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Human immunodeficiency virus (HIV)-associated anaplastic large cell lymphoma (ALCL) is not so common, and anaplastic lymphoma kinase protein (ALK)-negative ALCL is rare and has a low survival rate. We report a case of a 31-year-old Japanese man diagnosed with HIV-associated ALK-negative ALCL who presented with long-lasting fever of unknown origin. The diagnosis was based on a full work-up that included inguinal lymph-node biopsy. Eight-cycle chemotherapy that included cyclophosphamide, doxorubicin, vincristine, and prednisone in addition to antiretroviral therapy for HIV infection provided a complete remission of his ALCL and over 5-year survival for him.
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BACKGROUND & AIMS: Early menopause in women with chronic hepatitis C virus (HCV) infection is associated with a low likelihood of a sustained virological response (SVR) in conjunction with their antiviral treatment. This is potentially related to their reduced estrogen secretion. The study was done to determine whether selective estrogen receptor modulator administration might improve the efficacy of the current standard of care (SOC) treatment, pegylated interferon (PegIFN) α2a plus ribavirin (RBV), for postmenopausal women. METHODS: One hundred and twenty-three postmenopausal women with genotype 1b chronic hepatitis C were randomly assigned to one of two treatment groups: raloxifene hydrochloride (RLX) (60 mg/day) plus SOC (PegIFNα2a 180 µg/week and RBV 600-1,000 mg/day) (n=62) or SOC only (n=61). Genotyping was performed of the polymorphism in the interleukin-28B (IL28B) gene region (rs8099917) of DNA collected from each patient. RESULTS: One RLX-treated patient discontinued RLX because of a systemic rash following 2 weeks of treatment. Twenty-four weeks after treatment, the SVR rate was significantly higher for RLX plus SOC patients (61.3%) than for SOC only patients (34.4%) (p=0.0051). Further, the SVR rate was significantly higher for RLX plus SOC patients with IL28B TT (72.5%) than for SOC only patients with IL28B TT (39.2%) (p=0.0014), but no such relationship was observed in patients carrying the minor IL28B allele. CONCLUSIONS: RLX improved the efficacy of SOC in the treatment of postmenopausal women with chronic hepatitis C. RLX shows promise as an adjuvant to the standard antiviral treatment of such patients.
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Adyuvantes Farmacéuticos/uso terapéutico , Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Posmenopausia , Clorhidrato de Raloxifeno/uso terapéutico , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Anciano , Femenino , Genotipo , Hepatitis C Crónica/virología , Humanos , Interferón-alfa/uso terapéutico , Interferones , Interleucinas/genética , Persona de Mediana Edad , Polietilenglicoles/uso terapéutico , Estudios Prospectivos , ARN Viral/análisis , Proteínas Recombinantes/uso terapéutico , Ribavirina/uso terapéuticoAsunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Insuficiencia Suprarrenal/etiología , Síndrome Inflamatorio de Reconstitución Inmune/etiología , Neumonía por Pneumocystis/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Pneumocystis cariniiRESUMEN
BACKGROUND & AIMS: Recent studies have suggested that insulin resistance exerts a strong influence on chronic hepatitis C virus (HCV) infection. We analyzed pretreatment factors useful for predicting sustained virological response (SVR), especially interleukin (IL) 28B polymorphism and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). METHODS: This cohort study consisted of 328 chronic hepatitis C patients with HCV genotype 1 who were treated for 48 weeks with pegylated interferon (PegIFN) α-2b and ribavirin (RBV). Genotyping of the polymorphisms in the IL28B gene region (rs8099917) on chromosome 19 was performed on DNA collected from each patient. RESULTS: No significant difference in IL28B genotype distribution was found according to HOMA-IR. Multivariate analysis identified the IL28B TT genotype (OR=5.97, 95% CI 2.15-16.55, p=0.0006) and the baseline HOMA-IR (OR=0.65, 95% CI 0.48-0.87, p=0.0044) as significant, independent pretreatment predictors of SVR. Receiver operating characteristic analyses to determine the optimal threshold values of HOMA-IR for predicting SVR showed that the areas under the curve (AUC) were high for both IL28B TT (AUC=0.774, HOMA-IR cut-off value: 2.45) and IL28B TG/GG genotypes (AUC=0.772, HOMA-IR cut-off value: 1.55). CONCLUSIONS: For HCV genotype 1, both IL28B and baseline HOMA-IR are independent pretreatment predictors of SVR in patients treated with PegIFNα-2b and RBV. Insulin resistance undermines the advantages of IL28B polymorphism to obtain SVR.
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Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/genética , Resistencia a la Insulina , Interferón-alfa/uso terapéutico , Interleucinas/genética , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Anciano , Área Bajo la Curva , Estudios de Cohortes , Intervalos de Confianza , Femenino , Genotipo , Hepacivirus/genética , Homeostasis , Humanos , Interferón alfa-2 , Interferones , Masculino , Persona de Mediana Edad , Modelos Biológicos , Análisis Multivariante , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , Curva ROC , Proteínas Recombinantes/uso terapéutico , Resultado del TratamientoRESUMEN
Coinfection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) is common worldwide. The current guidelines for the treatment of HIV infection recommend that HIV patients coinfected with HBV receive antiretoroviral therapy (ART) with two nucleoside analogs against HBV. However, an increase in liver enzymes that is usually attributed to HBV immune reconstitution inflammatory syndrome (IRIS) sometimes occurs in HBV/HIV-coinfected patients after the commencement of ART. We report a case of HBV/HIV-coinfection in which the chronic hepatitis B was successfully treated using interferon (IFN) therapy followed by ART without the development of IRIS. A Japanese man in thirties was referred to our hospital because of an acute HIV infection two months after the diagnosis of an acute HBV infection, which had progressed to a chronic HBV infection. The laboratory test results were as follows:hepatitis B surface antigen (HBsAg) positive, hepatitis B e antigen (HBeAg) positive, HBV DNA level of 8.8 Log copies/mL, HBV genotype A, alanine aminotransferase of 834 IU/L, HIV RNA level of 5 Log copies/mL, and a CD4+ T cell count of 437/microL. The initial treatment was natural IFNalpha therapy for chronic hepatitis B, and HBeAg seroclearance was achieved 20 weeks after the start of therapy. Four months after the end of IFN therapy for 24 weeks, ART including tenofovir and emtricitabine against HBV was commenced. Six months after starting ART, the patient's serum HBV DNA level had decreased and become undetectable and HBsAg seroclearance was achieved without an elevation in liver enzymes. The present case suggests that IFN therapy prior to ART contributes to a successful outcome for chronic hepatitis B patients coinfected with HIV, if the HIV status does not require the immediate start of ART.
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Coinfección , Infecciones por VIH/complicaciones , Infecciones por VIH/terapia , Antígenos de la Hepatitis B/análisis , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/terapia , Adulto , Antirretrovirales/uso terapéutico , Humanos , Interferones/uso terapéutico , MasculinoRESUMEN
AIM: To evaluate the association between liver stiffness measured by transient elastography (FibroScan) and the efficacy of long-term nucleoside analog (NA) treatment for patients with chronic hepatitis B. METHODS: Study 1: Forty-four chronic HBV patients had liver stiffness measured by FibroScan and underwent liver biopsy. Study 2: Group A: 22 patients started NA treatment at entry and FibroScan was done annually for 3 years. Group B: 23 patients started NA treatment prior to pretreatment FibroScan measurement, and FibroScan was done for from 3 to 5 years after the start of NA treatment. RESULTS: Study 1: The FibroScan values were significantly correlated with fibrosis stage (r = 0.672, P < 0.0001). Optimal cutoff of FibroScan values were 6.1 kPa for ≥ F1, 6.3 kPa for ≥ F2, 8.9 kPa for ≥ F3 and 12.0 kPa for F4. Study 2: For Group A, the baseline median FibroScan value was 8.2 kPa. FibroScan values significantly decreased annually for 3 years after the start of NA treatment (6.4 kPa, 5.8 kPa and 5.3 kPa at years 1, 2 and 3, respectively). For Group B, the FibroScan values did not significantly improve over the 3 years after the start of NA treatment. CONCLUSIONS: Liver stiffness, measured by transient elastography, of chronic hepatitis B patients treated with NA showed a rapid decline in the first 3 years followed by a more steady transition for from 3 to 5 years irrespective of long term virological effect.
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AIM: To analyze the association between the emergence of tyrosine-methionine-asparatate-asparatate (YMDD) mutants (reverse transcription; rtM204I/V) and deterioration of liver function during long-term lamivudine treatment of Japanese patients with chronic hepatitis B virus (HBV) infection. METHODS: The data of 61 consecutive Japanese patients with chronic hepatitis B who underwent continuous lamivudine treatment for more than 24 mo and had a virological response were analyzed. Analysis of YMDD mutants was done by real-time polymerase chain reaction with LightCycler probe hybridization assay for up to 90 mo (mean, 50.8 mo; range, 24-90 mo). RESULTS: A mixed mutant-type (YMDD + tyrosine-isoleucine-asparatate-asparatate: YIDD or tyrosine-valine-asparatate-asparatate: YVDD) or a mutant-type (YIDD or YVDD) were found in 57.4% of 61 patients at 1 year, 78.7% of 61 patients at 2 years, 79.6% of 49 patients at 3 years, 70.5% of 34 patients at 4 years, 68.4% of 19 patients at 5 years, 57.1% of 14 patients at 6 years, and 33.3% of 6 patients at 7 years. Of the 61 patients, 56 (92%) had mixed mutant- or a mutant-type. Only 5 (8%) had no mutants at each observation point. Virological breakthrough was found in 26 (46.4%) of 56 patients with YMDD mutants, 20 of whom had a hepatitis flare-up: the remaining 30 (53.6%) had neither a virological breakthrough nor a flare-up. All 20 patients who developed a hepatitis flare-up had a biochemical and virological response after adefovir was added to the lamivudine treatment. CONCLUSION: Our results suggest that it is possible to continue lamivudine treatment, even after the emergence of YMDD mutants, up to the time that the patients develop a hepatitis flare-up.
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Pueblo Asiatico/genética , Farmacorresistencia Viral/genética , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/genética , Lamivudine/uso terapéutico , Adulto , Anciano , ADN Viral/sangre , ADN Viral/genética , Progresión de la Enfermedad , Femenino , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B Crónica/fisiopatología , Humanos , Lamivudine/farmacología , Masculino , Persona de Mediana Edad , Mutación , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , TiempoRESUMEN
This study was done to evaluate the utility of the Abbott RealTime PCR assay (ART) for the monitoring of chronic hepatitis C patients. The serum samples of 183 patients infected with hepatitis C virus (HCV) genotype 1b who had completed a 48-week period of pegylated interferon (PEG-IFN) alpha-2b plus ribavirin treatment were prospectively analyzed. Serum HCV RNA levels were measured both by ART and by the Roche COBAS Amplicor Monitor test, version2.0 (CAM) at baseline and at weeks 4, 12, 24, 36, and 48 of treatment, and at 24 weeks after the end of treatment (EOT). A significant positive correlation of pretreatment HCV RNA levels was found between ART and CAM (r = 0.595, P < 0.0001). Of the 183 patients, 66 (36.0%) achieved a sustained virological response (SVR). The logarithmic decline of the HCV RNA level from the pretreatment level determined by ART in SVR patients was significantly higher than that in non-SVR patients at all time points tested. The logarithmic decline determined by CAM in SVR patients was significantly higher than that in non-SVR patients only at week 4, but there was no significant difference at other weeks. Of 124 patients who were HCV RNA-negative at EOT by ART, 58 (46.8%) had a relapse of viremia at 24 weeks after EOT, whereas 77 of 143 patients (53.8%) who were HCV RNA-negative at EOT by CAM had a relapse. The relapse rate was lower when determined by ART than by CAM, but not significantly so. ART is more useful than CAM for evaluating the virological response to antiviral treatment for chronic hepatitis C.
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Antivirales/uso terapéutico , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Anciano , Femenino , Hepatitis C Crónica/sangre , Humanos , Interferón alfa-2 , Interferón-alfa/uso terapéutico , Masculino , Persona de Mediana Edad , Polietilenglicoles/uso terapéutico , ARN Viral/sangre , Proteínas Recombinantes/uso terapéutico , Ribavirina/uso terapéutico , Estadísticas no Paramétricas , Resultado del Tratamiento , Carga Viral/efectos de los fármacos , Carga Viral/métodosRESUMEN
Kaposi's sarocoma (KS) is a well-known complication of the acquired immunodeficiency syndrome (AIDS). A 23-year-old man with AIDS complicated by multiple KS seen in January 2008 for anorexia and 10 kg weight loss had a CD4 cell count of 7/microL and a serum HIV RNA level of 29,000 copies/mL. Computed tomography (CT) and endoscopy showed multiple KS lesions in both lungs, the duodenum, small intestine, colon, liver, and both kidneys but not of the skin. Despite the administration of pegylated liposomal doxorubicin (PLD) and highly active antiretroviral therapy, he died in disease progression, unable to complete PLD, KS-related respiratory failure.
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Terapia Antirretroviral Altamente Activa , Neoplasias Duodenales/secundario , Humanos , Neoplasias Intestinales/secundario , Neoplasias Renales/secundario , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Masculino , Sarcoma de Kaposi/tratamiento farmacológico , Sarcoma de Kaposi/patología , Adulto JovenRESUMEN
BACKGROUND: An early virological response (EVR) after the start of interferon (IFN) treatment for chronic hepatitis C leads to a successful virological outcome. To analyze an association between sustained virological response (SVR) and EVR by comparing TaqMan with Amplicor assays in HCV genotype 1-infected patients treated with pegylated (PEG)-IFN alpha-2b plus ribavirin (RBV). METHODS: We retrospectively analyzed a total of 80 HCV genotype 1 patients (39 SVR and 41 non-SVR patients), who received an enough dosage and a complete 48-week treatment of PEG-IFN alpha-2b plus RBV. Serum HCV RNA levels were measured by both TaqMan and Amplicor assays for each patients at Weeks 2, 4, 8 and 12 after the start of the antiviral treatment. RESULTS: Of the 80 patients with undetectable HCV RNA by Amplicor, 17 (21.3%) patients were positive for HCV RNA by TaqMan at Weeks 12. The quantification results showed that no significant difference in the decline of HCV RNA level between TaqMan and Amplicor 10-fold method assays within the initial 12 weeks of the treatment was found. However, the qualitative analysis showed significant differences of the positive predictive rates for SVR were found between TaqMan (100% at weeks 4 and 100% at weeks 8) and Amplicor (80.0% and 69.6%, respectively). CONCLUSIONS: The COBAS TaqMan HCV assay is very useful for monitoring HCV viremia during antiviral treatment to predict a SVR in HCV genotype 1 patients.
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Antivirales/uso terapéutico , Hepacivirus/patogenicidad , Hepatitis C Crónica/virología , Interferón-alfa/uso terapéutico , Hígado/virología , Polietilenglicoles/uso terapéutico , ARN Viral/análisis , Ribavirina/uso terapéutico , Administración Oral , Antivirales/administración & dosificación , Biopsia , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/patología , Humanos , Inyecciones Subcutáneas , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Hígado/patología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Proteínas Recombinantes , Estudios Retrospectivos , Ribavirina/administración & dosificación , Resultado del Tratamiento , VirulenciaRESUMEN
Flow cytometry (FCM) using propidium iodide (PI)/bis-oxonol (BOX) staining can distinguish live, dead, and sublethally injured Escherichia coli by detecting intact vs. nonintact membranes (PI) and membrane potential (BOX). However, live bacteria, especially Mycobacterium tuberculosis, are not likely to be successfully discriminated from injured bacterium by FCM when utilizing the live/dead staining agents currently on the market. As injured cell membranes have integrity like that of live cells and are regarded as such by FCM, the distinction between live and injured cells has depended on the culture method, where injured bacteria cannot grow in general. We have previously shown that photoactivated ethidium monoazide (EMA) directly cleaves bacterial DNA both in vivo and in vitro. In this study, we found that the chromosomal DNA of antibiotic-injured, but not live, M. tuberculosis could be cleaved within 2 h by EMA, and that the resultant decrease in the spaces of DNA base pairs could greatly inhibit the intercalation of SYTO9 in FCM. The percentage value of SYTO9(+)/PI(-) quadrant from antibiotic-injured M. tuberculosis after EMA treatment decreased by at least 80%, compared with that before EMA, but such a phenomenon did not take place in live cells. FCM (SYTO9/PI) following EMA treatment is a very rapid, simple, and effective method for discriminating live, antibiotic-injured, and dead M. tuberculosis without culture.
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Antituberculosos/farmacología , Citometría de Flujo/métodos , Viabilidad Microbiana , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/fisiología , Azidas/metabolismo , Compuestos Orgánicos/metabolismo , Coloración y Etiquetado/métodosRESUMEN
Bacteria living in soil collected from a rice paddy in Fukuoka, Japan, were examined by electron microscopy using a freeze-substitution fixation method. Most of the observed bacteria could be categorized, based on the structure of the cell envelope and overall morphology, into one of five groups: (i) bacterial spore; (ii) Gram-positive type; (iii) Gram-negative type; (iv) Mycobacterium like; and (v) Archaea like. However, a few of the bacteria could not be readily categorized into one of these groups because they had unique cell wall structures, basically resembling those of Gram-negative bacteria, but with the layer corresponding to the peptidoglycan layer in Gram-negative bacteria being extremely thick, like that of the cortex of a bacterial spore. The characteristic morphological features found in many of these uncultured, soil-dwelling cells were the nucleoid being in a condensed state and the cytoplasm being shrunken. We were able to produce similar morphologies in vitro using a Salmonella sp. by culturing under low-temperature, low-nutrient conditions, similar to those found in some natural environments. These unusual morphologies are therefore hypothesized to be characteristic of bacteria in resting or dormant stages.
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Archaea/aislamiento & purificación , Archaea/ultraestructura , Bacterias/aislamiento & purificación , Bacterias/ultraestructura , Microbiología del Suelo , Pared Celular/ultraestructura , Citoplasma/ultraestructura , Japón , Microscopía Electrónica de Transmisión , Esporas Bacterianas/ultraestructuraRESUMEN
Ethidium monoazide (EMA) is a DNA cross-linking agent and eukaryotic topoisomerase II poison. We previously reported that the treatment of EMA with visible light irradiation (EMA + Light) directly cleaved chromosomal DNA of Escherichia coli (T. Soejima, K. Iida, T. Qin, H. Taniai, M. Seki, A. Takade, and S. Yoshida, Microbiol. Immunol. 51:763-775, 2007). Herein, we report that EMA + Light randomly cleaved chromosomal DNA of heat-treated, but not live, Listeria monocytogenes cells within 10 min of treatment. When PCR amplified DNA that was 894 bp in size, PCR final products from 10(8) heat-treated L. monocytogenes were completely suppressed by EMA + Light. When target DNA was short (113 bp), like the hly gene of L. monocytogenes, DNA amplification was not completely suppressed by EMA + Light only. Thus, we used DNA gyrase/topoisomerase IV and mammalian topoisomerase poisons (here abbreviated as T-poisons) together with EMA + Light. T-poisons could penetrate heat-treated, but not live, L. monocytogenes cells within 30 min to cleave chromosomal DNA by poisoning activity. The PCR product of the hly gene from 10(8) heat-treated L. monocytogenes cells was inhibited by a combination of EMA + Light and T-poisons (EMA + Light + T-poisons), but those from live bacteria were not suppressed. As a model for clinical application to bacteremia, we tried to discriminate live and antibiotic-treated L. monocytogenes cells present in human blood. EMA + Light + T-poisons completely suppressed the PCR product from 10(3) to 10(7) antibiotic-treated L. monocytogenes cells but could detect 10(2) live bacteria. Considering the prevention and control of food poisoning, this method was applied to discriminate live and heat-treated L. monocytogenes cells spiked into pasteurized milk. EMA + Light + T-poisons inhibited the PCR product from 10(3) to 10(7) heat-treated cells but could detect 10(1) live L. monocytogenes cells. Our method is useful in clinical as well as food hygiene tests.
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Recuento de Colonia Microbiana/métodos , Listeria monocytogenes/genética , Viabilidad Microbiana , Reacción en Cadena de la Polimerasa/métodos , Azidas/metabolismo , Toxinas Bacterianas/genética , Topoisomerasa de ADN IV/antagonistas & inhibidores , ADN Bacteriano/metabolismo , Inhibidores Enzimáticos/farmacología , Proteínas de Choque Térmico/genética , Proteínas Hemolisinas/genética , Calor , Humanos , Luz , ARN Ribosómico 23S/genética , Sensibilidad y Especificidad , Inhibidores de Topoisomerasa IIRESUMEN
Streptococcus pneumoniae was shown to possess lactate oxidase in addition to well-documented pyruvate oxidase. The activities of both H(2)O(2)-forming oxidases in wild-type cultures were detectable even in the early exponential phase of growth and attained the highest levels in the early stationary phase. For each of these oxidases, a defective mutant was constructed and compared to the parent regarding the dynamics of pyruvate and lactate in aerobic cultures. The results obtained indicated that the energy-yielding metabolism in the wild type could be best described by the following scheme. (i) As long as glucose is available, approximately one-fourth of the pyruvate formed is converted to acetate by the sequential action of pyruvate oxidase and acetate kinase with acquisition of additional ATP; (ii) the rest of the pyruvate is reduced by lactate dehydrogenase to form lactate, with partial achievement of redox balance; (iii) the lactate is oxidized by lactate oxidase back to pyruvate, which is converted to acetate as described above; and (iv) the sequential reactions mentioned above continue to occur as long as lactate is present. As predicted by this model, exogenously added lactate was shown to increase the final growth yield in the presence of both oxidases.
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Metabolismo Energético , Lactatos/metabolismo , Oxigenasas de Función Mixta/metabolismo , Piruvato Oxidasa/metabolismo , Streptococcus pneumoniae/fisiología , Aerobiosis , Regulación Bacteriana de la Expresión Génica , Consumo de Oxígeno , Piruvato Oxidasa/genética , Streptococcus pneumoniae/enzimología , Streptococcus pneumoniae/genéticaRESUMEN
Streptococcal toxic shock syndrome (STSS) is the severest form of human infections caused by Streptococcus pyogenes. In our animal model of STSS [Saito M, Kajiwara H, Ishikawa T, et al. Delayed onset of systemic bacterial dissemination and subsequent death in mice injected intramuscularly with Streptococcus pyogenes. Microbiol Immunol 2001;45:777-86], mice inoculated intramuscularly with S. pyogenes strains initially suffer from a short illness, then recover and remain healthy for about 20 days, and finally become sick and incur a sudden death. Here we report that the death during the convalescent period was facilitated by artificially bruising an extremity remote from the site of the initial inoculation. Bacterial burden was found to be higher in the bruised site than in a non-bruised control extremity of each mouse examined. Bacteremia started to occur approximately 20 days after infection. These findings imply that a fresh bruise serves as a focus for bacterial multiplication in the presence of bacteremia, thereby facilitating the development of STSS.
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Contusiones/complicaciones , Modelos Animales de Enfermedad , Choque Séptico/microbiología , Choque Séptico/fisiopatología , Infecciones Estreptocócicas/patología , Streptococcus pyogenes , Animales , Bacteriemia/microbiología , Bacteriemia/fisiopatología , Contusiones/patología , Muerte Súbita , Humanos , Pierna/microbiología , Pierna/patología , Masculino , Ratones , Infecciones Estreptocócicas/microbiologíaRESUMEN
Ethidium monoazide (EMA) is a DNA intercalating agent and a eukaryotic topoisomerase II poison. We found that EMA treatment and subsequent visible light irradiation (photoactivation or photolysis) shows a bactericidal effect, hence the mechanism was analyzed. When bacterial cells were treated with more than 10 microg/ml of EMA for 1 hr plus photoactivation for 20 min, cleavage of bacterial DNA was confirmed by agarose gel electrophoresis and electron microscopic studies. The cleavage of chromosomal DNA was seen when it was treated in vitro with EMA and photolysis, which showed that the cleavage directly took place without the assistance of DNA gyrase/topoisomerase IV and the DNA repair enzymes of bacteria. It was also verified, by using negatively supercoiled pBR322 DNA, that medium/high concentrations of EMA (1 to 100 microg/ml) led to breaks of double-stranded DNA and that low concentrations of EMA (10 to 100 ng/ml) generated a single-stranded break. EMA is known to easily penetrate dead but not live bacteria. After treatment of 10 microg/ml of EMA for 30 min and photoactivation for 5 min, EMA cleaved the DNA of dead but not live Klebsiella oxytoca. When the cleaved DNA was used for templates in PCR targeting 16S rDNA, PCR product from the dead bacteria was completely suppressed. We demonstrated that EMA and photolysis directly cleaved bacterial DNA and are effective tools for discriminating live from dead bacteria by PCR.
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Azidas/farmacología , ADN Bacteriano/efectos de los fármacos , Reacción en Cadena de la Polimerasa/métodos , Azidas/química , Azidas/efectos de la radiación , División del ADN , ADN Bacteriano/química , ADN Bacteriano/efectos de la radiación , ADN Superhelicoidal/química , ADN Superhelicoidal/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Escherichia coli/efectos de la radiación , Viabilidad Microbiana/genética , Microscopía Electrónica/métodos , Compuestos Orgánicos/química , FotólisisRESUMEN
A 25-year-old Japanese man was diagnosed with steroid-resistant Adult Still's Disease (ASD) in August 2000. No evidence of chronic myelogenous leukemia (CML) had been found during admissions in 2000 and 2001. In August 2002, he was diagnosed with CML with a peripheral white blood count of 69,940/microl and positivity for Philadelphia chromosome and BCR/ABL fusion gene on bone marrow aspiration. No case of CML was reported to develop from ASD. Because a diagnosis of ASD is based on the exclusion of other diseases, we must be cognizant of the possibility of the development of concurrent diseases.
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Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Enfermedad de Still del Adulto/complicaciones , Adulto , Ciclosporina/uso terapéutico , Resistencia a Medicamentos , Genes abl , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Masculino , Esteroides/uso terapéutico , Enfermedad de Still del Adulto/diagnóstico , Enfermedad de Still del Adulto/tratamiento farmacológico , Factores de TiempoRESUMEN
A 22-year-old man was admitted to our hospital with a high fever, fatigue, mild arthritis, and bilateral pleural effusions. Laboratory tests revealed a high ESR, leukocytosis, high serum C-reactive protein level, and high serum ferritin level. Various antibiotics had been given by a local hospital with no response. He was diagnosed as having severe refractory adult Still's disease and was subsequently treated with high-dose steroid therapy and low-dose cyclosporin A. The serum interleukin-18 level was monitored throughout treatment and was found to be a potentially useful marker of disease activity as well as of the response to cyclosporin A therapy.