RESUMO
Left main coronary artery ostial atresia (LMCAOA) is an extremely rare condition. Here, we report the case of a 14-year-old boy with Noonan syndrome-like disorder in whom LMCAOA was detected following cardiopulmonary arrest. The patient had been diagnosed with Noonan syndrome-like disorder with a pathogenic splice site variant of CBL c.1228-2 A > G. He suddenly collapsed when he was running. After administering two electric shocks using an automated external defibrillator, the patient's heartbeat resumed. Cardiac catheterization confirmed the diagnosis of LMCAOA. Left main coronary artery angioplasty was performed. The patient was discharged without neurological sequelae. Brain magnetic resonance imaging revealed asymptomatic Moyamoya disease. In addition, RNF213 c.14429 G > A p.R4810K was identified. There are no reports on congenital coronary malformations of compound variations of RNF213 and CBL. In contrast, the RNF213 p.R4810K polymorphism has been established as a risk factor for angina pectoris and myocardial infarction in adults, and several congenital coronary malformations due to genetic abnormalities within the RAS/MAPK signaling pathway have been reported. This report aims to highlight the risk of sudden death in patients with RASopathy and RNF213 p.R4810K polymorphism and emphasize the significance of actively searching for coronary artery morphological abnormalities in these patients.
Assuntos
Anormalidades Múltiplas , Parada Cardíaca , Doença de Moyamoya , Síndrome de Noonan , Adulto , Masculino , Humanos , Criança , Adolescente , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/metabolismo , Síndrome de Noonan/complicações , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/genética , Predisposição Genética para Doença , Adenosina Trifosfatases/genética , Ubiquitina-Proteína Ligases/genética , Doença de Moyamoya/genética , Parada Cardíaca/genéticaRESUMO
BACKGROUND: We report a rare case of left ventricular inflow obstruction from a branch of the left circumflex coronary artery to the right atrium caused by a coronary arteriovenous fistula (CAVF) in a young Japanese male child. CASE PRESENTATION: The patient was diagnosed with CAVF following a heart murmur shortly after birth. The left-to-right shunt caused right ventricular volume overload and pulmonary congestion. An emergency surgical intervention was performed for the CAVF on day 6 after birth. However, by 5 years of age, his left ventricular inflow obstruction worsened. We found an abnormal blood vessel originating from the proximal part of a branch of the left circumflex coronary artery, circling the outside of the mitral valve annulus along the medial side of the coronary sinus. As the child gets older, the blood inflow into the left ventricle might get restricted further, resulting in left-sided heart failure. CONCLUSION: Our findings suggest that even after CAVF closure surgery, it is essential to monitor for complications caused by progressive dilatation of a persistent CAVF.
Assuntos
Fístula Arteriovenosa/complicações , Anomalias dos Vasos Coronários/complicações , Ventrículos do Coração , Hiperemia/etiologia , Fatores Etários , Fístula Arteriovenosa/cirurgia , Pré-Escolar , Seio Coronário , Anomalias dos Vasos Coronários/cirurgia , Dilatação Patológica/complicações , Humanos , Hipocinesia/diagnóstico por imagem , Recém-Nascido , Masculino , Valva Mitral , Veias Pulmonares , Disfunção Ventricular Esquerda/diagnóstico por imagemRESUMO
The development of drug delivery systems for use in the treatment of cardiovascular diseases is an area of great interest. We report herein on an evaluation of the therapeutic potential of a myocardial mitochondria-targeting liposome, a multifunctional envelope-type nano device for targeting pancreatic ß cells (ß-MEND) that was previously developed in our laboratory. Resveratrol (RES), a natural polyphenol compound that has a cardioprotective effect, was encapsulated in the ß-MEND (ß-MEND (RES)), and its efficacy was evaluated using rat myocardioblasts (H9c2 cells). The ß-MEND (RES) was readily taken up by H9c2 cells, as verified by fluorescence-activated cell sorter data, and was observed to be colocalized with intracellular mitochondria by confocal laser scanning microscopy. Myocardial mitochondrial function was evaluated by a Seahorse XF Analyzer and the results showed that the ß-MEND (RES) significantly activated cellular maximal respiratory capacity. In addition, the ß-MEND (RES) showed no cellular toxicity for H9c2 cells as evidenced by Premix WST-1 assays. This is the first report of the use of a myocardial mitochondria-targeting liposome encapsulating RES for activating mitochondrial function, which was clearly confirmed based on analyses using a Seahorse XF Analyzer.
Assuntos
Respiração Celular/efeitos dos fármacos , Lipossomos/química , Mitocôndrias Cardíacas/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Resveratrol/farmacologia , Animais , Linhagem Celular , Células Secretoras de Insulina/efeitos dos fármacos , Nanopartículas/química , Polifenóis/química , Ratos , Resveratrol/químicaRESUMO
AIMS: Mitochondrial cardiomyopathy (MCM) is difficult to make a definite diagnosis because of various cardiovascular phenotypes and no diagnostic criteria in the pathology examination. We aim to add myocardial pathology to the diagnostic criteria for mitochondrial respiratory chain disorders. METHODS: Quantitative analysis of mitochondria using electron microscopy and immunohistopathological analysis with respiratory chain enzyme antibodies were performed in 11 patients with hypertrophic or restrictive cardiomyopathy who underwent endomyocardial biopsy for possible MCM . Respiratory chain enzymatic assay in biopsied myocardium and genetic studies were also performed in all the subjects to define MCM. RESULTS: Four patients were diagnosed with MCM according to the recent criteria of mitochondrial respiratory chain disorders. Using electron microscopy with quantitative analysis, the volume density of mitochondria within cardiac muscle cells was significantly increased in the MCM group compared with the non-MCM group (p=0.007). Immunohistopathological results were compatible with the result of the respiratory chain enzymatic assay. CONCLUSIONS: Pathological diagnosis of MCM could be confirmed by a quantitative study of electron microscopy and immunohistopathological analysis using the mitochondrial respiratory chain enzyme subunit antibody.
RESUMO
Congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH) is one of the major complications in patients with CHD. A timely closure of the left-to-right shunt will generally result in the normalization of the pulmonary hemodynamics, but a few patients have severe prognosis in their early childhood. We hypothesized that wide-ranging pathological mechanism in PAH could elucidate the clinical state of severe CHD-PAH. Using electronic medical records, we retrospectively analyzed six infants with severe CHD-PAH who had treatment-resistant PH. All patients were born with congenital malformation syndrome. After starting on a pulmonary vasodilator, five of the six patients developed complications including pulmonary edema and interstitial lung disease (ILD), and four patients had alveolar hemorrhage. After steroid therapy, the clinical condition improved in four patients, but two patients died. The autopsy findings in one of the deceased patients indicated the presence of recurrent alveolar hemorrhage, pulmonary venous hypertension, ILD, and PAH. Based on the clinical course of these CHD-PAH in patients and the literature, CHD-PAH can occur with pulmonary vascular obstructive disease (PVOD)/pulmonary capillary hemangiomatosis (PCH), ILD, and/or alveolar hemorrhage. The severity of CHD-PAH may depend on a genetic disorder, respiratory infection, and upper airway stenosis. Additionally, pulmonary vasodilators may be involved in the development of PVOD/PCH and ILD. When patients with CHD-PAH show unexpected deterioration, clinicians should consider complications associated with PVOD/PCH and/or pulmonary disease. In addition, the choice of upfront combination therapy for pediatric patients with CHD-PAH should be selected carefully.
Assuntos
Anti-Hipertensivos/efeitos adversos , Pressão Arterial/efeitos dos fármacos , Cardiopatias Congênitas/complicações , Hipertensão Arterial Pulmonar/tratamento farmacológico , Artéria Pulmonar/efeitos dos fármacos , Vasodilatadores/efeitos adversos , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/fisiopatologia , Cardiopatias Congênitas/cirurgia , Hemangioma Capilar/complicações , Hemangioma Capilar/fisiopatologia , Hemorragia/etiologia , Hemorragia/fisiopatologia , Humanos , Lactente , Recém-Nascido , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/fisiopatologia , Masculino , Hipertensão Arterial Pulmonar/diagnóstico , Hipertensão Arterial Pulmonar/etiologia , Hipertensão Arterial Pulmonar/fisiopatologia , Artéria Pulmonar/fisiopatologia , Edema Pulmonar/etiologia , Edema Pulmonar/fisiopatologia , Pneumopatia Veno-Oclusiva/etiologia , Pneumopatia Veno-Oclusiva/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVES: Acute leukemia often causes osteoarthralgia. The aim of this study is characterization of leukemia-associated osteoarthralgia in comparison with juvenile idiopathic arthritis (JIA). METHODS: We retrospectively reviewed clinical records of 31 patients with acute leukemia and 13 patients with articular JIA diagnosed between January 2008 and March 2013. Clinical and laboratory findings at the initial examination were compared among the three groups; 10 leukemia with and 21 leukemia without osteoarthralgia and 13 JIA groups. RESULTS: Eleven of the 31 leukemic patients (35%) had osteoarthralgia before the diagnosis of leukemia. Peripheral leukemic cells were initially absent in 10 of the 31 leukemia patients including three with osteoarthralgia. Platelet counts over 300 × 109/L were common in JIA, but not in osteoarthralgia group. Mean serum lactate dehydrogenase levels were higher in both of the leukemia groups than JIA group but often within normal or near-normal levels in the leukemia groups. Magnetic resonance imaging was examined in three leukemic patients and demonstrated osteomyelitis-like bone marrow edema in two and periarticular infiltration similar to synovitis in one patient. Three leukemic patients with osteoarthralgia showed partial and transient responses to antibiotic therapy. CONCLUSIONS: Leukemia-associated osteoarthralgia is often indistinguishable from rheumatic diseases by imaging and laboratory findings and should be confirmed by bone marrow examination.
Assuntos
Artralgia/diagnóstico por imagem , Artrite Juvenil/diagnóstico por imagem , Medula Óssea/diagnóstico por imagem , Edema/diagnóstico por imagem , Leucemia/diagnóstico por imagem , Dor/diagnóstico por imagem , Artralgia/etiologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Leucemia/complicações , Imageamento por Ressonância Magnética/métodos , Masculino , Dor/etiologia , Estudos RetrospectivosRESUMO
We describe a boy with Schinzel-Giedion syndrome who developed refractory sacrococcygeal germ cell tumor with elements of embryonal carcinoma and immature teratoma. He developed local recurrence soon after tumor resection. The tumor was highly resistant to platinum-based combination chemotherapy, local irradiation, and salvage chemotherapy. Frequent infections resulted in a delay in treatment, although apparent fragility had not been observed clinically. He died from tumor progression at 32 months of age. Intensification of chemotherapy does not seem to be feasible for tumors in patients with Schinzel-Giedion syndrome.