ABSTRACT
UNLABELLED: The sentinel lymph node (SLN) biopsy is currently the procedure of choice for axillary node staging in initial stages of breast cancer. The purpose of this study is to establish our false negative rate within a 5-year follow-up period in 258 patients with breast cancer staged with this procedure. METHODS: A retrospective study on 258 consecutive T1-T2<3 cm pN0 staged breast carcinomas treated from January 1, 2001 to December 31, 2005 was performed. The combined technique of isotope plus blue dye was used for detection. The subjects underwent a minimum follow-up of 5 years, mean 81 months, with an end of follow-up at December 31, 2010. Evidence of axillary recurrence, tumor recurrence in the breast and signs of disease progression or death were the events collected and analyzed. RESULTS: Of the 258 patients, 3 false negatives (1.1%) with axillary recurrence were detected at 10, 11 and 29 months of the surgery. This did not have a significant repercussion in the survival analysis on the contrary to the existence of breast recurrence or the appearance of distant metastasis in 4.7% and 6.2% patients, respectively. Global survival related with the cancer was 93.0 (240/258) and disease free survival was 89.1% (230/258). CONCLUSION: The risk of developing axillary recurrence after a negative SLN without axillary node dissection is low enough to consider the SLN procedure to be the best approach for axilla staging in early breast cancer. This staging technique also makes it possible to achieve local disease control without diminishing the survival of the patients.
Subject(s)
Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/secondary , Lymphatic Metastasis , Sentinel Lymph Node Biopsy/statistics & numerical data , Adult , Aged , Aged, 80 and over , Axilla , Breast Neoplasms/surgery , Breast Neoplasms/therapy , Carcinoma, Ductal, Breast/diagnosis , Carcinoma, Ductal, Breast/epidemiology , Carcinoma, Ductal, Breast/surgery , Carcinoma, Lobular/diagnosis , Carcinoma, Lobular/epidemiology , Carcinoma, Lobular/secondary , Carcinoma, Lobular/surgery , Chemotherapy, Adjuvant , Combined Modality Therapy , Disease-Free Survival , Estrogens , False Negative Reactions , Female , Follow-Up Studies , Humans , Incidence , Lymph Node Excision , Lymphatic Metastasis/diagnostic imaging , Mastectomy/methods , Middle Aged , Neoplasm Staging , Neoplasms, Hormone-Dependent/diagnosis , Neoplasms, Hormone-Dependent/epidemiology , Neoplasms, Hormone-Dependent/secondary , Neoplasms, Hormone-Dependent/surgery , Progesterone , Prognosis , Radionuclide Imaging , Radiotherapy, Adjuvant , Retrospective Studies , Rosaniline Dyes , Sentinel Lymph Node Biopsy/methods , Survival Analysis , Technetium Tc 99m Sulfur ColloidABSTRACT
La biopsia selectiva del ganglio centinela (GC) es en la actualidad el procedimiento de elección en la estadificación axilar en cánceres de mama en estadios iniciales. El objetivo de este trabajo es establecer nuestra tasa de falsos negativos a lo largo de un período mínimo de 5 años de seguimiento de 258 pacientes con cáncer de mama estadificados mediante este procedimiento. Método. Estudio retrospectivo de 258 pacientes con cáncer de mama consecutivos T1-T2<3cm estadificados como pN0 mediante GC entre enero-2001 y diciembre-2005.Se empleó la técnica combinada isotópica y colorante para la detección. Fueron sometidos a seguimiento con un período mínimo de 5 años, la media fue 81 meses, siendo el punto final del seguimiento el 31 de diciembre de 2010. La evidencia de recurrencia axilar, recidiva tumoral en la mama, presencia de enfermedad a distancia, y muerte fueron los eventos recogidos y analizados. Resultados. De las 258 pacientes, se detectaron 3 falsos negativos (1,1%), con recurrencia axilar a los 10, 11 y 29 meses de la cirugía. En el análisis de supervivencia este hecho no tuvo repercusión significativa, a diferencia de la existencia de recidiva mamaria o la aparición de metástasis a distancia que ocurrieron en un 4,7 y un 6,2% de las pacientes. La supervivencia global relacionada con el cáncer fue de un 93,0% (240/258) y la supervivencia libre de enfermedad del 89,1% (230/258). Conclusión. El riesgo de recurrencia axilar tras un ganglio centinela negativo sin vaciamiento linfático completo es lo suficientemente bajo como para considerar a este procedimiento como de elección en la estadificación axilar del cáncer de mama en estadios iniciales. Además, permite alcanzar un adecuado control local de la enfermedad sin disminuir la supervivencia de los pacientes(AU)
The sentinel lymph node (SLN) biopsy is currently the procedure of choice for axillary node staging in initial stages of breast cancer. The purpose of this study is to establish our false negative rate within a 5-year follow-up period in 258 patients with breast cancer staged with this procedure. Methods. A retrospective study on 258 consecutive T1-T2<3cm pN0 staged breast carcinomas treated from January 1, 2001 to December 31, 2005 was performed. The combined technique of isotope plus blue dye was used for detection. The subjects underwent a minimum follow-up of 5 years, mean 81 months, with an end of follow-up at December 31, 2010. Evidence of axillary recurrence, tumor recurrence in the breast and signs of disease progression or death were the events collected and analyzed. Results. Of the 258 patients, 3 false negatives (1.1%) with axillary recurrence were detected at 10, 11 and 29 months of the surgery. This did not have a significant repercussion in the survival analysis on the contrary to the existence of breast recurrence or the appearance of distant metastasis in 4.7% and 6.2% patients, respectively. Global survival related with the cancer was 93.0 (240/258) and disease free survival was 89.1% (230/258). Conclusion. The risk of developing axillary recurrence after a negative SLN without axillary node dissection is low enough to consider the SLN procedure to be the best approach for axilla staging in early breast cancer. This staging technique also makes it possible to achieve local disease control without diminishing the survival of the patients(AU)
Subject(s)
Humans , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Sentinel Lymph Node Biopsy/methods , Breast Neoplasms/epidemiology , Prognosis , Neoplasm Recurrence, Local/complications , Neoplasm Recurrence, Local/diagnosis , /instrumentation , /methods , Mastectomy/methods , Mastectomy , /trends , Immunohistochemistry/methods , Immunohistochemistry , Axilla/pathology , AxillaABSTRACT
OBJECTIVES: To assess the results of sentinel lymph node (SLN) detection in the initial stages of vulvar cancer and the recurrences that may appear. STUDY DESIGN: 76 patients with vulvar carcinoma, Stage I and II. Between 2000 and 2010, identification of the SLN was performed with a perilesional injection of Tc99m and vital dye. Ninety sentinel lymph nodes were found. They were removed separately, and lymphadenectomy was performed depending on the involved areas. Vulvar tumour was also removed. RESULTS: 76 patients were included in the study; 20 (22.22%) out of 90 SLNs presented metastases and 70 (77.77%) did not. There were no false negatives, and the sensitivity and negative predictive value reached 100%. Thirty-six months after treatment, one patient presented recurrence with a negative SLN, and two with positive SLNs. CONCLUSION: Biopsy of the SLN is a reasonable alternative to lymphadenectomy in patients with vulvar cancer Stage I and II.
Subject(s)
Carcinoma, Squamous Cell/pathology , Lymph Node Excision , Melanoma/pathology , Neoplasm Recurrence, Local/pathology , Sentinel Lymph Node Biopsy , Vulvar Neoplasms/pathology , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/surgery , Female , Humans , Lymphatic Metastasis , Melanoma/surgery , Neoplasm Staging , Predictive Value of Tests , Retrospective Studies , Vulvar Neoplasms/surgeryABSTRACT
Objetivo. Determinar la utilidad clínica de la gated-SPECT de perfusión miocárdica en la detección de isquemia silente en pacientes diabéticos sin síntomas ni eventos cardiovasculares previos y evaluar implicaciones pronósticas. Material y métodos. Estudio retrospectivo de 56 pacientes diabéticos asintomáticos tras una gated-SPECT de perfusión miocárdica para diagnóstico de enfermedad isquémica. El criterio de isquemia fue: ligera SDS<4, moderada SDS de 4 a 8, severa SDS>8. Se realizó un análisis estadístico multivariante para identificar variables predictoras de un estudio anormal y se registraron hasta diciembre de 2010 los eventos cardiovasculares. Resultados. Una alta proporción de los 56 pacientes presentó un estudio de perfusión anormal (46,4%), existiendo isquemia moderada-severa en el 10,7%, necrosis con isquemia en el 5,4% y necrosis en el 7,1%. No encontramos diferencias en cuanto al tipo de esfuerzo (tapiz rodante o dipiridamol). Existió una alta combinación de factores de riesgo cardiovascular. En el análisis multivariante, la nefropatía diabética fue la única que se relacionó con una SPECT anormal (p=0,043). En el seguimiento, los eventos fueron: 2 revascularizaciones precoces, 5 ingresos en cardiología, 10 muertes de no origen cardíaco. La existencia de isquemia en la SPECT se relacionó de forma significativa con la aparición de eventos cardiovasculares (p<0,05). Conclusión. La SPECT de perfusión miocárdica en diabéticos asintomáticos con alta asociación de factores de riesgo detecta la existencia de isquemia silente, la cual parece relacionarse con futuros eventos cardiovasculares. La nefropatía diabética sugiere mayor probabilidad de estudios anormales; sin embargo, es preciso establecer los criterios de cribado para un mayor rendimiento y un menor coste económico(AU)
Aim. To determine the clinical utility of the gated myocardial perfusion SPECT to detect silent ischemia in asymptomatic diabetic patients without previous coronary events and to evaluate the prognosis of this population. Material and methods. A retrospective study of 56 asymptomatic diabetics referred for a gated myocardial perfusion SPECT for diagnosis of ischemic disease was performed. The criteria for ischemia were: mild SDS<4, moderate SDS 4-8, severe SDS>8. A multivariable statistical analysis was carried out to identify possible predictive variables of an abnormal SPECT. The cardiovascular events were recorded up to December-2010. Results. A high proportion of the 56 patients had an abnormal perfusion study (46.4%), there being moderate-severe ischemia in 10.7%, necrosis with ischemia in 5.4% and necrosis in 7.1%. We found no statistical differences in the type of stress used (treadmill or dipyridamole). The patients had a high combination of cardiovascular risk factors. In the multivariate analysis, diabetic nephropathy was the only factor related to an abnormal SPECT (p=0.043). The events recorded in the follow-up were: 2 early revascularizations, 5 cardiology admissions, 10 non-cardiac related deaths. The existence of ischemia in the SPECT was significantly related to the appearance of cardiovascular events (p<0.05). Conclusion. A gated myocardial perfusion SPECT in asymptomatic diabetics with high combination of cardiovascular risk factors detects silent ischemia in a significant proportion and this seems to be related to future coronary events. Diabetic nephropathy implies a greater likelihood of abnormal studies. However, the screening criteria in this population still need to be established for better performance and lower cost(AU)
Subject(s)
Humans , Male , Female , Middle Aged , Heart Diseases/complications , Heart Diseases/diagnosis , Tomography, Emission-Computed, Single-Photon/instrumentation , Tomography, Emission-Computed, Single-Photon/methods , Perfusion/instrumentation , Perfusion/methods , Infusion Pumps , Risk Factors , Nuclear Medicine/methods , Nuclear Medicine/trends , Heart Diseases , Prognosis , Retrospective Studies , Multivariate Analysis , RadiopharmaceuticalsABSTRACT
AIM: To determine the clinical utility of the gated myocardial perfusion SPECT to detect silent ischemia in asymptomatic diabetic patients without previous coronary events and to evaluate the prognosis of this population. MATERIAL AND METHODS: A retrospective study of 56 asymptomatic diabetics referred for a gated myocardial perfusion SPECT for diagnosis of ischemic disease was performed. The criteria for ischemia were: mild SDS<4, moderate SDS 4-8, severe SDS>8. A multivariable statistical analysis was carried out to identify possible predictive variables of an abnormal SPECT. The cardiovascular events were recorded up to December-2010. RESULTS: A high proportion of the 56 patients had an abnormal perfusion study (46.4%), there being moderate-severe ischemia in 10.7%, necrosis with ischemia in 5.4% and necrosis in 7.1%. We found no statistical differences in the type of stress used (treadmill or dipyridamole). The patients had a high combination of cardiovascular risk factors. In the multivariate analysis, diabetic nephropathy was the only factor related to an abnormal SPECT (p=0.043). The events recorded in the follow-up were: 2 early revascularizations, 5 cardiology admissions, 10 non-cardiac related deaths. The existence of ischemia in the SPECT was significantly related to the appearance of cardiovascular events (p<0.05). CONCLUSION: A gated myocardial perfusion SPECT in asymptomatic diabetics with high combination of cardiovascular risk factors detects silent ischemia in a significant proportion and this seems to be related to future coronary events. Diabetic nephropathy implies a greater likelihood of abnormal studies. However, the screening criteria in this population still need to be established for better performance and lower cost.
Subject(s)
Diabetes Complications/epidemiology , Myocardial Ischemia/epidemiology , Myocardial Perfusion Imaging , Tomography, Emission-Computed, Single-Photon , Aged , Asymptomatic Diseases , Comorbidity , Diabetes Complications/diagnostic imaging , Diabetes Complications/mortality , Dipyridamole , Exercise Test , Female , Humans , Hypercholesterolemia/epidemiology , Incidence , Male , Middle Aged , Myocardial Ischemia/diagnostic imaging , Myocardial Revascularization/statistics & numerical data , Necrosis , Obesity/epidemiology , Organophosphorus Compounds , Organotechnetium Compounds , Patient Admission/statistics & numerical data , Predictive Value of Tests , Prognosis , Retrospective Studies , Risk , Smoking/epidemiology , Stroke VolumeABSTRACT
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Subject(s)
Humans , Female , Middle Aged , Skin Diseases, Papulosquamous/diagnosis , Granulomatosis with Polyangiitis/diagnosis , Hemoptysis/etiology , Granulomatosis with Polyangiitis/complicationsABSTRACT
OBJECTIVE: To present our experience in the application of sentinel node (SN) biopsy in patients with breast cancer T > 3 cm without clinical evidence of axillary metastasis. MATERIAL AND METHOD: Retrospective study of 393 cases in the period 2001--2006, divided into group (A) 47 patients with 3-5 cm T2N0 tumours and group (B) 346 patients T < 3 cm, N0. We employed the combined technique with 99mTc-colloidal rhenium sulphide and isosulfan blue dye. Preoperative lymphoscintigraphy was performed and the SN was located intraoperatively with a gamma ray detection probe and the blue dye. Axillary lymph node dissection was completed only when the SN was positive for metastasis in the histopathology analysis or not located. RESULTS: The SN detection rate for T2 > 3 cm was 94 % in the scintigraphy and 96 % with the probe, with no statistically significant differences between T < 3 cm (97 % and 98 %). In T2 > 3 cm, the final staging was 45 % pN0, 8 % pN1mi, 34 % pN1a, 11 % pN2a and 2 % pN3a. We found statistically significant differences (p < 0.05) when compared with palpable T < 3 cm and non-palpable cancer (62 % pN0 and 74 % pN0, respectively). In the follow-up of T2 > 3 cm (median 42.88 months) we did not find any axillary relapse which could be considered a false negative of the technique. CONCLUSION: The detection of sentinel lymph nodes is feasible and safe in tumours larger than 3cm with clinically negative axilla. Axillary lymph node dissection can be avoided in 45 % of these patients and therefore, we consider that they should be included as a general indication in breast cancer SN detection.
Subject(s)
Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/secondary , Neoplasm Staging/methods , Sentinel Lymph Node Biopsy , Adult , Aged , Aged, 80 and over , Axilla , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/pathology , Carcinoma, Lobular/pathology , Carcinoma, Lobular/secondary , Coloring Agents , Female , Follow-Up Studies , Humans , Lymphatic Metastasis/diagnosis , Lymphatic Metastasis/diagnostic imaging , Lymphatic Metastasis/pathology , Middle Aged , Palpation , Radionuclide Imaging , Radiopharmaceuticals , Retrospective Studies , Rosaniline Dyes , Sensitivity and Specificity , Technetium Tc 99m Sulfur ColloidABSTRACT
Objetivo. Presentar nuestra experiencia en la aplicación de la biopsia del ganglio centinela (GC) en la estadificación axilar del cáncer de mama de más de 3 cm sin evidencia clínica de metástasis. Material y método. Análisis retrospectivo de 393 casos entre enero-2001 y diciembre-2006 divididos en grupos: (A) 47 casos con tumores T2N0 entre 3 y 5 cm, y (B) 346 casos T < 3 cm N0. Empleamos la técnica combinada con 99mTc-sulfuro de renio coloidal y azul de isosulfán. Se realizó una linfogammagrafía preoperatoria y la localización intraoperatoria tuvo lugar con una sonda gammadetectora y con el colorante azul. Se completó la linfadenectomía axilar sólo en el caso de metástasis en el análisis histológico del GC o en ausencia de localización del GC. Resultados. La detección del GC en T2 > 3 cm fue en la gammagrafía del 94 % y con la sonda gammadetectora del 96 %, sin diferencias estadísticamente significativas frente a los T < 3 cm (97 y 98 %). En los T2 > 3 cm la estadificación axilar final fue 45 % pN0, 8% pN1mi, 34 % pN1a, 11 % pN2a y 2% pN3a. Existieron diferencias significativas (p < 0,05) al comparar con lesiones < 3 cm palpables y no palpables (62% pN0 y 74 % pN0 respectivamente). En el seguimiento de los T2 > 3 cm (media 42,88 meses) no encontramos ningún caso con recaída a nivel axilar que pueda considerarse como falso negativo de la técnica. Conclusiones. La detección del GC es posible y segura en tumores de más de 3 cm con axila clínicamente negativa, evitándose en un 45 % de los casos la linfadenectomía axilar, por lo que consideramos que es correcta su inclusión en los criterios de indicación de la técnica en el cáncer de mama (AU)
Objective. To present our experience in the application of sentinel node (SN) biopsy in patients with breast cancer T > 3 cm without clinical evidence of axillary metastasis. Material and Method. Retrospective study of 393 cases in the period 2001-2006, divided into group (A) 47 patients with 3-5 cm T2N0 tumours and group (B) 346 patients T < 3 cm, N0. We employed the combined technique with 99mTc-colloidal rhenium sulphide and isosulfan blue dye. Preoperative lymphoscintigraphy was performed and the SN was located intraoperatively with a gamma ray detection probe and the blue dye. Axillary lymph node dissection was completed only when the SN was positive for metastasis in the histopathology analysis or not located. Results. The SN detection rate for T2 > 3 cm was 94 % in the scintigraphy and 96 % with the probe, with no statistically significant differences between T < 3 cm (97 % and 98 %). In T2 > 3 cm, the final staging was 45 % pN0, 8% pN1mi, 34% pN1a, 11 % pN2a and 2% pN3a. We found statistically significant differences (p < 0.05) when compared with palpable T < 3 cm and non-palpable cancer (62% pN0 and 74 % pN0, respectively). In the follow-up of T2 > 3 cm (median 42.88 months) we did not find any axillary relapse which could be considered a false negative of the technique. Conclusion. The detection of sentinel lymph nodes is feasible and safe in tumours larger than 3cm with clinically negative axilla. Axillary lymph node dissection can be avoided in 45 % of these patients and therefore, we consider that they should be included as a general indication in breast cancer SN detection (AU)
Subject(s)
Humans , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/secondary , Neoplasm Staging/methods , Sentinel Lymph Node Biopsy , Technetium Tc 99m Sulfur Colloid , Axilla , Breast Neoplasms/surgery , Carcinoma, Lobular/pathology , Carcinoma, Lobular/secondary , Coloring Agents , Follow-Up Studies , Lymphatic Metastasis/diagnosis , Lymphatic Metastasis/pathology , Lymphatic Metastasis , Palpation , Radiopharmaceuticals , Retrospective Studies , Rosaniline Dyes , Sensitivity and SpecificityABSTRACT
PURPOSE: To present our experience in the therapeutic approach of the sentinel node biopsy (SNB) in patients with previous excision of the breast cancer, divided in non-palpable and palpable lesions, in comparison with time treatment and stagement of breast cancer. METHODS: In the period 2001-2006, 138 patients with prior diagnostic excisional biopsy (96 non-palpable and 42 palpable breast cancer) and 328 without previous surgery (32 non-palpable; 296 palpable cancer) were treated. The combined technique ((99m)Tc-colloidal rhenium and isosulfan blue dye) was the approach for sentinel lymph node (SLN) detection. Axillary lymph node dissection (ALND) was completed only when the SLN was positive for metastasis or not located. RESULTS: Detection rate, if there was prior surgery, was 95% for non-palpable and 98% for palpable cancer, and 99% for one-time treatment group. Metastasis rate in the SLN was 15% in non-palpable cancer (14/91), significantly smaller than in palpable breast cancer (39% if prior surgery and 37% in one-time surgery). According to tumoral size, ALND metastasis rate was similar for T1 and T2 tumors (43-44%). In the follow-up of the groups with prior diagnostic biopsy or surgery of the breast cancer we have not found any false negative in the axilla. CONCLUSION: The detection of the SLN is also feasible in patients with previous surgery of breast cancer. Because SLN metastasis rates are significantly smaller in non-palpable lesions, the effort in screening programs for early detection of breast cancer and also in improving histopathological confirmation of malignancy with ultrasound or stereotactic guided core biopsies must continue.
Subject(s)
Breast Neoplasms/pathology , Breast Neoplasms/surgery , Lymphatic Metastasis/diagnosis , Sentinel Lymph Node Biopsy/methods , Adult , Aged , Aged, 80 and over , Axilla , Breast Neoplasms/diagnostic imaging , Coloring Agents , Female , Humans , Lymphatic Metastasis/diagnostic imaging , Middle Aged , Neoplasm Staging/methods , Palpation , Radionuclide Imaging , Radiopharmaceuticals , Rhenium , Rosaniline Dyes , Technetium Tc 99m Sulfur ColloidABSTRACT
Kaposi's sarcoma is a multifocal neoplastic process with four clinical variants, all of them induced by human herpes virus 8. Currently there is no treatment of choice and it depends on the extension and location of the lesions as well as on the clinical type of the disease. Alitretinoin gel 0.1 % is approved for the treatment of cutaneous lesions of AIDS-associated Kaposi's sarcoma. The majority of its side effects appear at the site of application and can lead to therapy withdrawal. We report a case of Kaposi's sarcoma treated with topical alitretinoin that had a favourable evolution in spite of an intense local reaction.
Subject(s)
Antineoplastic Agents/administration & dosage , Sarcoma, Kaposi/drug therapy , Skin Neoplasms/drug therapy , Tretinoin/administration & dosage , Administration, Topical , Aged, 80 and over , Alitretinoin , Female , HumansABSTRACT
El sarcoma de Kaposi es un proceso neoplásico multifocal del cual existen 4 variantes clínicas, todas ellas inducidas por el virus herpes humano tipo 8. En la actualidad no existe un tratamiento de elección y éste depende de la extensión y la localización de las lesiones, así como del tipo clínico de la enfermedad. La alitretinoína al 0,1 % en gel está aprobada para el tratamiento de las lesiones cutáneas del sarcoma de Kaposi asociado a sida. La mayoría de sus efectos secundarios aparecen en el lugar de aplicación y pueden obligar a suspender el tratamiento. Presentamos un caso de sarcoma de Kaposi tratado con alitretinoína tópica con buena evolución pese a la intensa reacción local
Kaposi's sarcoma is a multifocal neoplastic process with four clinical variants, all of them induced by human herpes virus 8. Currently there is no treatment of choice and it depends on the extension and location of the lesions as well as on the clinical type of the disease. Alitretinoin gel 0.1 % is approved for the treatment of cutaneous lesions of AIDS-associated Kaposi's sarcoma. The majority of its side effects appear at the site of application and can lead to therapy withdrawal. We report a case of Kaposi's sarcoma treated with topical alitretinoin that had a favourable evolution in spite of an intense local reaction
Subject(s)
Female , Aged , Humans , Sarcoma, Kaposi/complications , Sarcoma, Kaposi/diagnosis , Sarcoma, Kaposi/drug therapy , Tretinoin/therapeutic use , Erythema/complications , Hyperpigmentation/complications , Hyperpigmentation/drug therapy , Molting , Skin , Skin/injuries , Herpes Zoster/etiology , Methotrexate/adverse effects , Prednisone/adverse effectsABSTRACT
Objetivo: Estudio de la demanda urgente y su proceso asistencial por insuficiencia cardiaca congestiva (ICC) en un hospital de área de salud de nivel II. Método: Diseño epidemiológico observacional de corte transversal sobre 242 pacientes mayores de 14 años con criterios de ICC, que demandaron asistencia por urgencias del 1 de junio al 20 de septiembre de 2000.Resultados: La edad media fue de 77,9 años ( =11,2). Había 113 (46,5 por ciento) hombres y 129 (53,1 por ciento) mujeres y sus edades medias (75,6 y 80 años, respectivamente) diferían significativamente (p<0,05).Demandan asistencia urgente un promedio de dos veces al año y uno de cada dos termina siendo ingresado. Los episodios se repiten en promedio cada 75 días. Sólo uno de cada tres fueron atendidos antes por su médico de atención primaria y sólo el 5 por ciento reingresan antes de las 72 horas tras el alta. Los principales factores de riesgo son la hipertensión, cardiopatía isquémica, diabetes, EPOC y obesidad (más diabetes en mujeres y más EPOC en hombres).El esquema terapéutico de la ICC sigue basándose en el diurético de asa, el inhibidor de la enzima conversiva de angiotensina y la digoxina. La práctica clínica analizada muestra poco uso de espironolactona (valvulopatía), IECAs (hipertensión y miocardiopatía) y Beta-bloqueantes (hipertensión). Conclusiones: El paciente tipo es un hombre o mujer de edad avanzada que acude a urgencias por iniciativa propia, siendo su primer ingreso. Sólo la mitad saben que tienen ICC. El varón presenta un mayor deterioro clínico en relación a su disfunción sistólica a diferencia de la mujer en la que descompensación se debe a una arritmia cardiaca por fibrilación auricular con función sistólica conservada. El esquema terapeútico sigue siendo el clásico (AU)
Subject(s)
Female , Male , Aged, 80 and over , Humans , Heart Failure/epidemiology , Emergency Medical Services , Cross-Sectional Studies , Risk Factors , Mortality , Clinical Protocols , Heart Failure/diagnosis , Heart Failure/therapyABSTRACT
The synthesis and pharmacological activity of a series of bicyclic pyrazolo[1,5-a]pyrimidines as potent and selective cyclooxygenase-2 (COX-2) inhibitors are described. The new compounds were evaluated both in vitro (COX-1 and COX-2 inhibition in human whole blood) and in vivo (carrageenan-induced paw edema and air-pouch model). Modification of the pyrimidine substituents showed that 6,7-disubstitution provided the best activity and led to the identification of 3-(4-fluorophenyl)-6,7-dimethyl-2-(4-methylsulfonylphenyl)pyrazolo[1,5-a]pyrimidine (10f) as one of the most potent and selective COX-2 inhibitor in this series.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Isoenzymes/antagonists & inhibitors , Pyrazoles/chemical synthesis , Pyrimidines/chemical synthesis , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Carrageenan , Cell Line , Cyclooxygenase 1 , Cyclooxygenase 2 , Edema/drug therapy , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Exudates and Transudates/enzymology , Humans , Male , Membrane Proteins , Prostaglandin-Endoperoxide Synthases , Pyrazoles/chemistry , Pyrazoles/pharmacology , Pyrimidines/chemistry , Pyrimidines/pharmacology , Rats , Rats, Inbred Lew , Rats, Sprague-Dawley , Stomach/enzymology , Structure-Activity RelationshipSubject(s)
Fluoresceins , Platelet Aggregation Inhibitors/analysis , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Adenosine Diphosphate/pharmacology , Blood Platelets/metabolism , Fibrinogen/metabolism , Fluorescent Dyes , Humans , Inhibitory Concentration 50 , Methods , Platelet Activation/drug effects , Platelet Adhesiveness/drug effects , Platelet Aggregation Inhibitors/chemistry , Protein Binding , Spectrometry, FluorescenceABSTRACT
1. The effect of two derivatives of salicylate, 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) and 2-acetoxy-4-trifluoromethylbenzoic acid (triflusal), on the expression of several proteins displaying pro-inflammatory activities the regulation of which is associated to the transcription factor NF-kappaB, was assayed in the human astrocytoma cell line 1321N1. 2. Tumour necrosis factor-alpha (TNF-alpha) activated NF-kappaB as judged from both the appearance of kappaB-binding activity in the nuclear extracts, the degradation of IkappaB proteins in the cell lysates, and the activation of IkappaB kinases using an immunocomplex kinase assay with glutathione S-transferase (GST)-IkappaB proteins as substrates. 3. HTB up to 3 mM did not inhibit the nuclear translocation of NK-kappaB/Rel proteins as judged from electrophoretic mobility-shift assays; however, HTB inhibited the degradation of IkappaBbeta without significantly affecting the degradation of both IkappaBalpha and IkappaBepsilon. 4. In keeping with their inhibitory effect on IkappaBbeta degradation in the cell lysates, both HTB and triflusal inhibited the phosphorylation of GST-IkappaBbeta elicited by TNF-alpha, without affecting the phosphorylation of GST-IkappaBalpha. 5. The effect of both HTB and triflusal on kappaB-dependent trans-activation was studied by assaying the expression of both cyclo-oxygenase-2 (COX-2) and vascular cell adhesion molecule-1 (VCAM-1). HTB and triflusal inhibited in a dose-dependent manner the expression of COX-2 and VCAM-1 mRNA and the induction of COX-2 protein at therapeutically relevant concentrations. 6. These findings show the complexity of the biochemical mechanisms underlying the activation of NF-kappaB in the different cell types and extend the anti-inflammatory effects of HTB and triflusal to neural cells.
Subject(s)
Astrocytoma/metabolism , Brain Neoplasms/metabolism , NF-kappa B/metabolism , Salicylates/pharmacology , Blotting, Western , Cyclooxygenase 2 , DNA, Complementary/biosynthesis , Electrophoresis , Humans , Indicators and Reagents , Isoenzymes/biosynthesis , Membrane Proteins , Neoplasm Proteins/biosynthesis , Neurons/drug effects , Neurons/metabolism , Prostaglandin-Endoperoxide Synthases/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured , Vascular Cell Adhesion Molecule-1/biosynthesisABSTRACT
El factor de transcripción nuclear NF-kB controla la expresión de diversos genes implicados en la patogénesis de la ateroclerosis. El triflusal (ácido 2-acetoxi-4-trifluorometilbenzoico) es un fármaco antiagregante que, aunque relacionado estructuralmente con la aspirina y otros salicilatos, muestra un perfil farmacológico y farmacocinético característico. Dado que recientemente se ha demostrado que los salicilatos pueden inhibir el NF-kB, el objetivo del presente estudio ha sido probar la actividad inhibitoria tanto del triflusal como de su metabolito desacetilado, el HTB, sobre la activación de NF-kB. Los resultados aquí descritos muestran que ambos compuestos, trifulsal y HTB, son inhibidores de la activación de NF-kB más potentes que la aspirina o el salicilato, y como consecuencia de ello, pueden bloquear la inducción de la síntesis de citocinas (TNF-a), quimiocinas (MCP-1), moléculas de adhesión (VCAM-1) y enzimas proinflamatorios (COX-2, NOS 2).Además, a diferencia de la aspirina, estos efectos antiinflamatorios del trifulsal se alcanzan a concentraciones similares a las obtenidas en su uso terapeútico como fármaco antiagregante plaquetario. El trifulsal puede ejercer efectos antiinflamatorios en trastornos cardiovasculares en los que se ha observado que genes controlados por el NF-kB están sobrexpresados (AU)
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