RESUMEN
OBJECTIVE: There are limited studies on urogenital symptoms in women who experience menopause before the age of 40 years due to primary ovarian insufficiency (POI) or bilateral oophorectomy (surgical POI). This study aimed to compare the urogenital symptoms, including sexuality, of women with POI to those without the condition. METHODS: This cross-sectional study conducted was in seven Latin American countries, in which postmenopausal women (with POI and non-POI) were surveyed with a general questionnaire, the Menopause Rating Scale (MRS) and the six-item Female Sexual Function Index (FSFI-6). The association of premature menopause with more urogenital symptoms and lower sexual function was evaluated with logistic regression analysis. RESULTS: Women with POI experience more urogenital symptoms (MRS urogenital score: 3.54 ± 3.16 vs. 3.15 ± 2.89, p < 0.05) and have lower sexual function (total FSFI-6 score: 13.71 ± 7.55 vs. 14.77 ± 7.57 p < 0.05) than women who experience menopause at a normal age range. There were no significant differences in symptoms when comparing women based on the type of POI (idiopathic or surgical). After adjusting for covariates, our logistic regression model determined that POI is associated with more urogenital symptoms (odds ratio [OR]: 1.38, 95% confidence interval [CI] 1.06-1.80) and lower sexual function (OR: 1.67, 95% CI 1.25-2.25). CONCLUSION: POI, whether idiopathic or secondary to bilateral oophorectomy, is associated with symptoms that affect vaginal and sexual health.
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Menopausia Prematura , Insuficiencia Ovárica Primaria , Disfunciones Sexuales Fisiológicas , Humanos , Femenino , Estudios Transversales , Insuficiencia Ovárica Primaria/complicaciones , Persona de Mediana Edad , Disfunciones Sexuales Fisiológicas/etiología , Adulto , Encuestas y Cuestionarios , Ovariectomía/efectos adversos , Enfermedades Urogenitales Femeninas , América Latina , Modelos Logísticos , Menopausia/fisiologíaRESUMEN
PURPOSE: The purpose was to estimate the risk and severity of cardiovascular toxicities associated with selected targeted agents. METHODS: We searched English-language literature for randomized clinical trials published between January 1, 2000 and November 30, 2013 of targeted cancer therapy drugs approved by the FDA by November 2010. One hundred ten studies were eligible. Using meta-analytic methods, we calculated the relative risks of several cardiovascular toxicities [congestive heart failure (CHF), decreased left ventricular ejection fraction (DLVEF), myocardial infarction (MI), arrhythmia, and hypertension (HTN)], adjusting for sample size using the inverse-variance technique. For each targeted agent and side effect, we calculated the number needed to harm. RESULTS: Regarding CHF, trastuzumab showed significantly greater risk of all-grade and high-grade CHF. There was significant increased risk of all-grade DLVEF with sorafenib, sunitinib, and trastuzumab and high-grade DLVEF with bevacizumab and trastuzumab. Sorafenib was associated with significant increased all-grade risk of MI based on one study. None was associated with high-grade risk of MI or increased risk of arrhythmia. Bevacizumab, sorafenib, and sunitinib had significant increased risk of all-grade and high-grade HTN. CONCLUSIONS: Several of the targeted agents were significantly associated with increased risk of specific cardiovascular toxicities, CHF, DLVEF, and HTN. Several had significant increased risk for high-grade cardiovascular toxicities (CHF, DLVEF, and HTN). Patients receiving such therapy should be closely monitored for these toxicities and early and aggressive treatment should occur. However, clinical experience has demonstrated that some of these toxicities may be reversible and due to secondary effects.
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Antineoplásicos/efectos adversos , Enfermedades Cardiovasculares/inducido químicamente , Neoplasias/tratamiento farmacológico , Humanos , Neoplasias/fisiopatologíaRESUMEN
BACKGROUND: There is scanty experience concerning robot-assisted Ivor-Lewis oesophagectomy, so every new experience is helpful. METHODS: We describe the techniques and short-term results of Ivor-Lewis oesophagectomy using a laparoscopic approach and robot-assisted thoracoscopy, and an observational study of prospective surveillance of the first 14 patients treated for oesophageal cancer. A gastric tube was created laparoscopically. Oesophagectomy was performed through a robot-assisted thoracoscopy followed by hand-sewn intrathoracic anastomosis. RESULTS: There were no conversion cases. Mortality was zero. Six patients had a major complication. There were no cases of respiratory complication or recurrent laryngeal nerve palsy. Three patients had a radiological fistula (21.4%), successfully treated by endoscopic stenting, and one (7.1%) had an anastomosis leak needing reoperation. There were two cases of chylothorax (14.3%). CONCLUSIONS: Our initial results suggest that the reported technique is safe and satisfies the oncological principles. It provides the advantages of minimally invasive surgery by overcoming some limitations of conventional thoracoscopy.
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Anastomosis Quirúrgica/métodos , Neoplasias Esofágicas/cirugía , Esofagectomía/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Adulto , Anciano , Esofagectomía/efectos adversos , Femenino , Humanos , Laparoscopía , Masculino , Persona de Mediana Edad , Posición Prona , ToracoscopíaRESUMEN
BACKGROUND: Cancer patients receiving chemotherapy are at increased risk for thrombosis. Apixaban, a factor Xa inhibitor, is oral and does not require laboratory monitoring. OBJECTIVES: A pilot study was conducted to evaluate whether apixaban would be well tolerated and acceptable in cancer patients receiving chemotherapy. PATIENTS/METHODS: Subjects receiving either first-line or second-line chemotherapy for advanced or metastatic lung, breast, gastrointestinal, bladder, ovarian or prostate cancers, cancer of unknown origin, myeloma or selected lymphomas were randomized to 5 mg, 10 mg or 20 mg once daily of apixaban or placebo in a double-blind manner for 12 weeks. Use of the study drug began within 4 weeks of the start of chemotherapy. The primary outcome was either major bleeding or clinically relevant non-major (CRNM) bleeding. Secondary outcomes included venous thromboembolism (VTE) and grade III or higher adverse events related to the study drug. Thirty-two patients received 5 mg, 30 patients 10 mg, 33 patients 20 mg, and 30 patients placebo. In these groups, there were 0, 0, 2 and 1 major bleeds, respectively. The corresponding data for CRNM bleeds were 1, 1, 2, and 0. The rate of major bleeding in the 93 apixaban patients was 2.2% (95% confidence interval 0.26-7.5%). There were no fatal bleeds. Three placebo patients had symptomatic VTE. CONCLUSIONS: Apixaban was well tolerated in our study population. These results support further study of apixaban in phase III trials to prevent VTE in cancer patients receiving chemotherapy.
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Antineoplásicos/uso terapéutico , Fibrinolíticos/uso terapéutico , Neoplasias/tratamiento farmacológico , Pirazoles/uso terapéutico , Piridonas/uso terapéutico , Tromboembolia/prevención & control , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Biomarcadores/sangre , Canadá , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Factor Xa/metabolismo , Inhibidores del Factor Xa , Femenino , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Hemorragia/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias/sangre , Neoplasias/complicaciones , Neoplasias/patología , Proyectos Piloto , Pirazoles/administración & dosificación , Pirazoles/efectos adversos , Piridonas/administración & dosificación , Piridonas/efectos adversos , Medición de Riesgo , Factores de Riesgo , Tromboembolia/sangre , Tromboembolia/etiología , Tromboembolia/patología , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos , Adulto JovenRESUMEN
Our understanding of the mechanisms by which nonalcoholic fatty liver disease (NAFLD) progresses from simple steatosis to steatohepatitis (NASH) is still very limited. Despite the growing number of studies linking the disease with altered serum metabolite levels, an obstacle to the development of metabolome-based NAFLD predictors has been the lack of large cohort data from biopsy-proven patients matched for key metabolic features such as obesity. We studied 467 biopsied individuals with normal liver histology (n=90) or diagnosed with NAFLD (steatosis, n=246; NASH, n=131), randomly divided into estimation (80% of all patients) and validation (20% of all patients) groups. Qualitative determinations of 540 serum metabolite variables were performed using ultraperformance liquid chromatography coupled to mass spectrometry (UPLC-MS). The metabolic profile was dependent on patient body-mass index (BMI), suggesting that the NAFLD pathogenesis mechanism may be quite different depending on an individual's level of obesity. A BMI-stratified multivariate model based on the NAFLD serum metabolic profile was used to separate patients with and without NASH. The area under the receiver operating characteristic curve was 0.87 in the estimation and 0.85 in the validation group. The cutoff (0.54) corresponding to maximum average diagnostic accuracy (0.82) predicted NASH with a sensitivity of 0.71 and a specificity of 0.92 (negative/positive predictive values=0.82/0.84). The present data, indicating that a BMI-dependent serum metabolic profile may be able to reliably distinguish NASH from steatosis patients, have significant implications for the development of NASH biomarkers and potential novel targets for therapeutic intervention.
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Hígado Graso/metabolismo , Obesidad/metabolismo , Adulto , Anciano , Área Bajo la Curva , Biomarcadores/sangre , Biomarcadores/metabolismo , Índice de Masa Corporal , Progresión de la Enfermedad , Hígado Graso/sangre , Femenino , Humanos , Masculino , Metaboloma , Persona de Mediana Edad , Análisis Multivariante , Enfermedad del Hígado Graso no Alcohólico , Obesidad/sangre , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The underlying mechanisms responsible for allergic sensitization to food proteins remain elusive. To investigate the intrinsic properties (as well as the effect of pasteurization) of the milk proteins alpha-lactalbumin, beta-lactoglobulin and casein that promote the induction of milk allergy. METHODS: Alteration of structure and immune-reactivity of native and pasteurized proteins was assessed by gel filtration and ELISA. Uptake of these proteins was compared in vitro and in vivo. The biological effect was assessed by orally sensitizing C3H/HeJ mice with milk proteins followed by a graded oral challenge. Required dose to induce anaphylaxis, symptoms and mean body temperature was recorded. Antigen-specific antibodies and cytokine production by splenocytes were analyzed. RESULTS: Soluble beta-lactoglobulin and alpha-lactalbumin but not insoluble casein were readily transcytosed through enterocytes in vitro and in vivo. Pasteurization caused aggregation of beta-lactoglobulin and alpha-lactalbumin inhibiting uptake by intestinal epithelial cells in vitro and in vivo. Furthermore, aggregation redirected uptake to Peyer's patches, which promoted significantly higher Th2-associated antibody and cytokine production in mice than their native counterparts. Despite this only the soluble forms of beta-lactoglobulin and alpha-lactalbumin elicited anaphylaxis (following priming) when allergens were administered orally. Aggregated beta-lactoglobulin and alpha-lactalbumin as well as casein required systemic administration to induce anaphylaxis. CONCLUSIONS: These results indicate that triggering of an anaphylactic response requires two phases (1) sensitization by aggregates through Peyer's patches and (2) efficient transfer of soluble protein across the epithelial barrier. As the majority of common food allergens tend to form aggregates, this may be of clinical importance.
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Alérgenos/inmunología , Manipulación de Alimentos/métodos , Lactalbúmina/inmunología , Lactoglobulinas/inmunología , Hipersensibilidad a la Leche/inmunología , Ganglios Linfáticos Agregados/inmunología , Administración Oral , Anafilaxia/inmunología , Animales , Formación de Anticuerpos , Temperatura Corporal , Caseínas/inmunología , Citocinas/inmunología , Relación Dosis-Respuesta Inmunológica , Enterocitos/inmunología , Femenino , Calor , Lactalbúmina/metabolismo , Ratones , Ratones Endogámicos C3HRESUMEN
OBJECTIVE: It has been reported that the incidence of testicular cancer has plateaued in some parts of the USA, especially among non-Hispanic Whites in Los Angeles. Temporal trends analysis was conducted over three decades to assess the evidence for such a plateau, and to examine whether the incidence of testicular cancer remains stable across racial/ethnic groups. This study also investigated the influence of age at diagnosis on the incidence of testicular cancer. STUDY DESIGN: Population-based temporal trends analysis. METHODS: Using the Surveillance Epidemiology and End Results (SEER), 16,580 newly diagnosed cases of testicular cancer in males aged 15-49 years were identified between 1975 and 2004. Incidence rates were examined by calculating the age-adjusted rates and their 95% confidence interval (CI) for age at diagnosis, SEER areas and race for the year of diagnosis. The percentage change and annual percentage change were examined for trends. RESULTS: The incidence of testicular cancer is continuing to increase among US males, despite the plateau of the 1990s. Between 1975 and 2004, the age-adjusted incidence rate for males aged 15-49 years increased from 2.9 (1975) to 5.1 (2004) per 100,000. The trends indicated a percentage change of 71.9% and a statistically significant annual percentage change of 1.6% (95%CI 1.3-2.0; P<0.05). Although the incidence of testicular cancer in Blacks remained strikingly low (0.3-1.4 per 100,000), the highest annual percentage change was observed among this group (2.3%, 95%CI 0.8-3.9; P<0.05 for trends). The rates were intermediate among Asians/Pacific Islanders and American Indian and Alaska Natives (0.7-2.9 per 100,000), with a percentage change of 117.3% and a statistically significant annual percentage change of 1.5% (95%CI 0.3-2.7; P<0.05 for trends). The highest rates were reported among Whites (3.2-6.3 per 100,000), with a percentage change of 90.4% and a statistically significant annual percentage change of 2.0% (95%CI 1.6-2.3; P<0.05). The most common age at diagnosis was 30-34 years, while the lowest rates were reported in those aged 15-19 years. Likewise, incidence rates varied by SEER areas, with predominantly White states representing areas associated with the highest reported rates of testicular cancer. CONCLUSIONS: Overall, the incidence of testicular cancer continues to plateau in the USA, while racial variance persists. Black males demonstrate the greatest increase in annual percentage change. Further studies are needed to examine the recent increase among Black males and the potential determinants.
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Negro o Afroamericano/estadística & datos numéricos , Neoplasias Testiculares/etnología , Neoplasias Testiculares/epidemiología , Población Blanca/estadística & datos numéricos , Adolescente , Adulto , Distribución por Edad , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Programa de VERF , Estados Unidos/epidemiología , Adulto JovenRESUMEN
La cisticercosis quística parenquimal múltiple (CQPM) en fase degenerativa puede ocasionar un cuadro clínico de curso agudo o subagudo, de pronóstico reservado, frecuente en niños y que desde 1983 se conoce como encefalitis. Por el análisis retrospectivo de 6 casos de una serie de 64 con estudio anatomopatológico se determina que la encefalitis por NCC no es infrecuente en el adulto y se puede presentar en una cisticercosis quística parenquimal múltiple en fase vesicular o viable; puede ser precedida de crisis epilépticas por muchos años y tener un curso crónico. De otra parte, una CQPM puede llegar a la fase final de calcificación determinando sólo crisis epilépticas. Anatomopatológicamente se trata de una encefalitis edematosa.
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Humanos , Masculino , Adolescente , Adulto , Femenino , Persona de Mediana Edad , Encefalitis , NeurocisticercosisRESUMEN
Se compara la prevalencia de la neurocisticercosis en pacientes dados de alta de dos servicios de hospitalización, el Servicio de Neuropediatría y un servicio de adultos del Instituto Especializado de Ciencias Neurológicas (IECN) en dos períodos diferentes, determinando que ha habido un subdiagnóstico por deficiencia en los métodos de diagnóstico. Esta parasitosis se ha extendido en los últimos años a las grandes ciudades, como Lima. Las principales manifestaciones clínicas en el niño son las cirisis epilépticas (96.97 por ciento) en la presente serie, siendo las crisis parciales el tipo más frecuente (55.47 por ciento). Los niños tienen un menor grado de infestación, el cisticerco único en fase degenerativa es el hallazgo radiológico más frecuente. Por lo general, los niños con neurocisticercosis tienen menos manifestaciones clínicas que los adultos, siendo la única excepción la encefalitis, debido a una neurocisticercosis quística parenquimal múltiple.
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Neurocisticercosis , Niño , Estudios EpidemiológicosRESUMEN
Fatigue is a commonly reported and observed symptom among patients at the University of Texas M.D. Anderson Cancer Center. Caring for patients with this debilitating symptom is a major challenge. The nurse practitioner in the Fatigue Clinic has a special role in the management of these patients.
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Fatiga/prevención & control , Neoplasias/enfermería , Fatiga/diagnóstico , Fatiga/etiología , Fatiga/enfermería , Humanos , Neoplasias/complicaciones , Evaluación en Enfermería/métodos , PsicometríaRESUMEN
AIM: To study the influence of the depth of parietal invasion (mucosal-submucosal), the presence or absence of ganglionic invasion and type of gastrectomy performed (subtotal or total) on survival in patients with early gastric cancer. STUDY DESIGN: Longitudinal study. PATIENTS: A clinical-pathologic study of 101 patients who underwent surgery for early gastric cancer was performed. Probability of survival was estimated using the Kaplan-Meier and logrank tests and multivariate analysis was performed using the Cox test. RESULTS: Mucosal involvement was found in 46 patients (45.5%) and submucosal involvement in 55 patients (54.5%). The presence of ganglionic metastases was greater in tumors reaching the submucosa (14 [25.5%]) than in those limited to the mucosa (4 [8.7%]). Partial gastrectomy was performed according to tumor location in 84 patients (83.2%), total gastrectomy was performed in 16 patients (15.8%) and 1 wedge resection was performed. The mean postoperative follow-up was 84.04 55.89 months (range: 2-264). Comparison of survival in patients with tumors limited to the mucosal or submucosal layers revealed a p-value of 0.06 (NS). Comparison of survival in patients with metastases and in those without metastases revealed a p-value of < 0.0001. Comparison of survival between patients who underwent total gastrectomy and those who underwent partial gastrectomy showed a p-value of 0.38 (NS). Postoperative mortality was nil. Overall survival at 5 years was 79.24% and at 10 years was 68.14%. Multivariate analysis revealed that ganglionic involvement and depth of parietal invasion influenced survival. CONCLUSIONS: Survival is influenced by ganglionic involvement but not by submucosal invasion. Partial gastrectomy may be an appropriate procedure since survival is similar to that associated with total gastrectomy.
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Neoplasias Gástricas/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Gastrectomía , Mucosa Gástrica/patología , Humanos , Estudios Longitudinales , Metástasis Linfática , Masculino , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/cirugía , Análisis de SupervivenciaRESUMEN
Cancer-related fatigue is now the most prevalent symptom of cancer, occurring in 60-90% of patients. Fatigue has been identified by cancer patients as a factor influencing functionality and quality of life. Our objectives in developing a fatigue specialty clinic at The University of Texas M. D. Anderson Cancer Center were to improve our patients' quality of life by decreasing fatigue; educate health care providers, patients, and patients' families about cancer-related fatigue; develop an appropriate clinical and diagnostic evaluation for this symptom; correlate objective measures of fatigue with its clinical evaluation; and develop innovative treatment plans for cancer-related fatigue. This article describes the general clinic design and operations and the preliminary analysis of the first 40 patients evaluated in the fatigue clinic.
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Fatiga/terapia , Neoplasias/complicaciones , Servicio Ambulatorio en Hospital , Adulto , Anciano , Fatiga/diagnóstico , Fatiga/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Servicio Ambulatorio en Hospital/organización & administraciónRESUMEN
BACKGROUND: Biliopancreatic diversion (BPD) was designed to avoid the serious complications of jejunoileal bypass (steatohepatitis and hepatic failure). Although this is today considered a safe and effective procedure, a few reports of patients who developed steatohepatitis and subsequently died in hepatic failure exist. METHODS: We report a morbidity obese patient who developed subacute hepatitis resulting in hepatic failure 1 year after BPD. RESULTS: Because of irreversible liver failure the decision to perform a liver transplantation was made. The patient underwent emergency liver transplant and lengthening of the common limb. The course of liver transplantation and the patient's recovery were uneventful. CONCLUSION: Severe liver disease may rarely follow BPD. Liver transplantation and lengthening of the common bowel may be performed to treat these patients.
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Desviación Biliopancreática , Fallo Hepático/etiología , Trasplante de Hígado , Obesidad Mórbida/cirugía , Complicaciones Posoperatorias/cirugía , Adulto , Hígado Graso/etiología , Femenino , Encefalopatía Hepática/etiología , Humanos , Fallo Hepático/cirugíaRESUMEN
DNA polymerase eta is unique among eukaryotic polymerases in its proficient ability to replicate through a variety of distorting DNA lesions. We report here the crystal structure of the catalytic core of S. cerevisiae DNA polymerase eta, determined at 2.25A resolution. The structure reveals a novel polydactyl right hand-shaped molecule with a unique polymerase-associated domain. We identify the catalytic residues and show that the fingers and thumb domains are unusually small and stubby. In particular, the unexpected absence of helices "O" and "O1" in the fingers domain suggests that openness of the active site is the critical feature which enables DNA polymerase eta to replicate through DNA lesions such as a UV-induced cis-syn thymine-thymine dimer.
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Reparación del ADN , Replicación del ADN , ADN Polimerasa Dirigida por ADN/química , Estructura Terciaria de Proteína , Saccharomyces cerevisiae/enzimología , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Sitios de Unión , Catálisis , Dominio Catalítico , Cristalografía por Rayos X , Daño del ADN , ADN Polimerasa Dirigida por ADN/metabolismo , Genes Reporteros/genética , Humanos , Modelos Moleculares , Datos de Secuencia Molecular , Conformación Proteica , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Saccharomyces cerevisiae/química , Alineación de Secuencia , Moldes Genéticos , Xerodermia Pigmentosa/genéticaRESUMEN
A substantial proportion of cancer patients presenting to an emergency center (EC) or clinic with acute dyspnea survives fewer than 2 weeks. If these patients could be identified at the time of admission, physicians and patients would have additional information on which to base decisions to continue therapy to extend life or to refocus treatment efforts on palliation and/or hospice care alone. The purpose of this study was to identify risk factors for imminent death (survival = 2 weeks) and short-term survival (1, 3, or 6 months) in cancer patients presenting to an EC with acute dyspnea and to combine these factors into a model to help clinicians identify patients with short life expectancies. A random sample of 122 patients presenting to an EC with acute dyspnea was selected for a retrospective analysis. Data that were available to physicians during the initial EC visit included patient histories, triage and discharge vital signs, chest radiographs, and laboratory results. These variables were used in univariate and logistic regression models to develop predictive models for imminent death and short-term survival. Variables and interactions meeting a univariate criterion of P < 0.10 were included in stepwise regression by using forward and backward stepping. Models were compared with the use of Hosmer-Lemeshow statistics and receiver operating characteristics curves. Underlying cancers were 30% breast, 37% lung, and 34% other cancers. Triage respiration greater than 28/min., triage pulse greater than or equal to 110 bpm, uncontrolled progressive disease, and history of metastasis were found to be statistically significant predictors (alpha = 0.05) of imminent death. Patients with uncontrolled progressive disease had a relative risk of imminent death of 21.93. Relative risks for triage respiration, pulse, and metastases were 12.72, 4.92, and 3.85, respectively. Cancer diagnosis was not predictive of imminent death but was predictive when longer time periods were modeled. It may be possible to identify patients whose death is imminent from a group of cancer patients with acute dyspnea. Some factors that predict imminent death (triage pulse and respiration) differ from those (cancer diagnosis) that predict short-term survival. Extent of disease/response to treatment is common to all models. These factors need further examination and validation. If these findings are confirmed, this quantified information can help physicians in making difficult end-of-life decisions.
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Disnea/complicaciones , Neoplasias/complicaciones , Neoplasias/mortalidad , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Teóricos , Análisis Multivariante , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
We show that the IRF-2 oncoprotein represses virus-induced IFN-beta gene transcription via a novel mechanism. Virus infection induces recruitment of IRF-2 to some of the endogenous IFN-beta enhancers as part of the enhanceosome. Enhanceosomes bearing IRF-2 cannot activate transcription, due to the presence of a domain in IRF-2 that prevents enhanceosome-dependent recruitment of the CBP-Pol II holoenzyme complex. As a consequence, IRF-2 incorporation into enhanceosomes restricts the number of IFN-beta promoters directing transcription. Remarkably, deletion of the IRF-2 gene increases IFN-beta expression by expanding the number of cells capable of inducing IFN-beta gene transcription in response to virus infection.
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Proteínas de Unión al ADN/metabolismo , Elementos de Facilitación Genéticos , Regulación de la Expresión Génica , Interferón beta/genética , Factores de Transcripción , Transcripción Genética , Virus/inmunología , Animales , Células COS , Núcleo Celular/metabolismo , Chlorocebus aethiops , Cromatina/fisiología , Proteínas de Unión al ADN/genética , Genes Reporteros , Proteínas Fluorescentes Verdes , Células HeLa , Humanos , Factor 2 Regulador del Interferón , Proteínas Luminiscentes/genética , Ratones , Ratones Noqueados , Regiones Promotoras Genéticas , ARN sin Sentido/genética , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , TransfecciónRESUMEN
Low-molecular-weight heparins provide new options for outpatient management of deep venous thrombosis. Because elderly patients with cancer are at increased risk of developing deep venous thrombosis, outpatient therapy for treatment of deep venous thrombosis may be important in this population. We compared the severity of illness, outcomes, and cost of deep venous thrombosis in elderly patients with cancer to those seen in younger patients with cancer. We examined all 766 episodes of deep venous thrombosis treated at the University of Texas M.D. Anderson Cancer Center between January 1, 1994 and December 31, 1996. Severity of illness level and predicted risks of mortality and readmission were obtained from a commercially available disease staging system (Inforum System). Observed outcomes and cost were based on data collected from the 766 episodes of deep venous thrombosis at our institution. One hundred nineteen (16%) episodes of deep venous thrombosis occurred in patients 70 years of age or older. The severity of illness scale (1-5, least-most severe) were identical (3.7) in the 3 groups studied (< 70 years, 70-79, years and > or = 80 years). The predicted risk of death during hospitalization (6%, 9%, 8%, respectively, by group, P = 0.12) and readmission in 30 days (5%, 4%, 3%, respectively, P = 0.04) were similar among the groups. The observed death rates during hospitalization were 5%, 6%, and 6%, respectively (P = 0.91), and the rates of hospitalization for deep venous thrombosis recurrence were 22%, 16%, and 28%, respectively (P = 0.27). The similarities in outcomes and resource use between elderly and younger patients suggest that elderly patients with cancer are not at greater risk of serious clinical outcomes or a prolonged clinical course. There is significant potential for outpatient management of these patients.
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Neoplasias/complicaciones , Trombosis de la Vena/terapia , Anciano , Anciano de 80 o más Años , Recursos en Salud/estadística & datos numéricos , Humanos , Neoplasias/mortalidad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Resultado del Tratamiento , Trombosis de la Vena/mortalidad , Trombosis de la Vena/fisiopatologíaRESUMEN
Midkine (MK), a retinoic acid-inducible heparin-binding protein, is a mitogen which initiates a cascade of intracellular protein tyrosine phosphorylation mediated by the JAK/STAT pathway after binding to its high affinity p200(+)/MKR cell surface receptor in the G401 cell line [Ratovitski, E. A. (1998) J. Biol. Chem. 273, 3654-3660]. In this study, we determined the biophysical characteristics of purified recombinant murine MK and analyzed the requirements for ligand multimerization and cell surface proteoglycan binding for the G401 cell mitogenic activity of MK. Our studies indicate that the secreted form of MK (M = 13 kDa) exists in solution as an asymmetric monomer with a frictional coefficient of 1. 48 and a Stokes radius of 23.7 A. By constructing bead models of MK using the program AtoB and the program HYDRO to predict the hydrodynamic properties of each model, our data suggest that MK has a dumb-bell shape in solution composed of independent N- and C-terminal domains separated by an extended linker. This asymmetric MK monomer is a biologically active ligand with mitogenic activity on G401 cells in vitro. Neither heparin-induced formation of noncovalent MK multimers nor tissue transglutaminase II covalent multimerization of MK enhanced MK mitogenic activity in this system. Since neither heparin competition nor cell treatment with chondroitinase ABC or heparinase III abolished the mitogenic effects of MK on G401 cells, cell-surface proteoglycan binding by MK does not appear to be a requirement for its observed mitogenic effects. These results provide strong evidence that the MK-specific p200(+)/MKR has distinctive biochemical properties which distinguish it from the receptor tyrosine phosphatase cell-surface proteoglycan PTPzeta/RPTPbeta and support the hypothesis that the diverse biological effects of MK are mediated by multiple cell-specific signal transduction receptors.
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Proteínas Portadoras/fisiología , Citocinas , Sustancias de Crecimiento/fisiología , Proteoglicanos de Heparán Sulfato/metabolismo , Animales , Células CHO , Proteínas Portadoras/antagonistas & inhibidores , Proteínas Portadoras/biosíntesis , Proteínas Portadoras/metabolismo , Membrana Celular/genética , Membrana Celular/metabolismo , Cromatografía en Gel , Cricetinae , Dimerización , Inhibidores de Crecimiento/fisiología , Sustancias de Crecimiento/biosíntesis , Sustancias de Crecimiento/genética , Sustancias de Crecimiento/metabolismo , Heparina/metabolismo , Heparina/farmacología , Antagonistas de Heparina/farmacología , Ligandos , Ratones , Midkina , Mitógenos/antagonistas & inhibidores , Mitógenos/química , Mitógenos/metabolismo , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Transglutaminasas/antagonistas & inhibidores , Transglutaminasas/fisiología , Células Tumorales Cultivadas , Ultracentrifugación , Tumor de Wilms/patologíaRESUMEN
BACKGROUND: Vertical banded gastroplasty (VBG) has been found to result in significant reduction in body mass index (BMI) during the first postoperative year. We investigated the impact of some intrinsic and extrinsic factors on long-term BMI evolution in morbidly obese patients who underwent VBG, with the aim of establishing a long-term weight-loss prognosis. METHODS: 67 consecutive morbidly obese patients who underwent VBG were followed for 2 years; of these, 34 were followed 3 more years, for a total follow-up of 5 years. BMI was monitored and correlated with demographic (preoperative BMI, obese relatives, age and gender) and lifestyle variables (physical activity, habitual dietary transgression and occupational status). RESULTS: Global BMI fell from 47.5 at the time of the intervention to 32.1 when patients were examined 12 months after surgery. From the second year, an upward trend was observed, and at 5 years, mean BMI was above 35, considered in the high-risk range. Modifiable variables affecting lifestyle have shown significantly favorable effects on BMI evolution. Among intrinsic variables, BMI before surgery and obese parents also affect long-term evolution. CONCLUSION: Different variables should be considered in order to establish a long-term weight-loss prognosis for each patient, thus making it possible to act more specifically on modifiable variables.
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Índice de Masa Corporal , Gastroplastia/métodos , Obesidad Mórbida/cirugía , Adulto , Femenino , Estudios de Seguimiento , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Aumento de Peso , Pérdida de Peso/fisiologíaRESUMEN
These guidelines propose a treatment algorithm in which patients are evaluated regularly for fatigue, using a brief screening instrument, and are treated as indicated by their fatigue level. The algorithm's goal is to identify and treat all patients with fatigue that causes distress or interferes with daily activities or functioning. Management of fatigue begins with primary oncology team members who perform the initial screening and either provide basic education and counseling or expand the initial screening to a more focused evaluation for moderate or higher levels of fatigue. At this point the patient is assessed for the five primary factors known to be associated with fatigue: pain, emotional distress, sleep disturbance, anemia, and hypothyroidism. If any of these conditions are present, it should be treated according to practice guidelines, and the patient's fatigue should be reevaluated regularly. If none of the primary factors is present or the fatigue is unresolved, a more comprehensive assessment is indicated--with referral to other care providers as appropriate. The comprehensive assessment should include a thorough review of systems, review of medications, assessment of comorbidities, nutritional/metabolic evaluation, and assessment of activity level. Management of fatigue is cause-specific when conditions known to cause fatigue can be identified and treated. When specific causes, such as infection, fluid and electrolyte imbalances, or cardiac dysfunction, cannot be identified and corrected, nonpharmacologic and pharmacologic treatment of the fatigue should be considered. Nonpharmacologic interventions may include a moderate exercise program to improve functional capacity and activity tolerance, restorative therapies to decrease cognitive alterations and improve mood state, and nutritional and sleep interventions for patients with disturbances in eating or sleeping. Pharmacologic therapy may include drugs such as antidepressants for depression or erythropoietin for anemia. A few clinical reports of the use of corticosteroids and psychostimulants suggest the need for further research on these agents as a potential treatment modalities in managing fatigue. Basic to these interventions, the effective management of cancer-related fatigue involves an informed and supportive oncology care team that assesses patients' fatigue levels regularly and systematically and incorporates education and counseling regarding strategies for coping with fatigue (Johnson, 1999), as well as using institutional fatigue management experts for referral of patients with unresolved fatigue.