Lipoprotein(a) determination and risk of cardiovascular disease in South African patients with familial hypercholesterolaemia.

OBJECTIVE: A raised plasma level of lipoprotein(a) (Lp(a)) is an established genetic risk factor for coronary heart disease (CHD), particularly in patients with concomitant elevation of low-density lipoprotein (LDL) cholesterol. The current study focused on the comparison of two commercially available Lp(a) assay kits to determine whether differences observed in measured Lp(a) levels could be deemed negligible in CHD risk assessment in familial hypercholesterolaemic (FH) patients. DESIGN: To compare results obtained on duplicate plasma samples using two commercially available Lp(a) measuring kits, the immunoradiometric assay (RIA) and the enzyme-linked immunoabsorbent assay (ELISA). SETTING: Division of Human Genetics, Department of Obstetrics and Gynaecology, University of Stellenbosch, Tygerberg, South Africa and the Institute for Medical Biology and Human Genetics, University of Innsbruck, Austria. SUBJECTS: Plasma samples were obtained from 146 family members of 65 molecularly characterised South African FH families for comparative analysis. RESULTS: Using the RIA method, 34 samples (23%) considered to be in the normal range by the ELISA technique, were placed in the high-risk group (> 30 mg/dl). Only one sample, considered to have a normal Lp(a) level with the RIA method, was categorised by the ELISA technique as high risk. CONCLUSION: Our data demonstrate that measurements of Lp(a) using the RIA method (the only assay available in South Africa at the time of this study) differ significantly from those obtained by the reference ELISA technique, suggesting that misclassification could lead to inaccurate CHD risk assessment. This is an important consideration in Afrikaner FH families, where plasma levels of Lp(a) have been shown to be elevated significantly in FH patients compared with non-FH individuals.

Endemic goitre in the absence of iodine deficiency in schoolchildren of the Northern Cape Province of South Africa.

OBJECTIVE: The study was undertaken to investigate whether endemic goitre still exists in the Northern Cape Province of South Africa more than 55 years after it was reported and, if so, whether iodine deficiency, or fluoride in the drinking water, is linked to the goitres. DESIGN: Cross-sectional study of children in three pairs of towns. SUBJECTS: The 6-, 12- and 15-year-old children (n = 671) who had been lifetime residents in two Northern Cape towns with low levels, two towns with near optimal levels and two towns with high levels of fluoride in the drinking water were recruited through the schools as study participants. RESULTS: Endemic goitre was found in all the towns except one, ranging from 5% to 29%. Iodine deficiency did not prevail in the study area because the median urinary iodine concentration, exceeding 1.58 micromol/l in all but one of the towns, indicated a more than adequate iodine consumption. The drinking water and, to a lesser extent, iodised salt were important sources of iodine. No relationship was found between fluoride in the water and the mild goitre prevalence (5% to 18%) in the four towns with either a low or near optimal fluoride content in the water. The causal factor(s) responsible for the goitres in these four towns were not clear from our data. However, the prevalence of goitre was higher (28% and 29%) in the two towns with high levels of fluoride in the water. CONCLUSION: These results indicate that either a high fluoride level in the water or another associated goitrogen, other than iodine deficiency, may have been responsible for these goitres.

Effects of a prudent diet containing either lean beef and mutton or fish and skinless chicken on the plasma lipoproteins and fatty acid composition of triacylglycerol and cholesteryl ester of hypercholesterolemic subjects.

In this two-phase crossover study, 39 hypercholesterolemic subjects followed a prudent diet with either lean red meat or fish and skinless chicken (treatment groups), and 13 subjects (reference group) followed their habitual diet. Fasting blood samples were analyzed for plasma total cholesterol, triacylglycerol (TAG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein one- and two-cholesterol, apolipoprotein-B, very low density lipoprotein cholesterol, and very low density lipoprotein TAG, and fatty acid composition of plasma TAG and cholesteryl ester (CE). Body mass and blood pressure were determined. Seven-day dietary records were kept once at baseline and twice during the treatment periods. Significant differences were observed in dietary intake between the baseline and treatment diets and between the two treatment diets. HDL-C (P < 0.05) and diastolic blood pressure (P < 0.01) were higher in patients on the red meat diet than in those on the chicken-fish diet. No other significant differences in lipoproteins were observed between the effects of the two treatment diets. The linoleic acid (%), eicosapentaenoic acid (%), and the eicosapentaenoic acid/arachidonic acid ratios in TAG and CE were higher (P < 0.01) in subjects on the chicken-fish diet than in those on the red meat diet. In conclusion, this study showed that the effect of two lipid-lowering diets containing either lean red meat or skinless chicken and fish on the atherogenic lipoproteins did not differ significantly. A prudent diet with skinless chicken and fish, however, had a more favorable effect on the fatty acid composition of the plasma TAG and the CE than did the lean red meat diet.

Iodine deficiency and endemic goitre in the Langkloof area of South Africa.

OBJECTIVE: To quantify the prevalence of iodine deficiency and endemic goitre in the Langkloof area. DESIGN: A cross-sectional study. SETTING: Four primary schools in four communities in the Langkloof. SUBJECTS: 565 primary schoolchildren from Standard 2 to Standard 5. OUTCOME MEASURES: Clinical diagnosis of thyroid size by palpation, level of iodine in urine and drinking water samples, level of iodine in iodised salt samples from the area, percentage of households with iodised salt on the premises, and anthropometric measures of body height and weight. RESULTS: The prevalence of endemic goitre varied from 14.3% to 30.2% in the four communities and, based on urinary iodine levels, the iodine deficiency ranged from mild to severe. Both iodised and non-iodised salt were available at the local grocery stores but only small percentages of households had iodised salt in the house. The iodine content of drinking water was low. Anthropometric indices of undernutrition indicated medium to high levels of stunting in three of the four communities, the worst being in the community with the highest goitre prevalence. CONCLUSIONS: Endemic goitre caused by iodine deficiency is a public health problem in the Langkloof, varying in severity from mild to severe in the different communities. The impact of mandatory iodisation of table salt, introduced at the end of 1995, needs to be assessed in these communities.

Nutritional status of rural children in the Lesotho Highlands.

A baseline cross-sectional study was done to evaluate the nutritional status of the population of the Mohale Dam catchment area before construction of the dam commenced. In this article we report on the anthropometric, clinical and dietary assessment of the children less than 15 years of age in the study population. A two stage stratified sampling technique was used to randomly select 29 of the 83 villages in the study area. Children under 15 years of age from 395 households, representing approximately 50% of households in the selected villages, were included in the study. Anthropometric measurements of body height and weight in relation to age and sex indicated undernutrition varying, with few exceptions, from high to very high levels in children under 15 years. Stunting, indicating chronic undernutrition, was of particular concern in children, even from the first year of life. Very few clinical signs of nutritional deficiencies were found except for a goitre prevalence of 17.5% in 10 to 14 year old children. This was supported by the very low urinary iodine excretion (median 1.3 micrograms/dL) which indicated a severe iodine deficiency. Dietary evaluation showed high initiation rates of breastfeeding as well as a long duration of breastfeeding. Complementary foods were introduced at an early age, resulting in low exclusive breastfeeding rates. Regular meals were reported but qualitative analysis of the diet showed that a too small variety of foods were eaten, with an irregular intake of protein-rich foods and milk. Quantitative data on 3- < 5-year-old children showed that micro-nutrient intakes were low and that the energy intake of these children was inadequate. The results showed that these nutritionally vulnerable children should be monitored for the impact of the dam construction on their nutritional status.

PIP: The nutritional status of children under 15 years of age, from South Africa's Mohale Dam catchment area, was investigated in a cross-sectional baseline study conducted before dam construction began. 323 children, from 29 of the 83 villages in the study area, underwent anthropometric, clinical, and dietary assessment. The mean Z-score of height-for-age varied between -1.39 and -1.93 in the different sex and age groups. The percentage of children with a height-for-age less than -2 standard deviations (SDs) below the median of the reference population (indicating stunting) was 38.5-44.9% among boys and 30.7-37.0% among girls. Weight-for-height scores below -2 SDs (indicating wasting) occurred in 0.7-3.4% of children under 10 years old. 15-17% of children under 10 years old were underweight, but this rate increased to 34.8% in boys aged 12-15 years, and declined to 7.7% in older girls. The prevalence of stunting increased from 21.5% in the first year of life to 38.5% in the second year, while that of underweight increased from 7.7% to 19.2%. Goiter was present in 17.5% of 10-14 year olds, consistent with a median urinary iodine excretion of only 1.3 mcg/dl (severe iodine deficiency). Although breast feeding was widespread and of long duration, complementary foods were introduced early (mean, 4.0 months for liquids other than milk; 4.5 months for solids). Dietary analysis revealed irregular intake of protein-rich foods and milk, as well as a lack of variety; fewer than 10 foods represented almost the entire selection. The energy intakes of children 3-5 years old were inadequate. The high prevalence of stunting in this population indicates a need for interventions such as increased food availability and quality, salt iodization, adequate supplies of potable water, and treatment and prevention of infectious diseases. The impact of dam construction and resettlement on these nutritionally vulnerable children should be monitored.

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.

Dietary patterns and nutritional status in free-living older white men with established vascular disease.

Thirty-nine white men aged 51-84 years with established vascular disease were studied to investigate the effect of fish oil capsules on the regression of these lesions. This article deals with the baseline data of the study. The subjects completed a 7-day dietary record, weight and height were measured and a fasting blood sample was analysed for proteins, haematological values and certain vitamins. Dietary analysis indicated that the mean energy intake was 8,552 kJ (SD = 2,095). The energy distribution was 15.5% protein, 33.6% fat and 46.4% carbohydrate. In the light of the recommended dietary allowances the diet was lacking in zinc, vitamin B6 and folic acid, which suggests that the subjects might be deficient in these micronutrients. Although the diets were lacking in these nutrients, no clinical stigmata were observed. The subjects averaged a body mass index of 26.1 and could therefore be classified as overweight. The mean haematological values as well as the plasma vitamins were within the normal range. In conclusion it can be said that the men consumed a diet that was too high in fat and that the diet lacked certain micronutrients.

DNA screening of hyperlipidemic Afrikaners for familial hypercholesterolemia.

Three different point mutations of the low-density lipoprotein receptor (LDLR) gene are responsible for familial hypercholesterolemia (FH) in about 90% of Afrikaner patients. Screening of hyperlipidemic Afrikaner individuals for these founder-related mutations was performed to determine the distribution of the mutations in individuals with different lipid profiles, and to provide guidelines for screening of the mutations in hyperlipidemics. Rapid DNA methods, based on restriction enzyme analysis or allele-specific hybridisation of enzymatically-amplified genomic DNA, have been used to analyse the LDLR gene mutations in four groups of Afrikaner individuals. Group 1 included 84 individuals in whom FH was diagnosed on clinical data. Groups 2-4 included 89 hyperlipidemic individuals who did not fulfil the criteria for inclusion in the FH study group. The founder-related LDLR gene mutations were present in 36% of the hyperlipidemics whose clinical diagnosis excluded them from the FH study group. This indicates that conventional methods for the diagnosis of FH, based mainly on lipid determinations and a family history of coronary heart disease, do not always allow an accurate diagnosis of the disease. Screening of hyperlipidemic Afrikaner individuals for specific founder-related LDLR gene mutations can provide a definite diagnosis of FH, which may lead to better counselling and optimal treatment.

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.

Isolation and characterization of adult bovine heart muscle chalones.

A three-step purification procedure for the isolation of heart muscle chalones is described. The method uses ultrafiltration followed by concanavalin A-Sepharose affinity chromatography and subsequent sucrose density gradient centrifugation. Analytical ultracentrifugation of the highly purified chalone fraction indicated a sedimentation coefficient of 16.7 S and an average Mr of 715,527. Chemical analyses have confirmed this protein to be a glycoprotein, and polypeptide analysis indicated the involvement of identical subunits in its composition. In vivo studies confirmed that the chalone isolated from adult bovine hearts inhibits DNA synthesis of newborn hamster hearts. In addition, it was found to be tissue and not species specific and had no cytotoxic effects on the target cells.

[A new method of measuring serotonin in plasma and cerebrospinal fluid]. / 'n Nuwe metode vir die bepaling van serotonien in bloed en serebrospinale vloeistof.

A new rapid method for the microdetermination of serotonin (5-hydroxytryptamine) in plasma and cerebrospinal fluid is described. A recovery coefficient of 98% was obtained in the present method, with the use of [3H]-hydroxytryptamine creatinine sulphate as an internal standard, compared with recovery coefficients of 31% and 66% for the two existing methods generally used for serotonin determination. This method involves a one-step sample deproteinization by perchloric acid, resulting in a high stability of serotonin.