[Epicardial atrial pacing using an active fixation bipolar endocardial lead in children].

Good performance was observed over 10 years after implantation of bipolar epicardial atrial pacing using an active fixation bipolar endocardial lead in 3 pediatric patients with congenital heart block. The bipolar endocardial lead which was supposed to be fixed transvenously was implanted on the atrial surface by first screwing the lead's helix into the myocardium. The catheter was then laid down on the atrial surface, and both electrodes were wrapped by the atrial tissue. The good performance of this pacing lead seemed to depend on stable positioning of the electrode. This lead is superior to the commercially available, and steroid eluting epicardial bipolar pacing lead, on the point of its small size in head and body, and could be applied to dual chamber pacing in smaller children.

[Delayed onset malignant hyperthermia after a closure of ventricular septal defect].

An 18 month-old girl was diagnosed as ventricular septal defect (VSD) with mild aortic valve prolapse. She underwent a closure of VSD. Intra-and early postoperative course was uneventful. However, 20 hours after surgery, sudden bradycardia led to cardiac arrest and strong muscle rigidity was seen. Hyperkalemia and metabolic acidosis rapidly progressed and resuscitation was failed. Extracorporeal life support and continuous hemodialysis were initiated, but the patient died with multiple organ failure on 5th postoperative day. Her clinical course supported the diagnosis of delayed onset malignant hyperthermia. Histopathological findings of muscle biopsy were consistent with rhabdomyolysis, and immunopathological stains demonstrated changes as in a Duchenne type muscular dystrophy carrier. Delayed onset malignant hyperthermia is an extremely rare complication of general anesthesia. We should be aware of this lethal condition, which occurs with a certain time lag after surgery, especially when the patient has possible background of myopathy.

[Asplenia syndrome with total anomalous pulmonary venous connection].

Three patients of asplenia syndrome with total anomalous pulmonary venous connection (TAPVC) were reported. Case 1 with exceeding pulmonary blood flow, underwent TAPVC repair and pulmonary artery banding as a first palliation before bi-directional Glenn shunt. Case 2 did not require any surgery to control the pulmonary blood flow before the simultaneous procedure of TAPVC repair and bi-directional Glenn shunt. Case 3 with decreased pulmonary blood flow underwent a complicated course with 3 times of Blalock-Taussig shunts and the repair of TAPVC to prepare for bi-directional Glenn shunt. Simultaneous repair of TAPVC with the procedure which aimed to control the pulmonary blood flow at the first palliation surgery will simplify the control of pulmonary blood flow and prepare good condition of the lung for the Fontan operation in the future.

Interstitial deletion of the long arm of chromosome 6 associated with absent pulmonary valve.

We report on a newborn infant with a deletion of 6q and absent pulmonary valve. His chromosome constitution was 46,XY,del (6) (q15q21). To our knowledge this is the first case with such combination. Some of his clinical features were found in common in 2 previous 6q- cases with the same breakpoints.

Screening for 22q11 deletions in a schizophrenia population.

Since the recognition that adults with velocardiofacial syndrome (VCFS), which is associated with hemizygous interstitial deletions of chromosome 22q11, frequently show psychotic symptoms, deletion of the 22q11.2 region has been proposed as a common genetic abnormality associated with schizophrenia. In studies of schizophrenia patients, such deletions have been detected in more than 1% of schizophrenics, indicating the likely presence of this deletion in a significant number of patients. In this study, we screened for 22q11.2 deletions by genotyping microsatellite markers in 300 schizophrenics and 300 normal controls. The 22q11.2 deletion was confirmed by fluorescent in situ hybridization (FISH). One patient with schizophrenia was found to have a 22q11.2 deletion. The patient was mildly retarded but did not have craniofacial, palatal, or cardiac malformations characteristic of VCFS. Our results indicate that 22q11.2 deletion does not contribute substantially to the development of schizophrenia in general. However, our findings establish the existence of physically near-normal individuals with 22q11.2 deletion among learning disabled or mildly retarded persons with schizophrenia.

Therapeutic effect of glycyrrhetinic acid in MRL lpr/lpr mice: implications of alteration of corticosteroid metabolism.

Glycyrrhetinic acid (GA) inhibits 11beta-hydroxysteroid dehydrogenase and increases the levels and thus the action of endogenous glucocorticoid. We considered that GA could be used effectively for treatment of autoimmune diseases that have been treated by synthetic glucocorticoids. In this report, we demonstrated that GA delayed the development of autoimmune disease in spontaneously autoimmune strain MRL lpr/lpr (referred to as lpr) mice. GA was administered via drinking water at approximately 5 mg/kg/day for 170 days. An increase of urine protein levels in the mice treated with GA was delayed as compared to the control mice. After GA treatment began, urinary protein levels in the GA-treated mice were found to be significantly lower than vehicle-treated mice (p<0.05) between days 18 to 50. At 3 weeks of GA treatment serum IgG levels were lowered significantly in comparison with the control mice (p<0.03). In this circumstance, 11beta-HSD activities in liver and kidney were significantly inhibited by GA treatment (p<0.03, p<0.04 respectively). Concentration of corticosterone and dehydrocorticosterone in liver significantly increased after 3 weeks of GA treatment (p<0.02, p<0.01 respectively). In contrast to the local tissue levels of corticosteroids, the serum concentration of dehydrocorticosterone significantly decreased with GA treatment (p<0.02). These data suggest that GA could modify the local and systemic homeostasis of steroid metabolism in lpr mice. We concluded that the continuous treatment of GA is able to retard the development of autoimmune disease by suppressing urinary protein excretion and serum IgG levels in lpr mice. Modulation of local tissue levels as well as serum levels of corticosteroid by GA may thus be implicated in the therapeutic efficacy of GA.

Oxidized glucocorticoids counteract glucocorticoid-induced apoptosis in murine thymocytes in vitro.

11Beta-hydroxyglucocorticoids (HGCs) are known to induce apoptosis in immature T cells. Here we show that 11-oxoglucocorticoids (OGCs), which are oxidized metabolites of HGCs, counteract the apoptosis-inducing effects of HGC in murine thymocytes in vitro. Corticosterone at concentrations ranging from 0.1-100 microM induced apoptosis in thymocytes obtained from C57BL/6J mice aged 4 weeks, as demonstrated by cell staining with anti-phosphatidylserine antibody, a decrease in mitochondrial membrane potential, and DNA fragmentation. Co-culture of the cells with 10-100 microM of OGCs, dehydrocorticosterone, cortisone, and prednisone significantly inhibited thymocyte apoptosis induced by 1 microM corticosterone, (p<0.006). Among the other 6 physiological metabolites of the HGCs we tested, 20alpha-dehydrocortisol also showed considerable inhibitory effect on corticosterone-induced thymocyte apoptosis. Corticosterone-treatment of thymocytes in vitro decreased the number of CD4 and CD8 double positive cells, while co-culturing the cells with dehydrocorticosterone significantly attenuated this corticosterone effect (p<0.0001). Numbers of double-negative cells and single-positive cells were not significantly affected by corticosterone, dehydrocorticosterone, or both together. These results raised the possibility that OGCs and probably other HGC metabolites can regulate apoptotic cell death of immature double-positive thymocytes induced by HGC.

Sudden fatal cardiac arrest in a child with an unrecognized anterior mediastinal mass.

We report a case of sudden fatal cardiac arrest in a 3-year-old boy. The arrest occurred when he was placed in the supine position by force for a venipuncture. Autopsy revealed a large anterior mediastinal mass. The death was attributed to the airway obstruction and cardiac compression by the mass. Postural change to supine position by force was believed to have triggered compression of the cardiopulmonary system by an unrecognized anterior mediastinal mass, resulting in cardiac arrest.

Delayed onset of systemic lupus erythematosus in a child with endothelial tubuloreticular inclusion.

We report here on an 11-year-old Japanese girl who was found to have proteinuria by routine mass screening urinalysis for school children, and who developed systemic lupus erythematosus (SLE) 21 months later. The initial renal biopsy, performed 3 months after the first visit to Tokyo Medical University Kasumigaura Hospital (TMUKH), revealed membranous glomerulonephritis. In an immunofluorescent study, IgG was the only positive immunoglobulin found. A "full-house" immunofluorescence glomerulopathy, well known as a predictive finding for lupus nephritis, was not detected. Endothelial tubuloreticular inclusions (ETI) were found by electron microscopy. Because the diagnosis of SLE was not established clinically and serologically, the patient was followed every 3 months without drugs. Her urinary findings returned to normal within 18 months. Three months after the last visit, she was sent to Tsukuba University Hospital (TUH) for fever, arthralgia, dyspnea and butterfly rash. She was diagnosed as having SLE, pleuritis, and pericarditis. Although she was treated with methylpredonisolone and oral prednisolone, she developed cardiac tamponade on the 12th day of admission during the course of pneumococcal septicemia. Finally, she was treated successfully with surgical procedures, antibiotics and oral prednisolone and was discharged. We conclude that ETI is a more significant early sign of SLE than "full-house" immmunofluorescence glomerulopathy, especially in pediatric cases.

Prenatal diagnosis of QT prolongation by fetal magnetocardiogram--use of QRS and T-wave current-arrow maps.

To determine the T wave of a fetal magnetocardiogram (FMCG), we have evaluated the T/QRS ratio and obtained current-arrow maps that indicate weak currents. We measured FMCG signals for 52 normal fetuses and two abnormal fetuses with prolonged QT waves by using three superconducting quantum interference device (SQUID) systems: a nine-channel system, a 12-channel vector system and a 64-channel system. The T/QRS ratio was calculated for all the normal fetuses from the maximum magnitudes of the QRS complex and the T wave. Current-arrow maps of the QRS complex (R wave) and T wave were obtained by using the 64-channel system, and the phase differences of the total-current vectors were calculated by using the current-arrow maps. The results showed that the T/QRS ratio had a wide variability of 0.35 for the normal fetuses. However, the magnitude of the prolonged T wave was as weak as the detection limit of the SQUID magnetometer. Although the T/QRS ratios for the fetuses with QT prolongation were within the normal range (< 0.35), the weak magnitude of the prolonged T wave could be evaluated. On the other hand, by comparing the current-arrow maps of the R and T waves for the normal fetuses, we found that the maximum-current arrows were indicated as either in the same direction or in opposite directions. These patterns could be identified clearly by the phase differences. Very weak prolonged T waves for the two abnormal fetuses could be determined by using these current-arrow maps and phase differences. Consequently, although the T/QRS ratios of FMCG signals have a wide distribution, we have concluded that the current-arrow map and phase difference can be used to determine the T wave of an FMCG signal.

Coexistence of primary biliary cirrhosis and myasthenia gravis: a case study.

We present a case that suggests a relationship between primary biliary cirrhosis and myasthenia gravis. A 43-year-old Japanese woman was admitted to the Nagoya City University Medical School, First Department of Internal Medicine with abnormal liver function in August 1991. She had had ptosis of the right eye since 1990. She had not been treated for liver disease. Ptosis of the right eye and hepatomegaly were present. Serum laboratory examinations revealed elevated biliary enzymes and IgM levels; tests were positive for antimitochondrial antibody and antiacetylcholine antibody. Liver histology revealed chronic non-suppurative destructive cholangitis and led to a diagnosis of primary biliary cirrhosis. The tensilon test was positive. Electromyography with repetitive motor nerve stimulation revealed a neuromuscular junction defect; i.e., the primary characteristic of myasthenia gravis. The patient was diagnosed with myasthenia gravis. Although the development of myasthenia gravis has previously been reported in patients with primary biliary cirrhosis during D-penicillamine administration, this is a very rare case of the coexistence of both diseases before such treatment.

Diagnosis of small hepatocellular carcinoma--imaging diagnosis and significance of tumor biopsy.

BACKGROUND/AIMS: To compare the effectiveness of different imaging modalities and the significance of tumor biopsy for diagnosing small hepatocellular carcinoma. METHODOLOGY: Nodules (n = 352) with diameters of 30 mm or less newly detected by periodic ultrasonography and computed tomography in 234 patients with chronic liver disease were investigated with magnetic resonance imaging and digital subtraction angiography. These findings were compared with histologic findings. Histologic diagnoses were dysplastic nodule (n = 23), well-differentiated hepatocellular carcinoma (n = 163), moderately differentiated hepatocellular carcinoma (n = 159), and poorly differentiated hepatocellular carcinoma (n = 7). We compared three groups based on-diameters of 10, 11-20, and 21-30 mm. Nodules were diagnosed as hepatocellular carcinoma if they had hypervascular staining on digital subtraction angiography, hyperintensity on magnetic resonance T2-weighted images, arterial phase enhancement on enhanced magnetic resonance imaging, or low-high-low density on enhanced computed tomography. RESULTS: Imaging alone was sufficient to diagnose hepatocellular carcinoma in 66.3% of the well-differentiated nodules and 91.6% of the moderately and poorly differentiated nodules (P < 0.001) The size of the nodule influenced the diagnosis of hepatocellular carcinoma by imaging alone in 65.5% (< or = 10 mm), 77.2% (11-20 mm), and 92.3% (21-30 mm) (< or = 10 vs. 21-30: P < 0.0001, 11-20 vs. 21-30: P < 0.0005). It was impossible to determine the degree of differentiation of the hepatocellular carcinoma by imaging alone. CONCLUSIONS: The effectiveness of imaging for the diagnosis of hepatocellular carcinoma improved with decreasing differentiation and increasing diameter of the nodules. Tumor biopsy was required to make a histological accurate diagnosis.

Percutaneous radiofrequency ablation therapy using a clustered electrode in the animal liver.

BACKGROUND/AIMS: The aim of the present study was to examine the safety and effectiveness of percutaneous radiofrequency ablation therapy using a needle with cluster radiofrequency electrodes in an animal model. METHODOLOGY: A total of 10 radiofrequency applications were performed in the normal liver of 5 domestic pigs with real-time ultrasonography until roll-off occurred two times. Aspartate aminotransferase, alanine aminotransferase, lactic dehydrogenase, and total bilirubin were evaluated before the procedure and 1 h, 24 h, and 7 days following percutaneous radiofrequency ablation therapy. The animals were euthanized 1 or 2 weeks after percutaneous radiofrequency ablation therapy, and the livers were removed for gross and histopathologic analysis for coagulation necrosis. RESULTS: There were no complications in any of the experimental animals. Aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels peaked 24 h following percutaneous radiofrequency ablation therapy, and decreased with time thereafter. Total bilirubin was not elevated in any of the animals at any time. Macroscopic examination revealed that the area of coagulated necrosis was 28 x 21 mm when using a 2.0-cm needle, and 41 x 35 mm when using a 3.5-cm needle. Coagulation necrosis did not occur near large vessels. Microscopic examination of the fixed tissue revealed that coagulation necrosis occurred in preserving lobular structure. CONCLUSIONS: Percutaneous radiofrequency ablation therapy using a clustered electrode is a safe and effective treatment for liver tumor. Incomplete coagulation necrosis, however, can occur when percutaneous radiofrequency ablation therapy is performed for tumors located near large vessels.

Treatment of solitary small hepatocellular carcinoma: consideration of hepatic functional reserve and mode of recurrence.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) recurs frequently after initial treatment. The subsequent prognosis varies with the mode of recurrence. Some patients die of hepatic failure even though the HCC is controlled. We consider the clinical stage (CS), using the modified Child-Pugh classification, to be an important factor influencing the prognosis of these patients. METHODOLOGY: To determine the most effective treatment for HCC, we examined 105 patients with solitary small HCC who were followed-up for more than 1 year after initial treatment. All of them were judged to be cured according to imaging or histological studies. The initial treatments were hepatic resection (n = 43), percutaneous ethanol injection therapy (PEIT, n = 33), and percutaneous microwave coagulation therapy (PMCT, n = 29). The modes of recurrence were divided into intrahepatic metastasis (IM) and multicentric occurrence (MO). RESULTS: Prognosis of MO was superior to that of IM in CS I patients, but there was no difference in prognosis between these modes in CS II. The hepatic resection group had more MO recurrences in CS I patients and more IM recurrences in CS II patients. IM developed frequently after PEIT and PMCT, regardless of the CS. Prognosis with hepatic resection was superior to that of the other treatments in CS I patients, but there was no difference in prognosis among the 3 treatment modalities in CS II patients. CONCLUSIONS: These data indicate that hepatic resection is the first choice for treating HCC in CS I patients, and that PEIT or PMCT is preferable for CS II patients.

Endoscopic injection sclerotherapy for esophagogastric variceal bleeding in children with biliary atresia.

BACKGROUND/AIMS: To determine the safety and effectiveness of endoscopic injection sclerotherapy (EIS) for children with biliary atresia. METHODOLOGY: Subjects were 7 patients with biliary atresia with esophagogastric varices and variceal bleeding. Intravariceal injection using 5% ethanolamine oleate was performed under fluoroscopy until varices were eradicated. RESULTS: Endoscopic examination revealed that bleeding occurred in the junctional gastric varices in most of the cases. The mean number of EIS sessions required for obliteration of the varices was 2.3. In the observation period (mean: 21 months), recurrent esophagogastric varices occurred in 2 patients. One had variceal bleeding that was treated successfully by additional EIS. There were no severe complications associated with EIS. CONCLUSIONS: EIS under fluoroscopy was safe and effective for variceal bleeding in children with biliary atresia.

Sensitivity of foetal magnetocardiograms versus gestation week.

Foetal magnetocardiograms (FMCGs) were measured using a nine-channel SQUID system equipped with first-order gradiometers (60 mm baseline, 20 mm diameter). The system was installed in a magnetically shielded room in a hospital. The white noise level was less than 10 fT/square root of Hz, and FMCGs above 1 pT were detected. These results and the depth to the foetal heart were used to estimate the current dipole. The relationship between the current dipole (Q) and the gestation week (G) was calculated and the average performance was determined as Q = 18G - 295. By using the estimated foetal current dipole, the measurement limit (average value) between depth and gestation weeks was determined. When the depth from the pickup coil to the foetal heart is 50, 60, 70 and 80 mm, the first detectable gestation weeks of FMCGs above 1 pT measured by a first-order gradiometer with 60 mm baseline were determined at 21, 23, 26, and 30 weeks respectively, and the detectable gestation weeks in the case of a 30 mm baseline were determined at 22, 26, 30 and 36 weeks respectively.

Right ventricular volume unloading evaluated by tangential magnetocardiography.

OBJECTIVE: The evaluation of right ventricular volume overload in the presence of a right bundle branch block based solely on the results of an electrocardiogram is difficult. The purpose of this study was to purify acute right ventricular volume unloading from the tangential magnetocardiography. METHODS: We measured the tangential (x-y plane) magnetocardiogram and electrocardiogram simultaneously in nine patients with a secundum atrial septal defect. The magnetocardiograms were obtained before surgical closure and during the immediate postoperative period using the 32-channel superconducting quantum interference device system in a magnetically shielded room. RESULTS: The QRS duration on the surface electrocardiogram decreased significantly (p < 0.05) in the immediate postoperative period. The right ventricular depolarization time as measured by the magnetocardiogram was shortened from 40.3 +/- 6.1 to 25.3 +/- 7.4 milliseconds (p < 0.0005). The maximum peak amplitude during right ventricular depolarization decreased from 17.9 +/- 4.8 to 11.1 +/- 4.9 pT (p < 0.01). CONCLUSIONS: We conclude that acute volume unloading of the right ventricle was indicated quantitatively by shortening of the right ventricular depolarization time and a reduction in the amplitude of current vectors originating from the right ventricular depolarization on the tangential magnetocardiography.

Persistent fifth aortic arch associated with type A aortic arch interruption. Histological study and morphogenesis.

A male infant, having a persistent fifth aortic arch and interruption of the aorta distal to the left subclavian artery, underwent successful surgical treatment. A histological study of the excised segment of the aorta showed that the ductal tissue extended to the junction between the fifth arch and the descending aorta with consequent narrowing in the corresponding region. The ductal tissue, however, did not contribute to occlusion in the fourth aortic arch. The morphogenesis of this combination of aortic arch anomalies was also discussed.

[Anomalous origin of the left coronary artery from the pulmonary trunk with myocardial infarction and severe left ventricular dysfunction in infancy--assessment of myocardial damage using SPECT studies with 201TlCl and 123I-BMIPP].

A 4-month-old male infant with Bland-White-Garland (BWG) syndrome complicated myocardial infarction was reported. Signs included tachypnea, coughing, and failure to thrive. However, there was no sign of myocardial infarction. A chest radiograph revealed cardiomegaly (CTR = 65%) and electrocardiogram showed abnormal Q waves in I, aVL, V6 leads. Cardiac catheterization and angiography revealed marked dilatation of left ventricle (end-diastolic volume = 384 ml/m2) and extremely depressed ejection fraction (16%), confirming the diagnosis of BWG syndrome. A 201TlCl-myocardial SPECT demonstrated apical defect and hypoperfusion in the anterolateral, inferoposterior walls, whereas 123I-beta-methyl-p-iodophenylpentadecanoic-acid (123I-BMIPP) SPECT showed a wider defect area. SPECT studies with 201TlCl and 123I-BMIPP, are useful to assess myocardial viability more accurately in BWG syndrome.

[Postoperative bronchial stenosis associated with IAA complex and transendoscopic resection of intrabronchial granulation].

Problem with stenosis of the left bronchus was encountered in a patient with type B interrupted aortic arch complex after the arch reconstruction and pulmonary artery banding. Bronchoscopic study disclosed the intraluminal granulation of left bronchus and transendoscopic resection of the granulation successfully relieved the stenosis and brought the patient to full recovery.