RESUMEN
SETTING: Tuberculosis (TB) incidence is declining overall in France, but not in Paris where some areas remain relative hot spots for TB.OBJECTIVES: To obtain a better knowledge of local TB epidemiology in order to facilitate control measures.DESIGN: Analysis of demographic data of TB patients diagnosed at the Bichat-Claude Bernard Hospital from 2007 to 2016, with spoligotyping of Mycobacterium tuberculosis complex isolates.RESULTS: During the study period, 1096 TB patients were analysed. The incidence of TB diagnosis was stable, averaging 115 patients per year, predominantly males (71%), foreign-born (81%), with pulmonary TB (77%) and negative HIV serology (88%). The mean age of foreign-born TB patients decreased over the study period, most significantly in recent arrivals in France, whose average age decreased by two years (P = 0.001). The time period between arrival in France and being diagnosed with active TB decreased annually significantly by 0.75 years (P = 0.02). The proportion of L4.6.2/Cameroon and L2/Beijing sub-lineages increased annually by 0.7% (P < 0.05). Multi-drug resistant strains, representing 4% of all strains, increased annually by 0.75% (P = 0.03)CONCLUSION: The number of TB patients remained high in northern Paris and the surrounding suburbs, suggesting the need for increased control measures.
Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis , Beijing , Camerún , Preescolar , Francia/epidemiología , Humanos , Masculino , Paris/epidemiología , Tuberculosis/diagnóstico , Tuberculosis/epidemiologíaRESUMEN
INTRODUCTION: Pre-analytical phase is a critical step in the haemostasis laboratory cycle. Numerous variations affect tests results, and it is crucial to detect them in order to reject improper specimens before reporting test results. Comparing to prior results or requesting, a repeat sample can help in pre-analytical irregularity assessment. METHODS: Each time a sample addressed to our laboratory displayed aberrant results or discordant with a prior report, another specimen was asked and both were analysed through calcium (Ca) level, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen concentration, factor II, factor VII+X and factor V coagulant activity measurements. Among these, all the primary citrated samples from inpatients without anticoagulant treatment, displaying very low calcium level ('Ca 0' samples), were selected for this 2 years study. RESULTS: A total of 17 samples could be identified. Ca level in their paired repeat samples was always >1.00 mmol/L. Coagulation testing for 'Ca 0' samples showed a significant prolongation of PT, APTT, TT and a significant decrease for fibrinogen concentration and factor V coagulant activity. CONCLUSION: We identified factor V coagulant activity, as the parameter with the most important variation in case of very low calcium level in presumed citrated sample tubes probably contaminated with EDTA.
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Factor V , Fibrinógeno , Tiempo de Tromboplastina Parcial , Tiempo de Protrombina , Tiempo de Trombina , Coagulación Sanguínea , Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/diagnóstico , Pruebas de Coagulación Sanguínea , Humanos , Tiempo de Tromboplastina Parcial/métodos , Tiempo de Tromboplastina Parcial/normas , Tiempo de Protrombina/métodos , Tiempo de Protrombina/normas , Tiempo de Trombina/métodos , Tiempo de Trombina/normasRESUMEN
BACKGROUND: Intravesical bacillus Calmette-Guerin (BCG) therapy is an effective and widely used treatment for superficial bladder carcinoma. Local complications are frequent whereas systemic complications are rare but can be serious, and their management is not well known. METHODS: We describe retrospectively the records of 22 patients treated in 3 infectious disease departments, for complications related to intravesical BCG therapy as treatment of bladder cancer. RESULTS: All the patients were male, with a median age of 68 years (range 56-88). Complications occurred after a median of 5 instillations (range 1-11) and were observed within 24 h following BCG instillation for 14 patients. Common symptoms were fever (n = 20), impaired general condition (n = 14), and shortness of breath (n = 7). Six patients had a systemic septic reaction leading to transfer into the intensive care unit for five of them. Lung infiltration was the most frequent presentation (n = 11). Mycobacterium bovis was isolated from only two patients, but histology showed the presence of a granuloma in nine patients. Antimycobacterial treatment was initialized in 17 patients; the outcome was favorable in 16 patients, with a median length of symptoms resolution of 22.5 days (range 5-425 days). Eleven patients received corticosteroids in addition to specific treatment and had a more rapid improvement. One patient died with disseminated BCGitis proved by biopsy. CONCLUSIONS: Complications following intravesical BCG therapy are rare but can be severe and fatal. Histology seems to be the method that contributes most in confirmation of the diagnosis. Antimycobacterial therapy is effective, and probably more efficient when combined with corticosteroids, but the regimen and duration of the treatment are not standardized.
Asunto(s)
Antineoplásicos/efectos adversos , Vacuna BCG/administración & dosificación , Vacuna BCG/efectos adversos , Mycobacterium bovis/aislamiento & purificación , Neoplasias de la Vejiga Urinaria/terapia , Administración Intravesical , Corticoesteroides/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Animales , Antineoplásicos/administración & dosificación , Bovinos , Quimioterapia Combinada , Granuloma/microbiología , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium bovis/efectos de los fármacos , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/complicacionesRESUMEN
BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis (TB) constitute a major public health concern. OBJECTIVE: To determine the timing of pncA mutations that confer pyrazinamide (PZA) resistance in relation to mutations conferring resistance to isoniazid (INH) and rifampicin (RMP). DESIGN: Isolates from two major urban centres--Paris (101 strains) and Shanghai (171 strains)--were investigated for the association of pncA mutations with resistance to drugs other than PZA. RESULTS: The proportion of pncA mutations found in INH-monoresistant strains was not increased. CONCLUSION: pncA mutations associated with PZA resistance were found almost exclusively in MDR-TB strains, underlining the importance of determining PZA resistance when treating MDR- or XDR-TB.
Asunto(s)
Antituberculosos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Fluoroquinolonas/uso terapéutico , Mycobacterium tuberculosis/efectos de los fármacos , Pirazinamida/uso terapéutico , Rifampin/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Amidohidrolasas/genética , China/epidemiología , Análisis Mutacional de ADN , ADN Bacteriano/genética , Farmacorresistencia Bacteriana Múltiple/genética , Tuberculosis Extensivamente Resistente a Drogas/diagnóstico , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Tuberculosis Extensivamente Resistente a Drogas/microbiología , Frecuencia de los Genes , Genotipo , Humanos , Pruebas de Sensibilidad Microbiana , Mutación , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Paris/epidemiología , Fenotipo , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiologíaRESUMEN
BACKGROUND: Transforming growth factor-ß1 (TGF-ß1) is a profibrotic cytokine that plays a major role in vascular biology, and is known to regulate the phenotype and activity of various vascular cell populations. Because most fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF), are associated with vascular remodeling, and as endothelial progenitor cells (EPCs) may be involved in this process, we investigated the impact of TGF-ß1 modulation of EPC angiogenic properties. METHODS: TGF-ß1 plasma levels were determined in 64 patients with IPF and compared with those in controls. The effect of TGF-ß1 on angiogenesis was studied in vivo in a Matrigel plug model and in vitro on endothelial colony-forming cells (ECFCs). We studied the effects of inhibiting the expression of the three main receptors of TGF-ß1 in ECFCs by using short interfering RNA. RESULTS: Total TGF-ß1 plasma levels were significantly increased in patients with IPF as compared with controls (P < 0.0001). TGF-ß1 had proangiogenic effects in vivo by increasing hemoglobin content and blood vessel formation in Matrigel plugs implanted in C57/Bl6 mice, and in vitro by enhancing ECFC viability and migration. The effects were abolished by silencing the three main TGF-ß1 receptors. CONCLUSIONS: TGF-ß1 is proangiogenic in vivo and induces ECFC angiogenic properties in vitro, suggesting that TGF-ß1 may play a role during vascular remodeling in fibrotic disease states via EPCs.
Asunto(s)
Células Endoteliales/metabolismo , Fibrosis Pulmonar Idiopática/metabolismo , Neovascularización Fisiológica , Células Madre/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Animales , Estudios de Casos y Controles , Movimiento Celular , Supervivencia Celular , Células Cultivadas , Femenino , Sangre Fetal/citología , Francia , Hemoglobinas/metabolismo , Humanos , Fibrosis Pulmonar Idiopática/sangre , Fibrosis Pulmonar Idiopática/fisiopatología , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Estudios Prospectivos , Interferencia de ARN , Receptores de Factores de Crecimiento Transformadores beta/genética , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Transfección , Factor de Crecimiento Transformador beta1/sangre , Regulación hacia ArribaRESUMEN
In a study performed in Cambodia, a higher number of tuberculosis (TB) strains with mutations in the pncA gene associated with pyrazinamide resistance (PZA-R) was found in fluoroquinolone-resistant (FQ-R) multidrug-resistant (MDR) strains (93%), compared with 47% in MDR and 3% in non-MDR strains. This emphasises the need for easy and rapid tests for identification of PZA-R for efficient treatment of MDR-TB.
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Amidohidrolasas/genética , ADN Bacteriano/genética , Fluoroquinolonas/uso terapéutico , Mutación , Mycobacterium tuberculosis/genética , Pirazinamida/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Antituberculosos/uso terapéutico , Cambodia/epidemiología , Genotipo , Humanos , Incidencia , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Estudios Retrospectivos , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/microbiologíaAsunto(s)
Células de la Médula Ósea/citología , Isquemia/inmunología , Pierna/irrigación sanguínea , Pierna/patología , Leucocitos Mononucleares/citología , Células Madre Mesenquimatosas/metabolismo , Enfermedad Arterial Periférica/patología , Anciano , Animales , Humanos , Células Madre Mesenquimatosas/citología , RatonesRESUMEN
Multidrug-resistant (MDR) strains were identified in 40% of 54 strains from patients presenting with tuberculosis (TB) treatment failure or relapse in Bangui, Central African Republic. Results obtained with the MTBDRplus line-probe assay or rpoB sequencing were 86% concordant with rifampicin (RMP) resistant phenotypes, while the amplification refractory mutation system test was 71% concordant. No mutation was found in RMP-susceptible strains. MTBDRplus and sequencing were concordant with the detection of the S315T mutation in katG in 95% of MDR strains. Sequencing of pncA suggested pyrazinamide resistance in 50% of MDR strains. Knowledge of these resistances should help to implement treatment in low-income countries.
Asunto(s)
Antituberculosos/uso terapéutico , ADN Bacteriano/genética , Farmacorresistencia Bacteriana Múltiple/genética , Mutación , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , República Centroafricana/epidemiología , Humanos , Incidencia , Mycobacterium tuberculosis/genética , Reacción en Cadena de la Polimerasa , Prevalencia , Recurrencia , Estudios Retrospectivos , Insuficiencia del Tratamiento , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiologíaRESUMEN
Bruton's disease is the most frequently primary X-linked immunodeficiency. Bruton's tyrosine kinase (Btk) is encoded by the XLA gene that when mutated causes bruton's disease. This protein acts in multiple intracellular signaling pathways where the BCR (B-cell receptor) pathway is the most elucidated. Moreover 400 mutations were found and identified as responsible for B-cells differentiation block; consequences are a lack of B-cells in peripheral blood and hypo/agammaglobulinemia. Thus, patients are more susceptible to early and recurring infections occurring before the age of one year. Laboratory testing allow differential diagnosis among primary immunodeficiencies in which others hypogammaglobulinemia. Genetic analyses help physicians for clinical and biological diagnosis, and allow prenatal diagnosis for patient's family. Patient's management is based upon polyclonal immunoglobulin supplementation, infectious diseases prevention and genetic advice.
Asunto(s)
Agammaglobulinemia/genética , Cromosomas Humanos X/genética , Proteínas Tirosina Quinasas/genética , Adulto , Agammaglobulinemia Tirosina Quinasa , Agammaglobulinemia/diagnóstico , Agammaglobulinemia/fisiopatología , Agammaglobulinemia/terapia , Apoptosis , Linfocitos B/inmunología , Preescolar , Diagnóstico Diferencial , Femenino , Regulación de la Expresión Génica , Asesoramiento Genético , Ligamiento Genético , Humanos , Inmunoglobulina G/sangre , Inmunoglobulinas/inmunología , Lactante , Masculino , Mutación , Fenotipo , Embarazo , Diagnóstico PrenatalRESUMEN
Bruton's disease is the most frequently primary X-linked immunodeficiency. Patients are more susceptible to early and recurring infections associated with hypo/agammaglobulinemia and a severe B-cell deficiency. Moreover, 400 mutations were found in the XLA gene which codes the Btk tyrosine kinase and were identified as responsible for Bruton's disease. Genetic study was carried out with one group of patients named NECKER, composed by five XLA patients and two parents whose XLA gene was sequenced by an Italian crew. Results were obtained by PCR of 19 exons and initial/terminal intron's parts, followed by PCR-sequencing with universal primers and sequencing. The results from this study allowed the validation of the sequencing technique by comparing NECKER group data (equivalent results with Italian data). In addition, the mutation multiplicity (described or not, coding/non coding) need an exact analysis that should be given to clinicians through clear and trustful results. In this way, a strategy to analyse untreated results was created based on the mutation type. The genetic analysis could help physicians for uncertain diagnosis in immune defficiencies, allows proposing a genetic advice to the patient's family and the construction of a data base permits a best understanding of this disease.
Asunto(s)
Agammaglobulinemia/genética , Proteínas Tirosina Quinasas/genética , Cromosomas Sexuales/genética , Agammaglobulinemia Tirosina Quinasa , Agammaglobulinemia/diagnóstico , Linfocitos B/inmunología , Secuencia de Bases , Niño , Bases de Datos como Asunto , Exones/genética , Femenino , Asesoramiento Genético , Ligamiento Genético , Heterocigoto , Humanos , Intrones/genética , Masculino , Mutación , Reacción en Cadena de la PolimerasaRESUMEN
Seeds of bean (Phaseolus vulgaris cv. Vernel) were collected throughout their development on the plant and dried at 15 degrees C and 75% relative humidity to a final moisture content of about 16% (fresh weight basis) to determine whether the onset of tolerance to this drying condition was related to changes in soluble sugars or the activities of the main antioxidant enzymes, namely superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR). Measurements of soluble sugars and enzyme activities were made after drying the seeds, and drying tolerance was evaluated by the ability of dried seeds to germinate and to produce normal seedlings. Seeds became tolerant to drying at 45 d after anthesis, a time marking physiological maturity. At physiological maturity, the moisture content of seeds was about 50-55% (fresh weight basis) and seed dry matter reached about 190 mg per seed. Seed vigour, evaluated by controlled deterioration and conductivity measurements, continued to increase after seed mass maturity, but decreased when seeds remained thereafter for more than 7 d on the plant. Acquisition of drying tolerance was coincident with an accumulation of raffinose and stachyose. Dried-tolerant seeds were also characterized by a high amount of sucrose, the most abundant sugar, and by a low content of monosaccharides. The (raffinose+stachyose)/sucrose ratio increased during seed filling, reaching a value close to 1 when all the seeds became tolerant to drying, and maintaining this proportion during the final stages of maturation. Acquisition of drying tolerance was also related to a reorientation of the enzymatic antioxidant defence system. Drying-tolerant dried seeds displayed high CAT and GR activities and low SOD and APX activities, while the opposite condition was observed in immature dried seeds. The shift in antioxidant enzymes corresponded to the beginning of the maturation-drying phase. These results suggest that oligosaccharide metabolism and enzymatic antioxidant defences may be involved in acquisition of drying tolerance during bean seed development, but are not related to seed vigour.
Asunto(s)
Catalasa/metabolismo , Fabaceae/embriología , Glutatión Reductasa/metabolismo , Oligosacáridos/metabolismo , Peroxidasas/metabolismo , Plantas Medicinales , Semillas/enzimología , Semillas/metabolismo , Superóxido Dismutasa/metabolismo , Adaptación Fisiológica , Ascorbato Peroxidasas , Fabaceae/fisiología , Germinación , Semillas/crecimiento & desarrolloRESUMEN
We report a case of epithelioid granulomatous allergic lung disease in a patient given intra-bladder BCG therapy for treatment of a tumor. This uncommon complication is sometimes related to bacterial dissemination or to an immunoallegic reaction occurring from the third to eigth week after onset of the instillation. Clinically, the patient presents a flu-like syndrome. The standard chest X-ray followed by computed tomography, demonstrates the extension of the pulmonary lesions. Miliary dissemination is rarely reported (10 cases in the literature). Histological proof can be obtained from an endoscopic bronchial biopsy or a surgical specimen of the pulmonary parenchyma. Treatment is based on corticosteroid therapy in combination with antituberculosis antibiotics. Prognosis is generally good with treatment.
Asunto(s)
Adyuvantes Inmunológicos/efectos adversos , Vacuna BCG/efectos adversos , Granuloma del Sistema Respiratorio/inducido químicamente , Tuberculosis Miliar/inducido químicamente , Tuberculosis Pulmonar/inducido químicamente , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Adyuvantes Inmunológicos/administración & dosificación , Anciano , Antiinflamatorios/uso terapéutico , Antituberculosos/uso terapéutico , Vacuna BCG/administración & dosificación , Biopsia , Granuloma del Sistema Respiratorio/diagnóstico por imagen , Granuloma del Sistema Respiratorio/tratamiento farmacológico , Humanos , Instilación de Medicamentos , Masculino , Pronóstico , Esteroides , Factores de Tiempo , Tomografía Computarizada por Rayos X , Tuberculosis Miliar/diagnóstico por imagen , Tuberculosis Miliar/tratamiento farmacológico , Tuberculosis Pulmonar/diagnóstico por imagen , Tuberculosis Pulmonar/tratamiento farmacológicoRESUMEN
Partial sequencing of the hsp65 gene was used for the identification of rapidly growing mycobacteria (RGM). A 441-bp fragment (A. Telenti, F. Marchesi, M. Balz, F. Bally, E. Böttger, and T. Bodmer, J. Clin. Microbiol. 31:175-178, 1993) was amplified and sequenced by an automated fluorescence-based method involving capillary electrophoresis. Type strains of 10 RGM species were first studied. Each species had a unique nucleotide sequence, distinguishing it clearly from the other species. A panel of strains from the four main RGM species responsible for human infections, Mycobacterium abscessus, Mycobacterium chelonae, Mycobacterium fortuitum, and Mycobacterium peregrinum, was also studied. There were few sequence differences within each of these species (<2% of bases were different from the type strain sequence), and they had no effect on species assignment. hsp65 sequencing unambiguously differentiated M. chelonae and M. abscessus, two species difficult to identify by classical methods and 16S rRNA gene sequencing. The devised procedure is a rapid and reliable tool for the identification of RGM species.
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Proteínas Bacterianas , Chaperoninas/genética , Infecciones por Mycobacterium/diagnóstico , Mycobacterium/clasificación , Mycobacterium/genética , Antígenos Bacterianos/genética , Secuencia de Bases , Chaperonina 60 , Variación Genética , Humanos , Datos de Secuencia Molecular , Mycobacterium/crecimiento & desarrollo , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/crecimiento & desarrollo , Filogenia , Reacción en Cadena de la Polimerasa/métodos , ARN Bacteriano/genética , ARN Ribosómico 16S/genética , Alineación de Secuencia , Homología de Secuencia de Ácido NucleicoAsunto(s)
Adenocarcinoma/patología , Antidiarreicos/uso terapéutico , Neoplasias del Colon/secundario , Diarrea/complicaciones , Linitis Plástica/secundario , Octreótido/uso terapéutico , Neoplasias Gástricas/patología , Adenocarcinoma/complicaciones , Adenocarcinoma/cirugía , Neoplasias del Colon/complicaciones , Diarrea/tratamiento farmacológico , Gastrectomía , Humanos , Linitis Plástica/complicaciones , Linitis Plástica/patología , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/cirugíaRESUMEN
Forty-three percent of the tuberculosis cases reported in France are from the Ile de France region. The incidence of tuberculosis in this region is 33 cases per 100,000 inhabitants, twice the national average. A restriction fragment length polymorphism (RFLP) analysis was performed with clinical isolates of Mycobacterium tuberculosis isolated during 1995 in 10 hospitals in Paris and surrounding areas to detect tuberculosis transmission and define the factors associated with clustering in this population. The molecular markers used were the insertion sequence IS6110 and the direct repeat (DR) sequence. Social, demographic, and clinical data were collected from the patients' medical files. Ten patients with isolates with a single copy of IS6110 were excluded from further analysis. Twenty-four patients with false-positive cultures due to laboratory contamination (based on RFLP analysis with IS6110 and examination of patient data) were also excluded. The study was then conducted with 272 strains isolated from 272 patients. Further fingerprinting was performed by using the DR element with strains with patterns by RFLP analysis with IS6110 that differed by one band only and strains with identical patterns by RFLP analysis with IS6110 and with low numbers of copies of IS6110. The combined use of both markers identified unique patterns for 177 strains and clustered 95 (35.7%) strains in 26 groups, each containing isolates from 2 to 12 patients. The clustering was strongly associated with homelessness and the male sex. It was not associated with age, birth in a foreign country, human immunodeficiency virus positivity, or residence in hostels or prison. Isolates from homeless people were often included in large clusters, and homeless people could be the source of tuberculosis transmission for more than 50% of the clustered patients. These results suggest that homeless people play a key role in the spread of M. tuberculosis in the community and that poor socioeconomic conditions are the main risk factors associated with active tuberculosis transmission.
Asunto(s)
ADN Bacteriano/análisis , Mycobacterium tuberculosis/genética , Tuberculosis/epidemiología , Tuberculosis/transmisión , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Infecciones Oportunistas Relacionadas con el SIDA/transmisión , Factores de Edad , Sondas de ADN , ADN Bacteriano/genética , ADN Bacteriano/aislamiento & purificación , Errores Diagnósticos , Emigración e Inmigración , Reacciones Falso Positivas , Femenino , Seropositividad para VIH , Personas con Mala Vivienda , Hospitales , Humanos , Incidencia , Masculino , Epidemiología Molecular , Mutagénesis Insercional , Mycobacterium tuberculosis/aislamiento & purificación , Paris/epidemiología , Polimorfismo de Longitud del Fragmento de Restricción , Prisiones , Secuencias Repetitivas de Ácidos Nucleicos , Factores Sexuales , Clase Social , Tuberculosis/diagnósticoRESUMEN
Mycobacterium smegmatis is a common environmental mycobacterium that was first identified in 1884, yet is a rare pathogen in humans. The few M. smegmatis infections reported to date have been localized and have occurred in association with a primary lesion in otherwise immunocompetent individuals. To our knowledge, no case of disseminated M. smegmatis infection has ever been reported, even in patients with severe immune deficiencies. We report a case of disseminated mycobacterial infection that was diagnosed in a 3-year-old girl. The pathogen was not identified as M. smegmatis until the patient was 6 years old. Her condition gradually worsened, and she died when she was 8 years old despite appropriate antimycobacterial therapy. No other opportunistic infections were documented. Immunological investigations revealed an inherited interferon gamma receptor 1 deficiency. This report identifies M. smegmatis as a new opportunistic agent that may be responsible for disseminated disease in immunocompromised individuals.
Asunto(s)
Bacteriemia/inmunología , Huésped Inmunocomprometido , Infecciones por Mycobacterium/inmunología , Infecciones Oportunistas/inmunología , Receptores de Interferón/deficiencia , Bacteriemia/diagnóstico , Bacteriemia/microbiología , Preescolar , Resultado Fatal , Femenino , Humanos , Infecciones por Mycobacterium/diagnóstico , Infecciones por Mycobacterium/microbiología , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/microbiología , Receptores de Interferón/genética , Receptor de Interferón gammaRESUMEN
Interhuman transmission of Mycobacterium tuberculosis was investigated by using molecular typing, including restriction fragment length polymorphism with probes IS6110, DR (direct repeat) and PGRS (polymorphic GC-rich sequence) and a PCR method using the inverted repeat sequences of IS6110 as primers. From 105 patients hospitalized for tuberculosis during a 1-year survey in three hospitals in Paris, France, 111 isolates were collected and analyzed. Eighty-eight patients were infected with genetically different isolates, demonstrating the clonal heterogeneity of M. tuberculosis in these patients originating from various geographical areas. Fourteen patients were infected by strains clustered with identical fingerprints. An epidemiological relatedness was demonstrated for isolates from only seven of these patients. Thus, the typing of isolates from all tuberculous patients in hospitals during 1 year allows the detection of transmission in the general community. This would improve the case findings, thereby further improving the detection of outbreaks.
Asunto(s)
Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis/microbiología , Tuberculosis/transmisión , Adulto , Técnicas de Tipificación Bacteriana , Secuencia de Bases , Cartilla de ADN/genética , Elementos Transponibles de ADN , ADN Bacteriano/genética , Brotes de Enfermedades , Farmacorresistencia Microbiana , Femenino , Humanos , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Datos de Secuencia Molecular , Mycobacterium tuberculosis/genética , Paris/epidemiología , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Polimorfismo de Longitud del Fragmento de Restricción , Secuencias Repetitivas de Ácidos Nucleicos , Tuberculosis/epidemiologíaRESUMEN
More rapid and more sensitive techniques have replaced traditional methods of direct examination and culturing for diagnosing mycobacterial infections. Among the most recent methods are Isolator blood culture, radiometric detection, hybridization and amplification, each with its advantages and disadvantages. The Isolator blood culture system improves the sensitivity of mycobacteria detection, especially for Mycobacterium avium-intracellulare. In terms of cost and culture time, this system is similar to traditional methods, although it is limited to blood cultures. Radiometric detection, associated with culture in a liquid medium, greatly improves diagnostic power. The main advantage lies in the reduced delay before detection, 13.4 days compared with 21.7 days on solid media (for M. tuberculosis) and 5.1 days instead of 18.6 days for other mycobacteria. A culture is considered to be negative after 6 weeks without growth compared with 12 weeks for the Löwenstein-Jensen medium. The disadvantages of this system include the cost of equipment, personnel and radio-active products. In addition, as for all culture methods, a sufficient bacterial population is required in the sample. Hybridization techniques rely on DNA or RNA probes which recognize mycobacterial sequences. The Gen-Probe recognizes M. tuberculosis, M. avium, M. intracellulare and M. gordonae ribosomal RNA. Syngene probes recognize M. tuberculosis and M. avium-intracellulare DNA sequences. Rapid identification in less than 2 hours is a major advantage. At the present time 50 pg of DNA are required, a quantity which is not usually present in clinical samples. Combining this technique with primary culture in liquid medium or amplification techniques improves sensitivity. Polymerase chain reaction amplifies a specific sequence of double strand DNA. This method provides a means of identifying mycobacterial DNA in a clinical sample within 24-48 hours, a major improvement over traditional culture. Cost however may be a barrier although the cost/benefit ration remains to be determined.
Asunto(s)
Infecciones por Mycobacterium/diagnóstico , Mycobacterium/aislamiento & purificación , Hibridación de Ácido Nucleico/métodos , Reacción en Cadena de la Polimerasa/métodos , Radiometría/métodos , Humanos , Infecciones por Mycobacterium/microbiologíaRESUMEN
We evaluated the repertoire of V beta segments used in forming the T-cell receptor of lavage and blood T lymphocytes from 11 sarcoid patients and 10 normal subjects using procedures based on quantitative polymerase chain reaction, permitting analysis of both the abundance of transcripts using each of 20 different V beta families and the diversity of the VDJC beta rearrangements within each V beta family. Blood and lung T cells from sarcoid patients had a very diverse V beta repertoire. For all V beta families but one, the abundance of the V beta transcripts fell within the mean +/- 2 SD of that observed for normal blood lymphocytes; no difference in the overall abundance was observed comparing lavage and blood T cells, and the length of VDJC beta rearrangements for a given V beta family in samples from sarcoid patients was usually quite heterogeneous. Despite the overall polyclonality, evidence for selective expansion of T cells was found, in that an increased abundance of V beta 19 transcripts was observed for sarcoid blood and/or lung T cells in eight out of 11 patients studied, and rearrangements of a single predominant length using certain (e.g., V beta 19, V beta 14), but not all, V beta families were present. Sequencing confirmed the presence of a single predominant VDJC beta rearrangement in these cases. These findings suggest that the alveolitis in sarcoidosis results from two distinct processes, a local clonal expansion of T cells associated with an apparently nonspecific accumulation of T cells with an extremely diverse V beta repertoire.
Asunto(s)
Líquido del Lavado Bronquioalveolar/citología , Receptores de Antígenos de Linfocitos T alfa-beta/análisis , Sarcoidosis Pulmonar/sangre , Sarcoidosis Pulmonar/patología , Linfocitos T/química , Adulto , Secuencia de Bases , Estudios de Casos y Controles , Femenino , Expresión Génica , Reordenamiento Génico , Humanos , Masculino , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Sarcoidosis Pulmonar/diagnósticoRESUMEN
In isolated rat liver cells, the inhibition of L-pyruvate kinase (L-PK) by a cyclic AMP-dependent phosphorylation mechanism is involved in the hormonal control of glycolysis and gluconeogenesis. The aim of this study was to ascertain whether or not the in vivo phosphorylation state of the enzyme was maintained during the liver perfusion used to prepare isolated liver cells. When the L-PK phosphorylation state was studied indirectly in liver extracts by kinetic measurement, it was found that, during the perfusion, the S0.5 of phosphoenol pyruvate (PEP) for L-PK was decreased in a time-dependent manner from 1 +/- 0.08 to 0.64 +/- 0.1 mM (P less than 0.01) and 0.58 +/- 0.06 mM in liver cells. This shift was prevented only by the addition of glucagon to the perfusion medium. The extent of phosphorylation of L-PK was also estimated by incubation of the liver extract with [gamma-32P]ATP, protein kinase, and cyclic AMP, and measurement of 32Pi incorporated in L-PK by specific immunoprecipitation. In liver extracts removed at the beginning of the perfusion, 0.4 mol Pi/mol L-PK was incorporated and there was no stimulation by cyclic AMP. In contrast, in the liver extracts removed after 30 min of perfusion, cyclic AMP stimulated 32P incorporation two to threefold, and 1.6 mol Pi/mol L-PK was incorporated. These data suggest that L-PK was activated by a dephosphorylation mechanism during rat liver perfusion. This phenomenon could be involved in the classical inactivation of gluconeogenesis observed in the perfused rat liver model.