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1.
J Med Virol ; 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34411312

RESUMO

This study aimed to determine the frequency of SARS-CoV-2 RNA in serum and its association with the clinical severity of COVID-19. This retrospective cohort study performed at Toyama University Hospital included consecutive patients with confirmed COVID-19. The prevalence of SARS-CoV-2 RNAemia and the strength of its association with clinical severity variables were examined. Fifty-six patients were included in this study. RNAemia was detected in 19.6% (11/56) patients on admission, and subsequently in 1.0% (1/25), 50.0% (6/12), and 100.0% (4/4) moderate, severe, and critically ill patients, respectively. Patients with RNAemia required more frequent oxygen supplementation (90.0% vs. 13.3%), ICU admission (81.8% vs. 6.7%), and invasive mechanical ventilation (27.3% vs. 0.0%). Among patients with RNAemia, the median viral loads of nasopharyngeal (NP) swabs that were collected around the same time as the serum sample were significantly higher in critically ill (5.4 log10 copies/µl; interquartile range [IQR]: 4.2-6.3) than in moderate-severe cases (2.6 log10 copies/µl; [IQR: 1.1-4.5]; p = 0.030) and were significantly higher in nonsurvivors (6.2 log10 copies/µl [IQR: 6.0-6.5]) than in survivors (3.9 log10 copies/µl [IQR: 1.6-4.6]; p = 0.045). This study demonstrated a relatively high proportion of SARS-CoV-2 RNAemia and an association between RNAemia and clinical severity. Moreover, among the patients with RNAemia, the viral loads of NP swabs were correlated with disease severity and mortality, suggesting the potential utility of combining serum testing with NP tests as a prognostic indicator for COVID-19, with higher quality than each separate test.

2.
Sci Rep ; 11(1): 16535, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34400739

RESUMO

Adaptive immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics remain largely unknown. The neutralizing antibody (NAb) levels in patients with coronavirus disease 2019 (COVID-19) are helpful for understanding the pathology. Using SARS-CoV-2 pseudotyped virus, serum sample neutralization values in symptomatic COVID-19 patients were measured using the chemiluminescence reduction neutralization test (CRNT). At least two sequential serum samples collected during hospitalization were analyzed to assess NAbs neutralizing activity dynamics at different time points. Of the 11 patients, four (36.4%), six (54.5%), and one (9.1%) had moderate, severe, and critical disease, respectively. Fifty percent neutralization (N50%-CRNT) was observed upon admission in 90.9% (10/11); all patients acquired neutralizing activity 2-12 days after onset. In patients with moderate disease, neutralization was observed at earliest within two days after symptom onset. In patients with severe-to-critical disease, neutralization activity increased, plateauing 9-16 days after onset. Neutralization activity on admission was significantly higher in patients with moderate disease than in patients with severe-to-critical disease (relative % of infectivity, 6.4% vs. 41.1%; P = .011). Neutralization activity on admission inversely correlated with disease severity. The rapid NAb response may play a crucial role in preventing the progression of COVID-19.


Assuntos
Imunidade Adaptativa , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/diagnóstico , SARS-CoV-2/imunologia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/imunologia , COVID-19/sangue , COVID-19/imunologia , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19 , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Neutralização/estatística & dados numéricos , Estudos Retrospectivos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Fatores de Tempo
3.
J Infect Chemother ; 27(7): 1122-1125, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33853730

RESUMO

This study aimed to assess the nasopharyngeal viral load at discharge or time of discontinued isolation in coronavirus 2019 (COVID-19) patients admitted to our hospital and discharged under the current symptom-based criteria in Japan. Patients diagnosed with COVID-19 by reverse transcription polymerase chain reaction and hospitalized at Toyama University Hospital were included in the analysis. Nasopharyngeal viral load was measured when symptom-based criteria for discharge or end of isolation in the accommodations were met, and examined the relationship between viral load and days after onset or age. From the perspective of virus isolation limit, the amount of infectious viral load was defined at 50 copies/µL by nasopharyngeal sample. Thirty-three patients with laboratory-confirmed COVID-19 were included in the analysis, after excluding critical and fatal cases. Mean nasopharyngeal viral load at discharge or end of isolation was 1.90 log-copies/µL, and 64% of patients were discharged with over 50 copies/µL. No correlation was apparent between age and viral load at discharge, and viral load remained relatively high at discharge or end of isolation in all age groups. Although attempts at infectious virus isolation are necessary, infection control precautions even after discharge or discontinued isolation in accommodations may be needed, as the date of onset mostly depended on self-reporting by patients.


Assuntos
COVID-19 , Alta do Paciente , Humanos , Japão , SARS-CoV-2 , Carga Viral
4.
Int J Infect Dis ; 106: 33-35, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33746092

RESUMO

As of October 2020, there is still no specific drug to treat COVID-19 as it rages worldwide. Favipiravir, indicated for the treatment of new and re-emerging influenza infections, has been suggested to be effective against SARS-CoV-2, although this is not yet fully validated. We administered favipiravir to a 64-year-old female patient with COVID-19. Her symptoms resolved quickly after the start of treatment, with reduction of SARS-CoV-2 viral load, but she developed a fever again on day 12. Since the fever was relieved by discontinuation of favipiravir, and based on positive results with a drug-induced lymphocyte stimulation test, we diagnosed her with favipiravir-induced drug fever. A decrease in the serum concentration of favipiravir was observed along with resolution of the fever. The present case suggests that drug fever should be considered in the differential diagnosis of relapsing fever episodes in COVID-19 patients receiving favipiravir.


Assuntos
Amidas/efeitos adversos , COVID-19/tratamento farmacológico , COVID-19/imunologia , Febre/induzido quimicamente , Ativação Linfocitária/efeitos dos fármacos , Pirazinas/efeitos adversos , Amidas/farmacologia , Amidas/uso terapêutico , COVID-19/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Pirazinas/farmacologia , Pirazinas/uso terapêutico , Carga Viral/efeitos dos fármacos
5.
J Infect Chemother ; 27(7): 1119-1121, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33781692

RESUMO

INTRODUCTION: The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) is the standard method for the diagnosis of coronavirus disease 2019 (COVID-19). This PCR test can be positive even in patients who have recovered from the disease, and the duration for achieving viral clearance has not been clarified yet. METHODS: This study was conducted between April 3, 2020, and June 17, 2020, at the Toyama University Hospital and the Toyama Rehabilitation Home. We collected the data of patients with COVID-19, analyzing the duration until twice-consecutive negative qRT-PCR test. RESULTS: A total of 42 patients were enrolled. The median duration of the twice-consecutive negative qRT-PCR test was 29.0 d (interquartile range: 25.75-35.25). The longest duration of viral shedding was 73 d. The duration of viral clearance was significantly longer in the older (>65 years) group than in the younger group (34.5 d vs. 25.0 d, P < 0.0001). CONCLUSION: This study demonstrated that viral clearance tends to be sustained in the older adults.


Assuntos
COVID-19 , SARS-CoV-2 , Idoso , Humanos , Pessoa de Meia-Idade , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Eliminação de Partículas Virais
6.
Virol J ; 18(1): 16, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33435994

RESUMO

BACKGROUND: SARS-CoV-2 is a novel coronavirus that emerged in 2019 and is now classified in the genus Coronavirus with closely related SARS-CoV. SARS-CoV-2 is highly pathogenic in humans and is classified as a biosafety level (BSL)-3 pathogen, which makes manipulating it relatively difficult due to its infectious nature. METHODS: To circumvent the need for BSL-3 laboratories, an alternative assay was developed that avoids live virus and instead uses a recombinant VSV expressing luciferase and possesses the full length or truncated spike proteins of SARS-CoV-2. Furthermore, to measure SARS-CoV-2 neutralizing antibodies under BSL2 conditions, a chemiluminescence reduction neutralization test (CRNT) for SARS-CoV-2 was developed. The neutralization values of the serum samples collected from hospitalized patients with COVID-19 or SARS-CoV-2 PCR-negative donors against the pseudotyped virus infection evaluated by the CRNT were compared with antibody titers determined from an enzyme-linked immunosorbent assay (ELISA) or an immunofluorescence assay (IFA). RESULTS: The CRNT, which used whole blood collected from hospitalized patients with COVID-19, was also examined. As a result, the inhibition of pseudotyped virus infection was specifically observed in both serum and whole blood and was also correlated with the results of the IFA. CONCLUSIONS: In conclusion, the CRNT for COVID-19 is a convenient assay system that can be performed in a BSL-2 laboratory with high specificity and sensitivity for evaluating the occurrence of neutralizing antibodies against SARS-CoV-2.


Assuntos
Anticorpos Neutralizantes/sangue , Teste Sorológico para COVID-19/métodos , COVID-19/sangue , Testes de Neutralização/métodos , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vírus da Estomatite Vesicular Indiana/genética , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Linhagem Celular , Convalescença , Humanos , Concentração Inibidora 50 , Luminescência , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética
7.
PLoS One ; 15(12): e0243597, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33296437

RESUMO

OBJECTIVE: To investigate the relationship between viral load and secondary transmission in novel coronavirus disease 2019 (COVID-19). METHODS: Epidemiological and clinical data were obtained from immunocompetent laboratory-confirmed patients with COVID-19 who were admitted to and/or from whom viral loads were measured at Toyama University Hospital. Using a case-control approach, index patients who transmitted the disease to at least one other patient were analysed as "cases" (index patients) compared with patients who were not the cause of secondary transmission (non-index patients, analysed as "controls"). The viral load time courses were assessed between the index and non-index symptomatic patients using non-linear regression employing a standard one-phase decay model. RESULTS: In total, 28 patients were included in the analysis. Median viral load at the initial sample collection was significantly higher in symptomatic than in asymptomatic patients and in adults than in children. Among symptomatic patients (n = 18), non-linear regression models showed that the estimated viral load at onset was higher in the index than in the non-index patients (median [95% confidence interval]: 6.6 [5.2-8.2] vs. 3.1 [1.5-4.8] log copies/µL, respectively). In adult (symptomatic and asymptomatic) patients (n = 21), median viral load at the initial sample collection was significantly higher in the index than in the non-index patients (p = 0.015, 3.3 vs. 1.8 log copies/µL, respectively). CONCLUSIONS: High nasopharyngeal viral loads around onset may contribute to secondary transmission of COVID-19. Viral load may help provide a better understanding of why transmission is observed in some instances, but not in others, especially among household contacts.


Assuntos
COVID-19 , Modelos Biológicos , Nasofaringe , SARS-CoV-2/metabolismo , Carga Viral , Adolescente , Adulto , Idoso , COVID-19/metabolismo , COVID-19/transmissão , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Nasofaringe/metabolismo , Nasofaringe/virologia
8.
J Infect Chemother ; 26(12): 1324-1327, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32900659

RESUMO

Most patients with coronavirus disease 2019 (COVID-19) have just only mild symptoms, but about 5% are very severe. Although extracorporeal membranous oxygenation (ECMO) is sometimes used in critically patients with COVID-19, ECMO is only an adjunct, not the main treatment. If the patient's condition deteriorates and it is determined to be irreversible, it is necessary to decide to stop ECMO. A 54-year-old man was admitted on day 6 of onset with a chief complaint of high fever and cough. Computed tomography (CT) showed a ground glass opacity in both lungs, and reverse transcription-polymerase chain reaction (RT-PCR) diagnosed COVID-19. He was admitted to the hospital and started to receive oxygen and favipiravir. After that, his respiratory condition deteriorated, and he was intubated and ventilated on day 9 of onset, and ECMO was introduced on day 12. Two days after the introduction of ECMO, C-reactive protein (CRP) increased, chest X-p showed no improvement in pneumonia, and PaO2/FiO2 decreased again. As D-dimer rose and found a blood clot in the ECMO circuit, we had to decide whether to replace the circuit and continue with ECMO or stop ECMO. At this time, the viral load by RT-PCR was drastically reduced to about 1/1750. We decided to continue ECMO therapy and replaced the circuit. The patient's respiratory status subsequently improved and ECMO was stopped on day 21 of onset. In conclusion, viral load measurement by RT-PCR may be one of the indicators for promoting the treatment of severe COVID-19 patients.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Oxigenação por Membrana Extracorpórea/métodos , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Carga Viral/métodos , Amidas/uso terapêutico , Antivirais/uso terapêutico , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Tomada de Decisões , Hospitalização , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pirazinas/uso terapêutico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2 , Tomografia Computadorizada por Raios X , Resultado do Tratamento
9.
Biochem Biophys Res Commun ; 528(1): 21-27, 2020 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-32448506

RESUMO

Mutarotases catalyze the α-ß anomeric conversion of monosaccharide, and play a key role in utilizing sugar as enzymes involved in sugar metabolism have specificity for the α- or ß-anomer. In spite of the sequential similarity to l-rhamnose mutarotase protein superfamily (COG3254: RhaM), the ACAV_RS08160 gene in Acidovorax avenae ATCC 19860 (AaFucM) is located in a gene cluster related to non-phosphorylative l-fucose and l-galactose metabolism, and transcriptionally induced by these carbon sources; therefore, the physiological role remains unclear. Here, we report that AaFucM possesses mutarotation activity only toward l-fucose by saturation difference (SD) NMR experiments. Moreover, we determined the crystal structures of AaFucM in the apo form and in the l-fucose-bound form at resolutions of 2.21 and 1.75 Å, respectively. The overall structural folding was clearly similar to the RhaM members, differed from the known l-fucose mutarotase (COG4154: FucU), strongly indicating their convergent evolution. The structure-based mutational analyses suggest that Tyr18 is important for catalytic action, and that Gln87 and Trp99 are involved in the l-fucose-specific recognition.


Assuntos
Carboidratos Epimerases/química , Carboidratos Epimerases/metabolismo , Fucose/metabolismo , Calorimetria , Domínio Catalítico , Comamonadaceae/enzimologia , Cristalografia por Raios X , Análise Mutacional de DNA , Evolução Molecular , Fucose/química , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Fosforilação , Relação Estrutura-Atividade
10.
Int Heart J ; 58(5): 787-793, 2017 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-28966311

RESUMO

A large amount of norepinephrine (NE) released from cardiac sympathetic nerve terminals might accelerate myocardial ischemic injury. Nicorandil (NICO), KATP channel opener, could attenuate cardiac NE release from the sympathetic nerve terminals during ischemia. The present study aimed to investigate the effects of NICO-induced attenuation of cardiac NE release on myocardial ischemia-reperfusion (I/R) injury in rats, by comparison with the effect of cardiac sympathetic denervation on I/R injury.Cardiac interstitial NE (iNE) concentrations were determined using a microdialysis method. Rats were divided into 3 groups; control, NICO, and denervation groups. Cardiac sympathetic denervation was performed by painting 10% phenol on the left ventricular epicardium 7 days before producing ischemia. The left coronary artery was ligated for 30 minutes and then re-perfused for 120 minutes. NICO (50 µg/kg/minute) was infused intravenously starting 20 minutes before the coronary occlusion to the end of the ligation.The infarct size of the left ventricle was smaller in rats treated with NICO than in control rats (20.2 ± 3.0 versus 50.6 ± 14.7%, P < 0.01). Sympathetic denervation also reduced infarct size (28.5 ± 10.4 %, P < 0.01), which was not significantly different from that in the NICO group. At the end of 30-minute ischemia, iNE increased markedly in control rats (0.1 ± 0.1 to 20.6 ± 5.3 × 103 pg/mL), whereas the increase was completely inhibited in denervated rats. NICO markedly attenuated the increase (4.9 ± 3.0 × 103 pg/mL, P < 0.01) during ischemia.NICO-induced attenuation of neural NE release during ischemia might, at least in part, contribute to myocardial protection against I/R injury.


Assuntos
Ventrículos do Coração/inervação , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miocárdio/metabolismo , Nicorandil/farmacologia , Norepinefrina/antagonistas & inibidores , Fibras Simpáticas Pós-Ganglionares/metabolismo , Animais , Modelos Animais de Doenças , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Masculino , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Norepinefrina/metabolismo , Ratos , Ratos Wistar , Fibras Simpáticas Pós-Ganglionares/efeitos dos fármacos , Complexo Vitamínico B/farmacologia
11.
Heart Vessels ; 31(8): 1361-9, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26686369

RESUMO

Cardiac hypertrophy and fibrosis in heart failure with preserved ejection fraction are associated with a pro-inflammatory state and reduced NO bioavailability. Effects on myocardial structural and molecular alterations were compared between Waon therapy (WT; repeated dry sauna therapy) and statin in hypertensive rats. Seven-week-old Dahl salt-sensitive rats were assigned to 4 groups: low-salt (LS) diet, high-salt (HS) diet, HS diet with oral fluvastatin (FL; 10 mg/kg/day for 4 weeks) starting from the age of 9 weeks, and HS diet with WT treatment in a far-infrared dry sauna (39 °C for 15 min followed by 34 °C for 20 min once daily for 4 weeks). HS rats developed left ventricular (LV) hypertrophy with preserved LV systolic function. WT reduced LV wall thickness and myocyte cross-sectional area along with decreased levels of myocardial ANP and BNP mRNA expression compared with HS rats. Reduction in LV fibrosis and increase in capillary density in WT animals were accompanied by reductions in myocardial levels of TGF-ß1, MMP2, p22(phox) and gp91(phox) mRNA expression, and increases in myocardial levels of VEGF and HSP90 mRNA and phosphorylated eNOS protein. These effects were comparable between WT and FL animals. WT improves structural and molecular alterations in salt-induced hypertensive rats similarly to fluvastatin.


Assuntos
Ácidos Graxos Monoinsaturados/farmacologia , Temperatura Alta , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipertensão/terapia , Indóis/farmacologia , Miocárdio/patologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Capilares/efeitos dos fármacos , Modelos Animais de Doenças , Ecocardiografia , Fibrose , Fluvastatina , Proteínas de Choque Térmico HSP90/metabolismo , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertensão/induzido quimicamente , Óxido Nítrico Sintase Tipo III/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos Dahl , Sódio na Dieta , Fator A de Crescimento do Endotélio Vascular/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular
12.
Lancet Infect Dis ; 15(9): 1055-1065, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26145194

RESUMO

BACKGROUND: Appropriate initial antibiotics are essential for the treatment of infectious diseases. However, some patients with pneumonia might develop adverse outcomes, despite receiving appropriate initial antibiotics. We aimed to clarify the risk factors for 30-day mortality in patients who received appropriate initial antibiotics and to identify potential candidates who would benefit from adjunctive therapy. METHODS: From March 15, to Dec 22, 2010, we did a prospective, observational study at ten medical institutions in hospitalised patients (aged ≥20 years) with pneumonia. We did a multivariable logistic regression analysis to calculate odds ratios (ORs) and 95% CI to assess the risk factors for 30-day mortality. This study was registered with the University Medical Information Network in Japan, number UMIN000003306. FINDINGS: The 30-day mortality was 11% (61 of 579 patients) in the appropriate initial antibiotic treatment group and 17% (29 of 168) in the inappropriate initial antibiotic treatment group. Albumin concentration of less than 30 mg/L (adjusted OR 3·39, 95% CI 1·83-6·28), non-ambulatory status (3·34, 1·84-6·05), pH of less than 7·35 (3·13, 1·52-6·42), respiration rate of at least 30 breaths per min (2·33, 1·28-4·24), and blood urea nitrogen of at least 7·14 mmol/L (2·20, 1·13-4·30) were independent risk factors in patients given appropriate initial antibiotic treatment. The 30-day mortality was 1% (one of 126 patients), 1% (two of 168), 17% (23 of 137), 22% (20 of 89), and 44% (14 of 32) for patients with no, one, two, three, and four or five risk factors, respectively. INTERPRETATION: Patients with two or more risk factors were at a higher risk of death during the 30 days assessed than were individuals with no or one risk factor, despite appropriate initial antibiotic treatment. Therefore, adjunctive therapy might be important for improving outcomes in patients with two or more risk factors. FUNDING: Central Japan Lung Study Group.


Assuntos
Antibacterianos/uso terapêutico , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/mortalidade , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Nitrogênio da Ureia Sanguínea , Feminino , Humanos , Concentração de Íons de Hidrogênio , Prescrição Inadequada , Masculino , Estudos Prospectivos , Curva ROC , Taxa Respiratória , Fatores de Risco , Albumina Sérica/metabolismo , Caminhada
13.
Int Heart J ; 56(2): 203-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25740582

RESUMO

Waon therapy (WT), which in Japanese means soothing warmth, is a repeated sauna therapy that improves cardiac and vascular endothelial function in patients with chronic heart failure (CHF). We investigated whether WT could improve the quality of life (QOL) of CHF patients in addition to improving cardiac function and exercise capacity.A total of 49 CHF patients (69 ± 14 years old) were treated with a 60°C far infrared-ray dry sauna bath for 15 minutes and then kept in a bed covered with blankets for 30 minutes once a day for 3 weeks. At baseline and 3 weeks after starting WT, cardiac function, 6-minute walk distance (6MWD), flow mediated dilation (FMD) of the brachial artery, and SF36-QOL scores were determined.WT significantly improved left ventricular ejection fraction (LVEF), B-type natriuretic peptide (BNP), 6MWD, and FMD (3.6 ± 2.3 to 5.1 ± 2.8%, P < 0.01). Moreover, WT significantly improved not only the physical (PC) but also mental component (MC) of the QOL scores. WT-induced improvement of PC was negatively correlated with changes in BNP (r = -0.327, P < 0.05), but MC improvement was not related directly to changes in BNP, LVEF, or 6MWD. WT-induced changes in MC were not parallel to PC improvement.WT improved QOL as well as cardiac function and exercise capacity in patients with CHF. Mental QOL improved independently of WT-induced improvement of cardiac function and exercise capacity.


Assuntos
Endotélio Vascular/fisiopatologia , Tolerância ao Exercício/fisiologia , Insuficiência Cardíaca/terapia , Qualidade de Vida , Banho a Vapor , Vasodilatação/fisiologia , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Volume Sistólico/fisiologia
14.
Case Rep Oncol ; 7(2): 583-90, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-25298764

RESUMO

About 3% of all cancer patients suffer from carcinoma of unknown primary site (CUP). In spite of its rarity, we will encounter them. While CUPs manifest a wide variety of clinical presentations, they have often resulted in poor prognosis. Although platinum/taxane combination chemotherapy, e.g. carboplatin (CBDCA) + paclitaxel (PTX) is widely used for patients suffering from CUP, the response rate is only about 30-40% and the median overall survival (OS) is only 9 months, which means that improvement is needed. Among the new regimens, the combination of CBDCA, PTX, bevacizumab (BEV) and erlotinib is thought to be highly promising. Herein, we report a case with CUP treated with this regimen and his maintenance therapy. Our patient was a 75-year-old man who was admitted with a left neck lump. CT revealed systemic massive lymphadenopathy. In spite of various investigations for primary origin, he was diagnosed with CUP and treated with CBDCA + PTX + BEV + erlotinib (AUC 6 + 175 mg/m(2) + 15 mg/kg + 150 mg). Since the evaluation of the efficacy indicated partial response, maintenance chemotherapy (BEV and erlotinib) was performed. Chemotherapy was continued for 9 months until the patient was in a progressive disease state with meningeal dissemination. He died 12 months after the initiation of chemotherapy, which is a longer period than the previously reported OS. Of note, according to our case, CBDCA + PTX + BEV + erlotinib and its maintenance chemotherapy are feasible and well tolerated for CUP.

15.
Ann Thorac Cardiovasc Surg ; 20 Suppl: 602-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23575002

RESUMO

Primary tracheal tumors are uncommon, making up only 0.2% of all respiratory malignancies. Adenoid cystic carcinoma (ACC) is the most common tumor, accounting for about 30% of primary tracheal tumors. It is often difficult to manage these tumors surgically, due to its expansion and submucosal invasion, and furthermore, due to the patient's condition. Thus, it is essential to perform palliative treatment in order to maintain the airway through and to control the progress. Herein, we report a case of ACC treated by repeated bronchoscopic argon plasma coagulation (APC) as palliative therapy.A 71-year-old Japanese male was referred to our hospital's emergency department for dyspnea. Bronchoscopic examination revealed expanded intraluminal obstructive bronchial tumors from the left bronchus to right. The patient had undergone bronchoscopic APC treatment several times. The obstruction was improved, and no worsening was seen for 26 months. Repeated bronchoscopic APC as a palliative therapy is promising and useful therapy without heavy adverse reactions to control the tumor growth.


Assuntos
Coagulação com Plasma de Argônio/métodos , Broncoscopia/métodos , Carcinoma Adenoide Cístico/terapia , Cuidados Paliativos/métodos , Neoplasias da Traqueia/terapia , Idoso , Biópsia , Carcinoma Adenoide Cístico/patologia , Humanos , Masculino , Fatores de Tempo , Tomografia Computadorizada por Raios X , Neoplasias da Traqueia/patologia , Resultado do Tratamento
16.
Case Rep Oncol ; 7(3): 780-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25722669

RESUMO

Granulocyte colony-stimulating factor (G-CSF)-producing nonhematopoietic malignancies have been reported in various organs and are associated with a poor clinical outcome. Moreover, carcinoma of unknown primary site (CUP) is an uncommon malignancy that occurs in about 2-6% of cancer patients. CUP also has a poor prognosis due to its missing profile. Since both G-CSF-producing carcinoma and CUP are rare, G-CSF-producing CUP (GCSF-CUP) is considered to have an even poorer prognosis and is seldom encountered. Herein, we report the case of a GCSF-CUP patient. A 75-year-old man was admitted to our hospital complaining of cervical lymphadenopathy. Multiple bulky lymph nodes without a primary site were revealed by image analysis. His complete blood count showed leukocytosis, and his blood chemistry panel indicated highly elevated levels of G-CSF. Although the patient was treated with combination chemotherapy of carboplatin, paclitaxel, bevacizumab and erlotinib, he died of intestinal perforation due to tumor invasion 23 days after the start of the therapy. An autopsy confirmed that the tumor was positive for anti-G-CSF antibody, but the primary site was still not detected.

17.
Am J Respir Crit Care Med ; 188(8): 985-95, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-23855620

RESUMO

RATIONALE: Identification of patients with drug-resistant pathogens at initial diagnosis is essential for treatment of pneumonia. OBJECTIVES: To elucidate clinical features of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP), and to clarify risk factors for drug-resistant pathogens in patients with CAP and HCAP. METHODS: A prospective observational study was conducted in hospitalized patients with pneumonia at 10 institutions in Japan. Pathogens identified as not susceptible to ceftriaxone, ampicillin-sulbactam, macrolides, and respiratory fluoroquinolones were defined as CAP drug-resistant pathogens (CAP-DRPs). MEASUREMENTS AND MAIN RESULTS: In total, 1,413 patients (887 CAP and 526 HCAP) were analyzed. CAP-DRPs were more frequently found in patients with HCAP (26.6%) than in patients with CAP (8.6%). Independent risk factors for CAP-DRPs were almost identical in patients with CAP and HCAP. These included prior hospitalization (adjusted odds ratio [AOR], 2.06; 95% confidence interval [CI], 1.23-3.43), immunosuppression (AOR, 2.31; 95% CI, 1.05-5.11), previous antibiotic use (AOR, 2.45; 95% CI, 1.51-3.98), use of gastric acid-suppressive agents (AOR, 2.22; 95% CI, 1.39-3.57), tube feeding (AOR, 2.43; 95% CI, 1.18-5.00), and nonambulatory status (AOR, 2.45; 95% CI, 1.40-4.30) in the combined patients with CAP and HCAP. The area under the receiver operating characteristic curve for counting the number of risk factors was 0.79 (95% CI, 0.74-0.84). CONCLUSIONS: The clinical profile of HCAP was different from that of CAP. However, physicians can predict drug resistance in patients with either CAP or HCAP by taking account of the cumulative number of the risk factors. Clinical trial registered with https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000004001&language=E ; number UMIN000003306.


Assuntos
Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecção Hospitalar/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/etiologia , Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/etiologia , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana Múltipla , Nutrição Enteral/efeitos adversos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Imunossupressão/efeitos adversos , Japão , Masculino , Pneumonia Bacteriana/etiologia , Pneumonia Bacteriana/microbiologia , Estudos Prospectivos , Curva ROC , Fatores de Risco
18.
Respir Investig ; 51(2): 98-102, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23790738

RESUMO

Fulminant hepatic failure (FHF) is defined as a liver disease that causes encephalopathy within 8 weeks of onset in the absence of pre-existing liver disease. Although liver metastases are commonly found in cancer patients, FHF secondary to diffuse liver infiltration is rare. Here, we report the rare autopsy cases of patients with small cell lung carcinoma (SCLC) and secondary FHF. These patients presented with remarkable hepatomegaly and a near complete replacement of the liver parenchyma with metastatic tumor. Neoplastic involvement of the liver should be considered in the differential diagnosis of FHF.


Assuntos
Carcinoma de Células Pequenas/patologia , Hepatomegalia/etiologia , Falência Hepática Aguda/etiologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/patologia , Idoso , Autopsia , Humanos , Masculino , Pessoa de Meia-Idade
19.
Case Rep Oncol ; 5(3): 546-53, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23139670

RESUMO

Based on the AVAPERL trial (36th ESMO 2011), CBDCA + pemetrexed + bevacizumab and its maintenance chemotherapy with pemetrexed + bevacizumab is a new promising regimen for the treatment of advanced non-small-cell lung adenocarcinoma. Herein, we report the rare case of a patient with solitary breast metastasis from a lung adenocarcinoma, which was effectively treated using CBDCA + pemetrexed + bevacizumab and its maintenance chemotherapy. A 57-year-old female was admitted to the hospital due to pleural effusion and cardiac tamponade caused by a lung adenocarcinoma possessing a mutation of the epidermal growth factor receptor (EGFR) gene (deletion of exon 19). The patient was treated by first-line chemotherapy (gefitinib 250 mg/body/day) which resulted in complete response. After 12 months, carcinoembryonic antigen was gradually increasing and she complained of a right breast mass. With a core-needle biopsy, the breast tumor was pathologically diagnosed as recurrence and solitary metastasis of a lung adenocarcinoma. Further study of the second mutation of EGFR revealed a T790M mutation. The patient was treated by second-line chemotherapy [CBDCA + pemetrexed + bevacizumab (AUC 6 + 500 mg/m(2) + 15 mg/kg)] and its maintenance chemotherapy (pemetrexed + bevacizumab). The cases of patients with breast metastasis from other organs are very rare. Immunohistopathological analysis is very useful to diagnose whether the malignancy is primary or not. In the case of a breast tumor with present or previous malignancy, a metastatic breast tumor should be considered. Furthermore, the biopsy of the breast metastasis also revealed the second mutation of resistance to gefitinib, T790M. Of note, according to our case, CBDCA + pemetrexed + bevacizumab and its maintenance chemotherapy is feasible and well tolerated for breast metastasis from a lung adenocarcinoma which is resistant to gefitinib and possesses the T790M mutation in the EGFR gene.

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