RESUMO
We report the development of a new interferometer with two stable, high-power, 320 GHz solid-state sources in Heliotron J. A heterodyne Michelson interferometer optical scheme is employed. Two solid-state oscillators are utilized as sources with a fixed frequency at 320 GHz and frequency tunable of 312-324 GHz. Quasi-optical techniques are used for beam transmission. The beam is elongated in the vertical direction with two off-axis parabolic mirrors and injected into the plasma as a sheet beam for the multi-channel measurement (>5 ch.). Passing through the plasma, the beam is reflected at a retroreflector-array installed at the vacuum chamber wall. The retroreflector-array is a bunch of retroreflector structures, which can suppress the beam refraction caused by plasma without much space inside a vacuum chamber unlike a single retroreflector and can facilitate the system design. The source, detectors, and the retroreflector-array are tested to evaluate their basic performance on a tabletop experiment.
RESUMO
BACKGROUND: Trials of salvage therapy for advanced urothelial carcinoma have required prior platinum-based therapy. This practice requires scrutiny because non-platinum-based first-line therapy may be offered to cisplatin-ineligible patients. PATIENTS AND METHODS: Data of patients receiving salvage systemic chemotherapy were collected. Data on prior first-line platinum exposure were required in addition to treatment-free interval, hemoglobin, Eastern Cooperative Oncology Group performance status, albumin, and liver metastasis status. Cox proportional hazard regression was used to evaluate their association with overall survival (OS) after accounting for salvage single-agent or combination chemotherapy. RESULTS: Data were obtained from 455 patients previously exposed to platinum-based therapy and 37 not exposed to platinum. In the group exposed to prior platinum therapy, salvage therapy consisted of a single-agent taxane (n = 184) or a taxane-containing combination chemotherapy (n = 271). In the group not exposed to prior platinum therapy, salvage therapy consisted of taxane or vinflunine (n = 20), 5-fluorouracil (n = 1), taxane-containing combination chemotherapy (n = 12), carboplatin-based combinations (n = 2), and cisplatin-based combinations (n = 2). The median OS for the prior platinum therapy group was 7.8 months (95% confidence interval, 7.0, 8.1), and for the group that had not received prior platinum therapy was 9.0 months (95% confidence interval, 6.0, 11.0; P = .50). In the multivariable analysis, prior platinum therapy versus no prior platinum exposure did not confer an independent impact on OS (hazard ratio, 1.10; 95% confidence interval, 0.75, 1.64; P = .62). CONCLUSION: Prior platinum- versus non-platinum-based chemotherapy did not have a prognostic impact on OS after accounting for major prognostic factors in patients receiving salvage systemic chemotherapy for advanced urothelial carcinoma. Lack of prior platinum therapy should not disqualify patients from inclusion onto trials of salvage therapy.
Assuntos
Antineoplásicos/uso terapêutico , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Compostos Organoplatínicos/uso terapêutico , Terapia de Salvação/métodos , Taxoides/uso terapêutico , Neoplasias Urológicas/tratamento farmacológico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Resultado do TratamentoAssuntos
Infecções Relacionadas a Cateter/cirurgia , Infecções por Mycobacterium não Tuberculosas/cirurgia , Micobactérias não Tuberculosas , Diálise Peritoneal/instrumentação , Peritonite/microbiologia , Peritonite/cirurgia , Idoso , Infecções Relacionadas a Cateter/microbiologia , Cateterismo/efeitos adversos , Remoção de Dispositivo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/microbiologia , Diálise Peritoneal/efeitos adversosRESUMO
WHAT IS KNOWN AND OBJECTIVE: Montelukast, a cysteinyl leukotriene receptor 1 antagonist, is safe and efficacious in patients with asthma. The mechanisms underlying the significant interpatient variability in response to montelukast are not clear but are believed to be, in part, because of genetic variability. METHODS: To examine the associations between polymorphisms in candidate genes in the leukotriene pathway and outcomes in patients with asthma on montelukast for 4-8 weeks, we evaluated the changes in peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV(1·0) ) and patients' subjective symptom before and after montelukast treatment. DNA was collected from 252 Japanese participants. RESULTS AND DISCUSSION: Two single-nucleotide polymorphisms (SNPs) in the ALOX5 (rs2115819) and LTA4H (rs2660845) genes were successfully typed. There was no difference between members of the general population (n = 200) and patients (n = 52) in each genotype frequency. Significant associations were found between SNP genotypes in the LTA4H gene and changes in PEF and FEV(1·0) . The PEF and FEV(1·0) responses to montelukast in the A/A genotypes (n = 4) for the LTA4H SNP were significantly higher than those in the G allele carriers (A/G+G/G) (n = 17). WHAT IS NEW AND CONCLUSION: Despite the small sample size, our results suggest that genetic variation in leukotriene pathway candidate genes contributes to variability in clinical responses to montelukast in Japanese patients with asthma.
Assuntos
Acetatos/farmacologia , Antiasmáticos/farmacologia , Araquidonato 5-Lipoxigenase/genética , Asma/tratamento farmacológico , Epóxido Hidrolases/genética , Quinolinas/farmacologia , Acetatos/uso terapêutico , Adulto , Idoso , Alelos , Antiasmáticos/uso terapêutico , Povo Asiático/genética , Asma/genética , Ciclopropanos , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Genótipo , Humanos , Japão , Antagonistas de Leucotrienos/farmacologia , Antagonistas de Leucotrienos/uso terapêutico , Leucotrienos/genética , Masculino , Pessoa de Meia-Idade , Pico do Fluxo Expiratório/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único , Quinolinas/uso terapêutico , Análise de Sequência de DNA , Sulfetos , Resultado do TratamentoRESUMO
Inguinal hernia is one of the long-term complications requiring surgical interventions after retropubic radical prostatectomy (RRP), and its incidence has been reported to range from 12 to 21%. The number of open gasless laparoendoscopic single-site surgery, especially minimum incision endoscopic radical prostatectomy (MIES-RRP) is increasing in Japan. The incidence of post-operative inguinal hernia was compared between conventional RRP and MIES-RRP. The medical records of 333 patients who underwent conventional RRP (n=214) or MIES-RRP (n=119) with pelvic lymphadenectomy at our hospital were retrospectively evaluated. There were no significant differences between the two groups in age, pre-operative PSA levels, or previous major abdominal surgery (cholecystectomy, gastrectomy and colectomy), appendectomy or inguinal hernia repair. MIES-RRP was carried out with a 5-8-cm lower abdominal midline incision. Inguinal hernia developed postoperatively in 41 (19%) of the 214 men undergoing conventional RRP during mean follow-up of 58 months (range: 7-60 months). In contrast, 7 (5.9%) of the 119 men receiving MIES-RRP, developed inguinal hernia during mean follow-up of 21 months (range: 13-31 months). The hernia-free survival was significantly higher after MIES-RRP than after conventional RRP (P=0.037). Our results suggest that MIES-RRP is less associated with post-operative inguinal hernia than conventional RRP.
Assuntos
Endoscopia/métodos , Hérnia Inguinal/epidemiologia , Prostatectomia/efeitos adversos , Idoso , Endoscopia/instrumentação , Desenho de Equipamento , Seguimentos , Hérnia Inguinal/etiologia , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prostatectomia/métodos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: Postoperative deep venous thrombosis (DVT) is usually asymptomatic but can result in a fatal pulmonary embolism (PE). To assess the ability of transcranial Doppler (TCD) ultrasound apparatus to detect venous emboli in patients who had undergone total knee arthroplasty (TKA). METHODS: Forty-eight patients undergoing TKA were examined postoperatively by using compression ultrasonography, computed tomographic angiography, and TCD ultrasonography that detected high-intensity transient signals (HITS) in femoral veins. An original scoring system based on both the number of HITS and the locations of DVT was tested for its accuracy in predicting PE development. RESULTS: Twenty-three of the 48 patients had DVT postoperatively, and 8 had an asymptomatic PE. The sensitivity and specificity of the HITS assessment alone in identifying PE development were 75% and 92.5%, respectively. The scoring system, however, had a sensitivity of 100% and a specificity of 85% and the area under the receiver operating characteristic (ROC) curve (AUC) was 0.96. CONCLUSIONS: Application of a scoring system based on the detection of both DVT and HITS may be an effective and efficient method of screening for PE after knee arthroplasty.
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Artroplastia do Joelho/efeitos adversos , Veia Femoral/diagnóstico por imagem , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/diagnóstico por imagem , Ultrassonografia Doppler , Tromboembolia Venosa/diagnóstico por imagem , Idoso , Feminino , Humanos , Masculino , Embolia Pulmonar/etiologia , Tromboembolia Venosa/etiologiaRESUMO
Previous studies have suggested that maximum tumor diameter (MTD) is a predictor of PSA recurrence or biochemical recurrence (BCR) in prostate cancer after radical prostatectomy (RP). The significance of MTD in BCR prediction was evaluated using RP specimens of 364 patients with a BCR of 18% (n=66) during a mean follow-up of 37.4 months (range: 10-109 months). MTD was defined as the largest diameter of the largest tumor, and its median MTD was 15 mm (range: 0.9-50 mm). MTD was significantly associated with pre-operative PSA levels, pathological T stage, Gleason's score and positive surgical margin. In a univariate analysis, pathological T stage, Gleason's score, positive surgical margin and MTD were associated significantly with the risk of BCR. Patients with >20 mm MTD had a significantly higher risk of BCR than did those with < or =20 mm MTD (P<0.001). Cox multivariate models indicated that pathological stage, Gleason's score, positive surgical margin and MTD were independent prognostic factors for BCR. MTD would be a useful tool for predicting BCR, as calculation of MTD is a simple and reliable measure.
Assuntos
Recidiva Local de Neoplasia/diagnóstico , Próstata/patologia , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Próstata/cirurgia , Antígeno Prostático Específico/metabolismo , Taxa de SobrevidaRESUMO
PURPOSE: In order to assess the efficacy and toxicity of oral estramustine phosphate (EMP) administration, low-dose EMP monotherapy (study 1) and very low-dose EMP therapy with luteinizing hormone-releasing hormone (LH-RH) agonist (study 2) were conducted in previously untreated prostate cancer and long-term outcomes were compared between the 2 study groups. MATERIALS AND METHODS: Studies 1 and 2 were independently performed beginning in June 1999 and November 2001, respectively. Study 1 was composed of 87 patients including 85 assessable patients. All 108 patients recruited for study 2 were assessable. Low-dose EMP monotherapy (2 capsules/day or 280 mg/day) was used in study 1 and very low-dose EMP (1 capsule/day or 140 mg/day) combined with LH-RH agonist was adopted in study 2. RESULTS: Overall prostate specific antigen (PSA) -response rates in studies 1 and 2 were 92.3% and 94.2%, respectively, and overall toxicity rates were 54.1% and 38.9%, respectively. EMP discontinuation due to side effects was encountered more often in study 1 (45.9%) than in study 2 (27.8%). Among the adverse side effects gastrointestinal toxicity was most prevalent in both studies. One patient died of acute pulmonary embolism in study 1, but no one died in study 2. There were 6 cancer deaths in the gastrointestinal tract in study 1 but only 2 cancer deaths in study 2. CONCLUSION: Our data indicate that the overall PSA response rate was comparable between both studies. However, rates in overall toxicity and drug discontinuation were higher in study 1 than in study 2. We consider that study 2 is more promising for the treatment of previously untreated advanced prostate cancer, although the rate of adverse side effects is still high as compared with other hormonal therapies. In order to overcome the high toxicity rate, especially the gastrointestinal toxicity, we recently elaborated a method employing tailor-made medicine using SNPs of 1A1 gene in cytochrome P-450 for decreasing the rate of gastrointestinal toxicity. Using this method of patient selection, study 3 has been successfully launched on September 2005 with high drug compliance. Better clinical results are being accumulated.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Alquilantes/administração & dosagem , Estramustina/administração & dosagem , Hormônio Liberador de Gonadotropina/agonistas , Gosserrelina/administração & dosagem , Leuprolida/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Adenocarcinoma/patologia , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/efeitos adversos , Biomarcadores Tumorais/sangue , Causas de Morte , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Estramustina/efeitos adversos , Seguimentos , Gosserrelina/efeitos adversos , Humanos , Injeções Intravenosas , Estimativa de Kaplan-Meier , Leuprolida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologiaRESUMO
AIMS: Reticulon 3 (RTN3), a member of the reticulon family of proteins, interacts with the beta-secretase, beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1), and inhibits its activity to produce beta-amyloid protein. The aim of the present study was to clarify the biological role of RTN3 in the brain and its potential involvement in the neuropathology of Alzheimer's disease (AD). METHODS: We performed immunohistochemical and biochemical analyses using a specific antibody against RTN3 to investigate the expression and subcellular localization of RTN3 in control and AD brain tissue samples. RESULTS: Western blot analysis revealed no significant differences in the RTN3 levels between control and AD brains. Immunohistochemical staining showed that RTN3 immunoreactivity was predominantly localized in pyramidal neurones of the cerebral cortex. The patterns of RTN3 immunostaining were similar in control and AD cerebral cortices, and senile plaques were generally negative for RTN3. Biochemical subcellular fractionation disclosed that RTN3 colocalized with BACE1 in various fractions, including the endoplasmic reticulum and the Golgi apparatus. Double-immunofluorescence staining additionally indicated that RTN3 was localized in both endoplasmic reticulum and Golgi compartments in neurones. CONCLUSIONS: These results show that RTN3 is primarily expressed in pyramidal neurones of the human cerebral cortex and that no clear difference of RTN3 immunoreactivity is observable between control and AD brains. Our data also suggest that there is considerable colocalization of RTN3 with BACE1 at a subcellular level.
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Doença de Alzheimer/patologia , Encéfalo/patologia , Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Ácido Aspártico Endopeptidases/metabolismo , Western Blotting , Encéfalo/metabolismo , Retículo Endoplasmático/metabolismo , Feminino , Complexo de Golgi/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Células Piramidais/metabolismoRESUMO
BACKGROUND: Isoprostanes are prostaglandin (PG)-like compounds synthesized by oxidative stress, not by cyclooxygenase, and increase in bronchoalveolar lavage fluid of patients with asthma. The airway inflammation implicated in this disease may be amplified by oxidants. Although isoprostanes are useful biomarkers for oxidative stress, the action of these agents on airways has not been fully elucidated. OBJECTIVE: This study was designed to determine the intracellular mechanisms underlying the effects of oxidative stress on airway smooth muscle, focused on Ca(2+) signalling pathways involved in the effect of 8-iso-PGF(2 alpha). METHODS: Using simultaneous recording of isometric tension and F(340)/F(380) (an indicator of intracellular concentrations of Ca(2+), [Ca(2+)]i, we examined the correlation between tension and [Ca(2+)]i in response to 8-iso-PGF(2 alpha) in the fura-2 loaded tracheal smooth muscle. RESULTS: Augmented tension and F(340)/F(380) by 8-iso-PGF(2 alpha) were attenuated by ICI-192605, an antagonist of thromboxane A(2) receptors (TP receptors). Moreover, D609, an antagonist of phosphatidylcholine-specific phospholipase C, markedly reduced both the tension and F(340)/F(380) induced by 8-iso-PGF(2 alpha), whereas U73122, an antagonist of phosphatidylinositol-specific phospholipase C, modestly inhibited them by 8-iso-PGF(2 alpha). SKF96365, a non-selective antagonist of Ca(2+) channels, markedly reduced both tension and F(340)/F(380) by 8-iso-PGF(2 alpha). However, diltiazem and verapamil, voltage-dependent Ca(2+) channel inhibitors, modestly attenuated tension although their reduction of F(340)/F(380) was not different from that by SKF96365. Y-27632, an inhibitor of Rho-kinase, significantly attenuated contraction induced by 8-iso-PGF(2 alpha) without reducing F(340)/F(380), whereas GF109203X and Go6983, protein kinase C inhibitors, did not markedly antagonize them although reducing F(340)/F(380) with a potency similar to Y-27632. CONCLUSION: 8-iso-PGF(2 alpha) causes airway smooth muscle contraction via activation of TP receptors. Ca(2+) mobilization by SKF96365- and D609-sensitive Ca(2+) influx and Ca(2+) sensitization by Rho-kinase contribute to the intracellular mechanisms underlying the action of 8-iso-PGF(2 alpha). Rho-kinase may be a therapeutic target for the physiologic abnormalities induced by oxidative stress in airways.
Assuntos
Sinalização do Cálcio/fisiologia , Dinoprosta/análogos & derivados , Músculo Liso/efeitos dos fármacos , Traqueia/efeitos dos fármacos , Traqueia/fisiologia , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Amidas/farmacologia , Animais , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Diltiazem/farmacologia , Dinoprosta/farmacologia , Dioxanos/farmacologia , Inibidores Enzimáticos/farmacologia , Estrenos/farmacologia , Cobaias , Imidazóis/farmacologia , Técnicas In Vitro , Indóis/farmacologia , Masculino , Maleimidas/farmacologia , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Músculo Liso/fisiologia , Norbornanos , Piridinas/farmacologia , Pirrolidinonas/farmacologia , Receptores de Tromboxano A2 e Prostaglandina H2/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Tiocarbamatos , Tionas/farmacologia , Fosfolipases Tipo C/antagonistas & inibidores , Vasoconstritores/farmacologia , Verapamil/farmacologia , Quinases Associadas a rho/antagonistas & inibidoresRESUMO
Sodium potassium niobate, (Na(0.5)K(0.5))NbO(3), fine powder has been successfully synthesized at the low temperature of 550 degrees C through a modified solid-state reaction method, in which urea [CO(NH(2))(2)] plays an important role. High-density (Na(0.5)K(0.5))NbO(3) ceramics could be obtained by conventional sintering of the synthesized (Na(0.5)K(0.5))NbO(3) fine powder with the addition of 0.03 mol% Co(3)O(4) as a sintering additive. The crystal structure, microstructure, and dielectric and piezoelectric properties were characterized. The (Na(0.5)K(0.5))NbO(3) ceramic showed a comparatively saturated P-E hysteresis loop. The (Na(0.5)K(0.5))NbO(3) ceramic also displayed piezoelectricity with a piezoelectric constant d(33) of 126 pC/N and a planar electromechanical coupling factor k(p) of 33%.
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Cerâmica/química , Cristalização/métodos , Eletroquímica/métodos , Impedância Elétrica , Chumbo/química , Teste de Materiais , Transição de FaseAssuntos
3-Iodobenzilguanidina , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Compostos Radiofarmacêuticos , Neoplasias das Glândulas Suprarrenais/diagnóstico , Idoso , Catecolaminas/sangue , Evolução Fatal , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Masculino , Cintilografia , Tomografia Computadorizada por Raios XAssuntos
Indicadores Básicos de Saúde , Pneumonia/mortalidade , Infecções Respiratórias/mortalidade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Avaliação Geriátrica , Mortalidade Hospitalar/tendências , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/diagnóstico , Pneumonia/terapia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Infecções Respiratórias/diagnóstico , Medição de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Análise de SobrevidaAssuntos
Pressão Positiva Contínua nas Vias Aéreas , Obesidade/complicações , Apneia Obstrutiva do Sono/complicações , Composição Corporal , Sistema Cardiovascular , Humanos , Inflamação , Resistência à Insulina , Síndrome Metabólica/complicações , Placebos , Fatores Sexuais , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Recent studies have revealed that in asthma, mast cells infiltrate to the smooth muscle layer and release tryptase, an enzymatic activator of protease-activated receptor 2 (PAR2). This phenomenon, mast cell myositis, is proposed as a new feature of asthma. However, little is known about the involvement of mast cell myositis in the pathophysiology of asthma. OBJECTIVE: This study was designed to determine whether mast cell degranulation has any functional impact on beta-adrenoceptors via PAR2 in airway smooth muscle. Moreover, we focused on Ca(2+) signalling as a mechanism underlying alteration of smooth muscle tone and responsiveness. METHODS: Isometric tension and F(340)/F(380), an indicator of the concentration of intracellular Ca(2+) ([Ca(2+)](i)), were simultaneously measured using fura-2-loaded tissues isolated from guinea-pig tracheal smooth muscle. RESULTS: Tryptase (1-100 nm) caused tension with elevated F(340)/F(380), and after exposure to tryptase for 15 min the inhibitory effect of isoprenaline (ISO) against methacholine was attenuated without elevating F(340)/F(380) in a concentration-dependent manner. Tryptase (<1 nm) had a modest effect on tension, but prolonged treatment (=120 min) with 0.1 nm tryptase also reduced the effects of ISO in a time-dependent manner. When tissues were incubated with tryptase in the presence of Y-27632, a Rho-kinase inhibitor, reduced responsiveness to ISO by tryptase was reversed without affecting F(340)/F(380). In contrast, pre-treatment with SKF96365, a non-selective inhibitor of Ca(2+) channels, did not antagonize the effect of tryptase. Moreover, pre-treatment with SLIGKV-NH(2), a non-enzymatic activator of PAR2, resulted in a loss of beta-adrenergic efficacy, similar to tryptase. The effect of cAMP-related agents bypassing beta-adrenoceptors was not attenuated after exposure to tryptase. CONCLUSION: In mast cell myositis, tryptase released from mast cells acts on airway smooth muscle, leading to homologous beta-adrenergic desensitization mediated by [Ca(2+)](i)-independent mechanisms via PAR2 activation.