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The original version of this Article omitted the author Dr Mathias Chamaillard from the l'Institut de Pasteur, Lille, France. This has been corrected in both the PDF and HTML versions of the Article.
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Upon oral infection with Toxoplasma gondii cysts (76 K strain) tachyzoites are released into the intestinal lumen and cross the epithelial barrier causing damage and acute intestinal inflammation in C57BL/6 (B6) mice. Here we investigated the role of microbiota and IL-22 in T.gondii-induced small intestinal inflammation. Oral T.gondii infection in B6 mice causes inflammation with IFNγ and IL-22 production. In IL-22-deficient mice, T.gondii infection augments the Th1 driven inflammation. Deficiency in either IL-22bp, the soluble IL-22 receptor or Reg3γ, an IL-22-dependent antimicrobial lectin/peptide, did not reduce inflammation. Under germ-free conditions, T.gondii-induced inflammation was reduced in correlation with parasite load. But intestinal inflammation is still present in germ-free mice, at low level, in the lamina propria, independently of IL-22 expression. Exacerbated intestinal inflammation driven by absence of IL-22 appears to be independent of IL-22 deficiency associated-dysbiosis as similar inflammation was observed after fecal transplantation of IL-22-/- or WT microbiota to germ-free-WT mice. Our results suggest cooperation between parasite and intestinal microbiota in small intestine inflammation development and endogenous IL-22 seems to exert a protective role independently of its effect on the microbiota. In conclusion, IL-22 participates in T.gondii induced acute small intestinal inflammation independently of microbiota and Reg3γ.
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Microbioma Gastrointestinal/inmunología , Inflamación/inmunología , Interleucinas/metabolismo , Intestinos/inmunología , Toxoplasma/fisiología , Toxoplasmosis/inmunología , Animales , Células Cultivadas , Progresión de la Enfermedad , Interleucinas/genética , Intestinos/parasitología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Asociadas a Pancreatitis/genética , Proteínas Asociadas a Pancreatitis/metabolismo , Carga de Parásitos , Receptores de Interleucina/genética , Receptores de Interleucina/metabolismo , Interleucina-22RESUMEN
OBJECTIVES: Fungi belonging to the Metarhizium anisopliae complex comprise ubiquitous arthropod pathogenic moulds used as mycopesticides. Rare cases of human infections due to M. anisopliae have been reported. We hypothesize misidentifications of fungal strains implicated in these cases or used in mycopesticides. METHODS: A review of the literature was conducted to identify previously published cases. We collected some of these previous described strains and reported new cases, and a French mycopesticide containing M. anisopliae. All identifications were performed based on elongation factor-1α gene sequencing. RESULTS: We report eight new cases of Metarhizium infection in humans (three from France and five from Australia). The strains isolated from these cases, and three others from already published cases and reported as M. anisopliae, were molecularly identified based on elongation factor-1α (Ef1-α) gene sequencing as follows: Metarhizium robertsii (six), Metarhizium guizhouense (three), Metarhizium brunneum (one) and Metarhizium pingshaense (one). CONCLUSIONS: In this study, we report new human cases of Metarhizium infections, and, based on Ef-1α gene sequencing, we demonstrate the misidentification of species in case reports. We also correct the species identification of a strain reported as M. anisopliae used in a commercially available mycopesticide. According to our results, none of the strains from the human infection reports reviewed belongs to the species M. anisopliae.
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Metarhizium , Micosis/microbiología , Adolescente , Adulto , Anciano , Antifúngicos/uso terapéutico , Niño , Preescolar , Errores Diagnósticos , Femenino , Genes Fúngicos/genética , Humanos , Masculino , Metarhizium/genética , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Micosis/diagnóstico , Micosis/tratamiento farmacológico , Filogenia , Estudios Retrospectivos , Análisis de Secuencia de ADNRESUMEN
Lung transplantation (LT) is now considered as an excellent treatment option for selected patients with end-stage pulmonary diseases, such as COPD, cystic fibrosis, idiopathic pulmonary fibrosis, and pulmonary arterial hypertension. The 2 goals of LT are to provide a survival benefit and to improve quality of life. The 3-step decision process leading to LT is discussed in this review. The first step is the selection of candidates, which requires a careful examination in order to check absolute and relative contraindications. The second step is the timing of listing for LT; it requires the knowledge of disease-specific prognostic factors available in international guidelines, and discussed in this paper. The third step is the choice of procedure: indications of heart-lung, single-lung, and bilateral-lung transplantation are described. In conclusion, this document provides guidelines to help pulmonologists in the referral and selection processes of candidates for transplantation in order to optimize the outcome of LT.
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Trasplante de Pulmón/métodos , Trasplante de Pulmón/estadística & datos numéricos , Selección de Paciente , Conducta de Elección , Contraindicaciones , Fibrosis Quística/terapia , Humanos , Fibrosis Pulmonar Idiopática/terapia , Trasplante de Pulmón/normas , Enfermedad Pulmonar Obstructiva Crónica/terapia , Insuficiencia Respiratoria/terapia , Factores de Tiempo , Listas de EsperaRESUMEN
Graft-versus-host disease (GVHD) is a classic and frequent multisystemic complication of bone marrow allografts. It has also been reported after the transplantation of solid organs such as the liver or gut. Recent cases of GVHD have been reported after lung and heart-lung transplant. Skin, liver, gastrointestinal tract and bone marrow are the organ preferentially affected by GVHD. Corticosteroid is the first line treatment of GVHD. The prognosis reported in solid organ transplants is poor with infectious complications favoured by immunosuppressive therapy. In this article, we report a case of a patient with cystic fibrosis who presented a probable GVHD 18 months after a lung transplant and a literature review of similar cases.
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Fibrosis Quística/terapia , Enfermedad Injerto contra Huésped/patología , Trasplante de Pulmón/efectos adversos , Adulto , Femenino , Humanos , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapiaRESUMEN
INTRODUCTION: Tuberculosis-related morbidity and mortality remain important. Emergence and diffusion of multidrug-resistance tuberculosis (MDR-TB) is a global public health concern. Cases of MDR-TB in children are a sentinel event indicating the spread of a mycobacterial strain within a community. Latent TB precedes MDR-TB and screening and follow-up of contact individuals are key points of TB infection control. METHODS: We performed the case-investigation of 20 adult cases of MDR-TB managed in our institution. RESULTS: Forty-six pediatric contact individuals were identified. A high proportion of these children were lost to follow-up (80% at 12 months), showing that monitoring this reservoir population with migrant history is challenging. Five (11%) children presented a secondary infection: one child was diagnosed with active TB infection (positive tuberculin skin test associated with abnormalities on chest computer tomography [CT] scan). Four children were diagnosed with latent TB infection (isolated positive tuberculin skin test with normal CT scan). Two of these children received a treatment adjusted to the strain of the index case. DISCUSSION: In the setting of emerging MDR-TB, tuberculin skin test may be likely replaced by specific interferon-gamma release assays (IGRA), independent of prior BCG vaccination. In addition, chest CT scan is preferred to chest X-ray to detect TB lesions. The management of latent TB infection is controversial: immediate treatment with second-line anti-TB drugs adapted to the index case strain or, consistently with WHO guidelines, a simple follow-up with subsequent treatment in case of active TB.
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Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/transmisión , Amicacina/uso terapéutico , Antibacterianos/uso terapéutico , Niño , Preescolar , Femenino , Francia/epidemiología , Humanos , Lactante , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/tratamiento farmacológico , Tuberculosis Latente/epidemiología , Levofloxacino/uso terapéutico , Perdida de Seguimiento , Masculino , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológicoRESUMEN
Multidrug-resistant (MDR) tuberculosis (TB) is an emerging concern in communities with a low TB prevalence and a high standard of public health. Twenty-three consecutive adult MDR TB patients who were treated at our institution between 2007 and 2013 were reviewed for demographic characteristics and anti-TB treatment management, which included surgical procedures and long-term patient follow-up. This report of our experience emphasizes the need for an individualized approach as MDR TB brings mycobacterial disease management to a higher level of expertise, and for a balance to be found between international current guidelines and patient-tailored treatment strategies.
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Manejo de Caso/organización & administración , Enfermedades Transmisibles Emergentes/diagnóstico , Enfermedades Transmisibles Emergentes/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/terapia , Adulto , Antituberculosos/uso terapéutico , Enfermedades Transmisibles Emergentes/epidemiología , Femenino , Humanos , Masculino , Medicina de Precisión/métodos , Prevalencia , Estudios Retrospectivos , Procedimientos Quirúrgicos Operativos , Tuberculosis Resistente a Múltiples Medicamentos/epidemiologíaAsunto(s)
Actinomicosis/diagnóstico , Alcoholismo/complicaciones , Enfermedades Pulmonares/diagnóstico , Actinomyces/aislamiento & purificación , Actinomicosis/complicaciones , Actinomicosis/microbiología , Adulto , Diagnóstico Diferencial , Estudios de Seguimiento , Humanos , Enfermedades Pulmonares/complicaciones , Enfermedades Pulmonares/microbiología , Masculino , Radiografía Torácica , Índice de Severidad de la Enfermedad , Esputo/microbiología , Tomografía Computarizada por Rayos XAsunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico por imagen , Seropositividad para VIH/complicaciones , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Tuberculosis Miliar/diagnóstico por imagen , Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Adulto , Terapia Antirretroviral Altamente Activa/métodos , Diagnóstico Diferencial , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Radiografía , Resultado del TratamientoRESUMEN
Clozapine is an atypical antipsychotic known for its efficacy in refractory schizophrenia. However, according to different epidemiological studies clozapine can induce neutropenia in less than 3% of patients and may represent a major problem for the management of treatment-resistant patients not responding to conventional or other atypical antipsychotics. Recently, a few case of neutropenia have been reported following the addition of other medications to clozapine, notably paroxetine, risperidone, trimethoprim-sulfamethoxazole and erythromycin. In our report we present the case of Mr A., a 40-year-old Caucasian patient with a 20-year history of paranoid schizophrenia. After numerous trials with conventional antipsychotics, partial remission of psychotic symptoms was obtained with clozapine. Over the past eight years during his treatment with clozapine, the patient presented 2 episodes of neutropenia. The first episode came five years after starting clozapine and was attributed to the addition 6 weeks earlier of haloperidol (2 mg/day) to clozapine (250 mg/day) and divalproex (1,500 mg/day). Recently, one week after the addition of risperidone (2 mg/day) to clozapine (550 mg/day), leukocytes count dropped from 12 100/mm(3) to 5 700/mm(3) and neutrophils from 7 400/mm(3) to 900/mm(3). The patient was also taking haloperidol (4 mg/day), methotrimeprazine (35 mg/day), procyclidine (5 mg/day) and valproic acid (1,500 mg/day). Twelve days after discontinuation of risperidone, leukocytes and neutrophils count increased to 11,100/mm(3) and 6,300/mm(3) respectively while the treatment with clozapine was continued. The first eighteen weeks of treatment represent the period where the risk of neutropenia is the highest. In our patient neutropenia occurred 5 and 7 years after starting clozapine. It is proposed that the two neutropenic episode were precipitated by adding respectively haloperidol and risperidone to clozapine. Also, divalproex can potentially cause a decrease in white blood cell count and may have contributed to the two neutropenic episode. It is suggested that drug interactions may be responsible for neutropenia in clozapine treated patients and that clozapine should not necessarily be discontinued in the presence of neutropenia. Also we propose that hematological surveillance should be done on a weekly basis for 4 to 6 weeks following the addition of psychotropic drugs known for their potential to cause neutropenia when associated with clozapine. Therefore polypharmacy may contribute to cause neutropenia in clozapine treated patients and that discontinuation of an antipsychotic should be done before introducing another one.
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Antipsicóticos/efectos adversos , Clozapina/efectos adversos , Neutropenia/inducido químicamente , Esquizofrenia/tratamiento farmacológico , Adulto , Anticonvulsivantes/efectos adversos , Antiparkinsonianos/uso terapéutico , Quimioterapia Combinada , Haloperidol/efectos adversos , Humanos , Masculino , Metotrimeprazina/efectos adversos , Prociclidina/efectos adversos , Risperidona/efectos adversos , Ácido Valproico/efectos adversosRESUMEN
Pro-collagen III (PC III) has been proposed as a useful value for diagnosis and follow-up of myeloproliferative disorders. A significant difference is observed between polycythaemia vera (PV) and essential thrombocythaemias (ET) on one hand, and the pure erythrocytoses (PE) on the other hand, but a large overlap makes this test of low diagnostic value. High values are observed in primary and post-PV myelofibrosis, but excessive PC III levels in active PV are not predictive of evolution toward myelofibrosis. PC III level is lower in myelo-suppressed patients (32P, or hydroxy-urea) than in active cases or in patients treated by phlebotomies. We conclude that PC III measurement is of low diagnostic value for discriminating PV and PE, does not appear to allow short-term prediction of evolution to myelofibrosis, but may be useful to evaluate the role of treatment in delaying progression of PV toward myelofibrosis.
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Trastornos Mieloproliferativos/sangre , Procolágeno/sangre , Anciano , Venodisección , Humanos , Hidroxiurea/uso terapéutico , Policitemia/sangre , Policitemia Vera/sangre , Policitemia Vera/complicaciones , Policitemia Vera/terapia , Mielofibrosis Primaria/etiología , Trombocitemia Esencial/sangreRESUMEN
Between January 15 and April 30, 1988, one thousand assays of serum vitamin B12 and folates were performed, and the reasons why they were requested as well as their clinical usefulness are discussed. In 50 cases these assays were requested for a suspected myeloproliferative syndrome; in some of the patients with polycythaemia vera an excess of B12 was observed without hyperleukocytosis, an argument for keeping the B12 assay as an element of initial evaluation. In numerous cases the assays were performed for aetiological evaluation of a macrocytosis of suspected alcoholic origin in most patients; more than 50 per cent of the patient had folate deficiency and only a few had low B12 values. Folate levels were frequently low and B12 levels generally normal in patients with gastrointestinal disease, but many of them had been supplemented with folate and/or B12 prior to the assay. More than 20 per cent of the 1,000 assays were performed in patients aged 80 years or more, and more than 50 per cent of them had a low folate level; this has no consequences for individual subjects, but it may be of epidemiological or sociological interest. It must be mentioned that too many blood samples (more than 40 per cent) were sent to the laboratory without adequate information and after supplementation in 20 per cent of the cases. Very few patients with very low B12 levels were subjected to Schilling's test, so that the clinical usefulness of this assay, as currently utilized, is questionable in a large number of cases.