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OBJECTIVE: To describe efficacy, safety, and patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) with an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) treated with tofacitinib or biological DMARDs (bDMARDs) in real-life conditions. METHODS: A noninterventional study was performed between March 2017 and September 2019 at 13 sites in Colombia and Peru. Outcomes measured at baseline and at the 6-month follow-up were disease activity (RAPID3 [Routine Assessment of Patients Index Data] score), functional status (HAQ-DI [Health Assessment Questionnaire] score), and quality of life (EQ-5D-3L [EuroQol Questionnaire]). The Disease Activity Score-28 (DAS28-ESR) and frequency of adverse events (AEs) were also reported. Unadjusted and adjusted differences from baseline were estimated and expressed as the least squares mean difference (LSMD). RESULTS: Data from 100 patients treated with tofacitinib and 70 patients with bDMARDs were collected. At baseline, the patients' mean age was 53.53 years (SD 13.77), the mean disease duration was 6.31 years (SD 7.01). The change from baseline at month 6 was not statistically significant different in the adjusted LSMD [SD] for tofacitinib vs. bDMARDs for RAPID3 score (-2.55[.30] vs. -2.52[.26]), HAQ-DI score (-.56[.07] vs. -.50[.08]), EQ-5D-3L score (.39[.04] vs. .37[.04]) and DAS28-ESR (-2.37[.22] vs. -2.77[.20]). Patients from both groups presented similar proportions of nonserious and serious AEs. No deaths were reported. CONCLUSION: Changes from baseline were not statistically significantly different between tofacitinib and bDMARDs in terms of RAPID3 scores and secondary outcomes. Patients from both groups presented similar proportions of nonserious and serious AEs. CLINICAL TRIAL NUMBER: NCT03073109.
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Antirreumáticos , Artrite Reumatoide , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , América Latina , Resultado do Tratamento , Pirróis/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Medidas de Resultados Relatados pelo PacienteRESUMO
OBJECTIVE: To evaluate work productivity of adult Latin American patients with rheumatoid arthritis (RA) treated with tofacitinib and biological disease-modifying anti-rheumatic drugs (bDMARDs) measured by the Work Productivity and Activity Impairment (WPAI) in RA questionnaire at 0- and 6-month follow-up. METHODS: This non-interventional study was performed in Colombia and Peru. Evaluated the effects of tofacitinib and bDMARDs in patients with RA after failure of conventional DMARDs. The WPAI-RA questionnaire was administered at baseline and at the 6-month (±1 month) follow-up. The results are expressed as least squares means (LSMs), and standard errors (SEs). RESULTS: One hundred patients treated with tofacitinib and 70 patients treated with bDMARDs were recruited. Twenty-eight percent of patients from the tofacitinib group and 40.0% from the bDMARDs group were working for pay at baseline. At month 6, the changes in absenteeism, presenteeism, and work impairment due to health were -18.3% (SE 7.7), -34.8% (SE 5.9), and -11.0% (SE 16.5), respectively, in the tofacitinib group and -19.4% (SE 8.0), -34.8% (SE 6.2), and -15.9% (SE 15.0), for the bDMARD group. CONCLUSION: For patients who reported working, there were improvements in presenteeism, absenteeism, and work impairment due to health in both groups. TRIAL REGISTRATION: NCT03073109.
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Antirreumáticos , Artrite Reumatoide , Adulto , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Eficiência , Humanos , América Latina , Piperidinas/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/efeitos adversos , Resultado do Tratamento , Desempenho ProfissionalRESUMO
The influence of mycorrhizal symbiosis on ecosystem processes depends on the mycorrhizal type and status of plants. Early research hypothesized that the proportion of arbuscular mycorrhizal (AM) species decreases and of ectomycorrhizal (ECM) and ericoid mycorrhizal (ERM) species increases along increasing elevations and latitudes. However, there is very scarce information about this pattern along elevation gradients. We aimed to test this hypothesis and to describe the trends in plant mycorrhizal status by examining the Pyrenean mountain range (from 400 to 3400 m asl). The distribution of plant mycorrhizal types: AM, ECM, ERM, and non-mycorrhizal (NM) and status (obligately, OM, or facultatively, FM mycorrhizal plants, FM) were identified based on the Pyrenean Floristic Atlas and analyzed for climatic and edaphic drivers. The proportion of AM plants decreased slightly with elevation, while ECM species peaked at 1000 m asl. The proportion of ERM and NM plant species rose with increasing elevation. The proportion of FM species increased, and OM species decreased with increasing elevation. The change of AM and ECM species, and OM and FM species, along the elevational gradient, corresponds broadly to changes along the latitudinal gradient, driven by a combination of climatic and edaphic factors. Differently, the elevational occurrence of NM plant species is mainly driven only by climatic factors (low temperature) and that of ERM species by only edaphic factors (low pH). Large-scale macroecological studies (≥ 50 km grid cell) well reflect the effects of climate on the distribution of plant mycorrhizal traits, but local data (≤ 1 km grid cell) are needed to understand the effects of soil conditions and land use.
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Micorrizas , Ecossistema , Plantas , Solo , SimbioseRESUMO
INTRODUCTION: Cervicouterine cancer (CC) is a health problem worldwide and is the fourth most common cancer in women, with a greater proportion of individuals affected by advanced stages of the disease in developing countries. OBJECTIVE: To determine the sensitivity and specificity of the TruScreen™ opto-electronic device vs. conventional cytology in CC screenings. METHODOLOGY: This is a prospective observational study that included individuals who presented for the first time at the Dysplasia Clinic of the Instituto Nacional de Cancerología from March 1 through April 30, 2016, and those referred due to abnormal conventional cytology. The patients were evaluated with the TruScreen™ device, conventional cytology, colposcopy and, if necessary, cervical biopsy. The results were analyzed by descriptive statistics as well as the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the TruScreen™, using conventional cytology as the standard. RESULTS: Thirty-two patients were included who met the inclusion criteria. The average age of the patients was 40 years (range, 23-61 years). For the diagnosis of high-grade intraepithelial lesions, the TruScreen™ device showed a 43% sensitivity, a 92% specificity, a PPV of 60%, and a NPV of 85%, whereas evaluation via cervical biopsy exhibited a 33% sensitivity, an 86% specificity, a 33% PPV, and an 86% NPV. The Kappa agreement index of the TruScreen™ with the colposcopies was 0.70. CONCLUSIONS: TruScreen™ demonstrated low sensitivity and high specificity compared with conventional cytology, which had a high NPV.
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Resumen OBJETIVO: describir la bibliografía donde se identificaron biomarcadores moleculares en muestras de citología cervical en base líquida para detectar cáncer epitelial de endometrio y ovario. METODOLOGÍA: búsqueda electrónica en las principales bases de datos de artículos relacionados con la detección de cáncer de ovario y de endometrio con los siguientes términos: citología en base líquida, cáncer epitelial de ovario, cáncer epitelial de endometrio, biomarcadores moleculares. RESULTADOS: los cánceres epitelial de ovario y de endometrio son enfermedades que carecen de un método de tamizaje eficaz. La citología en base líquida ofrece una manera eficaz de detectar alteraciones celulares y moleculares. Mediante la asociación entre la citología en base líquida y los métodos moleculares en el aparato genital inferior es posible identificar biomarcadores específicos; esto abre la posibilidad de desarrollar métodos de tamizaje para cáncer epitelial de endometrio y ovario. CONCLUSIONES: mediante el uso de la citología en base líquida es posible detectar cáncer epitelial de endometrio y ovario.
Abstract OBJECTIVE: To describe the literature that has identified molecular biomarkers in liquid-based cervical cytology samples to detect endometrial and ovary epithelial cancer. METHODOLOGY: An electronic search was conducted in the main databases in articles related to the detection of ovarian and endometrial cancer with the following search terms: liquid-based cytology, ovarian epithelial cancer, endometrial epithelial cáncer, molecular biomarkers. RESULTS: Epithelial ovarian and endometrial cancer are diseases that lack an effective screening method. Liquid-based cytology provides an effective way to detect cellular and molecular alterations in the detection of these neoplasms. Through the association between liquid-based cytology and molecular methods it is possible to identify specific biomarkers in the lower genital tract, opening up the possibility of developing screening methods for endometrial and ovary epithelial cancer. CONCLUSIONS: It is possible the detection of endometrial cancer and, to a lesser extent of epithelial ovarian cancer by using liquid-based Pap test.
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OBJECTIVES: To evaluate the risk of opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with tofacitinib. METHODS: Phase II, III and long-term extension clinical trial data (April 2013 data-cut) from the tofacitinib RA programme were reviewed. OIs defined a priori included mycobacterial and fungal infections, multidermatomal herpes zoster and other viral infections associated with immunosuppression. For OIs, we calculated crude incidence rates (IRs; per 100 patient-years (95% CI)); for tuberculosis (TB) specifically, we calculated rates stratified by patient enrolment region according to background TB IR (per 100 patient-years): low (≤0.01), medium (>0.01 to ≤0.05) and high (>0.05). RESULTS: We identified 60 OIs among 5671 subjects; all occurred among tofacitinib-treated patients. TB (crude IR 0.21, 95% CI of (0.14 to 0.30)) was the most common OI (n=26); median time between drug start and diagnosis was 64â weeks (range 15-161â weeks). Twenty-one cases (81%) occurred in countries with high background TB IR, and the rate varied with regional background TB IR: low 0.02 (0.003 to 0.15), medium 0.08 (0.03 to 0.21) and high 0.75 (0.49 to 1.15). In Phase III studies, 263 patients diagnosed with latent TB infection were treated with isoniazid and tofacitinib concurrently; none developed TB. For OIs other than TB, 34 events were reported (crude IR 0.25 (95% CI 0.18 to 0.36)). CONCLUSIONS: Within the global tofacitinib RA development programme, TB was the most common OI reported but was rare in regions of low and medium TB incidence. Patients who screen positive for latent TB can be treated with isoniazid during tofacitinib therapy.
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Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Infecções Oportunistas/induzido quimicamente , Piperidinas/efeitos adversos , Pirimidinas/efeitos adversos , Pirróis/efeitos adversos , Tuberculose/induzido quimicamente , Antirreumáticos/uso terapêutico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/imunologia , Ensaios Clínicos como Assunto , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Incidência , Janus Quinase 3/antagonistas & inibidores , Infecções Oportunistas/epidemiologia , Infecções Oportunistas/imunologia , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Medição de Risco , Tuberculose/epidemiologia , Tuberculose/imunologiaRESUMO
Objetivo Evaluar la eficacia de un programa de recomendaciones nutricionales y ejercicios físicos en mujeres con síndrome metabólico.Diseño Ensayo clínico aleatorio multicéntrico.EmplazamientoAtención primaria de Holguín, Cuba.ParticipantesMuestreo por conglomerados de 150 mujeres obesas con síndrome metabólico, sin alteraciones de la glucemia. Se asignaron aleatoriamente a un grupo control (n=70) y a uno experimental (n=80). Completaron el estudio (junio 2008-julio 2009), 62 mujeres del control y 60 del grupo de intervención.IntervenciónEn el grupo experimental se aplicó una dieta hipocalórica balanceada y un programa de ejercicio físico. El grupo control recibió los cuidados habituales.Mediciones principalesPeso corporal, índice de masa corporal, circunferencia abdominal, presión arterial, glucemia y el perfil lipídico en sangre.ResultadosAl año, en relación al grupo control, en el grupo experimental se redujo más la presión diastólica (78±0,9 vs. 91±1,1mm Hg), el colesterol total (4,7±0,1 vs. 6,0±0,1mmol/L), los triglicéridos (1,9±0,1 vs. 2,9±0,1mmol/L) y el colesterol-LDL (2,5±0,0 vs. 3,5±0,1mmol/L), y aumentó más el colesterol-HDL (1,2±0,0 vs. 1,1±0,0mmol/L). No se produjeron cambios apreciables en el peso, el índice de masa corporal, la circunferencia abdominal, la presión arterial sistólica y la glucemia.ConclusionesSe demuestra la efectividad del programa de intervención sobre la presión arterial y el perfil de lípidos en sangre. (AU)
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Humanos , Feminino , Pessoa de Meia-Idade , Dieta Redutora , Exercício Físico , Síndrome Metabólica/complicações , Síndrome Metabólica/dietoterapia , Síndrome Metabólica/terapia , Obesidade/complicações , Obesidade/dietoterapia , Obesidade/terapiaRESUMO
We showed that when insulin-like growth factor II (IGF-II) is highly expressed in breast tissues and cell lines, the IGF-I receptor signaling pathway is highly activated. Since IGF-II activates the insulin receptor (INSR), we propose that the INSR signaling is also activated in this system. We examined the expression of both INSR isoforms, insulin receptor A (INSR-A) and insulin receptor B (INSR-B), and the downstream signaling pathways in breast cancer (BC) cells and in paired (normal/tumor) breast tissues from 100 patients. Analysis was performed by real-time PCR, Western blot, immunohistochemistry, and phospho-ELISA techniques. Tumor tissues and cell lines from African-American patients expressed higher levels of INSR-A, but lower levels of INSR-B. Accordingly, insulin receptor substrate 1 and focal adhesion kinase activation were significantly increased in these women. We conclude that higher INSR-A and lower INSR-B contribute to higher proliferation and lower metabolic response. Thus, differential expression of INSR isoforms represents a potential biological link between BC and diabetes.
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Antígenos CD/metabolismo , Neoplasias da Mama/metabolismo , Diabetes Mellitus/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Receptor de Insulina/metabolismo , Transdução de Sinais , Negro ou Afro-Americano , Antígenos CD/biossíntese , Antígenos CD/genética , Mama/metabolismo , Feminino , Proteína-Tirosina Quinases de Adesão Focal/biossíntese , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like II/genética , Fosforilação , Isoformas de Proteínas/metabolismo , Receptor de Insulina/biossíntese , Receptor de Insulina/genética , Células Tumorais Cultivadas , População BrancaRESUMO
The estrogen receptor (ER) is a primary target for breast cancer (BC) treatment. As BC progresses to estrogen-independent growth, the insulin-like growth factor-1 receptor (IGF-1R) and the ER interact in synergistic cross-talk mechanisms, which result in enhanced activation of both receptors' signaling cascades. Insulin-like growth factor-2 (IGF-2) is critical in BC progression and its actions are mediated by the IGF-1R. Our previous studies showed that IGF-2 regulates survival genes that protect the mitochondria and promote chemoresistance. In this study, we analyzed BC cells by subcellular fractionation, Western-Blot, qRT-PCR, and siRNA analysis. Our results demonstrate that IGF-2 activates ER-α and ER-ß, and modulates their translocation to the nucleus, membrane organelles, and the mitochondria. IGF-2 actions are mediated by the IGF-1R and the insulin receptor. This novel mechanism of IGF-2 synergistic cross-talk signaling with ER-α and ER-ß can promote estrogen-independent BC progression and provide new therapeutic targets for the treatment of BC patients.
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Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Receptor de Insulina/metabolismo , Idoso , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Núcleo Celular/metabolismo , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Feminino , Humanos , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Transdução de Sinais , Transcrição GênicaRESUMO
OBJECTIVE: African-American (AA) women with breast cancer are more likely to have advanced disease at diagnosis, higher risk of recurrence and poorer prognosis than Caucasian (CA) women. We have recently shown higher insulin-like growth factor II (IGF-II) expression in paired breast tissue samples from AA women as compared to CA women. IGF-II is a potent mitogen that induces cell proliferation and survival signals through activation of the IGF-I and Insulin receptors (IGF-IR, IR) while IGF-II circulating levels are regulated by cellular uptake through the IGF2 receptor. We hypothesize that differential expression of the IGF1R and IGF2R among AA and CA women potentiates IGF-II mitogenic effects, thus contributing to the health disparity observed between these ethnic groups. DESIGN: We examined IGF-IR and IGF2R mRNA, protein expression and IGF1R phosphorylation in paired breast tissue samples from AA and CA women by Real Time-PCR, Western blot analysis, immunohistochemistry and ELISA techniques. RESULTS: Our results showed significantly increased expression of IGF1R in AA normal tissues as compared to CA normal tissues. IGF1R expression was similar between AA normal and malignant tissues, while IGF1R, IRS-1 and Shc phosphorylation was significantly higher in AA tumor samples. Significantly higher levels of IGF2R were found in CA tumor samples as compared to AA tumor samples. CONCLUSIONS: We conclude that IGF1R and IGF2R differential expression may contribute to the increased risk of malignant transformation in young AA women and to the more aggressive breast cancer phenotype observed among AA breast cancer patients and represent, along with IGF-II, potential therapeutic targets in breast cancer.
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Negro ou Afro-Americano/genética , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Disparidades nos Níveis de Saúde , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 2/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/etnologia , Carcinoma Ductal de Mama/genética , Carcinoma Papilar/etnologia , Carcinoma Papilar/genética , Carcinoma Papilar/mortalidade , Feminino , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , População Branca/genética , Adulto JovemRESUMO
OBJECTIVE: Increased risk of cancer and other adult diseases have been associated with perinatal exposure to adverse conditions such as stress and famine. Recently, Insulin-like growth factor II (IGF-II) was identified as the first gene associated with altered expression caused by fetal exposure to poor nutrition. IGF-II regulates fetal development and breast cancer cell survival, in part, by regulating anti-apoptotic proteins through activation of the IGF-I and insulin receptors. African-American (AA) women have a lower overall breast cancer (BC) incidence, however, they present with advanced disease at diagnosis, poorer prognosis and lower survival than Caucasian (CA) women. The reasons for the BC survival disparity are not well understood. We hypothesize that IGF-II plays a role in the survival disparity observed among AA breast cancer patients by stimulating rapid tumor growth, inhibiting apoptosis, and promoting metastasis. DESIGN: This study examines IGF-II expression and regulation of the anti-apoptotic proteins Bcl-2, Bcl-X(L), and survivin in Hs578t (ER-), CRL 2335 (ER-), and CRL 2329 (ER+) breast cancer cells and compares with the expression of these proteins in paired breast tissue samples from AA and CA women by qRT-PCR and Western blotting. RESULTS: IGF-II expression was significantly higher in AA cell lines and tissue samples when compared to Caucasians. IGF-II siRNA treatment decreased anti-apoptotic protein levels in all cell lines (regardless of ER status). These effects were blocked by the addition of recombinant IGF-II. Of significance, IGF-II expression and regulation of Bcl-X(L) and survivin in cell lines correlated with their expression in paired breast tissues. CONCLUSIONS: IGF-II and the anti-apoptotic proteins differential expression among AA and CA patients may contribute to the breast cancer survival disparities observed between these ethnic groups.
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Neoplasias da Mama/mortalidade , Carcinoma/mortalidade , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/fisiologia , Adulto , Negro ou Afro-Americano/genética , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/etnologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma/etnologia , Carcinoma/genética , Carcinoma/patologia , Sobrevivência Celular , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Disparidades nos Níveis de Saúde , Humanos , Proteínas Inibidoras de Apoptose , Fator de Crescimento Insulin-Like II/antagonistas & inibidores , Fator de Crescimento Insulin-Like II/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Interferente Pequeno/farmacologia , Análise de Sobrevida , Survivina , Células Tumorais Cultivadas , População Branca/genética , População Branca/estatística & dados numéricos , Adulto JovemRESUMO
CONTEXT: Women's health is an often neglected component of health professions education despite the well-documented need to improve the health status of women, especially in low income countries. This paper was written on behalf of all members of The Network: Towards Unity for Health Women and Health Taskforce (WHTF) which unites leaders in women's health and higher education from different countries around the world. The WHTF objectives include teaching health providers the skills and knowledge necessary to improve care to women; encouraging universities to partner with community women's groups; promoting the inclusion of women's rights and gender issues in curricula; and cultivating leadership among female health professions students. OBJECTIVE/CONTENT: The main goal of the paper is to provide an overview of the collaborative processes, the accomplishments and the lessons learned in this project since the early 1990s. It includes the history and evolution of the Taskforce; the importance of human rights and gender issues in approaching women's health; teaching tools--the Women and Health Learning Package (WHLP); implementation of WHLP in health professions education and community settings; and main outcomes and future challenges. The WHLP was implemented in fourteen universities and seven university community programs. A new edition of WHLP will be available in 2009. CONCLUSION: The WHTF is a model of south-south collaboration in health professions education and community programs to improve women's health. It has been successful in reaching universities and communities all over the globe and provides a model for other education, health and community issues.
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Comitês Consultivos , Redes Comunitárias , Pessoal de Saúde/educação , Cooperação Internacional , Saúde da Mulher , Currículo , Feminino , Processos Grupais , Humanos , Desenvolvimento de Programas , Direitos da MulherRESUMO
Insulin-like growth factor II (IGF-II) plays a pivotal role in fetal and cancer development by signaling through the IGF-I and insulin receptors and activating the estrogen signaling cascade. We previously showed that precursor IGF-II (proIGF-II, the predominant form expressed in cancer) and not mature IGF-II (mIGF-II) blocks resveratrol (RSV) (a phytoalexin/anticancer agent)-induced cell death in MCF-7 cells. We hypothesize that proIGF-II regulates antiapoptotic proteins and/or the mitochondria to inhibit RSV actions and promote cell survival. This study examines the effect of mIGF-II and proIGF-II on survivin expression and mitochondrial polarization in response to RSV. RSV inhibits survivin expression and stimulates mitochondrial depolarization, caspase 7 activation and cell death. These effects were completely blocked by the addition of proIGF-II. RSV treatment had no effect on transfected MCF-7 cells constitutively expressing proIGF-II, while IGF-II siRNA transfection decreased survivin levels. Our results provide new insights for the potential use of proIGF-II as target for new anticancer therapies.
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Antineoplásicos Fitogênicos/farmacologia , Fator de Crescimento Insulin-Like II/fisiologia , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas de Neoplasias/metabolismo , Precursores de Proteínas/fisiologia , Estilbenos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama , Caspase 7/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ativação Enzimática , Humanos , Proteínas Inibidoras de Apoptose , Potencial da Membrana Mitocondrial , Mitocôndrias/fisiologia , Processamento de Proteína Pós-Traducional , Resveratrol , Transdução de Sinais/efeitos dos fármacos , SurvivinaRESUMO
Primary malignant lymphoma of the uterine cervix is a rare disease. Malignant lymphoma can be clinically and histopathologically misdiagnosed for the infrequent presentation in this are. A case of 56-year-old woman with uterine cervical tumor with infiltration to both parametria is presented. A biopsy was performed and histopathological studies reported a large cell B lymphoma. After the diagnosis CT abdominal, pelvic and thoracic scan was performed and shows infiltration to posterior bladder without evidence of disease in lymph nodes or another organ. The patient was treated with chemotherapy and radiotherapy. Six month after finish the treatment is well and free of disease.
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Linfoma de Células B/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma não Hodgkin/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Feminino , Humanos , Linfoma de Células B/complicações , Linfoma de Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/tratamento farmacológicoRESUMO
We report the results of a survey for the presence of Papaya ringspot virus (PRSV) along the coasts of the Gulf of Mexico and the Pacific Ocean, in 15 federal states of Mexico that account for over 98% of the national papaya production. More than 80 locations were visited in 58 counties. Out of a total of 267 papaya leaf samples, 157 tested positive for PRSV. We tested for the presence of three other viruses because of the occurrence of severe, atypical symptoms in plantations. Only Papaya mosaic virus (PapMV) was detected. PRSV was present in every county. PapMV was less frequent, but its overall distribution was almost identical. PRSV and PapMV occurred in single or mixed infections of papaya and other host species that could function as virus reservoirs. We investigated the diversity of the coat protein (CP) sequences of 36 PRSV isolates. The amino acid sequence divergence among all isolates ranged from 0.4 to 9.9%, and was comparable to that found in other regions of the world. In contrast to most of these world regions, there is a clear correlation between CP sequence variation and the geographical origins of the virus isolates.
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BACKGROUND: The purified protein derivative (PPD) skin test is the only widely used method which detects latent tuberculosis infection (LTBI) and is dependent on a normal T cell function. In rheumatoid arthritis (RA) the T cell function is altered, which may result in an inability to develop an adequate PPD reaction. OBJECTIVES: To evaluate the response to PPD in patients with RA and to compare it with that of control subjects. METHODS: 112 patients with RA and 96 healthy controls were studied. PPD 5 U was applied using the Mantoux method, and skin reaction was measured at 72 hours. The reaction was considered negative for PPD <5 mm. RESULTS: There were no significant differences in age, sex, history of bacille Calmette-Guerin vaccination, or tuberculosis contact between the two groups. The median size of the PPD induration in the patients with RA was significantly less than that in the control group (4.5 v 11.5 mm, p<0.01). 79 (70.6%) patients with RA compared with 25 (26%) of the control group had a negative reaction to PPD (p<0.01), a response not influenced by disease activity or duration of disease in the patients with RA. CONCLUSION: A PPD skin test is not an appropriate test for recognising LTBI in patients with RA in our population.
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Artrite Reumatoide/imunologia , Teste Tuberculínico , Tuberculose/diagnóstico , Adulto , Idoso , Artrite Reumatoide/complicações , Contraindicações , Reações Falso-Negativas , Feminino , Humanos , Tolerância Imunológica , Masculino , Pessoa de Meia-Idade , Tuberculose/complicaçõesRESUMO
The purpose of this retrospective study of 118 patients with squamous cell cervical cancer from January 1990 to December 1993 was to evaluate angiogenesis as predictive factor of recurrence in cervical cancer stages II-III treated with standard radiotherapy. Microvessel density (MVD) was evaluated and correlated with other prognostic factors. MVD was greater than 20 in 67.8% of patients with recurrence (P = 0.002) in comparison to 39% of patients without. Disease-free survival was shorter in stage IIA and MVD >20 (P = 0.0193) as well as for stage IIB (P < 0.05 ), but not for IIIB (P = 0.1613 ). Global survival was significantly shorter when MVD was >20 (P = 0.0316). For stage IIA and MVD >20 survival was shorter (P = 0.0008) for stage IIB (P < 0.05) but not for IIIB (P = 0.14). Patients younger than 40 years and MVD >20 had poorer disease-free interval and survival (P = 0.0029). MVD in patients with squamous cell cervical cancer stage II and age younger than 40 may play a role in predicting recurrence and survival.
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Carcinoma de Células Escamosas/irrigação sanguínea , Carcinoma de Células Escamosas/patologia , Recidiva Local de Neoplasia , Neovascularização Patológica , Neoplasias do Colo do Útero/irrigação sanguínea , Neoplasias do Colo do Útero/patologia , Adulto , Fatores Etários , Idoso , Carcinoma de Células Escamosas/radioterapia , Intervalo Livre de Doença , Feminino , Humanos , Microcirculação , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco , Neoplasias do Colo do Útero/radioterapiaRESUMO
Family studies of primary torsion dystonia have used the diagnostic categories of definite, probable, and possible dystonia for gene mapping and identification, but the validity of this hierarchical classification is not known. The authors assessed 147 DYT1 GAG deletion carriers and 113 blood-related noncarriers from 43 families. Only the category of definite dystonia was 100% specific. Probable dystonia, but not possible, was increased in carriers compared with noncarriers. The authors recommend that only those with definite signs of dystonia be considered affected in linkage and other genetic studies.
Assuntos
Proteínas de Transporte/genética , Distonia/diagnóstico , Distonia/genética , Chaperonas Moleculares , Adulto , Feminino , Deleção de Genes , Testes Genéticos , Genótipo , Heterozigoto , Humanos , Judeus , Funções Verossimilhança , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Valor Preditivo dos TestesRESUMO
BACKGROUND: Myoclonus-dystonia (M-D) is a movement disorder with involuntary jerks and dystonic contractions. Autosomal dominant alcohol-responsive M-D is associated with mutations in the epsilon-sarcoglycan gene (SGCE) (six families) and with a missense change in the D2 dopamine receptor (DRD2)gene (one family). OBJECTIVE: To investigate the clinical phenotype associated with M-D including motor symptoms, psychiatric disorders, and neuropsychological deficits. METHODS: Fifty individuals in three M-D families were evaluated and a standardized neurologic examination and DNA analysis were performed. Psychiatric profiles were established with the Diagnostic Interviews for Genetic Studies (DIGS) and the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Cognition was evaluated with standardized neuropsychological tests. RESULTS: Distinct truncating mutations in the SGCE gene were identified in each family. Additionally, a missense alteration in the DRD2 gene was previously found in one family. Motor expression was variable, with onset of myoclonus or dystonia or both affecting the upper body and progression to myoclonus and dystonia in most cases. Psychiatric profiles revealed depression, obsessive-compulsive disorder, substance abuse, anxiety/panic/phobic disorders, and psychosis in two families, and depression only in the third family. Averaged scores from cognitive testing showed impaired verbal learning and memory in one family, impaired memory in the second family, and no cognitive deficits in the third family. CONCLUSIONS: Cognitive deficits may be associated with M-D. Psychiatric abnormalities correlate with the motor symptoms in affected individuals. Assessment of additional M-D families with known mutations is needed to determine whether these are characteristic phenotypic manifestations of M-D.