Increased thrombogenesity in patients with cyanotic congenital heart disease.

BACKGROUND: The basic mechanisms of thromboembolism in cyanotic congenital heart disease (CCHD) have not been well clarified. P-selectin on the platelets reflects platelet activation. Thrombomodulin is a critical cofactor for thrombin-mediated activation of protein C and reflects the anticoagulant activity of the endothelium. The present study was performed to evaluate whether platelet activation exists in patients with CCHD. METHODS AND RESULTS: Platelet P-selectin as a marker of platelet activation, plasma thrombomodulin level and protein C activity as markers of anticoagulant activity of the endothelium and thrombin - antithrombin complex III (TAT) were examined in 35 patients with CCHD. Plasma thrombomodulin level (1.1+/-0.9 vs 2.2+/-0.3 FU/ml) and protein C activity (71.1+/-29.8 vs 117.8+/-24.8%) were significantly lower in patients with CCHD as compared with the control subjects. The levels of plasma TAT (255+/-811 vs 1.9+/-0.9 ng/ml) and P-selectin on platelets (6.3 +/-4.5 vs 3.3+/-0.3 mean fluorescence intensity) were significantly higher in the patients with CCHD than in the controls. Four of the CCHD patients who experienced thromboembolic events had elevated levels of platelet P-selectin (p=0.02) compared with CCHD patients without thromboembolic events. CONCLUSION: Platelet activation exists in patients with CCHD and it may play an important role in the thromboembolic events in CCHD.     

Effect of post-exposure prophylaxis with oseltamivir for those in contacts with influenza patients in pediatric wards

During the influenza season, outbreaks of influenza may occur in the pediatric wards due to spread from the patients hospitalized with influenza, or from those hospitalized during the latency period and develop influenza afterwards. Post-exposure prophylaxis with neuraminidase inhibitors has been reported to be effective in preventing outbreaks among household members and nursing home residents. However, for nosocomial spread, its effectiveness and possible adverse effects are to be determined. During the 2002/2003 influenza season, we experienced a total of 3 nosocomial outbreaks of influenza in the pediatric wards in two hospitals in the Kanto district, Japan. Since the number of contacts who developed influenza had been increasing despite the isolation precaution implemented, post-exposure prophylaxis with oseltamivir (2 mg/kg/dose, maximum 75 mg/dose, once a day for 7-10 days) was implemented with a permission from the parents to terminate the outbreaks. In the outbreaks (one with influenza A, two with influenza B), a total of 29 inpatients had contact with influenza patients: among those 29, 13 were given post-exposure prophylaxis, 16 were not. Out of 16 patients who did not receive post-exposure prophylaxis, 11 (69%) developed influenza: out of 13 with post-exposure prophylaxis, none developed influenza. Those patients who developed influenza were given oseltamivir (2 mg/kg/dose, maximum 75 mg/dose, twice a day for 5 days) and accommodated in a private room or a room with other patients with influenza of the same type. No significant adverse effects due to oseltamivir were observed among those who were enrolled in this study.     

Twenty Years’ Experience in Allogeneic Hematopoietic Stem Cell Transplantation for Philadelphia Chromosome—Positive Acute Lymphoblastic Leukemia in the Nagoya Blood and Marrow Transplantation Group

Between October 1981 and December 2000, 46 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) underwent allogeneic hematopoietic stem cell transplantation (HSCT) in the Nagoya Blood and Marrow Transplantation Group. The median age was 28.5 years (range, 4-51 years). All but one patient achieved engraftment. Grade II-to-IV acute graft-versus-host disease (GVHD) developed in 32.5% of patients, and chronic GVHD developed in 40.5%. The incidences of relapse and treatment-related mortality (TRM) at 5 years were 65% and 26%, respectively. The estimated overall survival rate at 5 years was 23%. Univariate analysis showed that improved disease-free survival (DFS) was independently associated with complete remission (CR) at transplantation (39%), compared with non-CR (8%) (P = .023). Non-CR at transplantation was associated with a higher risk of relapse. Donor type, acute GVHD, and time from diagnosis to HSCT all had a significant effect on TRM. In a multivariate analysis, 9 months or more from diagnosis to HSCT was the only variable statistically significant for DFS (relative risk, 3.22; P = .01). This study demonstrates that allogeneic HSCT cures a significant population of patients with Ph+ ALL. Relapse is the major obstacle limiting the success of HSCT. Early transplantation during CR from donors, including unrelated persons or mismatched relatives, may offer improved long-term DFS.     

Prognostic significance of PRAME expression based on immunohistochemistry for diffuse large B-cell lymphoma patients treated with R-CHOP therapy

The preferentially expressed antigen of melanoma (PRAME), a tumor-associated antigen, is considered a prognostic marker for various human malignancies. The prognostic significance of PRAME expression for diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab-containing chemotherapy has not been evaluated to date, and the ability of immunohistochemistry (IHC) to detect PRAME expression in these patients has not yet been studied, although IHC is simple to perform in clinical practice. We evaluated the prognostic significance of PRAME expression based on IHC analysis in 160 DLBCL patients treated with R-CHOP therapy. There was a significant association between higher PRAME expression and shorter progression-free survival (PFS), and a trend toward shorter overall survival (OS) in patients with higher PRAME expression than that in patients with lower PRAME expression (5-year PFS, 48.1 vs. 61.1 %; 5-year OS, 65.6 vs. 79.1 %). Patients with high PRAME expression tended to have lower chemotherapeutic responses. Thus, IHC is useful for detecting and assessing PRAME expression in DLBCL. Further, we found a positive correlation between IHC and quantitative real-time RT-PCR measurements of PRAME expression. Our findings indicate that IHC results of PRAME expression can be a novel prognostic maker in DLBCL patients treated with R-CHOP therapy.     

Comparison of behavioral and psychological symptoms in early-onset and late-onset Alzheimer's disease

BACKGROUND: When comparing with early-onset Alzheimer's disease (EO-AD) and late-onset Alzheimer's disease (LO-AD), some symptomatological differences in clinical features can be seen between them. Rapid progression, more severe language problems or visuospatial dysfunction occur more often in EO-AD patients. However, there have been very few reports about the differences in behavioral and psychological symptoms between these two groups. AIM: The aim of this study was to demonstrate the differences in behavioral symptoms between EO-AD and LO-AD groups. METHOD: Three hundred and seven consecutive outpatients with AD were put into an EO-AD group (46 patients) or a LO-AD group (261 patients). Comprehensive assessment batteries, including the Neuropsychiatric Inventory (NPI), were administered at the first medical assessment. RESULTS: Significant differences were found between the EO-AD and LO-AD groups in terms of NPI total score (EO-AD: 10.3 +/- 10.9, LO-AD: 17.8 +/- 17.0, p = 0.004) and number of patients who experienced each NPI subscale score (delusion; EO-AD: 13.0%, LO-AD: 50.6%, p < 0.001). There were no differences in cognitive functions or dementia severity between two groups. CONCLUSION: In EO-AD, behavioral and psychological symptoms are relatively fewer than LO-AD at the first medical assessment. Copyright (c) 2007 John Wiley & Sons, Ltd.