RESUMO
RATIONALE AND OBJECTIVES: To develop a human metastatic colorectal cancer (mCRC) model in a rabbit liver. MATERIALS AND METHODS: Immunosuppression in 4 adult New Zealand White rabbits weighing 3.5 to 4.5 kg was induced with daily subcutaneous injection of 15 mg/kg Cyclosporine A (CsA). On day 3 open mini-laparotomy was performed and 0.2 ml (1.8x105 cells) suspension of HCT-116 and HT-29 human CRC cells were injected into the left and right medial lobe respectively. On day 10 the CsA dose was reduced to 10 mg/kg daily maintenance dose. Rabbits were weighed weekly, closely monitored for CsA side effects (weight loss, gingival hyperplasia and gut modification). Rabbits were sacrificed 5, 6, 7, and 8 weeks after cells injection. Liver tumors were collected for histopathology and immunohistochemical analysis. RESULTS: HT-29 Tumor growth was observed in 3 rabbits (75%). Tumors measured 3, 4 and 6 mm after 5, 6 and 8 weeks respectively. Microscopically, tumors contained hyperchromatic, pleomorphic cells that stained for monoclonal carcinoembryonic antigen (CEA), polyclonal CEA, cytokeratin 20, vascular markers (CD31, CD34), and vascular endothelial growth factor (VEGF) by immunohistochemistry, supporting involvement by the poorly differentiated HT-29 colorectal cancer cell line. No gross tumor growth or microscopic viability was observed from HCT-116 cell injection. CsA extra-hepatic manifestations included minimal gum hyperplasia and decrease in gut motility in 3 rabbits (75%), which was treated with Azithromycin 15 mg/kg and Cisapride 0.5 mg/kg every 12 hours, respectively. CONCLUSION: We successfully developed a human metastatic colon cancer model in immunosuppressed rabbit liver using HT-29 cells.
Assuntos
Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Neoplasias Hepáticas/secundário , Fígado/patologia , Animais , Humanos , Terapia de Imunossupressão , Transplante de Neoplasias , Projetos Piloto , CoelhosRESUMO
PURPOSE: To show the effectiveness and safety of irreversible electroporation (IRE) in treating large tumor models. MATERIALS AND METHODS: VX2 liver tumor implantation was performed in 35 New Zealand White Rabbits. The rabbits were divided into three groups 1 week after implantation. The control group included 15 rabbits; the remaining 20 rabbits were divided into two IRE treatment groups. For the treatment groups, 10 rabbits underwent ablation with a single IRE application (IRE-S group), and 10 rabbits underwent ablation with multiple IRE applications (IRE-M group). Treatments and outcomes were analyzed using ultrasound, contrast-enhanced computed tomography (CT), and immunohistologic staining (hematoxylin and eosin [H&E], P-53, Ki-67, CD30, and vascular endothelial growth factor receptor [VEGFR] staining, and terminal deoxynucleotidyl-transferase-mediated 2'-deoxyuridine 5'-triphosphate [dUTP]-biotin nick-end labeling [TUNEL] assay). RESULTS: Multiple IRE ablations consistently produced complete cell death in all the animals in the IRE-M group (n = 10, IRE ablation time 2.45 minutes ± 0.3). The results were validated with ultrasound, CT, H&E, Ki-67, P53, and TUNEL assay. A high level of CD30-positive cells were identified in the IRE groups. A sharply demarcated ablation zone with no damage to surrounding vital structures was observed in all IRE-treated tissues. No complications during or after ablation were observed in any of the animals. CONCLUSIONS: The effects of IRE were shown in a large tumor model with single and multiple IRE ablations (IRE-S and IRE-M treatment groups); complete ablation of the tumor was seen in the IRE-M group. These findings successfully show the beneficial effects and safety of IRE in the treatment of tumors and validate its potential as a clinically translatable treatment.
Assuntos
Técnicas de Ablação , Eletroporação , Neoplasias Hepáticas/cirurgia , Animais , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Meios de Contraste , Estudos de Viabilidade , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Antígeno Ki-67/metabolismo , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Coelhos , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Fatores de Tempo , Tomografia Computadorizada por Raios X , Proteína Supressora de Tumor p53/metabolismo , UltrassonografiaRESUMO
PURPOSE: To evaluate the effectiveness of irreversible electroporation (IRE) in hepatic tissue ablation and the radiologic-pathologic correlation of IRE-induced cell death. MATERIALS AND METHODS: On approval of the animal research committee, 16 Yorkshire pigs underwent ultrasonography (US)-guided IRE of normal liver. A total of 55 ablation zones were created, which were imaged with US, magnetic resonance (MR) imaging, and computed tomography (CT) and evaluated with immunohistochemical analysis, including hematoxylin-eosin (H-E), Von Kossa, and von Willibrand factor (vWF) staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. RESULTS: At gross section examination, the mean diameter of the ablation zones was 33.5 mm + or - 3.0 (standard deviation) and was achieved in 6.9 minutes (mean total procedure time per ablation), with a mean difference of 2.5 mm + or - 3.6 between US and gross section measurements (r = 0.804). No complications were seen in any of the 16 animals. IRE ablation zones were well characterized with US, CT, and MR imaging, and real-time monitoring was feasible with US. H-E, Von Kossa, and vWF staining showed complete cell death, with a sharply demarcated treatment area. Bile ducts and vessels were completely preserved. Areas of complete cell death were stained positive for apoptotic markers (TUNEL, BCL-2 oncoprotein), suggesting involvement of the apoptotic process in the pathophysiology of cell death caused by IRE. CONCLUSION: In an animal model, IRE proved to be a fast, safe, and potent ablative method, causing complete tissue death by means of apoptosis. Cell death is seen with full preservation of periablative zone structures, including blood vessels, bile ducts, and neighboring nonablated tissues.
Assuntos
Eletroporação/métodos , Fígado/cirurgia , Animais , Morte Celular , Meios de Contraste/administração & dosagem , Estudos de Viabilidade , Feminino , Gadolínio DTPA/administração & dosagem , Marcação In Situ das Extremidades Cortadas , Iohexol/administração & dosagem , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética , Modelos Animais , Sus scrofa , Tomografia Computadorizada por Raios X , Ultrassonografia de IntervençãoRESUMO
Tuberculous (TB) meningitis in children under 5 years of age is a serious health problem in Argentina, with a rate of 0.39/100000 inhabitants, for 2003-2004. This rate indicates recent infections. It is an operational indicator for case finding and treatment of pulmonary adult cases, and for BCG vaccination of the newborn. The object of this study was to describe epidemic and clinical variables registered in cases of TB meningitis in children less than 5 years old in Argentina, from 1999 to 2001 and to determine the real number of TB meningitis cases in our country. Fifteen cases of TB meningitis out of 32 (46.8%) were studied through epidemic records. The average age was 14 months. Six children presented BCG scars but in only one child it was proved that he had been vaccinated at birth; 11/13 (92.3%) were at the second stage of illness, the bacteriological investigation was positive in 8/11 (72.7%) and in (46.8%) chest radiography revealed abnormal findings. The tuberculin reaction was negative in all tested cases. This study showed that the diagnosis was made at an advanced stage of disease. None of these patients was cured without sequels and a high death rate (46%) was observed. In order to control this epidemic situation, it is necessary to increase case finding and directly observed treatment of smear positive pulmonary TB cases, as well as BCG vaccination given at birth.
Assuntos
Tuberculose Meníngea/epidemiologia , Distribuição por Idade , Argentina/epidemiologia , Vacina BCG/uso terapêutico , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Fatores de Risco , Índice de Gravidade de Doença , Tuberculose Meníngea/diagnóstico , Tuberculose Meníngea/prevenção & controle , População Urbana/estatística & dados numéricosRESUMO
La tuberculosis menígea en menores de cinco años continúia siendo un serio problema de salud pública en Argentina, con una tasa de 0.39/100 000 en el bienio 2003-2004. Esta tasa refleja las infecciones recientes y es un indicador operac ional de la búsqueda y tratamiento de casos adultos pulmonares y de la cobertura de la vacunación con BCG en el recién nacido. Este estudio se realizó con el objecto de describir las variables epidemiológicas y clínicas de los casos de meningitis tuberculosa en menorees de cinco años en Argentina en el período 1999-2001 y para obtener mayor certeza sobre el número real de menigitis que se producen en el país. Se estudiaron con fichas epidemiológicas 15 casos de meningitis de los 32 notificados (46.8%). La mediana de la edad fue 14 meses, 6 niños tenían cicatriz de BCG, pero en sólo uno se pudo constatar que fue vacunado al nacer, 11/13 (92.3%) estaban en estadio 2 de la enfermedad, la investigación bacteriológica resultó positiva en 8/11 (72.7%), por lo menos 7(46.8%) presentaron imágenes compatibles con tuberculosis pulmonar, la prueba tuberculínica resultó no reactiva en todos los casos en que fue aplicada. Este estúdio puso en evidencia que los niños se diagnosticaron en estadios avanzados de la enfermedad, ninguno curó sin secuelas y tubo un muy alto porcentaje de letalidad (46%). Para contrarrestar esta situación epidemiológica es necessario incrementar la búsqueda y tratamiento supervisado de casos bacilíferos, el estudio de contactos y la cobertura de vacunación con BCG al nacimiento.
Tuberculous (TB) meningitis in children under 5 years of age is a serious health problem in Argentina, with a rate of 0.39/100 000 inhabitants, for 2003-2004. This rate indicates recent infections. It is an operational indicator for case finding and treatment of pulmonary adult cases, and for BCG vaccination of the newborn. The object of this study was to describe epidemic an clinical varialbles registered in cases of TB meningitis in children less than 5 years old in Argentina, from 1999 to 2001 and to determine the real number of TB meningitis in children less than 5 years old in Argentina, from 1999 to 2001 and to determine the real number of TB meningitis cases in our country. Fifteen cases of TB meningitis out of 32 (46.8%) were studied through epidemic records. The average age woas 14 months. Sis children presented BCG scars but in only one child it was proved that he had been vaccinated at birth; 11/13 (92.3%) were at the second stage of illness, the bacteriological investigation was positive in 8/11 (72.7%) and in (46.8%) chest radiography revealed abnormal findings. The tuberculin reaction was negative in all tested cases. This study showed that the diagnosis was made at an advanced stage of disease. None of these patients was cured without sequels and a hight death rate (46%) was observed. In order to control this epidemic situation, it is necessary to increase case finding and directly observed treatment of smear positive pulmonary TB cases, as well as BCG vaccination given at birth.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Tuberculose Meníngea/epidemiologia , Distribuição por Idade , Argentina/epidemiologia , Vacina BCG/uso terapêutico , Fatores de Risco , Índice de Gravidade de Doença , Tuberculose Meníngea/diagnóstico , Tuberculose Meníngea/prevenção & controle , População Urbana , VacinaçãoRESUMO
La tuberculosis menígea en menores de cinco años continúia siendo un serio problema de salud pública en Argentina, con una tasa de 0.39/100 000 en el bienio 2003-2004. Esta tasa refleja las infecciones recientes y es un indicador operac ional de la búsqueda y tratamiento de casos adultos pulmonares y de la cobertura de la vacunación con BCG en el recién nacido. Este estudio se realizó con el objecto de describir las variables epidemiológicas y clínicas de los casos de meningitis tuberculosa en menorees de cinco años en Argentina en el período 1999-2001 y para obtener mayor certeza sobre el número real de menigitis que se producen en el país. Se estudiaron con fichas epidemiológicas 15 casos de meningitis de los 32 notificados (46.8%). La mediana de la edad fue 14 meses, 6 niños tenían cicatriz de BCG, pero en sólo uno se pudo constatar que fue vacunado al nacer, 11/13 (92.3%) estaban en estadio 2 de la enfermedad, la investigación bacteriológica resultó positiva en 8/11 (72.7%), por lo menos 7(46.8%) presentaron imágenes compatibles con tuberculosis pulmonar, la prueba tuberculínica resultó no reactiva en todos los casos en que fue aplicada. Este estúdio puso en evidencia que los niños se diagnosticaron en estadios avanzados de la enfermedad, ninguno curó sin secuelas y tubo un muy alto porcentaje de letalidad (46%). Para contrarrestar esta situación epidemiológica es necessario incrementar la búsqueda y tratamiento supervisado de casos bacilíferos, el estudio de contactos y la cobertura de vacunación con BCG al nacimiento. (AU)
Tuberculous (TB) meningitis in children under 5 years of age is a serious health problem in Argentina, with a rate of 0.39/100 000 inhabitants, for 2003-2004. This rate indicates recent infections. It is an operational indicator for case finding and treatment of pulmonary adult cases, and for BCG vaccination of the newborn. The object of this study was to describe epidemic an clinical varialbles registered in cases of TB meningitis in children less than 5 years old in Argentina, from 1999 to 2001 and to determine the real number of TB meningitis in children less than 5 years old in Argentina, from 1999 to 2001 and to determine the real number of TB meningitis cases in our country. Fifteen cases of TB meningitis out of 32 (46.8%) were studied through epidemic records. The average age woas 14 months. Sis children presented BCG scars but in only one child it was proved that he had been vaccinated at birth; 11/13 (92.3%) were at the second stage of illness, the bacteriological investigation was positive in 8/11 (72.7%) and in (46.8%) chest radiography revealed abnormal findings. The tuberculin reaction was negative in all tested cases. This study showed that the diagnosis was made at an advanced stage of disease. None of these patients was cured without sequels and a hight death rate (46%) was observed. In order to control this epidemic situation, it is necessary to increase case finding and directly observed treatment of smear positive pulmonary TB cases, as well as BCG vaccination given at birth.(AU)
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Tuberculose Meníngea/epidemiologia , Tuberculose Meníngea/diagnóstico , Tuberculose Meníngea/prevenção & controle , Argentina/epidemiologia , Vacina BCG/uso terapêutico , Índice de Gravidade de Doença , Distribuição por Idade , Vacinação , Fatores de Risco , População UrbanaRESUMO
La tuberculosis menígea en menores de cinco años continúia siendo un serio problema de salud pública en Argentina, con una tasa de 0.39/100 000 en el bienio 2003-2004. Esta tasa refleja las infecciones recientes y es un indicador operac ional de la búsqueda y tratamiento de casos adultos pulmonares y de la cobertura de la vacunación con BCG en el recién nacido. Este estudio se realizó con el objecto de describir las variables epidemiológicas y clínicas de los casos de meningitis tuberculosa en menorees de cinco años en Argentina en el período 1999-2001 y para obtener mayor certeza sobre el número real de menigitis que se producen en el país. Se estudiaron con fichas epidemiológicas 15 casos de meningitis de los 32 notificados (46.8%). La mediana de la edad fue 14 meses, 6 niños tenían cicatriz de BCG, pero en sólo uno se pudo constatar que fue vacunado al nacer, 11/13 (92.3%) estaban en estadio 2 de la enfermedad, la investigación bacteriológica resultó positiva en 8/11 (72.7%), por lo menos 7(46.8%) presentaron imágenes compatibles con tuberculosis pulmonar, la prueba tuberculínica resultó no reactiva en todos los casos en que fue aplicada. Este estúdio puso en evidencia que los niños se diagnosticaron en estadios avanzados de la enfermedad, ninguno curó sin secuelas y tubo un muy alto porcentaje de letalidad (46%). Para contrarrestar esta situación epidemiológica es necessario incrementar la búsqueda y tratamiento supervisado de casos bacilíferos, el estudio de contactos y la cobertura de vacunación con BCG al nacimiento. (AU)
Tuberculous (TB) meningitis in children under 5 years of age is a serious health problem in Argentina, with a rate of 0.39/100 000 inhabitants, for 2003-2004. This rate indicates recent infections. It is an operational indicator for case finding and treatment of pulmonary adult cases, and for BCG vaccination of the newborn. The object of this study was to describe epidemic an clinical varialbles registered in cases of TB meningitis in children less than 5 years old in Argentina, from 1999 to 2001 and to determine the real number of TB meningitis in children less than 5 years old in Argentina, from 1999 to 2001 and to determine the real number of TB meningitis cases in our country. Fifteen cases of TB meningitis out of 32 (46.8%) were studied through epidemic records. The average age woas 14 months. Sis children presented BCG scars but in only one child it was proved that he had been vaccinated at birth; 11/13 (92.3%) were at the second stage of illness, the bacteriological investigation was positive in 8/11 (72.7%) and in (46.8%) chest radiography revealed abnormal findings. The tuberculin reaction was negative in all tested cases. This study showed that the diagnosis was made at an advanced stage of disease. None of these patients was cured without sequels and a hight death rate (46%) was observed. In order to control this epidemic situation, it is necessary to increase case finding and directly observed treatment of smear positive pulmonary TB cases, as well as BCG vaccination given at birth.(AU)
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Tuberculose Meníngea/epidemiologia , Tuberculose Meníngea/diagnóstico , Tuberculose Meníngea/prevenção & controle , Argentina/epidemiologia , Vacina BCG/uso terapêutico , Índice de Gravidade de Doença , Distribuição por Idade , Vacinação , Fatores de Risco , População UrbanaRESUMO
CONTEXT: Little is known about the use of complementary and alternative medicine among the approximately 1.6 million migrant farmworkers in the United States. PURPOSE: To evaluate the use of medicinal plants and natural remedies among a convenience sample of 100 migrant farmworkers living temporarily in a migrant worker center in El Paso, Texas. METHODS: A structured interview instrument was designed to elicit information about reasons for medicinal herb use, form in which herbs were ingested, serious side effects experienced, location of purchase, effectiveness of treatment, and use of allopathic medications. FINDINGS: The majority of workers used herbal remedies or other natural products because they believed them to be more effective than pharmaceuticals and because of tradition. Most learned about herbal remedies from a relative, primarily from their mother, and the majority who used herbal remedies believed them to be very helpful in treating specific illnesses. No adverse reactions to any herbal remedy were reported. The majority of participants did not inform their physician about their use of herbal remedies. According to the literature, potential adverse interactions between herbal remedies used and allopathic medications included gastrointestinal irritation, renal toxicity, and hypoglycemia. CONCLUSIONS: Health care providers must be knowledgeable about the use of herbal remedies among migrant farmworkers. By showing an understanding of and sensitivity to the use of these remedies, health care providers will be able to conduct more comprehensive health assessments of migrant workers and their families and provide them with more culturally competent care.
