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Biomedical subjects

J Westhuyzen

Publications and source records attributed to J Westhuyzen.

At least 19 recordsLinked to original sources
PubMed2005

Dosing strategy for enoxaparin in patients with renal impairment presenting with acute coronary syndromes.

BACKGROUND: Phase III clinical studies have confirmed that enoxaparin is superior to standard heparin in reducing the rate of recurrent ischaemic events in patients with non-ST elevation acute coronary syndromes. Patients with moderate to severe renal impairment were, however, excluded from these studies. Due to the hydrophilic disposition of enoxaparin, accumulation is likely in patients with renal dysfunction, thereby increasing the risk of haemorrhagic complications if standard weight adjusted treatment doses are used. Arbitrary dose reduction has been reported to increase the risk of ischaemic events, presumably due to inadequate enoxaparin concentrations. AIM: The aims of this study were to investigate the influence of glomerular filtration rate (GFR) on the pharmacokinetics of subcutaneously administered enoxaparin, and to develop a practical dosing algorithm in renal impairment that can easily be used at the bedside. METHODS: Thirty-eight patients, median age 78 years (range 44-87), mean GFR 32 ml min(-1) (range 16-117) and mean weight 69 kg (range 32-95), presenting with acute coronary syndrome were recruited into the study. Approximately 10 anti-Xa concentrations were taken per patient over their period of therapy. A population pharmacokinetic model was developed using non linear mixed effects modelling techniques, utilizing the software NONMEM. Stochastic simulations were performed to identify the most suitable dosing regimen. RESULTS: Three hundred and thirteen anti-Xa concentrations were collected. A two compartment, first order input model was identified as the best baseline model. Covariates found to improve model fitting were GFR as a linear function on clearance (CL) and weight as a linear function on the central volume compartment (Vc). The fraction of drug excreted unchanged (Fu) was estimated at 71%. CL and Vc from the final covariate model were estimated as; CL (l h(-1)) = 0.681 per 4.8 l hr(-1) (GFR) + 0.229 Vc (l) = 5.22 per 80 kg (total body weight) CONCLUSIONS: Clearance of enoxaparin was predictably related to GFR estimated using the Cockroft and Gault equation, with ideal body weight used as the size descriptor. According to our model no dosage adjustment from the standard 1.0 mg kg(-1) 12 hourly is required for the first 48 h of treatment. Maintenance doses thereafter can be calculated using standard proportional adjustments based on Fu equal to 0.71.

Administration, Cutaneous↗
PubMed2001

Effect of lipid-lowering dietary recommendations on the nutritional intake and lipid profiles of chronic peritoneal dialysis and hemodialysis patients.

Patients with end-stage renal failure are a high-risk group for atherosclerotic cardiovascular disease and commonly have dyslipidemia as a major factor. Dietary manipulation is the recommended first line of therapy for reducing lipid levels in people with normal renal function; however, complex dietary requirements of dialysis-treated patients with end-stage renal failure impose significant constraints. In this study, we evaluated the effect of trying to comply with established lipid-lowering recommendations superimposed on our normally prescribed dialysis diet over 14 weeks in stable subjects treated with either hemodialysis (HD) or chronic peritoneal dialysis (PD). Of 306 dialysis patients screened, 75 subjects were enrolled; 8 subjects did not complete the study. In the remainder, HD subjects (n = 41) decreased saturated fat intakes by 18% overall and cholesterol intakes by 16%. This was associated with a decrease in total cholesterol levels from 232 +/- 8 to 209 +/- 4 mg/dL (mean +/- SEM; P = 0.007) and low-density lipoprotein cholesterol levels from 147 +/- 4 to 131 +/- 4 mg/dL (P = 0.009). However, energy intakes decreased by almost 10%. There were no statistically significant changes in PD patients (n = 26). Only 24.4% of HD (10 of 41 patients) and 15.4% of PD patients (4 of 26 patients) normalized their lipid levels. Considerable problems were encountered in maintaining compliance with the modified dialysis diets. This study shows that if adhered to, properly constructed dialysis diets are close to optimal lipid-lowering recommendations. Further dietary manipulation is difficult, leads to little benefit in the majority, and is accompanied by added problems of adherence. We conclude that the vast majority of dyslipidemic patients with end-stage renal failure require pharmacological therapy.

Body Mass Index↗
PubMed2000

Review: Biology and relevance of C-reactive protein in cardiovascular and renal disease.

C-reactive protein (CRP) is a member of the pentraxin family of proteins, which are characterised by a cyclic pentameric structure and radial symmetry. The five identical 24-kDa protomers consist of 206 amino acids, and are noncovalently linked. CRP binds to a range of substances such as phosphocholine, fibronectin, chromatin, histones, and ribonucleoprotein in a calcium-dependent manner. It is a ligand for specific receptors on phagocytic leukocytes, mediates activation reactions on monocytes and macrophages, and activates complement. Plasma CRP is the classical acute-phase protein, increasing 1,000-fold in response to infection, ischemia, trauma, burns, and inflammatory conditions. A growing number of studies suggest that CRP is an independent risk factor for atherosclerotic vascular disease. Plasma CRP concentrations in the highest quartile are associated, depending on the subject group, with 1.5- to 7-fold increases in relative risk. In the high-risk endstage renal failure population, a raised CRP is associated with up to 5.5-fold increased relative risk of CVD and 4.6-fold increased relative risk of death. This review examines the relationships between CRP, cardiovascular disease, and mortality, with special reference to renal disease.

C-Reactive Protein↗
PubMed2000

Are metalloproteins and acute phase reactants associated with cardiovascular disease in end-stage renal failure?

End-stage renal failure (ESRF) is associated with a higher risk of cardiovascular disease (CVD) than predicted by the major risk factors. We investigate the hypothesis that metalloproteins such as transferrin and ceruloplasmin and the inflammatory response are associated with CVD risk in this population. In this cross-sectional study of 81 subjects stable on haemodialysis (HD), 43 with CVD and/or peripheral vascular disease (PAD) were compared to 38 subjects without clinical evidence of CVD/PAD. Serum concentrations of metalloproteins and acute phase reactants were compared by univariate analysis and logistic regression modelling. Body mass index, gender ratios, prevalence of diabetes, iron status, and homocysteine concentrations did not differ significantly between the groups. Those with CVD were older (P< 0.001) and had been on dialysis for longer (P = 0.004). CVD subjects had significantly higher concentrations of ceruloplasmin (325 vs 284 mg/L, P = 0.011), copper (18.2 vs 15.7 micromol/L, P = 0.002), and C-reactive protein (CRP) (median 9.0 vs 3.8 mg/L, P = 0.002). Transferrin iron binding capacity tended to be higher in the CVD group (P = 0.088). CVD risk for subjects with serum concentrations in the upper tertile was increased 9.4-fold (CI 2.8-31.0) for copper, 4.2-fold (CI 1.5-12.2) for ceruloplasmin, 3.9-fold (CI 1.3-12.1) for transferrin iron binding capacity, and 2.3-fold (CI 0.9-6.1) for CRP. In multivariate logistic regression models, age (P = 0.001) and time on dialysis (P = 0.002) were the strongest risk factors for CVD. After adjustment for age and time on dialysis, transferrin iron binding capacity (P = 0.013) and copper (P = 0.019) continued to be associated with CVD risk but ceruloplasmin (P = 0.065) and CRP (P = 0.634) were not. Total cholesterol was associated with a lower risk of CVD (ie protective), presumably due to cholesterol-lowering therapy in high-risk patients. In conclusion, copper and transferrin iron binding capacity may be associated with CVD risk in HD subjects.

Acute-Phase Proteins↗
PubMed1999

Comparison of low-molecular-weight heparin (enoxaparin sodium) and standard unfractionated heparin for haemodialysis anticoagulation.

BACKGROUND: Low-molecular-weight heparin (LMWH) has been suggested as providing safe, efficient, convenient and possibly more cost-effective anticoagulation for haemodialysis (HD) than unfractionated heparin, with fewer side-effects and possible benefits on uraemic dyslipidaemia. METHODS: In this prospective, randomized, cross-over study we compared the safety, clinical efficacy and cost effectiveness of Clexane (enoxaparin sodium; Rhône-Poulenc Rorer) with unfractionated heparin in 36 chronic HD patients. They were randomly assigned to either Clexane (1 mg/kg body weight, equivalent to 100 IU) or standard heparin, and followed prospectively for 12 weeks (36 dialyses) before crossing over to the alternate therapy for a further 12 weeks. Heparin anticoagulation was monitored using activated coagulation times. RESULTS: Dialysis with Clexane resulted in less frequent minor fibrin/clot formation in the dialyser and lines than with heparin (P<0.001), but was accompanied by increased frequency of minor haemorrhage between dialyses (P<0.001). Clexane dose reduction (to a mean of 0.69 mg/kg) eliminated excess minor haemorrhage without increasing clotting frequencies. Mean vascular compression times were similar in both groups. Over 24 weeks, no changes in standard serum lipid profiles were observed. CONCLUSIONS: This study suggests that a single-dose protocol of Clexane is an effective and very convenient alternative to sodium heparin, but currently direct costs are about 16% more. We recommend an initial dose of 0.70 mg/kg.

Adult↗
PubMed1998

Comparative response to single or divided doses of parenteral iron for functional iron deficiency in hemodialysis patients receiving erythropoietin (EPO).

EPO treatment rapidly corrects anemia in patients with end-stage renal failure treated with hemodialysis, as long as sufficient iron is available. Absolute and relative (to demand) iron deficiency blunts the erythropoietic response and parenteral iron is frequently required during the course of therapy to restore EPO efficacy. Since the optimum time course of iron administration to restore EPO response in the short term is unknown, we compared three protocols of i.v. iron dextran administration in apparent functionally iron-deficient HD patients on oral iron therapy (hemoglobin < 10.0 g/dl plus ferritin < 100 micrograms/l and/or transferrin saturation < 20%). Intravenous iron (Imferon; Fisons Pty Ltd.) was given either as a single 600 mg dose (n = 15, Group I) or in divided doses of 100 mg administered on 6 successive dialyses (n = 14, Group II) or weekly for 6 weeks (n = 14, Group III). Response was monitored for 8 weeks. No adverse effects were observed. Collectively, mean hemoglobin increased (p < 0.01) by 0.4-0.5 g/dl plateauing at 4 weeks (between group comparison, p = 0.92). Mean ferritin concentrations changed with time (p < 0.01), peaking at 2 weeks in Groups I and II and at 4 weeks in Group III. Mean transferrin saturation levels also increased during the study (p < 0.001). The between group comparisons for the trends in iron indices were significant (p < 0.01 and 0.05 respectively). As there were no clinically significant differences in hemoglobin response at 4 weeks, single dose iron infusion would seem to be the most expedient in the short term, however frequent small doses are similarly effective.

Aged↗
PubMed1997

Oxidation of low density lipoprotein in hemodialysis patients: effect of dialysis and comparison with matched controls.

End stage renal failure is associated with lipoprotein abnormalities and a high prevalence of premature atherosclerosis. Oxidative modification of low density lipoprotein (LDL) may be promoted by hemodialysis increasing its atherogenicity. The oxidative status of LDL was therefore examined in female subjects before and after routine hemodialysis (HD; n = 10) and compared with women of similar age without significant renal disease (n = 19). There were no significant differences between the groups in the LDL fatty acid composition, or in the content of reactive amino acid groups (lysine) before or after exposure to Cu2+. The kinetics of LDL oxidation by Cu2+ showed no significant differences between the groups with respect to the lag time, the level of conjugated dienes before and after oxidation, or the maximal rate of oxidation during the propagation phase. No acute effects of HD were demonstrated. The present study provides no evidence that circulating LDL isolated from HD patients is more extensively modified or more susceptible to oxidation in vitro than gender-matched controls without renal failure.

Aged↗
PubMed1997

Effect of preoperative supplementation with alpha-tocopherol and ascorbic acid on myocardial injury in patients undergoing cardiac operations.

Augmentation of antioxidant defenses may help protect tissues against ischemia-reperfusion injury associated with operations involving cardiopulmonary bypass. In this study we examined the effect of pretreating patients with alpha-tocopherol (vitamin E) and ascorbic acid (vitamin C) or placebo on injury to the myocardium. Seventy-six subjects undergoing elective coronary artery bypass grafting participated in a prospective, double-blind, placebo-controlled randomized trial, receiving either placebo or both 750 IU dl-alpha-tocopherol per day for 7 to 10 days and 1 gm ascorbic acid 12 hours before the operation. Plasma alpha-tocopherol concentrations, raised fourfold by supplementation, fell by 70% after the operation in the supplemented group and to negligible levels in the placebo group. There were no significant differences between the groups with respect to release of creatine kinase MB isoenzyme over 72 hours, nor in the reduction of the myocardial perfusion defect determined by thallium 201 uptake. Electrocardiography provided no evidence of a benefit from antioxidant supplementation. Thus the supplementation regimen prevented the depletion of the primary lipid soluble antioxidant in plasma, but provided no measurable reduction in myocardial injury after the operation.

Adolescent↗
PubMed1997

Simplified sizing of low-density lipoprotein using polyacrylamide gradient gel electrophoresis of plasma.

Low-density lipoprotein (LDL) particles can be separated into subfractions according to size by non-denaturing polyacrylamide gradient gel electrophoresis. Established research methods require specialised equipment and are frequently unsuited to the clinical laboratory. In this study, we utilised a colour flat bed scanner in conjunction with shareware image analysis software to compare LDL particle diameters of isolated LDL with LDL in whole plasma. LDL was isolated by ultracentrifugation and electrophoresed on 3-13% gels (Gradipore; Sydney, Australia) for 2400 Volt-hours in parallel with plasma and molecular size standards. Coomassie Blue-stained gels were scanned in reflexive mode using a colour flat-bed scanner and Adobe Photoshop 3.0 software. Density traces of each lane were obtained using NIH Image software (public domain, USA). LDL particle diameters were determined from calibration curves of the log of molecular diameter of standards against migration distance. There was a good correlation between LDL particle diameters obtained using isolated LDL and whole plasma (r = 0.87, P < 0.001; n = 22). However, the group means (+/- S.D.) (24.7 +/- 0.6 and 24.8 +/- 0.5 nm respectively) were statistically different on the paired t-test (P < 0.05). It is unclear whether this numerically small difference is due to alterations in LDL during the longer preparative procedures for LDL, or to matrix effects during electrophoresis of plasma samples. In conclusion, plasma samples stained with Coomassie Blue and scanned with a colour flat bed scanner can conveniently be used for LDL particle sizing by non-denaturing polyacrylamide gradient gel electrophoresis.

Adult↗
PubMed1996

Monitoring of extracellular and total body water during haemodialysis using multifrequency bio-electrical impedance analysis.

Multifrequency bio-electrical impedance analysis (MFBIA) was evaluated as a technique for monitoring changes in extracellular and total body water (ECW and TBW, respectively) of 15 subjects during dialysis. Dilution analysis, using deuterium oxide and sodium bromide, was also performed on each subject before dialysis so that prediction equations for ECW and TBW based on the MFBIA measures could be developed. These prediction equations were then used to estimate water compartment volume changes during dialysis and compared with volumetric measures of the dialysate removed. The results show that MFBIA does not accurately measure ECW and TBW changes during dialysis. The MFBIA measures tend to overestimate the changes and are not sufficiently precise to be clinically useful.

Adult↗
PubMed1995

Evidence for oxidative stress during in vitro dialysis.

The evidence for oxidative stress during haemodialysis is controversial. We therefore examined markers of oxidative stress and lipid peroxidation using an in vitro dialysis circuit. A unit of fresh blood (500 ml) therapeutically removed from each of 7 haemochromatosis patients was oxygenated and circulated for 4 h at 37 degrees C through a cuprophane dialyser (Clirans C08) against saline dialysate (1,000 ml recirculating; +FIL group). In a second series of experiments (n = 7), the dialyser was omitted from the circuit (-FIL group). Concentrations of anti-oxidants and malondialdehyde (MDA) were measured at 7 time points during the study. Blood thiol concentrations decreased by 25.6% in the +FIL group (p < 0.05) but were unchanged in the -FIL group (p > 0.05; group comparison, p = 0.006). There were no significant differences between the groups, for the lipid-soluble anti-oxidants alpha-tocopherol, retinol and beta-carotene. Plasma MDA concentrations increased in both circuits (p < 0.001, respectively, no difference between groups). However, the susceptibility of red blood cells to lipid peroxidation (as determined by MDA production following a challenge with hydrogen peroxide) was unchanged by 120 min of dialysis. These in vitro experiments provide supporting evidence that haemodialysis is accompanied by measurable oxidative stress and plasma lipid peroxidation.

Antioxidants↗
PubMed1994

Tubular nephrotoxicity after cardiac surgery utilising cardiopulmonary bypass.

Markers of renal tubular injury were examined in 21 patients (16 male, 5 female, mean age 57.4 years) undergoing cardiac surgery utilising cardiopulmonary bypass. Postoperative urine outputs were very high (200-250 ml/h at 1-2 h), decreasing to 100 ml/h by 6 h. Although creatinine clearances did not vary significantly in the postoperative period (P = 0.16), significant changes were noted in the urinary concentrations of three tubular markers relative to creatinine concentration (P < 0.001). Urinary beta 2-microglobulin increased from negligible levels (median 0.01 mg/mmol creatinine) to peak at 4 h (median 4.55 mg/mmol), in part due to interference with its reabsorption by the plasma volume expander Haemaccel. Concentrations of the brush border antigen adenosine deaminase binding protein increased 6-fold, from a median of 5.03 arbitrary units (AU)/mumol to 31.2 AU/mumol at 48 h. The lysosomal enzyme N-acetyl-beta-D-glucosaminidase increased nearly 4-fold, from 0.68 units/mmol to 2.64 units/mmol at 48 h. Our results suggest that cardiac surgery utilising cardiopulmonary bypass is associated with acute tubular injury which can occur in the absence of overt changes in creatinine clearance.

Acetylglucosaminidase↗
PubMed1993

23Na-NMR detects hypoxic injury in intact kidney: increases in sodium inhibited by DMSO and DMTU.

Hypoxic injury in the isolated perfused rat kidney (IPRK) was monitored using 23Na-NMR in the presence or absence of 1.5 and 15 mM dimethylthiourea (DMTU) or 15 mM dimethylsulphoxide (DMSO) before and after inducing hypoxia. Hypoxia induced a prompt exponential increase in total renal 23Na+, renal vascular resistance, and sodium excretion and decreased inulin clearance and adenine nucleotides and reduced glutathione concentrations. Lipid peroxide metabolites were unaltered. The increase in 23Na+ was significantly reduced (P < 0.001) by both DMTU and DMSO although hypoxic perturbations of function and biochemical parameters were not. Posthypoxic increases in renal 23Na+ include approximately 10% from the intratubular compartment, but principally reflect the intracellular and interstitial compartments. The results demonstrate that 23Na-NMR is a sensitive indicator of hypoxic renal injury in intact kidney and suggest that DMTU and DMSO protect against hypoxic injury by a mechanism independent of free radical-binding.

Animals↗
PubMed1993

Effect of withdrawal of folic acid supplementation in maintenance hemodialysis patients.

The requirement of patients on maintenance hemodialysis for dietary supplements of folic acid is controversial. High levels of folate carry the risk of toxicity as well as being unnecessary. We followed a group of 41 patients, not receiving erythropoietin, for 16 months after the cessation of folate supplementation (5 mg/day). Diet supplied 60-80 g protein and 120-260 micrograms folic acid/day. Red cell folate levels decreased linearly from a mean of 1931 +/- 888 micrograms/l (+/- SD) to 676 +/- 294 micrograms/l after 6 months before levelling off at 455 +/- 222 micrograms/l after 9 months. Mean values were unchanged 7 months later (491 +/- 319 micrograms/l). No patient developed folate deficiency. Hemoglobin values at 6, 9 and 16 months were slightly higher than the baseline value of 8.3 +/- 1.8 g/dl (p < 0.05). Mean corpuscular volumes were generally within normal limits, and vitamin B12 status was satisfactory. We conclude that folic acid supplements are unnecessary in adequately nourished hemodialysis patients who are not receiving erythropoietin.

Adult↗
PubMed1992

Effect of dialyzer reprocessing with Renalin on serum beta-2-microglobulin and complement activation in hemodialysis patients.

The peracetic acid-based sterilant Renalin is increasingly being used for reprocessing hemodialyzers. In order to evaluate the effects of reprocessing on beta 2-microglobulin (beta 2M) kinetics and complement activation in chronic hemodialysis patients, we compared 4 dialyzer membranes on 1st, 2nd and 4th use of the membrane. Dialysis with new cuprammonium rayon dialyzers (0.8 m2) for 4 h resulted in a nonsignificant increase in serum beta 2M concentrations of 10.7% (corrected for changes in extracellular volume) and significant generation of the complement component C3a des Arg. On reuse, minimal changes in serum beta 2M levels were noted and complement activation was absent. Dialysis with new cellulose acetate (CA, 1.5 m2), polyacrylonitrile (AN69 HF, 1.6 m2) or polymethylmethacrylate (PMMA, 1.6 m2) membranes resulted in significant decreases in serum beta 2M levels (19.5, 31.7 and 50.8%, respectively). Reprocessing had negligible effects on the removal of beta 2M by CA and AN69, but by the 4th use halved the effectiveness of PMMA. Reprocessing reduced the significant generation of C3a des Arg observed with new CA and PMMA membranes. We conclude that, except for PMMA, Renalin reprocessing has minor effects on the ability of the membranes to remove beta 2M and improves the biocompatibility of all membranes studied.

Acetic Acid↗
PubMed1992

Haematological nutrition of schoolchildren in the far northwestern cape.

The prevalence of anaemia and deficiencies of iron, folate and vitamin B12 were investigated in primary schoolchildren of mixed ethnic origin living in four towns in a remote semi-desert area of southern Africa, the Richtersveld. Anaemia was uncommon (6.3%); iron and vitamin B12 deficiencies were not observed. Sub-normal erythrocyte folate concentrations were present in 14.5%, but significant folate deficiency was rare (less than 2%). There were negligible differences in the haematological parameters of the children in the four towns, even though children living in Kuboes received milk at school and children at Dryfsandt a lunch of milk, brown bread and margarine. The results support the general observation that schoolchildren are not a risk group for nutritional anaemia.

Adolescent↗