No description available.

No description available.

No description available.

The cancer chemotherapeutic agent methotrexate inhibits the enzyme dihydrofolate reductase leading to a depletion of cellular reduced folates and inhibition of thymidylate synthase. A predicted consequence of this depletion of cellular thymidylate residues is that the nucleotide dUMP may be incorporated into DNA in place of dTMP. The subsequent cycle of uracil removal and reincorporation by an excision-repair pathway may cause DNA damage, a possible contributory factor leading ultimately to cell death. DNA. damage, in the form of single- and double-strand breaks, was -5 detected in HeLa cells treated with high dose (>10 M) methotrexate using the sensitive nucleoid sedimentation technique and alkaline filter elution. The maximum level of DNA damage, in the form of single-strand breaks, was detected after only 1 hour of drug incubation, but breaks were not detectable after this time, presumably because they had been repaired. DNA double-strand breaks were detectable from 18 hours onwards, along with a small level of single-strand breaks. The presence of hypoxanthine together with the irethotrexate to overcome the inhibition of de novo purine biosynthesis led to a similar occurrence of strand breaks, although a greater number of double-strand breaks was detected. The early appearance of single-strand breaks coincided with a substantial decrease in cellular dTTP levels and loss in colony-forming ability of the cells. No significant changes in cell viability, as measured by a dye-exclusion assay, were detected until at least 12 hours drug incubation. The greater level of double-strand breaks in cells grown with methotrexate and hypoxanthine coincided with a greater loss in colony-forming ability in these cells. 6. Changes in chromatin structure in cells treated with drug for 24 hours or longer were detected as a faster sedimentation of nucleoids compared to control cells. These changes were not due to the supercoiled state of the DNA but were related to the protein component of the nucleoid cage structure. 7. The enzyme ADP-ribosyltransferase was found to be stimulated in response to the appearance of single-strand breaks, reaching a maximum stimulation of 2 - 3 fold after 3 hours incubation with methotrexate. With hypoxanthine present no activation was detected, even though single-strand breaks were present. In neither case was there a change in the degradation rate of ADP-ribose protein conjugates nor a significant change in intracellular NAD+ levels. 8. In methotrexate-treated cells, the activation of the transferase led to an increase in the ADP-ribosylation of three specific proteins, probably by the addition of mono (ADP-ribose) residues. 9. The complete inhibition of ADP-ribosyltransferase activity by 3-aminobenzamide, or the prevention by hypoxanthine of its activation by methotrexate, did not have any significant effect on changes in cell number, cell viability or colony-forming ability in cells incubated with methotrexate. Thus ADP-ribosylation of proteins is not an effective component during the cytotoxic action of methotrexate.

No description available.

No description available.

ABSTRACT The aim of this study was to review the clinical presentation and contribution of various independent variables to the clinical outcome of surgically treated chronic subdural haematoma at the time of discharge. The records of one hundred fifty patients harbouring chronic subdural haematomas who were treated at Chris Hani Baragwanath Hospital between November 2001 and March 2004 were studied, for the following data • Demographic details such as age, gender and race. • Pre-operative clinical data including clinical presentation, predisposing factors, neurological grade, duration of symptoms to treatment, pupillary size and reaction, CT brain appearance. • Type of operation. • Post-operative data including presence of symptomatic recurrence and outcome data as expressed by Glasgow outcome score.It was found that the clinical presentation varies between the age group below sixty years and above sixty years. The following factors were found to be statistically significant in determining likelihood of poor outcome. • Neurological grade on admission. • Abnormal pupils. • Associated co morbid conditions.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Science in Epidemiology and Biostatistics / Background: Malaria causes an overwhelmingly large number of cases and deaths around the globe every year, with over 90% of deaths occurring in sub-Saharan Africa. Namibia is among the sub Saharan countries that have malaria as a major public health problem, affecting most pregnant women and children in the northern regions. Insecticide treated net (ITN) distribution has been expanded in the northern regions since 2005, yet there is low ITN utilization. The associated factors for low ITN utilization are not well established. Objective: This study aimed to determine factors affecting the utilization of ITN among pregnant women in northern regions of Namibia. Specific objectives were to: (1) describe coverage of ITNs among pregnant women in terms of possession; (2) describe the utilization rate of ITN among pregnant women in northern regions; and (3) determine the association between various factors and utilization of ITN among pregnant women. The first study outcome measure was utilization of ITN, defined as an individual pregnant woman who had used an ITN the night before the survey day. The second outcome measure was coverage of ITNs, defined as possession of at least one ITN in each household, irrespective of whether or not it was being used. Methods: A cross sectional study design was used, using secondary data from a nationally representative survey which collected data on malaria interventions in regions of Namibia. The original survey collected data from a representative sample of 3000 households from 120 primary sampling units (PSUs) in nine regions country wide, using a stratified sampling method of two stages. This study targeted pregnant women in four northern regions, namely; Kavango, Ohangwena, Oshana and Omusati, in both rural and urban areas; who participated in the 2009 Namibia Malaria Indicator Survey (NMIS) from 4 April to 10 June 2009. A total of 83 pregnant women were included in the analysis out of 194 pregnant women who were interviewed during the 2009 survey. In the descriptive analyses, we described the demographic characteristics of pregnant women. In the analytic analyses, univariable and multivariable analysis (logistic regression) were conducted. Logistic regression was used to determine risk factors associated with ITN utilization. Results: The utilization of ITN was high (47%) for young women aged 15-24 years old. Overall, 67% of pregnant women aged 15-44 years old slept under bed nets the night prior the survey day. In the univariable analyses, being 35-44 years of age (OR 0.25; 95% CI: 0.07-0.89, p<0.02) and having information about malaria (OR 0.28, 95% CI: 0.09-0.85, p<0.03), were independently associated with ITN utilization. In the multivariate logistic regression model, none of the explanatory variables were significant at the 5% level. The study showed 98.8% overall coverage of ITNs among pregnant women in terms of possession. Conclusion: These findings have implications for malaria interventions in Namibia. While almost all the pregnant women recruited in the study possessed ITNs, a significant proportion did not utilize them. Older women were more likely to utilize ITNs. Interventions to improve utilization among pregnant women should target younger women below the age of 35. Women that had information on malaria were more likely to utilize ITN. Sensitising women about the epidemiology of malaria across Namibia could lead to improved utilization of ITNs. A national malaria strategic plan needs to incorporate targeted reproductive women’s education for malaria control in Namibia.

No description available.

No description available.