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1.
Physiol Int ; 105(1): 86-99, 2018 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-29602291

RESUMEN

This study aimed to evaluate neuromuscular activation in the scalene and sternocleidomastoid muscles using surface electromyography (EMG) during progressively increased inspiratory flow, produced by increasing the respiratory rate under inspiratory-resistive loading using a mask ventilator. Moreover, we attempted to identify the EMG inflection point (EMGIP) on the graph, at which the root mean square (RMS) of the EMG signal values of the inspiratory muscles against the inspiratory flow velocity acceleration abruptly increases, similarly to the EMG anaerobic threshold (EMGAT) reported during incremental-resistive loading in other skeletal muscles. We measured neuromuscular activation of healthy male subjects and found that the inspiratory flow velocity increased by approximately 1.6-fold. We successfully observed an increase in RMS that corresponded to inspiratory flow acceleration with ρ ≥ 0.7 (Spearman's rank correlation) in 17 of 27 subjects who completed the experimental protocol. To identify EMGIP, we analyzed the fitting to either a straight or non-straight line related to the increasing inspiratory flow and RMS using piecewise linear spline functions. As a result, EMGIP was identified in the scalene and sternocleidomastoid muscles of 17 subjects. We believe that the identification of EMGIP in this study infers the existence of EMGAT in inspiratory muscles. Application of surface EMG, followed by identification of EMGIP, for evaluating the neuromuscular activation of respiratory muscles may be allowed to estimate the signs of the respiratory failure, including labored respiration, objectively and non-invasively accompanied using accessory muscles in clinical respiratory care.


Asunto(s)
Potenciales de Acción , Resistencia de las Vías Respiratorias , Electromiografía , Inhalación , Unión Neuromuscular/fisiología , Músculos Respiratorios/inervación , Adulto , Estudios Transversales , Voluntarios Sanos , Humanos , Masculino , Respiración Artificial , Frecuencia Respiratoria , Factores de Tiempo
2.
Bone Joint J ; 98-B(9): 1167-74, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27587515

RESUMEN

AIMS: Femoroacetabular impingement (FAI) has been highlighted and well documented primarily in Western countries and there are few large studies focused on FAI-related morphological assessment in Asian patients. We chose to investigate this subject. PATIENTS AND METHODS: We assessed the morphology of the hip and the prevalence of radiographic FAI in Japanese patients by measuring predictors of FAI. We reviewed a total of 1178 hips in 695 men and 483 women with a mean age of 58.2 years (20 to 89) using CT images that had been obtained for reasons unrelated to symptoms from the hip. We measured the lateral centre edge angle, acetabular index, crossover sign, alpha angle and anterior femoral head-neck offset ratio. RESULTS: A total of 441 hips (37.4%) had pincer-type deformity (41.7% men, 31.3% women) and 534 (45.3%) had cam-type deformity (54.4% men, 32.3% women). Moreover, 773 hips (65.6%) had at least one parameter that predisposes to FAI (74.0% men, 53.6% women) and 424 hips (36.0%) had two or more parameters (43.6% men, 25.0% women). CONCLUSION: The prevalence of radiographic FAI was common in Japanese patients who are generally considered to have dysplastic hips. Cite this article: Bone Joint J 2016;98-B:1167-74.


Asunto(s)
Pinzamiento Femoroacetabular/diagnóstico , Pinzamiento Femoroacetabular/epidemiología , Imagenología Tridimensional , Tomografía Computarizada por Rayos X/métodos , Acetábulo/anomalías , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Cabeza Femoral/anomalías , Luxación de la Cadera/diagnóstico , Luxación de la Cadera/epidemiología , Humanos , Japón/epidemiología , Persona de Mediana Edad , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Prevalencia , Rango del Movimiento Articular/fisiología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Distribución por Sexo , Adulto Joven
3.
Br J Surg ; 103(1): 60-9, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26572241

RESUMEN

BACKGROUND: The aim of this study was to evaluate whether MRI at 3 T with superparamagnetic iron oxide (SPIO) enhancement is an accurate and useful method for detecting metastases in sentinel nodes identified by CT-lymphography (CT-LG) in patients with breast cancer. The results were compared with those obtained using CT-LG alone and diagnosing metastasis according to size criteria. METHODS: Patients with clinically node-negative breast cancer were included. Sentinel nodes identified by CT-LG were evaluated prospectively using SPIO-enhanced MRI at 3 T. Sentinel node size was measured on CT-LG, and a node larger than 5 mm in short-axis diameter was considered metastatic. Sentinel nodes localized by CT-LG were removed, and imaging results and histopathological findings were compared. RESULTS: Sentinel nodes were identified successfully by CT-LG in 69 (99 per cent) of 70 patients. All 19 patients with a finding of metastasis in sentinel nodes at pathology were also shown to have metastases on MRI. Forty-eight of 50 patients with non-metastatic sentinel nodes diagnosed at pathology were classified as having non-metastatic nodes on MRI. On a patient-by-patient basis, the sensitivity, specificity and accuracy of MRI for the diagnosis of sentinel node metastases were 100, 96 and 97 per cent; respective values for CT-LG were 79, 56 and 62 per cent. The specificity and accuracy of MRI were superior to those of CT-LG (P < 0·001 and P = 0·002 respectively). CONCLUSION: SPIO-enhanced MRI at 3 T is useful for accurate diagnosis of metastatic sentinel nodes, indicating that sentinel node biopsy may be avoided in patients with breast cancer who have non-metastatic sentinel nodes on imaging.


Asunto(s)
Neoplasias de la Mama/patología , Medios de Contraste , Compuestos Férricos , Ganglios Linfáticos/patología , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X , Adulto , Anciano , Axila , Neoplasias de la Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/patología , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Lobular/diagnóstico por imagen , Carcinoma Lobular/patología , Femenino , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Sensibilidad y Especificidad
4.
Clin Oncol (R Coll Radiol) ; 26(10): 653-60, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25034088

RESUMEN

AIMS: Data on primary central nervous system lymphoma that had been collected through surveys for four consecutive periods between 1985 and 2009 were analysed to evaluate outcomes according to treatment. MATERIALS AND METHODS: All had histologically proven disease and had received radiotherapy. No patients had AIDS. Among 1054 patients, 696 died and 358 were alive or lost to follow-up. The median follow-up period for surviving patients was 37 months. RESULTS: For all patients, the median survival time was 24 months; the 5 year survival rate was 25.8%. Patients treated with methotrexate-based chemotherapy and radiation had a higher 5 year survival rate (43%) than those treated with radiation alone (14%) and those treated with non-methotrexate chemotherapy plus radiation (20%), but differences in relapse-free survival were smaller among the three groups. The 5 year survival rate was 25% for patients treated with whole-brain irradiation and 29% for patients treated with partial-brain irradiation (P = 0.80). Patients receiving a total dose of 40-49.9 Gy had a higher 5 year survival rate (32%) than those receiving other doses (21-25%, P = 0.0004) and patients receiving a whole-brain dose of 30-39.9 Gy had a higher 5 year survival rate (32%) than those receiving ≥40 Gy (13-22%, P < 0.0005). Patients receiving methotrexate-based chemotherapy and partial-brain radiotherapy (≥30 Gy) had a 5 year survival rate of 49%. CONCLUSIONS: The optimal total and whole-brain doses may be in the range of 40-49.9 and <40 Gy, respectively, especially in combination with chemotherapy. Patients receiving partial-brain irradiation had a prognosis similar to that of those receiving whole-brain irradiation. With methotrexate-based chemotherapy, partial-brain radiotherapy may be worth considering for non-elderly patients with a single tumour.


Asunto(s)
Neoplasias del Sistema Nervioso Central/radioterapia , Quimioradioterapia/mortalidad , Irradiación Craneana , Linfoma/radioterapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/mortalidad , Neoplasias del Sistema Nervioso Central/patología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Linfoma/tratamiento farmacológico , Linfoma/mortalidad , Linfoma/patología , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Dosificación Radioterapéutica , Tasa de Supervivencia , Factores de Tiempo
5.
Ann Oncol ; 23(12): 3051-3057, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22767585

RESUMEN

BACKGROUND: The aim of this study was to investigate the clinicopathological characteristics of GATA binding protein 3 (GATA3)-positive breast cancers as well as the association of GATA3 expression with response to chemotherapy. PATIENTS AND METHODS: Tumor specimens obtained before neoadjuvant chemotherapy [paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide)] from breast cancer patients (n = 130) were subjected to immunohistochemical and mutational analysis of GATA3 and DNA microarray gene expression analysis for intrinsic subtyping. RESULTS: Seventy-four tumors (57%) were immunohistochemically positive for GATA3. GATA3-positive tumors were significantly more likely to be lobular cancer, estrogen receptor (ER)-positive, progesterone receptor (PgR)-positive, Ki67-negative, and luminal A tumors. Somatic mutations were found in only three tumors. Pathological complete response (pCR) was observed in 8 (11%) GATA3-positive tumors and in 22 (39%) GATA3-negative tumors. multivariate analysis showed that tumor size, human epidermal growth factor receptor 2 (her2), and gata3 were independent predictors of pcr. CONCLUSIONS: GATA3-positive breast cancers showed luminal differentiation characterized by high ER expression and were mostly classified as luminal-type tumors following intrinsic subtyping. Interestingly, GATA3 was an independent predictor of response to chemotherapy, suggesting that GATA3 might be clinically useful as a predictor of a poor response to chemotherapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama , Factor de Transcripción GATA3/metabolismo , Paclitaxel/uso terapéutico , Adulto , Anciano , Secuencia de Bases , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Ciclofosfamida/uso terapéutico , Epirrubicina/uso terapéutico , Receptores ErbB/metabolismo , Femenino , Fluorouracilo/uso terapéutico , Factor Nuclear 3-alfa del Hepatocito/metabolismo , Humanos , Antígeno Ki-67/metabolismo , Persona de Mediana Edad , Mucina-1/metabolismo , Terapia Neoadyuvante , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Análisis de Secuencia de ADN , Resultado del Tratamiento
6.
Cancer Lett ; 314(2): 206-12, 2012 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-22018777

RESUMEN

Association of estrogen receptor (ER), progesterone receptor (PR), HER2, Ki67 and 70-gene classifier (70-GC) with a response to paclitaxel (PAC) (n=79) or docetaxel (DOC) (n=55) was investigated in the neoadjuvant setting for breast cancer patients. Sensitivity of breast tumors to PAC, but not to DOC, was found to be significantly associated with ER negativity (P=0.003), PR negativity (P=0.007), and Ki67 positivity (P=0.007). Breast tumors classified into the responders by 70-GC showed a significantly (P=0.005) higher reduction rate to PAC and interestingly a significantly (P=0.009) lower reduction rate to DOC than those classified into the non-responders by 70-GC, suggesting that 70-GC might be useful for the differentiation of PAC-sensitive and DOC-sensitive breast tumors.


Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Paclitaxel/uso terapéutico , Taxoides/uso terapéutico , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Docetaxel , Femenino , Perfilación de la Expresión Génica , Humanos , Antígeno Ki-67/análisis , Receptor ErbB-2/análisis , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis
7.
Ann Oncol ; 23(4): 891-7, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21821547

RESUMEN

BACKGROUND: We established the cell cycle profiling (C2P) assay for specific activity (SA; activity/expression) of cyclin-dependent kinases (CDKs). C2P risk score (C2P-RS) based on CDK1 and CDK2 SAs was significantly associated with relapse in breast cancer (BC). This study was conducted to investigate the predictive value of C2P-RS for neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: Among 124 eligible patients, 122 were treated with weekly paclitaxel followed by 5-fluorouracil, epirubicin and cyclophosphamide (P-FEC) and 2 were treated with paclitaxel monotherapy. C2P-RS was determined via C2P using frozen biopsy samples before NAC. RESULTS: Negative estrogen receptor (ER), negative progesterone receptor (PR), positive human epidermal growth factor receptor 2 (HER2), high Ki-67 expression and intermediate + high C2P-RS were significantly associated with high pathological complete response (pCR) rates compared with positive ER (30% versus 9%), positive PR (25% versus 6%), negative HER2 (34% versus 11%), low Ki-67 expression (24% versus 7%) or low C2P-RS (24% versus 9%), respectively. The combination of C2P-RS and Ki-67 had a stronger impact on pCR than each parameter alone, and a multivariate analysis showed that the combination was an independent predictor of pCR (odds ratio 3.3, 95% confidence interval 1.1-9.5). CONCLUSIONS: C2P-RS was significantly associated with pCR after P-FEC and may be a useful predictor for chemotherapy in BCs.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/enzimología , Proteína Quinasa CDC2/metabolismo , Carcinoma Ductal de Mama/enzimología , Quinasa 2 Dependiente de la Ciclina/metabolismo , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/enzimología , Adulto , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/cirugía , Ciclofosfamida/administración & dosificación , Epirrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Antígeno Ki-67/metabolismo , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia/prevención & control , Paclitaxel/administración & dosificación , Receptores de Esteroides/metabolismo , Factores de Riesgo , Resultado del Tratamiento
8.
J Am Soc Hypertens ; 5(6): 456-62, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21890446

RESUMEN

We reported a remarkable regional difference within Japan in the incidence of end-stage renal disease. Regional differences were also well-known for salt intake, blood pressure (BP), and mortality from stroke, which remains one of the leading causes of death. Noting these regional differences, we examined mutual relationships among salt intake, BP, and stroke mortality in 12 regions of Japan. Data of salt intake, BP, and stroke mortality in 12 regions were collected from National Nutrition Survey (NNS-J), reanalysis of NNS-J, and Vital Statistics of National Population Dynamic Survey (Ministry of Health, Labor and Welfare), respectively. Significant regional differences were found in salt intake (P < .0001), mean arterial BP (P = .0001), and stroke mortality (P < .0001). Although annual changes in these parameters were also significant, their regional differences persisted. Salt intake had positive relationships with both mean arterial BP (r = 0.26, P = .0009) and stroke mortality (r = 0.26, P < .0001) across 12 regions, whereas mean arterial BP was not correlated with stroke mortality. Multiple regression analysis further identified salt intake as an independent factor to increase stroke mortality, but mean arterial BP was not a determinant. Compared with the four regions with lowest salt intake, odds ratios of stroke mortality adjusted by mean arterial BP were 1.04 (95% CI, 1.03-1.06) for the intermediate four regions and 1.25 (95% CI, 1.23-1.27) for the four regions with highest salt intake. These findings suggest that salt intake may have an adverse effect on stroke mortality independently of BP.


Asunto(s)
Cloruro de Sodio Dietético/administración & dosificación , Accidente Cerebrovascular/mortalidad , Presión Sanguínea/fisiología , Enfermedades Cardiovasculares/etiología , Encuestas Epidemiológicas , Humanos , Japón/epidemiología , Factores de Riesgo , Cloruro de Sodio Dietético/efectos adversos , Accidente Cerebrovascular/etiología
9.
Eur J Surg Oncol ; 37(2): 155-61, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21111561

RESUMEN

PURPOSE: Recently, Ki67 index (cell proliferation marker) has been attracting a considerable attention as a prognostic factor in breast cancer but the prognostic significance of Ki67 after neoadjuvant chemotherapy (NAC) has rarely been examined. EXPERIMENTAL DESIGN: Primary breast cancer patients (n = 102) treated with NAC (sequential paclitaxel 12 cycles (q1w) and 5-FU/epirubicin/cyclophosphamide 4 cycles (q3w)) were recruited in the study. Ki67, estrogen receptor (ER) and progesterone receptor (PR) and breast cancer resistant protein (BCRP) and P-glycoprotein were determined by immunohistochemistry and HER2 was determined by FISH in tumor tissues obtained before and after NAC, and their association with patient prognosis (relapse-free survival) was examined. RESULTS: Of the 102 patients, pCR was achieved in 30 (29.4%). In the 72 non-pCR patients, Ki67 index significantly (P < 0.001) decreased after NAC. Ki67 index after NAC, but not Ki67 index before NAC, was significantly associated with a patient prognosis (P = 0.022). Multivariate analysis has shown that Ki67 index after NAC is a marginally significant (P = 0.05) prognostic factor and that other biomarkers including ER, PR, BCRP, and P-glycoprotein before and after NAC are not significant. CONCLUSIONS: Ki67 after NAC, but not before NAC, is prognostic in breast cancer patients, and might be clinically useful in the prognosis prediction of patients who do not achieve pCR after NAC. On the other hand, BCRP and P-glycoprotein before and after NAC are unlikely to be useful as prognostic factors in these patients.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Antígeno Ki-67/genética , Adulto , Supervivencia sin Enfermedad , Femenino , Marcadores Genéticos , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Pronóstico
10.
J Oral Rehabil ; 37(8): 575-82, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20337866

RESUMEN

Influences of bolus volumes on activity patterns of the suprahyoid muscles during swallowing were examined using the T(P) technique (which quantitatively evaluates muscle activity patterns and indicates a negatively skewed pattern at lower T(P) values) in healthy young adults (eight men and four women). One of six volumes of tea ranging from 10 to 32 mL was delivered randomly to each subject while recording an electromyogram of the suprahyoid muscles and a laryngeal mechanogram with a piezoelectric sensor. Each subject was asked to swallow the full volume of liquid in a gulp if possible. T(P) values were calculated as deciles from T(0) to T(100) during intervals that were defined by the trajectory of the laryngeal mechanogram recorded during swallowing. Seven significant differences were detected in the average T(P) values from T(30) to T(60): between 16 mL (e.g., 0.448 in T(30)) and 25 mL (0.408 in T(30)) and between 20 mL (0.453 in T(30)) and 25 mL. There were significant differences among the 12 subjects for all of the nine average T(P) values (Ps < 0.001), suggesting a notable intersubject variation in the suprahyoid (SH) activity patterns. The average peak amplitudes of the integrated suprahyoid activity differed significantly among the six volumes (P < 0.001), while the average durations measured by the laryngeal mechanogram did not. The present results suggest that the swallowing volume mainly affects SH activity patterns, which were evaluated by the T(P) technique, during the early period of each swallow.


Asunto(s)
Deglución/fisiología , Electromiografía , Músculos del Cuello/fisiología , Adulto , Bebidas , Femenino , Humanos , Hueso Hioides/fisiología , Músculos Laríngeos/fisiología , Masculino , , Factores de Tiempo , Adulto Joven
11.
Oral Dis ; 14(5): 435-9, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18208475

RESUMEN

BACKGROUND: Handicapped persons living in nursing homes have special risks for oral diseases. OBJECTIVE: To investigate the specific factors related to the occurrence of dental caries and tooth extraction in patients with severe motor and intellectual disabilities (PSMI) residing in an institution. METHODS: One hundred eighty-nine PSMI residing in a single institution in Japan were followed for 3 years. Oral examinations were conducted at baseline and 3 years later. The following items were investigated: age of subject at admission, period of institutionalization, age at baseline oral examination, status of rumination, drooling, type of ward, dietary mode, and etiology of the impairment. Logistic regression analyses were conducted to examine factors associated with new dental caries and tooth extraction occurring during the study period. RESULTS: By multivariate analysis, rumination and tube feeding were identified as significant factors associated with new dental caries. On the other hand, infancy or childhood impairment and drooling were identified as significant factors related to tooth extraction. CONCLUSION: Some specific factors in this patient population affect the dental caries and tooth extraction and oral programs targeting these factors may reduce dental degeneration in these patients.


Asunto(s)
Atención Dental para la Persona con Discapacidad , Caries Dental/complicaciones , Personas con Discapacidad , Discapacidad Intelectual/complicaciones , Trastornos de la Destreza Motora/complicaciones , Adolescente , Adulto , Factores de Edad , Anciano , Niño , Estudios de Cohortes , Atención Dental para Enfermos Crónicos , Encuestas de Salud Bucal , Trastornos de Ingestión y Alimentación en la Niñez/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Institucionalización , Modelos Logísticos , Masculino , Persona de Mediana Edad , Instituciones Residenciales , Factores de Riesgo , Índice de Severidad de la Enfermedad , Sialorrea/complicaciones
12.
Ann Oncol ; 19(1): 68-72, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17956886

RESUMEN

BACKGROUND: We recently established a novel assay for specific activity (SA) of cyclin-dependent kinases (CDKs) using small tumor samples (>/=8 mm(3)). The aim of this study was to investigate the prognostic significance of CDK1SA and CDK2SA in human breast cancer. METHODS: CDK1SA and CDK2SA were determined in 284 breast cancer patients and their prognostic significance was investigated. RESULTS: Tumors with high CDK1SA and high CDK2SA showed significantly poorer 5-year relapse-free survival than those with low CDK1SA and low CDK2SA, respectively (66.9% vs 84.2% for CDK1SA; 43.6% vs 83.6% for CDK2SA). Moreover, combined analysis of CDK1SA and CDK2SA enabled the classification of breast tumors into high-risk and low-risk groups, where tumors in the high-risk group were strongly associated with unfavorable prognosis (5-year relapse-free survival 69.4% for the high-risk group and 91.5% for the low-risk group). Multivariate analysis showed that the risk determined by combined analysis of CDK1SA and CDK2SA is a significant (hazard ratio 3.09, P < 0.001) prognostic indicator for relapse, especially in node-negative patients (hazard ratio 6.73, P < 0.001). CONCLUSION: Determination of CDK1SA and CDK2SA may be useful in the prediction of outcomes in breast cancer patients and has potential for use as a routine laboratory test.


Asunto(s)
Neoplasias de la Mama/enzimología , Proteína Quinasa CDC2/análisis , Carcinoma Ductal de Mama/enzimología , Quinasa 2 Dependiente de la Ciclina/análisis , Proteínas de Neoplasias/análisis , Adulto , Anciano , Antineoplásicos Hormonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/mortalidad , Carcinoma Ductal de Mama/cirugía , Terapia Combinada , Supervivencia sin Enfermedad , Estrógenos , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Mastectomía , Persona de Mediana Edad , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Neoplasias Hormono-Dependientes/enzimología , Neoplasias Hormono-Dependientes/mortalidad , Neoplasias Hormono-Dependientes/cirugía , Pronóstico , Modelos de Riesgos Proporcionales , Riesgo
13.
Eur J Surg Oncol ; 34(7): 734-8, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17764884

RESUMEN

AIMS: It has been reported that glutathione S-transferase P1 (GSTP1) expression is implicated in resistance to taxanes (docetaxel and paclitaxel) in human breast cancer cells in vitro. In the study presented here, we examine whether GSTP1 expression is associated with resistance to docetaxel or paclitaxel in human breast cancers. We also investigated the relationship between GSTP1 methylation status and response to these taxanes. MATERIAL AND METHODS: Sixty two primary breast cancer patients were treated with docetaxel or paclitaxel as primary systemic treatment (PST). GSTP1 expression was detected immunohistochemically and the hypermethylation status GSTP1 gene was identified with a methylation specific primer assay. RESULTS: The mean tumor reduction rate for all patients (n=62) was significantly (p<0.001) higher in GSTP1 negative (0.73+/-0.04; mean+/-standard error) than GSTP1 positive (0.31+/-0.09) tumors. The subset analysis showed that the mean reduction rate was significantly (p=0.005) higher in GSTP1 negative (0.59+/-0.06) than GSTP1 positive (0.11+/-0.13) tumors in the docetaxel group as well as in the paclitaxel group (p=0.006; GSTP1 negative tumors: 0.84+/-0.05; GSTP1 positive tumors: 0.56+/-0.08). On the other hand, GSTP1 methylation showed no significant association with the reduction rate. CONCLUSION: Our present study has suggested that GSTP1 protein expression, but not GSTP1 methylation status, might be associated with response to docetaxel and paclitaxel. This suggests that GSTP1 immunohistochemical expression might be a potentially clinically useful predictive factor for response to docetaxel and paclitaxel.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Resistencia a Antineoplásicos/genética , Gutatión-S-Transferasa pi/metabolismo , Paclitaxel/farmacología , Taxoides/farmacología , Antineoplásicos/farmacocinética , Neoplasias de la Mama/patología , Metilación de ADN , Docetaxel , Femenino , Marcadores Genéticos , Gutatión-S-Transferasa pi/genética , Humanos , Inmunohistoquímica , Paclitaxel/farmacocinética , Taxoides/farmacocinética
14.
Br J Ophthalmol ; 91(1): 100-4, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16987905

RESUMEN

OBJECTIVE: To investigate the expression of proangiogenic and antiangiogenic factors, vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in retinal pigment epithelial (RPE) cells after photodynamic therapy (PDT), especially focusing on their change in the presence of triamcinolone acetonide. METHODS: Firstly, the cellular uptake of verteporfin was quantified after confluent ARPE-19 (human retinal pigment epithelial) cells were exposed to 5 microg/ml verteporfin combined with or without 1 microg/ml triamcinolone acetonide for 1 h. Secondly, ARPE-19 cells exposed to various doses of verteporfin were irradiated with 120 mJ/cm(2) light. After incubation with or without 1 microg/ml triamcinolone acetonide for 2 days, cell viability and expressions of VEGF and PEDF were assessed. RESULTS: Cellular uptake of verteporfin was not significantly changed by the presence of 1 microg/ml triamcinolone acetonide. In addition, 0.01-0.1 microg/ml of verteporfin showed a dose-dependent toxicity on the ARPE-19 cells 2 days after the light exposure. The presence of verteporfin at a concentration of 0.01 microg/ml did not affect the cell viability but significantly increased VEGF (p<0.001) and reduced PEDF (p = 0.03) expression. Administration of triamcinolone acetonide significantly suppressed both this increase in VEGF (p<0.001) and decrease in PEDF (p = 0.001). CONCLUSIONS: VEGF was increased and PEDF reduced in cultured RPE cells shortly after PDT even at a sublethal dose. Triamcinolone acetonide suppressed this proangiogenic response.


Asunto(s)
Glucocorticoides/farmacología , Neovascularización Patológica/tratamiento farmacológico , Fotoquimioterapia/métodos , Epitelio Pigmentado Ocular/irrigación sanguínea , Triamcinolona Acetonida/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayo de Inmunoadsorción Enzimática/métodos , Proteínas del Ojo/análisis , Humanos , Factores de Crecimiento Nervioso/análisis , Fármacos Fotosensibilizantes/farmacología , Epitelio Pigmentado Ocular/efectos de los fármacos , Porfirinas/farmacocinética , Porfirinas/farmacología , Inhibidores de Proteasas/análisis , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Serpinas/análisis , Factor A de Crecimiento Endotelial Vascular/análisis , Verteporfina
16.
Eur J Ophthalmol ; 15(5): 641-2, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16167296

RESUMEN

PURPOSE: To report a peculiar curvilinear pigmentary lesion in the peripheral fundus in a rod-cone dystrophy. METHODS: Observational case report. Fundus examination of a 57-year-old woman who was known to have a generalized rod-cone dystrophy since she was 8 years old. RESULTS: The peripheral fundus examination revealed a curvilinear lesion which resembles a well-known finding associated with a presumed ocular histoplasmosis syndrome or multifocal choroiditis. CONCLUSIONS: The differential diagnosis of a peculiar curvilinear pigmentary lesion in the peripheral fundus may be expanded to include a generalized rod-cone dystrophy.


Asunto(s)
Células Fotorreceptoras de Vertebrados/patología , Epitelio Pigmentado Ocular/patología , Retinitis Pigmentosa/diagnóstico , Coroiditis/diagnóstico , Diagnóstico Diferencial , Infecciones Fúngicas del Ojo/diagnóstico , Femenino , Histoplasmosis/diagnóstico , Humanos , Persona de Mediana Edad
17.
Eye (Lond) ; 19(4): 464-8, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15184935

RESUMEN

PURPOSE: To investigate the in vivo effects of tissue factor pathway inhibitor 2 (TFPI-2), which stimulates proliferation of retinal pigment epithelial cells, but not the proliferation of fibroblast and vascular endothelial cells in vitro, on retinal degeneration using a sodium-iodate (SI)-induced model in rabbits and Royal Collage of Surgeons (RCS) rats. METHODS: 79 microg of recombinant TFPI-2 (rTFPI-2) or vehicle alone was injected intravitreously to 18 eyes of 12 pigmented rabbits a day after 20 mg/kg of SI was intravenously administered. Retinal function was assessed 4, 7, 14, and 21 days after the injection by analysing amplitudes of the c-wave of a bright flash electroretinogram. Additionally, 10 microg of rTFPI-2 or vehicle alone was injected intravitreously to 11 eyes of RCS rats at both 3 and 4 weeks old, then the retina was examined histologically at 5 weeks old. RESULTS: The rTFPI-2-treated eyes in rabbits showed a significantly less decrease in the relative amplitude of the c-wave than control eyes on days 4 and 7. The thickness of the outer nuclear layer was significantly thicker and the vacuole in the photoreceptor layer was less frequently observed in the rTFPI-2-treated RCS rats than the controls. CONCLUSIONS: Intravitreal injection of TFPI-2 rescues SI-induced retinal degeneration in rabbits and naturally occurring retinal degeneration in RCS rats at least partly. These results may suggest that this compound can be utilized in the treatment of retinal degeneration.


Asunto(s)
Glicoproteínas/uso terapéutico , Degeneración Retiniana/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Electrorretinografía , Inyecciones , Yodatos , Masculino , Epitelio Pigmentado Ocular/efectos de los fármacos , Epitelio Pigmentado Ocular/patología , Conejos , Proteínas Recombinantes/uso terapéutico , Degeneración Retiniana/inducido químicamente , Degeneración Retiniana/patología , Cuerpo Vítreo
19.
Eye (Lond) ; 18(5): 474-7, 2004 May.
Artículo en Inglés | MEDLINE | ID: mdl-15131677

RESUMEN

AIMS: To compare the newly devised fluorescein angiography (FA) - guided indocyanine green angiography (ICGA) with conventional ICGA for detecting feeder vessels in subfoveal choroidal neovascularization (CNV). METHODS: The detection of feeder vessels was attempted in 86 AMD patients with subfoveal CNV: 44 (age 70.4+/-4.5 years) underwent conventional ICGA (control group) and 42 (age 70.9+/-4.0 years) underwent an FA-guided ICGA (FA-guided group) using a double-detector scanning laser ophthalmoscope (SLO). In the control group, indocyanine green (ICG) was injected simultaneously with fluorescein. The patients were instructed to gaze forward localizing the fovea at the centre. In the FA-guided group, fluorescein sodium was injected a few minutes prior to ICG, and the patients were instructed to fixate in the appropriate direction by referring to the ongoing FA on the monitoring screen. In both groups, a 20 degrees visual angle was used to capture good images of feeder vessels in ICGA and, in case ICGA missed the first images of the entire CNV filling, an additional injection of ICG was given in the late phase to record the choroidal filling again. The overall detection rate, single-injection detection rate, double-injection rate and examination time were analysed using Fisher's direct exact probability test or Mann-Whitney's U-test. RESULTS: There was no significant difference in the overall detection of feeder vessels between the two groups (50% in the control group and 52.3% in the FA-guided group; P=0.49 with Fisher's direct exact probability test). However, in the FA-guided group, the single injection detection rate was significantly higher (45.1 and 15.9%, respectively; P<0.001 with Fisher's direct exact probability test); significantly less double injections were required (7.1 and 50%, respectively; P=0.003 with Fisher's direct exact probability test); and significantly shorter examination times were needed (9.6+/-3.7 and 14.1+/-6.8 min, respectively; P=0.02 with Mann-Whitney's U-test). CONCLUSION: FA-guided ICGA is effective for detecting feeder vessels of subfoveal CNV, minimizing the amount of ICG injected and the examination time compared to conventional ICGA.


Asunto(s)
Neovascularización Coroidal/patología , Colorantes , Angiografía con Fluoresceína/métodos , Verde de Indocianina , Anciano , Coroides/irrigación sanguínea , Colorantes/administración & dosificación , Fóvea Central , Humanos , Verde de Indocianina/administración & dosificación , Inyecciones , Factores de Tiempo
20.
Eye (Lond) ; 18(6): 615-8, 2004 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-14739926

RESUMEN

PURPOSE: To report the therapeutic outcome of transpupillary thermotherapy (TTT) for subfoveal choroidal neovascularizarion (CNV) in brown retina using a diode-laser with the setting of lower energy level compared to the previous studies on light-pigmented Caucasian patients. METHODS: A total of 19 subfoveal CNVs in 18 patients were treated with TTT. The power of diode-laser was set 160 mW for 1.2 mm beam, 270 mW for 2.0 mm beam, and 400 mW for 3.0 mm beam, and the laser was delivered for 1 min through a slit-lamp mounted-delivery system. Patients were followed up for a mean of 8.8 months (4-12 months). Visual acuity and the fundus change as judged by funduscopic examination and simultaneous fluorescein and indocyanine green angiography were evaluated. Visual acuity was measured by a Japanese standard Landolt visual acuity chart and converted to logarithm of the minimal angle resolution (log MAR) visual acuity for statistical analysis. Improvement or decline in vision was defined as change of more than 0.2 in log MAR visual acuity. RESULTS: In eyes with minimally classic or occult only CNV, visual acuity improved in two eyes (18%) stabilized in seven eyes (64%) and worsened in two eyes (18%). In eyes with predominantly classic CNV, visual acuity improved in two eyes (25%), stabilized in four eyes (50%) and worsened in two eyes (25%). In all, 15 (84%) eyes of all studied subjects had improvement in exudation. Two (11%) and one (5%) eye(s) were noted to have a significant post-treatment haemorrhage and retinal pigment epithelial tear, respectively. CONCLUSION: In patients with brown retinal colour, the treatment outcome of TTT was comparable to that of light-pigmented Caucasian patients with approximately half the laser power energy. Further randomized control studies are warranted.


Asunto(s)
Color del Ojo , Hipertermia Inducida/métodos , Degeneración Macular/etnología , Degeneración Macular/terapia , Anciano , Anciano de 80 o más Años , Neovascularización Coroidal/etnología , Neovascularización Coroidal/fisiopatología , Neovascularización Coroidal/terapia , Femenino , Estudios de Seguimiento , Humanos , Japón , Degeneración Macular/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Agudeza Visual
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