No description available.

No description available.

Creutzfeldt-Jakob disease (CJD) and new variant Creutzfeldt-Jakob disease (nvCJD) are among many of the insidious infectious diseases that are incurable once a person becomes infected. Similar to HIV in the early 1980's, very little is known about the enigmatic infectious agent. How the infectious agent is expressly transmitted is as inexplicable as CJD itself. The purpose of this study was to evaluate the extent of current research literature and other scholarly works in order to synthesize what is known about this fatal disease. The scope of this study was confined to the years 1993 to 1998. In addition to the information in the literature, consultation was sought from Yale University's Dr. L. Manuledis and a graduate student, Christopher A. Baker, was volunteered as a conduit for information on CJD/nvCJD. Three questions guided this study: 1) How are CJD/nvCJD diagnosed? 2) How is it transmitted?, and 3) What are the existing clinical recommendations for the management of CJD/nvCJD? One out of a million people are affected by it, and nvCJD has the potential of being spread by Bovine Spongiform Encephalopathy (BSE[Mad Cow]) tainted beef. Through this study I discovered that CJD and nvCJD have multiple routes for infection and current speculation remains divided on the dynamics of its transmission. Some of the literature was specialized and focused on proving the value of one discipline's diagnostic technique over another. While healthcare is shifting to a competitive business environment, my focus was on what were the most effective techniques regarding the diagnosis of it, limiting the spread of the infectious agent, and the medical management of infected patients.

No description available.

La Enfermedad de Creutzfeldt–Jakob es la encefalopatía espongiforme humana más común, producida por una proteína infectante llamada prion, el cual es codificado en el gen PRNP del cromosoma 20. Ésta tiene una distribución mundial, cuyas tasas de mortalidad se encuentran entre 0,5 y 1 por millón de habitantes, mientras en Chile afecta a 2 o más personas por millón de habitantes. Por esto último, el objetivo de este estudio fue determinar la distribución regional de la enfermedad en el país, a través de un estudio descriptivo y retrospectivo de tasas de hospitalizaciones y mortalidad de la enfermedad del año 2001 al 2007, calculadas a partir de los datos de egresos hospitalarios y mortalidad del MINSAL de los años 2001 al 2007 registrados con diagnóstico de enfermedad de Creutzfeldt Jakob, según el código CIE 10 A-810. Los resultados obtenidos correspondieron: en hospitalizaciones 230 egresos cuya edad promedio fue 57.8 años (SD ±12). La tasa promedio de hospitalizaciones para el país (2001-2007) por millón de habitantes con 95% IC fue; 2.00 (1.31-2.69). Las tasas en macro regiones con 95% IC fueron; Norte 0.67 (-0.49-1.82); Centro 2.03 (1.15-2.92) y Sur 2.61 (1.08-4.14). El ratio hombre-mujer fue 2:3. En mortalidad se registraron 339 fallecimientos cuya edad promedio fue 58.93 años (SD±10.2). La tasa promedio de mortalidad con 95 % IC para el país (2001-2007) fue; 2.96 (2.12 a 3.80). Las tasas en macro regiones con 95% IC fueron; Norte 1.34 (-0.30-2.97); Centro 2.86 (1.80-3.91) y Sur 4.11 (2.19-6.04). El ratio hombre-mujer fue 5:6. En conclusión las tasas de mortalidad son ligeramente mayores que las tasas de hospitalizaciones. La distribución de las tasas es mayor en la macro región sur, siendo significativo para las de mortalidad. La mayor cantidad de muertes y hospitalizaciones se presentan en el rango de 60 o más años, siendo significativo en el primero. / Creutzfeldt-Jakob disease (CJD) is the most common human spongiform encephalopathy, caused by an infectious protein called a prion, which is encoded in the PRNP gene on chromosome 20. This is a disease has a worldwide distribution, with mortality rates between 0.5 and 1 per million inhabitants, while in Chile it affects 2 or more persons per million inhabitants. Because of the latter, the aim of this study was to determine the regional distribution of the disease in the country, through a descriptive and retrospective study of hospitalization and mortality rates of CJD from 2001 to 2007, calculated from MINSAL hospital data’s discharge and mortality between the years 2001 to 2007 registered with a diagnosis of Creutzfeldt Jakob disease, according to the CIE10 A-810 code. The results corresponded to: 230 hospitalizations discharges whose average age was 57.8 years (SD ± 12). The average rate of hospitalizations for the country (2001-2007) per million inhabitants was 95% IC was; 2.00 (1.31-2.69). The rates on macro regions with a 95% IC were; North 0.67 (-0.49-1.82), Centre 2.03 (1.15-2.92) and South 2.61 (1.08-4.14). The male-female ratio was 2:3. On Mortality were registered 339 deaths whose average age was 58.93 years (SD ± 10.2). The average mortality rate with 95% IC for the country (2001-2007) was; 2.96 (2.12 to 3.80). The rates on macro regions with 95% IC were: North 1.34 (-0.30-2.97), Centre 2.86 (1.80-3.91) and South 4.11 (2.19-6.04). The male-female ratio was 5:6. In conclusion mortality rates are slightly higher than hospitalization rates. The distribution rate is higher in the southern macro region, being significant for mortality’s. Most deaths and hospitalizations occur in the range of 60 or more years, being significant in the first.

Reproduction de : Thèse d'exercice : Médecine : Nancy 1 : 2003. / Titre provenant de l'écran-titre.

Les Encéphalopathies Spongiformes transmissibles (EST) sont des maladies neurodégénératives fatales caractérisées par l’accumulation d’un conformère anormal (PrPSc) d’une protéine de l’hôte (PrP). Chez l’homme, plusieurs centaines de cas de transmissions iatrogènes de la maladie de Creutzfeldt Jakob (MCJ) ont été identifiées, notamment chez des patients ayant fait l’objetd’ une greffe de dure-mère, de cornée ou des injections d’hormones de croissance extractives. Plus récemment, plusieurs cas du variant de la maladie de Creutzfeldt Jakob (vMCJ) ont été observés chez des patients transfusés avec des produits sanguins issus de donneurs en incubation de la maladie. D’un point de vue sanitaire, l’évaluation du risque de contamination interindividuelle par des tissus ou des fluides biologiques issus de patients atteints représente un enjeu important en matière de santé publique. La première partie de notre travail a consisté à comparer la sensibilité relative de modèles de souris transgéniques sur-exprimant la PrP à celle de l’hôte conventionnel exprimant la même séquence. Les résultats obtenus ont validé le concept d’une absence d’impact du niveau d’expression de la PrP ou du fond génétique de l’hôte sur la sensibilité finale du modèle à l’infection. A l’aide de ces modèles de souris transgéniques, nous avons alors mesuré les niveaux d’infectiosité dans le sang de patients atteints de différentes formes d’’EST. Chez un patient atteint de vMCJ, nous avons mis en évidence de faibles niveaux d’infectiosité dans les concentrés de globules rouges, les leucocytes et le plasma. Nous avons également pu détecter de l’infectiosité dans le plasma issu de 2 patients atteints de sMCJ sur 4 testés. Parallèlement à ces expériences, nous avons démontré dans un modèle expérimental d’infection chez le mouton, que l’administration de 104 à 105 leucocytes suffisent à transmettre par voire transfusionnelle la maladie. Ces résultats soulignent l’intérêt et les limites de la leuco-déplétion appliquée de manière standard en médicine transfusionnelle, pour limiter les risques de transmission du vMCJ. Enfin, nous avons testé la capacité de différents outils in vitro à détecter la présence des Prions dans le sang. / Transmissible spongiform encephalopathies (TSE) are fatal neurodegenerative disorders occurring in a wide spectrum of animals. They are characterized by accumulation of abnormally folded conformers (PrPSc) derived from normal cellular PrP protein (PrP) of the host. In human, many iatrogenic transmissions of Creutzfeldt Jakob disease (CJD) have been reported after dura mater graft, corneal graft or extractive growth hormone injections, prepared from affected donors. More recently, several cases of vCJD transmissions were reported in individuals that were transfused with blood from asymptomatic donors that subsequently developed vCJD. Risk assessment of interindividual transmission with contaminated tissues or body fluids remains a major public health issue. In a first part, we validated the final pertinence of infectious titers as measured in mice overexpressing PrP to the risk of transmitting the disease in the natural host species. In a second time, we used this model to evaluate the presence of infectivity in blood from TSE affected patients. We were able to detect the presence of infectivity in erythrocytes, leukocytes, and plasma of 1 person with vCJD and in the plasma of 2 out of 4 persons whose tests were positive for sporadic CJD. We then demonstrated in a sheep TSE model, that intravenous administration of 104 to 105 leucocytes was sufficient to cause disease in recipient sheep, underlying the efficacy and potential limits of leuko-reduction processes that are currently applied in transfusion medicine to mitigate the TSE transmission risk. Finally, using the same model, we tested different in vitro methods to detect prions in blood.

Transmissible spongiform encephalopathies (TSEs) or prion diseases are a group of fatal neurodegenerative diseases affecting humans and animal species. Prion diseases are characterized by the conversion of the host encoded prion protein (PrPC) into a disease-associated isoform (PrPSc), which (according to the prion hypothesis) is thought to be the main component of the infectious agent. PrPSc has been traditionally distinguished from PrPC by its biochemical properties, such as partial resistance to proteolysis and detergent-insolubility. In the absence of a foreign nucleic acid genome associated with prion diseases, efforts to provide a molecular basis for the biological diversity of prions have focused on biochemical characterization of PrPSc. In Creutzfeldt-Jakob disease (CJD) and other forms of human prion disease, the biochemical characterization of PrPSc has been largely restricted to the analysis of PK-resistant fragments of PrPSc (PrPres) by Western blot. However, given recent findings on the complexity of PrPSc identified in laboratory prion strains, PrPres analysis alone may not provide a complete description of PrPSc present in CJD brains. For a more complete characterization of PrPSc in human prion diseases, this study investigated biochemical properties of PrPSc in different forms of CJD by employing approaches that differ in principle from conventional Western blot analysis of PrPres. The novel biochemical approaches used in this study have identified further complexity of PrPSc accumulated in CJD brains, not only between different forms of CJD but also within single cases of individual disease entities. In this study, the two biochemical criteria most frequently used to define PrPSc (3F4 epitope accessibility versus resistance to limited proteolysis) did not always correlate, indicating probable non-uniform distribution of PK-sensitive isoform of PrPSc within the same CJD brains. In variant CJD (vCJD) brains, the thalamic region, which is characterized by distinct neuropathological features, could also be distinguished from frontal cortex and cerebellum by the sedimentation profiles of PrPC and PrPSc on sucrose step gradients. Moreover, the conformational stability of PrPSc was found not to be uniform among human prion diseases and did not correlate with PrPres type or prion protein genotype. Taken together, the results from this study provide a more complete description of PrPSc species occurring in CJD brains and contribute to a fuller understanding of the agents and the disease processes involved in humans.

Thèse d'exercice : Pharmacie : Université de Nantes : 2004. / Bibliogr. f. 110-117 [163 réf.].

Thèse d'exercice : Pharmacie : Université de Nantes : 2004. / Bibliogr. f. 84-88 [39 réf.].