Contribution of toxicological analysis to the care of dimethyl fumarate dermatitis

Background: Dimethyl fumarate (DMFu) is a fungicide which is used in Chinese manufactures of furniture and shoes to avoid mould spoiling of fabrics. In 2008, DMFu was found the responsible allergen for several cases of contact dermatitis from armchairs and shoes observed in Europe. In France a national toxicovigilance survey was set up and importation of products containing dimethyl fumarate is now forbidden. Case report: a 36 year-old woman, with no history of previous allergy, was hospitalized because of a severe acute eczema of her feet after wearing a new pair of boots inside which she had noticed desiccant sachets. She strongly reacted on patch testing to DMFu and to the content of a sachet which was identified as DMFu, both at 0.01%, 0.1%, 1% in petrolatum, and also to a piece of the fabric of her boots, patch tested as is. Materials and method: Boot fabrics and mould-proof sachets found in the boots were analysed by HPLC/UV/DAD and GC/MS after methanol extraction. Further samples of anti mould agent sachets or shoe fabrics from 5 other patients with suspicion of DMFu dermatitis were analysed with the same procedure. Some of them were transferred to the laboratory several months after healing of the dermatitis. Results: DMFu was found in all the samples from 1 to 100% in sachets or from 20 to 2000 μg/g in the fabrics of shoes, even after one year. These findings contributed to ensure the responsibility of DMFu in the dermatitis of the patients and demonstrate that DMFu may remain a long time in the contaminated fabrics after removal of the sachets. This study also points out the usefulness of the collaboration between dermatologists, biologists and poison centre practitioners

Geometric Laws of Vortex Quantum Tunneling

In the semiclassical domain the exponent of vortex quantum tunneling is dominated by a volume which is associated with the path the vortex line traces out during its escape from the metastable well. We explicitly show the influence of geometrical quantities on this volume by describing point vortex motion in the presence of an ellipse. It is argued that for the semiclassical description to hold the introduction of an additional geometric constraint, the distance of closest approach, is required. This constraint implies that the semiclassical description of vortex nucleation by tunneling at a boundary is in general not possible. Geometry dependence of the tunneling volume provides a means to verify experimental observation of vortex quantum tunneling in the superfluid Helium II.Comment: 4 pages, 2 figures, revised version to appear in Phys. Rev.

Analytical Estimate of the Critical Velocity for Vortex Pair Creation in Trapped Bose Condensates

We use a modified Thomas-Fermi approximation to estimate analytically the critical velocity for the formation of vortices in harmonically trapped BEC. We compare this analytical estimate to numerical calculations and to recent experiments on trapped alkali condensates.Comment: 12 page

Josephson effects in dilute Bose-Einstein condensates

We propose an experiment that would demonstrate the ``dc'' and ``ac'' Josephson effects in two weakly linked Bose-Einstein condensates. We consider a time-dependent barrier, moving adiabatically across the trapping potential. The phase dynamics are governed by a ``driven-pendulum'' equation, as in current-driven superconducting Josephson junctions. At a critical velocity of the barrier (proportional to the critical tunneling current), there is a sharp transition between the ``dc'' and ``ac'' regimes. The signature is a sudden jump of a large fraction of the relative condensate population. Analytical predictions are compared with a full numerical solution of the time dependent Gross-Pitaevskii equation, in an experimentally realistic situation.Comment: 4 pages, 1 figur

Tuning the spin Hamiltonian of NENP by external pressure: a neutron scattering study

We report an inelastic neutron scattering study of antiferromagnetic spin dynamics in the Haldane chain compound Ni(C2H8N2)2NO2ClO4 (NENP) under external hydrostatic pressure P = 2.5 GPa. At ambient pressure, the magnetic excitations in NENP are dominated by a long-lived triplet mode with a gap which is split by orthorhombic crystalline anisotropy into a lower doublet centered at $\Delta_\perp\approx$ 1.2meV and a singlet at $\Delta_\parallel\approx$ 2.5meV. With pressure we observe appreciable shifts in these levels, which move to $\Delta_\perp{(2.5GPa)}\approx$ 1.45 meV and $\Delta_\parallel(2.5GPa)\approx$ 2.2meV. The dispersion of these modes in the crystalline c-direction perpendicular to the chain was measured here for the first time, and can be accounted for by an interchain exchange J'_c approximately 3e-4*J which changes only slightly with pressure. Since the average gap value $\Delta_H\approx$ 1.64 meV remains almost unchanged with P, we conclude that in NENP the application of external pressure does not affect the intrachain coupling J appreciably, but does produce a significant decrease of the single-ion anisotropy constant from D/J = 0.16(2) at ambient pressure to D/J = 0.09(7) at P = 2.5 GPa.Comment: LaTeX file nenp_p.tex, 10 pages, 1 table, 5 figures. Submitted to Phys. Rev.

Clinical setting influences off-label and unlicensed prescribing in a paediatric teaching hospital

Purpose - To estimate the prevalence of off-label and unlicensed prescribing during 2008 at a major paediatric teaching hospital in Western Australia. Methods - A 12-month retrospective study was conducted at Princess Margaret Hospital using medication chart records randomly selected from 145,550 patient encounters from the Emergency Department, Inpatient Wards and Outpatient Clinics. Patient and prescribing data were collected. Drugs were classified as off-label or unlicensed based on Australian registration data. A hierarchical system of age, indication, route of administration and dosage was used. Drugs were classified according to the Anatomical Therapeutic Chemical Code. Results - A total of 1,037 paediatric patients were selected where 2,654 prescriptions for 330 different drugs were prescribed to 699 patients (67.4%). Most off-label drugs (n = 295; 43.3%) were from the nervous system; a majority of unlicensed drugs were systemic hormonal preparations excluding sex hormones (n = 22, 32.4%). Inpatients were prescribed more off-label drugs than outpatients or Emergency Department patients (p < 0.0001). Most off-label prescribing occurred in infants and children (31.7% and 35.9% respectively) and the highest percentage of unlicensed prescribing (7.2%) occurred in infants (p < 0.0001). There were 25.7% of off-label and 2.6% of unlicensed medications prescribed across all three settings. Common reasons for off-label prescribing were dosage (47.4%) and age (43.2%). Conclusion - This study confirmed off-label and unlicensed use of drugs remains common. Further, that prevalence of both is influenced by the clinical setting, which has implications in regards to medication misadventure, and the need to have systems in place to minimise medication errors. Further, there remains a need for changes in the regulatory system in Australia to ensure that manufacturers incorporate, as it becomes available, evidence regarding efficacy and safety of their drugs in children in the official product information

Prescrição e preparo de medicamentos sem formulação adequada para crianças: um estudo de base hospitalar

Este trabalho teve como objetivo identificar medicamentos cuja forma ou formulação farmacêutica representa um problema em pediatria (Medicamento Problema - MP), bem como analisar as estratégias empregadas pelos médicos, para sua utilização nas crianças e os riscos envolvidos. Trata-se de um estudo descritivo, que tem como base um inquérito com pediatras de um hospital de referência do SUS em Fortaleza-Ceará, conduzido para identificação dos MPs em julho-agosto de 2004; uma análise das prescrições contendo adaptação de formas sólidas e uma observação direta do preparo dos medicamentos, que foram conduzidas em dezembro de 2004 e janeiro de 2005, respectivamente. Os medicamentos foram agrupados pela classificação ATC e pelo cálculo de frequências das variáveis. Os pediatras (N=48, 98%) identificaram: 16 produtos sem forma injetável, 32 injetáveis necessários em concentrações menores e 30 MP sem formulação líquida para uso oral. Foram analisadas 89 prescrições contendo adaptação de formas sólidas, envolvendo 119 itens de medicamentos; todas continham inadequações, sendo a principal a partição de comprimidos. As doses prescritas corresponderam ao preconizado em 33,6% dos casos. Adaptações foram realizadas em local inadequado, por profissional não qualificado e sem as boas práticas. Concluindo, a carência de formulações apropriadas ao uso pediátrico repercute na prática médica e é agravada pela inexistência de condições adequadas para a manipulação de medicamentos por farmacêuticos, nos hospitais brasileiros.This work aimed to identify medicines whose form or pharmaceutical formula presents a problem to pediatrics (Problem Medication - PM), the strategies employed by doctors to use them in children, and the potential risks involved. Descriptive study: based on a survey with pediatricians from a SUS (Public Health System) reference hospital in Fortaleza-CE (Northeastern Brazil), in order to identify PMs, from July to August 2004; an analysis of prescriptions containing modification of medicines in the solid forms; and a follow-up of medicinal preparations, developed in December 2004 and January 2005, respectively. The medications were grouped by an anatomic, therapeutic and chemical classification and by means of a calculation of variables frequency. The pediatricians (N=48, 98% of the total) identified as PMs: 16 products without an injectable form; 32 in an injectable form that should be presented in lesser concentrations; and 30 without a liquid formula for oral use. Eighty two (82) prescriptions containing modifications of solid forms, involving 111 medicinal items were analyzed, all of which contained inadequacies; the main one being the partition of pills. In 33.6% of the cases, the prescribed doses were in accordance with that generally recommended. The modifications were carried out in inadequate places, by nonqualified professionals and without the use of best practices. The lack of appropriate formulae for pediatric use has an impact on medical practices. It is aggravated by the lack of appropriate conditions for medicines manipulation by pharmacists, in Brazilian hospitals, and this impact involves risks to patients