Abstract: Late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT) has been associated with BK virus (BKV). Antiviral drugs are of limited efficacy and the optimal treatment for HC has not yet been established. Hyperbaric oxygen (HBO) may benefit these patients. We, therefore, retrospectively evaluated the effectiveness of HBO therapy in 16 patients with HC after allogeneic HSCT. All 16 patients had macroscopic hematuria and BKV infection. Patients received 100% oxygen in a hyperbaric chamber at 2.1 atmospheres for 90 min, 5 days per week, with a median 13 treatments (range, 4-84). Fifteen patients (94%) showed complete resolution of hematuria. Median urinary DNA BKV titers declined after HBO (P<0.05). Patients started on HBO earlier after diagnosis of HC responded sooner (P<0.05). HBO was generally well tolerated and proved to be a reliable option for this difficult to manage condition.Bone Marrow Transplantation advance online publication, 14 November 2011; doi:10.1038/bmt.2011.228.
Abstract: The OPCML gene (opioid binding protein/cell adhesion molecule-like), a putative tumour suppressor gene, is frequently inactivated in carcinomas, namely through aberrant promoter methylation. Herein, we aimed to determine whether OPCML altered expression mediated by epigenetic mechanisms was implicated in bladder carcinogenesis and to assess its potential as a bladder cancer epi-marker. OPCML promoter methylation levels from 91 samples of bladder urothelial carcinoma, 25 normal bladder tissues and bladder cancer cell lines were assessed by quantitative methylation-specific polymerase chain reaction, and correlated with OPCML mRNA expression, determined by quantitative reverse-transcription polymerase chain reaction. To prove the epigenetic regulation of OPCML, five bladder cancer cell lines were exposed to 5-aza-2'deoxycytidine (5-aza-dC), a specific DNA methyltransferase inhibitor and trichostatin A (TSA), a histone deacetylase inhibitor. In bladder tumours, the overall frequency of methylation was 60% and methylation levels were significantly higher when compared with normal mucosa (P=0.0001). No correlation was found between methylation levels and clinicopathological parameters. Interestingly, OPCML promoter methylation was associated with worse disease-specific survival (P=0.022) in univariate analysis. Furthermore, a significant inverse correlation between OPCML promoter methylation and mRNA expression levels was found, although a significant re-expression was only achieved when 5-aza-dC and TSA were used simultaneously. The high frequency of OPCML promoter methylation in urothelial carcinomas suggests an important role for this epigenetic alteration in bladder carcinogenesis, highlighting its potential as an epigenetic biomarker for bladder urothelial carcinoma with prognostic significance.
Abstract: Introduction: Glioblastoma multiforme is the most aggressive tumor of the central nervous system. Despite advances in its management, overall prognosis remains poor, with a median survival time of less than one year. Good response to chemotherapy with temozolomide (TMZ) is usually associated with methylation of the promoter of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene. Case Report: We describe here a patient with glioblastoma multiforme, who had good prognostic clinical features, age and performance status, but unmethylated MGMT promoter and who survived for eight years while treated with a multi-modal approach. Conclusion: Good response to treatment, despite the absence of MGMT hypermethylation, suggests that other genetic or molecular factors may predict prognosis and therapeutic response in patients with glioblastoma multiforme.
Abstract: Severe toxicity to 5-fluorouracil (5-FU) based chemotherapy in gastrointestinal cancer has been associated with constitutional genetic alterations of the dihydropyrimidine dehydrogenase gene (DPYD).
Abstract: While humans require water for life, one-sixth of our species lives without access to safe water. In Africa, the situation is particularly acute because of global warming, the progression of the Sahara desert, civil unrest and poor governance, population growth, migration and poverty. In rural areas, the lack of adequate safe water and sanitary infrastructures leaves millions with doubtful water quality, increasing the harshness of daily life. In this paper, a pilot study was conducted during the wet season on Bolama Island (Guinea-Bissau, West Africa), a UNESCO Man and the Biosphere Reserve. Twenty-eight shallow wells, supplying water to most of the population, were sampled for microbiological, physical and chemical water quality characteristics. A ten-parameter water quality index (WQI) adapted to tropical conditions was applied to compare the different wells. About 79% of the wells showed moderate to heavy fecal contamination. From the surveyed parameters, it was found that chemical contamination was less important, although all samples were acidic, with the pH averaging 5.12+/-0.08. The WQI was 43+/-4% (0%-worst; 100%-best quality), showing that the water from the majority of wells was polluted but should be suitable for domestic use after appropriate treatment. At the onset of the wet season, diarrhea represented 11.5% of all medical cases, 92.5% of which were children aged <15. This paper suggests inexpensive steps to reduce the fecal contamination and control the pH in order to increase the potability of the well water and, concomitantly, to raise the living standards of the population in one of the poorest countries of the world.
