The scourge of HIV-related tuberculosis: a cohort study in a district general hospital in Malawi

Malawi is similar to a number of other African countries in having an escalating, HIV-related, tuberculosis (TB) epidemic. A prospective study was carried out to determine the pattern of disease and HIV serostatus in unselected, adult, TB patients consecutively admitted to a large, district general hospital in Zomba (in the Southern region of Malawi). Clinical details were obtained, from the district TB register, for the 714, adult TB patients, aged > or = 15 years, who were registered with the district TB officer between 1 July and 31 December in 1995. Patients were counselled, and offered HIV testing using an ELISA and particle agglutination test. Concordant HIV-test results were available for 686 (96%) of the subjects: 547 (80%) of these were HIV-seropositive and 139 seronegative. The HIV-positive patients were significantly younger than the HIV-negative patients and significantly more HIV-positive patients were males (P < 0.05 for each). The proportions of HIV-positive subjects who were new patients, had been previously treated for TB, had pulmonary TB (PTB), had smear-positive PTB or had different types of extrapulmonary TB were similar to those of the HIV-negative. A high percentage of an unselected cohort of adult TB patients admitted to a district, general hospital in Malawi, particularly of the younger age groups was therefore HIV-positive. The pattern of disease was uninfluenced by the HIV serostatus. The large number of cases registered emphasises the severity of the current epidemic of TB in Malawi and its impact upon young adults.     

Comparison of a novel microaerobic system with three other gas-generating systems for the recovery of Campylobacter species from human faecal samples

Three commercial gas-generating systems--CampyGen (Oxoid, UK), Oxoid BR56 (Oxoid, UK), and CampyPak Plus (Becton Dickinson, USA)--and the evacuation replacement technique were compared for the recovery of Campylobacter spp. from 500 human faecal samples collected from patients with gastroenteritis. Four hundred fifty faecal samples were tested upon receipt in the laboratory. Fifty faecal samples that had been previously found to be positive for Campylobacter spp. were tested retrospectively; these had been stored at 4 degrees C for more than 48 h. A total of 41 (9.1%) of the fresh faecal samples and 41 of 50 (82%) of the stored faecal samples were positive for thermophilic campylobacters. The CampyGen, the Oxoid BR56, the CampyPak Plus, and the evacuation replacement system detected Campylobacter spp. in 40 (97.6%), 39 (95.1%), 41 (100%), and 41 (100%) of the positive fresh faecal samples and in 37 (90.2%), 40 (97.6%), 39 (95.1%), and 40 (97.6%) of the stored samples, respectively. There was no statistical difference in performance of any of the four gas systems used (p = 0.98; chi-square test). Eighty-six percent of the isolates were Campylobacter jejuni and 14% were Campylobacter coli. Biotyping and phage typing of the isolates demonstrated that they were of a diverse range of subtypes. This study demonstrates that thermophilic campylobacters can be isolated from human diarrhoeal faecal samples using any of the four microaerobic-atmosphere-generating systems.     

Response to cognitive-behavioral therapy in depression: effects of pretreatment cognitive dysfunction and life stress

Response to cognitive-behavioral therapy (CBT) for depression is variable and the factors that account for differences in response are not yet well established. Level of cognitive dysfunction and the occurrence of negative life stress have been theorized as patient variables, which may account for differences in response to CBT. The relationship between response to CBT and the interaction of cognitive dysfunction with negative life events was examined in a sample of 53 depressed outpatients. Overall, there was little support for the prediction of a difference in acute outcome between patients with or without pretreatment cognitive dysfunction and negative stressors.     

In vitro selection of RNA lectins: using combinatorial chemistry to interpret ribozyme evolution

BACKGROUND: It has been hypothesized that the fact that both ribosomal RNA and the group I intron can bind to aminoglycoside antibiotics implies that these RNAs are evolutionarily related. This hypothesis requires the assumption that there are relatively few ways for RNA molecules to form aminoglycoside-binding sites. RESULTS: We have used in vitro selection to determine the diversity of aminoglycoside-binding sites that can be formed by RNA molecules. We have generated RNA 'lectins' that can bind aminoglycosides tightly and specifically. Sequence analysis indicates that there are many different ways to form tight and specific aminoglycoside binding sites. These artificially selected binding sites are functionally similar to those that have arisen from natural selection. CONCLUSIONS: Our results suggest that the presence of aminoglycoside-binding sites on RNA molecules may not be a useful trait for determining evolutionary relatedness. Instead, the fact that RNA molecules can bind these 'low molecular-weight effectors' may indicate that natural products such as aminoglycosides have evolved to exploit sequence- and structure-specific recognition of nucleic acids, in much the same way that lexitropsins have been designed by chemists to recognise specific nucleic acid sequences.     

Functional limitations to daily living tasks in the aged: a focus group analysis

We assessed constraints on daily living of 59 healthy, active adults 65-88 years of age in focus group interviews. Individual comments about specific problems were coded along the dimensions of (a) the locus of the problem (motor, visual, auditory, cognitive, external, or health limitations); (b) the activity involved (e.g., transportation, leisure, housekeeping); (c) whether the problem was attributable to task difficulty or the perception of risk; and (d) response to limitations (perseverance, cessation, compensation, or self-improvement). The data provide information about the types of difficulties encountered in everyday activities as well as the way in which individuals respond to such difficulties. Each comment was also coded in terms of whether it was remediable via training, design changes, or some combination of the two. More than half of the problems that were reported had the potential to be improved in some way, thus providing direction for future research in human factors and aging. Actual or potential applications of this research include identifying problems and difficulties that older adults encounter in daily activities such as transportation and leisure; more specifically, determining the degree to which such problems are potentially remediable by human factors solutions. Applications of this research also include understanding the types of systems, products, and technologies that older adults interact with currently, or are interested in learning to use.     

CD95 expression in aged mice infected with tuberculosis

The interaction between CD95 and its ligand is an important homeostatic mechanism that leads to the induction of apoptosis in activated T cells. In view of recent evidence that this pathway might be defective in aged mice, this study investigated CD95 expression on T cells in old mice activated by infection with Mycobacterium tuberculosis. The results of the study do not support the hypothesis that CD95 is poorly expressed on CD4 T cells from old mice; instead, it was found that similar numbers of T cells from young and old mice expressed CD95, with the intensity of expression if anything higher on the cells from the old mice. In addition, the study demonstrated that changes in CD44 and CD45RB expression previously observed in young infected mice proceeded in a similar fashion in old animals and, as would be predicted, that CD95(hi) expression was primarily associated with CD4 T cells expressing the activated CD44(hi) CD45RBhi phenotype.     

Purification and characterization of human topoisomerase I mutants

A system for rapid purification and characterization of eukaryotic topoisomerase-I mutants has been developed. The system utilizes six-histidine tagging of human topoisomerase I expressed in Saccharomyces cerevisiae to enable purification by nickel-affinity chromatography. Virtually homogenous mutant proteins are then tested for their ability to relax supercoiled DNA plasmids and their capacity for binding, cleaving and religating short defined DNA substrates. Relaxation-deficient mutants were obtained by site-directed mutagenesis of selected highly conserved amino acids. The mutants Tyr723Phe (active site mutation), Arg488Gln and Lys532Glu were inert in relaxation of DNA, whereas Lys720Glu showed a 50-fold reduction in specific relaxation activity. Accordingly, only Lys720Glu showed low, but detectable cleavage activity on suicide DNA substrates, uncoupling the cleavage and religation events of topoisomerase I. The relative religation efficiency of Lys720Glu comparable to that of wild-type topoisomerase I, indicating that Lys720 is involved in interactions important for normal DNA cleavage, but not for the religation reaction. All mutants could be cross linked by ultraviolet light to bromo-dUTP-substituted DNA oligonucleotides carrying a topoisomerase-I-binding site, indicating that the deficiency of Tyr723Phe, Arg488Gln and Lys532Glu in DNA relaxation and cleavage is not due to an inability of these mutants to bind DNA non-covalently.