An open-label randomized controlled study of pegylated interferon/ribavirin combination therapy for chronic hepatitis C with versus without fluvastatin.

Pegylated interferon (PEG-IFN)/ribavirin combination therapy is the standard-of-care (SOC) treatment for chronic hepatitis C patients infected with hepatitis C virus (HCV) genotype 1b and high viral load. The addition of fluvastatin to SOC treatment has been suggested to be effective for better outcome in retrospective pilot analyses. We investigated whether the combination of fluvastatin with PEG-IFN/ribavirin could actually improve sustained viral response (SVR) in patients with HCV genotype 1b and high viral load. A randomized, open-labeled, controlled study was conducted between July 2008 and December 2009 in 101 chronic hepatitis C patients allocated to PEG-IFN/ribavirin combination therapy with or without fluvastatin. SVR rates were calculated in groups, stratifying host and viral factors. We also analyzed predictive factors for SVR among patients on fluvastatin with multivariate regression analysis. Rapid and early virological, and end of treatment response rates in the fluvastatin group were not significantly different from those in the non-fluvastatin group. Notwithstanding, SVR rate was significantly higher in the fluvastatin group than in the non-fluvastatin group (63.0%vs 41.7%, P = 0.0422). Comparison of the two groups stratifying demographic data and HCV characteristics showed significantly higher SVR rates to more than 80% in males, more than two mutations in the interferon sensitivity determining region (ISDR), and a history of relapse among the fluvastatin group than the non-fluvastatin group. Being male and major genotype IL28B single nucleotide polymorphisms (SNPs) were independent predictive factors for SVR among patients on fluvastatin with multivariate analysis. Fluvastatin-combined with PEG-IFN/ribavirin therapy significantly improves SVR rates in patients with HCV genotype 1b and high viral load. Male and major genotype IL28B SNPs were independent predictors for SVR among patients on fluvastatin combination therapy.

Involvement of the Thalamus, Hippocampus, and Brainstem in Hypsarrhythmia of West Syndrome: Simultaneous Recordings of Electroencephalography and fMRI Study.

BACKGROUND AND PURPOSE: West syndrome is a developmental and epileptic encephalopathy characterized by epileptic spasms, neurodevelopmental regression, and a specific EEG pattern called hypsarrhythmia. Our aim was to investigate the brain activities related to hypsarrhythmia at onset and focal epileptiform discharges in the remote period in children with West syndrome using simultaneous electroencephalography and fMRI recordings. MATERIALS AND METHODS: Fourteen children with West syndrome underwent simultaneous electroencephalography and fMRI at the onset of West syndrome. Statistically significant blood oxygen level-dependent responses related to hypsarrhythmia were analyzed using an event-related design of 4 hemodynamic response functions with peaks at 3, 5, 7, and 9 seconds after the onset of each event. Six of 14 children had focal epileptiform discharges after treatment and underwent simultaneous electroencephalography and fMRI from 12 to 25 months of age. RESULTS: At onset, positive blood oxygen level-dependent responses were seen in the brainstem (14/14 patients), thalami (13/14), basal ganglia (13/14), and hippocampi (13/14), in addition to multiple cerebral cortices. Group analysis using hemodynamic response functions with peaks at 3, 5, and 7 seconds showed positive blood oxygen level-dependent responses in the brainstem, thalamus, and hippocampus, while positive blood oxygen level-dependent responses in multiple cerebral cortices were seen using hemodynamic response functions with peaks at 5 and 7 seconds. In the remote period, 3 of 6 children had focal epileptiform discharge-related positive blood oxygen level-dependent responses in the thalamus, hippocampus, and brainstem. CONCLUSIONS: Positive blood oxygen level-dependent responses with hypsarrhythmia appeared in the brainstem, thalamus, and hippocampus on earlier hemodynamic response functions than the cerebral cortices, suggesting the propagation of epileptogenic activities from the deep brain structures to the neocortices. Activation of the hippocampus, thalamus, and brainstem was still seen in half of the patients with focal epileptiform discharges after adrenocorticotropic hormone therapy.

Absent cyclicity on aEEG within the first 24 h is associated with brain damage in preterm infants.

OBJECTIVE: Our aim was to clarify the relationship between amplitude-integrated electroencephalographic (aEEG) findings before 24 h of age in preterm infants and neurodevelopmental outcome. DESIGN: 12 infants born between 27 and 32 weeks of gestation were eligible. The recordings of aEEG and conventional EEG were started within 12 h after birth. The background aEEG findings were evaluated and classified. Additionally, we evaluated the absence or presence of changes on the lower border of the aEEG. RESULTS: All infants had discontinuous normal voltage background on aEEG, corresponding to decreased or normal continuity on conventional EEG. Cyclicity on aEEG was seen in 8 of 12 infants within 24 h of age, and all of these infants had favourable outcomes. Cyclicity on aEEG was not recognized in 4 infants. 3 of the 4 infants with absent cyclicity had abnormal neurodevelopmental outcomes at 12 months. One of these infants had intraventricular haemorrhage (grade 2) with delayed development, and 2 had cystic periventricular leukomalacia followed by spastic diplegia. CONCLUSION: Absent cyclicity on aEEG within 24 h of age was associated with poor outcome in preterm infants.

Longitudinal Findings of MRI and PET in West Syndrome with Subtle Focal Cortical Dysplasia.

BACKGROUND AND PURPOSE: Despite the development of neuroimaging, identification of focal cortical dysplasia remains challenging. The purpose of this study was to show the longitudinal changes of MR imaging and FDG-PET in patients with West syndrome and subtle focal cortical dysplasia. MATERIALS AND METHODS: Among 52 consecutive patients with West syndrome, 4 were diagnosed with subtle focal cortical dysplasia on 3T MR imaging. MR imaging and PET findings were evaluated longitudinally at onset and at 12 and 24 months of age. RESULTS: At the onset of West syndrome, MR imaging demonstrated focal signal abnormalities of the subcortical white matter in 2 patients. In the other 2 patients, focal subcortical high-intensity signals became visible on follow-up T2WI as myelination progressed. PET at onset showed focal cortical hypometabolism in 3 patients, with 1 of these patients also having focal hypermetabolism and 1 having normal findings. On PET at 24 months, hypometabolism persisted in 2 patients and disappeared in 1, and hypermetabolism disappeared in 1. In 1 patient with normal MR imaging and PET findings at onset, focal hyperintensity and hypometabolism first appeared at 24 months of age. The findings on MR imaging and PET in these patients evolved differently with brain maturation and the clinical course. CONCLUSIONS: Subtle focal cortical dysplasia can be undetectable on MR imaging at the onset of West syndrome and is not always accompanied by hypometabolism or hypermetabolism on PET. Longitudinal MR imaging and PET studies may be useful for detecting such lesions. Even in West syndrome with a congenital structural abnormality, PET findings evolve differently with brain maturation and the clinical condition.

Predominant area of brain lesions in neonates with herpes simplex encephalitis.

OBJECTIVE: Nonspecific manifestations and a varied distribution of brain lesions can delay the diagnosis of herpes simplex encephalitis (HSE) in neonates. The aim of this study was to report predominant brain lesions in neonatal HSE, and then to investigate the association between pattern of predominant brain lesions, clinical variables and neurodevelopmental outcome. STUDY DESIGN: A multicenter retrospective study was performed in neonates diagnosed with HSE between 2009 and 2014. Magnetic resonance (MR) images, including diffusion-weighted images, were obtained in the acute and chronic phase. RESULTS: Three predominant areas of brain injury could be defined based on characteristic MRI findings in 10 of the 13 infants (77%). The inferior frontal/temporal pole area was involved in five (38%) patients. The watershed distribution was present in six (46%) patients. Four (31%) infants involved the corticospinal tract area. No significant association was found between any predominant distribution of brain lesion pattern and sex, country, viral type or viral load. However, the corticospinal tract involvement was significantly associated with motor impairment (P=0.045). CONCLUSION: Three predominant areas of brain lesion could be recognized in neonatal HSE. Recognition of those areas can improve prediction of neurodevelopmental outcome.

White Matter Abnormality Correlates with Developmental and Seizure Outcomes in West Syndrome of Unknown Etiology.

BACKGROUND AND PURPOSE: West syndrome is an epileptic encephalopathy characterized by epileptic spasms, a specific pattern on electroencephalography of hypsarrhythmia, and developmental regression. Our aim was to assess white matter abnormalities in West syndrome of unknown etiology. We hypothesized that diffusion tensor imaging reveals white matter abnormalities, especially in patients with poor seizure and developmental outcomes. MATERIALS AND METHODS: We enrolled 23 patients with new-onset West syndrome of unknown etiology. DTI was performed at 12 and 24 months of age. Fractional anisotropy images were compared with those of controls by using tract-based spatial statistics. We compared axial, radial, and mean diffusivity between patients and controls in the fractional anisotropy skeleton. We determined correlations of these parameters with developmental quotient, electroencephalography, and seizure outcomes. We also compared DTI with hypometabolism on fluorodeoxyglucose positron-emission tomography. RESULTS: At 12 months of age, patients showed widespread fractional anisotropy reductions and higher radial diffusivity in the fractional anisotropy skeleton with a significant difference on tract-based spatial statistics. The developmental quotient at 12 months of age correlated positively with fractional anisotropy and negatively with radial and mean diffusivity. Patients with seizure and abnormal findings on electroencephalography after initial treatments had lower fractional anisotropy and higher radial diffusivity. At 24 months, although tract-based spatial statistics did not show significant differences between patients and controls, tract-based spatial statistics in the 10 patients with a developmental quotient of <70 had significant fractional anisotropy reduction. In patients with unilateral temporal lobe hypometabolism on PET, tract-based spatial statistics showed greater fractional anisotropy reduction in the temporal lobe ipsilateral to the side of PET hypometabolism. CONCLUSIONS: Diffuse abnormal findings on DTI at 12 months of age suggest delayed myelination as a key factor underlying abnormal findings on DTI. Conversely, asymmetric abnormal findings on DTI at 24 months may reflect underlying focal pathologies.

Protective effect of hyperbaric oxygen for the temporary ischaemic myocardium. Macroscopic and histological data.

A protective effect of hyperbaric oxygen immediately after reopening of occluded coronary blood flow for the temporary ischaemic myocardial muscle was studied. Thirty dogs were used in this study, and 20 dogs were sacrificed after 4 h and 10 dogs were sacrificed after 5 d. Temporary occlusion of coronary artery (from 30 min to 2 h) was produced by ligation. One group were controls and the other group were a hyperbaric group in which dogs breathed 100% oxygen at an absolute pressure of 2 atmospheres before and after release of coronary ligation. The macroscopic extent of ischaemic area was studied by using nitroblue tetrazolium and microscopic and ECG findings were examined. By breathing oxygen at high pressure immediately after reopening of occluded coronary blood flow, the ischaemic area was markedly reduced. In such cases, some myocardial muscles around the arterioles and sinusoids, even when these vessels existed in the ischaemic area, were kept in a viable state. The repair of necrotic myocardial muscles was promoted histologically. Serious arrhythmia, especially ventricular fibrillation, was also well suppressed, and the stable haemodynamic conditions were obtained during operative procedures. No harmful side effects of hyperbaric oxygen were observed. One of the most effective treatments of acute myocardial infarction involves reconstruction of the occluded coronary artery as soon as possible after the onset of myocardial infarction by using these advantages of hyperbaric oxygen.

[A case of systemic lupus erythematosus showing abnormal lipoproteins due to accompanied drug induced hepatitis].

We describe here a 28-years-male with AIHA and SLE who had lipid and lipoprotein abnormalities during cholestasis induced by PGE1 administration. High free cholesterol level, 792 mg/dl was found in his serum, and markedly elevated, phospholipid level 1,614 mg/dl. But, LCAT activity was within normal range in this case. An agarose gel electrophoresis of lipoproteins showed abnormal bands which were located in slow alpha 2, pre beta and slow beta, and between beta and origin point. Moreover, it was detected formation of Lp-X from serum of the patient. Serum levels of apoprotein B, C-II, C-III, and E were higher, while apoprotein A-I, A-II were very lower than reference value. From these results, it was suspected that the patient might occur transient abnormal lipid metabolism according to the drug induced hepatic injury.

[A case of cardiac lipoma in the ventricular septum].

A 45-year-old man was admitted because of systolic murmur after routine medical checking. Echocardiography and cardiac catheterization revealed a large mass in the ventricular septum which bulged into right ventricular cavity with pressure gradient of 29 mmHg. The diagnosis of cardiac lipoma was made by CT scanning which showed the mass with attenuation values of -94 Hounsfield units. MR imaging demonstrated the mass with high signal intensity which corresponded to that of subcutaneous fatty tissue. The tumor was resected through the right ventricular incision with the use of cardiopulmonary bypass. It was yellow, elastic soft, sized 6.5 x 4.3 x 3.5 cm, and weighed 44.7 g. On histological examination, the tumor was composed of mature fatty tissues contained with myocardial fibers. After operation, he had split of the ventricular septum, which was closed primarily after removal of the lipoma, and left-to-right shunt. Patch reinforcement was performed at the right ventricular side of the septum on the postoperative 18th day. Postoperative electrocardiogram showed left axis deviation and complete right bundle branch block. This finding seems to be resulted from injury to the anterior branch of left bundle. The postoperative course was uneventful. This patient is the second case of removal of cardiac lipoma in the ventricular septum on review of the literature in Japan.

[A case of ruptured azygos vein and diaphragmatic hernia due to blunt chest trauma].

A 47-year-old female was admitted to the emergency room following an automobile accident. She was shocked complaining of respiratory difficulty and chest pain. A chest X-ray showed right hemothorax which drained 2.5 liters of blood on insertion of chest tube. Emergency operation revealed rupture of azygos vein. The bleeding was controlled by the ligation of the azygos vein. Postoperative chest X-ray showed obscuration of the left diaphragma, and herniated stomach was identified by the gastrography. Second operation was performed and ruptured diaphragma was repaired. Her postoperative recovery was good. She was discharged from hospital at 7th week.

[Invasive treatment of ischemic events after coronary artery bypass grafting].

PTCA or reCABG was performed for ischemic events after CABG in 32 patients. Since 6 patients were operated on initially elsewhere, the incidence of reCABG among our own patients was 1.2% and that of PTCA was 4.5%. Only one patient of 15 patients, in whom internal thoracic artery (ITA) was utilized at the initial CABG, underwent reCABG and the other patients were treated by PTCA. The use of ITA reduced the necessity for re-CABG because of the superior long-term patency of ITA. PTCA was performed for 32 lesions (19 in saphenous vein grafts (SVG), 4 in ITA grafts, and 9 in native coronary arteries) of 23 patients with success rate of 88%. The rate of restenosis was 36%. There were no complications following PTCA. No patients were referred for emergent surgery. Intracoronary thrombolysis and PTCA for total occlusion of SVG were performed successfully if they were done early after the occurrence of ischemic events. Coronary angiography should be performed as soon as possible. Ten patients underwent re-CABG utilizing ITA in 9 patients and gastro-epiploic artery (GEA) in 3. One patient died of arrhythmia due to spasm. The other 9 patients were discharged and class I or II of NYHA functional classification. The coronary angiography, which was performed at the late follow-up period, showed occlusion of SVG and patency of ITA. The arterial conduits should be applied for reCABG because of the low long-term patency of SVG.

[Repeated valvular surgery with minimal heart dissection].

Between April 1989 and March 1994, sixteen patients underwent the reoperation for valvular disease. In early years, complete heart dissection performed during operation (group A, n = 7). And recently, minimal necessary dissection was applied (group B, n = 9). In group B, dissection was limited to the ascending aorta, both vena cavae and right upper pulmonary vein. If the adhesion would be dense, pleural cavity would be widely opened and both caval cannula and left atrial vent tube would be cannulated through pleural adhesion. Operation time of group B was significantly decreased in comparison with group A. (group A: 569 +/- 91 min, group B: 347 +/- 65 min, p < 0.01). Post-operative course of group B was considered to be better than group A. These result suggested that minimal necessary heart dissection would be extremely effective during the repeated valvular surgery.

[Staged sternal closure for the case of postoperative severe cardiac failure: a convenient method in the intensive care unit].

A convenient method of staged sternal closure in the intensive care unit for a patient with severe cardiac failure was reported. According to the patient's cardiac function, optimal intersternal space can be adjusted. When using this method on a infant, the adjustment has shown to be very easy and take only a short time. However we have no experience on adults with stronger sternum.

[Carpentier's procedure for Ebstein's anomaly: successful and failed cases].

Two adult cases of Ebstein's anomaly underwent Carpentier's procedure. In the first case longitudinal plication limited to free wall of atrialized ventricle was performed and postoperative course was uneventful. In the second case preoperative echocardiography showed apparently restricted movement of anterior leaflet of the tricuspid valve which was compatible with intraoperative findings. That is, inferior edge of anterior leaflet was partly adherent to ventricular wall and systolic bulging of leaflet was significantly impaired which was left untouched but should be repaired by additional procedure. Six days after operation the tricuspid valve replacement was required for persistent right heart failure due to residual tricuspid regurgitation. In the same case longitudinal plication of atrialized ventricle reported by Carpentier and colleagues resulted in excessively small annulus. Therefore we had to reduce the plication and did not perform following atrial plication to avoid direct injury to conduction system or disturbing coronary venous return. In conclusion exact preoperative evaluation of anterior leaflet of the tricuspid valve especially subvalvular anatomy is essential to Carpentier's procedure, as Carpentier and colleagues emphasized, and conservative longitudinal plication of the atrialized ventricle limited to free wall is favorable when excessively small annulus might be concerned.

[Vasodilator therapy utilizing nitroprusside and nitroglycerin after coronary artery surgery].

The hemodynamic effects of combined therapy utilizing sodium nitroprusside (SNP) and nitroglycerin (TNG) were compared with those of TNG therapy in patients who underwent coronary artery bypass grafting (CABG). Of 58 patients who received catecholamine infusion to maintain hemodynamics after CABG, 17 had perioperative myocardial infarction (PMI (+) cases) and the other 41 had not PMI (PMI (-) cases). 26 of 41 patients (PMI (-) cases) received nitroglycerin therapy (NTG group) and the other 15 patients received combined therapy (SNP + NTG group). 11 of 17 patients (PMI (+) cases) received NTG therapy and the other 6 patients received combined therapy. The hemodynamic valuables, which were studied, were as follows; cardiac index, stroke volume index, left ventricular stroke work index, systemic vascular resistance index, pulmonary vascular resistance index, and deep core temperature. SNP + TNG group revealed significantly lower systemic vascular resistance index and pulmonary vascular resistance index than TNG group in PMI (-) cases. In PMI (+) cases, SNP + TNG group revealed significantly higher cardiac index, stroke volume index, left ventricular stroke work index, and significantly lower pulmonary vascular resistance index than TNG group. These findings demonstrate that combined therapy can obtain more secure vasodilation than TNG therapy.

[A case of two-chambered right ventricle complicating infective endocarditis and tricuspid regurgitation].

A 31-year-old male of two-chambered right ventricle with ventricular septal defect, complicating infective endocarditis and tricuspid regurgitation, was presented. Two-dimensional echocardiographic study demonstrated tricuspid vegetations and a hypertrophied, anomalous muscle bundle in the right ventricle. Cardiac catheterization revealed 58 mmHg pressure gradient between inflow chamber and outflow chamber of the right ventricle. It seems that tricuspid regurgitation was resulted from infective endocarditis. He underwent resection of anomalous muscle bundle, repair of ventricular septal defect, and tricuspid valve replacement with satisfactory result. It has not been reported in Japan so far that tricuspid valve replacement was performed for the treatment of tricuspid regurgitation due to infective endocarditis in the patient with two-chambered right ventricle. In our case, cardiac catheterization was performed after subsidence of infective endocarditis. As echocardiography can detect vegetations and anomalous muscle bundle precisely, surgical intervention would be performed without cardiac catheterization in the case of infective endocarditis intractable to medical therapy.

[Analysis of factors influencing early patency of saphenous vein grafts].

To determine factors affecting early patency of saphenous vein grafts, 140 grafts in 65 patients were studied angiographically within 2 months after operation. Twenty of the 140 grafts were occluded. Sixteen variables were extracted from the angiographic findings, intraoperative measurements, clinical characteristics, and biochemical data. The univariate and multivariate analyses were performed to assess their predictive value. Of 16 variables, 3 (coronary artery internal diameter, graft flow, and coronary artery resistance) correlated significantly with graft patency in the univariate analysis. The multivariate analysis selected coronary artery resistance, coronary artery internal diameter, and degree of proximal stenosis as predictors of early graft patency. Of these 3 factors, the coronary artery resistance influenced graft patency mostly. Therefore, the coronary artery resistance was considered to be the most reliable predictor of early graft patency.

[A case of completely unroofed coronary sinus with persistent left superior vena cava].

A 34-year-old female presented with exertional dyspnea. Investigation by echocardiography and cardiac catheterization showed completely unroofed coronary sinus with persistent left superior vena cava (PLSVC) (coronary sinus atrial septal defect, absence of the coronary sinus, and PLSVC-left atrium connection) combined with tricuspid valve regurgitation. Angiocardiography made by injection into the PLSVC demonstrated that the PLSVC was connected to the hemiazygos vein before it drained into the left atrium and the left innominate vein was absent. Although jugular vein pressure rose up to 18 mmHg when the PLSVC was temporarily occluded, it remained unchanged. Therefore, simple ligation of the PLSVC was selected for therapy. Patch closure of the atrial septal defect, tricuspid valve repair, and ligation of the PLSVC was performed successfully.