Browsing by Author "Marais, David"

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    Cardiovascular risk factors in patients with Addison's disease: a comparative study of South African and Swedish patients
    (Public Library of Science, 2014) Ross, Ian Louis; Bergthorsdottir, Ragnhildur; Levitt, Naomi; Dave, Joel Alex; Schatz, Desmond; Marais, David; Johannsson, Gudmundur
    BACKGROUND: Patients with Addison's disease (AD) in Scandinavia have an increased risk for premature death due to cardiovascular disease (CVD). Serum lipids are important risk factors for CVD and vascular mortality. Replacement doses of hydrocortisone have historically been higher in Sweden than South Africa. The primary aim was to study the lipid profiles in a large group of patients with AD with the hypothesis that the lipid profile in patients in Sweden would be worse than in South Africa. METHODS: In a cross-sectional study, 110 patients with AD (55 from South Africa, 55 from Sweden) matched for age, gender, ethnicity and BMI were studied. Anthropometric measures, blood pressure, lipids, highly sensitive C-reactive protein (hs-CRP) and adiponectin were studied. RESULTS: All patients were Caucasian and the majority were women N = 36 (65.5%). Mean (standard deviation; SD) ages of the Swedish and South African patients were 52.9 (13.0) and 52.6 (14.4) years and BMI 25.3 (3.2) and 25.8 (4.1) kg/m 2 , respectively. The mean total daily hydrocortisone dose was greater in the Swedish patients than the South African patients, [33.0 (8.1) versus 24.3 (8.0) mg; p<0.0001]. South African patients had higher median (interquartilerange; IQR) triglycerides (TG) [1.59 (1.1-2.46) versus 0.96 (0.74-1.6) mmol/l; p<0.001], total cholesterol (TC) [6.02(1.50) versus 5.13 (0.87) mmol/l; p<0.001], LDL-C [4.43 (1.44) versus 2.75 (0.80) mmol/l; p<0.001] and median hs-CRP [2.15 (0.93-5.45) versus 0.99 (0.57-2.10) mg/L; p<0.003] and lower HDL-C [0.80 (0.40) versus 1.86 (0.46) mmol/l; p<0.001] than the Swedish patients. Approximately 20% of the patients in both cohorts had hypertension and diabetes mellitus. CONCLUSIONS: South African patients with AD have worse lipid profiles and higher hs-CRP compared to their matched Swedish patients, despite lower doses of hydrocortisone. It is uncertain at this time whether these are due to genetic or environmental factors.
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    The db mouse as a model for steatohepatitis
    (2006) Sutherland, Jason Robert; Hall, Pauline de la Motte; Marais, David
    Fatty liver disease is a collective phrase for a spectrum of diseases characterised by increased liver fat content. It ranges from fatty infiltration of the liver to an inflammatory condition, steatohepatitis, which may lead onto cirrhosis. Although not associated with alcohol consumption, non-alcoholic steatohepatitis (NASH) has strong associations with obesity, diabetes and dyslipidaemia. Overlapping pathological mechanisms may be involved. The course of the disease will remain unpredictable, and specific treatment will only be able to be instituted once the pathogenesis is fully understood. This thesis reviews current understanding of the pathogenesis and explores the suitability of a recently defined obese diabetic mouse model for its value as a model in the heterozygous and homozygous states. Observations revealed that the db/wt phenotype has a larger mass than the wt/wt and responds with hyperglycaemia. Lipid accumulation occurs in this model when alcohol is administered and lipid peroxidation occurs but histological changes of steatosis and steatohepatitis do not occur. The db/db model is phenotypically distinguished by a large amount of fat storage, diabetes and macrovesicular steatosis that has more lipid peroxidation but no steatohepatitis even when alcohol further increases lipid peroxidation. The model, as explored, did not reveal steatohepatitis either alone, or with alcohol as a single additional stressor, but both the db/wt and db/db mouse model could be further investigated to explore whether additional stressors could induce steaotohepatitis in this model.
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    Dyslipidaemia
    (2003) Marais, David
    Modern clinical practice commonly deals with the complications of atherosclerosis both in acute and potentially life-threatening and severely debilitating manifestations, and in chronic manifestations that may result in marked impairment of exercise and working capacity. Epidemiological information and intervention with drugs clearly indicate that atherosclerosis can be limited. Plasma lipids have been implicated in the pathogenesis of atherosclerosis, with variable strength of association: severe metabolic errors increasing risk profoundly while ‘moderate’ hypercholesterolaemia and low concentrations of high-density lipoprotein in concert with other risk factors can also signify a high risk. Other clinical problems linked with errors in lipid and lipoprotein metabolism include pancreatitis, malabsorption and many other rarer syndromes.
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    The effect of anabolic-androgenic hormones on postprandial triglyceridaemia and lipoprotein profiles in man
    (1997) Hislop, Michael Stuart; Marais, David; Noakes, Timothy D
    It has been hypothesised that endogenous testosterone and AAS may predispose humans to premature CHD. However, there is no direct evidence to link these hormones with a greater prevalence of premature CHD. The aim of this thesis was to better describe atherosclerotic risk associated with these hormones by clarifying their effect on additional risk factors for premature atherosclerosis. Little is known about the effect of testosterone and AAS on 'atherogenic dyslipidaemia', a phenotype characterised by elevated postprandial triglyceridaemia, small dense LDL and a low HDLC concentration, which confers a high risk of CHD. Accordingly, the magnitude of postprandial triglyceridaemia, LDL and HDL particle size, and LDLC, HDLC and Lp(a) concentration were compared in male (n=9) and female (n=3) bodybuilders after self administration of AAS for 5-6 weeks (ON cycle) and again after a 4-6 week 'washout' period (OFF cycle), and in normal males (T) (n=10) before and during a reversible suppression of endogenous testosterone, induced using a GnRH agonist (triptorelin), and in a control group (C) (n=8). Lipoprotein size was assessed by gradient gel electrophoresis (GGE), lipoprotein concentrations by immuno and enzymatic assay, and postprandial triglyceridaemia by a standardised oral fat tolerance test (65g/m² ). HDLC decreased in male bodybuilders (0.94±0.30 vs 0.70±0.27 mmol/L, p=0.004; x ± SD) and female bodybuilders (1.3±0.5 vs 0.8±0.2 mmol/L) ON cycle. GGE studies suggested that mostly HDL₂ was reduced. There were no significant reductions in LDL particle size ON cycle. Two males had larger LDL species ON cycle. Lp(a) decreased in male bodybuilders (124.7±128.0 to 69.3±73.3 U/L, p=0.008). ON cycle postprandial triglyceride excursion was unchanged in female bodybuilders and reduced (11.6±10.0 vs 7.5±5.4 mmol/L.hr; p=0.027) in male bodybuilders. In the triptorelin study, HDLC was increased in T (1.07±0.18 vs 1.41±0.28 mmol/L, p=0.002) and not in C. GGE studies indicated an increase of HDL₂ in five T subjects and no increase in C. Total cholesterol increased in T (4.77±0.80 vs 5.24±1.04 mmol/L, p=0.039) but not in C. LDL size increased in four T subjects, and not in C. Lp(a) increased in T (277.9±149.l vs 376.5±222.2 U/L, p=0.004), but not in C. Postprandial triglyceridaemia was unchanged in both T and C. The results of these studies did not show any additional atherogenic effects of endogenous testosterone or AAS in humans. Rather, a suppression of Lp(a) may be an antiatherogenic effect of these hormones. A reduced postprandial triglyceridaemia and increased LDL size in individuals who are predisposed to 'atherogenic dyslipidaemia', may be further antiatherogenic effects of AAS use.
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    How has the OSD affected our state hospitals?
    (2009) Parkes, Jeannette; Abratt, Raymond; Taylor, Allan; Le Feuvre, David; Murray, Elizabeth; Robertson, Barbara; Kotze, Tessa; Marais, David; Khan, Del; Kilborn, Tracy; Wieselthaler, Nicky; Gajjar, Himal; Handler, Lenny; Fagan, Johan; Spitaels, Ariane; Morrison, Adrian; Davidson, Alan; Salie, Shamiel; Urban, Mike; Rajkumar, Ash; Pretorius, Vincent; van Niekerk, Magriet; Ferreira, Germaine; Wolmerans, Marli; Cyster, Lyall; King, Darren; Okwuosa, Sebastian; van Staden, Sanet; van Niekerk, Margarethe; Winckler, Jana; Meissenheimer, Heinrich; Botes, Annie; Tait, Deon; Visagie, Jodine; Swarts, Steve; Klocke, Marina; Lomas, Vanessa; Marais, Ilke; Vijoen, Werner; Perry, Jennie; Nkosi, Nokwazi; Stuve, Katrin
    The long-awaited occupation-specific dispensation (OSD) process for state-employed doctors has now been concluded. The final offer, signed and accepted in the bargaining chamber despite being rejected by 92% of doctors in a SAMA survey, has not received much attention or fanfare. At the conclusion of this process, which has been drawn out over several years, many points have emerged that are extremely worrying for the future of health care in this country.
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    Lipoprotein metabolism and its derangements
    (2003) Marais, David
    The purpose of this article is to provide the medical practitioner with an understanding of lipids, lipoproteins and their metabolism and disorders. Such an understanding would enhance the assimilation of the sections on clinical assessment and treatment of dyslipoproteinaemia. Lipids may be defined as organic chemicals that are insoluble in water. In the biological context lipids are either carboxylic acids (fatty acids) or sterols, and their derivatives. Lipids are less dense than water and will float spontaneously or under centrifugal force. Cholesterol is the principal sterol in the animal kingdom and promotes the impenetrability of the phospholipid bilayer that constitutes the cell membrane. Additionally cholesterol is found in lipoproteins and in bile and is used to synthesise hormones and bile acids.
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    Nonalcoholic steatohepatitis (NASH) : animal studies of interactive hepatoxicity
    (2004) Clarkson, Vivian; Hall, Pauline de la Motte; Marais, David; Shephard, Enid
    The term "Nonalcoholic steatohepatitis" (NASH) describes a form of liver disease indistinguishable from alcoholic liver disease, but present in persons who consume insignificant amounts of alcohol. The spectrum of non-alcoholic liver disease ranges from non-progressive steatosis, through to NASH and sometimes to cirrhosis. Risk factors predisposing to NASH include obesity, diabetes mellitus, hypertriglyceridermia and procedures leading to rapid and profound weight loss such as gastric bypass and bulimia. Given the high incidence of type II diabetes, obesity and various types of hyperlipidaemia in the Western Cape, NASH has become one of the most commonly encountered liver diseases in the Liver Clinic, Groote Schuur Hospital. Statistics also suggest nonalcoholic fatty liver disease underlies most cases of elevated liver enzymes in many other parts of the world. The exact pathogenic mechanisms involved are not well understood, and no effective treatment options are currently available. However, animal models of NASH now provide unique opportunities for study of this disease in the laboratory setting. This thesis employs a dietary animal model, which restricts methionine and choline intake, to replicate aspects of the injurious process in human NASH. Two lines of inquiry are pursued. The first involves an assessment of the effect of alcohol consumption on fatty liver of non- alcoholic aetiology. Elevated liver enzymes, altered levels of lipid peroxides, and increased cytochrome P450 activity recorded in this study, suggest alcohol may exacerbate nonalcoholic fatty liver disease. The second line of inquiry is an exploration of the role of Tumor Necrosis Factor alpha (TNFα, a cytokine implicated in pathogenesis of alcoholic liver disease and thought to be pivotal in NASH pathogenesis. The role of TNFα in the dietary model of NASH is investigated using mice lacking functional TNFα genes, as well as wild type mice in which expression of this cytokine is induced by endotoxin challenge. Endotoxin challenge does elicit a marked inflammatory response and enhanced generation of lipid peroxides in the fatty liver, both of which may contribute to injury. However, as knockout mice still develop experimental NASH, TNFα cannot be considered the sole driving force required for the development of NASH. This strength of the project lies in the use of a variety of techniques (in the fields of Pathology, Immunology and Lipid Biochemistry) to investigate a range of aspects of NASH. The results of the alcohol study may provide the first empirical evidence supporting the need to restrict alcohol intake in patients with NASH, while the data on TNFα is vital for illuminating the complex, (potentially) counter-intuitive role of this cytokine in NASH. Where definitive conclusions cannot be drawn from the data, the questions posited may constitute the basis for future research.
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    Phytosterol-enriched margarine substitution in the management of familial hypercholesterolaemia
    (2002) Hamdulay, Zarina; Marais, David; Visser, Marianne
    The primary objective was to substitute phytosterol and regula margarine into the diets of familial hypercholesterolaemia (FH) patients and to investigate whether the phytosterol containing margarine had a cholesterol lowering effect. Another objective was to investigate immune responses to phytosterols. A randomized double-blind cross-over study in which subjects with FH consumed 20g of regular or phytosterol margarine for a period of 6 weeks on each margarine, after which a washout period of 4 weeks was followed. There were 5 visits in total, visit 1 being the collection of baseline data, visit 2 the randomisation to either of the regular of phytosterol margarine periods, visit 3 for the cross-ver to the alternative margarine form, visit 4 marked the onset of washout period and visit 5, was the last evaluation visit. Margarine use was in addition to current, albeit limite, pharmacological treatment with statins.
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    Polyacrylamide gradient gel electrophoresis for the diagnosis of dysbetalipoproteinaemia (Type III hyperlipidaemia)
    (2001) Blom, Dirk Jacobus; Marais, David
    Accurate phenotypic diagnosis of this disorder has generally relied on the quantitative analysis of centrifugally isolated VLDL. Analysis of VLDL chemical composition is not widely available due to the expense of acquiring ultracentrifuges and the highly-skilled staff necessary to perform the analyses. Genotypic diagnosis is somewhat more widely available, especially testing for the E2/E2 genotype which is the commonest underlying genotype in dysbetalipoproteinaemia. Testing for the rarer autosomal mutations of ApoE is restricted to a small number of centres only. In this study I will review dysbetalipoproteinaemia briefly and then describe and evaluate GGE as a new diagnostic technique for this disorder.
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    Risk assessment and clinical management of children and adolescents with Heterozygous Familial Hypercholesterolaemia. a position paper of the associations of preventive pediatrics of Serbia, mighty medic and international lipid expert panel
    (2021-10-25) Bjelakovic, Bojko; Stefanutti, Claudia; Reiner, Željko; Watts, Gerald F; Moriarty, Patrick; Marais, David; Widhalm, Kurt; Cohen, Hofit; Harada-Shiba, Mariko; Banach, Maciej
    Heterozygous familial hypercholesterolaemia (FH) is among the most common genetic metabolic lipid disorders characterised by elevated low-density lipoprotein cholesterol (LDL-C) levels from birth and a significantly higher risk of developing premature atherosclerotic cardiovascular disease. The majority of the current pediatric guidelines for clinical management of children and adolescents with FH does not consider the impact of genetic variations as well as characteristics of vascular phenotype as assessed by recently developed non-invasive imaging techniques. We propose a combined integrated approach of cardiovascular (CV) risk assessment and clinical management of children with FH incorporating current risk assessment profile (LDL-C levels, traditional CV risk factors and familial history) with genetic and non-invasive vascular phenotyping. Based on the existing data on vascular phenotype status, this panel recommends that all children with FH and cIMT ≥0.5 mm should receive lipid lowering therapy irrespective of the presence of CV risk factors, family history and/or LDL-C levels Those children with FH and cIMT ≥0.4 mm should be carefully monitored to initiate lipid lowering management in the most suitable time. Likewise, all genetically confirmed children with FH and LDL-C levels ≥4.1 mmol/L (160 mg/dL), should be treated with lifestyle changes and LLT irrespective of the cIMT, presence of additional RF or family history of CHD.