Adipokine serum concentrations, anthropometric measurements and socio-economic status in two ethnic groups with different prevalence levels for cardiovascular diseases and type 2 diabetes.

Obesity is more common in African than Asian-Indian populations and yet type 2 diabetes and cardiovascular diseases are more common in the latter populations. The main purpose of the current study was therefore to determine whether ethnic differences in body fat distribution, adipokine levels, and socio-economic status may explain population differences in the prevalence of these metabolic disorders. Leptin, IL-6, CRP, visceral fat, education level, and socio-economic status were measured in 50 African and the same number of Indian women residing in Johannesburg, South Africa. Serum leptin levels were significantly higher in Indian than African subjects (41.3±2.0 and 34.2±2.9 ng/ml, respectively; p<0.05). TNF-α levels were significantly higher in the African group, (5.22±0.86 vs. 2.54±0.52 pg/ml; p<0.05), whilst visceral fat levels were significantly lower (56.1±5.5 vs. 77.9±6.5 cm(2); p<0.05). The CRP and IL-6 levels were not different between groups. Education levels (p<0.005) and socio-economic status (p<0.0001) were both lower in the African subjects, however, adjusting for these variables in ANCOVA did not attenuate differences in adipokine or visceral fat levels. We hypothesise that one of the reasons for the higher prevalence of obesity in the African than Indian population may be related to lower leptin levels, whilst ethnic differences in the prevalence of metabolic disorders cannot be explained by differences in adipokine levels, but maybe related to higher visceral adiposity in the Indian group.

Performance of the CardioChek PA and Cholestech LDX point-of-care analysers compared to clinical diagnostic laboratory methods for the measurement of lipids.

Point-of-care (POC) blood testing is intended to provide results more rapidly than can be obtained from a central laboratory. Precision and accuracy of the CardioChek PA and Cholestech LDX analysers were compared to clinical diagnostic laboratory methods. In 100 patients, total cholesterol (TC), triglycerides (TG), HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) levels were measured by both analysers and compared to those analysed by the National Health Laboratory Service (NHLS) laboratory. Data were evaluated for conformance with National Cholesterol Education Program (NCEP) guidelines. Results were grouped into low, middle and high ranges and were similar to those obtained by the NHLS, except in the high range where TC and LDL-C levels were under-read by both analysers. All analytes measured by both analysers correlated significantly with NHLS (p < 0.0001). With the exception of LDL-C, both analysers showed reasonable compliance with NCEP goals for coefficients of variation and bias measurements. Both analysers met NCEP guidelines for all analytes at two clinical cut-off points. We concluded that, compared to NHLS methods, performance of the CardioChek PA and Cholestech LDX analysers is acceptable and that they offer healthcare professionals a rapid, POC method for the measurement of lipids.

Quantity versus quality of LDL cholesterol in patients with familial hypercholesterolemia--which is more important?

BACKGROUND: The aim of this study was to determine the effects of low-density lipoprotein (LDL) particle size and composition on the susceptibility of LDL to oxidation in subjects with Familial Hypercholesterolemia (FH). METHODS: LDL was isolated from 20 FH homozygotes, 20 FH heterozygotes and 20 normal controls. Susceptibility of LDL to ex vivo copper-mediated oxidation was assessed by measuring conjugated diene production at 234 nm. Other factors known to influence LDL oxidation, namely particle size, vitamin E levels, and fatty acid composition of the LDL particles were also measured. RESULTS: The mean duration of the lag phase was 1.42-fold longer in the FH homozygotes, and 1.21-fold longer in the FH heterozygotes than in the normal controls. LDL particle size was significantly larger in the FH homozygotes (26.45+/-0.37 nm) and FH heterozygotes (26.01+/-0.40 nm) compared to the normal control group (25.17+/-0.39 nm). LDL vitamin E concentrations, when expressed relative to LDL cholesterol concentrations, were similar in all the groups. In addition, no significant differences were observed in the total saturated, monounsaturated or polyunsaturated fatty acid content of LDL in the three groups of subjects. CONCLUSION: These results suggest that it is the great excess in LDL quantity, rather than LDL 'quality', that is responsible for the severe and premature atherosclerosis in patients with FH.

The prolactin response to sulpiride in major depression: the role of the D2 receptor in depression.

Multiple lines of investigations have implicated the role of the dopaminergic system in depression. The aim of the study was to characterise the Dopamine D2 receptor sensitivity status in depressed patients versus controls by means of a novel neuro-endocrine challenge test, the prolactin response to sulpiride. In this intervention, ten patients and ten age matched male volunteers were studied. The patients were diagnosed according to DSM-IV criteria, and Montgomery Asberg and Zung scales were done. There was no significant difference in baseline levels of prolactin between the depressed and control groups. Significantly higher prolactin levels after sulpiride challenge were however found in depressed patients than controls at all time points after sulpiride administration. This neuroendocrine challenge paradigm suggests that the prolactin response to sulpiride, a D2 receptor antagonist, is enhanced in depression, which suggests that this receptor might be supersensitive in depression compared to controls. This adds to the data implicating the dopaminergic system in the pathophysiology of depression, and suggests that dopaminergic mechanisms might be a target of therapeutic interest.

Co-inheritance of mutations in the uroporphyrinogen decarboxylase and hemochromatosis genes accelerates the onset of porphyria cutanea tarda.

Porphyria cutanea tarda is a skin disease caused by photosensitization by porphyrins whose accumulation is caused by deficiency of hepatic uroporphyrin- ogen decarboxylase activity. Mutations in the uroporphyrinogen decarboxylase gene are present in the low-penetrant, autosomal dominant familial form but not in the commoner sporadic form of porphyria cutanea tarda. We have investigated the relationship between age of onset of skin lesions and mutations (C282Y, H63D) in the hemochromatosis gene in familial (19 patients) and sporadic porphyria cutanea tarda (65 patients). Familial porphyria cutanea tarda was identified by mutational analysis of the uroporphyrinogen decarboxylase gene. Five previously described and eight novel mutations (A80S, R144P, L216Q, E218K, L282R, G303S, 402-403delGT, IVS2 + 2 delTAA) were identified. Homozygosity for the C282Y hemochromatosis mutation was associated with an earlier onset of skin lesions in both familial and sporadic porphyria cutanea tarda, the effect being more marked in familial porphyria cutanea tarda where anticipation was demonstrated in family studies. Analysis of the frequencies of hemochromatosis genotypes in each type of porphyria cutanea tarda indicated that C282Y homozygosity is an important susceptibility factor in both types but suggested that heterozygosity for this mutation has much less effect on the development of the disease.

Auto-antibodies against oxidized LDL as a marker of coronary artery disease in patients with familial hypercholesterolaemia.

Auto-antibodies to oxidized low-density lipoprotein (ox-LDL) are thought to play a pivotal role in the pathogenesis of atherosclerosis. This study investigates the value of auto-antibodies to ox-LDL as a predictive marker of atherosclerosis in patients with both homozygous and heterozygous familial hypercholesterolaemia (FH), who are known to suffer from severe premature atherosclerosis. The influences of well-established risk factors for atherosclerosis such as age, LDL-cholesterol levels and smoking on the results were also determined. Auto-antibody titres to ox-LDL and fasting lipid profiles were measured in 26 homozygous FH patients, 20 heterozygous FH patients without documented coronary artery disease (CAD), 24 heterozygotes with overt CAD and 10 healthy normocholesterolaemic controls. Carotid intima media thickness, used as an in vivo assessment of atherosclerosis, was also measured in the homozygous FH patients. Ox-LDL titres did not differ between the groups. There was also no association between ox-LDL titres and the LDL-cholesterol level (P=0.14), presence or absence of CAD (P=0.69), age (P=0.50), carotid intima-media thickness (P=0.51) or smoking (P=1.0). In conclusion, antibody titres against ox-LDL cannot be used as a predictive marker of the presence or severity of atherosclerosis in patients with FH.

Cell adhesion molecules - can they be used to predict coronary artery disease in patients with familial hypercholesterolaemia?

Adhesion of leukocytes to endothelial cells via cell adhesion molecules (CAMS) is thought to be pivotal in the initiation of atherosclerosis. As patients with familial hypercholesterolaemia (FH) are known to develop severe, premature coronary artery disease (CAD), we investigated the usefulness of soluble forms of CAMS namely vascular cellular adhesion molecule-1 (VCAM), intercellular cell adhesion molecule-1 (ICAM) and E-selectin as predictive markers of the presence and severity of atherosclerosis in this patient group. Twenty heterozygous FH patients without CAD; 24 heterozygous FH patients with CAD; 17 homozygous FH patients without documented CAD; nine homozygous FH patients with overt CAD; and 50 healthy controls were studied. Carotid artery intima media thickness (IMT) was also measured in the homozygous patients. Levels of the adhesion molecules VCAM, ICAM and E-selectin were not significantly elevated in homozygous FH patients and heterozygous FH patients, both with and without CAD, compared to the normal control subjects. In addition the range of results was so wide and the overlap of values with normal controls so great, that the use of an individual level of either VCAM, ICAM or E-selectin was not predictive of either the presence or degree of atherosclerosis in the FH subjects.

High nocturnal body temperatures and disturbed sleep in women with primary dysmenorrhea.

Primary dysmenorrhea is characterized by painful uterine cramps, near and during menstruation, that have an impact on personal life and productivity. The effect on sleep of this recurring pain has not been established. We compared sleep, nocturnal body temperatures, and hormone profiles during the menstrual cycle of 10 young women who suffered from primary dysmenorrhea, without any menstrual-associated mood disturbances, and 8 women who had normal menstrual cycles. Dysmenorrheic pain significantly decreased subjective sleep quality, sleep efficiency, and rapid eye movement (REM) sleep but not slow wave sleep (SWS), compared with pain-free phases of the menstrual cycle and compared with the controls. Even before menstruation, in the absence of pain, the women with dysmenorrhea had different sleep patterns, nocturnal body temperatures, and hormone levels compared with the controls. In the mid-follicular, mid-luteal, and menstrual phases, the dysmenorrheics had elevated morning estrogen concentrations, higher mean in-bed temperatures, and less REM sleep compared with the controls, as well as higher luteal phase prolactin levels. Both groups of women had less REM sleep when their body temperatures were high during the luteal and menstrual phases, implying that REM sleep is sensitive to elevated body temperatures. We have shown that dysmenorrhea is not only a disorder of menstruation but is manifest throughout the menstrual cycle. Furthermore, dysmenorrheic pain disturbs sleep, which may exacerbate the effect of the pain on daytime functioning.

A double-blind randomised placebo controlled trial of postnatal norethisterone enanthate: the effect on postnatal depression and serum hormones.

OBJECTIVES: To determine the effect of postnatal administration of the long-acting progestogen contraceptive, norethisterone enanthate, on postnatal depression and on serum hormone concentrations, and their association with depression. DESIGN: Double-blind randomised placebo-controlled trial. SETTING: A tertiary care hospital in Johannesburg, South Africa. POPULATION Postnatal women using a non-hormonal method of contraception (n = 180). METHODS: Random allocation within 48 hours of delivery to norethisterone enanthate by injection, or placebo. MAIN OUTCOME MEASURES: Depression scores in the three months postpartum as rated by the Montgomery-Asberg Depression Rating Scale (MADRS) and the Edinburgh Postnatal Depression Scale (EPDS); 2. serum 17beta-oestradiol, progesterone, testosterone and the 17beta-oestradiol:progesterone ratio at six weeks postpartum. RESULTS: There was a chance excess of caesarean section deliveries in the progestogen group. Mean depression scores were significantly higher in the progestogen group than in the placebo group at six weeks postpartum (mean MADRS score 8.3 vs 4.9; P = 0.0111; mean EPDS score 10.6 vs 7.5; P = 0.0022). Mean serum 17beta-oestradiol and progesterone concentrations were significantly lower in the progestogen group compared with the placebo group at six weeks postpartum. There were no correlations between any of the hormone parameters and depression at six weeks except in the formula feeding subgroup of the placebo group, where formula feeding and 17beta-oestradiol concentrations were positively associated with depression. CONCLUSIONS: Long-acting norethisterone enanthate given within 48 hours of delivery is associated with an increased risk of developing postnatal depression and causes suppression of endogenous ovarian hormone secretion.

Dietary iodine deficiency in South Africa. Surveys before the introduction of universal salt iodisation.

OBJECTIVE: To survey iodine nutritional status in several geographically separated communities in South Africa. DESIGN: In an initial study total goitre prevalence (TGP) was correlated with urinary iodine concentration (UIC) in some 300 primary school children in a single district. Thereafter only UIC was surveyed in children from 5 additional communities. RESULTS: In the initial survey in Mpumalanga TGP was 74.2% (23.4% visible) and the median UIC was 15.6 micrograms/l, both data indicating severe iodine deficiency in this district. Median UIC values indicated mild to severe iodine deficiency in districts in the Northern Province, moderate deficiency in the Eastern Cape, and mild deficiency in Soweto, Gauteng. Only non-black African children in Johannesburg were iodine-replete (UIC > 100.0 micrograms/l.) CONCLUSION: Before the introduction of compulsory iodisation of salt in December 1995, dietary iodine deficiency was widespread in South Africa.

Effect of calcium supplement preparation containing small amounts of citrate on the absorption of aluminium in normal subjects and in renal failure patients.

It is well known that Al absorption is markedly enhanced by citrate. The aim of the study was to document whether low-dose citrate ingestion (4 g/day) contained in a well-known effervescent calcium supplement was sufficient to increase Al absorption in 16 normal volunteers and 15 subjects with stable chronic renal failure under conditions of either Ca carbonate or Al hydroxide supplementation. Serum and urine Al levels were measured using flameless atomic absorption spectrophotometry as previously described. After Ca carbonate plus Ca citrate ingestion, there was no rise over baseline (Ca Carbonate alone) serum or urine Al levels in either group. Ca carbonate and Al hydroxide taken together produced a significant rise in serum and urine Al levels in both groups. Maintaing Al hydroxide but substituting Ca citrate for the carbonate (same dose of elemental Ca) produced a further significant increment in serum Al (0.47 +/- 0.28-1.15 +/- 0.8 mumol/l; p < 0.001) and in urine Al(1.37 +/- 0.46-5.77 +/- 5.21 mumol/l; p < 0.001) in the chronic renal failure group as well as in serum Al (0.42 +/- 0.2-0.76 +/- 0.48 mumol/l; p < 0.001) and urine Al (2.70 +/- 1.24-8.24 +/- 3.96 mumol/l; p < 0.001 in the normal volunteer group. Due to decreased urine excretion, the increment in serum Al in the CRF group was significantly greater than in the normal subjects (p < 0.02). Thus small quantities of citrate present in effervescing Ca supplements can significantly enhance intestinal Al absorption even in normal subjects. All citrate-containing preparations are totally contra-indicated in chronic renal failure patients ingesting Al-containing compounds.(ABSTRACT TRUNCATED AT 250 WORDS)