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1.
Scand J Rheumatol ; 51(6): 431-440, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34511031

RESUMO

OBJECTIVE: Currently, biological disease-modifying anti-rheumatic drugs (bDMARDs) with different modes of action [tumour necrosis factor inhibitor (TNFi), interleukin-6 receptor inhibitor (IL-6Ri), or cytotoxic T-lymphocyte antigen 4-immunoglobulin (CTLA4-Ig)] are used in clinical practice to treat rheumatoid arthritis (RA). However, it is unclear which type of bDMARD is the most efficacious for a specific clinical situation. C-reactive protein (CRP) is an acute-phase reactant driven by IL-6 signalling. Here, we aimed to establish whether therapeutic efficacy differs between IL-6Ri and other bDMARDs with alternative modes of action in RA patients according to their CRP level. METHOD: RA patients treated with bDMARDs were enrolled from an observational multicentre registry in Japan. Patients were classified into three groups according to baseline CRP tertiles. The overall 3 year retention rates of each bDMARD category were assessed. The Clinical Disease Activity Index (CDAI) was also assessed before and 3, 6, and 12 months after bDMARD initiation. RESULTS: A total of 1438 RA patients were included and classified into three groups according to tertiles of baseline CRP levels (CRP1, 0-0.3; CRP2, 0.3-1.8; CRP3, 1.8-18.4 mg/dL). In CRP3, the overall 3 year drug retention rates were significantly higher for IL-6Ri than for TNFi and CTLA4-Ig (77.5 vs 48.2 vs 67.3, respectively). No significant difference was evident in terms of CDAI 12 months after bDMARD initiation in CRP1-CRP3. CONCLUSION: IL-6Ri may be a favourable therapeutic option over TNFi and CTLA4-Ig in RA patients with high CRP levels.


Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Abatacepte/uso terapêutico , Estudos de Coortes , Artrite Reumatoide/tratamento farmacológico , Antirreumáticos/uso terapêutico , Inibidores do Fator de Necrose Tumoral , Anticorpos , Resultado do Tratamento
2.
Ann Oncol ; 31(2): 191-201, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31959336

RESUMO

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of early and locally-advanced non-small-cell lung cancer (NSCLC) was published in 2017, and covered the diagnosis, staging, management and treatment of both early stage I and II disease and locally-advanced stage III disease. At the ESMO Asia Meeting in November 2018, it was decided by both the ESMO and the Korean Society of Medical Oncology (KSMO) to convene a special face-to-face guidelines meeting in 2019 in Seoul. The aim was to adapt the ESMO 2017 guidelines to take into account potential differences related to ethnicity, cancer biology and standard practices associated with the treatment of locally-advanced, unresectable NSCLC in Asian patients. These guidelines represent the consensus opinions reached by those experts in the treatment of patients with lung cancer who represented the oncology societies of Korea (KSMO), China (CSCO), India (ISMPO), Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and it was independent of both local current treatment practices and the treatment availability and reimbursement situations in the individual participating Asian countries.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Ásia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , China , Humanos , Índia , Japão , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Malásia , Oncologia , República da Coreia , Taiwan
3.
Lett Appl Microbiol ; 71(6): 679-683, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32920889

RESUMO

Rhodococcus equi emerged as a zoonotic pathogen of human immunodeficiency virus-infected patients over the last three decades. Two virulence plasmid types of R. equi, pVAPA and pVAPB associated with equine and porcine isolates, have been recognized, and more recently, pVAPN, a novel host-associated virulence plasmid in R. equi, was found in bovine and caprine isolates. We reinvestigated 39 previously reported isolates of R. equi from patients with and without acquired immunodeficiency syndrome (AIDS) by detecting vapA, vapB and vapN using PCR and plasmid profiling. After excluding one isolate that could not be cultured from frozen storage, eight isolates carried a virulence plasmid encoding vapA (pVAPA), 10 carried a virulence plasmid encoding vapB (pVAPB), seven carried a virulence plasmid encoding vapN (pVAPN) and 13 were negative for those genes. Of the 29 isolates from patients with AIDS, 7, 10 and 5 harboured pVAPA, pVAPB and pVAPN respectively. Among nine isolates from patients without AIDS, one and two harboured pVAPA and pVAPN respectively. This study demonstrated that pVAPN-positive R. equi existed in human isolates before 1994 and reaffirmed that equine-associated pVAPA-positive, porcine-associated pVAPB-positive and bovine- or caprine-associated pVAPN-positive R. equi are widely spread globally. Because domestic animals might be major sources of human infection, further research is needed to reveal the prevalence of pVAPN-positive R. equi infection in cattle and goats.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Síndrome da Imunodeficiência Adquirida/complicações , Infecções por Actinomycetales/microbiologia , Rhodococcus equi/patogenicidade , Síndrome da Imunodeficiência Adquirida/virologia , Infecções por Actinomycetales/etiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , HIV/fisiologia , Humanos , Plasmídeos/genética , Plasmídeos/metabolismo , Reação em Cadeia da Polimerase , Rhodococcus equi/classificação , Rhodococcus equi/genética , Rhodococcus equi/metabolismo , Virulência
4.
Br J Anaesth ; 123(1): 51-59, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31084986

RESUMO

BACKGROUND: Macrophage phagocytosis constitutes an essential part of the host defence against microbes and the resolution of inflammation. Hyperglycaemia during sepsis is reported to reduce macrophage function, and thus, potentiate inflammatory deterioration. We investigated whether high-glucose concentrations augment lipopolysaccharide-induced reduction in macrophage phagocytosis via the endoplasmic stress-C/EBP homologous protein (CHOP) pathway using animal and laboratory investigations. METHODS: Peritoneal macrophages of artificially ventilated male Wistar rats, divided into four groups based on target blood glucose concentrations achieved by glucose administration with or without lipopolysaccharide, were obtained after 24 h. Human macrophages were also cultured in normal or high glucose with or without lipopolysaccharide exposure for 72 h. Changes in the phagocytic activity, intranuclear CHOP expression, and intracellular Akt phosphorylation status of macrophages were evaluated. These changes were also evaluated in human macrophages after genetic knock-down of CHOP by specific siRNA transfection or resolvin D2 treatment. RESULTS: Lipopolysaccharide impaired phagocytosis, increased intranuclear expression of CHOP, and inhibited Akt phosphorylation in both rat peritoneal and human macrophages. Hyperglycaemic glucose concentrations augmented these changes. Genetic knock-down of CHOP restored phagocytic ability and Akt phosphorylation in human macrophages. Furthermore, resolvin D2 co-incubation restored the inhibited phagocytosis and Akt phosphorylation along with the inhibition of intranuclear CHOP expression in human macrophages. CONCLUSIONS: These findings imply that controlling endoplasmic reticulum stress might provide new strategies for restoring reduced macrophage phagocytosis in sepsis-induced hyperglycaemia.


Assuntos
Hiperglicemia/metabolismo , Lipopolissacarídeos/metabolismo , Macrófagos/metabolismo , Fagocitose/fisiologia , Fator de Transcrição CHOP/metabolismo , Adulto , Animais , Células Cultivadas , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/genética , Humanos , Masculino , Ratos , Ratos Wistar , Transdução de Sinais , Fator de Transcrição CHOP/genética
6.
Br J Anaesth ; 119(6): 1118-1126, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29040496

RESUMO

Background: Anucleate platelets can undergo apoptosis in response to various stimuli, as do nucleated cells. Cardiopulmonary bypass (CPB) causes platelet dysfunction and can also activate platelet apoptotic pathways. We therefore evaluated time-dependent changes in blood platelet Bax (a pro-apoptotic molecule) levels and platelet dysfunction after cardiac surgery. Methods: We assessed blood samples obtained from subjects having on-pump or off-pump coronary artery bypass graft surgery ( n =20 each). We also evaluated the in vitro effects of platelet Bax increase in eight healthy volunteers. Results: Thrombin-induced platelet calcium mobilisation and platelet-surface glycoprotein Ib (GPIb) expression were lowest at weaning from CPB and did not recover on postoperative day one. On-pump surgery increased platelet expression of Bax, especially the oligomerised form, along with translocation of Bax from the cytosol to mitochondria and platelet-surface tumour necrosis factor-alpha (TNF-α)-converting enzyme (TACE) expression. In contrast, mitochondrial cytochrome c expression was reduced. While similar in direction, the magnitude of the observed changes was smaller in patients having off-pump surgery. In vitro , a cell-permeable Bax peptide increased platelet Bax expression to the same extent seen during bypass and produced similar platelet changes. These apoptotic-like changes were largely reversed by Bcl-xL pre-administration, and were completely reversed by combined application of inhibitors that stabilise outer mitochondrial membrane permeability and TACE. Conclusions: CPB increases platelet Bax expression, which contributes to reduced platelet-surface GPIb expression and thrombin-induced platelet calcium changes. These changes in platelet apoptotic signalling might contribute to platelet dysfunction after CPB. Clinical trial registration: UMIN Clinical Trials Registry (number UMIN000006033).


Assuntos
Plaquetas/patologia , Ponte Cardiopulmonar , Complicações Pós-Operatórias/sangue , Trombina/farmacologia , Proteína X Associada a bcl-2/sangue , Idoso , Idoso de 80 Anos ou mais , Apoptose , Western Blotting , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária , Agregação Plaquetária , Complicações Pós-Operatórias/patologia , Estudos Prospectivos , Proteína X Associada a bcl-2/genética
7.
Biochim Biophys Acta ; 1848(9): 1744-56, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25922225

RESUMO

Biological membranes are essential for normal function and regulation of cells, forming a physical barrier between extracellular and intracellular space and cellular compartments. These physical barriers are subject to mechanical stresses. As a consequence, nature has developed proteins that are able to transpose mechanical stimuli into meaningful intracellular signals. These proteins, termed Mechanosensitive (MS) proteins provide a variety of roles in response to these stimuli. In prokaryotes these proteins form transmembrane spanning channels that function as osmotically activated nanovalves to prevent cell lysis by hypoosmotic shock. In eukaryotes, the function of MS proteins is more diverse and includes physiological processes such as touch, pain and hearing. The transmembrane portion of these channels is influenced by the physical properties such as charge, shape, thickness and stiffness of the lipid bilayer surrounding it, as well as the bilayer pressure profile. In this review we provide an overview of the progress to date on advances in our understanding of the intimate biophysical and chemical interactions between the lipid bilayer and mechanosensitive membrane channels, focusing on current progress in both eukaryotic and prokaryotic systems. These advances are of importance due to the increasing evidence of the role the MS channels play in disease, such as xerocytosis, muscular dystrophy and cardiac hypertrophy. Moreover, insights gained from lipid-protein interactions of MS channels are likely relevant not only to this class of membrane proteins, but other bilayer embedded proteins as well. This article is part of a Special Issue entitled: Lipid-protein interactions.


Assuntos
Membrana Celular/metabolismo , Mecanotransdução Celular , Lipídeos de Membrana/metabolismo , Proteínas de Membrana/metabolismo , Animais , Membrana Celular/química , Humanos , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Lipídeos de Membrana/química , Proteínas de Membrana/química , Modelos Moleculares , Ligação Proteica , Estrutura Terciária de Proteína
8.
J Periodontal Res ; 51(6): 768-778, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26791469

RESUMO

BACKGROUND AND OBJECTIVE: A diagnosis of periodontitis progression is presently limited to clinical parameters such as attachment loss and radiographic imaging. The aim of this multicenter study was to monitor disease progression in patients with chronic periodontitis during a 24-mo follow-up program and to evaluate the amount of bacteria in saliva and corresponding IgG titers in serum for determining the diagnostic usefulness of each in indicating disease progression and stability. MATERIAL AND METHODS: A total of 163 patients with chronic periodontitis who received trimonthly follow-up care were observed for 24 mo. The clinical parameters and salivary content of Porphyromonas gingivalis, Prevotella intermedia and Aggregatibacter actinomycetemcomitans were assessed using the modified Invader PLUS assay, and the corresponding serum IgG titers were measured using ELISA. The changes through 24 mo were analyzed using cut-off values calculated for each factor. One-way ANOVA or Fisher's exact test was used to perform between-group comparison for the data collected. Diagnostic values were calculated using Fisher's exact test. RESULTS: Of the 124 individuals who completed the 24-mo monitoring phase, 62 exhibited periodontitis progression, whereas 62 demonstrated stable disease. Seven patients withdrew because of acute periodontal abscess. The ratio of P. gingivalis to total bacteria and the combination of P. gingivalis counts and IgG titers against P. gingivalis were significantly related to the progression of periodontitis. The combination of P. gingivalis ratio and P. gingivalis IgG titers was significantly associated with the progression of periodontitis (p = 0.001, sensitivity = 0.339, specificity = 0.790). CONCLUSIONS: It is suggested that the combination of P. gingivalis ratio in saliva and serum IgG titers against P. gingivalis may be associated with the progression of periodontitis.


Assuntos
Anticorpos Antibacterianos/sangue , Periodontite Crônica/patologia , Imunoglobulina G/sangue , Saliva/microbiologia , Aggregatibacter actinomycetemcomitans , Carga Bacteriana , Infecções por Bacteroidaceae/microbiologia , Infecções por Bacteroidaceae/patologia , Periodontite Crônica/sangue , Periodontite Crônica/metabolismo , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Pasteurellaceae/microbiologia , Infecções por Pasteurellaceae/patologia , Porphyromonas gingivalis , Prevotella intermedia , Estudos Prospectivos
10.
Pflugers Arch ; 467(1): 3-13, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24819593

RESUMO

The mechanosensitive channel of small conductance (MscS)-like channel superfamily is present in cell-walled organisms throughout all domains of life (Bacteria, Archaea and Eukarya). In bacteria, members of this channel family play an integral role in the protection of cells against acute downward shifts in environmental osmolarity. In this review, we discuss how evolutionary 'tinkering' has taken MscS-like channels from their currently accepted physiological function in bacterial osmoregulation to potential roles in processes as diverse as amino acid efflux, Ca(2+) regulation and cell division. We also illustrate how this structurally and functionally diverse family of channels represents an essential industrial component in the production of monosodium glutamate, an attractive antibiotic target and a rich source of membrane proteins for the studies of molecular evolution.


Assuntos
Bactérias/genética , Membrana Celular/genética , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Evolução Molecular , Canais Iônicos/química , Canais Iônicos/genética , Mecanotransdução Celular/genética , Sequência de Aminoácidos , Bactérias/química , Sequência de Bases , Membrana Celular/química , Membrana Celular/ultraestrutura , Proteínas de Escherichia coli/ultraestrutura , Variação Genética/genética , Ativação do Canal Iônico/genética , Canais Iônicos/ultraestrutura , Fluidez de Membrana/genética , Dados de Sequência Molecular , Estresse Mecânico , Relação Estrutura-Atividade
11.
Br J Anaesth ; 114(1): 91-102, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25303988

RESUMO

BACKGROUND: Thromboelastometric evaluation of coagulation might be useful for prediction and management of bleeding after paediatric cardiac surgery. We tested the hypothesis that the use of a thromboelastometry-guided algorithm for blood product management reduces blood loss and transfusion requirements. METHODS: We studied 78 patients undergoing paediatric cardiac surgery with cardiopulmonary bypass (CPB) for the initial 12 h after operation. Stepwise multiple linear regression was used to develop an algorithm to guide blood product transfusions. Thereafter, we randomly assigned 100 patients to conventional or algorithm-guided blood product management, and assessed bleeding and red cell transfusion requirements. RESULTS: CPB time, post-bypass rotational thromboelastometry (ROTEM(®)) EXTEM amplitude at 10 min (A10), and FIBTEM-A10 were independently associated with chest tube drainage volume during the initial 12 h after operation. Discriminative analysis determined cut-off values of 30 mm for EXTEM-A10 and 5 mm for FIBTEM-A10, and estimated optimal intraoperative fresh-frozen plasma and platelet concentrate transfusion volumes. Thromboelastometry-guided post-bypass blood product management significantly reduced postoperative bleeding (9 vs 16 ml kg(-1), P<0.001) and packed red cell transfusion requirement (11 vs 23 ml kg(-1), P=0.005) at 12 h after surgery, and duration of critical care stay (60 vs 71 h, P=0.014). CONCLUSIONS: Rotational thromboelastometry-guided early haemostatic intervention by rapid intraoperative correction of EXTEM-A10 and FIBTEM-A10 reduced blood loss and red cell transfusion requirements after CPB, and reduced critical care duration in paediatric cardiac surgical patients. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000006832 (December 4, 2011).


Assuntos
Procedimentos Cirúrgicos Cardíacos/estatística & dados numéricos , Transfusão de Eritrócitos/estatística & dados numéricos , Hemostáticos/uso terapêutico , Monitorização Intraoperatória/métodos , Hemorragia Pós-Operatória/prevenção & controle , Cirurgia Assistida por Computador/métodos , Tromboelastografia/métodos , Coagulação Sanguínea/fisiologia , Procedimentos Cirúrgicos Cardíacos/métodos , Ponte Cardiopulmonar/métodos , Pré-Escolar , Transfusão de Eritrócitos/métodos , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos
12.
Eur J Gynaecol Oncol ; 36(2): 192-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26050359

RESUMO

AIMS: For the screening of cervical abnormalities, human papillomavirus (HPV) DNA testing is widely used along with Papanicolaou (Pap) testing. Although the sensitivity of the HPV DNA testing is good, its specificity is relatively low. In the present study, the authors evaluated the use of the Gen-Probe APTIMA HPV Assay for the detection of HPV mRNA and compared it with HPV DNA testing. MATERIALS AND METHODS: Liquid cervical Pap specimens collected from 410 women were assessed using the APTIMA test, the Qiagen Hybrid Capture 2 HPV DNA (HC2) Test, and the AMPLICOR HPV Test. RESULTS: The sensitivity and specificity for the detection of high-risk HPV were 85.6% and 99.2% for the APTIMA test, 94.1% and 98.4% for the HC2 test, and 90.2% and 95.7% for the AMPLICOR test, respectively. As the severity of the cervical lesion progressed, the positive rate of the three tests indicated a similar increase. The clinical sensitivity and specificity for the detection of squamous intraepithelial lesion (SIL) were 91.2% and 84.2% for the APTIMA test, 94.5% and 80.4% for the HC2 test, and 87.9% and 78.2% for the AMPLICOR test, respectively. CONCLUSION: The APTIMA is sensitive and specific for the detection of high-risk HPV. In the specimens with SIL, the APTIMA test is more specific than the HC2 and the AMPLICOR tests. This indicates that the APTIMA test may improve patient management and reduce the cost of screening.


Assuntos
Papillomaviridae/isolamento & purificação , RNA Mensageiro/análise , RNA Viral/análise , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/virologia , Adulto , Idoso , DNA Viral/análise , Feminino , Humanos , Pessoa de Meia-Idade , Teste de Papanicolaou , Papillomaviridae/genética , Neoplasias do Colo do Útero/diagnóstico , Displasia do Colo do Útero/diagnóstico
13.
Public Health Pract (Oxf) ; 7: 100471, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38328526

RESUMO

Background: Drastic changes such as school closures and stay-at-home measures due to the global COVID-19 pandemic, may have long-term negative effects on children's mental health; however, longitudinal studies after 2021 are limited. This study aimed to observe the long-term effects of the COVID-19 pandemic on children's mental health by exploring changes in their mental health over a period of 18 months. Study design: We conducted a longitudinal study at Chiba Prefecture in Japan, focusing on schoolchildren's mental health changes. Methods: Data were obtained from the Strengths and Difficulties Questionnaire (SDQ) questionnaire conducted at single primary school three times from October 2021 to March 2023 which and included 183 participants. This study adopted a linear-mixed model to evaluate changes in children's SDQ scores, with sex and grade as the independent variables, and participants as a random effect. Results: Regarding changes in SDQ scores, there were no significant changes in the total difficulty scores or in each subscale; Emotional Symptoms, Conduct Problems, Hyperactivity/Inattention, Peer Problems, and Prosocial Behavior. There was no statistically significant interaction between changes in SDQ scores and sex. Conclusions: This report indicates that the impact of the COVID-19 pandemic on the mental health of Japanese primary schoolchildren was negligible in the later phase of the pandemic. However, the impact may differ from country to country owing to factors such as social restrictions during the COVID-19 pandemic.

14.
J Viral Hepat ; 20(4): 281-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23490373

RESUMO

Genetic variation in the IL-28B (interleukin-28B; interferon lambda 3) region has been associated with sustained virological response (SVR) rates in patients with chronic hepatitis C treated with peginterferon-α and ribavirin. However, the mechanisms by which polymorphisms in the IL-28B gene region affect host antiviral responses are not well understood. Using the HCV 1b and 2a replicon system, we compared the effects of IFN-λs and IFN-α on HCV RNA replication. The anti-HCV effect of IFN-λ3 and IFN-α in combination was also assessed. Changes in gene expression induced by IFN-λ3 and IFN-α were compared using cDNA microarray analysis. IFN-λs at concentrations of 1 ng/mL or more exhibited concentration- and time-dependent HCV inhibition. In combination, IFN-λ3 and IFN-α had a synergistic anti-HCV effect; however, no synergistic enhancement was observed for interferon-stimulated response element (ISRE) activity or upregulation of interferon-stimulated genes (ISGs). With respect to the time course of ISG upregulation, the peak of IFN-λ3-induced gene expression occurred later and lasted longer than that induced by IFN-α. In addition, although the genes upregulated by IFN-α and IFN-λ3 were similar to microarray analysis, interferon-stimulated gene expression appeared early and was prolonged by combined administration of these two IFNs. In conclusion, IFN-α and IFN-λ3 in combination showed synergistic anti-HCV activity in vitro. Differences in time-dependent upregulation of these genes might contribute to the synergistic antiviral activity.


Assuntos
Antivirais/farmacologia , Produtos Biológicos/farmacologia , Hepacivirus/efeitos dos fármacos , Hepacivirus/fisiologia , Interferon-alfa/farmacologia , Interleucinas/farmacologia , Replicação Viral/efeitos dos fármacos , Linhagem Celular , Sinergismo Farmacológico , Perfilação da Expressão Gênica , Hepatócitos/imunologia , Hepatócitos/virologia , Humanos , Interferons , Análise em Microsséries
15.
Acta Neurol Scand ; 128(2): 100-6, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23398608

RESUMO

OBJECTIVE: It is difficult to stimulate leg motor areas with magnetic current using a figure-of-eight coil due to the deep anatomical location of the areas. However, a double cone coil is useful for stimulating deep brain regions. We postulated that the use of the same coil may allow repetitive transcranial magnetic stimulation (rTMS) to modulate the neural activity of the same areas. The purpose of this study is to investigate the effect of high-frequency rTMS applied over bilateral leg motor areas with a double cone coil on walking function after stroke. MATERIALS AND METHODS: Eighteen post-stroke hemiparetic patients with gait disturbances attended two experimental sessions with more than 24 h apart, in a cross-over, double-blind paradigm. In one session, high-frequency rTMS of 10 Hz was applied over the leg motor area bilaterally in a 10-s train using a double cone coil for 20 min (total 2,000 pulses). In the other session, sham stimulation was applied for 20 min at the same site. To assess walking function, walking velocity, and Physiological Cost Index (PCI) were evaluated serially before, immediately after, and 10 and 20 min after each stimulation. RESULTS: The walking velocity was significantly higher for 20 min after stimulation in the high-frequency rTMS group than the sham group. PCI was lower in the high-frequency rTMS group than the sham group, but this was significant only immediately after stimulation. CONCLUSIONS: High-frequency rTMS of bilateral leg motor areas using a double cone coil can potentially improve walking function in post-stroke hemiparetic patients.


Assuntos
Transtornos Neurológicos da Marcha/terapia , Estimulação Magnética Transcraniana/instrumentação , Estimulação Magnética Transcraniana/métodos , Adulto , Análise de Variância , Feminino , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Caminhada/fisiologia
16.
Am J Transplant ; 12(9): 2322-34, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22594431

RESUMO

The lymphotoxin system (LT) regulates interactions between lymphocytes and stromal cells to maintain lymphoid microenvironmental homeostasis. Soluble LT beta-receptor-Ig (LTßRIg) blocks lymphocyte LTα1ß2-stromal cell LTßR signaling. In a murine cardiac allograft model, LTbRIg treatment reversed the tolerance induced by anti-CD40L antibody leading to graft inflammation and fibrosis. LTßRIg treatment decreased PD-L1 expression by blood endothelial cells, and decreased VCAM-1 while increasing CXCL1, CXCL2, CXCL12, CCL5, CCL21 and IL-6 expression in fibroblastic reticular cells. In secondary lymphoid organs these effects caused T- and B cell zone disruption, loss of CD35(+) follicular dendritic cells and abnormal recruitment of CD11b(+) Ly6G(+) neutrophils. These disruptions correlated with increased numbers of CD8(+) T cells and CD11b(+) Ly6G(+) neutrophils, and decreased numbers of CD4(+) T cells and Foxp3(+) regulatory T cells in the grafts. Depleting neutrophils or blocking neutrophil-attracting chemokines restored normal histology in lymph node, spleen and grafts. Taken together, LTßRIg treatment altered stromal subset, particularly fibroblastic reticular cell, production of cytokines and chemokines, resulting in changes in neutrophil recruitment in spleen, lymph node and grafts, and inflammation and fibrosis associated with decreased Foxp3(+) regulatory T cells and increased CD8(+) T cell infiltration of grafts.


Assuntos
Fibrose/etiologia , Transplante de Coração , Inflamação/etiologia , Receptor beta de Linfotoxina/antagonistas & inibidores , Animais , Quimiocinas/metabolismo , Imunoglobulinas/imunologia , Imuno-Histoquímica , Receptor beta de Linfotoxina/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia
17.
Phys Rev Lett ; 109(2): 022501, 2012 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-23030155

RESUMO

The unbound excited states of the neutron drip-line isotope 24O have been investigated via the 24O(p,p')23O + n reaction in inverse kinematics at a beam energy of 62 MeV/nucleon. The decay energy spectrum of 24O* was reconstructed from the momenta of 23O and the neutron. The spin parity of the first excited state, observed at E(x) = 4.65±0.14 MeV, was determined to be J(π) = 2+ from the angular distribution of the cross section. Higher-lying states were also observed. The quadrupole transition parameter ß2 of the 2(1)+ state was deduced, for the first time, to be 0.15±0.04. The relatively high excitation energy and small ß2 value are indicative of the N = 16 shell closure in 24O.

18.
Colorectal Dis ; 14(9): 1090-4, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22107065

RESUMO

AIM: Colonoscopy provides imperfect protection against colorectal cancer (CRC). In an attempt to improve cancer detection we evaluated the clinical features of invasive CRC detected within 5 years of a negative colonoscopy. METHOD: The details of colonoscopies performed in a rural hospital in Japan were prospectively recorded at the time of the examination. The patients were followed over 5 years for the subsequent occurrence of cancer. RESULTS: In a 5-year period, 10148 patients underwent colonoscopy and 202 without previous colonoscopy were diagnosed with invasive CRC. Of 3212 patients with a colonoscopy negative for cancer, nine developed invasive cancer within 5 years. The ratios for invasive CRC detected without/with previous colonoscopy were 60:1 in the rectum, 54:1 in the sigmoid colon, 15:1 in the descending colon, 28:0 in the transverse colon, 31:5 in the ascending colon and 14:1 in the caecum (P=0.041). The ratio between left- and right-sided colonic cancer was also significantly different (129:3 and 45:6, P=0.0078). Six (67%) of the invasive CRCs were in the ascending colon or caecum. Five of six patients with invasive CRC in the ascending colon and caecum had right-sided small adenomas at prior colonoscopy. CONCLUSION: The majority of early/missed CRCs were right-sided and associated with prior right-sided colonic adenomas. Repeated colonoscopy of patients with right-sided adenomas at a shorter surveillance interval deserves consideration.


Assuntos
Carcinoma/patologia , Pólipos do Colo/patologia , Neoplasias Colorretais/patologia , Adenoma , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/diagnóstico , Ceco/patologia , Colo Ascendente/patologia , Colo Descendente/patologia , Colo Sigmoide/patologia , Colo Transverso/patologia , Pólipos do Colo/diagnóstico , Colonoscopia , Neoplasias Colorretais/diagnóstico , Erros de Diagnóstico , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Reto/patologia , Fatores de Tempo
19.
Colorectal Dis ; 14(5): 623-7, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21689313

RESUMO

AIM: Endoscopic decompression of malignant colorectal obstruction is often dealt with using expandable metallic stents. Endoscopic decompression of benign large bowel obstruction is more difficult. We report the technique and outcome of transanal endoscopic decompression for benign large bowel obstruction. METHOD: From January 2001 to June 2010, endoscopic decompression using a transanal drainage tube placement was attempted in consecutive patients with benign large bowel obstruction. The clinical features, technical success, complications, treatment after the tube placement and clinical success were retrospectively evaluated. RESULTS: There were 13 patients (seven males, age 47-87, mean 69 years). The sites of obstruction were transverse colon [5 (38%)], sigmoid colon [3 (23%)], ileocecal valve [2 (15%)], splenic flexure [1 (8%)], descending colon [1 (8%)] and rectum [1 (8%)]. The most common cause of obstruction was anastomotic stricture [9 (69%)]. In 12 (92%) patients transanal decompression was technically successful with one perforation. An overtube, the reinsertion of colonoscope along the decompression tube, or the use of a small-diameter endoscope was required for the tube placement in seven (54%). In seven (54%) patients tube placement alone resulted in relief of bowel obstruction without operation. CONCLUSION: Endoscopic decompression using a transanal drainage tube is effective for the management of benign large bowel obstruction.


Assuntos
Doenças do Colo/terapia , Colonoscopia/métodos , Obstrução Intestinal/terapia , Doenças Retais/terapia , Idoso , Idoso de 80 Anos ou mais , Doenças do Colo/etiologia , Colonoscopia/efeitos adversos , Colonoscopia/instrumentação , Constrição Patológica/complicações , Constrição Patológica/terapia , Feminino , Humanos , Obstrução Intestinal/etiologia , Masculino , Pessoa de Meia-Idade , Doenças Retais/etiologia , Estudos Retrospectivos
20.
Colorectal Dis ; 14(10): e735-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22630138

RESUMO

AIM: Colonoscopy may need to be rescheduled because of inadequate bowel preparation. We evaluated the effectiveness of colonoscopic enema as rescue for an inadequate 1-day bowel preparation before colonoscopy. METHOD: Patients referred for afternoon colonoscopy were prospectively enrolled in the study during a 1-year period. Patients took bowel preparation (polyethylene glycol) solution on the morning of the endoscopy. If during colonoscopy the bowel preparation was poor, an enema of polyethylene glycol solution (500 ml) was instilled into the colon at the level of the hepatic flexure via the biopsy channel of the colonoscope which was then removed. The patient was allowed to recover from the propofol sedation and used the bathroom to evacuate the enema. The colonoscope was then introduced and the examination continued. RESULTS: Of 504 patients undergoing colonoscopy, 26 (4.9%) received an enema. The median age was 59 (29-79) years and 19 (73%) were female. A subsequent successful colonoscopy was achieved in 25/26 (96%). There were no complications. The mean time spent for the entire colonoscopy from the initial preparation to the end of the examination including the enema was 7.6± 1.1h (5.4 h preparation, 0.2h first colonoscopy+enema, 0.66h waiting in the lavatory, 0.33h second colonoscopy and 1 h for recovery). CONCLUSION: Colonoscopic enema was highly successful as rescue for patients with inadequate bowel preparation and avoided postponement of the procedure.


Assuntos
Catárticos/administração & dosagem , Colonoscopia/métodos , Enema/métodos , Polietilenoglicóis/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Colonoscópios , Colonoscopia/instrumentação , Esquema de Medicação , Enema/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Fatores de Tempo
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