Mitochondrial mutations in patients with congenital heart defects by next generation sequencing technology.

It has been shown that mitochondrial deoxyribo nucleic acid mutations may play an important role in the development of cardiomyopathy, and various types of cardiomyopathy can be attributed to disturbed mitochondrial oxidative energy metabolism. Several studies have described many mutations in mitochondrial genes encoding for subunits of respiratory chain complexes. Thus, recent studies confirm that pathologic mitochondrial deoxyribo nucleic acid mutations are a major reason of diseases and determining them by next-generation sequencing will improve our understanding of dysregulation of heart development. To analyse mitochondrial deoxyribo nucleic acid mutations, the entire mitochondrial deoxyribo nucleic acid was amplified in two overlapping polymerase chain reaction fragments from the cardiac tissue of the 22 patients with congenital heart disease, undergoing cardiac surgery. Mitochondrial deoxyribo nucleic acid was deep sequenced by next-generation sequencing. A total of 13 novel mitochondrial deoxyribo nucleic acid mutations were identified in nine patients. Of the patients, three have novel mutations together with reported cardiomyopathy mutations. In all, 65 mutations were found, and 13 of them were unreported. This study represents the most comprehensive mitochondrial deoxyribo nucleic acid mutational analysis in patients with congenital heart disease.

A novel ATP8 gene mutation in an infant with tetralogy of Fallot.

We report the case of a novel mitochondrial DNA mutation in the MT-ATP8 gene in an infant with tetralogy of Fallot. Next-generation sequencing was applied to sequence whole mitochondrial DNA of the patient. A known Leber's hereditary optic neuropathy-associated mutation (G9804A), a heteroplasmic T7501C mutation (17%), and a novel C8481 T Pro > Leu missense mutation in the MT-ATP8 gene was identified.

Primary myxoma of the pulmonary artery.

Cardiac myxomas are most commonly found within the left atrium. We now report a patient presenting with dyspnea, palpitation, and chest pain who was found to have myxoma arising from the pulmonary valve commissure. Urgent surgical treatment is curative and warranted for these lesions, in order to prevent outflow obstruction and thromboembolic phenomena.

Prognostic evidence of LEF1 isoforms in childhood acute lymphoblastic leukemia.

INTRODUCTION: The lymphoid enhancer factor 1 (LEF1) is a DNA-binding transcription factor that functions in the Wnt signaling pathway. Increased LEF1 activity is associated with progression of several types of cancer including leukemia. Here, we investigated LEF1 isoform expression and genomic variations in acute lymphoblastic leukemia (ALL). METHODS: LEF1 isoform expression was evaluated by quantitative real-time PCR in 87 newly diagnosed childhood ALL patients and controls. Moreover, Western blot analysis was performed for detection of LEF1 expression and the hotspot region of LEF1 was screened by deep sequencing. RESULTS: The LEF1 mRNA expression of B cell ALL patients was higher than the controls (LEF1-total P = .011, LEF1-long P = .026). Moreover, B-ALL samples showing higher total LEF1 expression had significantly shorter relapse-free survival (P = .008) and overall survival (P = .011). Although full-length LEF1 expression was similar to the controls in T-ALL, 50% (n = 15) of the ALL patients had increased full-length LEF1 protein expression. Imbalance between short- and full-length LEF1 isoforms may lead to cell survival in ALL. Beside the LEF1 activation, LEF1 gene variations were rarely observed in our cohort. CONCLUSION: The results indicate that the Wnt pathway may have a pathogenic function in a group of ALL patients and high LEF1-total expression might be a marker for shorter relapse-free survival time in B cell ALL.

Influence of methylprednisolone on levels of neuron-specific enolase in cardiac surgery: a corticosteroid derivative to decrease possible neuronal damage.

BACKGROUND: Cerebral injury is a well-known complication after cardiac surgery with cardiopulmonary bypass (CPB), especially in adult patients. Specific biochemical markers like neuron-specific enolase (NSE) and S-100beta protein were developed previously for early detecting neuronal damage after CPB. Corticosteroids are shown to reduce multisystemic deleterious effects of cardiopulmonary bypass due to their anti-inflammatory characteristics. The aim of this study is to demonstrate the decrease of serum neuron-specific enolase levels in patients who received corticosteroids before CPB. METHODS: Thirty patients scheduled for elective coronary bypass surgery were included in the study. Patients were divided randomly into two groups as the control group (n = 15) who underwent a standard coronary bypass surgery without any additional medication and the study group (n = 15) who received 1 gm of methylprednisolone before CPB. Blood samples for analysis of serum NSE, interleukin-6 (IL-6), and IL-10 were drawn before CPB, 4 and 24 hours after the end of extracorporeal circulation. RESULTS: Serum cytokine and NSE levels were significantly increased after CPB above their normal range in both groups. In the study group, IL-6 and NSE levels were significantly reduced while IL-10 levels were much higher after CPB. High NSE levels significantly correlated with IL-6 levels in the control group. CONCLUSION: The lower levels of NSE in patients who received methylprednisolone may suggest that corticosteroids might be useful in decreasing possible neuronal damage during heart surgery. However, we were not able to demonstrate an adverse neurological outcome.

Congenital heart disease in children with Down's syndrome: Turkish experience of 13 years.

BACKGROUND: Down's syndrome (DS) is the most common chromosomal abnormality due to a trisomy of chromosome 21 commonly associated with congenital heart defects (CHDs). This study aimed to evaluate the frequency and types of CHD patterns in Turkish children with DS. METHOD: The data relate to paediatric patients with DS who underwent cardiologic screening between 1994 and 2007 and were reviewed in our Paediatric Cardiology unit. RESULTS: Four hundred and twenty-one out of the 1042 paediatric patients with DS studied over a 13-year period had associated CHD. Of these, 320 (77.6%) had a single cardiac lesion, while the remaining 92 patients (22.4%) had multiple defects. The most common single defect was an atrioventricular septal defect (AVSD) found in 141 patients (34.2%), followed by 69 patients (16.7%) showing secundum type atrial septal defect, and ventricular septal defect in 68 patients (16.5%). AVSDs were the leading type, isolated or combined with other cardiac anomalies with an overall occurrence of 19.8% of paediatric patients with DS, and 49.2% of paediatric patients with both DS and CHD. CONCLUSION: This is the first study concerning the frequency and type of CHD observed in Turkish children with DS. The high frequency of AVSD in Turkish children with DS implied that early screening for CHDs by echocardiography is crucial. The correction of AVSDs in paediatric patients with DS should be performed in the first 6 months of life to avoid irreversible haemodynamic consequences of the defect.

Over 14 years of experience with cardiac myxomas.

Atrial myxomas are the most commonly encountered tumours of the heart and can present at different ages with different clinical symptoms. They are one of the curable tumours of the heart. Appropriate surgical treatment and surgery must be performed with great precautions in order to prevent fatal systemic embolizations. In this retrospective study we will present our experience of 14 years, between 1990 and 2004, in 27 patients who had been operated for cardiac myxomas. Diagnosis of the myxomas were made by echocardiography in all cases. Surgical approach to the tumour was biatrial in nine, left atrial in II, and transseptal in seven patients. Associated procedures included coronary artery bypass grafting in one, mitral valve repair with tricuspid annuloplasty in two patients, mitral valve replacement in one and bilateral femoral embolectomy in one patient. One hospital mortality occurred as a result of multiorgan failure in a patient with peripheral embolization. None of the patients required recurrent operation, however, mitral valve insufficiency was surgically corrected in one patient.

Childhood mediastinal masses in infants and children.

We reviewed all cases of primary pediatric mediastinal masses diagnosed and treated over a 24-year period. In this study, out of 187 primary mediastinal mass cases diagnosed between 1980 and 2004 in Istanbul University Istanbul Faculty of Medicine, Cardiovascular Surgery Department, 37 pediatric primary mediastinal mass cases were retrospectively evaluated according to age, sex, symptoms, diagnostic procedure, anatomical location, surgical treatment, histopathological evaluation and postoperative adjuvant therapy. The patients ranged in age from 2 months to 15 years at the time of diagnosis, with a mean age of 8 years. There were 24 benign (64.8%) and 13 malignant (35.2%) tumors. The cases were lymphoma (27%), neurogenic tumors (21.6%), cystic lesions (18.9%), germ cell tumors (13.5%), thymic lesions (10.8%) and cardiac tumors (8.1%). Complete and partial resections of the tumor were the surgical procedures performed in 24 patients (64.8%) and 3 patients (8.1%), respectively. The three patients with a malignant tumor, in whom the entire mass could not be removed, received chemotherapy and radiation after surgery. In 10 patients with lymphoma, surgery was not a part of treatment and they received medical and radiation therapy after the establishment of the definitive diagnosis. All patients survived and were discharged from the hospital. Except for the cases with lyphoma, all patients are now free of recurrent disease. Compared to adults, children had more lymphomas and neurogenic tumors. Primary pediatric mediastinal malignancies are relatively common in infants and children. Lymphoma, neurogenic tumors and cystic lesions predominated. These differences between the age groups should also be considered when dealing with a mediastinal mass.

Iatrogenic coarctation after coil occlusion of arterial duct.

Coil occlusion of a patent ductus arteriosus was performed in an 8.5-month-old girl with a large left-to-right shunt through a wide arterial duct. Post-occlusion echocardiography revealed iatrogenic obstruction of the aorta caused by protrusion of the loops of the Jackson coil into the descending aorta. The problem resolved spontaneously during follow-up.

Primary endobronchial schwannoma.

Primary intrabronchial neurilemmas, also called schwannomas, are extremely rare tumors that originate from Schwann cells. We report a case of intrabronchial schwannoma arising in the left main bronchus in an 8-year-old child. The diagnosis was made by bronchofiberscopic biopsy. Although the tumor was benign, the patient was subjected to left pneumonectomy because of destruction of the pulmonary parenchyma distal to the obstruction. The diagnosis of intrabronchial schwannoma was supported pathologically with characteristic findings on Antoni A and Antoni B areas. This case is unique in that it is the youngest case in the literature.

Echocardiographic diagnosis of a giant thrombus passing through a patent foramen ovale from right atrium to the left atrium.

Pulmonary embolus sourced by right atrial thrombus trapped in a patent foramen ovale is an unusual, rare condition. Thus in suspicion of massive pulmonary thromboembolus, echocardiographic examination carries great importance evaluate right ventricular functions and diagnose right sided intracardiac thrombus. We report a 76-year-old female with massive pulmonary embolism caused by a gigantic thrombus trapped in a patent foramen ovale. The echocardiography was the diagnostic procedure to display the source of the thromboembolism and urgent cardiac surgery was successful and life-saving treatment in this case.

Left-sided aortic arch, right-sided descending aorta, and right-sided arterial duct associated with interruption of the aortic arch and presence of Abbott's artery.

We describe a male infant, seen at the age of 10 days, with a very rare form of vascular ring. The aortic arch was left-sided, but the aorta descended on the right, with a right-sided persistently patent arterial duct associated with interruption of the aortic arch and presence of Abbott's artery. We performed end-to-side anastomosis of the descending aorta to the ascending aorta, divided the Abbott's artery and the right-sided arterial duct, and banded the pulmonary trunk. Despite our best efforts, the patient died on the eighth day after the surgical intervention.

Successful bleomycin pleurodesis in a patient with prolonged pleural effusion after extracardiac fontan procedure.

Pleural effusions after modified Fontan operations are unpredictable and contribute significantly to the morbidity and prolonged hospitalization. Chemical pleurodesis is widely performed in adults for malignant pleural effusions, but has found less chance of usage for benign cases or the cases with unidentified etiology. Although it is a safe and easily performed procedure, the use of bleomycin for the treatment of pleural effusions in the pediatric age population has been rarely reported in the literature. In this manuscript, we present a case with prolonged pleural effusion after extracardiac Fontan operation, which was successfully treated with bleomycin pleurodesis.

Serum lactate level has prognostic significance after pediatric cardiac surgery.

OBJECTIVE: The determination of postoperative course after cardiac surgery has always been a challenging issue. It is more sophisticated in the pediatric age group. The aim of this investigation was to identify whether increased concentrations of lactate in arterial blood has a predictive value for postoperative morbidity and mortality after heart surgery. METHODS: From May 2002 to June 2003, 60 infants operated on at the authors' institution were included in this prospective study. The patients were divided into 2 groups according to their respective postoperative serum lactate values. After the stabilization period in the intensive care unit (first 3 hours postoperatively), samples for serum lactate were obtained from arterial blood at 3 (t1), 6 (t2), and 12 hours (t3) postoperatively. The patients were subdivided into 2 groups according to their respective mean serum lactate values. A value of 4.8 mmol/L (3 times the normal upper limit) was chosen as a threshold for serum lactate. The patients with a mean value of greater than 4.8 mmol/L (group 1) were compared with the remaining group of patients (group 2). The relationship between serum mean lactate level and intraoperative and postoperative clinical variables was evaluated. RESULTS: Among the patients in this study, 26 (43.3%) had a serum mean lactate level more than 4.8 mmol/L and 34 (56.7%) had a level of 4.8 mmol/L or less. Age, aortic cross-clamping time, cardiopulmonary bypass time, and the lowest hematocrit during cardiopulmonary bypass were significant variables that influenced the postoperative serum mean lactate level. Six patients died in the postoperative period and 54 infants survived. The hospital mortality was significantly higher in group 1 than in group 2 (19.0% v 2.9%; p = 0.037, kappa = 0.179). Multivariate analysis revealed that serum mean lactate level correlated significantly with inotrope score, intubation time, and intensive care unit stay. CONCLUSIONS: Blood lactate concentration of 4.8 mmol/L or higher during the early postoperative hours identifies a group of patients with increased risk of postoperative morbidity and mortality.

Idiopathic aneurysm of the inferior caval vein.

Idiopathic aneurysms of the inferior caval vein are uncommon in children and adults. We describe a 14 year old boy with a saccular aneurysm of the inferior caval vein, in whom no surgical intervention was required to repair the aneurysm. The patient is being followed-up periodically for the evaluation of any increase in the diameter of the inferior caval vein.

Results of surgical treatment for infective endocarditis in children.

OBJECTIVE: Infective endocarditis is uncommon condition, with a high degree of morbidity and mortality. It is less common in children, albeit tending to be associated with congenital cardiac malformations. We describe our experience of the need for surgical treatment in children with infective endocarditis. PATIENTS AND METHODS: We analyzed retrospectively the records of 9 children aged below 16 years seen between May 2003 and March 2005 with infective endocarditis, reviewing the demographic details, clinical presentation, microbiological and echocardiographic data, operative findings, and outcome. RESULTS: Apart from pre-existing renal insufficiency in 1 patient, congenital cardiac malformations were the predisposing factors. Blood cultures were positive in 3, but remained negative in the other 6 patients. The indications for surgical treatment included uncontrolled sepsis, congestive heart failure, recurrent endocarditis, patch or graft dehiscence, and pseudoaneursymal formation. Death due to uncontrolled sepsis resulting in multiorgan failure occurred in 1 patient, who had tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries. Another patient died late postoperatively due to cardiac failure after relapse of the endocarditis in the setting of negative blood cultures. CONCLUSION: Despite advances in antimicrobial therapy, diagnosis, and measures of treatment for infective endocarditis, complications continue to be responsible for substantial morbidity and mortality. Since blood cultures are frequently negative, clinical and echocardiographic findings should be the major determinants of strategies used for treatment. We believe that our small series of patients seen over the past two years in which surgical treatment was performed will be helpful in guiding the clinical perspectives for children with infective endocarditis.

Epitheloid hemangioendothelioma of the heart in infancy.

We report a case of primary cardiac epithelioid hemangioendothelioma arising from the right atrium of a 2-month-old infant. The tumor was found incidentally during exploratory sternotomy for recurrent pericardial effusion. This case represents a very rare situation, because this is the youngest patient found in relevant literature, and because it involves extensive infiltration by the tumor without any development of intracardiac mass appearance.

Antiphospholipid syndrome in a child: an insight into the pathology, identification, and means of cure.

Antiphospholipid syndrome (APS) has been well defined in adults; however, primary nontraumatic arterial thrombosis owing to this entity is unusual in the pediatric population. The authors report a case of APS with lower extremity arterial thrombosis who had discolored feet since delivery.

Cardiac and other malformations in parapagus twins.

INTRODUCTION: Conjoined twins occur in one 50-200,000 live births and approximately 75% of all cases are thoracopagus twins. Parapagus conjoined twins are rare and are not included in many review articles. CASE REPORT: The cardiovascular system of a male parapagus (dicephalus, tetrabrachius, dipus) conjoined twins was studied. Twin B had bilateral bilobed lungs and a normal heart, while bilateral trilobed lungs and right isomerism was found in twin A. They shared a diaphragm and an abdominal cavity. There were two complete heads on two necks, two thoraxes, one abdomen, four arms, two legs, two complete vertebral columns, a single pelvis, and severe cardiac abnormalities.

Results of surgical treatment for nonthymomatous myasthenia gravis.

PURPOSE: To clarify the factors that influence improvement and remission after thymectomy for patients with nonthymomatous myasthenia gravis (MG). METHODS: We retrospectively reviewed 204 patients with nonthymomatous MG who underwent thymectomy and anterior mediastinal dissection through a partial median sternotomy, between 1980 and 2001, and examined whether age, sex, preoperative classification, and duration of symptoms influenced their prognosis. RESULTS: There was no perioperative or hospital mortality. The mean follow-up period was 7.2 +/- 1.2 years, with early and late postoperative remission rates of 44.6% and 73%, respectively. Seven patients died; two from pneumonia and five from causes unrelated to MG. Preoperative treatment and classification, duration of symptoms, age, and sex did not seem to have a significant influence on remission, but the response to thymectomy was greater in patients with thymic hyperplasia. Remission and improvement rates were significantly better at the end of the first year, with the same status found at the last follow-up. CONCLUSION: Thymectomy is an effective and highly curative method of treatment for patients. with MG. It provides excellent symptomatic improvement, which is enhanced over the long term.