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1.
J Neuroradiol ; 48(4): 311-315, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31563590

RESUMO

BACKGROUND AND PURPOSE: Precise vessel measurement plays a major role in size selection of stents used for the treatment of intracranial aneurysms and became even more critical after the introduction of flow diverter stents. We assessed agreement between intracranial vessel diameters of aneurysm patients measured on 2D digital subtraction (2D DSA) and 3D volume rendering digital subtraction angiography (3D DSA) images using an automatic windowing algorithm. MATERIALS AND METHODS: Ten patients with intracranial aneurysms were enrolled and 120 measurement points were selected on both 2D and 3D DSA images acquired by a biplane angiographic system. Automatic windowing was applied to the 3D DSA images. Inter-method agreement of vessel measurements on 2D and 3D DSA images was assessed by Bland Altman plots and intraclass correlation coefficients (ICC). Inter- and intra-rater agreement of measurements on 3D DSA images were assessed by ICCs. RESULTS: The mean differences between measurements on 2D and 3D DSA images were 0.14mm for the ICA, and 0.18mm for the ACA and MCA, which is about the size of one 3D DSA image voxel. For ICA measurements, inter-method, inter-rater and intra-rater agreements were good or excellent (consistency and absolute ICC≥0.95). For ACA and MCA measurements, the inter-method, inter-rater and intra-rater agreements were also good or excellent (consistency ICC=0.94, 0.89 and 0.93, absolute ICC=0.83, 0.84 and 0.85 respectively). CONCLUSIONS: Vessel diameters may be measured on 3D DSA images with sufficient reliability for clinical use when applying an automatic windowing algorithm.


Assuntos
Aneurisma Intracraniano , Algoritmos , Angiografia Digital , Angiografia Cerebral , Humanos , Imageamento Tridimensional , Aneurisma Intracraniano/diagnóstico por imagem , Reprodutibilidade dos Testes
2.
J Clin Pharm Ther ; 41(4): 399-402, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27144370

RESUMO

WHAT IS KNOWN AND OBJECTIVE: The pharmacokinetic-pharmacodynamic parameter that best predicts the efficacy of vancomycin is the ratio of the area under the concentration versus time curve (AUC) to the minimum inhibitory concentration (MIC). A 24-h AUC (AUC24 )/MIC ratio ≥ 400 was recommended in an American consensus review, but vancomycin treatment occasionally fails despite maintenance of AUC24 /MIC ≥ 400. We evaluated the association between clinical efficacy of vancomycin and two novel pharmacokinetic parameters, the 'area under the trough level' (AUTL) and the 'area above the trough level' (AATL), in hospitalized elderly patients with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. METHODS: The subjects were hospitalized elderly patients who were administered vancomycin for treatment of MRSA pneumonia between 2006 and 2012 at Sasebo Chuo Hospital (Nagasaki, Japan). Pharmacokinetic parameters of vancomycin were estimated for each patient by Bayesian analysis using population pharmacokinetic parameters for Japanese patients. Based on the patient-specific parameters thus obtained, AUC24 values were calculated as the vancomycin dosage divided by vancomycin clearance. AUTL was calculated as the trough serum concentration multiplied by 24 h, whereas AATL was calculated by subtracting AUTL from AUC24 . RESULTS AND DISCUSSION: Logistic regression analysis demonstrated that efficacy of vancomycin was more strongly associated with AUTL than AUC24 . The optimal cut-off value of AUTL was 331 µg∙h/mL, which means that the optimal cut-off value of the trough serum concentration was 13·8 µg/mL. WHAT IS NEW AND CONCLUSION: Efficacy of vancomycin was associated with AUTL, a novel pharmacokinetic parameter. Determining the target AUTL or trough concentration may enhance the efficacy of vancomycin therapy in elderly patients with MRSA pneumonia. Given that nephrotoxicity may increase with a Ctrough in excess of 15 µg/mL, this level should ideally not be exceeded.


Assuntos
Antibacterianos/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Vancomicina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Área Sob a Curva , Teorema de Bayes , Infecção Hospitalar/microbiologia , Feminino , Hospitalização , Humanos , Japão , Modelos Logísticos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Pneumonia Bacteriana/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Resultado do Tratamento , Vancomicina/administração & dosagem , Vancomicina/farmacocinética
3.
Gene Ther ; 22(2): 127-37, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25503692

RESUMO

Age-related macular degeneration (AMD) is a vision-threatening disease characterized by choroidal fibrovascular membrane (FVM) formation, choroidal neovascularization (CNV) and choroidal fibrosis. No safe and effective therapeutic method has been developed for the choroidal fibrosis, although anti-vascular endothelial growth factor therapy can partially shrink the CNV. We recently reported that periostin (POSTN), which is produced by retinal pigment epithelial cells, has an important role in the formation of preretinal FVMs, but its role in choroidal FVMs has not been determined. In this study, we used Postn knockout mice to investigate the role played by POSTN in choroidal FVM formation. In addition, we used a new class of RNA interference (RNAi) agent (NK0144) that targets POSTN and determined its effect on choroidal FVM development. Genetic ablation of Postn had an inhibitory effect not only on CNV formation but also on choroidal fibrosis in a mouse CNV model. NK0144 also had a greater inhibitory effect on both the CNV and choroidal fibrosis than control RNAi with no apparent adverse effects. These findings suggest a causal relationship between POSTN and choroidal FVM formation, and also a potential therapeutic role of intravitreal NK0144 for AMD.


Assuntos
Moléculas de Adesão Celular/genética , Neovascularização de Coroide/terapia , Degeneração Macular/terapia , Interferência de RNA , Animais , Sequência de Bases , Adesão Celular , Moléculas de Adesão Celular/metabolismo , Movimento Celular , Proliferação de Células , Células Cultivadas , Corioide/irrigação sanguínea , Corioide/patologia , Técnicas de Silenciamento de Genes , Terapia Genética , Humanos , Injeções Intravítreas , Camundongos Endogâmicos C57BL , Camundongos Knockout , Dados de Sequência Molecular , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Epitélio Pigmentado da Retina/patologia , Epitélio Pigmentado da Retina/fisiologia , Receptor 3 Toll-Like/metabolismo
4.
Horm Metab Res ; 47(3): 176-83, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25295420

RESUMO

Type 2 diabetes results from the failure of beta-cells to adequately compensate for insulin resistance. Although the reduction of beta-cell mass is because of increased cell death and/or inadequate replication or neogenesis, the mechanism underlying beta-cell mass reduction is not fully understood. Here, we clarify the role of insulin signaling pathway in the beta-cell apoptosis using insulin resistant model mice. Wild-type mice and those carrying a mutation in the insulin receptor (mIR) were fed either regular chow or a high-fat diet for 6 weeks and subsequently investigated for beta-cell apoptosis, endoplasmic reticulum stress, and oxidative stress. Insulin tolerance tests revealed that mIR mice fed a high-fat diet (mIRHF) had higher insulin resistance. Beta-cell apoptosis was increased 2-fold in the wild-type mice fed a high-fat diet (wHF) compared with control mice, whereas beta-cell apoptosis in mIRHF mice did not increase compared with that in mIR mice. The expression of endoplasmic reticulum stress markers in isolated islets did not differ between the groups. Staining of 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal in islets of wHF mice significantly increased, but the staining in mIRHF mice was not different from that in control group. Gene expression of the antioxidant enzyme MnSOD was significantly higher in mIRHF mice than those in the other 3 groups. A mutation in the insulin receptor attenuated the oxidative stress and apoptosis in beta-cells even though high caloric nutrient was loaded. Our results suggest that reduced insulin signaling protects beta-cells thorough decline of oxidative stress.


Assuntos
Apoptose , Diabetes Mellitus Tipo 2/metabolismo , Células Secretoras de Insulina/metabolismo , Mutação , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Receptor de Insulina/genética , Animais , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatologia , Dieta Hiperlipídica/efeitos adversos , Humanos , Insulina/metabolismo , Células Secretoras de Insulina/citologia , Masculino , Camundongos , Receptor de Insulina/metabolismo , Transdução de Sinais
5.
Horm Metab Res ; 47(11): 826-32, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26305168

RESUMO

Approximately 10% of cases of hypertension in Japan are caused by primary aldosteronism (PA), amounting to about 4 million patients in total. Primary aldosteronism due to unilateral aldosterone hypersecretion is potentially curable by adrenalectomy. The clinical benefits of identifying and treating PA have been reported internationally, but its cost-effectiveness is unclear. We examined whether diagnosing and treating hidden PA in hypertensive population was cost-effective compared with suboptimal treatment. Our hypothetical patient was a 50-year-old man diagnosed with stage I-III hypertension. We established a Markov decision model based on plausible clinical pathways and prognoses of PA. We applied cost-effectiveness analysis comparing a comprehensive diagnostic strategy for PA (measurement of plasma aldosterone/renin ratio, 2 loading tests, imaging, and selective adrenal venous sampling) with a suboptimal strategy to manage hypertension by medication unless the typical signs of PA or other complication were manifest. Outcome measures were expected costs, expected effectiveness, and incremental cost-effectiveness ratio. The robustness of the findings was established by one-way and scenario sensitivity analyses. The comprehensive PA diagnostic strategy increased the expected costs by 64 004 JPY and expected life-years by 0.013 compared with standard treatment. The incremental cost-effectiveness ratio for the diagnosis of PA was 4 923 385 JPY per year. Our findings were sensitive to the outcomes of screening and treatment, and the costs of continuous or periodic medication for hypertension and the treatment of stroke and its complications.


Assuntos
Análise Custo-Benefício , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/terapia , Humanos , Hiperaldosteronismo/economia , Japão , Masculino , Cadeias de Markov , Pessoa de Meia-Idade
6.
Eur J Gynaecol Oncol ; 35(4): 443-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25118489

RESUMO

In recent years, the incidence of therapy-related myelodysplastic syndrome (t-MDS) and therapy-related acute myeloid leukemia (t-AML) that occur during chemotherapy for ovarian cancer has increased. While alkylating agents and topoisomerase II inhibitors are particularly mutagenic and have strong leukemogenic potential, paclitaxel and combination chemotherapy/radiation therapy also appear to induce t-MDS. The present authors report a case of t-MDS that developed during chemotherapy and radiation therapy for ovarian cancer. The patient was a 75-year-old woman who received six courses of cyclophosphamide/doxorubicin/cisplatin (CAP) therapy after initial surgery for Stage IIIc grade ovarian cancer in 1995. Beginning in February 2005, the patient experienced multiple recurrences due to sternal metastasis. Chemotherapy, including paclitaxel and carboplatin (TC), was administered intermittently and was combined with radiation therapy to a sternal metastatic lesion. Pancytopenia was observed in December 2008, and she was diagnosed with t-MDS (WHO subtype, refractory cytopenias with multilineage dysplasia [RCMD]): the time from first chemotherapy to t-MDS onset was 106 months. Without evidence of blast crisis, the recurrent lesions continued to grow and caused multiple cerebral infarctions, from which she eventually died. The cumulative doses of paclitaxel and carboplatin administered to this patient were 1,968 mg and 6,480 mg, respectively.


Assuntos
Neoplasias das Glândulas Suprarrenais/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/terapia , Quimiorradioterapia/efeitos adversos , Leucemia Mieloide Aguda/etiologia , Neoplasias Hepáticas/terapia , Síndromes Mielodisplásicas/etiologia , Segunda Neoplasia Primária/etiologia , Neoplasias Ovarianas/terapia , Neoplasias das Glândulas Suprarrenais/secundário , Idoso , Neoplasias Ósseas/secundário , Carboplatina/administração & dosagem , Infarto Cerebral/etiologia , Evolução Fatal , Feminino , Humanos , Neoplasias Hepáticas/secundário , Células Neoplásicas Circulantes , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem
7.
Knee Surg Relat Res ; 36(1): 12, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38539272

RESUMO

INTRODUCTION: Patient satisfaction is an important outcome of total knee arthroplasty (TKA). However, we cannot predict how and why patients are satisfied or dissatisfied with TKA. The hypothesis of this study was that patient-reported outcomes (PROs) correlate with in vivo kinematics after TKA. MATERIALS AND METHODS: One hundred knees were analyzed after TKA. The in vivo kinematics of deep knee bending motion were estimated from single-plane fluoroscopy using a two-to-three-dimensional registration technique. Active knee flexion, femoral rotation and rollback were evaluated. The PROs were obtained after surgery using the 2011 Knee Society Scoring System (KSS), and their relationship with in vivo kinematics was determined. RESULTS: The average minimum and maximum flexion were -2.4 ± 7.3° and 113.2 ± 13.6°, respectively. The average femoral rotation was 7.4 ± 3.4°, and the average medial and lateral rollback were 2.4 ± 4.8 mm and 7.2 ± 5.6 mm, respectively. The multiple regression analysis revealed that the maximum flexion angle significantly contributed to symptoms and satisfaction. In addition, lateral rollback was also a significant factor affecting patient satisfaction. Lateral rollback and lateral Anterior-Posterior (AP) position at maximum flexion were correlated with the maximum flexion angle, whereas femoral rotation did not correlate with flexion angles. CONCLUSIONS: Maximum flexion and lateral rollback are important for better patient satisfaction after TKA. To obtain the maximum flexion angle, it was necessary to perform the normal kinematic pattern with a large amount of lateral rollback.

8.
Radiography (Lond) ; 30(1): 408-415, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38176131

RESUMO

INTRODUCTION: This study aimed to compare the vascular enhancement and radiation dose in preoperative transcatheter aortic valve implantation (TAVI) computed tomography (CT) with a reduced contrast medium (CM) using volume scans in 256-multidetector row CT (MDCT) with a standard CM using 64-MDCT. METHODS: This study included 78 patients with preoperative TAVI CT with either 64- or 256-MDCT. The CM was injected at 1.5 mL/kg in the 64-MDCT group and 1.0 mL/kg in the 256-MDCT group. We compared vascular enhancement of the aortic root and access routes, image quality (IQ) scores, and radiation dose in both groups. RESULTS: Despite the reduced CM (by 33 %) in the 256-MDCT group, the mean vascular enhancement of the right and left subclavian arteries was significantly higher than that in the 64-MDCT group [284 and 267 Hounsfield units (HU) vs. 376 and 359 HU; p < 0.05]; however, no significant differences in the mean vascular enhancement in the ascending aorta, abdominal aorta at the celiac level, and bilateral common femoral arteries were observed between the two groups (p > 0.05 for all). The median IQ scores at the aortic root were higher in the 256-MDCT group than in the 64-MDCT group (3 vs. 4; p < 0.05), and those at the femoral access routes were comparable (4 vs. 4; p = 0.33). The mean effective dose was significantly reduced by 30 % in the 256-MDCT group (23.6 vs. 16.3 mSv; p < 0.05). CONCLUSION: In preoperative TAVI CT, volume scans using 256-MDCT provide comparable or better vascular enhancement and IQ with a 30 % reduction in CM and radiation dose than those using 64-MDCT. IMPLICATIONS FOR PRACTICE: Volume scan using 256-MDCT for preoperative TAVI CT may reduce CM and radiation dose in TAVI patients with renal dysfunction.


Assuntos
Estenose da Valva Aórtica , Iodo , Substituição da Valva Aórtica Transcateter , Humanos , Substituição da Valva Aórtica Transcateter/métodos , Tomografia Computadorizada Multidetectores , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Doses de Radiação , Aorta Abdominal
9.
Eur J Gynaecol Oncol ; 34(1): 104-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23590014

RESUMO

The present report describes a rare case of a uterine perivascular epithelioid cell tumor (PEComa) arising from a polypoid adenomyoma. The patient, a 44-year-old woman with tuberous sclerosis, was incidentally found to have a uterine mass with malignant-appearing features on a computed tomography (CT) scan. Pathological examination of the hysterectomy specimen demonstrated that the tumor was composed of pale, spindle-shaped, epithelioid tumor cells which were positive for SMA and HMB-45. These findings were consistent with a PEComa arising from a polypoid adenomyoma.


Assuntos
Adenomioma/patologia , Neoplasias de Células Epitelioides Perivasculares/patologia , Pólipos/patologia , Neoplasias Uterinas/patologia , Adulto , Feminino , Humanos , Imuno-Histoquímica
10.
Clin Exp Obstet Gynecol ; 40(3): 377-80, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24283169

RESUMO

In recent years, Shimane University Hospital has begun to see patients with pelvic inflammatory disease (PID) which has become severe and chronic after insufficient conservative treatment in primary or secondary medical care facilities. Serious chronic tubo-ovarian abscess (TOA) is complicated by intraperitoneal inflammatory adhesions to surrounding organs, so that it is difficult to determine the original anatomical position of organs at surgery. Forcible synechotomy can result in damage to the adhering organs and insufficient drainage after surgery can cause recurrence of inflammation. In order to increase the chances for a successful surgical treatment, careful preparation, such as preoperative administration of antibiotics and ureteral stent insertion are necessary. In addition, the chances for recurrence of inflammation can be lessened by thorough intraperitoneal irrigation and insertion of a drainage tube.


Assuntos
Abscesso/cirurgia , Doenças das Tubas Uterinas/cirurgia , Doenças Ovarianas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento
11.
AJNR Am J Neuroradiol ; 44(9): 1057-1063, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37536732

RESUMO

BACKGROUND AND PURPOSE: Contrast-induced encephalopathy can result from neurotoxicity of contrast medium in the affected area. The development of intermediate catheters has allowed guidance of catheters to more distal arteries. This study focused on the association between contrast-induced encephalopathy and contrast injection from an intermediate catheter guided into a distal intradural artery during neurointervention for cerebral aneurysms. MATERIALS AND METHODS: We retrospectively reviewed 420 consecutive aneurysms in 396 patients who underwent neurointervention for extracranial aneurysms and unruptured intracranial aneurysms at our institution from February 2012 to January 2023. Patients were divided into a group with contrast-induced encephalopathy and a group without. To identify risk factors for contrast-induced encephalopathy, we compared clinical, anatomic, and procedural factors between groups by multivariate logistic regression analysis and stepwise selection. RESULTS: Among the 396 patients who underwent neurointervention for cerebral aneurysms, 14 (3.5%) developed contrast-induced encephalopathy. Compared with the group without contrast-induced encephalopathy, the group with contrast-induced encephalopathy showed significantly higher rates of patients on hemodialysis, previously treated aneurysms, intradural placement of a catheter for angiography, nonionic contrast medium, and flow-diversion procedures in univariate analyses. Stepwise multivariate logistic regression analysis revealed intradural placement of a catheter for angiography (OR = 40.4; 95% CI, 8.63-189) and previously treated aneurysms (OR = 8.20; 95% CI, 2.26-29.6) as independent predictors of contrast-induced encephalopathy. CONCLUSIONS: Contrast injection from an intradural artery and retreatment of recurrent aneurysms were major risk factors for contrast-induced encephalopathy. Attention should be paid to the location of the intermediate catheter for angiography to avoid developing contrast-induced encephalopathy.


Assuntos
Encefalopatias , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/terapia , Estudos Retrospectivos , Artérias , Encefalopatias/induzido quimicamente , Encefalopatias/diagnóstico por imagem , Catéteres , Resultado do Tratamento , Angiografia Cerebral/métodos
12.
Br J Cancer ; 107(2): 300-7, 2012 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-22653145

RESUMO

BACKGROUND: This study examined the clinical significance of NAC1 and the expression level of its potential downstream target fatty acid synthase (FASN) in ovarian clear cell carcinomas (OCCCs), and evaluated the NAC1/FASN pathway as a potential therapeutic target. METHODS: NAC1 and FASN expression and NACC1 gene amplification were assessed in ovarian cancers by immunohistochemistry, fluorescence in situ hybridisation, and clinical data collected by a retrospective chart review. C75, a FASN inhibitor, was used to assess whether this pathway represented a therapeutic target in OCCC. RESULTS: High NAC1 expression was most frequent in clear cell tumours (40.0%:24/60). NACC1 gene amplification was identified in none of the 58 OCCCs. The frequency of NACC1 gene amplification was significantly higher in the high-grade serous histology than in the clear cell histology (P<0.01). NAC1 expression was significantly correlated with FASN expression in both OCCC samples and OCCC cell lines. Either high NAC1 expression or high FASN expression significantly correlated with shorter progression-free and overall survival (P=0.002 and 0.0048). NAC1 overexpression stimulated FASN expression, and NAC1 silencing using siRNA decreased FASN expression in OCCC cell lines. Profound growth inhibition was observed in C75-treated carcinoma cells with FASN overexpression when compared with the response in carcinoma cells without FASN expression. CONCLUSION: These findings indicate that NAC1/FASN overexpression is critical to the growth and survival of a subset of OCCC. The FASN silencing by the C75-induced phenotypes depends on the expression status of the targeted cell line. Therefore, NAC1/FASN pathway-targeted therapy may benefit selected OCCC patients.


Assuntos
Adenocarcinoma de Células Claras/metabolismo , Ácido Graxo Sintases/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Ovarianas/metabolismo , Proteínas Repressoras/metabolismo , Adenocarcinoma de Células Claras/enzimologia , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/patologia , Linhagem Celular Tumoral , Intervalo Livre de Doença , Ácido Graxo Sintases/antagonistas & inibidores , Ácido Graxo Sintases/genética , Feminino , Amplificação de Genes , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Imuno-Histoquímica , Terapia de Alvo Molecular , Proteínas de Neoplasias/genética , Neoplasias Ovarianas/enzimologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Proteínas Repressoras/genética , Estudos Retrospectivos , Transdução de Sinais
13.
J Clin Pharm Ther ; 37(6): 657-63, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22734557

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Various factors have been reported to be associated with the duration of regulatory review of new drug applications (NDAs). We investigated potential links between the review times in Japan and the attributes of NDAs, the regulatory agency and pharmaceutical companies. METHODS: We analysed new drugs approved in 2000-2009 in Japan using a proprietary database collected through annual surveys to pharmaceutical companies. Regression models in which individual firms were treated as either a fixed effect or a random effect were applied to examine factors associated with the overall review time and the duration of each step of the review. RESULTS AND DISCUSSION: The fixed effect model analysis using variations within each firm indicated that new molecular entities that were submitted to the Pharmaceuticals and Medical Devices Agency (PMDA), priority reviews and pre-NDA consultations were associated with a shorter overall review time, whereas additional studies during the review resulted in a longer review. In the random effect model analysis using both within- and between-firm variations, use of end-of-phase 2 consultations and foreign clinical data also had negative coefficients, suggesting the effect of these two vary among firms. Analysis of each step of the review process revealed NDAs reviewed by the Committee on Drugs under the Ministry of Health, Labour and Welfare, and the number of NDAs assigned to a review team were significantly linked with their duration, whereas consultation services and the number of reviewers had no relation. WHAT IS NEW AND CONCLUSION: Factors associated with each step of the review process as well as the differences in attributes and strategies among pharmaceutical companies should be considered to further improve the speed, quality and efficiency of the regulatory review.


Assuntos
Aprovação de Drogas/estatística & dados numéricos , Indústria Farmacêutica/estatística & dados numéricos , Aplicação de Novas Drogas em Teste/estatística & dados numéricos , Bases de Dados Factuais , Aprovação de Drogas/organização & administração , Humanos , Japão , Análise de Regressão , Fatores de Tempo
14.
Eur J Gynaecol Oncol ; 33(5): 546-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23185810

RESUMO

BACKGROUND: An enlarged Virchow's node or left supraclavicular lymph node is a classic precursor to the diagnosis of metastatic cancer, usually originating from an abdominal organ. It is rarely found in ovarian carcinoma. CASE REPORT: A 49-year-old woman presented a painless mass in her left supraclavicular fossa. A histopathological examination of the same mass was consistent with a serous adenocarcinoma of ovarian origin. The patient was initially asymptomatic, even with the disease in an advanced stage. Left supraclavicular adenopathy has not been previously reported as a presenting complaint of ovarian carcinoma. CONCLUSION: Ovarian carcinoma in contemporary with a Virchow's node is an isolated finding.


Assuntos
Cistadenocarcinoma Seroso/patologia , Linfonodos/patologia , Neoplasias Ovarianas/patologia , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade
15.
AJNR Am J Neuroradiol ; 42(2): 306-312, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33361373

RESUMO

BACKGROUND AND PURPOSE: Obtaining information on invisible vasculature distal to the occlusion site helps to deploy a stent retriever safely during mechanical thrombectomy for large-vessel occlusion. It is essential to reduce the amount of contrast used for detecting the vessels distal to the occlusion site because acute ischemic stroke patients tend to have chronic kidney disease and patients with severe chronic kidney disease are at an increased risk of contrast-associated acute kidney injury. We assessed whether vessels distal to the occlusion site during acute ischemic stroke with large-vessel occlusion could be visualized on angiographic images using flat panel detector CT acquired following intra-arterial diluted contrast injection, compared with MRA findings. MATERIALS AND METHODS: Between May 2019 and January 2020, we enrolled 28 consecutive patients with large-vessel occlusions of the anterior circulation eligible for mechanical thrombectomy following MR imaging. The patients underwent CBV imaging using flat panel detector CT with an intra-arterial diluted contrast injection instead of intravenous injection. Flat panel detector CT angiographic images reconstructed from the same dataset were evaluated for image quality, collateral status of the MCA territory, and visualization of the vessels distal to the occlusion site. These findings were compared with MRA findings. RESULTS: Twenty-two patients were retrospectively examined. Flat panel detector CT angiographic image quality in 20 patients (91%) was excellent or good. The distal portion of the occluded vessel segment was visualized in 14 patients (70%), while the proximal portion of the segment adjacent to the occluded vessel in 3 (15%) was visualized. No visualization was observed in only 1 patient (5%) with no collateral supply. Flat panel detector CT angiographic images were shown to evaluate vessels distal to the occlusion site more accurately than MRA. CONCLUSIONS: In acute ischemic stroke with large-vessel occlusion, flat panel detector CT angiographic images could successfully visualize vessels distal to the occlusion site with a small amount of contrast material.


Assuntos
Angiografia Cerebral/métodos , Angiografia por Tomografia Computadorizada/métodos , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/cirurgia , Trombectomia/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Cirurgia Assistida por Computador/métodos
16.
Artigo em Inglês | MEDLINE | ID: mdl-33301406

RESUMO

OBJECTIVE: To clarify whether there are any muscle synergy changes in individuals with knee osteoarthritis, and to determine whether muscle synergy analysis could be applied to other musculoskeletal diseases. METHODS: Subjects in this study included 11 young controls (YC), 10 elderly controls (EC), and 10 knee osteoarthritis patients (KOA). Gait was assessed on a split-belt treadmill at 3 km/h. A non-negative matrix factorization (NNMF) was applied to the electromyogram data matrix to extract muscle synergies. To assess the similarity of each module, we performed the NNMF analysis assuming four modules for all of the participants. Further, we calculated joint angles to compare the kinematic data between the module groups. RESULTS: The number of muscle modules was significantly lower in the EC (2-3) and KOA (2-3) groups than in the YC group (3-4), which reflects the merging of late swing and early stance modules. The EC and KOA groups also showed greater knee flexion angles in the early stance phase. Contrarily, by focusing on the module structure, we found that the merging of early and late stance modules is characteristic in KOA. CONCLUSION: The lower number of modules in the EC and KOA groups was due to the muscle co-contraction with increased knee flexion angle. Contrarily, the merging of early and late stance modules are modular structures specific to KOA and may be biomarkers for detecting KOA. SIGNIFICANCE: Describing the changes in multiple muscle control associated with musculoskeletal degeneration can serve as a fundamental biomarker in joint disease.


Assuntos
Osteoartrite do Joelho , Idoso , Fenômenos Biomecânicos , Marcha , Humanos , Articulação do Joelho , Músculos
17.
J Exp Med ; 139(6): 1540-52, 1974 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-4598018

RESUMO

The inhibition of activated T cells by products of the humoral immune response is almost abolished by systemic infection with BCG. As a result, BCG-infected mice develop very high levels of delayed-type hypersensitivity (DTH) in response to doses of sheep red blood cells (SRBC) that cause complete suppression of DTH in normal mice. This systemic effect of BCG is dose-dependent, and lasts for about 3 wk. Its main effect is to counteract the inhibition of T cells by products of the humoral response. As a result, and in contrast to the T-cell-potentiating effects of cyclophosphamide (CY) which depend on a diminished production of antibodies, increased levels of DTH in BCG-infected mice are associated with increased antibody production. Since BCG and CY act in different ways, their effects are additive. Very remarkable levels of DTH are achieved when they are used in combination.


Assuntos
Mycobacterium bovis/imunologia , Linfócitos T/imunologia , Animais , Soro Antilinfocitário , Ciclofosfamida/farmacologia , Eritrócitos/imunologia , Feminino , Vida Livre de Germes , Testes de Hemaglutinação , Hipersensibilidade Tardia/imunologia , Imunização , Masculino , Camundongos , Mycobacterium/imunologia , Infecções por Mycobacterium/imunologia , Ovinos/imunologia , Linfócitos T/efeitos dos fármacos
18.
J Exp Med ; 139(3): 543-59, 1974 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-4591171

RESUMO

An explanation was sought for the fact that delayed-type hypersensitivity (DTH) does not normally occur in response to T-cell-dependent antigens unless an adjuvant is used. But when sheep red blood cells (SRBC) were administered intravenously DTH did appear, provided that the dose of antigen was less than that required to give a maximum antibody response. Animals in which T-cell activity had been blocked by a large dose of antigen could not be sensitized adoptively, and their spleen cells failed to transfer DTH to normal recipients. The serum of blocked animals partially inhibited the induction of DTH, and after absorption with SRBC its blocking activity increased substantially. Moreover, absorbed serum inhibited DTH in previously sensitized animals, but it did not inhibit the proliferative response to SRBC in peripheral lymph nodes or reduce the number of plaque-forming cells produced therein. On the contrary, the hemagglutinating titer was actually increased by blocking serum even though DTH was totally suppressed. It is concluded that a product of the interaction between antigens and antibody blocks the activated T cells which mediate DTH without interfering with helper cells.


Assuntos
Hipersensibilidade Tardia , Imunização , Linfonodos/imunologia , Linfócitos T/imunologia , Animais , Formação de Anticorpos , Células Produtoras de Anticorpos , Líquido Ascítico/citologia , Vida Livre de Germes , Testes de Hemaglutinação , Técnica de Placa Hemolítica , Terapia de Imunossupressão , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos , Ovinos , Esplenectomia
19.
AJNR Am J Neuroradiol ; 41(2): 286-292, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32001447

RESUMO

BACKGROUND AND PURPOSE: Delayed leukoencephalopathy is a rare complication that occurs after endovascular coiling of cerebral aneurysms. We aimed to describe a clinical picture of delayed leukoencephalopathy and explore potential associations with procedural characteristics. MATERIALS AND METHODS: We considered endovascular coiling procedures for cerebral aneurysms performed between January 2006 and December 2017 in our institution with follow-up MRIs. We used logistic regression models to estimate the ORs of delayed leukoencephalopathy for each procedural characteristic. RESULTS: We reviewed 1754 endovascular coiling procedures of 1594 aneurysms. Sixteen of 1722 (0.9%) procedures demonstrated delayed leukoencephalopathy on follow-up FLAIR MR imaging examinations after a median period of 71.5 days (interquartile range, 30-101 days) in the form of high-signal changes in the white matter at locations remote from the coil mass. Seven patients had headaches or hemiparesis, and 9 patients were asymptomatic. All imaging-associated changes improved subsequently. We found indications suggesting an association between delayed leukoencephalopathy and the number of microcatheters used per procedure (P = .009), along with indications suggesting that these procedures required larger median volumes of contrast medium (225 versus 175 mL, OR = 5.5, P = .008) as well as a longer median fluoroscopy duration (123.6 versus 99.3 minutes, OR = 3.0, P = .06). Our data did not suggest that delayed leukoencephalopathy was associated with the number of coils (P = .57), microguidewires (P = .35), and guiding systems (P = .57). CONCLUSIONS: Delayed leukoencephalopathy after coiling of cerebral aneurysms may have multiple etiologies such as foreign body emboli, contrast-induced encephalopathy, or hypersensitivity reaction to foreign bodies.


Assuntos
Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/cirurgia , Leucoencefalopatias/etiologia , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Procedimentos Endovasculares/instrumentação , Feminino , Humanos , Incidência , Leucoencefalopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Stents , Resultado do Tratamento
20.
Science ; 263(5143): 62-4, 1994 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-8272866

RESUMO

Fluorescent x-ray interference patterns have been observed from monolayers of both a metal-containing protein (ferritin) and a nonmetal-containing protein [bovine serum albumin (BSA)] bound on a gold substrate. These interference patterns have been used to determine structure data. The nonmetal-containing protein was first reacted with metal ions by means of a chelate compound to place the necessary chromophore in the molecule. The size of the ferritin core measured by a scanning electron microscope agrees with the value obtained from the x-ray interference experiments. In the BSA molecule, the measured interference fringe is consistent with the model in which the short axes of BSA molecules are perpendicular to the surface substrate.


Assuntos
Ferritinas/química , Conformação Proteica , Soroalbumina Bovina/química , Difração de Raios X/métodos , Fluorescência , Microscopia Eletrônica de Varredura
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