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Children with cancer previously treated with radiotherapy face the likelihood of side effects that can be debilitating or fatal. This study aimed to assess the long-term effect of medulloblastoma radiotherapy on the DNA double-strand break (DSB) repair capability of primary fibroblasts derived from lung biopsies of previously irradiated young sheep. This study included biopsies from three control and five irradiated sheep. The treated sheep had previously received spinal radiotherapy at a total dose of 28 Gy, which is equivalent to pediatric medulloblastoma treatment. Lung biopsies were taken 4 years post-irradiation from high-dose (HD, >18 Gy) and low-dose (LD, <2 Gy) regions. Fifteen cell lines were extracted (six control, four LD and five HD). The cells were irradiated, and DNA DSB repair was analyzed by immunofluorescence. Clonogenic, trypan blue and micronuclei assays were performed. Both the HD and LD cell lines had a significantly higher number of residual γH2AX foci 24 h and a significant decrease in pATM activity post-irradiation compared to the control. There was no statistically significant difference in the clonogenic assay, trypan blue and micronuclei results. Our study showed that a previous irradiation can impair the DNA DSB repair mechanism of ovine lung fibroblasts. more...

Unlabelled: After liver transplantation (LT), postoperative pulmonary complications (PPC) occur in approximately 35% to 50% of the recipients. Among these PPC, pneumonia is the most frequently encountered. Pulmonary dysfunction has also been widely reported among patients awaiting LT. The links between this dysfunction and PPC have not been clearly established. In this present cohort study, we evaluated the incidence and profile of post-LT pneumonia and identified potential preoperative risk factors., Methods: The postoperative clinical course of 212 liver transplant recipients between January 2008 and April 2010 was analyzed. These patients were treated in a single intensive care unit and received standardized postoperative care., Results: During the postoperative period, 47 (22%) patients developed pneumonia, of whom 20 (43%) developed respiratory failure requiring mechanical ventilation. Univariate analysis showed that several preoperative factors (age of recipient, model for end-stage liver disease score, indication for LT, platelet count, and restrictive lung pattern revealed by preoperative pulmonary function tests) and the transfusion (blood units and fresh frozen plasma units) during the operative period were associated with pneumonia. Using multivariate analysis by logistic regression, only a restrictive lung pattern (odds ratio=3.14; 95% confidence interval, 1.51-6.51; P=0.002) and the international normalized ratio measured prior LT (OR=4.95; 95% confidence interval, 1.86-8.59; P=0.0004) were independent predictors of pneumonia after LT., Conclusion: Pneumonia is common among patients undergoing LT and is a major cause of morbidity. A restrictive pattern on preoperative pulmonary testing and a higher international normalized ratio measured prior LT were associated with more risk of postoperative pneumonia. more...

The standard antitubercular treatment (ATT), which consists of isoniazid (INH), rifampicin (RIF), ethambutol, and pyrazinamide (PZA), is the best available treatment for tuberculosis (TB). However, the hepatotoxicity of INH and PZA can be severe, and even after drug withdrawal, patients may require liver transplantation (LT). In these cases, the strategy for the treatment of TB is poorly defined. Between 1986 and 2008, 14 patients presented at our department with severe hepatitis secondary to INH and PZA treatment. Four of these patients were immunosuppressed: 2 after renal transplantation and 2 because of human immunodeficiency virus infection. In seven of the 14 patients an alternative ATT was begun on admission, which was well tolerated. Hepatitis improved spontaneously in 5 patients, and alternative ATT was continued for 9.3 ± 4.2 months; 1 patient deteriorated and underwent LT, and 1 patient died. ATT was stopped definitively in 2 patients. Six patients required urgent LT, and alternative ATT was started after transplantation and was successful. Five patients receiving RIF had an episode of acute rejection. In conclusion, hepatitis secondary to ATT can be successfully treated with alternative anti-TB regimens. The use of RIF in LT patients may lead to acute rejection. RIF should therefore be avoided in these patients., (© 2010 AASLD.) more...

Background: Few data are available on prescriber adherence to tuberculosis (TB) treatment guidelines. In particular, excessively long treatment carries a risk of avoidable adverse effects and represents a waste of healthcare resources. We examined factors potentially associated with excessively long treatment., Methods: We reviewed the medical records of patients diagnosed with TB in 2004 in the eastern Paris region. Sociodemographic and clinical factors associated with excessively long treatment were identified by logistic regression analyses. Based on contemporary guidelines, excessively long treatment was defined as more than 6 months of a four-drug regimen for thoracic TB with full sensitive strains, and more than 12 months for patients with extrathoracic TB., Results: Analyses concerned 478 patients with a median age of 36.0 +/- 13.5 years, of whom 48% were living in precarious conditions (i.e. poor living conditions and/or no health insurance), 80% were born abroad, and 17% were HIV-seropositive. TB was restricted to the chest in 279 patients (isolated pulmonary, pleuropulmonary, and isolated pleural TB in 245, 13, and 21 patients, respectively), exclusively extrathoracic in 115 patients, and mixed in the remaining 84 patients. Treatment was prescribed by a chest specialist in 211 cases (44.1%) and 295 patients (61.7%) were managed in a single institution. The treatment duration complied with contemporary guidelines in 316 cases (66.1%) and was excessively long in 162 cases (33.9%). The median duration of excessively long treatment was 313 days (IQR: 272-412). In multivariate analysis, isolated thoracic TB, previous TB, HIV infection, a prescriber other than a chest specialist, and management in more than one healthcare center during treatment were independently associated with excessively lengthy treatment., Conclusion: One-third of TB patients received excessively long treatment, reflecting inadequate awareness of management guidelines or unwillingness to implement them. more...

Background: France was one of the few European countries without a national tuberculosis (TB) treatment outcome monitoring system until 2007., Objective: To examine TB management and treatment outcomes in the eastern Paris region, and to identify patient- and management-dependent factors affecting treatment outcome., Methods: This retrospective study focused on all cases of microbiologically confirmed Mycobacterium tuberculosis cases diagnosed in 2004 in the eastern Paris region, one of the areas of France with the highest frequency of TB., Results: Treatment outcomes of 629 identified cases (males 69.6%, median age 37 years, socio-economically disadvantaged 44%, foreign-born 78%) were as follows: treatment success 70.1% (95%CI 66.5-73.7), treatment interruption 4.9% (95%CI 3.2-6.6), loss to follow-up 15.0% (95%CI 12.2-17.8), death 5.7% (95%CI 3.9-7.9), transfers 4.3% (95%CI 3.5-5.1). Non-completion of treatment was associated with sputum smear positivity, injection drug use, non-adherence and irregular follow-up in univariate analysis, and with irregular follow-up and non-adherence in multivariate analysis. Duration of TB treatment and follow-up medical visits were not applied as recommended in more than a third of cases., Conclusion: The treatment success rate observed in this study (70.1%) is below the World Health Organization target of 85%, and requires the implementation and evaluation of interventions to increase treatment success rates. more...

Background: Tuberculosis (TB) is a persistent public health problem in European cities. France has been unable to report on treatment outcomes until now, and it is not known whether the World Health Organization (WHO) target cure rate of 85% has been met., Methods: All patients placed under treatment in four hospitals and five out-patient Social Medical Centres in Paris were followed up between 1996 and 2005. Patient monitoring and evaluation were performed using a new software programme, TB-INFO., Results: In a cohort of 1127 patients, 76% had pulmonary TB, of whom 39% were smear-positive, 81% were foreign-born and 9.3% were human immunodeficiency virus positive. At the end of the follow-up, 16% were cured and 54% had completed treatment. Among the 1118 non-multidrug-resistant patients, these percentages were 17% and 46%, respectively, for smear-positive pulmonary patients. Some patients died (1.9%) or failed treatment (0.1%), but many more defaulted (20.5%) as they interrupted treatment (1.5%), were lost to follow-up (19.5%) or were transferred out (7.9%)., Conclusions: This 10-year follow-up of TB patients, managed with TB-INFO software, shows that a patient monitoring system can be implemented in France, providing essential information. Treatment success in this cohort of patients was far below the WHO target. more...

Most cases of infections described after steroid treatment for severe acute alcoholic hepatitis are of bacterial origin. However, the rate of bacterial infections in these patients is not higher than in those who are not treated by steroids. The opportunistic infections are even more rare. We report two cases of patients with cirrhosis and human immunodeficiency virus, treated for alcoholic hepatitis with steroids and who subsequently developed severe pneumopathy due to Pneumocystis carinii. One patient had a concommitant cytomegalovirus infection and both of them died. Pneumocystis carinii infections usually occur in patients a decreased immune cellular response. Steroid treatments and also alcohol may be responsible for these opportunistic infections. Alcohol may have an immunosuppressive effect by decreasing recruitment of CD4 and CD8 lymphocytes to the lungs. In conclusion, Pneumocystis carinii pneumonia is a potential complication of steroid treatments for acute alcoholic hepatitis and should be suspected in case of unexplained pulmonary infection. more...