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Animales , Escarabajos , Rabdítidos , Gorgojos , Virulencia , Control Biológico de VectoresAsunto(s)
Escarabajos , Rabdítidos , Gorgojos , Animales , Control Biológico de Vectores , VirulenciaRESUMEN
INTRODUCTION: This trial aimed to evaluate the safety and efficacy of epigenetic therapy associated with cisplatin chemoradiation in FIGO Stage IIIB patients. METHODS: Hydralazine containing either 182 mg for rapid-, or 83 mg for slow acetylators and magnesium valproate were administered at 30 mg/kg tid. Both drugs were taken until intracavitary therapy was finished. Pelvic external beam radiation and low-dose rate brachytherapy were administered at a total cumulative dose to point A of at least 85 Gy. Weekly cisplatin at 40 mg/m2 was delivered for six cycles. RESULTS: Twenty-two patients were included and 18 (82%) patients completed treatment. Mean dose to point A was 84.6 + 2.2. Median number of cisplatin cycles was 5.5 (range, 1-6). Brachytherapy was delayed for technical reasons; the mean overall treatment time was 11.8 weeks. Grade 3 anemia, leucopenia, neutropenia, and thrombocytopenia were observed in 9%, 45%, 45%, and 9% of patients, respectively. CONCLUSIONS: Hydralazine and valproate are well-tolerated and safe when administered with cisplatin chemoradiation. Unfortunately, the suboptimal administration of brachytherapy for technical reasons in this study, precluded assessing the efficacy of epigenetic therapy. However, the tolerability of this regimen administered concurrent to radiation needs to be further tested.
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Antineoplásicos/uso terapéutico , Braquiterapia , Cisplatino/uso terapéutico , Epigénesis Genética , Neoplasias del Cuello Uterino/terapia , Adulto , Anciano , Braquiterapia/efectos adversos , Cisplatino/efectos adversos , Terapia Combinada , Femenino , Humanos , Hidralazina/administración & dosificación , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patología , Ácido Valproico/administración & dosificaciónRESUMEN
Gemcitabine (2',2'-difluoro 2'deoxycytidine, dFdC) is an analog of cytosine with distinctive pharmacological properties and a wide antitumor-activity spectrum. The pharmacological characteristics of gemcitabine are unique because two main classes of genes are essential for its antitumor effects: membrane transporter protein-coding genes, whose products are responsible for drug intracellular uptake, as well as enzyme-coding genes, which catalyze its activation and inactivation. The study of the pharmacogenetics and pharmacoepigenetics of these two gene classes is greatly required to optimize the drug's therapeutic use in cancer. This review aims to provide an update of genetic and epigenetic bases that may account for interindividual variation in therapeutic outcome exhibited by gemcitabine.
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Antimetabolitos Antineoplásicos/uso terapéutico , Desoxicitidina/análogos & derivados , Epigenómica , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Farmacogenética , Desoxicitidina/uso terapéutico , Humanos , GemcitabinaRESUMEN
BACKGROUND: Epigenetic aberrations lead to chemotherapy resistance; hence, their reversal by inhibitors of DNA methylation and histone deacetylases may overcome it. PATIENTS AND METHODS: Phase II, single-arm study of hydralazine and magnesium valproate added to the same schedule of chemotherapy on which patients were progressing. Schedules comprised cisplatin, carboplatin, paclitaxel, vinorelbine, gemcitabine, pemetrexed, topotecan, doxorubicin, cyclophosphamide, and anastrozole. Patients received hydralazine at 182 mg for rapid, or 83 mg for slow, acetylators, and magnesium valproate at 40 mg/kg, beginning a week before chemotherapy. Response, toxicity, DNA methylation, histone deacetylase activity, plasma valproic acid, and hydralazine levels were evaluated. RESULTS: Seventeen patients were evaluable for toxicity and 15 for response. Primary sites included cervix (3), breast (3), lung (1), testis (1), and ovarian (7) carcinomas. A clinical benefit was observed in 12 (80%) patients: four PR, and eight SD. The most significant toxicity was hematologic. Reduction in global DNA methylation, histone deacetylase activity, and promoter demethylation were observed. CONCLUSIONS: The clinical benefit noted with the epigenetic agents hydralazine and valproate in this selected patient population progressing to chemotherapy' and re-challenged with the same chemotherapy schedule after initiating hydralazine and valproate' lends support to the epigenetic-driven tumor-cell chemoresistance hypothesis (ClinicalTrials.gov Identifier: NCT00404508).
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos , Hidralazina/administración & dosificación , Neoplasias/tratamiento farmacológico , Ácido Valproico/administración & dosificación , Adolescente , Metilación de ADN , Epigénesis Genética , Femenino , Histona Desacetilasas/metabolismo , Humanos , Hidralazina/efectos adversos , Hidralazina/sangre , Masculino , Neoplasias/genética , Ácido Valproico/efectos adversos , Ácido Valproico/sangreRESUMEN
Actinomycosis is an unusual, chronic granulomatous disease. Actinomyces israelli has been found to be related to infectious processes in those patients with affected skin integrity leading to abscess formation, fistulae or mass lesions. Actinomycosis mainly presents in three forms cervicofacial (50%), abdominal (20%) and thoracic (15%). Pelvic cases have been rarely reported and are usually associated with the use of intrauterine devices. We describe a case of a 23 y/o female without history of intrauterine device use, who was admitted with an ovarian cyst following an appendectomy. An ovarian abscess was drained. The pathology showed a granuloma and focal sulfur granules like particles compatible with Actinomyces. This is a case of pelvic Actinomyces, not related to the use of an intrauterine device
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Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Absceso Abdominal/diagnóstico , Absceso/microbiología , Actinomicosis/diagnóstico , Quistes Ováricos/complicaciones , Complicaciones Posoperatorias/diagnóstico , Enfermedades del Ovario/microbiología , Apendicectomía , Absceso Abdominal/etiología , Absceso Abdominal/microbiología , Absceso/tratamiento farmacológico , Absceso/cirugía , Actinomicosis/tratamiento farmacológico , Actinomicosis/cirugía , Actinomyces/aislamiento & purificación , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Amoxicilina/administración & dosificación , Amoxicilina/uso terapéutico , Quistes Ováricos/diagnóstico , Quistes Ováricos/microbiología , Diagnóstico Diferencial , Drenaje , Enfermedades del Ovario/tratamiento farmacológico , Enfermedades del Ovario/cirugía , Dispositivos Intrauterinos , Penicilina G/administración & dosificación , Penicilina G/uso terapéutico , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: To date, curative treatment options for hepatocellular carcinoma (HCC) include orthotopic liver transplantation or surgical resection. Most patients are detected with nonresectable or transplantable HCC due to disease extension or comorbid factors, and are therefore candidates for palliative treatments only. Few follow-up data are available in patients with HCC in Latin America. We therefore reviewed the experience of HCC treatment in a single institution over a 10-year period. PATIENTS AND METHOD: A total of 135 patients attending the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, a national referral center in Mexico, from January 1991 to December 2000 were included. In all patients etiology, stage, and diagnostic and therapeutic measures were documented. Survival time was calculated as a function of staging and therapy. RESULTS: Of 135 patients, 77 (57%) were men and 58 (43%) were women. The mean age at diagnosis was 59.17 years (range: 16-87 years). Cirrhosis was diagnosed in 89 patients (64.4%). The median overall survival for all patients with HCC was 7.9 months. Treatment included surgical resection (n=22), hepatic artery chemoembolization (n=10), percutaneous ethanol injection (n=6), systemic chemotherapy (n=5), tamoxifen (n=11), and thalidomide (n=1). Eighty patients received support measures. The median survival in the group of patients who underwent surgical resection (37.89 months) was significantly higher than that in the groups of patients who did not undergo resection. CONCLUSIONS: Patients with HCC who received no treatment had a median survival of 1.7 months. Hepatic resection offers the best chance of cure in patients with HCC. The strong association between HCC and cirrhotic liver disease makes surgical resection difficult in patients with low hepatic reserve.
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Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/mortalidad , Femenino , Instituciones de Salud , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , México , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
Post-remission high-dose chemotherapy has been an important advance in the treatment of adult acute leukemia (AAL). Without the use of colony-stimulating factors (CSFs) in this program, the mortality rate varies from 5 to 17%, and infectious complications arise in more than 50%. These findings limit the widespread use of such forms of therapy. The use of high-dose ara-C (HIDAC) alone or in combination with other drugs is the most common regimen studied, however neither other drug combinations nor the addition of supporting CSFs have been extensively explored. For this reason we studied the effect of high-dose cyclosphosphamide-etoposide (CECY) plus recombinant human granulocyte-macrophage (rHuGM)-CSF with the intention of decreasing morbimortality and prolonging disease-free survival (DFS). Since 1992 we have included 51 complete remission patients with AAL in the CECY plus rHuGM-CSF protocol. The maximal myelosuppression occurred in a mean of 6.4 days, and the mean days required for absolute neutrophil count recovery was 13 days and for platelets 21 days (p < 0.0001). No toxic deaths occurred and only two serious infectious complications were seen. After two years of follow-up, 50% of de novo acute myelogenous leukemia patients had relapsed at 13 months, and 50% of de novo adult acute lymphocytic leukemia patients had relapsed at 15 months. In a recent update, we have not seen a significant difference when compared to historic groups. The CECY protocol does not appear to be superior in prolonging DFS compared to HIDAC as a post-remission strategy for newly diagnosed AAL. The main difference was the absence of toxic deaths and minimal serious infectious complications in the CECY protocol. Therefore, we suggest that the use of rHuGM-CSF in post-remission programs should be included in future studies.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Proteínas Recombinantes/uso terapéutico , Enfermedad Aguda , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/administración & dosificación , Citarabina/efectos adversos , Citarabina/uso terapéutico , Etopósido/administración & dosificación , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/efectos adversos , Humanos , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/efectos adversosRESUMEN
Drug induced agranulocytosis (DIA) is a potentially lethal disorder characterized by selective neutropenia. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been utilized for its treatment. We report four cases of DIA treated with GM-CSF at the dose of 5 micrograms/kg/day. The patients presented infectious diseases at diagnosis. Median days to obtain 1 x 10(9)/L neutrophils and a normal neutrophil count (NNC), were 7(5-9) and 7.5 (6-10) days, respectively. The infectious disease at diagnosis improved and all patients are alive at the moment of this report. No other adverse effects than thrombocytosis (two cases) and thrombocytopenia (one case) were observed. We consider that GM-CSF could be a safe and effective alternative in the treatment of DIA.
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Agranulocitosis/terapia , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Factores Inmunológicos/uso terapéutico , Adulto , Anciano , Agranulocitosis/inducido químicamente , Antibacterianos/efectos adversos , Femenino , Enfermedad de Graves/complicaciones , Enfermedad de Graves/tratamiento farmacológico , Humanos , Recuento de Leucocitos , Masculino , Metimazol/efectos adversos , Neutrófilos , Tonsilitis/complicaciones , Tonsilitis/tratamiento farmacológicoRESUMEN
In 52 patients we performed endoscopic sclerotherapy during active bleeding with good results in stopping hemorrhage in 93%. Most patients were Child "C" (66%) and postnecrotic cirrhosis was the commonest etiology (50%). Major complications were pleural effusion (2%) and mediastinal inflammation (2%), no mortality was found directly by this method. Conclusions are that endoscopic sclerosis of variceal hemorrhage have a special role in stopping bleeding but has no effect in one year survival.
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Endoscopía Gastrointestinal , Várices Esofágicas y Gástricas/terapia , Hemorragia Gastrointestinal/terapia , Escleroterapia/métodos , Urgencias Médicas , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/mortalidad , Femenino , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/mortalidad , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Tasa de SupervivenciaRESUMEN
We present our experience with elective sclerotherapy in ten years. 64 male and 57 females, median age 52.5 years, were treated. Post-necrosis cirrhosis was the primordial etiology in 44% followed by alcoholic in 40%. In regards to Child classification, 51% were "C"; 24% "B" and 25% "A". With variceal eradication we found no rebleeding, but in those without changes in variceal size, it was 82%. At six months, control of variceal hemorrhage was respectively to groups A, B, and C. 86%, 71% and 63%. The control at long follow-up were respectively 74%, 68% & 57%. Survival was directly related to the level of hepatic function instead of sclerosis. Complications were 2 to be 3% being the most severe: pleural effusion; mediastinitis and fiber. Mortality was 0.8% in one patient with esophageal perforation.