RESUMO
INTRODUCTION: Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care. Everolimus has shown positive effects on subependymal giant cell astrocytomas, renal angiomyolipoma and refractory seizures associated with tuberous sclerosis complex. However, evidence supporting efficacy in symptomatic cardiac rhabdomyoma is limited to case reports. The ORACLE trial is the first randomised clinical trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma. METHODS: ORACLE is a phase II, prospective, randomised, placebo-controlled, double-blind, multicentre protocol trial. A total of 40 children with symptomatic cardiac rhabdomyoma secondary to tuberous sclerosis complex will be randomised to receive oral everolimus or placebo for 3 months. The primary outcome is 50% or more reduction in the tumour size related to baseline. As secondary outcomes we include the presence of arrhythmias, pericardial effusion, intracardiac obstruction, adverse events, progression of tumour reduction and effect on heart failure. CONCLUSIONS: ORACLE protocol addresses a relevant unmet need in children with tuberous sclerosis complex and cardiac rhabdomyoma. The results of the trial will potentially support the first evidence-based therapy for this condition.
Assuntos
Antineoplásicos/uso terapêutico , Everolimo/uso terapêutico , Neoplasias Cardíacas/tratamento farmacológico , Rabdomioma/tratamento farmacológico , Esclerose Tuberosa/complicações , Antineoplásicos/efeitos adversos , Criança , Ensaios Clínicos Fase II como Assunto , Método Duplo-Cego , Everolimo/efeitos adversos , Neoplasias Cardíacas/complicações , Humanos , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Rabdomioma/complicações , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacosRESUMO
OBJECTIVE: The association between renal hypoxia and the development of renal injury is well established. However, no adequate method currently exists to non-invasively measure functional changes in renal oxygenation in normal and injured patients. METHOD: R2* quantification was performed using renal blood oxygen level-dependent properties. Five healthy normotensive women (50 ± 5.3 years) underwent magnetic resonance imaging in a 1.5T Signa Excite HDx scanner (GE Healthcare, Waukesha, WI). A multiple fast gradient-echo sequence was used to acquire R2*/T2* images (sixteen echoes from 2.1 ms/slice to 49.6 ms/slice in a single breath hold per location). The images were post-processed to generate R2* maps for quantification. Data were recorded before and at 30 minutes after the oral administration of an angiotensin II-converting enzyme inhibitor (captopril, 25 mg). The results were compared using an ANOVA for repeated measurements (mean + standard deviation) followed by the Tukey test. ClinicalTrials.gov: NCT01545479. RESULTS: A significant difference (p<0.001) in renal oxygenation (R2*) was observed in the cortex and medulla before and after captopril administration: right kidney, cortex = 11.08 ± 0.56 ms, medulla = 17.21 ± 1.47 ms and cortex = 10.30 ± 0.44 ms, medulla = 16.06 ± 1.74 ms, respectively; and left kidney, cortex= 11.79 ± 1.85 ms, medulla = 17.03 ± 0.88 ms and cortex = 10.89 ± 0.91 ms, medulla = 16.43 ± 1.49 ms, respectively. CONCLUSIONS: This result suggests that the technique efficiently measured alterations in renal blood oxygenation after angiotensin II-converting enzyme inhibition and that it may provide a new strategy for identifying the early stages of renal disease and perhaps new therapeutic targets.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Captopril/farmacologia , Rim/metabolismo , Oxigênio/metabolismo , Feminino , Humanos , Rim/irrigação sanguínea , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Oxigênio/sangue , Fatores de TempoRESUMO
OBJECTIVE: The association between renal hypoxia and the development of renal injury is well established. However, no adequate method currently exists to non-invasively measure functional changes in renal oxygenation in normal and injured patients. METHOD: R2* quantification was performed using renal blood oxygen level-dependent properties. Five healthy normotensive women (50±5.3 years) underwent magnetic resonance imaging in a 1.5T Signa Excite HDx scanner (GE Healthcare, Waukesha, WI). A multiple fast gradient-echo sequence was used to acquire R2*/T2* images (sixteen echoes from 2.1 ms/slice to 49.6 ms/slice in a single breath hold per location). The images were post-processed to generate R2* maps for quantification. Data were recorded before and at 30 minutes after the oral administration of an angiotensin II-converting enzyme inhibitor (captopril, 25 mg). The results were compared using an ANOVA for repeated measurements (mean + standard deviation) followed by the Tukey test. ClinicalTrials.gov: NCT01545479. RESULTS: A significant difference (p<0.001) in renal oxygenation (R2*) was observed in the cortex and medulla before and after captopril administration: right kidney, cortex = 11.08 ± 0.56ms, medulla = 17.21 ± 1.47ms and cortex = 10.30 ± 0.44ms, medulla = 16.06 ± 1.74ms, respectively; and left kidney, cortex= 11.79 ± 1.85ms, medulla = 17.03 ± 0.88ms and cortex = 10.89 ± 0.91ms, medulla = 16.43 ± 1.49ms, respectively. CONCLUSIONS: This result suggests that the technique efficiently measured alterations in renal blood oxygenation after angiotensin II-converting enzyme inhibition and that it may provide a new strategy for identifying the early stages of renal disease and perhaps new therapeutic targets.
Assuntos
Feminino , Humanos , Pessoa de Meia-Idade , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Captopril/farmacologia , Rim/metabolismo , Oxigênio/metabolismo , Rim/irrigação sanguínea , Imageamento por Ressonância Magnética , Oxigênio/sangue , Fatores de TempoRESUMO
A acidose tubula renal (ATR) é uma manifestação extraglandular da síndrome de SJörgen que ocorre em aproximadamente 30 por cento dos pacientes. A ATR é geralmente assintomática, mas pode levar à acidose metabólica e perda renal de potássio, resultando em marcadas alterações clínicas. Descreve-se o caso de uma paciente com 33 anos e SS que desenvolveu paralisia hipocalêmica relacionada à ATR. Discute-se a apresentação clínica e a fisiopatologia do comprometimento renal na SS. Destaca-se a importância da investigação dos eletrólitos e do exame comum de urina em todos os indivídruos com SS, principalmente quando houver cálculo renal
Assuntos
Humanos , Feminino , Adulto , Acidose Tubular Renal , Hipopotassemia , Síndrome de Sjogren/complicaçõesRESUMO
O objetivo do presente trabalho foi o de verificar a incidência e quais os tipos de repercussöes fundoscópicas em criançäs com diagnóstico clínico de hipertensäo arterial sistêmica (HAS). Dezenove crianças foram examinadas e fotodocumentadas. Destas 11 com hipertensäo do tipo secundária. Do total, 7 (37 por cento) exibiram alguma modificaçäo atribuível a doença básica, sendo encontrados na seguinte frequência: estreitamentos arteriolares (16 por cento), aumento da tortuosidade (10,5 por cento) e entrecruzamentos patológicos (10,5 por cento). Nenhuma criança com déficit visual secundário a HAS. Os resultados säo significativos tanto por indicar uma incidência expressiva de alteraçöes retinianas como também por chamar a atençäo de que estes sinais devem ser motivos de investigaçäo clínica quando casualmente detectados durante exames de rotina