[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.

Multicentre study of fetal cardiac time intervals using magnetocardiography.

OBJECTIVE: A database with reference values of the durations of the various waveforms in a magnetocardiogram of fetuses in uncomplicated pregnancies is assessed. This database will be of help to discriminate between pathologic and healthy fetuses. A fetal magnetocardiogram is a recording of the magnetic field in a location near the maternal abdomen and reflects the electric activity within the fetal heart. It is a non-invasive method, which can be used with nearly 100% reliability from the 20th week of gestation onward. DESIGN: Durations of the waveforms were assembled from averaged magnetocardiograms and statistically processed. SETTING: Fetal magnetocardiograms were measured with different magnetocardiographs. All measurements were carried out in magnetically shielded rooms. SAMPLE: Fetal magnetocardiograms were obtained for 582 healthy patients. METHOD: The durations of the waveforms were extracted from fetal magnetocardiograms measured at the cooperating centres. The variables collected included the duration of the P-wave, the PR interval, the PQ interval, the QRS complex, the QT interval and the T-wave and QTc value. The results were compared with values extracted from electrocardiograms of fetuses measured via electrodes attached to the maternal abdomen, from electrocardiograms measured during labour using a scalp electrode, and from electrocardiograms recorded in newborns, that were found in the literature. MAIN OUTCOME MEASURES: Values of the durations are given as a function of gestational age including the regression line as well as the bounds marking the 90%, 95% and 98% prediction interval. RESULTS: The durations of the P-wave, the PR interval, the QRS complex, the QT interval and QTc value increase linearly with gestational age. The durations of the PQ interval and the T-wave are independent of fetal age. CONCLUSION: The values found agree with those found in the literature. The scatter of the data is wide due to the variation in normal physiology, the measuring system and signal processing and the subjectivity of the researcher. However, the system can define normal ranges and may be used in diagnosis.

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.

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.

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.

Conservative treatment of hemolytic complication following coil embolization in two adult cases of patent ductus arteriosus.

Two adult cases of relatively large patent ductus arteriosus (PDA) were treated by coil embolization, but were complicated by hemolysis that was successfully managed by medical treatment. Case 1 was a 67-year-old woman and Case 2 was a 71-year-old woman with a PDA of minimal diameter of 5.3 mm and 5.5 mm, respectively. The approach was via the pulmonary artery and 2 coils were delivered simultaneously into the ductus, known as the 'kissing coil technique'. Although immediately after the procedure only a small residual shunt was revealed by aortogram, hemolysis occurred for several hours after the procedure in both cases. A hemolytic complication usually needs additional coil embolization or surgical treatment, but in these 2 cases it was successfully treated by haptoglobin infusion to prevent nephropathy and by antiplasmin infusion to promote thrombus formation. Hemolytic complications of coil embolization of PDA can managed by medication when the residual shunt is minimal and the degree of hemolysis is mild.

Detection of cardiac hypertrophy in the fetus by approximation of the current dipole using magnetocardiography.

To determine the developmental changes in the myocardial current during fetal life, and to evaluate the clinical usefulness of magnetocardiography for prenatal diagnosis of cardiac hypertrophy or enlargement, we approximated the magnitude of the one-current dipole of the fetal heart using fetal magnetocardiography (fMCG). A total of 95 fetuses with gestational age of 20-40 wk were included in this study. fMCG was recorded with a nine-channel superconducting quantum interference device system in a magnetically shielded room. The magnitude of the dipole (Q) was calculated using an equation based on the fMCG amplitude obtained on the maternal abdomen and the distance between the maternal surface and fetal heart measured ultrasonographically. In uncomplicated pregnancies, the Q value correlated significantly with gestational age, reflecting an increase in the amount of myocardial current, i.e. myocardial mass. Moreover, the Q values in fetuses with cardiomegaly caused by various cardiovascular abnormalities tended to be higher than the normal values. Although there are some limitations of the methodology based on the half-space model, and fetal orientation may influence the magnitude of the dipole, making it smaller, fMCG recorded with a multichannel superconducting quantum interference device system is a clinically useful tool for noninvasive, prenatal, and electrical evaluation of fetal cardiac hypertrophy.

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.

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.

Percutaneous radio-frequency ablation therapy using a clustered electrode for malignant liver tumors.

GOALS: To examine the safety and effectiveness of percutaneous radio-frequency ablation therapy (PRAT) for malignant liver tumors, using a needle with cluster radio-frequency (RF) electrodes. STUDY: The subjects were 13 patients with solitary malignant liver tumors: 10 had hepatocellular carcinoma and 3 had metastatic liver tumors. One session of PRAT with cluster RF electrodes was performed until roll-off occurred two times. Dynamic computed tomography (CT) and fine needle tumor biopsy under ultrasonographic guidance were conducted to assess the therapeutic efficacy. Aspartate aminotransferase, alanine aminotransferase, lactic dehydrogenase, and total bilirubin were evaluated before and 1, 3, and 7 days after PRAT. RESULTS: There were no serious complications. Aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels peaked 1 day after PRAT and decreased thereafter. No icterus occurred. Of the 13 tumors, 12 showed complete necrosis on dynamic CT; however, one of them showed histologically incomplete necrosis in the tumor biopsy. In both of the ineffective cases, the tumors were located near relatively large vessels. There was no recurrence in the liver in all cases of PRAT that were effective (observation periods: 6--14 months; mean, 10 months). CONCLUSIONS: Percutaneous radio-frequency ablation therapy using a clustered electrode is a safe and effective treatment of malignant liver tumors, if the tumor is not located near the large vessels.

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.

Magnolol from Magnolia officinalis inhibits 11beta-hydroxysteroid dehydrogenase without increases of corticosterone and thymocyte apoptosis in mice.

Magnolol is an 11beta-hydroxysteroid dehydrogenase (11beta-HSD) inhibitor contained in Magnolia officinalis which is used in Chinese remedies. We have reported that glycyrrhetinic acid, a strong 11beta-HSD inhibitor isolated from licorice, induces apoptosis of murine thymocytes via accumulation of corticosterone. In this paper, we report that magnolol inhibited 11beta-HSD without increases in the blood concentration of corticosterone and in thymocyte apoptosis in mice. Oxidative activities of the enzyme (from corticosterone to 11-dehydrocorticosterone) in liver, kidney and thymus in vitro were examined 24 h after a single administration of magnolol. Magnolol inhibited the enzyme activity in kidney (P < 0.0001) and thymus (P < 0.002), while the activity in liver was not affected. Blood concentrations of corticosterone in the magnolol-treated mice were unexpectedly lower than those in the control animals (P < 0.002). This means that the inhibition of 11beta-HSD by magnolol did not increase the systemic level of corticosterone which is relevant to thymocyte apoptosis. Accordingly, our flow cytometric analysis of thymocytes after magnolol treatment showed no change in the number of apoptotic cells. We concluded that unlike glycyrrhetinic acid, magnolol selectively inhibited 11beta-HSD in kidney and thymus but not in liver, so that the blood concentrations of corticosterone could not exceed the control level.

Glycyrrhetinic acid induced apoptosis in murine splenocytes.

Glycyrrhetinic acid (GA) is known to inhibit glucocorticoid metabolism inhibiting 11beta-hydroxysteroid dehydrogenase (11beta-HSD). Moreover, GA administration to mice has been shown to affect the lymphoid organs through elevation of endogenous corticosterone concentration. The effect of GA administration on thymus has been demonstrated to show that considerable amounts of thymocytes undergo apoptosis by elevated levels of corticosterone in systemic circulation. However, the effect of GA administration on peripheral lymphocytes has remained unknown. In our current study, we demonstrated that a significant involution of spleen as well as thymus occurred within 24 h of a single administration of GA in mice. In addition, a flow cytometric analysis of the splenocytes taken from mice treated with GA showed a significant increase in the number of apoptotic cells which exhibited translocated phosphatidylserine outside the plasma membrane. Furthermore, considerable inhibition of 11beta-HSD activity in GA-treated mice was observed in liver and spleen, resulting in a significant increase in concentration of corticosterone in the blood. These facts showed that the apoptosis of splenocytes was the result of indirect effect of GA through elevated levels of corticosterone. We confirmed this using cultured splenocytes in vitro where no apoptotic effect of GA was observed. We concluded that GA administration induces cell death of not only thymocytes that are naive to corticosterone, but also splenocytes that are usually stable to its physiological concentrations.

Signal-averaged electrocardiogram in children and adolescents with insulin-dependent diabetes mellitus.

UNLABELLED: We report on the potential usefulness of the signal-averaged electrocardiogram (SA-ECG) in young patients with insulin-dependent diabetes mellitus (IDDM) to predict subclinical cardiovascular complications. Sixteen patients with IDDM and 18 age-matched healthy subjects were studied. The IDDM group included 4 males and 12 females, aged 7 to 20 y (mean 14.2 +/- 3.8 y, +/- SD). The duration from the onset of IDDM to the study ranged from 1.2 to 9.8 y (mean 5.4 +/- 3.8 y), and HbAlc value ranged from 6.6 to 12.4% (mean, 10.0 +/- 1.8%). SA-ECG was recorded and analyzed using the methods described by Simson. Values of filtered QRS duration (f-QRS), root mean square voltage (RMS), the duration of low amplitude signal (LAS) and late duration (LD) were calculated and compared between the groups. These parameters were not significantly different between the IDDM and control groups. However, in patients with poor glycemic control (HbAlc >10%), f-QRS was long and RMS was significantly low (p < 0.05, each) compared with the control group. Three patients with IDDM were positive for ventricular late potentials, although none had ventricular tachyarrhythmia. None of the control subjects showed ventricular late potentials. CONCLUSION: Certain parameters of SA-ECG showed abnormal values in IDDM patients with poor glycemic control. Thus, SA-ECG is a potentially useful and non-invasive method for the assessment of subclinical cardiac impairment in diabetic children and adolescents.