Characterization of antigenetic serotypes from the dengue virus in Venezuela by means of Grid Computing.

This work determines the molecular epidemiology of dengue virus in Venezuela by means of phylogenetic calculations performed on the EELA-2 Grid infrastructure with the PhyloGrid application, an open source tool that allows users performing phylogeny reconstruction in their research. In this study, a total of 132 E nucleotide gene sequences of dengue virus from Venezuela recorded in GenBank(R) have been processed in order to reproduce and validate the topology described in the literature.

Reproductive and contraceptive characteristics of premenopausal kidney transplant recipients.

OBJECTIVE: To obtain information on menstrual patterns before and after transplantation, desire for future pregnancy, and use of contraception among premenopausal kidney transplant recipients. STUDY DESIGN: This observational study collected information using self-administered anonymous questionnaires during a routine outpatient clinic visit. RESULTS: Of the 107 women who completed the questionnaire, 41 identified themselves as being premenopausal. Among the 41 premenopausal women, approximately half of the women reported their current menstrual patterns as normal and 26% were not using any form of contraception. Overall, 10 women (24%) reported a desire to become pregnant and 4 women (10%) had a successful pregnancy after transplantation. Most of the women who desired a future pregnancy (8/10) were receiving an immunosuppressive regimen that included mycophenolate mofetil. CONCLUSION: Kidney transplantation in the current era is associated with a return of normal menstrual function in the majority of female transplant recipients. A substantial fraction of women desire pregnancy after transplantation and many are using an immunosuppressive drug with limited safety data on use during pregnancy. More caution should be used with the use of newer immunosuppressive agents in sexually active premenopausal transplant recipients until more safety data are available.

A prospective, randomized, clinical trial of intraoperative versus postoperative Thymoglobulin in adult cadaveric renal transplant recipients.

BACKGROUND: Delayed graft function (DGF) is frequently observed in recipients of cadaveric renal transplants. Previous retrospective or nonrandomized studies have suggested that intraoperative administration of polyclonal antithymocyte preparations may reduce the incidence of DGF, possibly by decreasing ischemia-reperfusion injury. METHODS: We performed a prospective randomized study of Thymoglobulin induction therapy in adult cadaveric renal transplant recipients. Between January 2001 and January 2002, 58 adult cadaveric renal transplant recipients were randomized to receive intraoperative or postoperative Thymoglobulin induction therapy. Three to six doses of Thymoglobulin (1 mg/kg/dose) were administered during the first week posttransplant. Baseline immunosuppression consisted of tacrolimus (54 of 58) or cyclosporine A (4 of 58), steroids, and mycophenolate mofetil. DGF was defined by the requirement for hemodialysis within the first week posttransplant. RESULTS: There were no significant differences between the two groups in recipient demographics, donor age, cold ischemia time, or total number of doses of Thymoglobulin administered. Intraoperative Thymoglobulin administration was associated with significantly less DGF and a lower mean serum creatinine on postoperative days 10 and 14 (P<0.05). Posttransplant length of stay was also significantly shorter for the intraoperative Thymoglobulin patient group. The acute rejection rate was also lower in the intraoperative treatment group but this did not achieve statistical significance. There was no difference in the incidence of cytomegalovirus disease between the two groups. CONCLUSIONS: The results of this study indicate that intraoperative Thymoglobulin administration, in adult cadaveric renal transplant recipients, is associated with a significant decrease in DGF, better early allograft function in the first month posttransplant, and a decreased posttransplant hospital length of stay.

Acute humoral rejection in kidney transplantation: II. Morphology, immunopathology, and pathologic classification.

The incidence of acute humoral rejection (AHR) in renal allograft biopsies has been difficult to determine because widely accepted diagnostic criteria have not been established. C4d deposition in peritubular capillaries (PTC) of renal allografts has been proposed as a useful marker for AHR. This study was designed to test the relative value of C4d staining, histology, and serology in the diagnosis of AHR. Of 232 consecutive kidney transplants performed at a single institution from July 1995 to July 1999, all patients (n = 67) who developed acute rejection within the first 3 mo and had a renal biopsy with available frozen tissue at acute rejection onset, as well as posttransplant sera within 30 d of the biopsy, were included in this study. Hematoxylin and eosin and periodic acid-Schiff stained sections were scored for glomerular, vascular, and tubulointerstitial pathology. C4d staining of cryostat sections was done by a sensitive three-layer immunofluorescence method. Donor-specific antibodies (DSA) were detected in posttransplant recipient sera using antihuman-globulin-enhanced T cell and B cell cytotoxicity assays and/or flow cytometry. Widespread C4d staining in PTC was present in 30% (20 of 67) of all acute rejection biopsies. The initial histologic diagnoses of the C4d(+) acute rejection cases were as follows: AHR only, 30%; acute cellular rejection (ACR) and AHR, 45%; ACR (CCTT types 1 or 2) alone, 15%; and acute tubular injury (ATI), 10%. The distinguishing morphologic features in C4d(+) versus C4d(-) acute rejection cases included the following: neutrophils in PTC, 65% versus 9%; neutrophilic glomerulitis, 55% versus 4%; neutrophilic tubulitis, 55% versus 9%; severe ATI, 75% versus 9%; and fibrinoid necrosis in glomeruli, 20% versus 0%, or arteries, 25% versus 0%; all P < 0.01. Mononuclear cell tubulitis was more common in the C4d(-) group (70% versus 100%; P < 0.01). No significant difference between C4d(+) and C4d(-) acute rejection was noted for endarteritis, 25% versus 32%; interstitial inflammation (mean % cortex), 27.2 +/- 27% versus 38 +/- 21%; interstitial hemorrhage, 25% versus 15%; or infarcts, 5% versus 2%. DSA were present in 90% (18 of 20) of the C4d(+) cases compared with 2% (1 of 47) in the C4d(-) acute rejection cases (P < 0.001). The pathology of the C4d(+) but DSA(-) cases was not distinguishable from the C4d(+), DSA(+) cases. The C4d(+) DSA(-) cases may be due to non-HLA antibodies or subthreshold levels of DSA. The sensitivity of C4d staining is 95% in the diagnosis of AHR compared with the donor-specific antibody test (90%). Overall, eight grafts were lost to acute rejection in the first year, of which 75% (6 of 8) had AHR. The 1-yr graft failure rate was 27% (4 of 15) for those AHR cases with only capillary neutrophils versus 40% (2 of 5) for those who also had fibrinoid necrosis of arteries. In comparison, the 1-yr graft failure rates were 3% and 7%, respectively, in ACR 1 (Banff/CCTT type 1) and ACR 2 (Banff/CCTT type 2) C4d(-) groups. A substantial fraction (30%) of biopsy-confirmed acute rejection episodes have a component of AHR as judged by C4d staining; most (90%), but not all, have detectable DSA. AHR may be overlooked in the presence of ACR or ATI by histology or negative serology, arguing for routine C4d staining of renal allograft biopsies. Because AHR has a distinct therapy and prognosis, we propose that it should be classified separately from ACR, with further sub-classification into AHR 1 (neutrophilic capillary involvement) and AHR 2 (arterial fibrinoid necrosis).