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1.
Int J Oral Maxillofac Surg ; 48(8): 1102-1108, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30745243

RESUMO

The aim of this study was to compare the safety of tooth extraction in patients receiving direct oral anticoagulants (DOACs) or warfarin without cessation of their antithrombotic treatment. This prospective observational study included 367 patients undergoing tooth extraction (119 receiving DOACs and 248 receiving warfarin). All extractions in DOAC patients were performed 6-7h after taking DOACs in consideration of the half-life in blood under continued antithrombotic treatment. To examine the potential postoperative bleeding risk related to the time of extraction and the drug concentration of blood, activated partial thromboplastin time (APTT) in dabigatran and prothrombin time (PT) in rivaroxaban were measured three times after administration. A total of 390 tooth extractions were performed: 128 in the DOAC patients and 262 in warfarin patients. Postoperative bleeding occurred in four extractions (3.1%) in the DOAC group and in 23 (8.8%) in the warfarin group. There was no statistically significant difference between the two groups (odds ratio: 2.362, 95% confidence interval (CI) 0.819-6.815, p=0.112). APTT and PT prolongation in almost all cases decreased with time after taking the medicine. Our findings suggest that interruption of DOAC therapy is not necessary for tooth extraction if the procedure is performed at least 6h after the last dose.


Assuntos
Anticoagulantes , Varfarina , Administração Oral , Humanos , Estudos Prospectivos , Extração Dentária
2.
J Infect Dis ; 218(1): 95-108, 2018 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-29767739

RESUMO

Background: A 9-valent human papillomavirus-6/11/16/18/31/33/45/52/58 (9vHPV) vaccine extends coverage to 5 next most common oncogenic types (31/33/45/52/58) in cervical cancer versus quadrivalent HPV (qHPV) vaccine. We describe efficacy, immunogenicity, and safety in Asian participants (India, Hong Kong, South Korea, Japan, Taiwan, and Thailand) from 2 international studies: a randomized, double-blinded, qHPV vaccine-controlled efficacy study (young women aged 16-26 years; NCT00543543; Study 001); and an immunogenicity study (girls and boys aged 9-15 years; NCT00943722; Study 002). Methods: Participants (N = 2519) were vaccinated at day 1 and months 2 and 6. Gynecological samples (Study 001 only) and serum were collected for HPV DNA and antibody assessments, respectively. Injection-site and systemic adverse events (AEs) were monitored. Data were analyzed by country and vaccination group. Results: 9vHPV vaccine prevented HPV-31/33/45/52/58-related persistent infection with 90.4%-100% efficacy across included countries. At month 7, ≥97.9% of participants seroconverted for each HPV type. Injection-site AEs occurred in 77.7%-83.1% and 81.9%-87.5% of qHPV and 9vHPV vaccine recipients in Study 001, respectively, and 62.4%-85.7% of girls/boys in Study 002; most were mild to moderate. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Asian participants. Data support 9vHPV vaccination programs in Asia. Clinical Trials Registration: NCT00543543; NCT00943722.


Assuntos
Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/efeitos adversos , Vacinas contra Papillomavirus/imunologia , Adolescente , Adulto , Anticorpos Antivirais/sangue , Ásia/epidemiologia , Criança , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Genitália Feminina/virologia , Humanos , Masculino , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Vacinas contra Papillomavirus/administração & dosagem , Resultado do Tratamento , Adulto Jovem
3.
J Child Orthop ; 11(1): 20-27, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28439305

RESUMO

OBJECTIVES: The purpose of this study is to evaluate the effects of allogenic costal cartilage transplantation on preventing bony bridge formation and angular deformities for the treatment of partial growth plate injury using a rabbit model. METHODS: An experimental model of partial growth injury was created by resecting the medial part of the proximal tibial growth plate in male six-week-old New Zealand White rabbits. The rabbits were divided into four groups: no surgery; no transplantation; bone wax transplantation; and allogenic costal cartilage transplantation. The angular deformities of the tibia and bony bridge were analysed using radiographs and microcomputed tomography, and the repair of the injured growth plate cartilage and bony bridge formation rate were histologically evaluated. RESULTS: On radiographic evaluation, the varus deformities in the costal cartilage group were significantly improved compared with the no transplantation group at four and eight weeks after operation and with the bone wax group at eight weeks after operation. Micro-computed tomography showed that the bony bridge formation was prevented in the bone wax and costal cartilage groups. Histological findings showed that the bony bridge formation in the bone wax and costal cartilage group was decreased. In addition, the growth plate was continuous and stained with safranin O and immunohistochemically stained for type II collagen. CONCLUSION: Transplantation of costal cartilage improved angular deformities and decreased bony bridge formation in the partial growth plate injury. Costal cartilage might be a suitable graft for the treatment of growth plate injury.

4.
Bone Joint J ; 98-B(5): 666-71, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27143739

RESUMO

AIMS: To clarify the asymmetrical ossification of the epiphyseal ring between the convex and concave sides in patients with adolescent idiopathic scoliosis (AIS). PATIENTS AND METHODS: A total of 29 female patients (mean age, 14.4 years; 11 to 18) who underwent corrective surgery for AIS (Lenke type 1 or 2) were included in our study. In all, 349 vertebrae including 68 apical vertebrae and 87 end vertebrae in the main thoracic (MT) curve and thoracolumbar/lumbar (TL/L) curve were analysed. Coronal sections (anterior, middle and posterior) of the vertebral bodies were reconstructed from pre-operative CT scans (320-row detector; slice thickness, 0.5 mm) and the appearances of the ossification centre in the epiphyseal ring at four corners were evaluated in three groups; all vertebrae excluding end vertebrae, apical vertebrae and end vertebrae. The appearance rates of the ossification centre at the concave and convex sides were calculated and compared. RESULTS: The appearance rates of the ossification centres in all vertebrae excluding end vertebrae and apical vertebrae were significantly lower on the concave side than on the convex side in both MT and TL/L curves irrespective of curve flexibility. There was no significant difference in the rate of appearance of the ossification centres on the concave or convex sides in end vertebrae. CONCLUSION: The asymmetric bony growth of vertebral body came into existence at both structural and non-structural curves, and was more apparent around the apical vertebrae. Evaluation of the ossification centre in the epiphyseal ring could be a measure of the effectiveness of brace treatment. TAKE HOME MESSAGE: The ossification of the epiphyseal ring in patients with AIS was delayed or absent on the concave side particularly around the apical vertebrae. Cite this article: Bone Joint J 2016;98-B:666-71.


Assuntos
Epífises/anormalidades , Epífises/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Osteogênese , Escoliose/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagem , Adolescente , Criança , Feminino , Humanos , Vértebras Lombares/anormalidades , Vértebras Lombares/cirurgia , Masculino , Tomografia Computadorizada Multidetectores , Estudos Retrospectivos , Escoliose/cirurgia , Vértebras Torácicas/anormalidades , Vértebras Torácicas/cirurgia
5.
Osteoarthritis Cartilage ; 24(8): 1413-22, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26973329

RESUMO

OBJECTIVE: To assess whether synovial mesenchymal stem cells (SMSCs) from patients with osteoarthritis (OA) or rheumatoid arthritis (RA) can be used as an alternative cell source for cartilage repair using allogenic tissue engineered construct (TEC). METHODS: Twenty-five patients (17 female, average age 61.8 years) were divided according to their pathology (control trauma group; N = 6, OA group; N = 6) and RA patients were subdivided into two groups to evaluate the impact of biologics in accordance with whether treated with biologics [Bio(+)RA; N = 7] or not [Bio(-)RA; N = 6]. We compared the following characteristics among these groups: (1) The cell proliferation capacity of SMSCs; (2) The influence of passage number on features of SMSCs; (3) The weight and volume of TEC from the same number of SMSCs; (4) Inflammatory cytokine gene expressions levels of TEC; (5) The chondrogenic potential of TEC; and (6) Osteochondral repair using TEC in athymic nude rats. RESULTS: SMSCs from the four groups exhibited equivalent features in the above evaluation items. In in vivo studies, the TEC-treated repair tissues for all groups exhibited significantly better outcomes than those for the untreated group and no significant differences among the four TEC groups. CONCLUSION: SMSCs from OA or RA patients are no less appropriate for repairing cartilage than those from trauma patients and thus, may be an effective source for allogenic cell-based cartilage repair.


Assuntos
Células-Tronco Mesenquimais , Animais , Artrite Reumatoide , Cartilagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ratos , Membrana Sinovial , Engenharia Tecidual
6.
Vet Comp Oncol ; 14(4): 371-383, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25212092

RESUMO

Feline oral squamous cell carcinoma (SCC) has very poor prognosis. Here, a retrospective pilot study was conducted on 20 feline oral SCC patients who underwent stereotactic radiation therapy (SRT), to evaluate: (1) the value of putative tumour initiating cell (TIC) markers of human head and neck SCC (CD44, Bmi-1); (2) telomere length (TL) specifically in putative TICs; and (3) tumour relative telomerase activity (TA). Significant inverse correlations were found between treatment outcomes and Bmi-1 expression, supporting the predictive value of Bmi-1 as a negative prognostic indicator. While TL exhibited a wide range of variability, particularly in very short fractions, many tumours possessed high levels of TA, which correlated with high levels of Bmi-1, Ki67 and EGFR. Taken together, our results imply that Bmi-1 and telomerase may represent novel therapeutic targets in feline oral SCC, as their inhibition - in combination with SRT - would be expected to have beneficial treatment outcome.


Assuntos
Carcinoma de Células Escamosas/veterinária , Doenças do Gato/patologia , Neoplasias Bucais/veterinária , Células-Tronco Neoplásicas/patologia , Telomerase/metabolismo , Animais , Biomarcadores Tumorais , Carcinoma de Células Escamosas/patologia , Doenças do Gato/terapia , Gatos , Feminino , Masculino , Neoplasias Bucais/patologia , Valor Preditivo dos Testes , Telômero
7.
Vet Comp Oncol ; 14(1): 28-38, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23782408

RESUMO

18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (18FDG-PET/CT) has been shown to be effective for staging human oral squamous cell carcinoma (SCC) but its application for cats with oral SCC is unknown. Twelve cats with biopsy-proven oral SCC were imaged with whole body 18FDG-PET/CT to determine its value as a diagnostic imaging and staging tool and fine needle aspirates were obtained of accessible regional lymph nodes. All tumors were FDG avid and conspicuous on 18FDG-PET/CT images, with an average of the maximum standardized uptake value 9.88 ± 5.33 SD (range 2.9-24.9). Soft tissue infiltrative tumors that were subtle and ill defined on CT were highly visible and more extensive on FDG-PET/CT. Tumors invading the osseous structures were more similar in extent on 18FDG-PET/CT and CT although they were more conspicuous on PET images. Three cytologically confirmed metastases were hypermetabolic on PET, while two of those metastases were equivocal on CT.


Assuntos
Carcinoma de Células Escamosas/veterinária , Doenças do Gato/diagnóstico , Fluordesoxiglucose F18/farmacologia , Neoplasias Bucais/veterinária , Tomografia por Emissão de Pósitrons/veterinária , Tomografia Computadorizada por Raios X/veterinária , Animais , Carcinoma de Células Escamosas/diagnóstico , Doenças do Gato/patologia , Gatos , Feminino , Linfonodos/patologia , Masculino , Neoplasias Bucais/diagnóstico
8.
Vet Comp Oncol ; 14(1): 39-57, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23815402

RESUMO

This study evaluated molecular characteristics that are potentially prognostic in cats with oral squamous cell carcinoma (SCC) that underwent stereotactic radiation therapy (SRT). Survival time (ST) and progression-free interval (PFI) were correlated with mitotic index, histopathological grades, Ki67 and epidermal growth factor receptor expressions, tumour microvascular density (MVD), and tumour oxygen tension (pO(2)). Median ST and PFI were 106 and 87 days, respectively (n = 20). Overall response rate was 38.5% with rapid improvement of clinical symptoms in many cases. Patients with higher MVD or more keratinized SCC had significantly shorter ST or PFI than patients with lower MVD or less keratinized SCC (P = 0.041 and 0.049, respectively). Females had significantly longer PFI and ST than males (P ≤ 0.016). Acute toxicities were minimal. However, treatment-related complications such as fractured mandible impacted quality of life. In conclusion, SRT alone should be considered as a palliative treatment. MVD and degree of keratinization may be useful prognostic markers.


Assuntos
Carcinoma de Células Escamosas/veterinária , Doenças do Gato/radioterapia , Neoplasias Bucais/veterinária , Técnicas Estereotáxicas/veterinária , Animais , Carcinoma de Células Escamosas/radioterapia , Gatos , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Imuno-Histoquímica , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Masculino , Neoplasias Bucais/radioterapia , Consumo de Oxigênio , Prognóstico , Análise de Sobrevida
9.
Bone Joint Res ; 3(9): 280-8, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25237168

RESUMO

OBJECTIVE: Excessive mechanical stress on synovial joints causes osteoarthritis (OA) and results in the production of prostaglandin E2 (PGE2), a key molecule in arthritis, by synovial fibroblasts. However, the relationship between arthritis-related molecules and mechanical stress is still unclear. The purpose of this study was to examine the synovial fibroblast response to cyclic mechanical stress using an in vitro osteoarthritis model. METHOD: Human synovial fibroblasts were cultured on collagen scaffolds to produce three-dimensional constructs. A cyclic compressive loading of 40 kPa at 0.5 Hz was applied to the constructs, with or without the administration of a cyclooxygenase-2 (COX-2) selective inhibitor or dexamethasone, and then the concentrations of PGE2, interleukin-1ß (IL-1ß), tumour necrosis factor-α (TNF-α), IL-6, IL-8 and COX-2 were measured. RESULTS: The concentrations of PGE2, IL-6 and IL-8 in the loaded samples were significantly higher than those of unloaded samples; however, the concentrations of IL-1ß and TNF-α were the same as the unloaded samples. After the administration of a COX-2 selective inhibitor, the increased concentration of PGE2 by cyclic compressive loading was impeded, but the concentrations of IL-6 and IL-8 remained high. With dexamethasone, upregulation of PGE2, IL-6 and IL-8 was suppressed. CONCLUSION: These results could be useful in revealing the molecular mechanism of mechanical stress in vivo for a better understanding of the pathology and therapy of OA. Cite this article: Bone Joint Res 2014;3:280-8.

10.
Bone Joint J ; 96-B(2): 237-41, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24493190

RESUMO

We retrospectively assessed the value of identifying impinging osteophytes using dynamic computer simulation of CT scans of the elbow in assisting their arthroscopic removal in patients with osteoarthritis of the elbow. A total of 20 patients were treated (19 men and one woman, mean age 38 years (19 to 55)) and followed for a mean of 25 months (24 to 29). We located the impinging osteophytes dynamically using computerised three-dimensional models of the elbow based on CT data in three positions of flexion of the elbow. These were then removed arthroscopically and a capsular release was performed. The mean loss of extension improved from 23° (10° to 45°) pre-operatively to 9° (0° to 25°) post-operatively, and the mean flexion improved from 121° (80° to 140°) pre-operatively to 130° (110° to 145°) post-operatively. The mean Mayo Elbow Performance Score improved from 62 (30 to 85) to 95 (70 to 100) post-operatively. All patients had pain in the elbow pre-operatively which disappeared or decreased post-operatively. According to their Mayo scores, 14 patients had an excellent clinical outcome and six a good outcome; 15 were very satisfied and five were satisfied with their post-operative outcome. We recommend this technique in the surgical management of patients with osteoarthritis of the elbow.


Assuntos
Artroscopia/métodos , Simulação por Computador , Desbridamento/métodos , Articulação do Cotovelo/cirurgia , Osteoartrite/cirurgia , Amplitude de Movimento Articular , Adulto , Articulação do Cotovelo/diagnóstico por imagem , Articulação do Cotovelo/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/diagnóstico por imagem , Osteoartrite/fisiopatologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
11.
Bone Joint J ; 95-B(10): 1320-5, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24078526

RESUMO

We investigated differences in the location and mode of labral tears between dysplastic hips and hips with femoroacetabular impingement (FAI). We also investigated the relationship between labral tear and adjacent cartilage damage. We retrospectively studied 72 symptomatic hips (in 68 patients: 19 men and 49 women) with radiological evidence of dysplasia or FAI on high-resolution CT arthrography. The incidence and location of labral tears and modes of tear associated with the base of the labrum (Mode 1) or body of the labrum (Mode 2) were compared among FAI, mildly dysplastic and severely dysplastic hips. The locations predominantly involved with labral tears were different in FAI and mild dysplastic hips (anterior and anterosuperior zones) and in severely dysplastic hips (anterosuperior and superior zones) around the acetabulum. Significant differences were observed in the prevalence of Mode 1 versus Mode 2 tears in FAI hips (72% (n = 13) vs 28% (n = 5)) and severe dysplastic hips (25% (n = 2) vs 75% (n = 6)). The frequency of cartilage damage adjacent to Mode 1 tears was significantly higher (42% (n = 14)) than that adjacent to Mode 2 tears (14% (n = 3)). Hip pathology is significantly related to the locations and modes of labral tears. Mode 1 tears may be a risk factor for the development of adjacent acetabular cartilage damage.


Assuntos
Acetábulo/lesões , Cartilagem Articular/lesões , Impacto Femoroacetabular/complicações , Luxação Congênita de Quadril/complicações , Acetábulo/diagnóstico por imagem , Adolescente , Adulto , Idoso , Cartilagem Articular/diagnóstico por imagem , Criança , Feminino , Impacto Femoroacetabular/diagnóstico por imagem , Luxação Congênita de Quadril/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Adulto Jovem
12.
Br J Cancer ; 109(7): 1760-5, 2013 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-24002604

RESUMO

BACKGROUND: Radical hysterectomy is recommended for endometrial adenocarcinoma patients with suspected gross cervical involvement. However, the efficacy of operative procedure has not been confirmed. METHODS: The patients with endometrial adenocarcinoma who had suspected gross cervical involvement and underwent hysterectomy between 1995 and 2009 at seven institutions were retrospectively analysed (Gynecologic Oncology Trial and Investigation Consortium of North Kanto: GOTIC-005). Primary endpoint was overall survival, and secondary endpoints were progression-free survival and adverse effects. RESULTS: A total of 300 patients who underwent primary surgery were identified: 74 cases with radical hysterectomy (RH), 112 patients with modified radical hysterectomy (mRH), and 114 cases with simple hysterectomy (SH). Median age was 47 years, and median duration of follow-up was 47 months. There were no significant differences of age, performance status, body mass index, stage distribution, and adjuvant therapy among three groups. Multi-regression analysis revealed that age, grade, peritoneal cytology status, and lymph node involvement were identified as prognostic factors for OS; however, type of hysterectomy was not selected as independent prognostic factor for local recurrence-free survival, PFS, and OS. Additionally, patients treated with RH had longer operative time, higher rates of blood transfusion and severe urinary tract dysfunction. CONCLUSION: Type of hysterectomy was not identified as a prognostic factor in endometrial cancer patients with suspected gross cervical involvement. Perioperative and late adverse events were more frequent in patients treated with RH. The present study could not find any survival benefit from RH for endometrial cancer patients with suspected gross cervical involvement. Surgical treatment in these patients should be further evaluated in prospective clinical studies.


Assuntos
Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Neoplasias do Endométrio/cirurgia , Histerectomia , Neoplasias do Colo do Útero/cirurgia , Índice de Massa Corporal , Colo do Útero/cirurgia , Intervalo Livre de Doença , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Histerectomia/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidade
13.
Br J Cancer ; 109(6): 1703-10, 2013 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-23949151

RESUMO

BACKGROUND: We and others previously reported the prognostic significance of PTEN mutational status on favourable survival in endometrial carcinomas. Here, we demonstrate that loss of PTEN expression in immunohistochemistry is an independent prognostic marker for favourable survival in endometrial carcinomas. METHODS: We conducted immunohistochemical analyses of PTEN, PIK3CA, phosphorylated Akt (p-Akt), and p27 in primary endometrial carcinomas from 221 patients. Mutation of PTEN was analysed further. RESULTS: Expression of PTEN was lost in 56 patients (25%), and PIK3CA was overexpressed in 159 patients (72%). Overexpression of PIK3CA was associated with p-Akt overexpression (P<0.001), which was in turn associated with loss of nuclear p27 expression (P=0.028). Loss of PTEN expression was found to be associated with endometrioid histology (P=0.03), and was inversely associated with the presence of lymphovascular space invasion (P=0.03). Univariate and multivariate survival analyses revealed that factors of PTEN loss, age <70, histological grade 1, early International Federation of Gynecology and Obstetrics (FIGO) stage, and absence of lymphovascular invasion were independent prognostic indicators for better overall survival (P=0.03, 0.04, 0.01, <0.001, and 0.03, respectively). The subset analysis showed a stronger tendency of PTEN loss towards favourable survival in advanced-stage (III and IV) disease than in early-stage (I and II) disease (P=0.05 vs 0.14). Moreover, our mutational analysis demonstrated that PTEN expression loss was associated with PTEN-truncating mutations (P=0.03). CONCLUSION: The current observations further support the prognostic significance of PTEN aberration on favourable outcome in endometrial carcinomas, providing useful implications for the individualised management of the disease.


Assuntos
Neoplasias do Endométrio/enzimologia , PTEN Fosfo-Hidrolase/deficiência , Adulto , Idoso , Idoso de 80 Anos ou mais , Classe I de Fosfatidilinositol 3-Quinases , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , PTEN Fosfo-Hidrolase/biossíntese , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/biossíntese , Fosforilação , Análise de Sobrevida
14.
Cell Death Dis ; 4: e698, 2013 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-23807227

RESUMO

Small G proteins of the Rho family are pivotal regulators of several signaling networks. The Ras homolog family (Rho) and one of its targets, Rho-associated protein kinase (ROCK), participate in a wide variety of biological processes, including bone formation. A previous study has demonstrated that the ROCK inhibitor Y-27632 enhanced bone formation induced by recombinant human bone morphogenetic protein-2 (BMP-2) in vivo and in vitro. However, the effect of other Rho family members, such as Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division cycle 42 (Cdc42), on bone formation remains unknown. In this study, we investigated whether Rac1 also participates in BMP-2-induced osteogenesis. Expression of a dominant-negative mutant of Rac1 enhanced BMP-2-induced osteoblastic differentiation in C2C12 cells, whereas a constitutively active mutant of Rac1 attenuated that effect. Knockdown of T-lymphoma invasion and metastasis 1 (Tiam1), a Rac-specific guanine nucleotide exchange factor, enhanced BMP-2-induced alkaline phosphatase activity. Further, we demonstrated that BMP-2 stimulated Rac1 activity. These results indicate that the activation of Rac1 attenuates osteoblastic differentiation in C2C12 cells.


Assuntos
Proteína Morfogenética Óssea 2/fisiologia , Diferenciação Celular , Neuropeptídeos/genética , Osteoblastos/fisiologia , Proteínas rac1 de Ligação ao GTP/genética , Fosfatase Alcalina/metabolismo , Aminoquinolinas/farmacologia , Animais , Biomarcadores/metabolismo , Linhagem Celular , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Ativação Enzimática , Técnicas de Silenciamento de Genes , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Humanos , Camundongos , Neuropeptídeos/antagonistas & inibidores , Neuropeptídeos/metabolismo , Osteocalcina/metabolismo , Osteogênese , Pirimidinas/farmacologia , Transdução de Sinais , Proteínas Smad/metabolismo , Proteína 1 Indutora de Invasão e Metástase de Linfoma de Células T , Proteínas rac1 de Ligação ao GTP/antagonistas & inibidores , Proteínas rac1 de Ligação ao GTP/metabolismo
15.
Br J Cancer ; 108(10): 1957-63, 2013 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-23640393

RESUMO

BACKGROUND: A phase III trial was conducted to determine whether neoadjuvant chemotherapy (NACT) before radical surgery (RS) improves overall survival. METHODS: Patients with stage IB2, IIA2, or IIB squamous cell carcinoma of the uterine cervix were randomly assigned to receive either BOMP (bleomycin 7 mg days 1-5, vincristine 0.7 mg m(-2) day 5, mitomycin 7 mg m(-2) day 5, cisplatin 14 mg m(-2) days 1-5, every 3 weeks for 2 to 4 cycles) plus RS (NACT group) or RS alone (RS group). Patients with pathological high-risk factors received postoperative radiotherapy (RT). The primary end point was overall survival. RESULTS: A total of 134 patients were randomly assigned to treatment. This study was prematurely terminated at the first planned interim analysis because overall survival in the NACT group was inferior to that in the RS group. Patients who received postoperative RT were significantly lower in the NACT group (58%) than in the RS group (80%; P=0.015). The 5-year overall survival was 70.0% in the NACT group and 74.4% in the RS group (P=0.85). CONCLUSION: Neoadjuvant chemotherapy with BOMP regimen before RS did not improve overall survival, but reduced the number of patients who received postoperative RT.


Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Bleomicina/uso terapêutico , Braquiterapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Terapia Combinada , Feminino , Humanos , Histerectomia/métodos , Japão , Oncologia/organização & administração , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Mitomicina/uso terapêutico , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Vincristina/administração & dosagem , Vincristina/uso terapêutico , Adulto Jovem
16.
Technol Cancer Res Treat ; 12(5): 447-53, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23547976

RESUMO

The purpose of this study is to evaluate the real-time respiratory motion of the prostate and surrounding tissues/organs in the supine and prone positions and to investigate, using cine-MRI, whether a belly board can reduce respiratory-induced motion in the prone position. Cine-MRI scans were made of 13 volunteers in the supine and prone positions on a flat board and in two different prone positions using a belly board. Images in cine mode were recorded for 20 seconds. For each session, the points of interest (POIs) were located at the apex, base, mid-anterior surface and mid-posterior surface of the prostate; the tip of the seminal vesicle; the pubic symphysis; and the sacrum. The maximum range and standard deviation (SD) of the displacement from the mean value were calculated. The SDs for each of the four different positions were compared using a paired t-test. Respiratory-induced prostate motion was significantly larger in the prone position than in the supine position. However, when a belly board was used in the prone position, motion in the prostate and surrounding tissues/organs was significantly reduced. There were no significant differences between the two different positions using a belly board in any of the POIs.


Assuntos
Movimento , Posicionamento do Paciente/instrumentação , Próstata , Neoplasias da Próstata/radioterapia , Mecânica Respiratória , Adulto , Idoso , Pontos de Referência Anatômicos , Humanos , Imagem Cinética por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Decúbito Ventral , Sínfise Pubiana , Sacro , Glândulas Seminais , Decúbito Dorsal
17.
Scand J Rheumatol ; 42(4): 253-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23470089

RESUMO

OBJECTIVES: The retention of the anti-rheumatic agent tocilizumab (TCZ) has not been well documented in patients with rheumatoid arthritis (RA). We conducted an observational study to compare the retention of TCZ and anti-tumour necrosis factor (TNF) drugs in the treatment of patients with RA. METHOD: We reviewed continuation rates and causes of discontinuation of biological agents (biologics) by assessing medical records of patients with RA who were administered biologics at our institute from September 1999 to April 2012, using the Osaka University Biologics for Rheumatic Diseases (BiRD) registry. RESULTS: A total of 401 patients were included. TCZ, infliximab (IFX), etanercept (ETN), and adalimumab (ADA) were administered to 97, 103, 143, and 58 patients, respectively. There were some differences between the baseline characteristics of the groups. The median duration (range) of TCZ, IFX, ETN, and ADA administration was 2.5 (0.1-12.6), 1.9 (0.0-7.7), 2.9 (0.0-11.3), and 1.3 (0.0-3.4) years, respectively. Continuation rates for TCZ and ETN were significantly higher than those for IFX and ADA. Multivariate analyses showed that discontinuation due to lack or loss of efficacy was significantly less common in the TCZ group than in the other groups. Discontinuation due to overall adverse events was not significantly different between treatment groups. CONCLUSION: TCZ and ETN show better retention than IFX or ADA in the treatment of RA.


Assuntos
Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais/farmacocinética , Artrite Reumatoide/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Artrite Reumatoide/diagnóstico , Estudos de Coortes , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Infliximab , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
18.
J Hand Surg Eur Vol ; 38(2): 133-43, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22736743

RESUMO

To estimate the accuracy of radiographic deformity evaluation for distal radius malunion, we compared the results obtained from radiographic measurements (palmar tilt, radial angle, and ulnar variance) with those from the three-dimensional (3D) method using computer bone models in 20 dorsally tilted malunions. Dorsal tilt deformity, radial tilt deformity, and shortening deformity were calculated using the unaffected side as a reference. The 3D method showed a slightly lower value for dorsal tilt deformity than the radiographic evaluation, but the difference was < 10° in all cases. In patients with dorsal tilt ≥ 40°, notable differences in radial tilt evaluation were observed between the two methods compared with patients with less dorsal tilt. The 3D shortening showed positive correlations with radiographic evaluation, but a discrepancy of ≥ 2 mm was observed in eight cases. Palmar tilt is reliable for surgical planning, but radial angle and ulnar variance may be less accurate than previously thought.


Assuntos
Fraturas Mal-Unidas/diagnóstico por imagem , Imageamento Tridimensional/métodos , Fraturas do Rádio/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Distribuição de Qui-Quadrado , Feminino , Fixação de Fratura/métodos , Fraturas Mal-Unidas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Interpretação de Imagem Radiográfica Assistida por Computador , Fraturas do Rádio/terapia , Análise de Regressão , Reprodutibilidade dos Testes , Resultado do Tratamento
20.
Osteoarthritis Cartilage ; 20(11): 1383-90, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22846714

RESUMO

OBJECTIVE: Previous studies have shown that meniscectomy results in an increase of local load transmission and may cause degeneration of the knee cartilage. Using 3D reconstructed T2 mapping, we examined the influence on the femoral cartilage under loading after medial meniscectomy. DESIGN: Ten porcine knees were imaged using a pressure device and a 3.0-T magnetic resonance imaging (MRI) system. Consecutive sagittal T2 maps were obtained in neutral alignment with and without compression, and under compression at 10° varus alignment. After medial meniscectomy, the aforementioned MRI was repeated. Cartilage T2 before and after meniscectomy under each condition were compared at the 12 regions of interest (ROIs) defined on the 3D weight-bearing area of the femoral cartilage. RESULTS: Before meniscectomy, large decreases in T2 under neutral compression were mainly seen at the anterior and central ROIs of the medial cartilage, which shifted to the posterior ROIs after meniscectomy. There were significant differences in decrease in T2 ratio with loading before and after meniscectomy (9.8%/4.3% at the anterior zone, 4.0%/11.4% at the posterior zone, P < 0.05). By applying varus compression, a more remarkable decrease in the cartilage T2 in posterior ROIs after meniscectomy was achieved. (Before/after meniscectomy: 8.7%/2.5% at the anterior zone, 7.2%/18.7% at the posterior zone, P < 0.05). CONCLUSIONS: Assuming a decrease in T2 with loading correlated with the applied pressure, a deficiency of the medial meniscus resulted in a shift of the primary area with a maximal decrease of cartilage T2 with loading posteriorly in the porcine knee joint, presumably reflecting the intraarticular environment of load transmission.


Assuntos
Artroscopia/efeitos adversos , Cartilagem Articular/patologia , Meniscos Tibiais/cirurgia , Joelho de Quadrúpedes/patologia , Animais , Cartilagem Articular/fisiopatologia , Modelos Animais de Doenças , Imageamento por Ressonância Magnética , Meniscos Tibiais/fisiopatologia , Joelho de Quadrúpedes/fisiopatologia , Joelho de Quadrúpedes/cirurgia , Suínos , Suporte de Carga
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