RESUMEN
OBJECTIVE: The aetiology of OA is not fully understood although several adipokines such as leptin are known mediators of disease progression. Since leptin levels were increased in synovial fluid compared to serum in OA patients, it was suggested that joint cells themselves could produce leptin. However, exact mechanisms underlying leptin production by chondrocytes are poorly understood. Nevertheless, prednisolone, although displaying powerful anti-inflammatory properties has been recently reported to be potent stimulator of leptin and its receptor in OA synovial fibroblasts. Therefore, we investigated, in vitro, spontaneous and prednisolone-induced leptin production in OA chondrocytes, focusing on transforming growth factor-ß (TGFß) and Wnt/ß-catenin pathways. DESIGN: We used an in vitro dedifferentiation model, comparing human freshly isolated hip OA chondrocytes cultivated in monolayer during 1 day (type II, COL2A1 +; type X, COL10A1 + and type I collagen, COL1A1 -) or 14 days (COL2A1 -; COL10A1 - and COL1A1+). RESULTS: Leptin expression was not detected in day1 OA chondrocytes whereas day14 OA chondrocytes produced leptin, significantly increased with prednisolone. Activin receptor-like kinase 1 (ALK1)/ALK5 ratio was shifted during dedifferentiation, from high ALK5 and phospho (p)-Smad2 expression at day1 to high ALK1, endoglin and p-Smad1/5 expression at day14. Moreover, inactive glycogen synthase kinase 3 (GSK3) and active ß-catenin were only found in dedifferentiated OA chondrocytes. Smad1 and ß-catenin but not endoglin stable lentiviral silencing led to a significant decrease in leptin production by dedifferentiated OA chondrocytes. CONCLUSIONS: Only dedifferentiated OA chondrocytes produced leptin. Prednisolone markedly enhanced leptin production, which involved Smad1 and ß-catenin activation.
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Condrocitos/metabolismo , Leptina/metabolismo , Osteoartritis de la Cadera/metabolismo , ARN Mensajero/metabolismo , Receptores de Activinas Tipo II/efectos de los fármacos , Receptores de Activinas Tipo II/genética , Receptores de Activinas Tipo II/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Cartílago Articular/citología , Cartílago Articular/efectos de los fármacos , Cartílago Articular/metabolismo , Desdiferenciación Celular/efectos de los fármacos , Desdiferenciación Celular/genética , Condrocitos/efectos de los fármacos , Colágeno Tipo X/efectos de los fármacos , Colágeno Tipo X/genética , Colágeno Tipo X/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/efectos de los fármacos , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Femenino , Glucocorticoides/farmacología , Glucógeno Sintasa Quinasa 3/efectos de los fármacos , Glucógeno Sintasa Quinasa 3/genética , Glucógeno Sintasa Quinasa 3/metabolismo , Humanos , Técnicas In Vitro , Linfotoxina-alfa/efectos de los fármacos , Linfotoxina-alfa/genética , Linfotoxina-alfa/metabolismo , Masculino , Metaloproteinasa 13 de la Matriz/efectos de los fármacos , Metaloproteinasa 13 de la Matriz/genética , Metaloproteinasa 13 de la Matriz/metabolismo , Persona de Mediana Edad , Osteoartritis de la Cadera/genética , Prednisolona/farmacología , Proteínas Serina-Treonina Quinasas/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , ARN Mensajero/efectos de los fármacos , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/efectos de los fármacos , Receptores de Factores de Crecimiento Transformadores beta/genética , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Factor de Transcripción SOX9/efectos de los fármacos , Factor de Transcripción SOX9/metabolismo , Proteína Smad1/efectos de los fármacos , Proteína Smad1/genética , Proteína Smad1/metabolismo , Proteína Smad2/efectos de los fármacos , Proteína Smad2/genéticaRESUMEN
We report the successful control of an outbreak caused by imipenem-resistant VIM-1-producing Klebsiella pneumoniae (IR-Kp) in France. This outbreak occurred in a care centre for abdominal surgery that includes a 15-bed liver intensive care unit and performs more than 130 liver transplantations per year. The index case was a patient with acute liver failure transferred from a hospital in Greece for urgent liver transplantation who was carrying IR-Kp at admission as revealed by routine culture of a rectal swab. Infection control measures were undertaken and included contact isolation and promotion of hand hygiene with alcohol-based hand rub solution. Nevertheless, secondary IR-Kp cases were identified during the six following months from 3 December 2003 to 2 June 2004. From 2 June to 21 October, extended infection control measures were set up, such as cohorting IR-Kp carriers, contact patients and new patients in distinct sections with dedicated staff, limiting ward admission, and strict control of patient transfer. They led to a rapid control of the outbreak. The global attack rate of the IR-Kp outbreak was 2.5%, 13% in liver transplant patients and 0.4% in the other patients in the care centre (p<0.005). Systematic screening for IR-Kp of all patients admitted to the care centre is still maintained to date and no secondary IR-Kp case has been detected since 2 June 2004.
Asunto(s)
Infección Hospitalaria/prevención & control , Brotes de Enfermedades/prevención & control , Control de Infecciones/métodos , Infecciones por Klebsiella/epidemiología , Klebsiella pneumoniae/aislamiento & purificación , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Farmacorresistencia Bacteriana , Femenino , Francia/epidemiología , Hospitales con más de 500 Camas , Humanos , Imipenem/farmacología , Imipenem/uso terapéutico , Unidades de Cuidados Intensivos , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/prevención & control , Klebsiella pneumoniae/clasificación , Klebsiella pneumoniae/enzimología , Trasplante de Hígado , Masculino , Pruebas de Sensibilidad Microbiana , beta-Lactamasas/metabolismoRESUMEN
BACKGROUND: Erythema marginatum is one of the main Jones diagnostic criteria for rheumatic fever. However, since it rarely occurs in industrialized countries, this diagnosis is seldom suspected, especially in adult patients. CASE REPORT: We report a case of an annular facial eruption associated with fever and polyarthralgia seen twice in a 30-year-old woman following episodes of streptococcal throat infection. DISCUSSION: This case report underlines the fact that the rheumatic fever has not completely disappeared in the highly developed countries. Dermatologists should be careful not to overlook its clinical manifestations and should be vigilant about potential cardiac complications.
Asunto(s)
Eritema/etiología , Dermatosis Facial/etiología , Faringitis/microbiología , Fiebre Reumática/diagnóstico , Infecciones Estreptocócicas , Streptococcus pyogenes , Amoxicilina/administración & dosificación , Amoxicilina/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Femenino , Humanos , Faringitis/complicaciones , Recurrencia , Fiebre Reumática/etiología , Infecciones Estreptocócicas/tratamiento farmacológico , Factores de Tiempo , Resultado del TratamientoRESUMEN
UNLABELLED: Gastrostomy is frequently used in clinical practice for drug administration. However modalities of drug administration via a gastrostomy device have been poorly studied and remain uncodified. AIM: To assess the mode of administration of drugs as well as errors associated with the use of a gastrostomy devices for drug delivery in children. PATIENTS AND METHODS: Mode of administration of drugs was studied in 109 children (mean age 8.4+/-5.5 years, 72% neurologically impaired, 41% institutionalized children). A questionnaire was filled in by parents and/or caregivers. Errors of administration were classified as follows: galenic, due to preparation, physico-chemical interaction, lack of flushing the tube. Factors influencing the occurrence of errors were studied: living at home or in an institution, underlying disease, number of drugs administered via gastrostomy device. RESULTS: Errors were frequently observed: galenic (47%), due to preparation (42%), physico-chemical interaction (51%), lack of flushing (10%). Errors occurred more frequently in institutionalized children compared to children living at home (78 versus 25%, P<0.0005). Galenic errors were more frequent in neurologically impaired children (57 versus 30%, P<0.005). CONCLUSION: Many medications are administrated via gastrostomy tube in children. Errors are frequently observed and potentially dangerous.
Asunto(s)
Vías de Administración de Medicamentos , Gastrostomía/métodos , Errores Médicos/estadística & datos numéricos , Niño , Francia , HumanosRESUMEN
The medical emergency ward makes a link between outpatients and hospitalized ones, so we can study community bacterial ecology. The antibiotic susceptibility in Escherichia coli strains isolated from urinary tract infections (UTI) of patients consulting at emergency ward of our hospital in 2002 and 2004 was determined and compared with the susceptibility of the same strains isolated from UTI of hospitalized patients on the same period. The antibiotic susceptibility was performed with Microscan (Dade Behring). All bacteria were tested against the following antimicrobial agents: amoxicilline (Amx), l'amoxicilline+clavulanic acid (AMC), nalidixic acid (NA), ciprofloxacine (Cip), cotrimoxazole (SXT), nitrofurantoin (Ft). Susceptibility in E. coli strains isolated from outpatients vary from 58 to 54% for Amx, from 88 to 83% for NA, from 96 to 89% for Cip, from 82 to 79% for SXT, from 94 to 96% for Ft and remains at 60% for AMC from 2002 to 2004. Susceptibility in E. coli strains isolated from hospitalized patients vary from 52 to 47% for Amx, 55 to 53% for AMC, from 79 to 70% for NA, from 87 to 79% for Cip, from 74 to 69% for SXT, from 93 to 92% for Ft. Susceptibility in E. coli strains isolated in the community from UTI outpatients is decreasing and it becomes worrying particularly concerning the fluoroquinolones, therefore empiric treatment of pyelonephritis by fluoroquinolones must be assessed again.
Asunto(s)
Susceptibilidad a Enfermedades , Infecciones por Escherichia coli/epidemiología , Pacientes Internos/estadística & datos numéricos , Pacientes Ambulatorios/estadística & datos numéricos , Infecciones Urinarias/epidemiología , Antibacterianos/clasificación , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Servicio de Urgencia en Hospital/estadística & datos numéricos , Escherichia coli/efectos de los fármacos , Infecciones por Escherichia coli/tratamiento farmacológico , Francia/epidemiología , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones Urinarias/tratamiento farmacológicoRESUMEN
Pneumocystis jiroveci pneumonia (PCP) has become a rare opportunistic infection due to the efficacy of prophylactic regimens. We conducted a 6-year retrospective study at our institution. A total of 13 cases of PCP were diagnosed among 519 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) (2.5%). In three patients, PCP occurred within the first 5 months following HSCT. These severely immunocompromised patients were receiving prophylaxis and had concomitant aspergillosis that caused rapid death in two of them. In 10 other patients, PCP occurred a median of 14.5 months after HSCT. In all these patients, PCP prophylaxis had been discontinued, mainly because of the suspected bone-marrow toxicity of the prophylactic regimen. Median CD4+ T cell count was 131/microl at diagnosis. Seven of these 10 patients were receiving immunosuppressive therapy for chronic graft versus host disease and three had a relapse of their hematological malignancy. One patient died from PCP despite high doses of cotrimoxazole. We conclude that PCP is still occurring after allogeneic HSCT, mainly as a late complication in patients in whom PCP prophylaxis had been prematurely discontinued. Long-term PCP prophylaxis should be maintained in patients receiving immunosuppressive drugs, and in those with low CD4+ T cell counts or a relapse of their hematological malignancy.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Neumonía por Pneumocystis/prevención & control , Recuento de Linfocito CD4 , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Humanos , Inmunosupresores/efectos adversos , Incidencia , Infecciones Oportunistas/inducido químicamente , Infecciones Oportunistas/tratamiento farmacológico , Infecciones Oportunistas/prevención & control , Neumonía por Pneumocystis/inducido químicamente , Neumonía por Pneumocystis/tratamiento farmacológico , Premedicación , Estudios Retrospectivos , Trasplante Homólogo , Combinación Trimetoprim y Sulfametoxazol/uso terapéuticoAsunto(s)
Histoplasma/aislamiento & purificación , Histoplasmosis/diagnóstico , Histoplasmosis/tratamiento farmacológico , Peritonitis/tratamiento farmacológico , Corticoesteroides/administración & dosificación , Adulto , Antifúngicos/administración & dosificación , Quimioterapia Combinada , Estudios de Seguimiento , Histoplasma/efectos de los fármacos , Humanos , Masculino , Peritonitis/microbiología , Medición de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
UNLABELLED: The aim of this study was to evaluate the safety and efficacy of intravenous iron saccharate administration in iron-deficient anemic children, under long-term parenteral nutrition, who are unable to tolerate oral iron supplementation or are unresponsive to oral supplementation because of gastrointestinal dysfunction or iron malabsorption. METHODS: Twenty-two infants and children aged 5 months-17 years (median: 38 months) receiving long-term parenteral nutrition and presenting with iron deficiency anemia were included. Total iron to be infused was determined by the formula: total iron (mg) = 0.6 x W (100 - Hb x 100/12) (W: weight, Hb: hemoglobin). Intravenous iron saccharate was given at the hospital. Each patient received a test dose of 25 mg of iron saccharate prior to the initiation of the infusion. Hemoglobin values, reticulocytes count, serum iron, and serum ferritin were determined before iron administration (day 1), as well as 15 and 45 days after iron administration. RESULTS: Tolerance of intravenous iron saccharate was good except in one patient who developed transient exanthema and hypotension after completion of the last iron saccharate infusion. Intravenous iron led to a significative increase in hemoglobin concentration of 2.2 g/dl within 45 days (range: 0.4-4.3 g/dl). CONCLUSION: Intravenous iron supplementation with iron saccharate is an efficient procedure, replenishing iron body stores and significantly increasing the hemoglobin concentration. The possible occurrence of allergic reactions emphasizes the need for close medical supervision.
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Anemia Ferropénica/tratamiento farmacológico , Compuestos Férricos/administración & dosificación , Compuestos Férricos/efectos adversos , Nutrición Parenteral/efectos adversos , Adolescente , Anemia Ferropénica/sangre , Niño , Preescolar , Índices de Eritrocitos/efectos de los fármacos , Compuestos Férricos/sangre , Sacarato de Óxido Férrico , Ferritinas/sangre , Ácido Glucárico , Hemoglobinas/efectos de los fármacos , Humanos , Lactante , Infusiones Intravenosas , Hierro/sangre , Recuento de Reticulocitos , Factores de TiempoRESUMEN
The kinetics of the humoral response to Cryptococcus neoformans proteins were studied in outbred mice infected with isolate NIH52D. Future nonsurvivors had earlier and stronger (i.e., more bands recognized) humoral responses than survivors. In addition, antibodies to a 56- to 60-kDa membrane antigen and to a 39- to 40-kDa cytosolic antigen were detected more frequently in samples from future nonsurvivors and from survivors, respectively (P < 0.05).
Asunto(s)
Anticuerpos Antifúngicos/sangre , Antígenos Fúngicos/inmunología , Criptococosis/inmunología , Fungemia/inmunología , Animales , Criptococosis/mortalidad , Cinética , Masculino , Ratones , PronósticoRESUMEN
Fungal infections are a leading cause of mortality in patients with neutropenia. Candidiasis and aspergillosis account for most invasive fungal infections. General prophylactic measures include strict hygiene and environmental measures. Haemopoietic growth factors shorten the duration of neutropenia and thus may reduce the incidence of fungal infections. Fluconazole is appropriate for antifungal prophylaxis and should be offered to patients with prolonged neutropenia, such as high-risk patients with leukaemia undergoing remission induction or consolidation therapy and high-risk stem cell transplant recipients. Empirical antifungal therapy is mandatory in patients with persistent febrile neutropenia who fail to respond to broad-spectrum antibacterials. Intravenous amphotericin B at a daily dose of 0.6 to 1 mg/kg is preferred whenever aspergillosis cannot be ruled out. Lipid formulations of amphotericin B have demonstrated similar efficacy and are much better tolerated. Fluconazole is the best choice for acute candidiasis in stable patients; amphotericin B should be used in patients with unstable disease. Use of fluconazole is restricted by the existence of resistant strains (Candida krusei and, to a lesser extent, C. glabrata). Amphotericin B still remains the gold standard for invasive aspergillosis. Lipid formulations of amphotericin B are effective in aspergillosis and because they are less nephrotoxic are indicated in patients with poor renal function. Itraconazole is an alternative in patients who have good intestinal function and are able to eat. Mucormycosis, trichosporonosis, fusariosis and cryptococcosis are less common but require specific management. New antifungal agents, especially new azoles, are under development. Their broad in vitro spectrum and preliminary clinical results are promising.
Asunto(s)
Antifúngicos/uso terapéutico , Micosis/complicaciones , Neutropenia/complicaciones , Humanos , Micosis/tratamiento farmacológico , Neutropenia/tratamiento farmacológicoRESUMEN
PURPOSE: The most common complication of cataract surgery is the development of posterior capsule opacification (PCO). Hyperplasia of the lens epithelium is one of the main cellular events following phacoemulsification and was found to be an important feature contributing to opacification of the posterior capsule. We investigated the feasibility of killing the residual lens epithelial cells by retroviral-mediated transfer of the herpes simplex virus-thymidine kinase (HSV-tk) gene, a well-studied suicide gene, into rabbit lens epithelial cells followed by ganciclovir (GCV) treatment. METHODS: The capacity of retroviral vectors to transfer genes into rabbit lens epithelial cells was determined either in vitro (culture of rabbit lens epithelial cells) or in vivo (experimental model of PCO in rabbits) using cDNA encoding the beta-galactosidase (LacZ) reporter gene. To evaluate the efficiency of suicide gene therapy (infection with retroviral vectors encoding the HSV-tk gene followed by GCV treatment) we determined the sensitivity of HSV-tk infected lens epithelial cells to different concentrations of GCV in vitro. Then, in an experimental model of PCO, rabbits were treated with HSV-tk retroviral vectors at the end of the surgery and they received repeated intracameral and intravitreal injections of GCV at the concentration determined by the in vitro experiments. RESULTS: Infection efficiency using LacZ retroviral vectors was about 29% in vitro and 10% in vivo. After infection of the HSV-tk cDNA in vitro, the cell killing effect of GCV was evaluated. A significant enhancement (four- to five-fold) of the cell sensitivity to GCV was shown in FLY-DFGtk as compared with mock infected (P < 0.01) cells even without selection of the HSV-tk positive cells. The GCV concentration leading to 50% reduction in cell number (IC50) was 50 microg/ml. In vivo infection with a HSV-tk vector led to the tk gene transfer into lens epithelial cells. Despite this local HSV-tk gene expression, we could not prevent capsule opacification. CONCLUSIONS: Lens epithelial cells were successfully infected both in vitro and in vivo by beta-galactosidase and HSV-tk genes via retroviral vectors. In vitro infected lens epithelial cells displayed a strong sensitivity to GCV treatment. In vivo, we could not prevent capsule opacification in the rabbit model, very likely due to the limited level of the HSV-tk gene expression. However, our results suggest that virus-mediated suicide gene therapy might be a feasible treatment strategy to prevent capsule opacification with a more powerful vector.
Asunto(s)
Catarata/prevención & control , Técnicas de Transferencia de Gen , Cápsula del Cristalino/metabolismo , Timidina Quinasa/genética , Animales , Antivirales/farmacología , Antivirales/uso terapéutico , Catarata/genética , Recuento de Células/efectos de los fármacos , Células Cultivadas , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Epitelio/metabolismo , Femenino , Galactósidos/metabolismo , Ganciclovir/farmacología , Ganciclovir/uso terapéutico , Regulación Enzimológica de la Expresión Génica , Terapia Genética , Herpesvirus Humano 1/enzimología , Herpesvirus Humano 1/genética , Indoles/metabolismo , Cápsula del Cristalino/citología , Cápsula del Cristalino/patología , Conejos , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Retroviridae/genética , Coloración y Etiquetado , Transfección , beta-Galactosidasa/genética , beta-Galactosidasa/metabolismoRESUMEN
The most common complication of cataract surgery is the development of posterior capsule opacification (PCO). Hyperplasia of the lens epithelium is one of the main cellular events following phacoemulsification, and has been found to be an important feature contributing to opacification of the posterior capsule. Adenoviral vector-mediated transfer is a suitable method for transducing the herpes simplex virus thymidine kinase gene (HSV-tk) into proliferating cells, allowing for the selective killing of these cells by ganciclovir (GCV) treatment. To determine the potential of gene transduction for lens epithelial cells, we studied the transduction of rabbit lens epithelial cells with adenoviral vectors containing either the Escherichia coli beta-galactosidase (lacZ) gene or the HSV-tk gene in vitro and in vivo in an experimental model of PCO. The efficiency of lacZ gene transfer in rabbit lens epithelial cells was at least 95% both in vitro and in vivo. In vivo transduction with HSV-tk adenoviral vector followed by GCV treatment significantly inhibited the development of PCO (p<0.001). These results suggest that adenoviral vector-mediated transfer of HSV-tk into the proliferating lens epithelial cells is feasible and may provide a novel therapeutic strategy for PCO.