Cardiac Alterations in Human African Trypanosomiasis (T.b. gambiense) with Respect to the Disease Stage and Antiparasitic Treatment

In Human African Trypanosomiasis (HAT), neurological symptoms dominate and cardiac involvement has been suggested. Because of increasing resistance to the available drugs for HAT, new compounds are desperately needed. Evaluation of cardiotoxicity is one parameter of drug safety, but without knowledge of the baseline heart involvement in HAT, cardiologic findings and drug-induced alterations will be difficult to interpret. The electrocardiogram (ECG) is a tool to evaluate cardiac involvement and the risk of arrythmias. We analysed the ECG of 465 HAT patients and compared them with the ECG of 61 healthy volunteers. In HAT patients the QTc interval was prolonged. This comprises a risk of fatal arrhythmias if new drugs with antiarrhythmic potential will be used. Further, repolarization changes and low voltage were more frequent than in healthy controls. This could be explained by an inflammation of the heart. Treatment of HAT was associated with appearance of repolarization changes but not with a QTc prolongation. These changes appear to be associated with the disease, but not with a specific drug. The main conclusion of this study is that heart involvement is frequent in HAT and mostly well tolerated. However, it can become relevant, if new compounds with antiarrhythmic potential will be used

Constraints on models of the Higgs boson with exotic spin and parity using decays to bottom-antibottom quarks in the full CDF data set

A search for particles with the same mass and couplings as those of the standard model Higgs boson but different spin and parity quantum numbers is presented. We test two specific alternative Higgs boson hypotheses: a pseudoscalar Higgs boson with spin-parity JP=0- and a gravitonlike Higgs boson with JP=2+, assuming for both a mass of 125GeV/c2. We search for these exotic states produced in association with a vector boson and decaying into a bottom-antibottom quark pair. The vector boson is reconstructed through its decay into an electron or muon pair, or an electron or muon and a neutrino, or it is inferred from an imbalance in total transverse momentum. We use expected kinematic differences between events containing exotic Higgs bosons and those containing standard model Higgs bosons. The data were collected by the CDF experiment at the Tevatron proton-antiproton collider, operating at a center-of-mass energy of s=1.96TeV, and correspond to an integrated luminosity of 9.45fb-1. We exclude deviations from the predictions of the standard model with a Higgs boson of mass 125GeV/c2 at the level of 5 standard deviations, assuming signal strengths for exotic boson production equal to the prediction for the standard model Higgs boson, and set upper limits of approximately 30% relative to the standard model rate on the possible rate of production of each exotic state

Early Use of Mother's Own Raw Milk, Maternal Satisfaction, and Breastfeeding Continuation in Hospitalised Neonates: A Prospective Cohort Study.

Despite the critical importance of breast milk for preterm and sick neonates, there is no consensus regarding the use of raw mother's own milk (MOM) in neonatal units. This study aimed to describe the use of raw MOM in hospitalised neonates before day 7 (early use), and to investigate: (i) related factors, (ii) maternal satisfaction, and (iii) the association with breastfeeding continuation. This prospective cohort included 516 neonates intended to be breastfed in 2 French neonatal units. Neonates receiving raw MOM before day 7 were compared to those who did not. The association between early use of MOM and breastfeeding continuation at hospital discharge, and up to 6 months later, was measured by logistic regression. More than one-third (36.2%) of breastfed neonates did not receive any MOM during their first week, mainly due to organisational constraints and staff reluctance. Maternal satisfaction related to early raw MOM use was high (96%), and was coupled with a more frequent maternal feeling of being supported in breastfeeding (p = 0.003). There was a significant association between early use of MOM and breastfeeding continuation at discharge (OR 2.92, 95% CI 1.94-4.40, p < 0.0001), which persisted 6 months later (OR 2.70, 95% CI 1.21-6.03, p = 0.023). This association appeared independent in multivariable analyses (at discharge: aOR 2.03, 95% CI 1.27-3.25, p = 0.003; 6 months later: aOR 2.46, 95% CI 1.02-5.92, p = 0.045). While the early use of raw MOM in hospitalised neonates can be limited by multiple factors, it appears supportive for mothers, and might represent a simple opportunity to improve breastfeeding in neonatal units

Efficacy and safety of pafuramidine versus pentamidine maleate for treatment of first stage sleeping sickness in a randomized, comparator-controlled, international phase 3 clinical trial

Sleeping sickness (human African trypanosomiasis [HAT]) is a neglected tropical disease with limited treatment options that currently require parenteral administration. In previous studies, orally administered pafuramidine was well tolerated in healthy patients (for up to 21 days) and stage 1 HAT patients (for up to 10 days), and demonstrated efficacy comparable to pentamidine.; This was a Phase 3, multi-center, randomized, open-label, parallel-group, active control study where 273 male and female patients with first stage Trypanosoma brucei gambiense HAT were treated at six sites: one trypanosomiasis reference center in Angola, one hospital in South Sudan, and four hospitals in the Democratic Republic of the Congo between August 2005 and September 2009 to support the registration of pafuramidine for treatment of first stage HAT in collaboration with the United States Food and Drug Administration. Patients were treated with either 100 mg of pafuramidine orally twice a day for 10 days or 4 mg/kg pentamidine intramuscularly once daily for 7 days to assess the efficacy and safety of pafuramidine versus pentamidine. Pregnant and lactating women as well as adolescents were included. The primary efficacy endpoint was the combined rate of clinical and parasitological cure at 12 months. The primary safety outcome was the frequency and severity of adverse events. The study was registered on the International Clinical Trials Registry Platform at www.clinicaltrials.gov with the number ISRCTN85534673.; The overall cure rate at 12 months was 89% in the pafuramidine group and 95% in the pentamidine group; pafuramidine was non-inferior to pentamidine as the upper bound of the 95% confidence interval did not exceed 15%. The safety profile of pafuramidine was superior to pentamidine; however, 3 patients in the pafuramidine group had glomerulonephritis or nephropathy approximately 8 weeks post-treatment. Two of these events were judged as possibly related to pafuramidine. Despite good tolerability observed in preceding studies, the development program for pafuramidine was discontinued due to delayed post-treatment toxicity

Treatment outcomes for human African Trypanosomiasis in the Democratic Republic of the Congo: analysis of routine program data from the world's largest sleeping sickness control program

Objective To enable the human African trypanosomiasis (HAT) control program of the Democratic Republic of the Congo to generate data on treatment outcomes, an electronic database was developed. The database was piloted in two provinces, Bandundu and Kasai Oriental. In this study, we analysed routine data from the two provinces for the period 2006-2008. Methods Data were extracted from case declaration cards and monthly reports available at national and provincial HAT coordination units and entered into the database. Results Data were retrieved for 15 086 of 15 741 cases reported in the two provinces for the period (96%). Compliance with post-treatment follow-up was very poor in both provinces; only 25% had undergone at least one post-treatment follow-up examination, <1% had undergone the required four follow-up examinations. Relapse rates among those presenting for follow-up were high in Kasai (18%) but low in Bandundu (0.3%). Conclusions High relapse rates in Kasai and poor compliance with post-treatment follow-up in both provinces are important problems that the HAT control program urgently needs to address. Moreover, in analogy to tuberculosis control programs, HAT control programs need to adopt a recording and reporting routine that includes reporting on treatment outcomes

Treatment outcomes for human African Trypanosomiasis in the Democratic Republic of the Congo: analysis of routine program data from the world's largest sleeping sickness control program

OBJECTIVE: To enable the human African trypanosomiasis (HAT) control program of the Democratic Republic of the Congo to generate data on treatment outcomes, an electronic database was developed. The database was piloted in two provinces, Bandundu and Kasai Oriental. In this study, we analysed routine data from the two provinces for the period 2006-2008. METHODS: Data were extracted from case declaration cards and monthly reports available at national and provincial HAT coordination units and entered into the database. RESULTS: Data were retrieved for 15 086 of 15 741 cases reported in the two provinces for the period (96%). Compliance with post-treatment follow-up was very poor in both provinces; only 25% had undergone at least one post-treatment follow-up examination, <1% had undergone the required four follow-up examinations. Relapse rates among those presenting for follow-up were high in Kasai (18%) but low in Bandundu (0.3%). CONCLUSIONS: High relapse rates in Kasai and poor compliance with post-treatment follow-up in both provinces are important problems that the HAT control program urgently needs to address. Moreover, in analogy to tuberculosis control programs, HAT control programs need to adopt a recording and reporting routine that includes reporting on treatment outcomes.status: publishe

Grenzueberschreitende binationale Umwelterziehung in der Agrarausbildung. Projektband und Bd. 1: Das Grundmodul. Bd. 2: Die Aufbaumodule

Published in 3 volumesSIGLEAvailable from TIB Hannover: F02B1040: F02B1041: F02B1042 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDeutsche Bundesstiftung Umwelt, Osnabrueck (Germany)DEGerman