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1.
J Acquir Immune Defic Syndr ; 96(1): 1-10, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38427920

RESUMEN

BACKGROUND: Non-AIDS-defining cancers (NADCs) in patients infected with HIV have recently attracted attention because of the improved survival of this patient population. To obtain accurate data, a longitudinal study is warranted for the nationwide surveillance of the current status and national trend of NADCs in patients infected with HIV in Japan. SETTING: An annual nationwide surveillance of NADCs in patients infected with HIV-1 in Japan from 1999 to 2021. METHODS: An annual questionnaire was sent to 378 HIV/AIDS referral hospitals across Japan to collect data (clusters of differentiation 4-positive lymphocytes, time of onset, outcomes, and antiretroviral therapy status) of patients diagnosed with any of the NADCs between 1999 and 2021. RESULTS: The response and case-capture rates for the questionnaires in 2021 were 37.8% and 81.2%, respectively. The number of reported NADC cases subsequently increased since the beginning of this study. Evaluation of the case counts of NADCs demonstrated a high incidence of lung, colorectal, gastric, and liver cancers as the top 4 cancers. Pancreatic cancer (0.63), lung cancer (0.49), and leukemia (0.49) had the highest mortality rates among the NADCs. Trends of NADCs regarding transmission routes were maintained over the years in male individuals who have sex with male individuals compared with heterosexual male individuals and female individuals. CONCLUSIONS: We demonstrated an increasing trend in the incidence of NADCs over a period of 23 years in Japan. The current data highlighted the importance of raising awareness regarding cancer management for patients infected with HIV in Japan.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Neoplasias Hepáticas , Neoplasias , Humanos , Masculino , Femenino , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Estudios Longitudinales , Japón/epidemiología , Factores de Riesgo , Neoplasias/complicaciones , Neoplasias/epidemiología , Neoplasias Hepáticas/epidemiología , Hospitales , Derivación y Consulta , Incidencia
2.
PLoS One ; 16(8): e0256452, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34411193

RESUMEN

OBJECTIVES: The accurate prevalence of acquired immunodeficiency syndrome (AIDS)-defining illnesses (ADIs) in human immunodeficiency virus (HIV)-infected patients has not been well investigated. Hence, a longitudinal nationwide surveillance study analyzing the current status and national trend of opportunistic complications in HIV-infected patients in Japan is warranted. METHODS: A nationwide surveillance of opportunistic complications in HIV-infected patients from 1995 to 2017 in Japan was conducted. An annual questionnaire was sent to 383 HIV/AIDS referral hospitals across Japan to collect information (CD4+ lymphocyte count, time of onset, outcome, and antiretroviral therapy [ART] status) of patients diagnosed with any of 23 ADIs between 1995 and 2017. RESULTS: The response and case capture rates of the questionnaires in 2017 were 53% and 76%, respectively. The number of reported cases of opportunistic complications peaked in 2011 and subsequently declined. Pneumocystis pneumonia (38.7%), cytomegalovirus infection (13.6%), and candidiasis (12.8%) were associated with the cumulative incidence of ADIs between 1995 and 2017. The mortality rate in HIV-infected patients with opportunistic complications substantially decreased to 3.6% in 2017. The mortality rate was significantly higher in HIV patients who received ART within 14 days of diagnosis of complications than in those who received ART 15 days after diagnosis (13.0% vs. 3.2%, p < 0.01). CONCLUSIONS: We have demonstrated a 23-year trend of a newly diagnosed AIDS status in Japan with high accuracy. The current data reveal the importance of Pneumocystis pneumonia as a first-onset illness and that early initiation of ART results in poor outcomes in HIV patients in Japan.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones Oportunistas Relacionadas con el SIDA , Adolescente , Adulto , Recuento de Linfocito CD4 , Humanos , Japón , Persona de Mediana Edad
3.
J Antimicrob Chemother ; 72(6): 1709-1713, 2017 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-28201509

RESUMEN

Objectives: T-2307, a novel arylamidine, exhibits potent broad-spectrum activities against the majority of fungal pathogens. In this study, the antifungal activity of T-2307 against Cryptococcus gattii was evaluated in comparison with those of amphotericin B, fluconazole and voriconazole in vitro and in vivo . Methods: The MICs for 15 clinical isolates were determined according to CLSI guidelines and time-kill studies were performed using C. gattii YF2784. In a murine model for intranasal pulmonary infection caused by C. gattii YF2784, the test compounds were administered once daily for 7 days from 2 h or 14 days post-infection. The viable counts in the lungs and brain were determined at 21 days post-infection. Results: The MIC range, MIC 50 , MIC 90 and geometric mean MIC of T-2307 were 0.0078-0.0625, 0.0313, 0.0625 and 0.0394 mg/L, respectively. The MIC of T-2307 was significantly lower than those of fluconazole, voriconazole and amphotericin B. T-2307 showed concentration-dependent fungicidal activity at 4 times the MIC or higher. Administration of T-2307 at 2 mg/kg/day, amphotericin B at 1 mg/kg/day and fluconazole at 160 mg/kg/day from 2 h post-infection significantly reduced viable counts in the lungs and brain. However, when the administration was started 14 days post-infection, only T-2307 significantly reduced the viable counts in both the lungs and the brain at 1 mg/kg/day. Conclusions: T-2307 shows excellent in vitro and in vivo antifungal activities against C. gattii and would be a promising new candidate for the treatment of cryptococcosis.


Asunto(s)
Amidinas/administración & dosificación , Amidinas/farmacología , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Criptococosis/tratamiento farmacológico , Cryptococcus gattii/efectos de los fármacos , Amidinas/efectos adversos , Amidinas/uso terapéutico , Anfotericina B/administración & dosificación , Anfotericina B/efectos adversos , Anfotericina B/farmacología , Anfotericina B/uso terapéutico , Animales , Antifúngicos/administración & dosificación , Antifúngicos/efectos adversos , Encéfalo/microbiología , Criptococosis/microbiología , Cryptococcus gattii/patogenicidad , Cryptococcus neoformans/efectos de los fármacos , Modelos Animales de Enfermedad , Descubrimiento de Drogas , Farmacorresistencia Fúngica , Fluconazol/farmacología , Fluconazol/uso terapéutico , Humanos , Pulmón/microbiología , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Enfermedades Pulmonares Fúngicas/microbiología , Ratones , Pruebas de Sensibilidad Microbiana , Voriconazol/farmacología , Voriconazol/uso terapéutico
5.
Antivir Ther ; 20(1): 11-9, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-24517996

RESUMEN

BACKGROUND: Pneumococcal pneumonia often occurs secondary to influenza infection and accounts for a large proportion of the morbidity and mortality associated with seasonal and pandemic influenza outbreaks. Peramivir is a novel, intravenous neuraminidase inhibitor that exhibits potent antiviral activity against influenza A and B viruses. We investigated the efficacy of peramivir for modulating the severity of secondary pneumococcal pneumonia. METHODS: CBA/JNCrlj mice, infected with influenza virus and superinfected with Streptococcus pneumoniae, were treated with either intravenous peramivir (single or multiple doses of 60 mg/kg/day) or oral oseltamivir at doses of 10 or 40 mg/kg/day in divided doses. The survival rate, viable bacterial count and virus titre in the lungs, as well as cytokine/chemokine concentration and histopathological findings were compared between both groups. RESULTS: The median duration of survival of coinfected mice was significantly prolonged by treatment with multiple doses of peramivir, relative to mice treated with oseltamivir at either dose. Viable bacterial counts and virus titres in the lungs were significantly reduced by intravenous peramivir treatment compared with no treatment or oral oseltamivir treatment. The production of inflammatory cytokines/chemokines was also significantly suppressed by multiple dosing of peramivir compared with oseltamivir. Increased survival appeared to be mediated by decreased inflammation, manifested as lower levels of inflammatory cells and proinflammatory cytokines in the lungs and less severe histopathological findings. The lungs of mice treated with multiple doses of peramivir showed mild inflammatory changes compared to oseltamivir. CONCLUSIONS: This study demonstrated that a multiple-dose regimen of intravenous peramivir was more efficacious than a single peramivir dose or multiple doses of oseltamivir for improving outcomes in pneumococcal pneumonia following influenza virus infection in mice.


Asunto(s)
Antivirales/farmacología , Ciclopentanos/farmacología , Guanidinas/farmacología , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Oseltamivir/farmacología , Neumonía Neumocócica/mortalidad , Ácidos Carbocíclicos , Administración Intravenosa , Administración Oral , Animales , Quimiocina CXCL2/biosíntesis , Quimiocina CXCL2/inmunología , Quimiocinas/biosíntesis , Quimiocinas/inmunología , Coinfección , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Interferón gamma/biosíntesis , Interferón gamma/inmunología , Interleucina-6/biosíntesis , Interleucina-6/inmunología , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/microbiología , Pulmón/virología , Masculino , Ratones , Ratones Endogámicos CBA , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/mortalidad , Infecciones por Orthomyxoviridae/virología , Neumonía Neumocócica/inmunología , Neumonía Neumocócica/microbiología , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/inmunología , Análisis de Supervivencia , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/inmunología
6.
Clin Vaccine Immunol ; 20(7): 977-85, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23637040

RESUMEN

Coinfection with bacteria is a major cause of mortality during influenza epidemics. Recently, Toll-like receptor (TLR) agonists were shown to have immunomodulatory functions. In the present study, we investigated the effectiveness and mechanisms of the new TLR4 agonistic monoclonal antibody UT12 against secondary pneumococcal pneumonia induced by coinfection with influenza virus in a mouse model. Mice were intranasally inoculated with Streptococcus pneumoniae 2 days after influenza virus inoculation. UT12 was intraperitoneally administered 2 h before each inoculation. Survival rates were significantly increased and body weight loss was significantly decreased by UT12 administration. Additionally, the production of inflammatory mediators was significantly suppressed by the administration of UT12. In a histopathological study, pneumonia in UT12-treated mice was very mild compared to that in control mice. UT12 increased antimicrobial defense through the acceleration of macrophage recruitment into the lower respiratory tract induced by c-Jun N-terminal kinase (JNK) and nuclear factor kappaB (NF-κB) pathway-dependent monocyte chemoattractant protein 1 (MCP-1) production. Collectively, these findings indicate that UT12 promoted pulmonary innate immunity and may reduce the severity of severe pneumonia induced by coinfection with influenza virus and S. pneumoniae. This immunomodulatory effect of UT12 improves the prognosis of secondary pneumococcal pneumonia and makes UT12 an attractive candidate for treating severe infectious diseases.


Asunto(s)
Anticuerpos Antibacterianos/inmunología , Coinfección/inmunología , Inmunidad Innata , Infecciones por Orthomyxoviridae/inmunología , Infecciones Neumocócicas/inmunología , Neumonía/inmunología , Receptor Toll-Like 4/agonistas , Animales , Peso Corporal , Coinfección/microbiología , Coinfección/patología , Coinfección/virología , Modelos Animales de Enfermedad , Histocitoquímica , Humanos , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos CBA , Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/patología , Infecciones Neumocócicas/patología , Neumonía/microbiología , Neumonía/patología , Neumonía/virología , Streptococcus pneumoniae/inmunología , Análisis de Supervivencia
7.
Kansenshogaku Zasshi ; 86(3): 295-9, 2012 May.
Artículo en Japonés | MEDLINE | ID: mdl-22746053

RESUMEN

A 73-year-old man was admitted to our hospital with a high fever and left paresis. A rapid diagnosis test was positive for influenza A was positive by rapid diagnosis test and diffusion-weighted MRI imaging of the brain showed a high intensity lesion of the right cerebral peduncle. The patient was therefore diagnosed as having influenza A virus infection complicated with lacunar infarction. In spite of initial treatment with oseltamivir and anticoagulant therapy, he lost consciousness eight hours after admission. The high intensity lesion of the cerebral peduncle enlarged and new lesions in the thalamus, hippocampus and calcarine cortex were detected with brain MRI. Additionally, an electroencephalographic study showed an entire slow wave and as the other causative pathogens of central nerve system infection were not detected, the likely diagnosis was influenza-associated encephalitis. We administered a high dose of intravenous immunoglobulin since the low-grade fever and mild unconscious state had continued in spite of the treatment with methylprednisolone pulse therapy. His consciousness was restored and body temperature became normal immediately. We could confirm the efficacy of our treatment by measurement of IL-6 levels in the serum and cerebrospinal fluid during the entire clinical course. In conclusion, a high dose of intravenous immunoglobulin therapy might be one of the effective treatments for influenza-associated encephalitis.


Asunto(s)
Encefalitis Viral/tratamiento farmacológico , Inmunoglobulinas Intravenosas/administración & dosificación , Gripe Humana/tratamiento farmacológico , Anciano , Humanos , Masculino
8.
Jpn J Infect Dis ; 64(6): 451-7, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22116322

RESUMEN

The mechanisms of severe pneumonia caused by co-infection of bacteria and influenza A virus (IAV) have not been fully elucidated. We examined apoptosis and inflammatory responses in a murine model for pneumococcal pneumonia during IAV infection. Inflammation, respiratory epithelium apoptosis, and inflammatory-cell infiltration increased in a time dependent manner in the lungs of mice co-infected with Streptococcus pneumoniae and IAV, in comparison with those infected with either S. pneumoniae or IAV. According to appearance of terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling positive cells, caspases-3 and -8 were activated 24 h after S. pneumoniae infection, and caspase-3 activation decreased after 48 h, whereas inflammatory cytokine levels continued to increase in co-infected mice. In contrast, in mice infected with either IAV or S. pneumoniae, apoptosis and activation of factors related to caspase-3 peaked at 48 h. Furthermore, Fas-associated death domain was significantly expressed in the lungs of co-infected mice 24 h after S. pneumoniae infection. These data suggest that early onset of apoptosis and its related factors play important roles in fulminant pneumonia resulting from bacterial pneumonia complicated by co-infection with influenza virus.


Asunto(s)
Apoptosis , Pulmón/patología , Infecciones por Orthomyxoviridae/complicaciones , Infecciones por Orthomyxoviridae/patología , Neumonía Neumocócica/complicaciones , Neumonía Neumocócica/patología , Animales , Caspasa 3/análisis , Caspasa 8/análisis , Coinfección/microbiología , Coinfección/patología , Coinfección/virología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Etiquetado Corte-Fin in Situ , Virus de la Influenza A/patogenicidad , Pulmón/microbiología , Pulmón/virología , Masculino , Ratones , Ratones Endogámicos CBA , Infecciones por Orthomyxoviridae/virología , Neumonía Neumocócica/microbiología , Streptococcus pneumoniae/patogenicidad
9.
Jpn J Infect Dis ; 64(2): 116-20, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21519124

RESUMEN

The Cica Fungi Test Candida is a novel immunoassay test that is used in Japan to detect Candida mannan antigens. A total of 130 samples from 89 cases in which the ß-D-glucan assay (MK method) was positive were collected between July 2007 and August 2008 at Nagasaki University Hospital, and the Cica Fungi Test Candida and Cand-Tec were performed. Diagnosis of candidemia was based on a positive culture for Candida spp. from blood or other sterile clinical specimens. A total of 19 samples from 16 cases with candidemia, and 111 samples from 73 cases without microbiological evidence of candidemia, were obtained. The sensitivity and specificity of the Cica Fungi Test and Cand-Tec were 63.2 and 95.5%, and 52.6 and 50.5%, respectively. The Cica Fungi Test showed significantly higher specificity than Cand-Tec (P<0.01). The ß-D-glucan assay values were significantly higher in the candidemia samples than in the non-candidemia samples (P=0.0003), a result that was well correlated with the Cica Fungi Test (P=0.0005). The Cica Fungi Test was thus found to be more reliable and specific than Cand-Tec, and the combined evaluation with the ß-D-glucan assay was more efficient for diagnosis of candidemia.


Asunto(s)
Antígenos Fúngicos/sangre , Candidemia/diagnóstico , Técnicas de Laboratorio Clínico/métodos , Mananos/sangre , Micología/métodos , Juego de Reactivos para Diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunoensayo/métodos , Lactante , Japón , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Adulto Joven
10.
J Infect Chemother ; 17(3): 363-9, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20931256

RESUMEN

Healthcare-associated pneumonia (HCAP) is a newly identified condition, and epidemiologic studies in Japan are still limited. We retrospectively observed patients with HCAP and community-acquired pneumonia (CAP) who were hospitalized between December 2004 and March 2005, and compared their disease characteristics. A total of 34 patients (14 with HCAP and 20 with CAP) were evaluated. Of the patients with HCAP, seven (50%) were hospitalized for at least 2 days in the preceding 90 days and five (35.7%) resided in a nursing home or extended care facility. Compared with patients with CAP, patients with HCAP were older, had more complications, including central nerve diseases, had greater disease severity, but lower serum albumin level. More methicillin-resistant Staphylococcus aureus, Pseudomonas spp., and anaerobes were isolated from patients with HCAP than from those with CAP. Conversely, more Streptococcus pneumoniae was detected and more penicillin was used in patients with CAP. This study provides additional evidence that HCAP should be distinguished from CAP and suggests the pathogenesis and therapeutic strategy for HCAP may be similar to those for hospital-acquired pneumonia.


Asunto(s)
Infecciones Comunitarias Adquiridas/complicaciones , Infección Hospitalaria/fisiopatología , Neumonía/fisiopatología , Anciano , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/fisiopatología , Infección Hospitalaria/microbiología , Femenino , Hospitales , Humanos , Japón , Masculino , Persona de Mediana Edad , Casas de Salud , Neumonía/microbiología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
12.
Jpn J Infect Dis ; 62(2): 133-6, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19305053

RESUMEN

Lemierre's syndrome is characterized by a primary oropharyngeal infection in a young healthy person who subsequently develops septic thrombophlebitis of the internal jugular vein and metastatic abscesses. We here report an uncommonly severe case of Lemierre's syndrome with acute respiratory distress syndrome (ARDS), in which polymyxin B-immobilized fiber (PMX) was used as supportive therapy. A 30-year-old, previously healthy man presented with sore throat, fever, rigor, and dyspnea. Chest computed tomography scan revealed multiple bilateral peripheral pulmonary nodules with small bilateral pleural effusions. The patient's condition rapidly deteriorated into ARDS after admission. Intubation followed by mechanical ventilation was required, and hemoperfusion with PMX was useful in alleviating the patient's condition. Isolation of Fusobacterium necrophorum from the blood culture and the contrast-enhanced scan revealed thrombosis and thrombophlebitis in the left internal jugular vein. The patient was diagnosed with Lemierre's syndrome, and an alternative treatment regimen with prolonged administration of ampicillin, clindamycin, and metronidazole resulted in improvement of the patient's respiratory function and general condition. Our case indicated that PMX might be an effective supportive therapy in severe cases of Lemierre's syndrome with ARDS that possessed no indication of surgical interventions.


Asunto(s)
Antibacterianos/uso terapéutico , Infecciones por Fusobacterium/terapia , Hemoperfusión , Venas Yugulares/patología , Polimixina B/uso terapéutico , Síndrome de Dificultad Respiratoria/terapia , Tromboflebitis/terapia , Adulto , Sangre/microbiología , Infecciones por Fusobacterium/complicaciones , Fusobacterium necrophorum/aislamiento & purificación , Humanos , Masculino , Radiografía Torácica , Tromboflebitis/complicaciones
13.
Intern Med ; 47(19): 1727-31, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18827425

RESUMEN

Nontuberculous mycobacterium infection is rarely accompanied by pleural involvement. We describe a very rare occurrence of Mycobacterium (M) avium pleuritis with pleural effusion in a non-compromised 73-year-old woman patient who had been treated for sick sinus syndrome. She was admitted to our hospital with general malaise and left pleural effusion. To establish a definitive diagnosis, a biopsy specimen was obtained from the left parietal pleura by video-assisted thoracoscopic surgery. The pleural biopsy specimen revealed only diffuse lymphoid cell infiltration and neoplastic or granulomatous lesions were absent. Culture of the pleural biopsy specimen revealed M. avium, indicating that the pleuritis was caused by this organism. A course of anti-tubercular agents (rifampin, ethambutol and streptomycin sulfate) and clarithromycin gradually resolved the pleural effusion.


Asunto(s)
Infección por Mycobacterium avium-intracellulare/diagnóstico , Pleuresia/diagnóstico , Anciano , Femenino , Humanos , Inmunocompetencia , Infección por Mycobacterium avium-intracellulare/inmunología , Infección por Mycobacterium avium-intracellulare/microbiología , Pleuresia/inmunología , Pleuresia/microbiología , Tomografía Computarizada por Rayos X
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