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INTRODUCTION: The use of unlicensed drugs is an unsettling issue in medical circles. "Dear Doctor Letters", batch recalls and important notifications about them are not provided systematically. Unlicensed use is, however, sometimes the only promising option for further medical treatment. Approaches to improve vigilance of pharmaceutical agents are available in many countries. An outline of legislation on and experiences with unlicensed use in selected industrial countries is reviewed in this article. Research data, documentation and assessment of the legal status of unlicensed drugs in selected industrial countries were obtained and compared to the situation in Germany. Expert interviews with specifically recruited representative samples from academic centers as well as regulatory and industrial sources, health technology assessments and health insurance data were analysed (N = 44, t = 20-120 min, transcribed verbatim). Approaches and limitations of licensing in different countries compared: Granting of a license has been an obligatory condition and there has been a duty of disclosure (sometimes with the right of prohibition) as well as reservations on the granting of permission. Central administration of data has made it possible to quantify and identify required drugs and ensure surveillance of their use. High administrative costs involved in giving notice of approval has caused delays in patient care. Procedures by which a medical doctor has to obtain permission affect physicians' freedom of action. Unlicensed and off-label use is variably regulated across the analysed settings. Legislation and regulation continue to be highly heterogeneous. Most promising approaches include the duty of disclosure, which allows quantification of use and surveillance of safety, including the right of recall while ensuring doctors' freedom to treat with medicinal products.
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Legislación de Medicamentos , Austria , Aprobación de Drogas , Drogas en Investigación/uso terapéutico , Francia , Alemania , Humanos , Irlanda , Factores de Riesgo , Reino UnidoRESUMEN
Recently, we generated cells with multipotent properties from blood monocytes that in vitro differentiate into various somatic cell types. This experimental study investigated whether these programmable cells of monocytic origin (PCMO) succeed to restore left ventricular function after myocardial infarction (MI). PCMO were generated from monocytes by exposition to RPMI medium containing M-CSF and IL-3 for 6 days. MI was induced in female Lewis rats ligating the left coronary artery. PCMO of male Lewis donors were injected either intramyocardially (i.my.) or intravenously (i.v.) 24 h or 6 days post-infarction. Hemodynamic assessment after 60 days demonstrated significant improvement of left ventricular function following i.my. transplantation of PCMO as well as early (24 h post-infarction) i.v. application while nonmodulated monocytes failed to restore heart function. The Y-chromosome-specific SRY gene of male donor PCMO was detected exclusively in infarcted hearts of animals, which demonstrated improved cardiac function. Subdivision of infarcted hearts by microdissection localized the SRY gene-containing department to the left ventricle adjacent to the infarcted area whereas the right ventricle remained negative. Successful generation of PCMO in access numbers allows their autologous use as a new additive treatment for early restoration of cardiac function after MI.
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Pruebas de Función Cardíaca , Monocitos/trasplante , Infarto del Miocardio/terapia , Trasplante de Células Madre , Función Ventricular Izquierda , Animales , Capilares/patología , Circulación Coronaria , Modelos Animales de Enfermedad , Ecocardiografía , Femenino , Hemodinámica , Masculino , Reacción en Cadena de la Polimerasa , Ratas , Ratas Endogámicas Lew , Factor A de Crecimiento Endotelial Vascular/genética , Cromosoma YRESUMEN
The oxidative metabolism of polymorphonuclear leukocytes (PMNs) in rapidly progressive periodontitis (RPP, n = 19), localized juvenile periodontitis (LJP, n = 10), adults periodontitis (AP, n = 10) and healthy control subjects (HS, n = 39) was compared using the luminol chemiluminescence (CL) method. Possible influences of the isolation procedure on CL were circumvented by replacing starch with Haemaccell 35 as the sedimentation agent. In all groups, CL was significantly higher with autologous serum than with normal pooled serum (NPS) and there was a significant linear relationship between the two values. Comparisons of both pooled and autologous serum between patient groups and their matched controls were not statistically significant. There was a suggestion of serum-induced defects in 2 patients and 1 control. The range of individual values within each group was very heterogeneous, probably because of the many factors that are able to influence both the production of CL and the basal levels of CL observed.