Significant association between leukoaraiosis and metabolic syndrome in healthy subjects.

OBJECTIVE: To investigate the relationship between leukoaraiosis (LA), which has been considered as an intermediate substitute of ischemic brain damages, and metabolic syndrome (MetS), which attracts attention as a risk factor for cerebrovascular diseases, in healthy subjects derived from various age groups. METHODS: We studied 1,030 healthy persons at ages between 28 and 78 years (mean, 52.7 years) with no history of stroke who visited a health care facility for routine health checkups. MetS was defined using the criteria of the National Cholesterol Education Program Adult Treatment Panel III. LA was assessed using the rating scale of the Atherosclerosis Risk in Communities study on MRI. Logistic regression analysis was performed to examine associations between LA and MetS. RESULTS: A total of 296 (28.8%) subjects had LA on MRI. MetS was significantly associated with the presence of LA (adjusted OR, 3.33; 95% CI, 2.30, 4.84). The association was constant across grades of LA; the adjusted OR was 3.41 (95% CI, 2.30, 5.06) for minimal LA and 3.07 (95% CI, 1.75, 5.38) for LA combining mild, moderate, and severe grades. As for MetS components, elevated blood pressure (adjusted OR, 2.16; 95% CI, 1.57, 2.99), impaired fasting glucose (adjusted OR, 1.64; 95% CI, 1.13, 2.39), and hypertriglyceridemia (adjusted OR, 1.56; 95% CI, 1.08, 2.28) were independently associated with all grades of LA. CONCLUSIONS: Metabolic syndrome (MetS) was significantly associated with every grade of leukoaraiosis (LA), including the minimal LA. Impaired fasting glucose and hypertriglyceridemia were associated with LA independently of elevated blood pressure. MetS can play an important role in identifying healthy subjects who have an increased risk of LA.

Analysis of transcription factor expression during oogenesis and preimplantation development in mice.

The transition from a differentiated germ cell into a totipotent zygote during oogenesis and preimplantation development is critical to the creation of a new organism. During this period, cell characteristics change dynamically, suggesting that a global alteration of gene expression patterns occurs, which is regulated by global changes in various epigenetic factors. Among these, transcription factors (TFs) are essential in the direct regulation of transcription and also play important roles in determining cell characteristics. However, no comprehensive analysis of TFs from germ cells to embryos had been undertaken. We used mRNA amplification systems and microarrays to conduct a genomewide analysis of TFs at various stages of oogenesis and preimplantation development. The greatest alteration in TFs occurred between the 1- and 2-cell stages, at which time zygotic genome activation (ZGA) occurs. Our analysis of TFs classified by structure and function revealed several specific patterns of change. Basic transcription factors, which are the general components of transcription, increased transiently at the 2-cell stage, while homeodomain (HD) TFs were expressed specifically in the oocyte. TFs containing the Rel homology region (RHR) and Ets domains were expressed at a high level in 2-cell and blastocyst embryos. Thus, the global TF dynamics that occur during oogenesis and preimplantation development seem to regulate the transition from germ-cell-type to embryo-type gene expression.

Shortening patterns of the infundibulum in valvular pulmonary stenosis before and after balloon valvuloplasty.

We analyzed shortening patterns of the infundibulum in 11 patients with valvular pulmonary stenosis (PS) before and immediately after balloon valvuloplasty and at follow-up. The control group consisted of 32 patients with Kawasaki disease. The valvuloplasty was performed at the age of 5.8 +/- 2.9 (mean +/- SD) years and a satisfactory relief of obstruction was achieved in each. The follow-up study was done at 1.1 +/- 0.2 years after the valvuloplasty. With the use of lateral projection of right ventriculograms, transverse diameters of the midinfundibulum were measured over one cardiac cycle from initiation of the pulmonary valve opening. Indices demonstrating shortening patterns of the infundibulum were as follows: time to the beginning of shortening (TBS), time to the shortest diameter (TSD), and shortening fraction (SF). TBS were prolonged before the valvuloplasty, whereas it was comparable with that in the control group, immediately after the procedure and at follow-up. TSD was increased before and immediately after the valvuloplasty, but it was normalized at follow-up. SF was increased at every observation. Thus, shortening patterns of the infundibulum in PS were characterized by increasing TBS, TSD, and SF. At short-term follow-up following the valvuloplasty, TBS and TSD were normalized, which could be a result of a successful relief of pulmonary obstruction. In contrast, SF remained elevated, which indicates that the musculature of the infundibulum remains hypertrophic up to 1 year after the valvuloplasty.

Histopathologic changes in the infundibular septum after balloon pulmonary valvuloplasty in tetralogy of Fallot.

Balloon pulmonary valvuloplasty (BPV) has been applied to tetralogy of Fallot (TOF) as a palliative procedure. To investigate the histopathologic changes by BPV in the infundibular septum of TOF, we performed histopathologic examinations of the infundibular septum resected at corrective surgery. The subjects were 5 patients with TOF, who underwent BPV at the median age of 2.2 months and the corrective surgery at the median age of 15.0 months (BPV group), and 4 patients with TOF who had no prior BPV and who underwent the corrective surgery at the median age of 14.5 months (control group). There was no significant difference between the two groups in the endocardial thickness, myocardial vacuole degeneration, or fraction of fibrous and interstitial space. However, the specimens from 3 patients in the BPV group had localized dense fibrous lesions in the myocardium. The findings in this limited sample suggest that BPV for TOF does not produce overall histopathologic alterations such as fibrosis, thick endocardium, and myocardial vacuole degeneration, but may sometimes damage the myocardium of the infundibular septum resulting in the formation of localized dense fibrous lesions. The clinical significance of this damage is still unknown, and further cases should be investigated.

Management of functional pulmonary atresia with isoproterenol in a neonate with Ebstein's anomaly.

Ebstein's anomaly is a rare congenital cardiac anomaly showing significant clinical manifestations with a high mortality rate in the neonatal period. The prognosis of the patient is essentially determined by the severity in morphological changes, however, high pulmonary vascular resistance in the neonatal period may aggravate tricuspid regurgitation and lead to functional pulmonary atresia. We describe a critically ill neonate with morphologically mild Ebstein's anomaly who was successfully managed with intensive care including isoproterenol administration for functional pulmonary atresia. Isoproterenol is a potent pulmonary vasodilator with inotropic and chronotropic effects, and seemed to decrease the pulmonary vascular resistance allowing increased antegrade blood flow to the pulmonary artery and improved cardiac output. If tachycardia is not present, isoproterenol administration is recommended in critically ill neonates with anatomically mild Ebstein's anomaly and no associated cardiac defects.

Microangiopathic hemolytic anemia and thrombocytopenia in a child with atrial septal defect and pulmonary hypertension.

Microangiopathic hemolytic anemia and thrombocytopenia have been reported in patients with primary pulmonary hypertension, but not in patients with congenital heart disease even if accompanied with pulmonary hypertension. We present a 7-year-old boy with atrial septal defect and pulmonary hypertension who developed microangiopathic hemolysis and thrombocytopenia. Microangiopathic hemolytic anemia and thrombocytopenia should be remarked as a complication in patients with congenital heart disease.

Bentall operation for a child with Marfan syndrome: a case report.

Children with Marfan syndrome rarely undergo surgery for annuloaortic ectasia and aortic regurgitation in the first decade. A 7-year-old girl presented with congestive heart failure due to severe aortic regurgitation associated with annuloaortic ectasia (6 cm). She also had funnel chest. She underwent a Bentall operation and sternal turn-over with a satisfactory result. Since the aortic valve cusps had rolled edges, the aortic valve was not spared. Histology of the aortic valve cusps showed myxoid degeneration and fragmentation of elastic fibers.

Balloon pulmonary valvuloplasty for pulmonary valve stenosis with atrial septal defect.

We performed successful balloon pulmonary valvuloplasty (BPV) in 6 patients with pulmonary valve stenosis and atrial septal defect (ASD) accompanied by atrial left-to-right shunt without an increase of shunting immediately after BPV. It suggests that such patients should be treated by BPV initially and the need for ASD repair can be assessed during long-term follow-up.

Right and left ventricular function assessed by regional wall motion analysis in patients with tetralogy of Fallot.

We studied pre- and postoperative regional right and left ventricular wall motion and global ejection fraction in 18 patients with tetralogy of Fallot who had successful repair, and compared these values to those of patients with a history of Kawasaki disease as controls. Right ventricular ejection fraction was significantly lower in the preoperative group (52 +/- 4%) than that in the control group (57 +/- 4%), and that in the postoperative state (49 +/- 4%) was significantly lower than those in the control and preoperative groups. Left ventricular ejection fraction was significantly lower in the preoperative group (56 +/- 7%) than that in the control group (61 +/- 5%), while that in the postoperative state (64 +/- 6%) was significantly higher than those in the control and preoperative groups. Regional ventricular wall motion analysis revealed that shortening fractions in the tricuspid valve region were reduced in the preoperative patients and were persistent even after successful repair; those in the right ventricular outflow tract region were decreased after the correction. Regional left ventricular wall motion showed that shortening fractions in the anterolateral region were improved after the correction. We conclude that right ventricular dysfunction was present in the preoperative patients with tetralogy of Fallot and was persistent even after total correction.

Left and right ventricular volume characteristics in tetralogy of Fallot and their relationship to arterial oxygen saturation and age.

Left (LV) and right ventricular (RV) volume characteristics in 43 patients with tetralogy of Fallot (TOF) undergoing no prior surgical intervention, aged 3-50 months, were evaluated. The control group consisted of 45 patients with Kawasaki disease without cardiac lesions, aged 12-82 months. The TOF patients were divided into four groups: those having arterial oxygen saturation < 80% with an age at the time of study < 18 months (group 1a) or with that > or = 18 months (group 1b), and those with arterial oxygen saturation > or = 80% with an age < 18 months (group 2a) or with that > or = 18 months (group 2b). The results were compared with those in control subjects. In group 1a, each of LV end-diastolic volume (EDV), LV ejection fraction (EF), RVEDV and RVEF was reduced. In group 1b, LVEDV, LVEF and RVEF were decreased. In groups 2a and 2b, RVEF alone was depressed. From these results, the severity of hypoxemia was an important risk factor for ventricular dysfunctions. No influence of age on the volume characteristics was found. The investigations suggested that patients with TOF having an arterial oxygen saturation < 80% are probably candidates for early surgical intervention.

Body surface isopotential T map for assessment of right ventricular volume and pressure overloads in secundum atrial septal defect.

The body surface isopotential T map was analyzed to detect right ventricular volume and pressure overloads in 25 patients with secundum atrial septal defect. Three patterns were distinguished: a T map resembling normal (type A, n = 9); that with an isolated negative area in a positive area (type B, n = 11); and that with rightward movement of maximum (type C, n = 5). Right ventricular end-diastolic volumes in types B (161 +/- 19% of normal; %N) and C (175 +/- 40% N) were significantly (p < 0.01) greater than those in controls (100 +/- 9% N) and type A (113 +/- 18% N). Right ventricular systolic pressure in type C (48 +/- 11 mmHg) was significantly (p < 0.01) higher than those in the controls (30 +/- 5 mmHg), type A (31 +/- 4 mmHg), or type B (34 +/- 5 mmHg). These results suggest that the patients with type B have right ventricular volume overload and those with type C have both volume and pressure overloads.

Percutaneous balloon aortoplasty for restenosis after extended aortic arch anastomosis for type B interrupted aortic arch.

A 4-month-old boy underwent a percutaneous balloon aortoplasty for restenosis after extended aortic arch anastomosis for type B interrupted aortic arch (IAA). Balloon aortoplasty resulted in a decrease in the peak systolic pressure gradient across the obstructive segment from 84 mmHg to 19 mmHg and in an increase in diameter from 2.5 mm to 4.3 mm. No complications related to the procedure were observed. We assume that balloon aortoplasty can be effective and safe for relieving postoperative aortic obstruction associated with IAA.

Angiographic determination of left and right ventricular volumes and left ventricular mass in normal infants and children.

Left and right ventricular (LV and RV) volumes and LV mass were assessed by angiography in 63 infants and children without major cardiovascular abnormalities. LV and RV end-diastolic volumes (EDV) were excellently expressed as a function of body surface area (BSA) with an exponential equation: LVEDV = 83.7 (BSA)1.29 ml (r = 0.96, p < 0.001), RVEDV = 87.9 (BSA)1.29 ml (r = 0.94, p < 0.001). LV ejection fraction (EF) averaged 64 +/- 6 (mean +/- standard deviation) %, and RVEF 56 +/- 5%, each of which was independent of BSA. LV mass was well expressed as a function of BSA with an exponential equation: LV mass = 75.4 (BSA)1.22 g (r = 0.86, p < 0.001). LV mass/LVEDV was constant, and averaged 0.96 +/- 0.22 g/ml. Thus, the values of LVEDV, RVEDV, and LV mass in infants and children with various heart diseases may be estimated with reasonable accuracy as a percentage of normal values predicted from their BSA by using the above-proposed exponential equations. The normal values of LVEF, RVEF and LV mass/LVEDV themselves can be compared with these parameters in pediatric patients with heart diseases because of their independence of BSA.

[Body surface isopotential T map and ventricular volume characteristics in secundum atrial septal defect].

Body surface isopotential T map was analyzed to detect right ventricular volume and pressure overloads in 25 patients with secundum atrial septal defect. Three patterns were distinguished: the T map resembling normal (type A, n = 9); that with isolated negative area in positive area (type B, n = 11); and that with rightward movement of maximum (type C, n = 5). Right ventricular end-diastolic volumes in type B (161 +/- 19% of normal; %N) and C (175 +/- 40% N) were significantly (p < 0.01) greater than those in control (100 +/- 9% N) and type A (113 +/- 18% N). Right ventricular systolic pressure in type C (48 +/- 11 mmHg) was significantly (p < 0.01) higher than those in control (30 +/- 5 mmHg), type A (31 +/- 4 mmHg) and type B (34 +/- 5 mmHg). These results suggest that the cases with type B have right ventricular volume overload, and those with type C have both volume and pressure overloads.

Balloon pulmonary valvuloplasty for double outlet right ventricle with valvular pulmonary stenosis.

A male neonate presented with cyanosis. Echocardiograms showed a double outlet right ventricle, an absent outlet septum, a subaortic ventricular septal defect and valvular pulmonary stenosis. Balloon pulmonary valvuloplasty was performed at 19 days of age, resulting in an immediate increase of the systemic arterial oxygen saturation from 67 to 87%. As far as could be found, this is the first report of a patient with a double outlet right ventricle without the outlet septum who was clinically observed and underwent balloon pulmonary valvuloplasty.

Stromal cell-dependent bone marrow culture with a nearly protein-free defined medium.

We examined the ability of a defined medium mSFO2 to support stromal cell-dependent B lymphopoiesis and myelopoiesis. Both ST2 and PA6 stromal cell lines were able to form monolayers in the presence of mSFO2 alone. While the ST2 monolayer could last for long period of time, either bFGF or EGF were required for the maintenance of the PA6 monolayer with mSFO2. mSFO2 did support the generation of distinct stages of B precursors on the ST2 layer and this culture condition was efficient enough to be used for limiting dilution assay of in vitro clonable B progenitors. While ST2 cell line failed to support long-term myelopoiesis with mSFO2, PA6 in combination of bFGF was able to support sustained generation of various hematopoietic progenitors. Indeed, 20 times increase of IL-3 reactive colony-forming cells was induced upon culturing the normal bone marrow cells on the PA6 layer for 8 days with mSFO2. Because total protein concentration of mSFO2 is only 10 micrograms/ml consisting of transferrin and insulin, the present result that mSFO2 is able to support the proliferation of normal hematopoietic progenitor cells would make an important step towards the standardization of bone marrow culture.

Histopathologic findings of lung vessels in five children with primary pulmonary hypertension.

A histopathologic study was carried out on pulmonary vessels of lung tissues from 5 children with primary pulmonary hypertension (PPH), in whom diagnosis was made on the basis of cardiac catheterization. Histological sections of lung were obtained in 4 patients by open lung biopsy and in one patient by closed needle necropsy soon after death. In all cases the vascular diseases were classified as grade 6 of the Heath-Edwards. Morphologic studies of small pulmonary arteries revealed medial hypertrophy (41.0%), intimal cellular proliferation (2.5%), intimal fibroelastic proliferation (36.9%) and medial destructive changes (19.6%) such as dilatation lesions, plexiform lesions, arteritis, or fibrinoid necrosis. Index of pulmonary vascular disease (IPVD) was 1.6 to 3.4 (mean 2.5). The advancement of these pulmonary changes sufficiently explains the extremely poor prognosis of children with PPH.

Estimation of right ventricular pressure in children by thallium-201 myocardial imaging using single-photon emission computed tomography.

Thallium-201 myocardial imaging using single-photon emission computed tomography was performed to estimate right ventricular (RV) systolic pressure in 34 children (aged 4.1 to 16.1 years, mean 7.9 +/- 2.9). Acquisition of the images was performed using a semicircular arc of 180 degrees. On a short-axis slice, a line drawn perpendicular to the ventricular septum so as to cross the RV free wall showing maximum uptake was defined as the region of interest. Thallium-201 counts in regions of interest over both RV and left ventricular (LV) free walls were measured. The ratio of RV-to-LV peak thallium-201 counts was compared with RV peak systolic pressure and the ratio of RV-to-LV peak systolic pressure measured at cardiac catheterization. Both RV peak systolic pressure and the ratio of RV-to-LV peak systolic pressure correlated well with the ratio of RV-to-LV peak thallium-201 counts (r = 0.95 and 0.96, respectively). The ratio of RV-to-LV peak thallium-201 counts greater than or equal to 0.45 could predict RV pressure overloading with a sensitivity of 92%, and a specificity of 88%. Thus, the quantitative analysis of thallium-201 myocardial imaging using single-photon emission computed tomography permits the noninvasive and accurate estimation of RV systolic pressure in children.