Knowledge,attitudes & barriers to condom use among female sex workers and truck drivers in Uganda: a mixed-methods study

Background

There is limited documentation on knowledge, attitudes and barriers to condom use among female sex workers (FSWs) and truck drivers (truckers).

Objective

To explore knowledge, attitudes and barriers to condom use among FSWs and truckers operating along major transport corridors in Uganda

Methods

Structured questionnaires were administered to explore FSWs'' and truckers'' knowledge of and attitudes towards condom use among 259 FSWs and 261 truckers. Qualitative data were collected on barriers to condom use using focus group discussions. Quantitative data were analyzed using SPSS while qualitative data were audio-recorded, transcribed and thematically analyzed.

Results

Condom knowledge was high with 97% of FSWs and 95% of truckers agreeing with the statement, “using condoms properly and consistently reduces risk of HIV infection”. Attitudes towards condom use were generally favorable with 91% of FSWs and 82% of truckers agreeing with the statement, “condom use is the best method of HIV prevention”. Qualitative findings show that poverty, refusal to use condoms by male partners, alcohol use before sex and beliefs that condoms ‘kill the mood for sex’ remain key barriers to consistent condom use.

Conclusions

Consistent condom use among FSWs and truckers is still hampered by economic and relationship factors.     

Ex vivo expanded unselected peripheral blood: progenitor cells reduce posttransplantation neutropenia, thrombocytopenia, and anemia in patients with breast cancer

The safety and efficacy of administering ex vivo expanded peripheral blood progenitor cells (PBPC) to patients with breast cancer who undergo high-dose chemotherapy and PBPC transplantation was investigated. Unselected PBPC were cultured in gas-permeable bags containing 1-L serum-free media, granulocyte colony-stimulating factor, stem cell factor, and pegylated megakaryocyte growth and development factor for 9 days. Cell dose cohorts were assigned to have between 2 and 24 x 10(9) PBPC cultured at 1, 2, or 3 x 10(6) cells/mL. Twenty-four patients received high-dose chemotherapy followed by infusion of the cultured PBPC and at least 5 x 10(6) CD34(+) uncultured cryopreserved PBPC per kilogram. No toxicities resulted from infusions of the ex vivo expanded PBPC. The study patients had shorter times to neutrophil (P =.0001) and platelet (P =.01) recovery and fewer red cell transfusions (P =.02) than 48 historical controls who received the same conditioning regimen and posttransplantation care and at least 5 x 10(6) CD34(+) PBPC per kilogram. Improvements in all these endpoints were significantly correlated with the expanded cell dose. Nine of 24 (38%) patients recovered neutrophil counts above 500/microL by day 5 or 6 after transplantation, whereas none of the controls had neutrophil recovery before the eighth day. Seven (29%) patients had neutropenia for 3 or fewer days, and 9 (38%) patients did not experience neutropenic fevers or require broad-spectrum antibiotics. Therefore, ex vivo expanded PBPC are capable of ameliorating posttransplantation neutropenia, thrombocytopenia, and anemia in patients receiving high-dose chemotherapy.     

KRAS mutational subtype and copy number predict in vitro response of human pancreatic cancer cell lines to MEK inhibition

Background:

To study the molecular mechanism regulating sensitivity to MEK inhibition in pancreatic cancer cell lines.

Methods:

A growth inhibition assay determined sensitivity to MEK162 in a panel of 29 pancreatic cancer cell lines. For the same panel, KRAS mutational status and copy-number variation (CNV) was determine using PCR, array CGH and FISH. Two sensitive and two resistant cell lines were further interrogated for difference in baseline and MEK162-induced gene expression, as well as signal transduction using microarray and western blotting. Cell cycle and apoptosis analysis was measured by flow cytometry.

Results:

We report a strong correlation between both specific KRAS mutational subtype and CNV, and sensitivity to MEK inhibition. Cell lines with a KRAS (V12) mutation and KRAS gains or loss (n=7) are ∼10 times more resistant than those having neither a KRAS (V12) mutation nor KRAS CNV (n=14). Significant differences in baseline and MEK162-induced gene expression exist between the sensitive and resistant lines, especially in genes involved in RAS, EGF receptor and PI3K pathways. This was further supported by difference in signal transduction. MEK 162 blocked ERK1/2, as well as inhibited PI3K and S6 and increased p27KIP1 levels in the sensitive lines.

Conclusions:

Given the potency of MEK162, it may be a promising new therapy for patients with pancreatic cancer and KRAS mutational subtypes, and CNV may serve as important biomarkers for selecting patients that benefit from MEK-targeting based on these preclinical data.     

In vitro metabolism of a triclyclic alkaloid (M445526) in human liver microsomes and hepatocytes

The in vitro metabolism of M445,526 (ZD6,126 phenol) was investigated by incubating [(14)C]-M445,526 at a concentration of 10 microg ml(-1) with human hepatic microsomes (4 mg ml(-1)) or human hepatocytes (2 x 10(6) cells ml(-1)) for up to 180 min. Following incubation with microsomes and hepatocytes, up to 78% and 40% of [(14)C]-M445,526 was metabolized after 180 and 120 min, respectively. High-performance liquid chromatography (HPLC) with radiochemical detection confirmed extensive metabolism of [(14)C]-M445,526 by microsomes and hepatocytes. Mass spectrometry and (1)H-NMR spectroscopy enabled structural identification of up to eight metabolites. Human liver microsomes formed one major (O-desmethyl) and three minor (a further O-desmethyl and two different hydroxylated) phase I metabolites. Human hepatocytes produced one major metabolite, a sulphate conjugate of the major O-desmethyl metabolite formed by microsomes. Four minor metabolites were also formed, primarily by O-demethylation with subsequent glucuronidation. Taken collectively, [(14)C]-M445,526 underwent extensive in vitro metabolism by human liver fractions. These data were confirmed by subsequent human in vivo studies.