α-Conotoxin VnIB from Conus ventricosus is a potent and selective antagonist of α6ß4* nicotinic acetylcholine receptors.

α6-containing (α6*) nicotinic acetylcholine receptors (nAChRs) are expressed throughout the periphery and the central nervous system and constitute putative therapeutic targets in pain, addiction and movement disorders. The α6ß2* nAChRs are relatively well studied, in part due to the availability of target specific α-conotoxins (α-Ctxs). In contrast, all native α-Ctxs identified that potently block α6ß4 nAChRs exhibit higher potencies for the closely related α6ß2ß3 and/or α3ß4 subtypes. In this study, we have identified a novel peptide from Conus ventricosus with pronounced selectivity for the α6ß4 nAChR. The peptide-encoding gene was cloned from genomic DNA and the predicted mature peptide, α-Ctx VnIB, was synthesized. The functional properties of VnIB were characterized at rat and human nAChRs expressed in Xenopus oocytes by two-electrode voltage clamp electrophysiology. VnIB potently inhibited ACh-evoked currents at rα6ß4 and rα6/α3ß4 nAChRs, displayed ∼20-fold and ∼250-fold lower potencies at rα3ß4 and rα6/α3ß2ß3 receptors, respectively, and exhibited negligible effects at eight other nAChR subtypes. Interestingly, even higher degrees of selectivity were observed for hα6/α3ß4 over hα6/α3ß2ß3 and hα3ß4 receptors. Finally, VnIB displayed fast binding kinetics at rα6/α3ß4 (on-rate t½â€¯= 0.87 min-1, off-rate t½â€¯= 2.7 min-1). The overall preference of VnIB for ß4* over ß2* nAChRs is similar to the selectivity profiles of other 4/6 α-Ctxs. However, in contrast to previously identified native α-Ctxs targeting α6* nAChRs, VnIB displays pronounced selectivity for α6ß4 nAChRs over both α3ß4 and α6ß2ß3 receptors. VnIB thus represents a novel molecular probe for elucidating the physiological role and therapeutic properties of α6ß4* nAChRs.

A Rare Case of Multiple Myeloma Presenting as Evan's Syndrome.

Multiple myeloma is defined as the neoplastic proliferation of plasma cells resulting in a monoclonal gammopathy. The classic presentation of a patient is someone who presents with bone pain, osteopenia, or new onset fractures. We present a case of multiple myeloma presenting as Evan's syndrome (ES). Evan's syndrome is autoimmune hemolytic anaemia with autoimmune thrombocytopenia. A 44-year-old female was referred from her primary physician to the hospital as laboratory testing revealed haemoglobin of 5 gm/dL. The patient reported a two-month history of fatigue and a sixty-pound weight loss. Laboratory results demonstrated autoimmune hemolytic anaemia, C3 positivity, elevated immunoglobulin (Ig)G, elevated lactate dehydrogenase (LDH), low haptoglobin, elevated reticulocyte count, elevated RDW-CV (red blood cell distribution width-corpuscular volume), positive direct Coombs test, thrombocytopenia, and proteinuria, all of which led to an underlying ES. The patient was started on intravenous steroids followed by oral steroids. A flow cytometry, serum protein electrophoresis, and cytogenetics were obtained. A bone marrow biopsy revealed multiple myeloma and she was started on Bortezomib treatment. We present the fifth reported case of Evan's syndrome and multiple myeloma.

Responsabilidad ante el error y la mala práctica del actuar médico / Responsabilité vis-à-vis l'erreur et la négligence dans l'acte médical / Responsibility in view of medical error and malpractice

La percepción que tiene la población sobre la ocurrencia de una atención deficiente a pacientes por parte del personal facultativo que labora en instituciones de salud se ha hecho innegable, de la cual se han hecho eco incluso los medios masivos de comunicación. Ello ha motivado que se realice un trabajo concerniente a la responsabilidad que adquiere el profesional de la salud en el ejercicio de su faena y de la cual tendrá que responder, en ocasiones, ante autoridades civiles y judiciales por lesiones infringidas a personas a su cargo. El objetivo es considerar las causas que pueden conducir a error médico y a mala praxis; profundizar en la responsabilidad penal del facultativo, brindando información sobre los basamentos y procederes médico-legales, donde están reguladas la mayoría de las actuaciones que como profesional debe cumplir y hacer cumplir; exponer las consecuencias y sanciones que se pueden derivar de una irresponsabilidad profesional. Para ello se revisaron las violaciones de las reglas del arte médico encontradas en expedientes de fase preparatoria de casos reales, que han sido procesados por instructores policiales y fiscales, para que una comisión de responsabilidad penal emita un dictamen pericial que permita a un tribunal poder realizar un juicio en el cual esté involucrado un profesional de la salud. Se concluye que la exposición de esos hechos delictivos, contribuirá preventivamente para que debido a falta de conocimientos no se incurra en estos(AU)

The perception of the population about the occurrence of a deficient medical attention to patients from health personnel that works in different health care centres has been an undeniable fact which has echoed even around the massive means of communication. This has motivated us to carry out a work concerning the responsibility that a health professional has in his job in which he will have to answer, occasionally, to the civil and judicial authorities because of lesions present in people in their care. The aim is to consider the causes that can lead to medical error and malpractice, to go into the criminal responsibility of the practitioner providing information on the medico legal attitudes and behaviours which are regulated in most of the acts as an action that the professional should fulfil and makes fulfil, and also to state the consequences and disciplinary measures that can be derived from a professional irresponsibility. For this, we revised the rules violations in the medical arts, found in the records of the preparatory phase of real cases which have been processed by prosecutors and police instructors so that a committee of criminal responsibility delivers an expert report that allows a health professional who is involved in any irresponsibility to appear in court. It is concluded that, the exposure to those criminal acts will preventively contribute to avoid them when the implicated personnel lacks the necessary knowledge on this respect(AU)

La perception d'un service médical déficient, dont même les médias se font l'écho, dévient incontestable pour une population. Cela a motivé une analyse concernant la responsabilité assumée par le professionnel de la santé dans l'exercice de ses fonctions, parfois devant les autorités civiles et judiciaires, en raison des lésions causées à des personnes à sa charge. Le but de ce travail est de considérer les causes étant à l'origine d'une erreur médicale et d'une mauvaise praxis, d'approfondir dans la responsabilité pénale du médecin, en donnant des informations sur les fondements et les procédés médico-légaux, et d'exposer les conséquences et sanctions dérivées de l'irresponsabilité professionnelle. À cette fin, une révision des violations des règles de la médecine, trouvées dans les dossiers en phase préparatoire des cas réels, a été réalisée. On conclu que la présentation de ces délits contribuera efficacement à leur prévention(AU)