Incidence of ethambutol-related visual impairment during treatment of active tuberculosis.

BACKGROUND: Recent World Health Organization guidelines recommend the addition of ethambutol (EMB) throughout standardised treatment of new cases of active tuberculosis (TB) in populations with increased prevalence of isoniazid resistance to reduce the risk of creating multidrug resistance. This could expose patients to the risk of blindness. METHODS: We searched Cochrane, Embase and PubMed electronic databases from 1965 to February 2011 for original studies that prospectively followed all patients treated with EMB for active TB, and routinely ascertained the occurrence of visual toxicity using standard methods. Pooled estimates, overall and stratified by major covariates, were calculated using random effects meta-analysis. RESULTS: Pooled cumulative incidence of any visual impairment in all patients was 22.5 per 1000 persons treated with EMB (95%CI 10.2-35), and permanent impairment was 4.3/1000 (95%CI 0.3-9.0). After restricting the analyses to arms in which the average dose was 27.5 mg/kg/day or less and treatment was for 2-9 months, the incidence of any visual impairment was 19.2/1000 (95%CI 5.8-33), and permanent impairment was 2.3/1000 persons (95%CI 0-6.1) treated, as the majority of episodes were reversible. In reversible cases, resolution of impairment occurred after an average of 3 months. CONCLUSIONS: In this review, any visual impairment occurred in 22.5/1000 persons receiving EMB at standard doses for up to 9 months, and permanent impairment in 2.3/1000-an important risk. However, these estimates are imprecise, and the studies were of variable quality and the results heterogeneous. Well-designed prospective studies with repeated measurements of multiple visual parameters that clearly describe the degree of permanent impairment are needed.

The importance of a satisfactory biopsy for the diagnosis of lung cancer in the era of personalized treatment.

Advances in molecular biology are improving the understanding of lung cancer and changing the approach to treatment. A satisfactory biopsy that allows for histologic characterization and mutation analysis is becoming increasingly important. Most patients with lung cancer are diagnosed at an advanced stage, and diagnosis is often based on a small biopsy or cytology specimen. Here, we review the techniques available for making a diagnosis of lung cancer, including bronchoscopy, ultrasound-guided bronchoscopy, mediastinoscopy, transthoracic needle aspiration, thoracentesis, and medical thoracoscopy. We also discuss the indications, complications, and tissue yields of those techniques, especially as they pertain to testing for molecular markers.

Differential expression of Tie-2 receptors and angiopoietins in response to in vivo hypoxia in rats.

In this study, we assessed the effects of in vivo hypoxia on the expression of Tie-2 receptors and angiopoietins in various organs of conscious rats and correlated these effects with the expression of hypoxia-inducible factor-1 (HIF-1). RT-PCR and Southern blotting were used to amplify mRNA expression of angiopoietin-1, -2, and -3, Tie-2, and HIF-1 alpha in tissues of normoxic and hypoxic (fraction of inspired oxygen of 9--10% for either 12 or 48 h) rats. Hypoxia provoked a decline in angiopoietin-1 mRNA and Tie-2 mRNA, protein, and phosphorylation levels in the lung, liver, cerebellum, and heart but not in the kidney and diaphragm. In comparison, hypoxia raised the levels of angiopoietin-2 mRNA in the cerebellum and angiopoietin-3 mRNA in the lung, kidney, and diaphragm. HIF-1 alpha mRNA was abundant in most organs of normoxic rats but was significantly induced in the kidney and diaphragm of hypoxic rats. We conclude that in vivo hypoxia exerts inhibitory effects on the activity of the angiopoietin-1/Tie-2 receptor pathway through reduction of angiopoietin-1 and upregulation of angiopoietin-2 and -3. Induction of angiopoietin-3 in the kidney and diaphragm of hypoxic rats could be mediated through the HIF-1 transcription factor.