Association between promoter polymorphic haplotypes of interleukin-10 gene and schizophrenia.

BACKGROUND: Schizophrenia is one of the most severe psychiatric disorders, with a worldwide incidence of 1%. Several reports show abnormal cytokine levels in psychotic patients and indicate a possible role of the immune response system in the pathogenesis of schizophrenia. Increased concentrations of interleukin 10 (IL-10) have been found in plasma of schizophrenic patients, suggesting its potential role as a candidate gene for susceptibility to schizophrenia. IL-10 gene maps on chromosome 1 (q31-q32), a locus associated with genetic susceptibility to schizophrenia. Three functional haplotypes of the gene (GCC, ACC, ATA) have been described, derived from different combinations of three "single nucleotide polymorphisms" and directly related to the expression levels of the protein. METHODS: We analyzed allele, genotype, and haplotype distributions in an association case-control study involving 106 schizophrenic patients and 143 unrelated healthy volunteers using polymerase chain reaction (PCR)-Single Strand Conformation Polymorphism and PCR Restriction Fragment Length Polymorphism methods. RESULTS: Our results show a significant increase of GCC homozygotes (the high IL-10-producing haplotype) in schizophrenic patients compared to control subjects (chi(2) = 13, p =.023; odds ratio = 3.03; 95% confidence interval, 1.274-7.355). CONCLUSIONS: These data could partly explain the abnormal secretion of IL-10 occurring in schizophrenic patients in response to infections or different stressors and suggest a potential role of IL-10 as a candidate gene for susceptibility to schizophrenia.     

Liver transplant recipients mortality on the waiting list: long-term comparison to Child-Pugh classification and MELD

We sought to evaluate our experience concerning the high waiting list mortality rate for orthotopic liver transplantation (OLT) using the MELD (Model for End-Stage Liver Disease), which has been shown to predict short-term survival better than Child-Turcotte-Pugh (CTP) classification. The predominant end-stage disease was cirrhosis due to hepatitis C virus (67%), patient mean age was 36.8 years, and 72.1% were men. When the patients were included on a waiting list, the MELD score was stratified into W: 0 to 10; X: 11 to 20, and Y: 21 to 40 and the CPT as A: 5 to 6, B: 7 to 9, and C: 10 to 15. It was also observed that 77.8% of patients were on the waiting list, 16.4% underwent OLT and 5.8% had been removed. The estimated survival rate after 1 year was W = 85.4%; X = 83.3%, Y = 46.8%; A = 81.3%, B = 84.2%, C = 45.9%. Child median score was 8 +/- 1.5 (5 to 15) and the MELD was 14.7 +/- 5.1 (8 to 43). The mortality rate was 20.2%. Severe patients classified as Y or C showed greater mortality than the other groups (P <.001), but no significant difference between Y and C strata. The mortality rate was the same as in previous years.     

Can the use of marginal liver donors change recipient survival rate?

Liver transplantation as a therapeutic method for the treatment of end-stage liver disease is beclouded by a scarcity of organs. The aim of this study was to retrospectively analyze the relation between the classification of donors as marginal versus ideal and recipients survival after 148 of 197 orthotopic liver transplantations (OLT) performed from 1991 to 2001. Donors were classified as marginal if they showed the major criteria of: age over 55 years, aspartate aminotransferase greater than 150 UI/L; serum bilirubin greater than 2 mg/dL, serum sodium greater 150 mEq/L, high-dose dopamine or any other vasoactive amine, cardiac arrest, intensive care unit (ICU) stay over 5 days, and moderate severe macrosteatosis. The minor criteria for a marginal donor were: use of dopamine below 10 microg/kg/min, history of alcoholism, drug abuse, ICU stays less than 4 days, microsteatosis of any degree, and mild macrosteatosis. Statistical analysis was performed using Cox regression analyzing and the Kaplan-Meier survival method. The rate of marginal donors was 61.5%. The 180 postoperative day survival was 77.0%. Survival rates were 81.1% for recipients of marginal donor organs, and 70.7% for ideal donor recipients (P >.05). In conclusion, the use of marginal liver donors is viable and safely expands the numbers of liver transplants, thereby diminishing the number of waiting list deaths.     

Development of donor-specific microchimerism in liver transplant recipient with HLA-DRB1 and -DQB1 mismatch related to rejection episodes

Migration of donor-derived cells to recipient tissues after liver transplantation has been suggested as a mechanism to induce and maintain allograft tolerance, although important issues remain including acute rejection posttransplantation mortality, and complications related to immunosuppressive therapy. We therefore examined the relation of rejection to chimerism based upon recipient and donor mismatch of HLA-DRB1 and -DQB1 alleles. Laboratory analysis of peripheral blood was performed before and 10 days to 16 months after liver transplantation in 32 recipients, using ganglion or spleen cell samples of respective donors. DNA was extracted for HLA-DRB1 and DQB1 allele typing using polymerase chain reactions with sequence-specific primers (PCR-SSP). Microchimerism was analyzed through nested PCR. Our results confirmed that patients with one or two mismatched HLA-DRB1 and-DQB1 alleles showed microchimerism and no rejection (P <.05). Microchimerism was present in 71.88% of the patients, and a significant association of rejection P <.05 was found when microchimerism was correlated to graft rejection. These results suggest that the presence of microchimerism may be associated with acceptance, tolerance and survival of the allograft.     

Late hepatic artery thrombosis after liver transplantation: clinical setting and risk factors

The aim of this study was to assess the prevalence clinical presentation, and impact on outcome of late hepatic artery thrombosis (HAT) after OLT. We also sought risk factors other than technical problems that predispose to the pathogenesis of late HAT among 178 OLT performed from 1999 to 2002. Late HAT was diagnosed using Doppler ultrasonography and arteriography. Late HAT was observed in nine patients (3.8%), all of whom had experienced chronic HCV infection. Median time to HAT diagnosis was 4.88 months after OLT. Mean follow-up time was 40.25 months. Recipient age ranged from 30 to 61 years and median donor age, 28 years. Mean warm ischemia time was 63 minutes and mean cold ischemia time, 660 minutes. All of our study group were cigarette smokers. Postoperative CMV infection, presenting with hepatitis, had been treated in 55.6%. Before the diagnosis of HAT more than one episode of acute cellular rejection had been observed in six patients (55.6%) and 44.5% had chronic rejection. The diagnosis of CR was established after the diagnosis of HAT in all cases. Recurrence of HCV infection was histologically documented in 44.5%. Only one patient experienced graft loss (77 months after OLT). Six of nine patients had biliary complications, treated either by endoscopic stenting or by surgical drainage. Two patients were asymptomatic. In conclusion, late HAT shows a benign presentation that has no impact on graft survival. Possible risk factors have yet to be defined by multicenter trials.     

Visual field defects in obstructive hydrocephalus

Four cases are described in which visual field defects followed enlargement of the third ventricle. Three were due to aqueduct stenosis while in one case a left cerebellar hemisphere tumour was discovered. The visual field defects comprised a unilateral scotoma, bilateral scotomata and, in two patients, incongruous bitemporal hemianopia.     

Ischemia With Preconditioning in Wistar Rats Maintains Mitochondrial Respiration,Even With Mild Hepatocellular Disturbance

Introduction

In hepatectomy or liver transplantation, preconditioning is a procedure indicated to protect the organ from ischemia-reperfusion injury (I-R).

Underexpression of miR-126-3p in Patients with Cholangiocarcinoma

Objectives: To evaluate the expression of miR-126-3p and its potential as a biomarker for cholangiocarcinoma (CCA) and to better understand the prognosis, comorbidities, and lifestyle habits associated with the disease. Methods: Fifty-nine individuals were distributed into either the study group (38 CCA patients) or the control group (21 individuals without liver diseases). Total RNA was extracted, cDNA synthesis was performed, and miR-126-3p expression was assessed using real-time PCR. For statistical analysis, alpha error was set at 5%. Results: MiR-126-3p was found to be underexpressed in the study group relative to the controls (0.42; P=0.001). Additionally, marked underexpression was found in the study group in when associated with smoking (0.28; P=0.0001), alcoholism (0.19; P=0.0001), hypertension (0.29; P=000.1), and diabetes (0.12; P=0.0003) relative to the controls. No association was found between miR-126-3p expression and tumor subtypes (iCCA=0.42; pCCA=0.45; dCCA=0.72; P=0.9155). A total of 67% of dCCA patients were event-free at 16 months of follow up, while both pCCA and iCCA exhibited event-free survival rates of 25%, though there was no significant difference between these subgroups (P=0.273). Conclusion: The underexpression of mir-126-3p is associated with cholangiocarcinoma and can be potentiated by alcoholism, hypertension, diabetes, and smoking, the latter of which is an independent risk factor for this cancer. Furthermore, dCCA patients exhibit higher survival rates relative to patients with pCCA and iCCA.