Non-high-density lipoprotein cholesterol and the development of coronary heart disease and stroke subtypes in a general Japanese population: The Hisayama Study

Background and purpose

It has not been fully determined whether non-high-density lipoprotein cholesterol (non-HDLC) levels are involved in vascular events, especially stroke, in general Asian populations. We evaluated the association between non-HDLC levels and the risk of type-specific cardiovascular disease in a prospective cohort study in Japan.

Methods

A total of 2452 community-dwelling Japanese subjects aged ≥40 years were followed prospectively for 24 years.

Results

The age- and sex-adjusted incidence of coronary heart diseases (CHD) significantly increased with elevating non-HDLC levels (P for trend < 0.001), but no such association was observed for ischemic and hemorrhagic strokes. With regard to ischemic stroke subtypes, the age- and sex-adjusted incidence of lacunar infarction significantly increased with elevating non-HDLC levels (P for trend < 0.01), and such tendency was seen for atherothrombotic infarction (P for trend = 0.098), while a significant inverse association was observed for cardioembolic infarction (P for trend = 0.007). After adjustment for confounders, namely, age, sex, diabetes, body mass index, systolic blood pressure, electrocardiogram abnormalities, current drinking, current smoking, and regular exercise, the associations remained significant for CHD [adjusted hazard ratio (HR) for a 1 standard deviation of non-HDLC concentrations = 1.17, 95% confidence interval (CI) = 1.02 to 1.35], atherothrombotic infarction (adjusted HR = 1.39, 95% CI = 1.09 to 1.79), and cardioembolic infarction (adjusted HR = 0.64, 95% CI = 0.47 to 0.85).

Conclusions

Our findings suggest that elevated non-HDLC levels are a significant risk factor for the development of atherothrombotic infarction as well as CHD but reduce the risk of cardioembolic infarction in the general Japanese population.     

Two autopsy cases of desmoplastic small round cell tumor

Desmoplastic small round cell tumor (DSRCT) is a rare aggressive malignant tumor. It is a refractory tumor and the median overall survival is very short. We report two autopsy cases of DSRCT, both of which were already advanced and metastasized at the first medical examination. Both cases showed typical DSRCT findings in terms of localization of the lesions, histopathology and genetics, but the rate of disease progression was quite different. Survival after initial symptoms in Case 1 was only 12 months. On the other hand, survival after primary hospitalization in Case 2 was 42 months. The Case 2 patient initially received chemotherapy for advanced pancreatic carcinoma, because a nodule of the pancreatic tail was found on computed tomography (CT) scan. After chemotherapy, tumor regression was observed on CT scan. It is thus implied that adoption of the regimen for pancreatic carcinoma might have been one of reasons of the long survival in Case 2.     

Effects of the Implant Design on Peri‐Implant Bone Stress and Abutment Micromovement: Three‐Dimensional Finite Element Analysis of Original Computer‐Aided Design Models

Background: Occlusal overloading causes peri‐implant bone resorption. Previous studies examined stress distribution in alveolar bone around commercial implants using three‐dimensional (3D) finite element analysis. However, the commercial implants contained some different designs. The purpose of this study is to reveal the effect of the target design on peri‐implant bone stress and abutment micromovement. Methods: Six 3D implant models were created for different implant–abutment joints: 1) internal joint model (IM); 2) external joint model (EM); 3) straight abutment (SA) shape; 4) tapered abutment (TA) shapes; 5) platform switching (PS) in the IM; and 6) modified TA neck design (reverse conical neck [RN]). A static load of 100 N was applied to the basal ridge surface of the abutment at a 45‐degree oblique angle to the long axis of the implant. Both stress distribution in peri‐implant bone and abutment micromovement in the SA and TA models were analyzed. Results: Compressive stress concentrated on labial cortical bone and tensile stress on the palatal side in the EM and on the labial side in the IM. There was no difference in maximum principal stress distribution for SA and TA models. Tensile stress concentration was not apparent on labial cortical bone in the PS model (versus IM). Maximum principal stress concentrated more on peri‐implant bone in the RN than in the TA model. The TA model exhibited less abutment micromovement than the SA model. Conclusion: This study reveals the effects of the design of specific components on peri‐implant bone stress and abutment displacement after implant‐supported single restoration in the anterior maxilla.     

Incorporation of Optical Density into the Blending Design for a Biocement Solution

The engineering practices for applying the microbial precipitation of carbonates require a design of the blending biocement solution (BCS). The BCS is usually blended with concentrated strains NO-A10, reaction media, such as urea and CaCl₂, and a solvent, i.e., water or seawater. To characterize the BCS, the unknown microbial characteristics, such as the cell viability, are complex factors. Therefore, the optical density (OD) was redefined as Rcv OD*, in which OD* was the tentative OD of the BCS used and Rcv was the conversion rate concerning the cell viability. To determine Rcv values, a standard precipitation curve based on the precipitation rate at 24 h was determined. It was found that the curve was expressed by λ₁ OD+ λ₂ OD², in which λ₁ and λ₂ were 8.46 M and −17.633 M, respectively. With this, the Rcv and OD values of unknown BCS were estimated from the results of precipitation tests using arbitrary OD* values. By extending the testing time, the second order term of OD or OD* was negligible. Accordingly, the precipitation amount is expressed as 8.46 OD, in which the OD can be estimated by precipitation tests using arbitrary OD* values of BCSs. Unless the Ca²⁺ value is dominant, the optimum blending of BCS can be determined by OD. Thus, it is concluded that the blending design of BCS is achieved using 8.46 OD, or 8.46 Rcv OD*, and the standard precipitation curve was defined in this study.     

Effects of cardiac sympathetic innervation on regional wall motion abnormality in patients with long QT syndrome

AIM: To assess the spatial relation between regional cardiac sympathetic innervation and regional ventricular repolarisation indicated by ventricular wall motion abnormality in patients with congenital long QT syndrome. DESIGN: Regional percentage uptake and washout rate of (123)I metaiodobenzylguanidine (MIBG) were measured to assess cardiac sympathetic innervation in septum, anterior wall, lateral wall, and posterior wall. Left ventricular short axis images on echocardiography were digitised to reconstruct digitised M mode echocardiograms, from which left ventricular wall thickness curves were obtained. The wall thickening time (ThT) was defined as the period in which the instantaneous wall thickness exceeded 90% of the maximum wall thickness. The ThT was measured from the ventricular wall thickness curve at the same segments where regional percentage uptake and washout rate of (123)I MIBG were measured. PATIENTS: Seven patients with long QT syndrome. RESULTS: The regional washout rate (mean (SD)) of (123)I MIBG in patients with long QT syndrome was greater in the segments with decreased percentage uptake of (123)I MIBG than in those without (17.4 (10.6)% v 9.7 (16.5)%, p < 0. 03). ThT in segments both with and without decreased percentage uptake of (123)I MIBG was longer than in control subjects (p < 0. 0001). ThT was longer in the segments with decreased percentage uptake of (123)I MIBG than in those without (199 (70) ms v 150 (66) ms, p = 0.0018). CONCLUSIONS: Activation of regional cardiac sympathetic terminals is likely to participate in additional regional prolongation of ventricular repolarisation in patients with long QT syndrome.     

Expression of matrix metalloproteinases in cardiac allograft vasculopathy and its attenuation by anti MMP-2 ribozyme gene transfection

OBJECTIVE: Proliferation and migration of vascular smooth muscle cells (SMCs) causes intimal thickening during cardiac allograft vasculopathy (CAV). This process requires the degradation or remodeling of extracellular matrix (ECM) surrounding the cells. Imbalance between degradation and accumulation of ECM also contributes to the development of CAV. In this study, we investigated the contribution of matrix metalloprotenases (MMPs), enzymes regulating ECM turnover, to the development of CAV. METHODS: Donor hearts from male DBA mice were heterotopically transplanted to male B10.D2 recipient mice, and harvested at days 15 and 30 post transplantation. We examined expression MMP-2, -3, -9 and -13 of graft vessels using immunohistochemistry. To clarify the role of MMP-2 in CAV, anti MMP-2 ribozyme was delivered into donor hearts just before transplantation, mediated by a hemagglutinating virus of Japan-liposome complex to specifically suppress MMP-2 activity. RESULTS: All MMPs were immunopositive in SMCs from the slightly thickened neointima at day 15. In the advanced stage of intimal thickening at day 30, in addition to increased number of SMCs, accumulation of collagenous fibers was observed; expression of MMP-3, -9 and -13 was decreased. In contrast, MMP-2 expression remained distinctly positive throughout the progression of the vascular remodeling. After the gene transfer of MMP-2 ribozyme, luminal occlusion was significantly decreased compared to non-treated allografts [25.0+/-6.5 vs. 55.1+/-7.0% (P<0.05)] at day 30 post transplantation. CONCLUSION: MMP-2 is a principle MMP throughout the progression of the vascular remodeling in CAV. Anti MMP-2 therapy could therefore be one of the candidates for a supplemental therapy for CAV.     

Ankle arthrodesis using a retrograde intramedullary rod with fins for highly destructive joints in elderly patients with rheumatoid arthritis: A report of two cases

Herein, we present two cases of older adult patients with highly destructive changes in ankle joints (Larsen grade IV) who underwent retrograde intramedullary ankle nail fixation with fins. In both patients, bony union was achieved, and full weight‐bearing was attained at 3 months after surgery.     

Suppressing effects of daily oral supplementation of beta-glucan extracted from Agaricus blazei Murill on spontaneous and peritoneal disseminated metastasis in mouse model

Purpose: The Basidiomycete fungus Agaricus blazei Murill has traditionally been used as a health food for the prevention of cancer. Methods: We examined whether beta-(1–6)-D-glucan extracted from A. blazei is a potential anticancer agent in an in vitro and in vivo animal model. Results: Here we show that (1) beta-glucan had cytotoxic effect against human ovarian cancer HRA cells, but not against murine Lewis lung cancer 3LL cells, in vitro; (2) beta-glucan promotes p38 MAPK activity for suppressing HRA cell proliferation and amplifying the apoptosis cascade; (3) beta-glucan stimulates translocation of the proapoptotic protein, Bax, from the cytosol to mitochondria, cytochrome c release, and subsequent caspase-9 activation; (4) treatment with SB203580, a p38 MAPK-specific inhibitor, suppresses beta-glucan-induced effects, indicating that activation of p38 MAPK is involved in the suppression of cell proliferation and mitochondrial activation-mediated cell death pathway; (5) in mice, oral supplementation with beta-glucan reduces pulmonary metastasis of 3LL cells and peritoneal disseminated metastasis of HRA cells and inhibits the growth of these metastatic tumors in lung or peritoneal cavity, in part, by suppressing uPA expression; and (6) in an in vivo experimental metastasis assay, however, the oral supplementation with beta-glucan after i.v. tumor cell inoculation did not reduce the number of lung tumor colonies. Conclusion: Treatment with beta-glucan may be beneficial for cancer patients with or at risk for metastasis. The beta-glucan-dependent signaling pathways are critical for our understanding of anticancer events and development of cancer therapeutic agents.     

Neurotoxicity induced by tacrolimus after liver transplantation: relation to genetic polymorphisms of the ABCB1 (MDR1) gene

BACKGROUND: Tacrolimus is a substrate of P-glycoprotein (PGP) encoded by the multidrug resistant (MDR)1 gene (ABCB1). PGP, a multidrug efflux pump, restricts the distribution of tacrolimus in the brain. In this study, we investigate the correlation of ABCB1 gene polymorphism with tacrolimus-induced neurotoxicity in patients after liver transplantation. METHODS: The genotype of 6 patients with neurotoxic events and 11 patients without neurotoxic events was analyzed by polymerase chain reaction (PCR), and 8 mutations were detected. In addition to laboratory findings and patient characteristics, the contribution of mutations in the ABCB1 gene was evaluated with stepwise discriminant function analysis. RESULTS: High tacrolimus concentration, liver dysfunction, and mutation at position 2677 in exon 21 were demonstrated as positive predictors of tacrolimus-induced neurotoxicity. CONCLUSION: It is indicated that blood concentrations, liver function, graft weight, and polymorphism in the ABCB1 gene are important factors in tacrolimus-induced neurotoxicity.