Citations

Background: Hypertension during pregnancy (HDP) increases the risk of future coronary heart disease (CHD), but it is unknown whether this association is mediated by renal injury. Reduced renal function is both a complication of HDP and a risk factor for CHD. Methods: Logistic regression models were fit to examine the association between a history of HDP and the presence and extent of coronary artery calcification (CAC), a measure of subclinical coronary artery atherosclerosis, in 498 women from the Epidemiology of Coronary Artery Calcification Study (mean age 63.3 ± 9.3 years). Results: Fifty-two (10.4%) women reported a history of HDP. After adjusting for age at time of study participation, HDP was associated with increased serum creatinine later in life ( p = 0.014). HDP was positively associated with the presence of CAC after adjusting for age at time of study participation (OR = 2.7, 95% CI 1.4-5.4). This association was slightly attenuated with adjustment for body size and blood pressure (OR = 2.4, 95% CI 1.2-4.9) but was not further attenuated with adjustment for serum creatinine and urinary albumin/creatinine ratio (OR = 2.6, 95% CI 1.3-5.3). Results were similar for CAC extent. Conclusions: HDP may increase a woman's risk of future CHD beyond traditional risk factors and renal function. Women with a history of HDP should be monitored for potential increased risk of CHD as they age.

Abstract Pneumocystis jirovecii pneumonia is an opportunistic fungal infection that causes severe respiratory impairment in immunocompromised patients. The viability of Pneumocystis organisms is dependent on the cyst cell wall, a structural feature that is regulated by essential cell wall–associated enzymes. The formation of the glucan-rich cystic wall has been previously characterized, but glucan degradation in the organism—specifically, degradation during trophic excystment—is not yet fully understood. Most studies of basic Pneumocystis biology have been conducted in Pneumocystis carinii or Pneumocystis murina, the varieties of this genus that infect rats and mice, respectively. Furthermore, all known treatments for P. jirovecii were initially discovered through studies of P. carinii. Accordingly, in this study, we have identified a P. carinii β-1,3-endoglucanase gene (PCEng2) that is demonstrated to play a significant role in cell wall regulation. The cDNA sequence contained a 2.2-kb open reading frame with conserved amino acid domains homologous to similar fungal glycosyl hydrolases (GH family 81). The gene transcript showed up-regulation in cystic isolates, and the expressed protein was detected within both cyst and trophic forms. Complementation assays in Eng2-deleted Saccharomyces cerevisiae strains showed restoration of the cell wall separation defect during proliferation, demonstrating the importance of PCEng2 protein. during fungal growth. These findings suggest that regulation of cyst cell wall β-glucans is a fundamental process during completion of the Pneumocystis life cycle.

Abstract Our preclinical and clinical trials using a replication-defective adenoviral vector expressing IFN-β have shown promising results for the treatment of malignant mesothelioma. Based on the hypotheses that a replication-competent vesicular stomatitis virus (VSV) oncolytic vector would transduce more tumor cells in vivo, that coexpression of the immunostimulatory IFN-β gene would enhance the immune-based effector mechanisms associated both with regression of mesotheliomas and with VSV-mediated virotherapy, and that virus-derived IFN-β would add further safety to the VSV platform, we tested the use of IFN-β as a therapeutic transgene expressed from VSV as a novel treatment for mesothelioma. VSV-IFN-β showed significant therapy against AB12 murine mesotheliomas in the context of both local and locoregional viral delivery. Biologically active IFN-β expressed from VSV added significantly to therapy compared with VSV alone, dependent in part on host CD8+ T-cell responses. Immune monitoring suggested that these antitumor T-cell responses may be due to a generalized T-cell activation rather than the priming of tumor antigen–specific T-cell responses. Finally, IFN-β also added considerable extra safety to the virus by providing protection from off-target viral replication in nontumor tissues and protected severe combined immunodeficient mice from developing lethal neurotoxicity. The enhanced therapeutic index provided by the addition of IFN-β to VSV therefore provides a powerful justification for the development of this virus for future clinical trials. [Cancer Res 2009;69(19):7713–20]

Background and Aims. Colorectal cancer, a leading cause of cancer death, is preventable with colonoscopic screening. Colonoscopy cost is high, and optimizing resource utilization for colonoscopy is important. This study’s aim is to evaluate resource allocation for optimal use of facilities for colonoscopy screening. Method. The authors used data from a computerized colonoscopy database to develop a discrete event simulation model of a colonoscopy suite. Operational configurations were compared by varying the number of endoscopists, procedure rooms, the patient arrival times, and procedure room turnaround time. Performance measures included the number of patients served during the clinic day and utilization of key resources. Further analysis included considering patient waiting time tradeoffs as well as the sensitivity of the system to procedure room turnaround time. Results. The maximum number of patients served is linearly related to the number of procedure rooms in the colonoscopy suite, with a fixed room to endoscopist ratio. Utilization of intake and recovery resources becomes more efficient as the number of procedure rooms increases, indicating the potential benefits of large colonoscopy suites. Procedure room turnaround time has a significant influence on patient throughput, procedure room utilization, and endoscopist utilization for varying ratios between 1:1 and 2:1 rooms per endoscopist. Finally, changes in the patient arrival schedule can reduce patient waiting time while not requiring a longer clinic day. Conclusions. Suite managers should keep a procedure room to endoscopist ratio between 1:1 and 2:1 while considering the utilization of related key resources as a decision factor as well. The sensitivity of the system to processes such as turnaround time should be evaluated before improvement efforts are made.