RESUMEN
The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has triggered a serious global health crisis, resulting in millions of reported deaths since its initial identification in China in November 2019. The global disparities in immunization access emphasize the urgent need for ongoing research into therapeutic interventions. This study focuses on the potential use of molecular dihydrogen (H2) inhalation as an adjunctive treatment for COVID-19. H2 therapy shows promise in inhibiting intracellular signaling pathways associated with inflammation, particularly when administered early in conjunction with nasal oxygen therapy. This phase I study, characterized by an open-label, prospective, monocentric, and single ascending-dose design, seeks to assess the safety and tolerability of the procedure in individuals with confirmed SARS-CoV-2 infection. Employing a 3 + 3 design, the study includes three exposure durations (target durations): 1 day (D1), 3 days (D2), and 6 days (D3). We concluded that the maximum tolerated duration is at least 3 days. Every patient showed clinical improvement and excellent tolerance to H2 therapy. To the best of our knowledge, this phase I clinical trial is the first to establish the safety of inhaling a mixture of H2 (3.6%) and N2 (96.4%) in hospitalized COVID-19 patients. The original device and method employed ensure the absence of explosion risk. The encouraging outcomes observed in the 12 patients included in the study justify further exploration through larger, controlled clinical trials. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT04633980.
Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/terapia , Masculino , Persona de Mediana Edad , Administración por Inhalación , Estudios Prospectivos , Femenino , Adulto , Pandemias , Anciano , Tratamiento Farmacológico de COVID-19 , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/virología , BetacoronavirusRESUMEN
Neurofibrillary tangles (NFT), a neuronal lesion found in Alzheimer's disease (AD), are composed of fibrillary aggregates of modified forms of tau proteins. The propagation of NFT follows neuroanatomical pathways suggesting that synaptically connected neurons could transmit tau pathology by the recruitment of normal tau in a prion-like manner. Moreover, the intracerebral injection of pathological tau from AD brains induces the seeding of normal tau in mouse brain. Creutzfeldt-Jacob disease has been transmitted after ocular transplants of cornea or sclera and the scrapie agent can spread across the retino-tectal pathway after intraocular injection of scrapie mouse brain homogenates. In AD, a tau pathology has been detected in the retina. To investigate the potential risk of tau pathology transmission during eye surgery using AD tissue material, we have analysed the development of tau pathology in the visual pathway of mice models expressing murine tau, wild-type or mutant human tau after intraocular injection of pathological tau proteins from AD brains. Although these pathological tau proteins were internalized in retinal ganglion cells, they did not induce aggregation of endogenous tau nor propagation of a tau pathology in the retino-tectal pathway after a 6-month incubation period. These results suggest that retinal ganglion cells exhibit a resistance to develop a tau pathology, and that eye surgery is not a major iatrogenic risk of transmission of tau pathology, contrary to what has been observed for transmission of infectious prions in prion diseases.
Asunto(s)
Enfermedad de Alzheimer , Priones , Animales , Masculino , Ratones , Humanos , Proteínas tau/metabolismo , Enfermedad de Alzheimer/metabolismo , Ovillos Neurofibrilares/metabolismo , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Priones/metabolismo , Células Ganglionares de la Retina/metabolismo , Inyecciones Intraoculares , Ratones TransgénicosRESUMEN
Chronic granulomatous disease (CGD) is a rare inherited disorder in which phagocytes lack nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. The most common form is the X-linked CGD (X91-CGD), caused by mutations in the CYBB gene. Clinical, functional and genetic characterizations of 16 CGD cases of male patients and their relatives were performed. We classified them as suffering from different variants of CGD (X910 , X91- or X91+ ), according to NADPH oxidase 2 (NOX2) expression and NADPH oxidase activity in neutrophils. Eleven mutations were novel (nine X910 -CGD and two X91- -CGD). One X910 -CGD was due to a new and extremely rare double missense mutation Thr208Arg-Thr503Ile. We investigated the pathological impact of each single mutation using stable transfection of each mutated cDNA in the NOX2 knock-out PLB-985 cell line. Both mutations leading to X91- -CGD were also novel; one deletion, c.-67delT, was localized in the promoter region of CYBB; the second c.253-1879A>G mutation activates a splicing donor site, which unveils a cryptic acceptor site leading to the inclusion of a 124-nucleotide pseudo-exon between exons 3 and 4 and responsible for the partial loss of NOX2 expression. Both X91- -CGD mutations were characterized by a low cytochrome b558 expression and a faint NADPH oxidase activity. The functional impact of new missense mutations is discussed in the context of a new three-dimensional model of the dehydrogenase domain of NOX2. Our study demonstrates that low NADPH oxidase activity found in both X91- -CGD patients correlates with mild clinical forms of CGD, whereas X910 -CGD and X91+ -CGD cases remain the most clinically severe forms.
Asunto(s)
Enfermedad Granulomatosa Crónica/genética , Mutación Missense/genética , NADPH Oxidasa 2/genética , Adulto , Línea Celular , Exones/genética , Femenino , Enfermedad Granulomatosa Crónica/metabolismo , Humanos , Masculino , Glicoproteínas de Membrana/genética , Neutrófilos/metabolismo , Adulto JovenAsunto(s)
Dolor en el Pecho/parasitología , Enfermedades Pulmonares Parasitarias/diagnóstico , Paragonimiasis/diagnóstico , Adulto , Dolor en el Pecho/diagnóstico por imagen , Diagnóstico Diferencial , Humanos , Síndrome Hipereosinofílico/parasitología , Pulmón/diagnóstico por imagen , Pulmón/parasitología , Enfermedades Pulmonares Parasitarias/diagnóstico por imagen , Enfermedades Pulmonares Parasitarias/parasitología , Masculino , Paragonimiasis/diagnóstico por imagen , Pleuresia/diagnóstico por imagen , Trombosis de la Vena/diagnóstico por imagenRESUMEN
OBJECTIVES: To demonstrate the bioequivalence between 2 intravenous immunoglobulin (IVIG) preparations, TEGELINE® and ClairYg®, a ready-to-use 5% IVIG, in primary immunodeficiency (PID). Secondary objectives were to assess the efficacy, safety and pharmacokinetics of ClairYg®. METHODS: Twenty-two adult PID patients receiving stable doses of TEGELINE® (5% lyophilized IVIG) were switched to ClairYg® for 6 months. ClairYg® was administered under the same conditions as TEGELINE®, either every 3 or 4 weeks. The primary endpoint was mean average total IgG trough level at steady state with ClairYg® versus TEGELINE®. Clinical efficacy was also assessed in terms of infections and associated events. RESULTS: Bioequivalence was established with a mean average total IgG trough level at steady state being 8.05g/L with TEGELINE® and 9.17g/L with ClairYg® (i.e. geometric mean for the difference between ClairYg® and TEGELINE® was 1.136; [90% CI: 1.092-1.181] P<0.001), within the pre-specified margin to establish bioequivalence (0.80-1.25). Total IgG trough levels remained clinically adequate (>4-6g/L) throughout the study. No patient was hospitalized for infection or had serious bacterial infections while receiving ClairYg®. The median annualized infections rate per patient was similar for both products: 4.35 [0; 21.8] for TEGELINE® and 4.30 [0; 15.1] for ClairYg®. Infections were less common with higher IgG trough levels (>8.16g/L). ClairYg® showed good safety, in particular good hepatic and renal tolerance, and did not induce hemolysis. ClairYg® pharmacokinetics profile was comparable to that of TEGELINE®. CONCLUSION: ClairYg® is safe and effective in the treatment of adult PID.
Asunto(s)
Inmunoglobulinas Intravenosas/farmacocinética , Inmunoglobulinas Intravenosas/uso terapéutico , Síndromes de Inmunodeficiencia/terapia , Adulto , Femenino , Francia/epidemiología , Humanos , Inmunoglobulina G/metabolismo , Inmunoglobulina G/uso terapéutico , Síndromes de Inmunodeficiencia/epidemiología , Síndromes de Inmunodeficiencia/metabolismo , Inmunoterapia/métodos , Masculino , Persona de Mediana Edad , Equivalencia Terapéutica , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Lactobacillus bacteremia is a rare event and its epidemiology is poorly known. Whether Lactobacillus bacteremia is a contaminant, a risk factor, or a risk marker of death remains an open question. PATIENTS AND METHODS: We conducted a retrospective study of patients presenting with Lactobacillus bacteremia (LB), between January 2005 and December 2014, at the Grenoble University Hospital. RESULTS: LB was observed in 38 patients (0.34% of all positive blood cultures). Cancer (40%), immunosuppression (37%), and use of central venous devices (29%) were frequently associated with LB. We observed a significant increase with time in the number of Lactobacillus positive blood cultures among all blood cultures performed (P=0.04). LBs were divided into two clinical-biological presentations: secondary bacteremia with a known portal of entry (n=30) and isolated bacteremia (n=8). Case fatality was 31% at D28, 55.2% at 1 year in the secondary bacteremia group, and 12.5% (both at D28 and 1 year) in the isolated bacteremia group. Secondary bacteremia with a known portal of entry was significantly associated with case fatality after adjustment for age, co-infection, cancer, immunosuppression, diabetes, and sex (OR 14.9 [1.04-216] P=0.047) for fatality at one year, but not for D28 fatality (P=0.14). CONCLUSION: Lactobacillus bacteremia may be an important marker of disease severity rather than a pathogen, suggesting comorbidities. It should not be considered a contaminant, but should lead physicians to screen for associated infections and underlying diseases.
Asunto(s)
Bacteriemia/epidemiología , Bacteriemia/microbiología , Infecciones por Bacterias Grampositivas/epidemiología , Infecciones por Bacterias Grampositivas/microbiología , Anciano , Femenino , Humanos , Lactobacillus , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
Hepatitis E (HEV) is an emerging disease in our developed countries, but is not routinely tested for in case of liver cytolysis. However, a growing number of extra-hepatic manifestations of HEV infection associated with acute hepatitis are reported. In this article, we discuss two cases of HEV with neurological symptoms, one with encephalitis, and the other with Parsonage Turner syndrome. All these disorders appeared concomitantly with liver cytolysis and disappeared quickly, following the viral kinetics. Only twenty cases of neurological manifestation of HEV have been described before. The use of HEV serology in patients with concurrent liver cytolysis and neurological symptoms has to be improved.
Asunto(s)
Neuritis del Plexo Braquial/diagnóstico , Neuritis del Plexo Braquial/etiología , Encefalitis Viral/diagnóstico , Encefalitis Viral/etiología , Hepatitis E/complicaciones , Hepatitis E/diagnóstico , Adulto , Neuritis del Plexo Braquial/patología , Encefalitis Viral/patología , Hepatitis E/patología , Virus de la Hepatitis E/aislamiento & purificación , Humanos , Masculino , ViremiaRESUMEN
Although the mechanism of Aß action in the pathogenesis of Alzheimer's disease (AD) has remained elusive, it is known to increase the expression of the antagonist of canonical wnt signalling, Dickkopf-1 (Dkk1), whereas the silencing of Dkk1 blocks Aß neurotoxicity. We asked if clusterin, known to be regulated by wnt, is part of an Aß/Dkk1 neurotoxic pathway. Knockdown of clusterin in primary neurons reduced Aß toxicity and DKK1 upregulation and, conversely, Aß increased intracellular clusterin and decreased clusterin protein secretion, resulting in the p53-dependent induction of DKK1. To further elucidate how the clusterin-dependent induction of Dkk1 by Aß mediates neurotoxicity, we measured the effects of Aß and Dkk1 protein on whole-genome expression in primary neurons, finding a common pathway suggestive of activation of wnt-planar cell polarity (PCP)-c-Jun N-terminal kinase (JNK) signalling leading to the induction of genes including EGR1 (early growth response-1), NAB2 (Ngfi-A-binding protein-2) and KLF10 (Krüppel-like factor-10) that, when individually silenced, protected against Aß neurotoxicity and/or tau phosphorylation. Neuronal overexpression of Dkk1 in transgenic mice mimicked this Aß-induced pathway and resulted in age-dependent increases in tau phosphorylation in hippocampus and cognitive impairment. Furthermore, we show that this Dkk1/wnt-PCP-JNK pathway is active in an Aß-based mouse model of AD and in AD brain, but not in a tau-based mouse model or in frontotemporal dementia brain. Thus, we have identified a pathway whereby Aß induces a clusterin/p53/Dkk1/wnt-PCP-JNK pathway, which drives the upregulation of several genes that mediate the development of AD-like neuropathologies, thereby providing new mechanistic insights into the action of Aß in neurodegenerative diseases.
Asunto(s)
Péptidos beta-Amiloides/toxicidad , Clusterina/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Neuronas/efectos de los fármacos , Proteínas Wnt/metabolismo , Anciano , Enfermedad de Alzheimer/patología , Animales , Células Cultivadas , Clusterina/genética , Embrión de Mamíferos , Inhibidores Enzimáticos/farmacología , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Sistema de Señalización de MAP Quinasas/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratas , Ratas Sprague-DawleyRESUMEN
Conventional polymerase chain reaction (PCR) in respiratory samples does not differentiate between Pneumocystis pneumonia (PCP) and Pneumocystis jirovecii (Pj) colonization. We used Pj real-time quantitative PCR (qPCR) with the objective to discriminate PCP from Pj colonization in immunocompromised patients. All positive Pj qPCR [targeting the major surface glycoprotein (MSG) gene] obtained in respiratory samples from immunocompromised patients presenting pneumonia at the Grenoble University Hospital, France, were collected between August 2009 and April 2011. Diagnoses were retrospectively determined by a multidisciplinary group of experts blinded to the Pj qPCR results. Thirty-one bronchoalveolar lavages and four broncho aspirations positive for the Pj qPCR were obtained from 35 immunocompromised patients. Diagnoses of definite, probable, and possible PCP, and pneumonia from another etiology were retrospectively made for 7, 4, 5, and 19 patients, respectively. Copy numbers were significantly higher in the "definite group" (median 465,000 copies/ml) than in the "probable group" (median 38,600 copies/ml), the "possible group" (median 1,032 copies/ml), and the "other diagnosis group" (median 390 copies/ml). With the value of 3,160 copies/ml, the sensitivity and specificity of qPCR for the diagnosis of PCP were 100 % and 70 %, respectively. With the value of 31,600 copies/ml, the sensitivity and specificity were 80 % and 100 %, respectively. The positive predictive value was 100 % for results with more than 31,600 copies/ml and the negative predictive value was 100 % for results with fewer than 3,160 copies/ml. qPCR targeting the MSG gene can be helpful to discriminate PCP from Pj colonization in immunocompromised patients, using two cut-off values, with a gray zone between them.
Asunto(s)
Portador Sano/microbiología , Pneumocystis carinii/aislamiento & purificación , Neumonía por Pneumocystis/microbiología , Adulto , Anciano , Líquido del Lavado Bronquioalveolar/microbiología , Portador Sano/diagnóstico , Portador Sano/epidemiología , Femenino , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Pneumocystis carinii/genética , Neumonía por Pneumocystis/diagnóstico , Neumonía por Pneumocystis/inmunología , Curva ROC , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios RetrospectivosRESUMEN
Cytomegalovirus (CMV) strains resistant to ganciclovir, cidofovir and/or foscarnet were genotypically and phenotypically characterised in two haematopoietic stem cell transplant recipients and three solid-organ transplant recipients with CMV disease. The anti-malaria drug artesunate led to a favourable virological and clinical response in three cases with mild CMV diseases (fever and neutropaenia) but was ineffective in two fatal CMV diseases with lung involvement in spite of a decrease in the CMV DNA load in blood and bronchoalveolar fluid.
Asunto(s)
Antivirales/uso terapéutico , Artemisininas/uso terapéutico , Infecciones por Citomegalovirus/tratamiento farmacológico , Citomegalovirus/efectos de los fármacos , Farmacorresistencia Viral , Artesunato , Citomegalovirus/genética , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/virología , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Trasplante de Órganos/efectos adversos , Trasplante , Resultado del Tratamiento , Carga ViralAsunto(s)
Colonoscopía/efectos adversos , Endocarditis Bacteriana/etiología , Infecciones por Bacterias Grampositivas/etiología , Lactobacillus/aislamiento & purificación , Probióticos/efectos adversos , Anciano , Amoxicilina/administración & dosificación , Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Antimaníacos/efectos adversos , Antimaníacos/sangre , Antimaníacos/uso terapéutico , Artroplastia de Reemplazo de Cadera/efectos adversos , Bacteriemia/tratamiento farmacológico , Bacteriemia/etiología , Bacteriemia/microbiología , Traslocación Bacteriana , Trastorno Bipolar/complicaciones , Trastorno Bipolar/tratamiento farmacológico , Escalofríos/inducido químicamente , Escalofríos/etiología , Diagnóstico Tardío , Susceptibilidad a Enfermedades , Quimioterapia Combinada , Endocarditis Bacteriana/diagnóstico por imagen , Endocarditis Bacteriana/tratamiento farmacológico , Endocarditis Bacteriana/microbiología , Gentamicinas/administración & dosificación , Gentamicinas/uso terapéutico , Infecciones por Bacterias Grampositivas/diagnóstico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Lactobacillus/efectos de los fármacos , Lactobacillus/patogenicidad , Carbonato de Litio/efectos adversos , Carbonato de Litio/sangre , Carbonato de Litio/uso terapéutico , Masculino , Insuficiencia de la Válvula Mitral/complicaciones , Neoplasias de la Próstata/complicaciones , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/microbiología , Factores de Tiempo , Ultrasonografía , Yogur/microbiologíaRESUMEN
AIM: To describe the main characteristics and the treatment of cryptococcosis in patients with sarcoidosis. DESIGN: Multicenter study including all patients notified at the French National Reference Center for Invasive Mycoses and Antifungals. METHODS: Retrospective chart review. Each case was compared with two controls without opportunistic infections. RESULTS: Eighteen cases of cryptococcosis complicating sarcoidosis were analyzed (13 men and 5 women). With 2749 cases of cryptococcosis registered in France during the inclusion period of this study, sarcoidosis accounted for 0.6% of all the cryptococcosis patients and for 2.9% of the cryptococcosis HIV-seronegative patients. Cryptococcosis and sarcoidosis were diagnosed concomitantly in four cases; while sarcoidosis was previously known in 14/18 patients, including 12 patients (67%) treated with steroids. The median rate of CD4 T cells was 145 per mm(3) (range: 55-1300) and not related to steroid treatment. Thirteen patients had cryptococcal meningitis (72%), three osteoarticular (17%) and four disseminated infections (22%). Sixteen patients (89%) presented a complete response to antifungal therapy. After a mean follow-up of 6 years, no death was attributable to cryptococcosis. Extra-thoracic sarcoidosis and steroids were independent risk factors of cryptococcosis in a logistic regression model adjusted with the sex of the patients. CONCLUSIONS: Cryptococcosis is a significant opportunistic infection during extra-thoracic sarcoidosis, which occurs in one-third of the cases in patients without any treatment; it is not associated to severe CD4 lymphocytopenia and has a good prognosis.
Asunto(s)
Criptococosis/complicaciones , Infecciones Oportunistas/complicaciones , Sarcoidosis/complicaciones , Adolescente , Adulto , Antifúngicos/uso terapéutico , Recuento de Linfocito CD4 , Criptococosis/diagnóstico , Criptococosis/tratamiento farmacológico , Criptococosis/inmunología , Femenino , Glucocorticoides/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/tratamiento farmacológico , Infecciones Oportunistas/inmunología , Pronóstico , Estudios Retrospectivos , Sarcoidosis/tratamiento farmacológico , Sarcoidosis/inmunología , Adulto JovenRESUMEN
BACKGROUND: Infection is a major complication associated with the use of central venous catheters. Guidelines for medical management of catheter-related bacteraemia have been published, but no study has assessed the appropriateness of physician practices. AIM: To assess medical practices in cases of central venous catheter-related bacteraemia (CRB) in a university hospital. METHODS: Cases were recorded over a period of 12 months and their management was evaluated. All cases of positive blood cultures based on central venous catheter sampling were analysed, and episodes of CRB were determined in this group of patients. Medical management and patient outcome were analysed independently by two physicians. FINDINGS: In all, 187 cases of positive blood culture were recorded and 91 cases of CRB were analysed. Systemic antimicrobial therapy was optimal in 56% of the episodes. In 51 episodes, catheter salvage was attempted, for 29 with an indication in agreement with the guidelines but without antibiotic-lock therapy in 20 episodes. The overall medical management was appropriate in 41.8% of the episodes. The overall cure rate was 72.5%. CRB-related death occurred in 5.5% of the episodes. Cure was associated with guideline compliance (P = 0.03) and with adaptation of systemic antimicrobial therapy (P < 0.01). Conservative treatment success was associated with compliance with the guidelines for the indication (P = 0.01). CONCLUSION: Medical management of CRB did not closely adhere to international guidelines. CRB outcome was associated with the appropriateness of this management, particularly when conservative treatment was attempted.
Asunto(s)
Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Cateterismo Venoso Central/efectos adversos , Adhesión a Directriz , Guías de Práctica Clínica como Asunto , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Bacteriemia/diagnóstico , Bacteriemia/etiología , Bacteriemia/mortalidad , Niño , Preescolar , Femenino , Francia/epidemiología , Hospitales Universitarios , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
AIMS: The aim of our case study is to illustrate diagnostic and therapeutic difficulties as well as gravity related to tuberculous otitis media with intracranial complications. CASE PRESENTATION: A diabetic male patient of 65 years old was treated for subacute otitis media with mixed hearing loss. Early bacteriologic samples from ear exudates revealed opportunistic pathogens. Clinical evolution after four months was marked by the appearance of mastoiditis with facial paralysis. The patient presented petrositis and bilateral laryngeal paralysis with lymphocytic meningitis after six and eight months respectively. Tuberculosis was suspected after a positive ELlspot tests with appearance of biologic markers of hepatic dysfunction like cholestasis and hepatic cytolysis. Although antituberculous treatment was instaured even without isolation of acid fast bacilli, the patient died after ten months. CONCLUSION: Subacute otitis media complicated by labyrinthitis, early onset of facial paralysis or any other oranial nerve palsy should raise suspicion of tuberculosis. The prognosis depends on early diagnosis which remains difficult despite morphological and metabolic imaging. The diagnostic workup should include histological and bacteriologic samples, liver markers of intacellular damage as well as ELlspot test. The prognosis remains poor especially in immunocompromised patients despite appropriate treatment.
Asunto(s)
Meningitis Bacterianas/microbiología , Otitis Media/microbiología , Petrositis/microbiología , Tuberculosis/diagnóstico , Anciano , Antituberculosos/uso terapéutico , Diabetes Mellitus Tipo 1/complicaciones , Humanos , Masculino , Meningitis Bacterianas/tratamiento farmacológico , Otitis Media/diagnóstico , Otitis Media/tratamiento farmacológico , Petrositis/tratamiento farmacológico , Tuberculosis/tratamiento farmacológicoRESUMEN
The daily number of outdoor spores was counted and the cases of community-acquired invasive aspergillosis (IA) were observed over a period of 31 months. The outdoor fungal load preceding IA occurrences was significantly higher than that measured during IA-free periods, underlining the importance of preventive measures to protect high-risk patients, even at home.
Asunto(s)
Microbiología del Aire , Aspergilosis/microbiología , Infecciones Comunitarias Adquiridas/microbiología , Infección Hospitalaria/microbiología , Aspergilosis/transmisión , Recuento de Colonia Microbiana , Infecciones Comunitarias Adquiridas/transmisión , Infección Hospitalaria/transmisión , Humanos , Incidencia , Estudios Prospectivos , Esporas FúngicasRESUMEN
The complex bi-directional axoplasmic transport of mitochondria is essential for proper metabolic functioning of neurons and is controlled by phosphorylation. We have investigated by time-lapse imaging the effects of increased expression of glycogen synthase kinase-3beta (GSK-3beta) and of the p25 activator of cyclin dependent kinase 5 on mitochondria movements in mammalian cortical neurons and in PC12 cells. Both GSK-3beta and p25 increased the stationary behaviour of mitochondria in PC12 and in neurons, decreased their anterograde transport but did not affect the intrinsic velocities of mitochondria. The microtubule-associated tau proteins were more phosphorylated in GSK-3beta and p25 transfected neurons, but ultrastructural observation showed that these cells still contained microtubules and nocodazole treatment further reduced residual mitochondria movements in GSK-3beta or p25 transfected neurons, indicating that microtubule disruption was not the primary cause of increased mitochondrial stationary behaviour in GSK-3beta or p25 transfected neurons. Our results suggest that increased expression of GSK-3beta and p25 acted rather by decreasing the frequency of mitochondrial movements driven by molecular motors and that GSK-3beta and p25 might regulate these transports by controlling the time that mitochondria spend pausing, rather than their velocities.
Asunto(s)
Quinasa 5 Dependiente de la Ciclina/metabolismo , Glucógeno Sintasa Quinasa 3/fisiología , Mitocondrias/fisiología , Proteínas del Tejido Nervioso/fisiología , Neuronas/fisiología , Animales , Supervivencia Celular , Células Cultivadas , Corteza Cerebral/citología , Corteza Cerebral/metabolismo , Glucógeno Sintasa Quinasa 3/biosíntesis , Glucógeno Sintasa Quinasa 3/genética , Glucógeno Sintasa Quinasa 3 beta , Proteínas Fluorescentes Verdes/genética , Cinética , Ratones , Microtúbulos/ultraestructura , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/genética , Neuronas/ultraestructura , Células PC12 , Fosforilación , Ratas , Transfección , Proteínas tau/metabolismoRESUMEN
The usefulness of two quantitative real-time PCR assays (qrt-PCRmip targeting Legionella pneumophila, and qrt-PCR16S targeting all Legionella species) performed on lower respiratory tract (LRT) samples for diagnostic and prognostic purposes in 311 patients hospitalized for community-acquired pneumonia (CAP) in Rhône-Alpes (France) was evaluated. The Now Legionella urinary antigen test (UAT) from Binax (Portland, ME, USA) was used as a reference test. Samples were divided into two groups. Group A included 255 CAP patients admitted to Chambery hospital in 2005 and 2006. The Now Legionella UAT was positive in 14 patients. Sensitivities, specificities, positive predictive and negative predictive values for both qrt-PCR tests were 63.6, 98.7, 77.7 and 97.4%, respectively. Group B included 56 consecutive legionellosis patients diagnosed during a 4-year period (2003-2006) at the Grenoble University Hospital. The qrt-PCR16S and qrt-PCRmip displayed a sensitivity of 82.14 and 80.4%, respectively. Among the 70 legionellosis cases, L. pneumophila serogroup 1 was isolated in 15; qrt-PCRmip was positive in another 36, suggesting L. pneumophila infection, whereas the Legionella species involved could not be determined in the remaining 19 cases. The Legionella burden in LRT samples at the time of admission was determined in 46 patients using qrt-PCR16S tests, 44 for qrt-PCR mip groups A and B patients. It varied from 1.9 to 8.35 log(10) DNA copies/mL of LRT sample for qrt-PCR16S and from 1.9 to 8.11 log(10) DNA copies/mL of sample for qrt-PCRmip. High bacterial loads in LRT samples at hospital admission were significantly associated with higher Fine classes, the need for hospitalization in an intensive care unit and for prolonged hospitalization.
Asunto(s)
Legionelosis/diagnóstico , Reacción en Cadena de la Polimerasa/métodos , Adolescente , Adulto , Anciano , Infecciones Comunitarias Adquiridas/microbiología , ADN Bacteriano/análisis , Humanos , Legionella/genética , Persona de Mediana Edad , Neumonía/microbiología , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Diagnostic or interventional femoral artery catheterizations are more and more commonly practiced, so are haemostatic puncture closure devices, used to prevent bleeding complications and decrease hospital length of stay. Complications, such as infections, have been reported after using haemostatic puncture closure devices. We report the case of a female patient presenting with severe infection after Angio-Seal use: femoral artery infection with sepsis and multiple organ failure, septic embolism with embolic skin abscesses, bacterial arthritis and inferior limb necrosis. Studies comparing the infectious risk of manual compression versus haemostatic puncture closure devices are contradictory. Nevertheless, aseptic rules must be strictly observed. Indications for these devices concern only patients with high risk of hemorrhage and should be discussed for immunodepressed, diabetic, or obese patients.
Asunto(s)
Puente de Arteria Coronaria , Complicaciones Posoperatorias/etiología , Infecciones Estafilocócicas/etiología , Puente de Arteria Coronaria/instrumentación , Femenino , Humanos , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Tuberculosis prevention has been based on generalized BCG vaccination in France since 1949. The aim of this cross-sectional survey was to assess the impact of the change in BCG administration (in January 2006) and the end of compulsory vaccination (in July 2007). METHOD: A self-administered postal questionnaire was sent to a random sample of 2248 physicians practicing in 6 departments in the Rhône-Alpes region in 2008. RESULTS: Overall, 923 questionnaires were analyzed. The median age of the respondents was 52 years, 67 % were male, 93 % were general practitioners, and 91 % practiced in private practice offices. The median number of BCG vaccines administered on a quarterly basis was 5 (interquartile range [IQR], 3-10) before January 2006, one (IQR, 0-3) between January 2006 and July 2007, and zero (IQR, 0-1) after July 2007 (P<0.001). The rate of BCG vaccination was significantly lower for male physicians, physicians older than 50 years, general practitioners, practitioners working in private offices, and for some departments. Thirty-nine percent of the physicians were informed of the national program against tuberculosis 2007-2009, and 41 % wished to be trained in the practice of intradermal vaccination. CONCLUSION: This survey suggests that the withdrawal of Monovax and the lifting of generalized vaccination requirements were followed by a substantial decrease in the number of BCG vaccinations. The intradermal route constitutes an obstacle for BCG vaccination that might be overcome by specific training.