RESUMO
PURPOSE: Meningiomas are common brain tumors, the majority of which are considered benign. Despite surgery and/or radiation therapy, recurrence rates are approximately 8-10%. One likely cause is the dysregulation of cyclin D-cyclin-dependent kinases 4 and 6 (CDK4/6)-retinoblastoma (Rb) pathway, which controls the cell cycle restriction point. This pathway is commonly dysregulated in anaplastic meningioma cell lines (AM) and radiation-induced meningioma cells (RIM), making it a rational target for anti-meningioma therapy. In this study, we investigate the effect of a CDK4/6 inhibitor, palbociclib, with radiation in relevant pre-clinical models. METHODS: In vitro cell culture, ex vivo slice culture and in vivo cell line-derived orthotopic xenograft animal models of AM/RIM were utilized to assess treatment efficacy with palbociclib plus radiation. Treatment effects were examined by immunoblot, cell viability, apoptosis, and cell cycle progression. RESULTS: The in vitro and ex vivo studies demonstrate that palbociclib plus radiation treatment reduced proliferation and has additional effects on cell cycling, including induction of an RB-associated G (1) arrest in Rb+ AM and RIM cells, but not in Rb- cells. Our results also demonstrated reduced CDK4 and CDK6 expression as well as reduced E2F target gene expression (CCNA2 and CCNE2) with the combination therapy. MRI results in vivo demonstrated reduced tumor size at 5 weeks when treated with 14 days palbociclib (10 mg/kg) plus 6 Gy radiation compared to saline-treated tumors. Finally, no hepatic toxicity was found after treatments. CONCLUSION: A pre-clinical murine model provides preclinical evidence for use of palbociclib plus radiation as a therapeutic agent for Rb+ meningiomas.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Meníngeas/terapia , Meningioma/terapia , Neoplasias Induzidas por Radiação/terapia , Piperazinas/uso terapêutico , Piridinas/uso terapêutico , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Terapia Combinada , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Humanos , Masculino , Camundongos , Proteína do Retinoblastoma/metabolismoRESUMO
The processes of adaptation and speciation are expected to shape genomic variation within and between diverging species. Here we analyze genomic heterogeneity of genetic differentiation and introgression in a hybrid zone between two bird species (Manacus candei and M. vitellinus) using 59 100 SNPs, a whole genome assembly, and Bayesian models. Measures of genetic differentiation (FST) and introgression (genomic cline center [α] and rate [ß]) were highly heterogeneous among loci. We identified thousands of loci with elevated parameter estimates, some of which are likely to be associated with variation in fitness in Manacus populations. To analyze the genomic organization of differentiation and introgression, we mapped SNPs onto a draft assembly of the M. vitellinus genome. Estimates of FST, α, and ß were autocorrelated at very short physical distances (< 100 bp), but much less so beyond this. In addition, average statistical associations (linkage disequilibrium) between SNPs were generally low and were not higher in admixed populations than in populations of the parental species. Although they did not occur with a constant probability across the genome, loci with elevated FST, α, and ß were not strongly co-localized in the genome. Contrary to verbal models that predict clustering of loci involved in adaptation and isolation in discrete genomic regions, these results are consistent with the hypothesis that genetic regions involved in adaptive divergence and reproductive isolation are scattered throughout the genome. We also found that many loci were characterized by both exceptional genetic differentiation and introgression, consistent with the hypothesis that loci involved in isolation are also often characterized by a history of divergent selection. However, the concordance between isolation and differentiation was only partial, indicating a complex architecture and history of loci involved in isolation.
Assuntos
Adaptação Biológica/genética , Genética Populacional , Modelos Genéticos , Passeriformes/genética , Isolamento Reprodutivo , Animais , Teorema de Bayes , Costa Rica , Loci Gênicos , Genoma , Hibridização Genética , Desequilíbrio de Ligação , Panamá , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNARESUMO
Recent advances in the treatment of prostate cancer have resulted in improved outcomes, including longer survival, but new options are needed for treating patients with castration-resistant disease, particularly in the presence of bone metastasis. Data from preclinical models and clinical biomarker studies indicate that antiangiogenic agents should be a promising treatment for this patient population, and multiple agents in this class have demonstrated activity in early-stage clinical trials. Pivotal trials in prostate cancer with agents targeting vascular endothelial growth factor (VEGF) signalling have resulted in significant improvements in tumour response and progression-free survival. However, overall survival was not significantly improved. Recent preclinical studies suggest that the limited impact on overall survival may result from the development of evasive resistance after inhibition of angiogenesis, possibly through upregulation of MET (hepatocyte growth factor receptor) signalling. MET plays important roles in angiogenesis, tumour cell invasion and bone metastasis, all of which are key factors in castration-resistant prostate cancer. Inhibition of both the MET and VEGF pathways may improve the efficacy of angiogenesis inhibitors in prostate cancer.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Castração , Sinergismo Farmacológico , Humanos , Masculino , Neoplasias da Próstata/cirurgia , Proteínas Proto-Oncogênicas c-met/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: Paediatric and Perinatal HIV/AIDS remain significant health challenges in the Caribbean where the HIV seroprevalence is second only to Sub-Saharan Africa. METHOD: We describe a collaborative approach to the prevention, treatment and care of HIV in pregnant women, infants and children in Jamaica. A team of academic and government healthcare personnel collaborated to address the paediatric and perinatal HIV epidemic in Greater Kingston as a model for Jamaica (population 2.6 million, HIV seroprevalence 1.5%). A five-point plan was utilized and included leadership and training, preventing mother-to-child transmission (pMTCT), treatment and care of women, infants and children, outcomes-based research and local, regional and international outreach. RESULTS: A core group of paediatric/perinatal HIV professionals were trained, including paediatricians, obstetricians, public health practitioners, nurses, microbiologists, data managers, information technology personnel and students to serve Greater Kingston (birth cohort 20 000). During September 2002 to August 2007, over 69 793 pregnant women presented for antenatal care. During these five years, significant improvements occurred in uptake of voluntary counselling (40% to 91%) and HIV-testing (53% to 102%). Eight hundred and eighty-three women tested HIV-positive with seroprevalence rates of 1-2% each year. The use of modified short course zidovudine or nevirapine in the first three years significantly reduced mother-to-child transmission (MTCT) of HIV from 29% to 6% (RR 0.27; 95% CI - 0.10, 0.68). During 2005 to 2007 using maternal highly active antiretroviral therapy (HAART) with zidovudine and lamivudine with either nevirapine, nelfinavir or lopinavir/ritonavir and infant zidovudine and nevirapine, MTCT was further reduced to an estimated 1.6% in Greater Kingston and 4.75% islandwide. In five years, we evaluated 1570 children in four-weekly paediatric infectious diseases clinics in Kingston, St Andrew and St Catherine and in six rural outreach sites throughout Jamaica; 24% (377) had HIV/AIDS and 76% (1193) were HIV-exposed. Among the infected children, 79% (299 of 377) initiated HAART, resulting in reduced HIV-attributable childhood morbidity and mortality islandwide. An outcomes-based research programme was successfully implemented. CONCLUSION: Working collaboratively, our mission of pMTCT of HIV and improving the quality of life for families living and affected by HIV/AIDS in Jamaica is being achieved.
ANTECEDENTES: El VIH/SIDA pediátrico y el perinatal continúan siendo retos significativos para la salud en el Caribe, donde la seroprevalencia de VIH ocupa el segundo lugar tras el África Subsahariana. MÉTODO: Se describe un enfoque colaborativo para tratamiento, prevención y cuidado de embarazadas, bebés y niños en Jamaica. Un equipo de personal académico y gubernamental vinculados a la salud, colaboraron para abordar la epidemia de VIH pediátrico y perinatal en Greater Kingston, como modelo para Jamaica (población de 2.6 millones, 1.5% seroprevalencia VIH). Se utilizó un plan de cinco puntos que incluyó liderazgo y entrenamiento, prevención de la transmisión madre a hijo (PTMAH), tratamiento y cuidado de mujeres, bebés y niños, investigaciones basadas en resultados, y outreach local, regional e internacional. RESULTADOS: Un grupo básico de profesionales del VIH pediátrico/perinatal, que incluía pediatras, obstetras, trabajadores de la salud, enfermeras, microbiólogos, administradores de datos, así como personal y estudiantes de la tecnología de la información, fue entrenado para servir en Greater Kingston (cohorte de nacimiento 20 000). De septiembre de 2002 hasta Agosto de 2007, más de 69 793 embarazadas se presentaron para recibir atención prenatal. Durante estos cinco años, tuvieron lugar mejoras significativos en cuanto a la recepción de asesoramiento (40% to 91%) y pruebas (53% to 102%) de VIH voluntarios. Ochocientos ochenta y tres mujeres resultaron VIH positivas en las pruebas, con tasas de seroprevalencia de 1-2% cada año. El uso de un ciclo corto modificado de zidovudina o nevirapina en los primeros tres años, redujo la transmisión madre a hijo (TMAH) de VIH significativamente de 29% a 6% (RR 0.27; 95% CI - 0.10, 0.68). Durante el 2005 hasta 2007, usando terapia antiretroviral altamente activa (TARAA) materna, con zidovudina y lamivudina con nevirapina, nelfinavir o lopinavir/ritonavir y nevirapina y zidovudina para niños, la TMAH se redujo a un estimado de 1.6 % en Greater Kingston y a .75% a lo largo de la isla. En cinco años, evaluamos 1570 niños en cuatro clínicas infecciosas pediátricas semanales en Kingston, Saint Andrew y Saint Catherine, así como en seis otros lugares destinados al servicio comunitario (outreach) por toda Jamaica; 24% (377) tenían VIH/SIDA y 76% (1193) estaba expuestos al VIH. Entre los niños infectados, 79% (299 de 377) iniciaron el TARAA, lo que trajo como resultado una reducción de la mortalidad y la morbilidad infantil atribuible al VIH, en todo el país. Se implementó exitosamente un programa de investigación basado en resultados. CONCLUSIÓN: Trabajando en colaboración, estamos logrando nuestra misión de prevenir la TMAH del VIH, y mejorar la calidad de vida de las familias que viven afectadas por el VIH/SIDA en Jamaica.
Assuntos
Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Infecções por HIV/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , Desenvolvimento de Programas , Saúde Pública , Fármacos Anti-HIV/uso terapêutico , Região do Caribe/epidemiologia , Proteção da Criança , Intervalos de Confiança , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Bem-Estar do Lactente , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Cooperação Internacional , Jamaica/epidemiologia , Pediatria , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/epidemiologia , Estudos SoroepidemiológicosRESUMO
BACKGROUND: The Ministry of Health, Jamaica, is scaling-up programmes to improve the health of HIV-positive pregnant women according to the modified WHO recommended preventative mother to child transmission (pMTCT) regimens of therapy based upon the mother's clinical and immunological status. Highly-active antiretroviral drugs (HAART) can result in successful pMTCT to < 1%. We report the clinical and immunological characteristics of HIV/AIDS in an era of evolving treatment and care of HIV-infected pregnant Jamaican women. SUBJECTS AND METHOD: Clinical records were reviewed of patients registered in antenatal clinics in Greater Kingston and St Catherine, Jamaica (annual birth cohort - 20 000) between September 2002 and August 2006. Disease status was determined using the Centers for Disease Control and Prevention (CDC) classification system for adult HIV/AIDS. Demographic, clinical and laboratory data were documented and analyzed. RESULTS: During the four-year period, 571 HIV-infected women were enrolled; 62% from Victoria Jubilee Hospital, 25% from Spanish Town Hospital and 13% from the University Hospital of the West Indies. Mean age was 27-29 (range 15-41) years, median parity was 2 (range 0-9) and 68-70% were unemployed. Ninety-five per cent had live births. CDC categories of illnesses were A - mild disease in 82% (n = 473), B - moderate disease in 4.4% (n = 24) and C - severe disease in 1.4% (n = 8) while 12% (n = 66) had insufficient data. During the first three years, CD4+ cell counts were evaluated in only 2.5% (10 of 406) of patients with median of 344 cells/uL, compared to CD4 evaluation in 50% (83 of 165 women) in the last year with median of 573 cells/uL. Antiretroviral (ARV) medications primarily for pMTCT were given to 89% (n = 506) of women. Of these, uptake of HAART increased during years 1-3 from 2-3% to 62% in year four. Within two years post-partum, 24 women died, 92% (n = 22) from the direct complications of HIV/AIDS. CONCLUSION: A comprehensive system of care of HIV in the peripartum period has been developed in Jamaica. Detailed medical evaluation during pregnancy is performed with modern guidelines and increasing laboratory availability of CD4+ cell counts and viral loads. We believe declining HIV infection rates in Jamaican infants and healthier mothers are a direct consequence of increased testing in pregnancy with early diagnosis and initiation of HAART-based pMTCT regimens in pregnant women.
ANTECEDENTES: En la actualidad el Ministerio de Salud de Jamaica se halla en plena campaña por aumentar los programas de salud para mujeres embarazadas por el VIH positivo, sobre la base de regímenes terapéuticos para prevenir la transmisión de madre a hijo (PTMAH), de acuerdo con recomendaciones modificadas de la OMS, a partir del estatus inmunológico y clínico de la madre. Los medicamentos antiretrovirales altamente activos (TARAA) pueden traer como resultado un exitoso PTMAH a < 1%. Reportamos las características clínicas e inmunológicas del VIH/SIDA en una etapa en la que el tratamiento y cuidado de las mujeres embarazadas infectadas con VIH en Jamaica, se halla en evolución. SUJETOS Y MÉTODOS: Se revisaron las historias clínicas de pacientes registrados en las clínicas prenatales en Greater Kingston y Saint Catherine (cohorte de nacimiento anual - 20 000), entre septiembre de 2002 y agosto de 2006. El estatus de la enfermedad fue determinado usando el sistema de clasificación para el VIH/SIDA en adultos, según los Centros para el Control y Prevención de las Enfermedades (CCPE). Se documentario y analizaron datos demográficos, clínicos y de laboratorio. RESULTADOS: Durante el período de cuatro años, se reclutaron 571 mujeres infectadas con el VIH, 62% del Hospital Victoria Jubilee, 25% del Hospital de Spanish Town, y 13% del Hospital Universitario de West Indies. La edad promedio fue de 27-29 años (rango 15-41), la paridad mediana fue 2 (rango 0-9), y el 68-70% eran desempleadas. El noventa y cinco por ciento tuvo nacimientos vivos. Las categorías de enfermedades de CCPE fueron la enfermedad leve A- en 82% (n = 473), la enfermedad moderada B - en 4.4% (n = 24) y la enfermedad severa C - en 1.4% (n = 8) mientras que para el 12% (n = 66) los datos fueron insuficientes. Durante los primeros tres años, los conteos CD4+ fueron evaluados en sólo 2.5% (10 de 406) de los pacientes con la mediana de 344 células/uL, en comparación con la evaluación CD4 en 50% (83 de 165 mujeres) en el último año con una mediana de 573 células/uL. Los medicamentos antiretrovirales (ARV) fundamentalmente para PTMAH fueron dados al 89% (n = 506) de las mujeres. Entre éstas, el consumo de TARAA aumentó durante los años 1-3 de 2-3% a 62% en el cuarto año. En los dos años posteriores al parto, murieron 24 mujeres, 92% (n = 22) de complicaciones directas del VIH/SIDA, CONCLUSIÓN: Un sistema integral de atención al VIH en el período de periparto ha sido desarrollado en Jamaica. Durante el embarazo, se lleva a cabo una evaluación médica detallada con normas modernas y con aumento de la disponibilidad en los laboratorios del conteo CD4+ y cargas virales. Creemos que la disminución de las tasas de infección por VIH en los infantes jamaicanos y el número de madres más saludables, son consecuencia directa del aumento de las pruebas durante el embarazo con diagnóstico precoz y regímenes de PTMAH basados en TARAA en las mujeres embarazadas.
Assuntos
Adolescente , Adulto , Feminino , Humanos , Gravidez , Adulto Jovem , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Nevirapina/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Saúde Pública , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Jamaica/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/prevenção & controle , Cuidado Pré-Natal , Desenvolvimento de Programas , Estudos Retrospectivos , Inibidores da Transcriptase Reversa/uso terapêuticoRESUMO
BACKGROUND: The Ministry of Health, Jamaica, is scaling-up programmes to improve the health of HIV-positive pregnant women according to the modified WHO recommended preventative mother to child transmission (pMTCT) regimens of therapy based upon the mother's clinical and immunological status. Highly-active antiretroviral drugs (HAART) can result in successful pMTCT to < 1%. We report the clinical and immunological characteristics of HIV/AIDS in an era of evolving treatment and care of HIV-infected pregnant Jamaican women. SUBJECTS AND METHOD: Clinical records were reviewed of patients registered in antenatal clinics in Greater Kingston and St. Catherine, Jamaica (annual birth cohort--20,000) between September 2002 and August 2006. Disease status was determined using the Centers for Disease Control and Prevention (CDC) classification system for adult HIV/AIDS. Demographic, clinical and laboratory data were documented and analyzed. RESULTS: During the four-year period, 571 HIV-infected women were enrolled; 62% from Victoria Jubilee Hospital, 25% from Spanish Town Hospital and 13% from the University Hospital of the West Indies. Mean age was 27-29 (range 15-41) years, median parity was 2 (range 0-9) and 68-70% were unemployed. Ninety-five per cent had live births. CDC categories of illnesses were A--mild disease in 82% (n=473), B--moderate disease in 4.4% (n=24) and C--severe disease in 1.4% (n=8) while 12% (n=66) had insufficient data. During the first three years, CD4+ cell counts were evaluated in only 2.5% (10 of 406) of patients with median of 344 cells/microL, compared to CD4 evaluation in 50% (83 of 165 women) in the last year with median of573 cells/uL. Antiretroviral (ARV) medications primarily for pMTCT were given to 89% (n=506) ofwomen. Of these, uptake of HAART increased during years 1-3 from 2-3% to 62% in year four Within two years post-partum, 24 women died, 92% (n=22)from the direct complications of HIV/AIDS. CONCLUSION: A comprehensive system of care of HIV in the peripartum period has been developed in Jamaica. Detailed medical evaluation during pregnancy is performed with modern guidelines and increasing laboratory availability of CD4+ cell counts and viral loads. We believe declining HIV infection rates in Jamaican infants and healthier mothers are a direct consequence of increased testing in pregnancy with early diagnosis and initiation of HAART-based pMTCT regimens in pregnant women.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Nevirapina/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Saúde Pública , Adolescente , Adulto , Terapia Antirretroviral de Alta Atividade , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Humanos , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Jamaica/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/prevenção & controle , Cuidado Pré-Natal , Desenvolvimento de Programas , Estudos Retrospectivos , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto JovemRESUMO
BACKGROUND: Paediatric and Perinatal HIV/AIDS remain significant health challenges in the Caribbean where the HIV seroprevalence is second only to Sub-Saharan Africa. METHOD: We describe a collaborative approach to the prevention, treatment and care ofHIVin pregnant women, infants and children in Jamaica. A team of academic and government healthcare personnel collaborated to address the paediatric and perinatal HIV epidemic in Greater Kingston as a model for Jamaica (population 2.6 million, HIV seroprevalence 1.5%). A five-point plan was utilized and included leadership and training, preventing mother-to-child transmission (pMTCT), treatment and care of women, infants and children, outcomes-based research and local, regional and international outreach. RESULTS: A core group of paediatric/perinatal HIV professionals were trained, including paediatricians, obstetricians, public health practitioners, nurses, microbiologists, data managers, information technology personnel and students to serve Greater Kingston (birth cohort 20,000). During September 2002 to August 2007, over 69 793 pregnant women presented for antenatal care. During these five years, significant improvements occurred in uptake of voluntary counselling (40% to 91%) and HIV-testing (53% to 102%). Eight hundred and eighty-three women tested HIV-positive with seroprevalence rates of 1-2% each year The use of modified short course zidovudine or nevirapine in the first three years significantly reduced mother-to-child transmission (MTCT) of HIV from 29% to 6% (RR 0.27; 95%0 CI--0.10, 0.68). During 2005 to 2007 using maternal highly active antiretroviral therapy (HAART) with zidovudine and lamivudine with either nevirapine, nelfinavir or lopinavir/ritonavir and infant zidovudine and nevirapine, MTCT was further reduced to an estimated 1.6% in Greater Kingston and 4.75% islandwide. In five years, we evaluated 1570 children in four-weekly paediatric infectious diseases clinics in Kingston, St Andrew and St Catherine and in six rural outreach sites throughout Jamaica; 24% (377) had HIV/AIDS and 76% (1193) were HIV-exposed. Among the infected children, 79% (299 of 377) initiated HAART resulting in reduced HIV-attributable childhood morbidity and mortality islandwide. An outcomes-based research programme was successfully implemented. CONCLUSION: Working collaboratively, our mission of pMTCT of HIV and improving the quality of life for families living and affected by HIV/AIDS in Jamaica is being achieved.
Assuntos
Infecções por HIV/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , Desenvolvimento de Programas , Saúde Pública , Fármacos Anti-HIV/uso terapêutico , Região do Caribe/epidemiologia , Criança , Proteção da Criança , Pré-Escolar , Intervalos de Confiança , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Lactente , Bem-Estar do Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Cooperação Internacional , Jamaica/epidemiologia , Pediatria , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/epidemiologia , Estudos SoroepidemiológicosRESUMO
BACKGROUND: The seroprevalence of HIV among pregnant women in the Caribbean is 2-3 and increasing. The Kingston Paediatric and Perinatal HIV Programme is developing and implementing a unified programme to eliminate mother-to-child transmission (MTCT) of HIV in Kingston, Jamaica. METHODS: Pregnant women presenting to Kingston Metropolitan Antenatal Clinics, Victoria Jubilee Hospital, Spanish Town Hospital and the University Hospital of the West Indies had HIV serology performed by ELISA, or by the new Determine Rapid Test after receiving group counselling. HIV-positive women were referred to High Risk Antenatal Clinics. Antiretroviral prophylaxis with zidovudine (AZT), or nevirapine was given. Care was administered using a standard protocol by a multi-disciplinary team of public and academic healthcare personnel. RESULTS: In year one, 19,414 women delivered Among 14,054 women who started antenatal care for this period, 5,558 (40) received group counselling and 7,383 (53) received HIV-testing. During the fourth quarter of follow-up, these comparative rates were 66 (2049/3 118) and 72 (2260/3118) respectively. HIV seroprevalence overall was 2.1 (152/7 383). One hundred and seven HIV+ women at varying gestational ages were identified in the programme, 72 had so far received AZT and nine nevirapine (76). 0f 84 deliveries, birth outcomes were 75 live births (89), six neonatal deaths and four maternal deaths (all from HIV/AIDS). Major challenges include repeat pregnancies of 36 despite prior knowledge of HIV seropositivity and poor partner notification with only 30 (32) having a HIV-test. Although rates of HIV testing in pregnant women in Greater Kingston are increasing, rates of testing overall remain sub-optimal. On the labour ward, there was sub-optimal identification of the HIV+ pregnant woman and administration of AZT chemoprophylaxis, along with issues of patient confidentiality and stigma. CONCLUSION: This programme needs strengthening in order to reduce maternal-fetal transmission of HIV in Greater Kingston, Jamaica [quot]pMTCT-PLUS, or comprehensive family-centred care, is the next step[quot]
Assuntos
Humanos , Feminino , Gravidez , Adolescente , Adulto , Transmissão Vertical de Doenças Infecciosas , Avaliação de Programas e Projetos de Saúde , Complicações Infecciosas na Gravidez/prevenção & controle , Cuidado Pré-Natal , Infecções por HIV/prevenção & controle , Soroprevalência de HIV , Assistência Perinatal , Complicações Infecciosas na Gravidez/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Jamaica/epidemiologia , Nevirapina/administração & dosagem , Resultado da Gravidez , Soropositividade para HIV , Zidovudina/administração & dosagemRESUMO
BACKGROUND: The seroprevalence of HIV among pregnant women in the Caribbean is 2-3% and increasing. The Kingston Paediatric and Perinatal HIV Programme is developing and implementing a unified programme to eliminate mother-to-child transmission (MTCT) of HIV in Kingston, Jamaica. METHODS: Pregnant women presenting to Kingston Metropolitan Antenatal Clinics, Victoria Jubilee Hospital, Spanish Town Hospital and the University Hospital of the West Indies had HIV serology performed by ELISA, or by the new Determine Rapid Test after receiving group counselling. HIV-positive women were referred to High Risk Antenatal Clinics. Antiretroviral prophylaxis with zidovudine (AZT), or nevirapine was given. Care was administered using a standard protocol by a multi-disciplinary team of public and academic healthcare personnel. RESULTS: In year one, 19,414 women delivered Among 14,054 women who started antenatal care for this period, 5,558 (40%) received group counselling and 7,383 (53%) received HIV-testing. During the fourth quarter of follow-up, these comparative rates were 66% (2049/3 118) and 72% (2260/3118) respectively. HIV seroprevalence overall was 2.1% (152/7 383). One hundred and seven HIV+ women at varying gestational ages were identified in the programme, 72 had so far received AZT and nine nevirapine (76%). 0f 84 deliveries, birth outcomes were 75 live births (89%), six neonatal deaths and four maternal deaths (all from HIV/AIDS). Major challenges include repeat pregnancies of 36% despite prior knowledge of HIV seropositivity and poor partner notification with only 30% (32) having a HIV-test. Although rates of HIV testing in pregnant women in Greater Kingston are increasing, rates of testing overall remain sub-optimal. On the labour ward, there was sub-optimal identification of the HIV+ pregnant woman and administration of AZT chemoprophylaxis, along with issues of patient confidentiality and stigma. CONCLUSION: This programme needs strengthening in order to reduce maternal-fetal transmission of HIV in Greater Kingston, Jamaica "pMTCT-PLUS, or comprehensive family-centred care, is the next step".
Assuntos
Infecções por HIV/prevenção & controle , Soroprevalência de HIV , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , Cuidado Pré-Natal , Avaliação de Programas e Projetos de Saúde , Adolescente , Adulto , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Soropositividade para HIV , Humanos , Jamaica/epidemiologia , Nevirapina/administração & dosagem , Assistência Perinatal , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Resultado da Gravidez , Zidovudina/administração & dosagemRESUMO
The objective of this study was to identify the factors associated with size and proportionality at birth in a cohort of term infants established to investigate their growth and development. One hundred and forty term low-birth-weight (birth-weight < 2,500 g) infants and 94 normal birth-weight infants (2,500- < 4,000 g) were recruited within 48 hours of birth at the main maternity hospital, Kingston, Jamaica. Birth anthropometry and gestational age were measured, and maternal information was obtained by interview and from hospital records. Controlling for gestational age, variables independently associated with birth-weight were rate of weight gain in the second half of pregnancy, maternal height, haemoglobin level < 9.5 microg/dL, time of first attendance in antenatal clinic, birth order, pre-eclampsia, and consumption of alcohol, with 33% of the variance in birth-weight explained. Birth length was associated only with maternal height and age, while measures of proportionality (ponderal index and head/length ratio) were associated with characteristics of the environment in late pregnancy, including rate of weight gain, weight in late pregnancy, and pre-eclampsia. The variation in maternal characteristics associated with size or proportionality at birth may reflect the times during gestation when different aspects of growth are most affected.
Assuntos
Peso ao Nascer , Desenvolvimento Embrionário e Fetal , Adulto , Antropometria , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Jamaica , Estudos Longitudinais , Masculino , Estado Nutricional , Pré-Eclâmpsia/embriologia , Pré-Eclâmpsia/metabolismo , Gravidez , Resultado da Gravidez , Análise de Regressão , Aumento de PesoRESUMO
In western Panama, an unusual hybrid zone exists between white-collared manakins, Manacus candei, and golden-collared manakins, M. vitellinus. Unidirectional introgression of plumage traits from vitellinus into candei has created a region in which all definitively plumaged males have a collar that is lemon-colored. These males are nearly indistinguishable from white-collared candei genetically and morphometrically, but strongly resemble golden-collared vitellinus due to the introgression of secondary sexual plumage traits, particularly the lemon-colored collar. The introgression could be explained by sexual selection for golden-collared traits or by a series of mechanisms that do not invoke sexual selection (e.g., neutral diffusion, dominant allele). Sexual selection on male-male interactions implies behavioral differences among the plumage forms--specifically that golden- and lemon-collared males should be more aggressive than white-collared males. In contrast, the nonsexual hypotheses predict behavioral similarity between lemon- and white-collared males, based on their nearly identical genetics. We tested the sexual selection hypothesis experimentally, by presenting males with taxidermic mounts of the three forms. As response variables, we monitored vocalizations and attacks on the mounts by replicate subject males. Both golden-collared and lemon-collared males were more likely to attack than were white-collared males, as predicted under sexual selection but not by the nonsexual hypotheses. Lemon-collared males were more vocally reactive than either parental form, contrary to the prediction of the nonsexual hypotheses. Our study demonstrates that sexual selection on male-male interactions may play an important role in the dynamics of character evolution and hybrid zones.
Assuntos
Evolução Biológica , Aves/fisiologia , Plumas/fisiologia , Comportamento Sexual Animal/fisiologia , Comportamento Social , Agressão/fisiologia , Animais , Cor , Feminino , Geografia , Masculino , Modelos Biológicos , Panamá , Caracteres Sexuais , Vocalização Animal/fisiologiaRESUMO
A previous study of the hybrid zone in western Panama between white-collared (Manacus candei) and golden-collared manakins (M. vitellinus) documented the unidirectional introgression of vitellinus male secondary sexual traits across the zone. Here, we examine the hybrid zone in greater genetic and morphological detail. Statistical comparisons of clines are performed using maximum-likelihood and nonparametric bootstrap methods. Our results demonstrate that an array of six molecular and two morphometric markers agree in cline position and width. Clines for male collar and belly color are similar in width to the first eight clines, but are shifted in position by at least five cline widths. The result is that birds in intervening populations are genetically and morphometrically very like parental candei, but males have the plumage color of parental vitellinus. Neither neutral diffusion nor nonlinearity of color scales appear to be viable explanations for the large cline shifts. Genetic dominance of vitellinus plumage traits is another potential explanation that will require breeding experiments to test. Sexual selection remains a plausible explanation for the observed introgression of vitellinus color traits in these highly dimorphic, polygynous, lek-mating birds. Two other clines, including a nondiagnostic isozyme locus, are similar in position to the main cluster of clines, but are broader in width. Thus, introgression at some loci is greater than that detected with diagnostic markers. Assuming that narrow clines are maintained by selection, variation in cline width indicates that selection is not uniform throughout the genome and that diagnostic markers are under more intense selective pressure. The traditional focus on diagnostic markers in studies of hybrid zones may therefore lead to underestimates of average introgression. This effect may be more pronounced in organisms with low levels of genetic divergence between hybridizing taxa.
Assuntos
Evolução Biológica , Aves/genética , Variação Genética , Animais , Aves/anatomia & histologia , Constituição Corporal/genética , Clima , Costa Rica , DNA Mitocondrial/genética , Feminino , Marcadores Genéticos , Isoenzimas/genética , Funções Verossimilhança , Masculino , Panamá , Software , Estatísticas não ParamétricasRESUMO
OBJECTIVES: To examine factors associated with low birth weight (LBW) in term infants as part of a longitudinal study on the effects of term LBW. METHODS: Term LBW and normal birth weight (NBW) infants were recruited from the Victoria Jubliee Hospital, Kingston, Jamaica, between March and October, 1999. All LBW infants meeting the recruitment criteria were enrolled. The next eligible NBW infant of the same gender was enrolled for two of every three LBW infants. Gestational age was determined by the Dubowitz method. Anthropometric measurements were made and a questionnaire administered to determine maternal characteristics and antenatal history. Maternal height was measured and socioeconomic status assessed at home one week later. RESULTS: A total of 234 term infants (140 LBW and 94 NBW) were enrolled. There were no significant differences between the groups in maternal age, height, education, occupation or socioeconomic status. Mothers who reported alcohol consumption during pregnancy were more likely to have a LBW infant (Odds Ratio (OR) 2.26; 95 percent CI 1.01, 5.05) LBW infants were more likely to be first born (OR 1.73; 95 percent CI 1.01, 2.97). Mothers who had a previous LBW infant were at increased risk of having another LBW infant (OR 4.89; 95 percent CI 2.21, 10.84). CONCLUSION: Socioeconomic factors did not distinguish mothers at the Victoria Jubliee Hospital, who were likely to have a term LBW infant. Primiparous mothers and mothers who have given birth to a previous LBW infant are at risk of having a LBW infant and need special attention during the antenatal period.(Au)
Assuntos
Feminino , Gravidez , Recém-Nascido , Humanos , Estudo Comparativo , Recém-Nascido de Baixo Peso/fisiologia , Recém-Nascido/fisiologia , Estudos Longitudinais , Coleta de Dados , Fatores SocioeconômicosRESUMO
Mais de dez anos se passaram desde a publicação da primeira edição de Neoplasias Ósseas e Lesões Pseudotumorais das Articulações, em 1981. Durante este período, foram alcançados significativos progressos no campo do diagnóstico, particularmente na avaliação do processo evolutivo e tratamento dos tumores ósseos. Na maioria dos centros, a cirurgia para colocação de prótese de membros (limb-sparing) substituiu as cirurgias ablativas mais radicais, com ou sem quimioterapia pré-operatória. Isto se tornou possível graças à introdução, à aplicação cada vez mais freqüente de novas técnicas de imagem de alta qualidade (tomografia computadorizada e ressonância magnética) e, em particular, ao uso de novos métodos citomorfológicos de diagnóstico, especialmente a imunoistoquímica. Estes avanços no diagnóstico e tratamento levaram à publicação de novas edições de diversos livros de grande importância, uma vez que seus autores patologistas, cirurgiões ortopédicos e radiologistas sentiram a necessidade de atualizar seus trabalhos nos últimos anos. Entretanto, nestas publicações foram adotados diferentes critérios de classificação. O número de casos compilados no Registro Latino-Americano de Patologia Óssea aumentou, passando de 4.913 tumores ósseos primários e mais de 1.100 lesões pseudotumorais, quando da publicação da primeira edição deste livro, para 5.274 tumores ósseos e 1.665 lesões pseudotumorais ao final de dezembro de 1985, quando terminei meu trabalho como Chefe do Registro e passei a ocupar os cargos de Professor de Patologia Ortopédica no Centro Médico da Universidade de St. Louis e Professor Visitante no Centro Médico Rush-Presbyterian de Saint Luke, em Chicago. O material do Registro foi informatizado, o que permitiu os dados estatísticos para uso nesta nova edição
Assuntos
Humanos , Neoplasias Ósseas , Tumor de Células Gigantes do OssoRESUMO
In a survey of avian blood parasites in Costa Rica, 51 (11%) of 479 birds sampled were infected by at least one species of hematozoan. Fourteen of the 60 species of birds in the survey were examined for the first time. Infections were most common in ramphastids and emberizids and infrequent in other taxa. Among resident species, infections were more commonly detected during the wet season when most birds breed than during the dry season when few birds breed. Infections caused by Haemoproteus sp. were most common, while Plasmodium sp., Leucocytozoon sp., Trypanosoma sp., and microfilarial infections were rare. The intensity of the 40 Haemoproteus infections in adult birds was low, with a mean +/- SE of 12.5 +/- 3.7 infected cells per 10,000. Haemoproteus infections did not undergo seasonal changes in intensity.
Assuntos
Doenças das Aves/epidemiologia , Filariose/veterinária , Infecções Protozoárias em Animais , Animais , Doenças das Aves/sangue , Aves , Costa Rica/epidemiologia , Filariose/sangue , Filariose/epidemiologia , Malária Aviária/sangue , Malária Aviária/epidemiologia , Microfilárias , Prevalência , Infecções por Protozoários/sangue , Infecções por Protozoários/epidemiologia , Estações do Ano , Clima TropicalRESUMO
Stickler's syndrome is a much underdiagnosed entity in the ophthalmic population. It is a dominantly inherited disease of connective tissue whose ocular findings include moderate to severe myopia, vitreoretinal degeneration, retinal detachments, cataracts, and glaucoma. Non-ophthalmologic findings include cleft palate, midfacial hypoplasia, radiographic changes of spondyloepiphyseal dysplasia, narrow pelvis, and broad femoral neck. Twenty percent of patients with Stickler's syndrome will have a cleft palate. We undertook a study to determine the incidence of Stickler's syndrome in patients with an isolated cleft palate, and to see if this screening process would be useful in making an early diagnosis of the syndrome and in genetic counseling. It is important to distinguish this syndrome from that of isolated cleft palate in order to: 1) insure early detection of myopia and monitor for signs of retinal detachment, cataract, and glaucoma; and 2) provide definitive recurrence counseling for families (50% vs 2.3%).