J.N.P. de Villiers

Earlier Age of Onset of Alzheimer's Disease in Patients with Both the Transferrin C2 and Apolipoprotein E‐ɛ4 Alleles

Abstract: The etiology of Alzheimers disease is now known to be multifactorial. The genetic factors transferrin C2 (TfC2) and apolipoprotein E ɛ4 (ApoE‐ɛ4) have both been associated with Alzheimers disease (AD). Transferrin is the carrier protein for iron in the blood, while ApoE is involved with the transport and redistribution of lipids. In the present study, the polymerase chain reaction (PCR) method was used to determine the frequency of both TfC2 and ApoE‐ɛ4 in 27 AD patients, 9 vascular dementia (VaD) patients, and 27 controls. Patients were diagnosed according to the criteria as set out in the 4th edition of the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM‐IV).

Efficiency of a closed-coupled solar pasteurization system in treating roof harvested rainwater.

Many studies have concluded that roof harvested rainwater is susceptible to chemical and microbial contamination. The aim of the study was thus to conduct a preliminary investigation into the efficiency of a closed-coupled solar pasteurization system in reducing the microbiological load in harvested rainwater and to determine the change in chemical components after pasteurization. The temperature of the pasteurized tank water samples collected ranged from 55 to 57°C, 64 to 66°C, 72 to 74°C, 78 to 81°C and 90 to 91°C. Cations analyzed were within drinking water guidelines, with the exception of iron [195.59 μg/L (55°C)-170.1 μg/L (91°C)], aluminum [130.98 μg/L (78°C)], lead [12.81 μg/L (55°C)-13.2 μg/L (91°C)] and nickel [46.43 μg/L (55°C)-32.82 μg/L (78°C)], which were detected at levels above the respective guidelines in the pasteurized tank water samples. Indicator bacteria including, heterotrophic bacteria, Escherichia coli and total coliforms were reduced to below the detection limit at pasteurization temperatures of 72°C and above. However, with the use of molecular techniques Yersinia spp., Legionella spp. and Pseudomonas spp. were detected in tank water samples pasteurized at temperatures greater than 72°C. The viability of the bacteria detected in this study at the higher temperature ranges should thus be assessed before pasteurized harvested rainwater is used as a potable water source. In addition, it is recommended that the storage tank of the pasteurization system be constructed from an alternative material, other than stainless steel, in order for a closed-coupled pasteurization system to be implemented and produce large quantities of potable water from roof harvested rainwater.

Isoniazid elimination kinetics in children with protein-energy malnutrition treated for tuberculous meningitis with a four-component antimicrobial regimen.

The impact of changing environmental factors--disease, nutrition and a high-dose multi-drug treatment regimen--on isoniazid (INH) elimination kinetics in children of both sexes and various ages was investigated. Thirteen children (mean age 2.3 years), hospitalized for the treatment of tuberculous meningitis, participated in the trial. Although all the children had protein-energy malnutrition, none had marasmus or kwashiorkor. After an oral dose of 20 mg/kg of INH, the concentrations in plasma were determined by the liquid chromatographic method of Lacroix et al. The 2-hour post-dose isoniazid concentration, the apparent first-order elimination rate constant and the corresponding INH half-life were determined in each child on two occasions 6 months apart. All comparisons were tested for significance using the Wilcoxon matched-pair signed-ranks test. There was no significant difference in any of the pharmacokinetic parameters of INH in our patients evaluated at the extremes of the 6-month term of treatment. It was apparent that changing conditions of disease and nutrition and a high-dosage, multi-component antimicrobial agent regimen over a 6-month period of treatment did not significantly influence INH elimination parameters. The trend evident in the pharmacokinetic profile of isoniazid in our children supports a trimodal distribution of acetylator phenotypes.

Mutation analysis reveals an insertional hotspot in exon 4 of the LDL receptor gene

Abstract Mutation analysis of the low density lipoprotein receptor (LDLR) gene revealed a novel 8-bp duplication after nucleotide 681 in a Costa Rican patient with familial hypercholesterolaemia. The frameshift caused by this mutation results in a premature termination codon in the EGF precursor homology domain of the mature LDLR, whereby a truncated protein of the first 206 residues with an additional 39 abnormal residues would be created. The insertion overlaps with previously described duplications of 18 bp and 21 bp, thus revealing an insertional hotspot in exon 4 of the LDLR gene. We propose that the structural features of this region of the LDLR gene contribute significantly to genetic instability and the subsequent DNA duplication via an endogenous sequence-directed mechanism of mutagenesis.

Retrograde aortic placentography

Summary In the radiological diagnosis of placenta praevia, aortic placentography is the method of choice before the thirty-fourth week. After the thirty-fourth week soft tissue placentography, in the hands of experts, is a primary alternative examination.

Allelic variation in the promoter region of the LDL receptor gene: analysis of an African-specific variant in the FP2 cis-acting regulatory element

DNA samples of 2303 individuals from nine different population groups were screened for variant -175g-->t in the promoter region of the low-density lipoprotein receptor (LDLR) gene. The -175g-->t variant detected at carrier frequencies of 3-10% in different African population groups was absent in the Caucasian and Asian (Chinese) individuals studied. In contrast to previous findings in Black South Africans where this polymorphism predominated in patients with familial hypercholesterolaemia (FH), it occurred at a significantly lower frequency in hypercholesterolaemics from the recently admixed Coloured population of South Africa compared with population-matched controls (P<0.0001). Haplotype and mutation analysis excluded the likelihood that this finding is due to association with a specific disease-related mutation in FH patients, although reversal of the positive association with FH observed in the Black population may, at least in part, be due to admixture linkage disequilibrium. Transient transfection studies in HepG2 cells demonstrated that the -175t allele is associated with a non-significant decrease ( approximately 7%) of LDLR transcription in the absence of sterols. The data presented in this study raise the possibility that the -175g-->t polymorphism may have subtle effects that become clinically important within certain genetic and/or environmental contexts.