Pneumocystis jirovecii pneumonia (PCP) and cytomegalovirus (CMV) infection represent possible complications of medical immunosuppression. Between 2005 and 2010, non-human immunodeficiency virus (HIV) PCP patients admitted to a nephrology unit were analyzed for outcome, CMV comorbidity, and patient-to-patient contacts prior to PCP. In contrast to 2002-2004 (no cases) and 2008-2010 (10 cases), a PCP outbreak of 29 kidney-transplant recipients and one patient with anti-glomerular basement membrane disease occurred between 2005 and 2007. None of the patients were on PCP chemoprophylaxis. In four PCP patients, the genotyping data of bronchoalveolar lavage specimen showed an identical Pneumocystis strain. PCP cases had a higher incidence of CMV infection (12 of 30 PCP patients) and CMV disease (four patients) when compared to matched PCP-free controls (p < 0.05). Cotrimoxazole and, if applicable, ganciclovir were started 2.0 ± 4.0 days following admission, and immunosuppressive medication was reduced. In-hospital mortality was 10% and the three-year mortality was 20%. CMV co-infection did not affect mortality. CMV co-infection more frequently occurred during a cluster outbreak of non-HIV PCP in comparison to PCP-free controls. Here, CMV awareness and specific therapy of both CMV infection and PCP led to a comparatively favorable patient outcome. The role of patient isolation should be further investigated in incident non-HIV PCP.
Ultraviolet-A radiation represents a significant proportion of the ultraviolet solar spectrum that was recently shown to affect gene expression of epidermal keratinocytes by molecular mechanisms distinct from ultraviolet-B radiation. As ultraviolet-A either alone or in combination with ultraviolet-B may contribute to photocarcinogenesis, we aimed to explore the biologic effects of ultraviolet-A radiation on vascular endothelial growth factor gene expression by the immortalized keratinocyte cell line HaCaT. As keratinocyte-derived vascular endothelial growth factor not only provides the major cutaneous angiogenic activity but may also augment the malignant phenotype of tumor cells, we studied the molecular mechanisms of ultraviolet-A-induced vascular endothelial growth factor expression in HaCaT cells, serving as a transformed preneoplastic epithelial cell line. Whereas ultraviolet-B-mediated vascular endothelial growth factor expression has been previously indicated to be conveyed by indirect mechanisms, ultraviolet-A rapidly induced vascular endothelial growth factor mRNA expression in a fashion comparable to that seen with the transforming growth factor alpha, representing a direct and potent activator of vascular endothelial growth factor gene transcription. Ultraviolet-A was found to readily induce vascular endothelial growth factor promoter-based reporter gene constructs through a consensus element for activator protein-2 transcription factor. The critical role of activator protein-2 was substantiated by demonstration of ultraviolet-A-induced activator-protein-2-dependent nuclear DNA binding activity to this site, and by inhibition of ultraviolet-A-mediated vascular endothelial growth factor gene transcription through insertion of a critical mutation within the activator protein-2 sequence. Together, our data further elucidate photobiologic aspects of ultraviolet-A-induced gene expression by characterizing mechanisms of vascular endothelial growth factor upregulation at the molecular level. In addition, our experiments support the concept of a more general importance of activator protein-2 in ultra- violet-A-mediated responses by keratinocytes or keratinocyte-derived cell lines.
Based on our center's experience, TAVI appears to be an effective and safe alternative to conventional surgery for AVR in patients with prior renal transplantation. Renal transplantation is not currently identified as a risk factor in our traditional scoring system, and may need to be considered independently when weighing alternatives for AVR.
A new oral supplemental nutrition over 6 months had no treatment effect in surviving HIV-positive hemodialysis patients or in maintenance hemodialysis patients without HIV infection. The limitations of this study were small study size and unexpected high mortality among HIV-positive hemodialysis patients.
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