Drug interactions may be important risk factors for methotrexate neurotoxicity, particularly in pediatric leukemia patients

Purpose: Methotrexate administration is associated with frequent adverse neurological events during treatment for childhood acute lymphoblastic leukemia. Here, we present evidence to support the role of common drug interactions and low vitamin B12 levels in potentiating methotrexate neurotoxicity. Methods: We review the published evidence and highlight key potential drug interactions as well as present clinical evidence of severe methotrexate neurotoxicity in conjunction with nitrous oxide anesthesia and measurements of vitamin B12 levels among pediatric leukemia patients during therapy. Results: We describe a very plausible mechanism for methotrexate neurotoxicity in pediatric leukemia patients involving reduction in methionine and consequential disruption of myelin production. We provide evidence that a number of commonly prescribed drugs in pediatric leukemia management interact with the same folate biosynthetic pathways and/or reduce functional vitamin B12 levels and hence are likely to increase the toxicity of methotrexate in these patients. We also present a brief case study supporting out hypothesis that nitrous oxide contributes to methotrexate neurotoxicity and a nutritional study, showing that patients. Conclusions: Use of nitrous oxide in pediatric leukemia patients at the same time as methotrexate use should be avoided especially as many suitable alternative anesthetic agents exist. Clinicians should consider monitoring levels of vitamin B12 in patients suspected of having methotrexate- induced neurotoxic effects

Reply: Methotrexate neurotoxicity due to drug interactions: an inadequate folinic acid effect

No abstract available

Fluctuations of a Greenlandic tidewater glacier driven by changes in atmospheric forcing : observations and modelling of Kangiata Nunaata Sermia, 1859–present

Acknowledgements. The authors wish to thank Stephen Price, Mauri Pelto, and the anonymous reviewer for their reviews and comments that helped to improve the manuscript. RACMO2.1 data were provided by Jan van Angelen and Michiel van den Broeke, IMAU, Utrecht University. MAR v3.2 data used for runoff calculations were provided by Xavier Fettweis, Department of Geography, University of Liège. The photogrammetric DEM used in Figs. 1 and 3 was provided by Kurt H. Kjær, Centre for GeoGenetics, University of Copenhagen. This research was financially supported by J. M. Lea’s PhD funding, NERC grant number NE/I528742/1. Support for F. M. Nick was provided through the Conoco-Phillips/Lundin Northern Area Program CRIOS project (Calving Rates and Impact on Sea Level).Peer reviewedPublisher PD

Genetic variation of Pyrenophora teres f. teres isolates in Western Australia and emergence of a Cyp51A fungicide resistance mutation

Plant Pathology published by John Wiley & Sons Ltd on behalf of British Society for Plant Pathology. Genome-wide, unlinked, simple sequence repeat markers were used to examine genetic variation and relationships within Pyrenophora teres f. teres, a common pathogen of barley, in Western Australia. Despite the region's geographic isolation, the isolates showed relatively high allelic variation compared to similar studies, averaging 7.11 alleles per locus. Principal component, Bayesian clustering and distance differentiation parameters provided evidence for both regional genotypic subdivision together with juxtaposing of isolates possessing different genetic backgrounds. Genotyping of fungicide resistant Cyp51A isolates indicated a single mutation event occurred followed by recombination and long-distance regional dispersal over hundreds of kilometres. Selection of recently emergent favourable alleles such as the Cyp51A mutation and a cultivar virulence may provide an explanation, at least in part, for juxtaposed genotypes. Factors affecting genotypic composition and the movement of new genotypes are discussed in the context of grower practices and pathogen epidemiology, together with the implications for resistance breeding

The glacial geomorphology of upper Godthåbsfjord (Nuup Kangerlua) in south-west Greenland

© 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of Journal of Maps. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.The Greenland Ice Sheet (GrIS) is known to have experienced widespread retreat over the last century. Information on outlet glacier dynamics, prior to this, are limited due to both a lack of observations and a paucity of mapped or mappable deglacial evidence which restricts our understanding of centennial to millennial timescale dynamics of the GrIS. Here we present glacial geomorphological mapping, for upper Godthåbsfjord, covering 5800 km 2 at a scale of 1:92,000, using a combination of ASTER GDEM V2, a medium-resolution DEM (error < 10 m horizontal and < 6 m vertical accuracy), panchromatic orthophotographs and ground truthing. This work provides a detailed geomorphological assessment for the area, compiled as a single map, comprising of moraines, meltwater channels, streamlined bedrock, sediment lineations, ice-dammed lakes, trimlines, terraces, gullied sediment and marine limits. Whilst some of the landforms have been previously identified, the new information presented here improves our understanding of ice margin behaviour and can be used for future numerical modelling and landform dating programmes. Data also form the basis for palaeoglaciological reconstructions and contribute towards understanding of the centennial to millennial timescale record of this sector of the GrIS.Peer reviewedFinal Published versio

Plasma heating in highly excited GaN/AlGaN multiple quantum wells

Time-resolvedphotoluminescence(PL)spectroscopy was used to investigate carrier distributions in a GaN/AlGaN multiple quantum well(MQW) sample under high excitation intensities necessary to achieve lasing threshold. Room temperaturePL spectra showed optical transitions involving both confined and unconfined states in the quantum well structure. Analysis of the experimental results using a microscopic theory, indicates that at high excitation the carrier distributions are characterized by plasma temperatures which are significantly higher than the lattice temperature. The implications of our findings on GaN MQW laser design are also discussed

Follow-up study of sensory-motor polyneuropathy in Type 1 (insulin-dependent) diabetic subjects after simultaneous pancreas and kidney transplantation and after graft rejection

The influence of successful simultaneous pancreas and kidney transplantation on peripheral polyneuropathy was investigated in 53 patients for a mean observation period of 40.3 months. Seventeen patients were followed-up for more than 3 years. Symptoms and signs were assessed every 6 months using a standard questionnaire, neurological examination and measurement of sensory and motor nerve conduction velocities. While symptoms of polyneuropathy improved (pain, paraesthesia, cramps, restless-legs) and nerve conduction velocity increased, there was no change of clinical signs (sensation, muscle-force, tendon-reflexes). Following kidney-graft-rejection there was a slight decrease of nerve conduction verlocity during the first year, which was not statistically significant. Following pancreas-graft rejection there was no change of nerve conduction velocity during the first year. Comparing the maximum nerve conduction velocity of the patients with pancreas-graft-rejection to the nerve conduction velocities of these patients at the end of the study, there was a statistically significant decrease of 6.5 m/s. In conclusion, we believe that strict normalization of glucose metabolism alters the progressive course of diabetic polyneuropathy. It may be stabilized or partly reversed after successful grafting even in long-term diabetic patients