Pastoral production is associated with increased peste des petits ruminants seroprevalence in northern Tanzania across sheep, goats and cattle.

Peste des petits ruminants virus (PPRV) causes a contagious disease of high morbidity and mortality in small ruminant populations globally. Using cross-sectional serosurvey data collected in 2016, our study investigated PPRV seroprevalence and risk factors among sheep, goats and cattle in 20 agropastoral (AP) and pastoral (P) villages in northern Tanzania. Overall observed seroprevalence was 21.1% (95% exact confidence interval (CI) 20.1-22.0) with 5.8% seroprevalence among agropastoral (95% CI 5.0-6.7) and 30.7% among pastoral villages (95% CI 29.3-32.0). Seropositivity varied significantly by management (production) system. Our study applied the catalytic framework to estimate the force of infection. The associated reproductive numbers (R0) were estimated at 1.36 (95% CI 1.32-1.39), 1.40 (95% CI 1.37-1.44) and 1.13 (95% CI 1.11-1.14) for sheep, goats and cattle, respectively. For sheep and goats, these R0 values are likely underestimates due to infection-associated mortality. Spatial heterogeneity in risk among pairs of species across 20 villages was significantly positively correlated (R2: 0.59-0.69), suggesting either cross-species transmission or common, external risk factors affecting all species. The non-negligible seroconversion in cattle may represent spillover or cattle-to-cattle transmission and must be investigated further to understand the role of cattle in PPRV transmission ahead of upcoming eradication efforts.

Laboratory Setup for Scanning-Free Grazing Emission X-ray Fluorescence.

Grazing incidence and grazing emission X-ray fluorescence spectroscopy (GI/GE-XRF) are techniques that enable nondestructive, quantitative analysis of elemental depth profiles with a resolution in the nanometer regime. A laboratory setup for soft X-ray GEXRF measurements is presented. Reasonable measurement times could be achieved by combining a highly brilliant laser produced plasma (LPP) source with a scanning-free GEXRF setup, providing a large solid angle of detection. The detector, a pnCCD, was operated in a single photon counting mode in order to utilize its energy dispersive properties. GEXRF profiles of the Ni-Lα,ß line of a nickel-carbon multilayer sample, which displays a lateral (bi)layer thickness gradient, were recorded at several positions. Simulations of theoretical profiles predicted a prominent intensity minimum at grazing emission angles between 5° and 12°, depending strongly on the bilayer thickness of the sample. This information was used to retrieve the bilayer thickness gradient. The results are in good agreement with values obtained by X-ray reflectometry, conventional X-ray fluorescence and transmission electron microscopy measurements and serve as proof-of-principle for the realized GEXRF setup. The presented work demonstrates the potential of nanometer resolved elemental depth profiling in the soft X-ray range with a laboratory source, opening, for example, the possibility of in-line or even in situ process control in semiconductor industry.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in pediatric ovarian tumors: a novel treatment approach.

PURPOSE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been used in adults with ovarian carcinoma proving overall survival benefit in randomized trials, but measured in months. Diffuse peritoneal disease from pediatric type ovarian tumors is rare. We applied CRS and HIPEC to pediatric girls with diffuse peritoneal disease as part of a clinical trial. METHODS: In all patients complete cytoreduction was followed by HIPEC using 100 mg/m2 of cisplatin for 90 min in a closed technique. All received neoadjuvant chemotherapy. Patients with disease outside of the abdominal cavity were excluded. RESULTS: Of 101 pediatric CRS and HIPEC operations, 8 had ovarian primary tumors and multifocal peritoneal disease. There were three yolk sac tumors (germ cell, mixed teratoma), one Sertoli­Leydig, one PNET of the ovary, one choriocarcinoma, one juvenile granulosa cell tumor and one adenocarcinoma. Age ranged 4­18 years. Three of the 8 (37 %) recurred and died. The remaining 63 % are disease free 2­6 years post HIPEC. Overall survival and relapse-free survival in this cohort was 64 and 62 %, respectively [CI 0.64 (0.34, 1); 0.62 (0.37, 1)]. CONCLUSIONS: This is the first report of CRS and HIPEC in pediatric ovarian tumors. HIPEC may be effective in pediatric-type ovarian tumors. More study is needed in a larger cohort.

Post-mortem assessment of the short and long-term effects of the trophic factor neurturin in patients with α-synucleinopathies.

Substantial interest persists for developing neurotrophic factors to treat neurodegenerative diseases. At the same time, significant progress has been made in implementing gene therapy as a means to provide long-term expression of bioactive neurotrophic factors to targeted sites in the brain. Nonetheless, to date, no double-blind clinical trial has achieved positive results on its primary endpoint despite robust benefits achieved in animal models. A major issue with advancing the field is the paucity of information regarding the expression and effects of neurotrophic factors in human neurodegenerative brain, relative to the well-characterized responses in animal models. To help fill this information void, we examined post-mortem brain tissue from four patients with nigrostriatal degeneration who had participated in clinical trials testing gene delivery of neurturin to the putamen of patients. Each had died of unrelated causes ranging from 1.5-to-3-months (2 Parkinson's disease patients), to 4+-years (1 Parkinson's disease and 1 multiple-system atrophy-parkinsonian type patient) following gene therapy. Quantitative and immunohistochemical evaluation of neurturin, alpha-synuclein, tyrosine hydroxylase (TH) and an oligodendroglia marker (Olig 2) were performed in each brain. Comparable volumes-of-expression of neurturin were seen in the putamen in all cases (~15-22%; mean=18.5%). TH-signal in the putamen was extremely sparse in the shorter-term cases. A 6-fold increase was seen in longer-term cases, but was far less than achieved in animal models of nigrostriatal degeneration with similar or even far less NRTN exposure. Less than 1% of substantia nigra (SN) neurons stained for neurturin in the shorter-term cases. A 15-fold increase was seen in the longer-term cases, but neurturin was still only detected in ~5% of nigral cells. These data provide unique insight into the functional status of advanced, chronic nigrostriatal degeneration in human brain and the response of these neurons to neurotrophic factor stimulation. They demonstrate mild but persistent expression of gene-mediated neurturin over 4-years, with an apparent, time-related amplification of its transport and biological effects, albeit quite weak, and provide unique information to help plan and design future trials.

Mifamurtide in metastatic and recurrent osteosarcoma: a patient access study with pharmacokinetic, pharmacodynamic, and safety assessments.

PURPOSE: This non-randomized, patient-access protocol, assessed both safety and efficacy outcomes following liposomal muramyl-tripeptide-phosphatidylethanolamine (L-MTP-PE; mifamurtide) in patients with high-risk, recurrent and/or metastatic osteosarcoma. METHODS: Patients received mifamurtide 2 mg/m(2) intravenously twice-weekly ×12 weeks, then weekly ×24 weeks with and without chemotherapy. Serum concentration-time profiles were collected. Adverse events within 24 hours of drug administration were classified as infusion-related adverse events (IRAE); other AEs and overall survival (OS) were assessed. RESULTS: The study began therapy in January 2008; the last patient completed therapy in October 2012. Two hundred five patients were enrolled; median age was 16.0 years and 146/205 (71%) had active disease. Mifamurtide serum concentrations declined rapidly in the first 30 minutes post-infusion, then in a log-linear manner 2-6 hours post-dose; t1/2 was 2 hours. There were no readily apparent relationships between age and BSA-normalized clearance, half-life, or pharmacodynamic effects, supporting the dose of 2 mg/m(2) mifamurtide across the age range. Patients reported 3,679 IRAE after 7,482 mifamurtide infusions. These were very rarely grade 3 or 4 and most commonly included chills + fever or headache + fatigue symptom clusters. One- and 2-year OS was 71.7% and 45.9%. Patients with initial metastatic disease or progression approximated by within 9 months of diagnosis (N = 40) had similar 2-year OS (39.9%) as the entire cohort (45.9%) CONCLUSIONS: Mifamurtide had a manageable safety profile; PK/PD of mifamurtide in this patient access study was consistent with prior studies. Two-year OS was 45.9%. A randomized clinical trial would be required to definitively determine impact on patient outcomes.

The role of early and sufficient isolated venovenous ultrafiltration in heart failure patients with pulmonary and systemic congestion.

Hypervolemia, present in at least 70% of patients with decompensated heart failure, results in renal dysfunction due to increased renal venous pressure, impaired renal autoregulation, and decreased renal blood flow that are associated with increased morbidity and mortality. Loop diuretics, widely used in congested patients, result in the production of hypotonic urine and neurohormonal activation. In contrast, ultrafiltration (UF) removes isotonic fluid without increasing renin secretion by the macula densa. Simplified devices that permit us to perform UF with peripheral venous access, adjustable blood flows, and small extracorporeal blood volumes make this therapy feasible at most hospitals and in less acute care settings. Conflicting results on the effects of UF in heart failure patients underscore the challenges of patient selection and choice of fluid removal rates. Unfavorable outcomes in patients undergoing UF in the midst of cardiorenal syndrome type 1 are in contrast with the sustained benefits of UF initiated before unsuccessful use of high-dose intravenous (IV) diuretics. UF rates should be based on a precise knowledge of the degree of hypervolemia and careful assessment of blood volume changes, so that extracellular fluid gradually refills the intravascular space and volume depletion is avoided. Poor outcomes are likely to occur if fluid removal rates are not tailored to individual patients' clinical characteristics. A large trial is ongoing to determine if a strategy of early UF, initiated before renal function is worsened by other therapies, is superior to IV diuretics in reducing 90-day heart-failure-related hospitalizations in patients with pulmonary and systemic congestion.

Everolimus in combination with vandetanib in children, adolescents, and young adults: a phase I study.

BACKGROUND: Combined use of inhibitors of mammalian target of rapamycin (mTOR) and vascular endothelial growth factor (VEGF-2) receptors is a potential strategy to overcome resistance to either class of drugs when used alone. PATIENTS AND METHODS: We designed a phase 1 trial to test the drug combination of a multikinase VEGF receptor 2 inhibitor, vandetanib, and an mTOR inhibitor, everolimus, in a pediatric and young adult patient cohort with advanced cancers. Exceptional responders were probed for tumor mutational profile to explore possible molecular mechanisms of response. RESULTS: Among 21 enrolled patients, clinical benefit was observed in 38% (one patient with partial response and eight patients with stable disease) with a median progression-free survival of 3.3 months. The most common treatment-related adverse event was rash (n = 13). Other treatment-related toxicities included diarrhea, fatigue, hypertension, QT prolongation, hypertriglyceridemia/hypercholesterolemia, transaminitis, thrombocytopenia, and weight loss. None of the patients experienced dose-limiting toxicities. Three exceptional responders were analyzed and were found to harbor genetic alterations including kinase insert domain receptor (KDR) Q472H mutation, EWSR1-CREB3L1, CDKN2A/B loss, and ASPL/ASPSCR1-TFE3 fusion. CONCLUSIONS: The combination of vandetanib and everolimus showed early activity and tolerable toxicity profile in pediatric patients with advanced cancers.

Geographic distribution of hematopoietic cancers in the Nile delta of Egypt.

BACKGROUND: Previous evidence indicated that incidence rates of non-Hodgkin's lymphoma (NHL) are high in Egypt although little is known about risk factors. MATERIALS AND METHODS: Using data from the population-based cancer registry of Gharbiah governorate in Egypt, we assessed the 1999-2005 incidence of hematopoietic cancers (HCs) based on the ICD-O3 by age- and sex-specific urban-rural distribution. RESULTS: NHL showed the highest incidence among all HCs (11.7 per 100 000). Urban incidence of HCs was higher than rural incidence. Incidence rates of Hodgkin's lymphoma (HL) and NHL were high especially among urban males up to the 64-year age category. Rural incidence of HL and NHL was high below age 20. Among the districts of the governorate, we observed NHL incidence pattern similar to that observed for hepatocellular carcinoma because of the possible link to hepatitis C virus for both cancers. Comparison to the published HCs data from Algeria, Cyprus, and Jordan showed the highest NHL rate in Egypt than the other countries in the region. CONCLUSIONS: Future studies should define the role of environmental exposures in hematopoietic carcinogenesis in this population. In-depth studies should also investigate the role of access to health care in the urban-rural variation of HC distribution in this population.

Troponin I levels and postoperative myocardial infarction following renal transplantation.

BACKGROUND: The relationship of routine postoperative troponin I (TnI) monitoring in kidney transplant recipients and in-hospital myocardial infarction (MI) is not known. METHODS: This observational study evaluated the prevalence of abnormal postoperative TnI (Ortho Clinical Diagnostics assay) in 376 consecutive kidney or kidney/pancreas transplant recipients. In-hospital MI was adjudicated using the universal definition. Rates of death and coronary revascularizations at 1 year were studied. Logistic regression analysis was performed to identify independent predictors of abnormal TnI. RESULTS: Ninety-five (25%) recipients had abnormal TnI (>0.04 ng/ml) following transplantation. Abnormal TnI levels were more common in older (mean age: 52.2 ± 13.4 vs. 48.3 ± 13.2 years, p = 0.01), diabetic (57.9 vs. 45.6%, p = 0.04), and prior coronary artery disease (31.6 vs. 20.3%, p = 0.02) patients. In-hospital MI occurred in 6 patients (1.6%). All subsequent in-hospital cardiovascular events occurred in the abnormal postoperative TnI group; most in those with TnI levels >1 ng/ml. Previous coronary artery disease was the only independent predictor of a postoperative TnI level >1 ng/ml in multivariate analysis (odds ratio 4.61, 95% confidence interval 1.49-14.32). At 1 year there was no significant difference in death (3.2 vs. 1.8%, p = 0.42) and borderline significant difference in coronary revascularization (5.3 vs. 1.4%, p = 0.049) in abnormal versus normal TnI groups. CONCLUSIONS: In-hospital MI was infrequent, but abnormal TnI highly prevalent following renal transplantation. Normal TnI levels following renal transplantation had a high negative predictive value in excluding patients likely to develop subsequent postoperative MI. The role of a higher TnI cut-off for screening for postoperative MI in high-risk subgroups deserves future prospective evaluation.

Effects of early childhood otitis media and ventilation tubes on psychosocial wellbeing - A prospective cohort study within the Danish National Birth Cohort.

BACKGROUND: Otitis Media (OM) is one of the most common infections among children in developed countries and may result in temporary conductive hearing loss (HL) if accompanied by middle ear effusion (MEE). Ventilation tube insertion (VTI) is recommended as treatment for recurrent acute OM or chronic MEE with HL. HL may lead to impaired development of psychosocial skills. However, evidence for the developmental consequences of OM and the effect of VTI is inconsistent. The objectives of this study were to investigate 1) whether OM in early childhood is associated with long-term consequences of psychosocial development and 2) if VTI prevents the possible negative consequences of OM. METHODS: This study examined prospectively collected data from 52.877 children registered in the Danish National Birth Cohort (DNBC). Information about previous OM-episodes and VTI was obtained through systematic follow-up interviews at seven years, and The Strength and Difficulties Questionnaire (SDQ) containing questions about psychological wellbeing was completed. Five groups were defined based on OM-exposure and the presence of VTI. Baseline characteristics were analysed, and comparison of mean SDQ-scores for the five exposure groups was conducted. Means were adjusted for à priori defined confounding factors. RESULTS: Data from 52,877 children in the DNBC showed an association between OM and poorer SDQ-scores. VTI was associated with an additional increase, i.e. worsening, of the SDQ-score for boys, and only a slight beneficial effect on the girls' outcome. The groups differed in their baseline characteristics in e.g. maternal education, socio-economic status, breastfeeding, and prematurity. CONCLUSION: Significant associations between parent-reported OM in early childhood and later psychosocial health difficulties were found. VTI did not resolve this association.

Identifying Age Cohorts Responsible for Peste Des Petits Ruminants Virus Transmission among Sheep, Goats, and Cattle in Northern Tanzania.

Peste des petits ruminants virus (PPRV) causes a contagious disease of high morbidity and mortality in global sheep and goat populations. To better control this disease and inform eradication strategies, an improved understanding of how PPRV transmission risk varies by age is needed. Our study used a piece-wise catalytic model to estimate the age-specific force of infection (FOI, per capita infection rate of susceptible hosts) among sheep, goats, and cattle from a cross-sectional serosurvey dataset collected in 2016 in Tanzania. Apparent seroprevalence increased with age, reaching 53.6%, 46.8%, and 11.6% (true seroprevalence: 52.7%, 52.8%, 39.2%) for sheep, goats, and cattle, respectively. Seroprevalence was significantly higher among pastoral animals than agropastoral animals across all ages, with pastoral sheep and goat seroprevalence approaching 70% and 80%, respectively, suggesting pastoral endemicity. The best fitting piece-wise catalytic models merged age groups: two for sheep, three for goats, and four for cattle. The signal of these age heterogeneities were weak, except for a significant FOI peak among 2.5-3.5-year-old pastoral cattle. The subtle age-specific heterogeneities identified in this study suggest that targeting control efforts by age may not be as effective as targeting by other risk factors, such as production system type. Further research should investigate how specific husbandry practices affect PPRV transmission.

Metabolic changes following conversion from an anticalcineurin-based therapy to an everolimus-based one: a single-center experience.

Everolimus (EVL), an antagonist of mammalian target of rapamycin, has been recently introduced into solid organ transplantation either associated with low dose of anticalcineurins (CNI) or replacing them in an attempt to avoid nephrotoxicity and chronic allograft nephropathy. Due to the molecular similarities with sirolimus, it has been expected that there would be the same incidence of metabolic changes and adverse events. We retrospectively studied kidney allograft recipients converted from CNI to EVL during a 12-month period. Patients received a standard dose of EVL starting at 1.5 mg/d and thereafter titrating to achieve trough levels in the range of 3 to 5 ng/mL. Patients achieved mean EVL trough levels of 5.2, 4.0 and 4.5 ng/mL at 1, 6, and 12 months, respectively. One year following conversion, the calculated creatinine clearance increased from 57 to 63 mL/min and proteinuria did not change. Fasting blood glucose levels decreased significantly following conversion to EVL. During the same time, no significant changes were observed in body weight, body mass index, albumin, cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, lipid-lowering medication requirements, blood magnesium, and uric acid. We concluded that EVL did not negatively influence various nutritional parameters.

Alemtuzumab induction in kidney transplantation: clinical results and impact on T-regulatory cells.

Alemtuzumab (ALT), a humanized monoclonal anti-CD52 antibody, was introduced in solid organ transplantation as an induction agent. ALT associated with anticalcineurins has provided a low incidence of acute rejection episodes (ARE) and potential tolerogenic properties. We analyzed the clinical outcomes and effects on peripheral Treg of renal transplant recipients treated with ALT. Six-month data on kidney alone or kidney combined with pancreas or liver patients treated with ALT and tacrolimus (TAC) in standard doses were compared with those on renal transplant recipients of similar demography who were not treated with ALT. We evaluated patient and graft survivals, ARE incidence, hematological parameters, renal function, adverse events, and CD4+CD25+FoxP3+ T cells in peripheral blood. Demographics of recipients, donors, and transplants were similar in both groups. Mean HLA mismatch was slightly greater among ALT-treated patients (3.5 vs 2.5). No combined transplantation was performed in the ALT-untreated group. Patient and graft survivals were 100% without rejection or serious infections in both groups. ALT-treated recipients showed anemia and leukopenia in 3 patients as well as severe lymphopenia in 5 recipients, who partially recovered on day 90. Final mean plasma creatinine was 1.4 mg/dL, while calculated creatinine clearance was approximately 65 mL/min in both groups. Mean Treg cell percentage was higher among ALT-treated recipients than the comparative group or healthy controls (P < .05). In conclusion, renal transplantation results obtained using ALT with rigorous immunosuppressive therapy were excellent; serious adverse events and acute rejection were absent. The effect of the increased proportion of Treg cells must be evaluated with longer observation.

Oral Sciences PhD Program Enrollment, Graduates, and Placement: 1994 to 2016.

For decades, dental schools in the United States have endured a significant faculty shortage. Studies have determined that the top 2 sources of dental faculty are advanced education programs and private practice. Those who have completed both DDS and PhD training are considered prime candidates for dental faculty positions. However, there is no national database to track those trainees and no evidence to indicate that they entered academia upon graduation. The objective of this study was to assess outcomes of dental school-affiliated oral sciences PhD program enrollment, graduates, and placement between 1994 and 2016. Using the American Dental Association annual survey of advanced dental education programs not accredited by the Commission on Dental Accreditation and data obtained from 22 oral sciences PhD programs, we assessed student demographics, enrollment, graduation, and placement. Based on the data provided by program directors, the average new enrollment was 33, and graduation was 26 per year. A total of 605 graduated; 39 did not complete; and 168 were still in training. Among those 605 graduates, 211 were faculty in U.S. academic institutions, and 77 were faculty in foreign institutions. Given that vacant budgeted full-time faculty positions averaged 257 per year during this period, graduates from those oral sciences PhD programs who entered academia in the United States would have filled 9 (3.6%) vacant faculty positions per year. Therefore, PhD programs have consistently generated only a small pipeline of dental school faculty. Better mentoring to retain talent in academia is necessary. Stronger support and creative funding plans are essential to sustain the PhD program. Furthermore, the oral sciences PhD program database should be established and maintained by dental professional organizations to allow assessments of training models, trends of enrollment, graduation, and placement outcomes.

[Palliative treatment of primary lung tumors with transpulmonary chemoembolization (TPCE)]. / Transpulmonale Chemoembolisation (TPCE) als palliatives Behandlungskonzept bei primären Lungentumoren.

PURPOSE: To evaluate transpulmonary chemoembolization (TPCE) as a symptomatic palliative method for treating inoperable primary lung tumors. MATERIALS AND METHOD: From 2002 to 2005, 17 patients (17 males, 3 females; average age: 64.5 years) suffering from primary lung tumors were treated in 3.6 sessions (range: 2 to 8) using TPCE. The patients had the following primary tumors: adenocarcinoma (n = 6), pleural mesothelioma (n = 2), squamous cell carcinoma (n = 1), small cell carcinoma (n = 1), and non-small cell carcinoma (n = 7). After femoral vein puncture, tumor-supplying pulmonary arteries were selectively explored, and 5 - 10 mg mitomycin C and 5 - 10 mL lipiodol and microsphere particles (Spherex) (20 - 70 microm in diameter) were applied with balloon protection. Diagnosis and follow-up were performed in 4-week intervals with unenhanced and contrast-enhanced computed tomography (CT). The mean follow-up was 11.3 months. RESULTS: Treatment was well tolerated by all patients with no major side effects or complications. The laboratory parameters were not significantly influenced. 11.8 % of the patients (n = 2) showed high or moderate lipiodol uptake, and 76.5 % (n = 13) showed low lipiodol uptake. After evaluation of morphologic criteria, a mean volume regression of 12.1 ml (40.4 %) of the embolized areas was achieved in four patients (23.5 %), while a constant value was identified during follow-up for seven patients (41.2 %). In six patients (35.3 %), progression of the treated lung tumors was recorded. The tumor increased by a mean of 38.37 ml (165.38 %). CONCLUSION: TPCE is a well-tolerated palliative treatment option for patients with primary lung tumors.

Conversion from a calcineurin inhibitor-based immunosuppressive regimen to everolimus in renal transplant recipients: effect on renal function and proteinuria.

New immunosuppressive agents are being actively researched to avoid complications of chronic allograft nephropathy (CAN), calcineurin inhibitor (CNI) nephrotoxicity, and posttransplantation cancer. The family of mTOR inhibitors offers a unique immunosuppressive opportunity to avoid CNI toxicity and reduce the incidence of malignancy. Nevertheless, increasing data have demonstrated that sirolimus (SRL), the first mTOR introduced in the treatment of solid organ transplant recipients, induces proteinuria, an adverse event that could produce deterioration of long-term renal function. In this short-term study of patients followed for 1 to 16 months, we examined changes in renal function and proteinuria among renal transplant recipients converted from a CNI-based regimen to an everolimus (EVL)-based one, a recently introduced mTOR inhibitor. Our data showed that renal function can be optimized after conversion to EVL by up to 42% in recipients showing CAN grade 1 or 2, or CNI nephrotoxicity. Importantly, patients who improved their creatinine clearance did not show increased proteinuria measured in a voided specimen as the ratio of urinary protein and creatinine concentration (P/C). These results, if confirmed with long-term follow-up and a larger number of patients, would allow us to consider EVL as a promising agent for maintenance immunosuppressive regimens in kidney transplantation.

Pediatric liver retransplantation: indications and outcome.

INTRODUCTION: Liver transplantation is the only treatment for end-stage liver disease. Not all patients have a favorable outcome. Graft failure secondary to primary nonfunction, vascular complications, or chronic rejection among other problems may lead to retransplantation. Retransplantation represents 8% to 29% of liver transplantations in the pediatric population. The aim of this study was to present our experience with retransplanted children by analyzing the indications and the results. METHODS: All patients were prospectively included in our database, including 125 children. We included the indications for retransplantation, complications, and mortality. Kaplan-Meier curves were used for survival analysis. RESULTS: Since 1994, 125 patients were transplanted and 25 were retransplanted (20%), including 5 who received a third graft. Primary nonfunction represented 30% of the indications for retransplantation and hepatic artery thrombosis, 20%. Six of 25 patients who received a first retransplantation and 2 of 5 who received a second retransplantation died. The most frequent cause of death was multiorgans failure. The survivals at 1 and 5 years were 82% and 76% for children receiving a first retransplantation, and 60% at 1 and 5 years for those who received a second retransplantation. CONCLUSIONS: Organ failure after liver transplantation was a common event in pediatric transplantation. Survival was similar between patients transplanted once and those who received one retransplantation. Survival decreased among patients who received a third graft but was maintained at 60%, which is better than most published results for first retransplanted patients. Retransplantation is a valid option with good results for selected pediatric cases.

[In vivo proton MR spectroscopy of normal liver parenchyma: technique and results]. / In-vivo-Protonenspektroskopie des Leberparenchyms: Technik und Ergebnisse.

PURPOSE: To analyze the proton magnetic resonance spectroscopic data ( (1)H MRS) of normal liver parenchyma with regard to age, sex, body mass index and location in the liver. MATERIALS AND METHODS: 45 healthy volunteers age 24 to 65 years were examined with an optimized single-voxel (1)H MRS using a 1.5-T scanner. A spin echo sequence with a TR of 1500 ms and a TE of 135 ms was used, allowing in-phase detection of the choline signal. Weak water suppression was achieved using a chemical shift selective suppression (CHESS) technique. Each examination included the measurement of three voxels with a voxel size of 18 x 18 x 18 mm (3) in different areas of the liver. The volunteers were divided into different age-based groups (young: < or = 44 years; older: > or = 44 years), BMI (normal weighted: < 25 kg/m (2); obese: > 25 kg/m (2)) and sex. RESULTS: In the acquired spectra different lipid (e. g. [CH (2)] (n)), choline, glutamine, glutamate and glycogen-glucose-complex resonances were detected. The analysis of the spectra, however, only focused on the concentrations of choline and (CH (2)) (n) and the relative concentrations of the choline-to-(CH (2)) (n)-ratios. In the older volunteers the relative concentration of the choline-to-(CH (2)) (n)-ratio was significantly decreased by 0.213 +/- 0.193 in comparison to the younger subjects (p = 0,031). Further statistical analysis confirmed a significant decrease of the choline-to-(CH (2)) (n)-ratio by 0.223 +/- 0.180 in obese volunteers compared to volunteers of a standard weight (p = 0,016). The significant difference between the choline-to-(CH (2)) (n)-ratio in female versus male volunteers was calculated with an increase of 0.483 +/- 0.172 (p = 0,000). The location of the voxel in the liver parenchyma did not yield a significant difference in the choline-to-(CH (2)) (n)-ratio. CONCLUSION: The analysis of the proton liver MRS of healthy volunteers indicated a significant difference in the choline-to-(CH (2)) (n)-ratio depending on age, sex, and BMI with a confidence interval of 95 %. The different choline-to-(CH (2)) (n)-ratio could be the result of the body fat distribution depending on age and sex and also of the increased fat portion of the body in obese volunteers.

Various methods of analysis of mdr-1/P-glycoprotein in human colon cancer cell lines.

BACKGROUND: Multidrug resistance (MDR) mediated by high levels of mdr-1 (also known as PGY1)/P-glycoprotein (Pgp) has been studied in tissue culture systems; however, most tumor samples which express mdr-1/Pgp have much lower levels. PURPOSE: We wanted to determine if levels seen clinically could be detected by commonly used methods and to determine if these levels conferred MDR reversible by Pgp antagonists. METHODS: We studied multi-drug-resistant cell lines and sublines with levels of mdr-1/Pgp expression comparable to those seen clinically. We evaluated the expression of mdr-1 RNA by Northern blot analysis, slot blot analysis, polymerase chain reaction (PCR) analysis, and in situ hybridization. We evaluated protein expression by immunofluorescence, immunohistochemistry, fluorescence-activated cell sorting, and immunoblotting analyses. Drug resistance and reversibility were determined by cell growth during continuous drug exposure. RESULTS: In most cases, the low level of mdr-1/Pgp present in these cell lines could be detected by each method, but the assays were at the limit of sensitivity for all methods except the PCR method. These low levels of mdr-1/Pgp are capable of conferring MDR, which can be antagonized by verapamil. CONCLUSIONS: Levels of mdr-1/Pgp similar to those found in clinical samples can be detected by each of these methods, but the PCR method was the most sensitive and most reliably quantitative. IMPLICATIONS: In vitro sensitization by the addition of verapamil in cell lines with these low levels of mdr-1/Pgp suggests that clinically detected levels may confer drug resistance in vivo.

Deletion mapping of a putative tumor suppressor gene on chromosome 4 in mouse lung tumors.

Genetic and molecular studies have implicated the region of the alpha-interferon gene cluster on mouse chromosome 4 as the location of a putative tumor suppressor gene. A region of homology on human chromosome 9p21-22 that is frequently deleted in multiple human cancers has recently been found to contain a candidate tumor suppressor gene called multiple tumor suppressor-1 (MTS1); which was previously shown to encode an inhibitor of cyclin-dependent kinase 4. We performed loss of heterozygosity and deletion analyses to map the most commonly deleted region on chromosome 4 in F1 hybrid mouse lung tumors. Ten simple sequence length polymorphism markers were analyzed with focus on the alpha-interferon region. Allelic losses were detected in 29 of 61 (48%) of the lung adenocarcinomas but in only 1 of 38 (3%) of the lung adenomas examined. In most cases, the losses appeared to occur by nondisjunction. However, in three carcinomas, we detected homozygous deletions that overlapped at simple sequence length polymorphism marker D4MIT77. These data suggest a critical region of about 2 cM immediately distal to the alpha-interferon locus as the likely domain of a novel tumor suppressor gene on mouse chromosome 4, the loss of which appears to be involved in the progression of mouse lung tumorigenesis.