The Madrid Declaration: why we need a coordinated Europe-wide effort in mental health research

The Madrid Declaration is being promoted by representatives from seven nationally funded mental health research networks, along with leaders of ongoing European Union-funded mental health projects. It advocates the creation of a Network of Excellent Networks, based on a dynamic and adaptive cross-European network of distinctly qualified research centres.     

Recurrent neobladder rupture: conservative management

PurposeTo present a case of recurrent neobladder rupture treated in a conservative fashion. To review the articles on conservative management of cases like this one published from 1985.ResultsNineteen articles have been published since 1985 on spontaneous neobladder rupture, 4 of which describe the possibility of a successful conservative management, provided that the patients are carefully selected.ConclusionsFaced to abdominal pain in patients with neobladder, it is essential to suspect spontaneous perforation and, if possible, to confirm such suspicions by means of cystography or CT. An exploratory laparotomy may be necessary in many instances, sometimes due to lack of a diagnosis and sometimes because the patient’s status rules out any other procedure, but in selected and precisely diagnosed cases a conservative management can be resolvent.     

Colorectal cancer after start of nonsteroidal anti-inflammatory drug use

Purpose

Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, have been consistently shown to reduce the risk of colorectal cancer (CRC) in non-experimental studies, but little is known of the factors associated with starting and continuing regular NSAID use and their effect on the NSAID and CRC association.

Subjects and methods

We performed a prospective cohort study of 22,071 healthy male physicians aged 40 to 84 years without indications or contraindications to regular NSAID use at baseline. Annual questionnaires assessed quantity of NSAID use, occurrence of cancer, and risk factors for CRC. Propensity for regular NSAID use (>60 days/year) was estimated using generalized estimating equations. We used a time-varying Cox proportional hazards model to estimate the association between duration since initiation of regular NSAID use and risk for CRC.

Results

Regular non-aspirin and any NSAID use increased from 0% to 12% and 1% to 56% over time, respectively and was predicted by age, body mass index, alcohol consumption, medication use, coronary artery disease, gastrointestinal diseases, arthritis, hypertension, and headaches. Over a median follow-up of 18 years, 495 physicians were diagnosed with CRC. There was no trend of CRC risk with increased duration of regular NSAID use. Five or more years of regular use of any NSAID were associated with a relative risk for CRC of 1.0 (95% confidence interval: 0.7-1.5), after adjustment for predictors of regular NSAID use.

Conclusion

Regular NSAID use was not associated with a substantial risk reduction of CRC after controlling for time-varying predictors of both NSAID use and CRC.     

Immune response to lentiviral bilirubin UDP-glucuronosyltransferase gene transfer in fetal and neonatal rats

Gene therapy for inherited disorders might cause an immune response to the therapeutic protein. A solution would be to introduce the gene in the fetal or neonatal period, which should lead to tolerization. Lentiviral vectors mediate long-term gene expression, and are well suited for gene therapy early in development. A model for fetal or neonatal gene therapy is the inherited disorder of bilirubin metabolism, Crigler-Najjar disease (CN). The absence of bilirubin UDP-glucoronyltransferase (UGT1A1) activity in CN patients causes high serum levels of unconjugated bilirubin and brain damage in infancy. CN is attractive for the development of gene therapy because the mutant Gunn rat closely mimics the human disease. Injection of UGT1A1 lentiviral vectors corrected the hyperbilirubinemia for more than a year in rats injected as fetuses and for up to 18 weeks in rats injected the day of birth. UGT1A1 gene transfer was confirmed by the presence of bilirubin glucuronides in bile. All animals injected with UGT1A1 lentiviral vectors developed antibodies to UGT1A1. Animals injected with green fluorescent protein (GFP) lentiviral vectors did not develop antibodies to GFP. Our results indicate that fetal and neonatal gene therapy with immunogenic proteins such as UGT1A1 does not necessarily lead to tolerization.     

Memory B cell responses and malaria

Malaria is a serious cause of morbidity and mortality in millions of individuals each year. People living in endemic areas build up partial immunity only after repeated attacks of malaria over several years. At this meeting we discussed current knowledge about long-term protection and the challenges we face in the development of an effective malaria vaccine.     

Preoperative glucose and protein metabolism: the influence of diabetes mellitus type 2 in patients with colorectal tumors

Hypermetabolism, abnormal plasma amino acid profiles, increased gluconeogenesis, and changes in liver and muscle protein turnover are well-described undesirable effects in patients with cancer and diabetes mellitus type 2 (DM2) The aim of the present study was to analyze the specific impact and interaction of these 2 disease patterns on patients' preoperative glucose and protein metabolism. Eight nondiabetic and 8 diabetic patients devoid of cachexia underwent a stable isotope infusion study on the day before surgery for colorectal cancer or adenoma with high-grade dysplasia. Protein and glucose kinetics were assessed in a fasted state by L-[1-(13)C]leucine and [6,6(2)H(2)]glucose. In diabetic patients, glucose metabolism was found to be elevated as the plasma glucose level increased (P = 0.013) and endogenous rate of appearance of glucose tended to be higher compared to nondiabetic patients (P = 0.083). Protein metabolism was not affected by the metabolic state of the 2 groups. Resting energy expenditure was higher in diabetic patients (P = 0.028). Under postabsorptive conditions, noncachectic patients with DM2 suffering from colorectal tumors showed an elevated turnover in glucose metabolism whereas the nondiabetic counterparts failed to demonstrate any metabolic changes due solely to malignancy.