BRISK Study.

A cross sectional dietary study, utilising the 24 hour recall method, was conducted among 983 African adults aged 15 to 64 years resident in the Cape Peninsula during 1990. An evaluation of the dietary intake pattern revealed a diet confined to a relatively narrow range of foods, but little evidence of nutrient-empty food intake. In terms of recommendations, insufficient dairy products and vegetables and fruits were consumed, while requirements for intakes of cereals and components of the meat and fat groups were met. Supper emerged as the main meal of the day, contributing most of the energy and was consumed by 89 pc of respondents. Between meal eating made a valuable contribution to total nutrient intake. The low intakes of dairy products and vegetables and fruits and the apparent move away from the traditional diet present particularly great challenges.

Adolescent↗

Musculoskeletal manifestations in hyperlipidaemia: a controlled study.

Eighty eight patients with hyperlipidaemia (81 white patients from South Africa and seven patients of mixed race from the West Cape area) were studied. Forty eight had adult familial hypercholesterolaemia, 16 had juvenile familial hypercholesterolaemia, and 24 had mixed hyperlipidaemia (increased cholesterol and triglycerides). They were interviewed and examined and their musculoskeletal manifestations compared with 88 controls with normal lipid profiles, and matched for age, sex, and race for each group of patients. The following manifestations were significantly increased in the patients: (a) tendon xanthomas particularly of the tendo Achillis in patients with adult familial hypercholesterolaemia and mixed hyperlipidaemia; (b) tendo Achillis tendinitis in patients with adult familial hypercholesterolaemia and mixed hyperlipidaemia; and (c) oligoarthritis in patients with mixed hyperlipidaemia but not in those with adult familial hypercholesterolaemia. Migratory polyarthritis and transient tendo Achillis pain were rare. Thirty eight per cent of patients with juvenile familial hypercholesterolaemia had musculoskeletal system manifestations none of which was significantly increased compared with controls. There was a significant association between tendon xanthomas and tendo Achillis tendinitis. There was a significant difference in pretreatment cholesterol levels in the patients with adult familial hypercholesterolaemia and musculoskeletal system manifestations compared with those without and in all three groups combined. The study confirms an association between hyperlipidaemia and tendon xanthomas, tendo Achillis tendinitis, and to a lesser extent oligoarthritis but not migratory polyarthritis or transient tendo Achillis pain as reported in other studies. It also shows that musculoskeletal system manifestations antedated the diagnosis of hyperlipidaemia in 24/39 (62%) patients and that the manifestations improved or resolved completely in 19/30 (63%) patients after receiving lipid lowering treatment. It is therefore important to recognise the association between musculoskeletal system manifestations and hyperlipidaemia for diagnostic and therapeutic reasons.

Achilles Tendon↗

Phenotypic variation among familial hypercholesterolemics heterozygous for either one of two Afrikaner founder LDL receptor mutations.

Two common founder-related gene mutations that affect the low-density lipoprotein receptor (LDLR) are responsible for approximately 80% of familial hypercholesterolemia (FH) in South African Afrikaners. The FH Afrikaner-1 (FH1) mutation (Asp206-->Glu) in exon 4 results in defective receptors with approximately 20% of normal activity, whereas the FH Afrikaner-2 (FH2) mutation (Val408-->Met) in exon 9 completely abolishes LDLR activity (< 2% normal activity). We analyzed the contribution of these mutations and other factors on the variation of hypercholesterolemia and clinical features in Afrikaner FH heterozygotes. The type of FH mutation, plasma triglyceride levels, and age of patients each contributed significantly to the variation in hypercholesterolemia, whereas smoking status, high-density lipoprotein cholesterol levels, and gender had no influence. Although all FH heterozygotes had frank hypercholesterolemia, patients with the FH1 mutation had significantly lower cholesterol levels than those with the FH2 mutation. FH1 heterozygotes also tended to have milder clinical features. The differences between the two FH groups could not be explained by a difference in the common apolipoprotein E variants. This study demonstrates that mutational heterogeneity in the LDLR gene influences the phenotypic expression of heterozygous FH.

Adult↗

Nutrient intake in the urban African population of the Cape Peninsula, South Africa. The Brisk study.

In a dietary study on a representative sample of 983 adult African men and women aged 15-64 years, resident in the Cape Peninsula, South Africa, trained professional nurses administered a 24 hour recall interview. This formed part of a cross-sectional study on the prevalence of coronary risk factors (BRISK) in this population. The macronutrient profile reflected a diet meeting the Prudent Dietary Guidelines, but low in fibre. Mean intakes of vitamins and minerals indicated a nutritionally depleted diet. Comparisons with rural African populations have revealed that the dietary intake of this urbanising study population represents a transitional phase towards a progressively atherogenic Western diet.

Adolescent↗

The intervention effects of a community-based hypertension control programme in two rural South African towns: the CORIS Study.

The objective of the hypertension programme of the Coronary Risk Factor Study (CORIS) was to evaluate the effectiveness of the first 4 years of community-based intervention. The hypertension intervention model comprised a blood pressure station where the whole population was screened for hypertension, non-drug management was provided and hypertensives were monitored after referral to general practitioners for drug therapy. Two levels of intervention were maintained: in the high-intensity intervention town (N = 2,278) hypertensives were actively followed up, and in the low-intensity intervention town (N = 2,620) no active follow-up procedure existed. A third town acted as control (N = 2,290). In the cohort which was hypertensive at baseline, the net decreases in systolic blood pressure (mean +/- SE) after correction for changes in the control town were 0.5 +/- 2.2 mmHg (men) and 4.5 +/- 2.2 mmHg (women) in the low-intensity intervention town, and 5.6 +/- 2.3 mmHg (men) and 7.5 +/- 2.2 mmHg (women) in the high-intensity intervention town. The net decrease in diastolic blood pressure was 3.4 +/- 1.2 mmHg (men) and 4.4 +/- 1.1 mmHg (women) in the low-intensity intervention town, and 6.1 +/- 1.2 mmHg (men) and 5.9 +/- 1.1 mmHg (women) in the high-intensity intervention town. These reductions were statistically significant with one exception. The changes in the total population in the 3 communities after 4 years of intervention were similar to those found in the hypertensive cohort.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The first 6 years of the Tygerberg Hospital lipid clinic.

The Tygerberg Hospital Lipid Clinic was established in July 1983. The demographic characteristics, lipid abnormalities, coronary risk factor profile, treatment status and 6-month follow-up lipid changes of patients seen during its first 6 years are summarised. During this period 329 patients were seen and complete lipograms were available for 312 of them. This patient population, consisting of 87.2% whites and 12.8% coloureds, represented a wide age range (2-69 years), various occupations and the whole spectrum of educational qualifications. The plasma cholesterol levels of 78.8% of the patients could be described as high risk, according to the cholesterol action limits of the Heart Foundation of Southern Africa, and 33.2% had low high-density lipoprotein cholesterol (less than 1 mmol/l) levels. Approximately 20% of the patients had familial hypercholesterolaemia and 31.1% were already on lipid-lowering medication before registration. The Lipid Clinic succeeded in improving the mean overall plasma cholesterol levels by 8% during the 6 months after registration and provided essential information for the planning of treatment strategies for patients with hypercholesterolaemia.

Adolescent↗

The impact of chronic diseases of lifestyle and their major risk factors on mortality in South Africa.

The purpose of this study was to determine the impact of chronic diseases of lifestyle on the mortality pattern of South Africans and to estimate the number of South Africans affected by major risk factors for these diseases. The proportion of deaths due to chronic diseases of lifestyle was calculated from the deaths reported to the Central Statistical Services. This group of diseases was responsible for 24.5% of deaths of all South Africans and 28.5% of those aged 35-64 years whose deaths were reported in 1988. The major causes of death contributing to these figures were cerebrovascular diseases (7.2% of all deaths and 7.9% of deaths of persons aged 35-64 years) and ischaemic heart disease (8.7% of all deaths and 9.6% of deaths of persons aged 35-64 years). The age-standardised prevalence rates for the major risk factors reported in five cross-sectional studies in different areas and groups are compared. Estimates from the reported prevalence rates, based on the size of the South African population recorded in the 1985 census figures, were calculated for the major risk factors. Overall 4.88 million South Africans smoked, the largest group of smokers being black males (2.6 million). for hypertension 5.5 million South Africans had blood pressures above 140/90 mmHg; again the largest groups were blacks (3.0 million). For hypercholesterolaemia and raised low-density lipoprotein cholesterol levels, 4.8 million and 3.1 million South Africans respectively had an increased risk for ischaemic heart disease, blacks having the lowest levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗