Search

Objective: Patients with severe motor and intellectual disabilities (SMID) often develop complications, including paralysis of the extremities due to abnormal muscular tonicity. Furthermore, the incidence of sudden death, which may be caused by pulmonary thromboembolism (PTE), is approximately 4.2%. Deep vein thrombosis (DVT) is attracting attention as an embolic source. In this study, DVT was confirmed in SMID patients by lower extremity venous ultrasound. The oral anticoagulant, warfarin, and novel oral anticoagulant, edoxaban tosilate hydrate, were administered, and their efficacies and safeties were evaluated. Materials and Methods: DVT patients were randomly allocated to warfarin and edoxaban groups. The frequency of hemorrhagic events and incidence of adverse events were investigated to evaluate efficacy and safety. Results: DVT was detected in 14 (8.4%) out of 167 patients. Four (0.067/person-month) hemorrhagic events occurred in the warfarin group from subcutaneous hemorrhage due to bruises caused by postural changes. Three (0.042/person-month) events occurred in the edoxaban group due to nasal hemorrhage caused by tracheal aspiration. There was no significant difference (p=0.5383) between groups. Conclusion: No significant differences were observed in hemorrhagic events between SMID patients with DVT treated with warfarin and edoxaban.

Sudden death in patients with severe motor and intellectual disabilities (SMID) is sometimes caused in part by pulmonary thromboembolism (PTE), and deep venous thrombosis (DVT) has drawn attention as a possible embolic source. Warfarin, which is a conventional therapeutic agent, is not easy to control appropriately, and daily management can be especially difficult in SMID patients. On the other hand, edoxaban tosilate hydrate, which has been newly approved for insurance coverage for the treatment of DVT, is not listed in the Guidelines for the Diagnosis, Treatment and Prevention of Pulmonary Thromboembolism and Deep Vein Thrombosis (DVT-PTE guidelines). The aim of this study is to evaluate the efficacy and safety of anticoagulation therapy (warfarin vs. edoxaban) in DVT treatment in SMID patients by means of an open-label, randomized controlled trial. The primary endpoint is the incidence of hemorrhagic events during 12 months of follow up.

Background The indication for surgical repair of atrial septal defect (ASD) is pulmonary to systemic blood flow ratio ( Q p / Q s ) > 2.0, and therapeutic strategy depends on the facility in cases of Q p / Q s 1.5–2.0. Defect size increases with age, but hemodynamic changes of medium-sized ASD ( Q p / Q s 1.5–2.0) are unknown. Methods and results From April 1, 1985 to March 31, 2008, we experienced 125 cases of cardiac catheterization for ASD. Twelve cases were re-evaluated without surgical repair. The first and second catheterizations were performed at median ages of 7 years (range, 2–13 years) and 16 years (range, 5–19 years), respectively. The mean follow-up period was 7 years. Q p / Q s increased from 1.6 to 2.0 during follow-up ( p Q p / Q s Q p / Q s ≥ 1.5 at second inspection. Right ventricle diastolic volume (RVEDV/LVEDV) also increased. Conclusions Q p / Q s and RVEDV/LVEDV of medium-sized ASD increase together in childhood. Re-evaluation before adulthood should be considered in patients with no indications of ASD closure in childhood.

Background: Balloon angioplasty has recently been adopted as an acceptable form of treatment for stenotic vessel lesions of congenital heart diseases. However, precise mechanisms of restenosis and thrombosis, which are the most common complications after these procedures, are unknown. Methods: We examined the effects of antithrombin III (ATIII) on inflammation, thrombus formation, and remodeling of vascular wall after guidewire-induced injury in the femoral artery of mice. ATIII or saline was administered as a bolus intravenous infusion before injury. Results: Seventy-two hours after injury, approximately half of the saline-treated vessels showed macroscopic thrombus formation. In contrast, no thrombi were seen in the arteries pretreated with ATIII. Significantly higher levels of inflammation were induced in the injured vessels than in the sham-operated controls, as determined by CD11b-positive cell density in the adventitial area. ATIII treatment resulted in marked reduction of inflammatory cell infiltration. Twenty-eight days after injury, similar levels of neointimal proliferation were found in the injured arteries in both groups. Conclusions: Our results suggested that a high dose of ATIII may influence the sequelae of arterial injury by reducing mural thrombus formation and limiting the inflammatory reaction of the vessel wall without altering the process of vascular remodeling.

Unusual Epstein-Barr virus (EBV) infection into T or natural killer cells plays a pivotal role in the pathogenesis of acute EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and chronic active EBV infection (CAEBV). The precise frequency and localization of EBV genome in lymphocyte subpopulations especially within T-cell subpopulations are unclear in these EBV-related disorders. This study analyzed the frequency of EBV-infected cells in circulating lymphocyte subpopulations from 4 patients with acute EBV-HLH and 4 with CAEBV. EBV- encoded small RNA-1 in situ hybridization examination of peripheral blood lymphocytes showed a significantly higher frequency of EBV-infected cells of 1.0% to 13.4% in EBV-HLH and 1.6% to 25.6% in CAEBV, respectively. The patterns of EBV infection in lymphocyte subpopulations were quite different between acute EBV-HLH and CAEBV. EBV infection was predominant in CD8(+) T cells in all EBV-HLH patients, whereas the dominant EBV-infected cell populations were non-CD8(+) lymphocyte subpopulations in CAEBV patients. Phenotypical analysis revealed that EBV-infected cell populations from both EBV-HLH and CAEBV were activated. There was no predominance of any EBV substrain of latent membrane protein-1, EBV-associated nuclear antigen (EBNA)-1, and EBNA-2 genes between the 2 abnormal EBV-associated disorders, and self-limited acute infectious mononucleosis. These results showing differential virus-cell interactions between acute EBV-HLH and CAEBV indicated different pathogenic mechanisms against EBV infection between the 2 EBV-associated diseases, which accounts for the difference in clinical manifestations between the 2 diseases.

To examine the risk factors of hypocarnitinemia and hypocarnitinemic symptoms in children and adults with severe physical and mental disabilities.The status of hypocarnitinemia as well as the related symptoms were assessed in a total of 78 children and adults with severe physical and mental disabilities who were admitted to National Hospital Organization Iou National Hospital. Their enteral diets and the medication of antiepileptic drugs were evaluated.Markedly decreased blood carnitine levels were noted in patients undergoing an enteral diet without carnitine supplementation as well as in those receiving a combination of valproate sodium (VPA) and phenobarbital (PB). These hypocarnitinemic patients tended to have more frequent episodes of hypoglycemia and hyperammonemia.Supplemental L-carnitine is needed in patients receiving an enteral diet free of carnitine, those with combination therapy of VPA and PB under oral feeding conditions, and those who develop hyperammonemia during VPA therapy. Patients who received a carnitine-supplemented enteral diet maintained their serum carnitine levels with a relatively low supplemental dose of carnitine.

There has been increasing evidence suggesting the potent anti-inflammatory roles of heme oxygenase-1 (HO-1) in protecting renal tubular epithelial cells, vascular endothelial cells, and circulating monocytes. Based on these findings, novel therapeutic interventions have been proposed to control the expression of endothelial HO-1 levels to ameliorate various vascular diseases. We evaluated the effect of HO-1 gene transfer into an anchorage-dependent cell, ECV304. Effect of HO-1 production on the cell injury induced by hydrogen peroxide was evaluated after hemin stimulation and after HO-1 gene transfection. Morphological changes and the induction of various anti-apoptotic proteins were examined at the same time. Levels of HO-1 expression were variable in different clones of HO-1-transfected ECV304 cells. Among these, the clones with moderate levels of HO-1 expression were significantly more resistant to oxidative stress. In contrast, those with the highest levels of HO-1 exhibited paradoxically enhanced susceptibility to oxidative injury. Interestingly, the cell survival after oxidative stress was in parallel with the levels of Bcl-2 expression and of fibronectin receptor, alpha5 integrin. It is suggested from these results, that excessive HO-1 not only leads to enhanced cell injury, but also prolongs the repair process of the injured endothelial tissue. However, HO-1 reduces the oxidative cell injury and protects the endothelial cells, if its expression is appropriately controlled.

Heme oxygenase-1 (HO-1) constitutes one of the three isozymes of HO, which catalyze the degradation of heme into biliverdin, carbon monoxide (CO) and free iron.1, 2, 3, 4, 5 Recent experimental data indicate that one of the heme degradation products, CO acts on cellular metabolism to protect cells from oxidative stress and regulate production of inflammatory molecules.6, 7, 8 As a result, CO directly controls the inflammatory state of a given tissue and at the same time, regulates the level of microcirculation within the target organs acting as a gaseous vasodilator.9, 10, 11 Among three isozymes with similar enzyme activities, HO-1 is the only protein which is rapidly induced upon stimulation with various oxidative stresses.12, 13, 14 Therefore, it is suggested that any defect in its function will lead to uncontrollable inflammatory responses upon certain exogenous insults, such as infection and hemolysis.

Quantification of gated single-photon emission tomography (SPET) in small hearts has been considered to be inaccurate. To evaluate the validity of gated SPET in a small chamber volume, mathematical simulation and clinical application to paediatric patients were performed. Myocardium with various chamber sizes from 14 ml to 326 ml was generated assuming an arbitrary resolution (6.9-15.7 mm in full-width at half-maximum), noise and zooming factors. The cut-off frequency of the Butterworth filter for preprocessing was varied from 0.16 to 0.63 cycles/cm. The chamber volume was calculated by quantitative gated SPET software (QGS). The patients, aged 2 months to 19 years (n=27), were studied by gated technetium-99m methoxyisobutylisonitrile or tetrofosmin SPET. Image magnification as large as possible was performed during data acquisition to include the whole chest using 1.25-2.0 zooming. Based on the simulation study, an underestimation of the chamber volume occurred below a volume of 100 ml. The degree of underestimation for a 37-ml volume was 49% without zooming, but it improved to 3% with 2x zooming. Filters with a higher cut-off frequency, better system resolution and hardware zooming during acquisition improved quantitative accuracy in small hearts. For the subjects under 7 years old (n=7), quantification of volume and ejection fraction (EF) was possible in 72% of the patients. In those over 7 years old, gated SPET quantification was feasible in all cases. The correlation between gated SPET end-diastolic volume (SPET EDV) and both echocardiographic end-diastolic dimension (EDD) and echocardiographic EDV was good (r=0.84 between SPET EDV and echo EDD, r=0.85 between SPET EDV and echo EDV, P