Association between tuberculosis treatment outcomes and the mobile antiretroviral therapy programme in Zambia.

SETTING: Free antiretroviral therapy (ART) services in Zambia were introduced in hospitals beginning in 2005 and in selected rural health centres (RHCs) beginning in 2007 through the mobile ART programme. OBJECTIVE: To analyse the impact of scaling up ART services on tuberculosis (TB) treatment outcomes in Mumbwa District, Zambia. DESIGN: TB patients registered at all RHCs in the district between July 2006 and September 2009 were reviewed. RHCs were divided into two groups: 'ART sites', which provided ART services after 2007, and 'non-ART sites', which did not provide such services even after 2007. A before-after comparison analysis of TB patients was conducted between the groups. RESULTS: A total of 732 patients were enrolled (median age 34.5 years; female 44.4%). The overall human immunodeficiency virus (HIV) testing rate was 72.3% and 66.7% of these patients were HIV-positive. The TB treatment success rate at the ART sites increased significantly compared to non-ART sites after the mobile ART programme was started (P < 0.01). The HIV testing acceptance rate also increased dramatically at ART sites, which facilitated intensified case finding (P = 0.02). CONCLUSION: Scaling up ART services in rural health facilities through the mobile ART programme was found to be associated with greatly improved anti-tuberculosis treatment outcomes.

An Evaluation of a Refresher Training Intervention for HIV Lay Counsellors in Chongwe District; Zambia

To address a severe shortage of human resources for health; the Zambian Ministry of Health has begun to make use of lay counsellors for HIV counselling and testing. However; their skills and knowledge rarely have been reviewed or refreshed. We conducted a two-day refresher workshop for lay counsellors to review their performance and refresh their skills and knowledge. The objective of this study was to evaluate the refresher training intervention for HIV lay counsellors in the rural district of Chongwe in Zambia. The two-day refreshertraining workshop was held in November 2009. Twenty-five lay counsellors were selected by District Health Office and participated in the workshop. The workshop included: the opening; a pre-training exercise; lectures on quality assurance with regard to testing and safety precautions; lectures on counselling; filling the gap/QetA session; and a post-training exercise. In both the pre- and post-trainingexercise; participants answered 25 true/false questions and tested 10 blood panel samples to demonstrate their knowledge and skill on HIV counselling and testing. The average overall knowledge test score increased from 79 to 95 (p0.001). At the baseline; knowledge test scores in topic of standard precaution and post-exposure prophylaxis were relatively low (58) but rose to 95 after the training (p0.001). The per cent agreement of HIV testing by lay counsellors with reference laboratory was 99.2. Participants' knowledge was improved during the workshop and skill at HIV testing was found to remain at a high level of accuracy. Relatively weak knowledge of standard precautions and post-exposure prophylaxis suggests that lay counsellors are at risk of nosocomial infections; particularly in the absence of refresher training interventions. We conclude that the refresher training was effective for improving the knowledge and skills of lay counsellors and provided an opportunity to monitor their performance

The MM2-cortical form of sporadic Creutzfeldt-Jakob disease presenting with visual disturbance.

A subclass of sporadic Creutzfeldt-Jakob disease (sCJD) characterized by onset with visual symptoms (Heidenhain variant) has been reported to belong to the MM1 or MV1 type according to Parchi's classification. The authors report a 65-year-old woman with MM2-cortical sCJD with slowly progressive visual disturbance as the initial symptom. Diffusion-weighted MRIs revealed hyperintensity in both occipital cortices at an early stage.

Hypoxia down-regulates endostatin production by human microvascular endothelial cells and pericytes.

Endostatin is a potent anti-angiogenic factor derived from the C-terminal region of collagen XVIII and is implicated in the regulation of physiological and pathological angiogenesis. In this study, reverse transcription-polymerase chain reaction analysis of poly(A+) RNA demonstrated the presence of mRNA for collagen XVIII in human endothelial cells (EC) and pericytes, the very constituents of microvessels wherein angiogenesis takes place. Enzyme immunoassay revealed that both cell types liberated endostatin into culture media and that the endostatin levels were decreased by hypoxia, the principal cause of angiogenesis. Northern and Western blot analyses revealed that while the collagen XVIII/endostatin mRNA levels were invariant between hypoxic and normoxic conditions, the collagen XVIII protein levels in EC and pericytes decreased by hypoxia. Further, exogenously administered intact endostatin was significantly decreased when it was incubated with hypoxic conditioned media of endothelial cells or pericytes, but not with normoxic media. The results suggest that the reduction of autocrine endostatin may take an active part in hypoxia-driven angiogenesis.

Antiproliferative activity of REIC/Dkk-3 and its significant down-regulation in non-small-cell lung carcinomas.

We recently reported the cloning of the REIC/Dkk-3 gene, whose expression was shown to be down-regulated in many human immortalized and tumor-derived cell lines [T. Tsuji et al. (2000) Biochem. Biophys. Res. Commun. 268, 20-24]. In the present study, we demonstrated that expression of the exogenous REIC/Dkk-3 gene in tumor cells inhibited cell growth. Furthermore, the level of REIC/Dkk-3 mRNA in normal human cells was lowest in the late G(1) phase during the cell cycle. Then we found that the expression of REIC/Dkk-3 was significantly down-regulated in surgically resected non-small-cell lung carcinomas. We determined the REIC/Dkk-3 locus on chromosome 11p15, where loss of heterozygosity has frequently been observed in human tumors. These findings indicate that REIC/Dkk-3 may function as a tumor suppressor.

Reduced expression of REIC/Dkk-3 gene in non-small cell lung cancer.

Dickkopfs (Dkks) are secretory glycoproteins and are important for inducing amphibian head formation. Some Dkks have the ability to antagonize the Wnt proto-oncoprotein, which can promote cell proliferation and transformation when it is mutated or overexpressed. We recently cloned the REIC/Dkk-3 gene, one of the Dkks, and found that expression of the gene was markedly decreased in many human immortalized and tumor-derived cell lines. To further investigate the function of the REIC/Dkk-3 gene in vivo, the gene expression was quantified in 57 surgically-resected non-small cell lung cancer (NSCLC) tissues and their adjacent normal lung tissues by real-time quantitative PCR analysis based on TaqMan methodology. The REIC/Dkk-3 mRNA level was significantly lower in NSCLC tissues than in normal lung tissues. Reduced expression of REIC/Dkk-3 in NSCLC was observed in 36 (63%) of the 57 tumors. Reduced expression of REIC/Dkk-3 was frequently observed in poorly differentiated adenocarcinoma and squamous cell carcinoma. These results indicate that reduced expression of REIC/Dkk-3 may be correlated with rapid cell proliferation in human NSCLC.

Microsatellite instability correlates with normal expression of cyclin E in hepatocellular carcinomas.

It has been reported that microsatellite instability (MSI) strongly correlates with carcinogenesis and cancer progression. In the present study, we studied the incidence of MSI at 5 polymorphic microsatellite markers (D5S406, D13S153, D16S402, D17S796, and poly(A) tract BAT26), the expression of G1 cyclins (cyclin A, cyclin D and cyclin E), and Ki-67 labeling index in 30 surgically resected hepatocellular carcinomas (HCCs) and their adjacent non-cancerous tissues. The results of analysis showed that 43% of HCCs exhibited MSI in one locus, 10% in two loci, and 3% in three loci. Overexpressions of cyclin E and cyclin A were observed in 57% and 83% of HCCs, respectively. MSI in HCCs, however, correlated with normal expressions of cyclin E and cyclin A and with a low labeling index of Ki-67. Thus, patients with HCCs exhibiting MSI at these 5 markers may have less involvement of G1/S disregulation and may have better prognosis than other patients with HCC.

Establishment of a human hepatoma cell line, HLE/2E1, suitable for detection of p450 2E1-related cytotoxicity.

By transfection of an expression vector of human cytochrome P450 2E1 (CYP2E1) into a human hepatoma cell line (HLE), a new cell line (HLE/2E1) that stably expresses activity of CYP2E1 has been established. The HLE/2E1 cell line expressed a higher level of CYP2E1 messenger ribonucleic acid than did the mother HLE cell line. CYP2E1 enzyme activity determined by a p-nitrophenol oxidation assay was also higher in HLE/2E1 cells than in HLE cells. In addition, the enzyme activity of the HLE/2E1 cells was increased by ethanol treatment. Exposure to acetaminophen (APAP) or buthionine sulfoximine (BSO) caused a greater decrease in viability of the HLE/2E1 cells than that of the HLE cells, as determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. The cytotoxicity of APAP or BSO to HLE/2EI cells was inhibited by the addition of ethanol or vitamin E. However, the cytotoxicity of both APAP and BSO was enhanced by 24-h preincubation of HLE/2E1 cells with ethanol. These results show that this cell line provides a useful model for studying catalytic properties of CYP2E1 and cytotoxic mechanisms of chemicals metabolized by CYP2E1.

Invasive Ductal Carcinoma of the Nipple: A Case Report.

We report a very rare case of breast carcinoma which possibly arose from the duct of the nipple and formed a nipple mass. A 71-year-old woman presented with an elastically hard and enlarged right nipple, 3.5x 2.8 cm in size. Mammograms and ultrasonograms suggested a benign tumor of the nipple, but histological examination revealed invasive ductal carcinoma. No Paget's cells were found in the epidermis. Modified radical mastectomy was performed. Both estrogen and progesterone receptors were positive. One of the nine axillary nodes dissected had metastatic foci. To our knowledge, this case is only the second reported case of invasive ductal carcinoma originating from the nipple. Differential diagnosis and histogenesis are discussed.