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BACKGROUND: It is estimated that 5-10% of breast cancer cases are hereditary. The identification of pathogenic germline variants allows individualized preventive health care, improvement of clinical management and genetic counseling. Studies in ethnically admixed Latin American populations have identified regions with increased frequency of deleterious variants in breast cancer predisposing genes. In this context, the Brazilian population exhibits great genetic heterogeneity, and is not well represented in international databases, which makes it difficult to interpret the clinical relevance of germline variants. METHODS: We evaluated the frequency of pathogenic/likely pathogenic (P/LP) germline variants in up to 37 breast cancer predisposing genes, in a cohort of 105 breast and/or ovarian cancer Brazilian women referred to two research centers between 2014 and 2019. RESULTS: A total of 22 patients (21%) were found to carry P/LP variants, and 16 VUS were detected in 15 patients (14.3%). Additionally, a novel pathogenic ATM intragenic deletion was identified in an early-onset breast cancer. We also detected a BRCA1 pathogenic variant (c.5074+2T>C) in higher frequency (10×) than in other studies with similar cohorts. CONCLUSIONS: Our findings contribute to the characterization of the genetic background of breast cancer predisposition in the Brazilian population as a useful resource to discriminate between deleterious variants and VUS, thus enabling improvement in the preventive health care and clinical management of carriers.
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Proteínas Mutadas de Ataxia Telangiectasia/genética , Neoplasias da Mama/genética , Deleção de Genes , Heterogeneidade Genética , Células Germinativas/patologia , Mutação em Linhagem Germinativa , Neoplasias Ovarianas/genética , Adulto , Idoso , Proteína BRCA1/genética , Proteína BRCA2/genética , Brasil/epidemiologia , Neoplasias da Mama/epidemiologia , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Testes Genéticos , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/epidemiologia , Adulto JovemRESUMO
We describe monozygotic twin girls with genetic variation at two separate loci resulting in a blended phenotype of Prader-Willi syndrome and Pitt-Hopkins syndrome. These girls were diagnosed in early infancy with Prader-Willi syndrome, but developed an atypical phenotype, with apparent intellectual deficiency and lack of obesity. Array-comparative genomic hybridization confirmed a de novo paternal deletion of the 15q11.2q13 region and exome sequencing identified a second mutational event in both girls, which was a novel variant c.145+1G>A affecting a TCF4 canonical splicing site inherited from the mosaic mother. RNA studies showed that the variant abolished the donor splicing site, which was accompanied by activation of an alternative non-canonical splicing-site which then predicts a premature stop codon in the following exon. Clinical re-evaluation of the twins indicated that both variants are likely contributing to the more severe phenotypic presentation. Our data show that atypical clinical presentations may actually be the expression of blended clinical phenotypes arising from independent pathogenic events at two loci.
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Hiperventilação/genética , Deficiência Intelectual/genética , Patologia Molecular , Síndrome de Prader-Willi/genética , Fator de Transcrição 4/genética , Adolescente , Sequência de Bases/genética , Criança , Deleção Cromossômica , Cromossomos Humanos Par 15/genética , Hibridização Genômica Comparativa , Exoma/genética , Fácies , Feminino , Humanos , Hiperventilação/diagnóstico , Hiperventilação/fisiopatologia , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/fisiopatologia , Obesidade/diagnóstico , Obesidade/genética , Obesidade/fisiopatologia , Fenótipo , Síndrome de Prader-Willi/diagnóstico , Síndrome de Prader-Willi/fisiopatologia , Gêmeos MonozigóticosRESUMO
Los taxanos son una parte fundamental en el tratamiento del cáncer de mama. Las reacciones de Hipersensibilidad (RHS) a taxanos se registran en un 2-4% de las pacientes. Esta situación representa una gran dificultad y un impedimento para la administración del óptimo esquema elegido en cada caso. Los protocolos de desensibilización rápida a drogas (DRD) consisten en la administración de una dosis subóptima de la droga implicada en la RHS, seguida por progresivos incrementos de dosis, hasta lograr la infusión completa de la dosis calculada por ciclo. El objetivo de nuestro trabajo es evaluar la factibilidad, seguridad y efectividad de implementar el protocolo de DRD de 12 pasos desarrollado por el Brigham and Women´s Hospital, Harvard Medical School y el Dana Farber Cancer Institute (BWH/DFCI) en pacientescon cáncer de mama que reaccionaron a taxanos. Se analizaron en forma retrospectiva las historias clínicas (HC) de pacientes del Centro Mamario del Hospital Universitario Austral de Argentina (HUA) que presentaron RHS a taxanos en el período de enero de 2012 a junio de 2014. Se registraron 20 pacientes con RHS a taxanos en las cuales se implementó el protocolo de DRD del BWH/DFCI. Se realizaron 175 procedimientos en 20 pacientes, de los cuales 172 (98,3%) fueron exitosos y se completaron sin mediar síntomas de ningún tipo. Con lo cual, en nuestra serie, 17 pacientes (85%) lograron completar el esquema ideal de tratamiento para su enfermedad con la única implementación de un procedimiento de sencilla aplicación, bajo costo y alta efectividad...
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Neoplasias da Mama , Dessensibilização Imunológica , TaxoidesRESUMO
BACKGROUND: Certain rare syndromes with developmental delay or intellectual disability caused by genomic copy number variants (CNVs), either deletions or duplications, are associated with higher rates of obesity. Current strategies to diagnose these syndromes typically rely on phenotype-driven investigation. However, the strong phenotypic overlap between syndromic forms of obesity poses challenges to accurate diagnosis, and many different individual cytogenetic and molecular approaches may be required. Multiplex ligation-dependent probe amplification (MLPA) enables the simultaneous analysis of multiple targeted loci in a single test, and serves as an important screening tool for large cohorts of patients in whom deletions and duplications involving specific loci are suspected. Our aim was to design a synthetic probe set for MLPA analysis to investigate in a cohort of 338 patients with syndromic obesity deletions and duplications in genomic regions that can cause this phenotype. RESULTS: We identified 18 patients harboring copy number imbalances; 18 deletions and 5 duplications. The alterations in ten patients were delineated by chromosomal microarrays, and in the remaining cases by additional MLPA probes incorporated into commercial kits. Nine patients showed deletions in regions of known microdeletion syndromes with obesity as a clinical feature: in 2q37 (4 cases), 9q34 (1 case) and 17p11.2 (4 cases). Four patients harbored CNVs in the DiGeorge syndrome locus at 22q11.2. Two other patients had deletions within the 22q11.2 'distal' locus associated with a variable clinical phenotype and obesity in some individuals. The other three patients had a recurrent CNV of one of three susceptibility loci: at 1q21.1 'distal', 16p11.2 'distal', and 16p11.2 'proximal'. CONCLUSIONS: Our study demonstrates the utility of an MLPA-based first line screening test to the evaluation of obese patients presenting with syndromic features. The overall detection rate with the synthetic MLPA probe set was about 5.3% (18 out of 338). Our experience leads us to suggest that MLPA could serve as an effective alternative first line screening test to chromosomal microarrays for diagnosis of syndromic obesity, allowing for a number of loci (e.g., 1p36, 2p25, 2q37, 6q16, 9q34, 11p14, 16p11.2, 17p11.2), known to be clinically relevant for this patient population, to be interrogated simultaneously.
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AIMS AND BACKGROUND: In conservative early stage breast cancer surgery, the sample's margins are directly related to relapse, and positive or close margins indicate the need for additional surgery. Since the range of residual disease in secondary surgeries and the related pathological factors are highly variable, we intended to evaluate the number of additional surgeries due to compromised margins and identify the percentage of residual disease and factors related to it. METHODS: We retrospectively analyzed the clinical records of 659 tumorectomy or needle localization surgery patients with breast carcinoma at the Hospital Universitario Austral in Buenos Aires, Argentina, between December 2000 and December 2012. The variables considered were age, type of surgery, type of margin, tumor size, histological grade, extensive intraductal component and immunohistochemical profile. We investigated how they related to the presence of residual disease. RESULTS: We identified 68 patients (10%) who were reoperated because of positive (75%) or close (25%) margins. Residual disease was identified in 68% of them; the positive (66%) and close (70%) margin ratio was similar. The individual analysis of variables was statistically significant only for tumors larger than 3 cm (Pearson's chi square [1] = 6.7194; P = 0.0095; relative risk = 1.56 [95% CI 1.09-2.21]) with an association between age and tumor size: Pearson's chi square (1) = 3.8984; P = 0.0483; relative risk = 1.56 (95% CI 1.09-2.21). CONCLUSIONS: The need for second surgery due to compromised margins is not common, with variable residual tumor identifying ranges. Some pathological factors can predict the persistence of residual disease. In our series, tumor size >3 cm was the variable identified as an independent predictor.
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Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Mastectomia Segmentar , Recidiva Local de Neoplasia/prevenção & controle , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Adulto , Idoso , Argentina/epidemiologia , Neoplasias da Mama/epidemiologia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Lobular/patologia , Carcinoma Lobular/cirurgia , Feminino , Humanos , Prontuários Médicos , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasia Residual , Reoperação , Estudos RetrospectivosRESUMO
Introducción: La cirugía conservadora de la mama junto con la radioterapia es el tratamiento estándar del carcinoma mamario en estadios iniciales. El estado de los márgenes tiene una relación directa con las recidivas locales y la presencia de márgenes positivos o cercanos implica la necesidad de una cirugía adicional. Los rangos de enfermedad residual hallada en especímenes de segundas cirugías son altamente variables, al igual que los factores anatomopatológicos relacionados. Objetivos: Evaluar el número de cirugías adicionales necesarias por márgenes positivos o insuficientes en las pacientes operadas en el Centro Mamario del Hospital Universitario Austral (HUA). Identificar el porcentaje de enfermedad residual y factores relacionados con el mismo. Material y métodos: Se analizaron en forma retrospectiva las historias clínicas de 659 pacientes con cuadrantectomía o biopsia radioquirúrgica (BRQ) por carcinoma mamario en el HUA entre diciembre del 2000 y diciembre del 2012. Las variables consideradas fueron: edad, tipo de cirugía realizada, tipo de margen comprometido, tamaño tumoral, grado histológico, componente intraductal extenso (CIE) y perfil inmunohistoquímico, y su relación con la presencia de enfermedad residual. Resultados: Se identificaron 68 pacientes (10%) reoperadas por márgenes positivos (75%) o cercanos (25%). La enfermedad residual fue hallada en el 68% de los casos. Con rangos similares entre márgenes comprometidos (66%) o insuficientes (70%). En el análisis bivariado la única variable que se mostró significativa fue el tamaño tumoral >3 cm [chi de Pearson (1) = 6,7194; p=0,0095; RR: 1,56 (IC 95%:1,09-2,21) con una interacción entre edad y tamaño tumoral significativa: chi de 2 Pearson (1): 3,8984; p=0,0483; RR: 1,56 (IC 95%: 1,09-2,21)]. Conclusiones: La necesidad de una segunda cirugía por margen comprometido o insuficiente es una eventualidad poco frecuente con rangos variables de identificación de restos tumorales. (AU)
Assuntos
Neoplasias da Mama , Neoplasia ResidualRESUMO
Introducción: La cirugía conservadora de la mama junto con la radioterapia es el tratamiento estándar del carcinoma mamario en estadios iniciales. El estado de los márgenes tiene una relación directa con las recidivas locales y la presencia de márgenes positivos o cercanos implica la necesidad de una cirugía adicional. Los rangos de enfermedad residual hallada en especímenes de segundas cirugías son altamente variables, al igual que los factores anatomopatológicos relacionados. Objetivos: Evaluar el número de cirugías adicionales necesarias por márgenes positivos o insuficientes en las pacientes operadas en el Centro Mamario del Hospital Universitario Austral (HUA). Identificar el porcentaje de enfermedad residual y factores relacionados con el mismo. Material y métodos: Se analizaron en forma retrospectiva las historias clínicas de 659 pacientes con cuadrantectomía o biopsia radioquirúrgica (BRQ) por carcinoma mamario en el HUA entre diciembre del 2000 y diciembre del 2012. Las variables consideradas fueron: edad, tipo de cirugía realizada, tipo de margen comprometido, tamaño tumoral, grado histológico, componente intraductal extenso (CIE) y perfil inmunohistoquímico, y su relación con la presencia de enfermedad residual. Resultados: Se identificaron 68 pacientes (10%) reoperadas por márgenes positivos (75%) o cercanos (25%). La enfermedad residual fue hallada en el 68% de los casos. Con rangos similares entre márgenes comprometidos (66%) o insuficientes (70%). En el análisis bivariado la única variable que se mostró significativa fue el tamaño tumoral >3 cm [chi de Pearson (1) = 6,7194; p=0,0095; RR: 1,56 (IC 95%:1,09-2,21) con una interacción entre edad y tamaño tumoral significativa: chi de 2 Pearson (1): 3,8984; p=0,0483; RR: 1,56 (IC 95%: 1,09-2,21)]. Conclusiones: La necesidad de una segunda cirugía por margen comprometido o insuficiente es una eventualidad poco frecuente con rangos variables de identificación de restos tumorales.
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Neoplasias da Mama , Neoplasia ResidualRESUMO
Obesity is a major threat to public health worldwide, and there is now mounting evidence favoring a role for the central nervous system (CNS) in weight control. A causal relationship has been recognized in both monogenic (e.g., BDNF, TRKB, and SIM1 deficiencies) and syndromic forms of obesity [e.g., Prader-Willi syndrome (PWS)]. Syndromic obesity arising from chromosomal abnormalities, that typically also affect learning and development, are often associated with congenital malformations and behavioral characteristics. We report on nine unrelated patients with a diagnosis of learning disability and/or developmental delay (DD) in addition to obesity that were found to have copy number variants (CNVs) by single nucleotide polymorphism array-based analysis. Each patient also had a distinct and complex phenotype, and most had hypotonia and other neuroendocrine issues, such as hyperphagia and hypogonadism. Molecular and clinical characterization of these patients enabled us to determine with confidence that the CNVs we observed were pathogenic or likely to be pathogenic. Overall, the CNVs reported here encompassed a candidate gene or region (e.g., SIM1) that has been reported in patients associating obesity and DD and/or intellectual disability (ID) and novel candidate genes and regions.
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Anormalidades Múltiplas/diagnóstico , Variações do Número de Cópias de DNA , Deficiências do Desenvolvimento/diagnóstico , Deficiências da Aprendizagem/diagnóstico , Obesidade/diagnóstico , Anormalidades Múltiplas/genética , Adolescente , Criança , Pré-Escolar , Deficiências do Desenvolvimento/genética , Feminino , Humanos , Lactente , Deficiências da Aprendizagem/genética , Masculino , Técnicas de Diagnóstico Molecular , Obesidade/genética , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVES: Deletion of the chromosome 15q11-q13, the most common genetic mechanism associated with Angelman syndrome (AS), is highly associated with a severe phenotype. However, deletion is not a genetically homogeneous group as it is composed by two main groups: Class I with breakpoints at BP1 (proximal) and BP3 (distal) and Class II present breakpoints at BP2 (proximal) and BP3 (distal). In this study, we aimed to evaluate the impact of the breakpoint on the electroclinical profile. METHODS: We evaluated 16 patients with AS caused by 15q11-13 deletion (6 were Class I; 10 were Class II). We characterized epilepsy features by clinical history obtained from parents and caretakers with a pre-standard questionnaire. These data were corroborated by medical records, contact with previous physicians, and video-EEG monitoring. Suggestive EEG patterns for AS were classified according to the classical description of Boyd et al. (1988). RESULTS: AS patients with BP1-BP3 deletion had significantly more daily and disabling seizures than AS patients with BP1-BP2 deletion. They also presented a significant higher frequency of status epilepticus and epilepsy aggravated by fever. Need for polytherapy was significantly more frequent in BP1-BP3 patients. EEG features were similar in both groups. CONCLUSION: This study shows a significant correlation between the two deletion classes and AS clinical, but not the electrographic phenotype. Epilepsy is more severe and refractory to treatment in patients with larger deletions. Deletion is not a homogeneous group and knowledge on the breakpoint may have a clinical implication and represent an important factor in parental counseling.
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Síndrome de Angelman/genética , Pontos de Quebra do Cromossomo , Deleção de Genes , Estudos de Associação Genética/métodos , Síndrome de Angelman/diagnóstico , Síndrome de Angelman/fisiopatologia , Criança , Eletroencefalografia/métodos , Seguimentos , Humanos , Estudos ProspectivosRESUMO
Luego del desarrollo de los centros o unidades de mama a nivel mundial, en octubre de 2006 el Hospital Universitario Austral crea el Centro Mamario. El objetivo de este trabajo es comunicar los resultados que se obtuvieron en los primeros 5 años de trabajo multidisciplinario integrado. Se evaluaron en forma retrospectiva los cinco primeros años de funcionamiento del Centro Mamario del HUA. Para analizar el funcionamiento y resultados de los distintos procesos diagnósticos y terapéuticos se tuvieron como referencia los indicadores de calidad propuestos por EUSOMA, pudiendo cumplirlos en casi todos los ítems analizados, excepto en lo referente a la información pronóstica y de predicción completa (83,1% y 81,4%, para un mínimo del 95,0%) y en la indicación de radioterapia posmastectomía(79,4% para un mínimo de 90,0%). Como conclusión, nuestros resultados iniciales comprueban que la coordinación e integración de los distintos servicios involucrados en forma de unidad o centro mamario, permitió la optimización de la calidad de atención de las pacientes con cáncer de mama.(AU)
Assuntos
Neoplasias da Mama , Hospitais UniversitáriosRESUMO
Luego del desarrollo de los centros o unidades de mama a nivel mundial, en octubre de 2006 el Hospital Universitario Austral crea el Centro Mamario. El objetivo de este trabajo es comunicar los resultados que se obtuvieron en los primeros 5 años de trabajo multidisciplinario integrado. Se evaluaron en forma retrospectiva los cinco primeros años de funcionamiento del Centro Mamario del HUA. Para analizar el funcionamiento y resultados de los distintos procesos diagnósticos y terapéuticos se tuvieron como referencia los indicadores de calidad propuestos por EUSOMA, pudiendo cumplirlos en casi todos los ítems analizados, excepto en lo referente a la información pronóstica y de predicción completa (83,1% y 81,4%, para un mínimo del 95,0%) y en la indicación de radioterapia posmastectomía(79,4% para un mínimo de 90,0%). Como conclusión, nuestros resultados iniciales comprueban que la coordinación e integración de los distintos servicios involucrados en forma de unidad o centro mamario, permitió la optimización de la calidad de atención de las pacientes con cáncer de mama.
Assuntos
Neoplasias da Mama , Hospitais UniversitáriosRESUMO
OBJECTIVE: Prader-Willi Syndrome is a common etiology of syndromic obesity that is typically caused by either a paternal microdeletion of a region in chromosome 15 (microdeletions) or a maternal uniparental disomy of this chromosome. The purpose of this study was to describe the most significant clinical features of 35 Brazilian patients with molecularly confirmed Prader-Willi syndrome and to determine the effects of growth hormone treatment on clinical outcomes. METHODS: A retrospective study was performed based on the medical records of a cohort of 35 patients diagnosed with Prader-Willi syndrome. The main clinical characteristics were compared between the group of patients presenting with microdeletions and the group presenting with maternal uniparental disomy of chromosome 15. Curves for height/length, weight and body mass index were constructed and compared between Prader-Willi syndrome patients treated with and without growth hormone to determine how growth hormone treatment affected body composition. The curves for these patient groups were also compared with curves for the normal population. RESULTS: No significant differences were identified between patients with microdeletions and patients with maternal uniparental disomy for any of the clinical parameters measured. Growth hormone treatment considerably improved the control of weight gain and body mass index for female patients but had no effect on either parameter in male patients. Growth hormone treatment did not affect height/length in either gender. CONCLUSION: The prevalence rates of several clinical features in this study are in agreement with the rates reported in the literature. Additionally, we found modest benefits of growth hormone treatment but failed to demonstrate differences between patients with microdeletions and those with maternal uniparental disomy. The control of weight gain in patients with Prader-Willi syndrome is complex and does not depend exclusively on growth hormone treatment.
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Hormônio do Crescimento Humano/uso terapêutico , Síndrome de Prader-Willi/tratamento farmacológico , Adolescente , Fatores Etários , Composição Corporal , Índice de Massa Corporal , Brasil , Criança , Deleção Cromossômica , Transtornos Cromossômicos , Cromossomos Humanos Par 15/genética , Feminino , Seguimentos , Humanos , Deficiência Intelectual/genética , Masculino , Obesidade/complicações , Obesidade/genética , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/patologia , Estudos Retrospectivos , Convulsões/genética , Fatores Sexuais , Resultado do TratamentoRESUMO
OBJECTIVE: Prader-Willi Syndrome is a common etiology of syndromic obesity that is typically caused by either a paternal microdeletion of a region in chromosome 15 (microdeletions) or a maternal uniparental disomy of this chromosome. The purpose of this study was to describe the most significant clinical features of 35 Brazilian patients with molecularly confirmed Prader-Willi syndrome and to determine the effects of growth hormone treatment on clinical outcomes. METHODS: A retrospective study was performed based on the medical records of a cohort of 35 patients diagnosed with Prader-Willi syndrome. The main clinical characteristics were compared between the group of patients presenting with microdeletions and the group presenting with maternal uniparental disomy of chromosome 15. Curves for height/length, weight and body mass index were constructed and compared between Prader-Willi syndrome patients treated with and without growth hormone to determine how growth hormone treatment affected body composition. The curves for these patient groups were also compared with curves for the normal population. RESULTS: No significant differences were identified between patients with microdeletions and patients with maternal uniparental disomy for any of the clinical parameters measured. Growth hormone treatment considerably improved the control of weight gain and body mass index for female patients but had no effect on either parameter in male patients. Growth hormone treatment did not affect height/length in either gender. CONCLUSION: The prevalence rates of several clinical features in this study are in agreement with the rates reported in the literature. Additionally, we found modest benefits of growth hormone treatment but failed to demonstrate differences between patients with microdeletions and those with maternal uniparental disomy. The control of weight gain in patients with Prader-Willi syndrome is complex and does not depend exclusively on growth hormone treatment.
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Adolescente , Criança , Feminino , Humanos , Masculino , Hormônio do Crescimento Humano/uso terapêutico , Síndrome de Prader-Willi/tratamento farmacológico , Fatores Etários , Composição Corporal , Índice de Massa Corporal , Brasil , Deleção Cromossômica , /genética , Seguimentos , Deficiência Intelectual/genética , Obesidade/complicações , Obesidade/genética , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/patologia , Estudos Retrospectivos , Fatores Sexuais , Convulsões/genética , Resultado do TratamentoRESUMO
We describe a novel chromosome microdeletion at 15q26.1 detected by oligo-array-CGH in a 6-year-old girl presenting with global development delay, epilepsy, autistic behavior and facial dysmorphisms. Although these features are often present in Angelman syndrome, no alterations were present in the methylation pattern of the Prader-Willi-Angelman critical region. The deletion encompasses only 2 genes: CHD2, which is part of a gene family already involved in CHARGE syndrome, and RGMA which exerts a negative control on axon growth. Deletion of either or both genes could cause the phenotype of this patient. These results provide a further chromosome region requiring evaluation in patients presenting Angelman features.
Assuntos
Proteínas de Ligação a DNA/genética , Epilepsia/genética , Deleção de Genes , Deficiência Intelectual/genética , Síndrome de Angelman/genética , Criança , Cromossomos Humanos Par 15 , Feminino , Humanos , FenótipoRESUMO
Introducción: El dolor postoperatorio es un tipo especial de dolor agudo, de gran repercusión en el sector de la salud. Un control óptimo del mismo en procederes proctológicos y del periné es un verdadero reto. Su tratamiento correcto puede aliviar el sufrimiento y permitir la movilización temprana y acortar la estadía hospitalaria. Objetivos: Identificar la utilidad de opioides en analgesia postoperatoria en cirugía proctológica. Método: Se realizó un estudio experimental, a simple ciegas, comparativo y prospectivo, para seleccionar la dosis de morfina intratecal a utilizar para la analgesia postoperatoria en pacientes a quienes se les realizó cirugía proctológica en el Servicio de Anestesia y Reanimación del Hospital Docente Clínico Quirúrgico Dr. Salvador Allende durante el 2009. La muestra estuvo constituida por 210 pacientes, seleccionados de forma aleatoria. Se agruparon en tres grupos según la dosis de morfina administrada: Grupo I (74 pacientes) se administró 3 µg/Kg; Grupo II (68 pacientes) 4 µg/Kg y en el Grupo III (68 pacientes) 5 µg/Kg. Resultados: El valor medio de la duración de la analgesia en horas en el Grupo I fue de 11,97 ± 1,67 DS, en el grupo II fue de 21,54 ± 2,29 y en el III de 21,4 ± 2,03. El prurito fue el efecto adverso con mayor incidencia, seguido por la retención urinaria, las nauseas y los vómitos. Conclusiones: La dosis de 4 µg/Kg parece ser la más recomendable para la analgesia postoperatoria con morfina intratecal en cirugía proctológica si se toma en cuenta la duración de la analgesia y los efectos adversos encontrados en nuestro estudio.
Postoperative pain is a special type of acute pain of a great repercussion in the health sector. Its optimal control in proctologic procedures and of perineum is a real challenge. Its appropriate treatment may to relief suffering allowing an early mobilization and to shorten the hospital stay. Objectives: to identify the usefulness of opioids in postoperative surgery in proctologic anesthesia. Method: A prospective, comparative, double blind and experimental study was conducted to choice the dose of intrathecal morphine to be used for postoperative analgesia in patients underwent proctologic surgery in the Service of Anesthesia and Resuscitation of the "Dr. Salvador Allende" Clinical Surgical Teaching Hospital during 2009. Sample included 210 randomized patients divided into three groups according the dose of morphine administered: I Group (74 patients) received 3 µg/Kg; II Group (68 patients) received 4 µg/Kg and III group (68 patients) received 5 µg/Kg. Results: The mean value in hours of analgesia length in I group was of 11,97 ± 1,67 DS, in the II group it was of 21,54 ± 2,29, and in the III group, it was of 21,4 ± 2,03. Pruritus had the higher incidence as adverse effect, followed by urinary retention, nauseas and vomiting. Conclusions: Dose of 4 µg/Kg seems to be the more recommendable for the postoperative analgesia using intrathecal morphine in proctologic surgery if we take into account the analgesia length and the adverse effects found in our study.
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Supernumerary marker chromosomes (sSMC) may or may not be associated with an abnormal phenotype, depending on the presence of euchromatin, on their chromosomal origin and whether they are inherited. Over 80% of sSMCs are derived from acrocentric chromosomes and half of them include the short arm of chromosome 15. Generally, they appear as bisatellited isodicentric marker chromosomes, most of them are symmetric. These chromosomes are normally originated de novo and are associated with mild to severe intellectual disability but not with physical abnormalities. We report on a patient with an SMC studied using classical and molecular cytogenetic procedures (G and C banding, NOR staining, painting and centromeric fluorescent in situ hybridization (FISH), BAC-FISH, and SKY). The MLPA technique and DNA polymorphic markers were used in order to identify its parental origin. The marker chromosome, monosatellited and monocentric, was found to be derived from a maternal chromosome 15 and was defined as 15pter-q21.2. This is the report of the largest de novo monosatellited 15q marker chromosome ever published presenting detailed cytogenetic and clinical data. It was associated with a phenotype including cardiac defect, absence of septum pellucidum, and dysplasia of the corpus callosum.
Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 15/genética , Marcadores Genéticos , Trissomia , Síndrome Acrocalosal/genética , Deficiências do Desenvolvimento/genética , Feminino , Cardiopatias Congênitas/genética , Humanos , Lactente , Fenótipo , Septo Pelúcido/anormalidades , Cariotipagem EspectralRESUMO
Rearrangements of 1p36 are the most frequently detected abnormalities in diagnostic testing for chromosomal cryptic imbalances and include variably sized simple terminal deletions, derivative chromosomes, interstitial deletions, and complex rearrangements. These rearrangements result in the specific pattern of malformation and neurodevelopmental disabilities that characterizes monosomy 1p36 syndrome. Thus far, no individual gene within this region has been conclusively determined to be causative of any component of the phenotype. Nor is it known if the rearrangements convey phenotypes via a haploinsufficiency mechanism or through a position effect. We have used multiplex ligation-dependent probe amplification to screen for deletions of 1p36 in a group of 154 hyperphagic and overweight/obese, PWS negative individuals, and in a separate group of 83 patients initially sent to investigate a variety of other conditions. The strategy allowed the identification and delineation of rearrangements in nine subjects with a wide spectrum of clinical presentations. Our work reinforces the association of monosomy 1p36 and obesity and hyperphagia, and further suggests that these features may be associated with non-classical manifestations of this disorder in addition to a submicroscopic deletion of approximately 2-3 Mb in size. Multiplex ligation probe amplification using the monosomy 1p36 syndrome-specific kit coupled to the subtelomeric kit is an effective approach to identify and delineate rearrangements at 1p36.
Assuntos
Cromossomos Humanos Par 1 , Hiperfagia/genética , Obesidade/genética , Mapeamento Cromossômico , Estudos de Coortes , Humanos , Hibridização in Situ Fluorescente , FenótipoRESUMO
Introducción: La ventilación controlada por presión es un modo de ventilación ampliamente utilizado en el fallo respiratorio severo, donde ha demostrado que mejora la oxigenación arterial. Objetivo: Comparar la ventilación controlada por volumen comúnmente utilizado durante la ventilación unipulmonar con tres estrategias ventilatorias de ventilación controlada por presión. Método: Se realizó un estudio comparativo y prospectivo de 100 pacientes tratados por cirugía torácica divididos en cuatro grupos según modo ventilatorio utilizado. Grupo I VCV, con volumen minuto 100 mL/kg. Grupo II VCP con Vot de 10 mL/kg, Grupo III VCP con Vot de 8 mL/kg, y Grupo IV VCP con 5cm de H2O de PEEP y un Vot de 8 mL/kg. Se comparó PaO2, SatO2, Shunt Intrapulmonar, Presión Pico y Meseta a los 30 minutos de la ventilación unipulmonar y los episodios de desaturación arterial. Se utilizó Chi Cuadrado y ANOVA para el análisis estadístico. Resultados: La PaO2 presentó valores similares en los Grupos I y II, 148,28 ± 68,21 y 146,8 ± 67,8 mmHg, respectivamente, disminuyó en el Grupo III a 117,2 ± 51,0 mmHg y aumentó significativamente en el Grupo IV 189,0 ± 49,2 mmHg. La SatO2 se incrementó y el shunt intrapulmonar disminuyó con significación estadística en el Grupo IV. Las presiones en la vía aérea fueron menores durante la VCP. Conclusión: La ventilación controlada por presión "per se" no mejoró las variables de oxigenación durante la ventilación unipulmonar, pero sí, permite alcanzar menores presiones en la vía aérea. La administración de PEEP durante la ventilación controlada por presión evidenció mejoría significativa de la oxigenación.
Introduction: Pressure controlled ventilation is a very used way of ventilation in severe respiratory failure, where it has been showed that it improves arterial oxygenation. Objective: To compare volume controlled ventilation commonly used during unipulmonar ventilation with three ventilator strategies of pressure controlled ventilation. Method: We made a comparative and prospective study of 100 patients undergoing thoracic surgery divided into 4 groups by ventilator mode used: group I VCV with a minute volume 100 mL/kg, group II VCP with Vot of 10 mL/kg, group III VCP with Vot of 8 mL/kg, and group IV VCP with 5 cm of H2O of PEEP, and a Vot of 8 mL/kg. We compared PaO2, SatO2, intrapulmonary shunt, peak and plateau pressures at 30 minutes of unipulmonar ventilation, and the arterial desaturation episodes. We used Chi2 and ANOVA for statistical analysis. Results: The PaO2 yields similar values in Groups I and II, 148,28 ± 68,21 and 146,8 ± 67,8 mmHg, respectively, it decreased in Group III to 117,2 ± 51,0 mmHg, and then increased significantly in group IV 189,0 ± 49,2 mmHg. The SatO2 increased and intrapulmonary shunt decreased with statistical significance in group IV. Airway pressures were low during VCP. Conclusion: Pressure controlled ventilation "per se" not improved oxygenation variables during unipulmonar ventilation, but allowing lower pressures in airway. Administration of PEEP during pressure controlled evidenced a significant improvement of oxygenation.
RESUMO
The association of obesity, phenotypic abnormalities and mental retardation characterizes syndromic obesity. Its most common form is the Prader-Willi syndrome (PWS-- neonatal hypotonia, poor sucking, delayed psychomotor development, hyperphagia, severe obesity, short stature, small hands and feet, hypogonadism, mild to moderate mental retardation and behavioral disorders). A PWS-like phenotype has been described in patients with chromosome abnormalities involving the chromosome region 6q16.2 that includes the SIM1 gene. Herein we report cytogenetic and gene studies including a screening for the SIM1 gene deletion, performed on 87 patients with PWS-like phenotype, and describe the fifth case of syndromic obesity with an interstitial deletion of the chromosome segment 6q16-q21 and suggest that mutational analysis and further studies of the parental origin of chromosome alterations of 6q16.2 in patients with and without PWS-like phenotype are needed to evaluate possible imprinting effects of SIM1 gene and establish the contribution that alterations in this gene makes to the etiology of syndromic and non-syndromic obesity.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Deleção Cromossômica , Cromossomos Humanos Par 6 , Síndrome de Prader-Willi/genética , Proteínas Repressoras/genética , Criança , Pré-Escolar , Feminino , Testes Genéticos , Humanos , Lactente , Masculino , Obesidade/genética , Fenótipo , SíndromeRESUMO
Monosomy 1p36 is one of the most commonly observed mental retardation (MR) syndromes that results in a clinically recognizable phenotype including delayed psychomotor development and/or MR, hypotonia, epilepsy, hearing loss, growth delay, microcephaly, deep-set eyes, flat nasal bridge and pointed chin. Besides, a Prader-Willi syndrome (PWS)-like phenotype has been described in patients with 1p36 monosomy. Forty-one patients presenting hypotonia, developmental delay, obesity and/or hyperphagia and behavioral problems who tested negative for PWS were investigated by FISH and/or microsatellite markers. Twenty-six were analyzed with a 1p-specific subtelomeric probe, and one terminal deletion was identified. Thirty patients (15 of which also studied by FISH) were investigated by microsatellite markers, and no interstitial 1p36 deletion was found. Our patient presenting the 1p36 deletion did not have the striking features of this monosomy, but her clinical and behavioral features were quite similar to those observed in patients with PWS, except for the presence of normal sucking at birth. The extent of the deletion could be limited to the most terminal 2.5 Mb of 1p36, within the chromosomal region 1p36.33-1p36.32, that is smaller than usually seen in monosomy 1p36 patients. Therefore, chromosome 1p36.33 deletion should be investigated in patients with hypotonia, developmental delay, obesity and/or hyperphagia and behavioral problems who test negative for PWS.