The value of the QRS scoring system in assessing regional and global left ventricular ejection fraction early after myocardial infarction

In 71 patients with a myocardial infarction (MI) (anterior in27, inferior in 44 patients) global (GEF) and regional (REF)left ventricular ejection fractions were determined by radionuclideventriculography and estimated from a 12 lead electrocardiogram(ECG), using Selvester's QRS score, during the early phase ofa MI (15 to 21 days following MI). Global ejection fractionsdetermined by radionuclide ventriculography and from ECG usingPalmeri's method were: for all M140.8 ± 12.6% vs 39.6± 11.4%; in the group of anterior M132.0 ± 10.0%vs 30.0 ± 9.7% and in the group of inferior MI 48.9±12.0%vs 45.1 ± 8.2%. A good correlation was found betweenglobal ejection fractions determined by radionuclide ventriculographyand ECG, as well as between radionuclide GEF and ECG score.A weaker correlation was found between radionuclide GEF andenzymes among all MIs and in the group of anterior MI, whilein the group of inferior MI this correlation was insignificant.The analysis of REF determined by radionuclide ventriculographyand ECG showed the greatest abnormalities in the infarct region,but in the group of anterior MI, dysfunction was present inthe whole left ventricle. The comparison of infarct-relatedREF derived from radionuclide ventriculography, with the QRSscore showed a significantly higher correlation than the comparisonwith enzymes. ECG estimation of REF from a modified Palmeri'sequation showed a better correlation with radionuclide REF thandid GEF derived from the standard Palmeri's equation: anteriorMI; r = 0.90 vs r = 0.82, inferior MI; r = 0.84 vs r = 0.69,respectively. Our results underline the value of relativelysimple ECG methods for the assessment of left ventricular globalfunction, and new possibilities for the estimation of regionalfunction in patients with myocardial infarction.     

Evaluation of the Abbott m2000rt RealTime™ HIV-1 assay with manual sample preparation compared with the ROCHE COBAS AmpliPrep™/AMPLICOR™ HIV-1 MONITOR v1.5 using specimens from East Africa

The performance of the Abbott m2000rt RealTime™ HIV-1 assay (RealTime HIV-1) with manual sample preparation was compared against the ROCHE COBAS^® AmpliPrep™/AMPLICOR™ HIV-1 MONITOR^® Test v1.5 (CAP/CA HIV-1) using samples collected from 100 donors infected with HIV and 20 donors not infected with HIV in northern Tanzania where HIV-1 subtypes A, C, D, and their recombinant forms predominate. The RealTime HIV-1 appeared to have more within-run variability at high HIV-1 RNA concentrations, but total assay variability over the dynamic range tested was within the manufacturer's claim of <0.3 SD copies/mL. Accuracy studies showed 100% concordance for positive and negative values. When continuous values were examined, CAP/CA HIV-1 yielded higher values than the RealTime HIV-1 at higher nominal HIV-1 RNA concentrations. The RealTime HIV-1 assay showed excellent linearity between 2.5 and 7.0 log copies/mL. Of negative samples, 100% showed negative results, and >95% of samples with nominal concentrations of 40 copies/mL were detected at ≥40 copies/mL by RealTime HIV-1. Manual sample preparation may contribute to higher total assay variability. This study suggests that the Abbott m2000rt RealTime HIV-1 assay with manual sample preparation is an acceptable and feasible alternative to the conventional ROCHE COBAS AmpliPrep/AMLICOR HIV-1 Monitor v1.5 assay and that the RealTime HIV-1 assay performs well on samples from East Africa.     

Enhanced oxidative stress and increased mitochondrial mass during Efavirenz-induced apoptosis in human hepatic cells

BACKGROUND AND PURPOSE

Efavirenz (EFV) is widely used in the treatment of HIV-1 infection. Though highly efficient, there is growing concern about EFV-related side effects, the molecular basis of which remains elusive.

EXPERIMENTAL APPROACH

In vitro studies were performed to address the effect of clinically relevant concentrations of EFV (10, 25 and 50 µM) on human hepatic cells.

KEY RESULTS

Cellular proliferation and viability were reduced in a concentration-dependent manner. Analyses of the cell cycle and several cell death parameters (chromatin condensation, phosphatidylserine exteriorization, mitochondrial proapoptotic protein translocation and caspase activation) revealed that EFV triggered apoptosis via the intrinsic pathway. In addition, EFV directly affected mitochondrial function in a reversible manner, inducing a decrease in mitochondrial membrane potential and an increase in mitochondrial superoxide production, followed by a reduction in cellular glutathione content. The rapidity of these actions rules out any involvement of mitochondrial DNA replication, which, until now, was thought to be the main mechanism of mitochondrial toxicity of antiretroviral drugs. Importantly, we also observed an increase in mitochondrial mass, manifested as an elevated cardiolipin content and enhanced expression of mitochondrial proteins, which was not paralleled by an increase in the mtDNA/nuclear DNA copy number ratio. The toxic effect of EFV was partially reversed by antioxidant pretreatment, which suggests ROS generation is involved in this effect.

CONCLUSION AND IMPLICATIONS

Clinically relevant concentrations of EFV were shown to be mitotoxic in human hepatic cells in vitro, which may be pertinent to the understanding of the hepatotoxicity associated with this drug.     

Decline in HIV prevalence among women of childbearing age in Moshi urban, Tanzania

The objective of this study was to describe trends over time in HIV prevalence, sexually transmitted infections (STIs) and sexual behaviour among women in Moshi urban, Tanzania. Two cross-sectional studies were conducted in 1999 and in 2002-04 among women attending three primary health-care clinics. They were interviewed and screened for HIV and STIs. There was a significant decrease in HIV prevalence (11.5-6.9%). The decline was greatest among women aged 15-24 years. Syphilis, trichomoniasis, bacterial vaginosis, genital ulcers and reported STI symptoms also decreased significantly over the three-year inter-survey period. The proportion of women reporting casual sex decreased and knowledge of STI symptoms and health-care seeking behaviour improved. Herpes simplex virus type 2, genital warts, age at sexual debut, age at first pregnancy and condom use remained unchanged. In conclusion, decline in curable STIs and casual sex partners may partly explain the observed decline in HIV seroprevalence. Both STIs and sexual behaviour should be monitored in HIV sentinel surveillance. There remains a gap between knowledge of preventive behaviour and actual preventive practices.     

Generation of a panel of antibodies against proteins encoded on human chromosome 21

Background  

Down syndrome (DS) is caused by trisomy of all or part of chromosome 21. To further understanding of DS we are working with a mouse model, the Tc1 mouse, which carries most of human chromosome 21 in addition to the normal mouse chromosome complement. This mouse is a model for human DS and recapitulates many of the features of the human syndrome such as specific heart defects, and cerebellar neuronal loss. The Tc1 mouse is mosaic for the human chromosome such that not all cells in the model carry it. Thus to help our investigations we aimed to develop a method to identify cells that carry human chromosome 21 in the Tc1 mouse. To this end, we have generated a panel of antibodies raised against proteins encoded by genes on human chromosome 21 that are known to be expressed in the adult brain of Tc1 mice