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Background Cardiac rupture (CR) is a catastrophic complication of acute myocardial infarction. Primary percutaneous coronary intervention (pPCI) reduces the incidence of CR. This study aimed to investigate the clinical risk factors and characteristics of CR after pPCI. Methods This was a retrospective, case-control, multicenter study. We enrolled 2444 consecutive patients with ST-elevation myocardial infarction (STEMI) who had undergone pPCI between 2009 and 2015; 33 patients experienced CR (1.35%): 19 were assigned as early CR (≤72 h) and 14 as late CR (>72 h). The 132 controls were randomly selected from the 2411 STEMI patients without CR, by matching institutions at a 1:4 ratio. Results : Multivariate logistic regression revealed that female sex, acute hyperglycemia, thrombocytopenia (platelets 1, and post-PCI TIMI 1 and thrombocytopenia were strongly associated with late CR. Early CR occurred more frequently between 12:00 and 21:00 h, whereas the peak incidence of late CR was bimodal between 6:00–12:00 and 21:00–24:00 h. Conclusions In STEMI patients after pPCI, acute hyperglycemia and thrombocytopenia are new risk factors for early and late CR, respectively. Clinical risk factors and time of occurrence of early and late CR may differ in the PCI era.

The coronavirus disease 2019 pandemic occurred in several countries, making the conventional medical system difficult to maintain. Recent recommendations aim to prevent nosocomial infections and infections among health care workers. Therefore, establishing a cardiovascular medical system under an emergency for patients with ST-segment elevation myocardial infarction (STEMI) is desired. This study aimed to determine the relationship between prognosis and door-to-balloon time (DBT) shortening based on the severity on arrival.This retrospective, multi-center, observational study included 1,127 consecutive patients with STEMI. These patients were transported by emergency medical services and underwent primary percutaneous coronary intervention. Patients were stratified according to the Killip classification: Killip 1 (n = 738) and Killip ≥ 2 (n = 389) groups.Patients in the Killip ≥ 2 group were older, with more females, and more severity on arrival than those in the Killip 1 group. The 30-day mortality rate in the Killip 1 and Killip ≥ 2 groups was 2.2% and 18.0%, respectively. The Killip ≥ 2 group had a significant difference in the 30-day mortality between patients with DBT ≤ 90 minutes and those with DBT90 minutes; however, this did not occur in the Killip 1 group. Furthermore, multivariate analysis revealed that DBT ≤ 90 minutes was not a significant predictive factor in the Killip 1 group; however, it was an independent predictive factor in the Killip ≥ 2 group.DBT shortening affected the 30-day mortality in STEMI patients with Killip ≥ 2, although not those with Killip 1.

Autopsy was performed on a COVID-19 patient, who suddenly died despite the extensive anti-viral and anti-inflammatory therapies. Although moderate subpleural fibrosis was seen, pathology of DAD, a well-known cause for pulmonary failure, was minimum. Instead, severe hemorrhage was observed. Therapeutic effects were indicated, however why severe hemorrhage occurred was unclear.

Purpose: The effects of daily teriparatide (20 μg) (D-PTH), weekly high-dose teriparatide (56.5 μg) (W-PTH), or bisphosphonates (BPs) on areal bone mineral density (aBMD), bone turnover markers (BTMs), volumetric BMD (vBMD), microarchitecture, and estimated strength were investigated in postmenopausal osteoporosis patients. Methods: The study participants were 131 women with a history of fragility fractures. They were randomized to receive D-PTH, W-PTH, or BPs (alendronate or risedronate) for 18 months. Dual-energy X-ray absorptiometry (DXA), BTMs, and high-resolution peripheral quantitative CT (HR-pQCT) parameters were evaluated at baseline and after 6 and 18 months of treatment. The primary endpoint was the change (%) in cortical thickness (Ct.Th) after 18 months' treatment compared with baseline. Results: DXA showed that D-PTH, W-PTH, and BPs increased lumbar spine aBMD (+12.0%, +8.5%, and +6.8%) and total hip aBMD (+3.0%, +2.1%, and +3.0%), but D-PTH and W-PTH decreased 1/3 radius aBMD (− 4.1%, − 3.0%, − 1.4%) after 18 months. On HR-pQCT, D-PTH increased trabecular vBMD (Tb.vBMD) at the distal radius and tibia after 18 months (+6.4%, +3.7%) compared with the BPs group, decreased cortical volumetric tissue mineral density (Ct.vTMD) (− 1.8%, − 0.9%) compared with the other groups, increased Ct.Th (+1.3%, +3.9%), and increased failure load (FL) (+4.7%, +4.4%). W-PTH increased Tb.vBMD (+5.3%, +1.9%), maintained Ct.vTMD (− 0.7%, +0.2%) compared with D-PTH, increased Ct.Th (+0.6%, +3.6%), and increased FL (+4.9%, +4.5%). The BPs increased Tb.vBMD only in the radius (+2.0%, +0.2%), maintained Ct.vTMD (− 0.6%, +0.3%), increased Ct.Th (+0.5%, +3.4%), and increased FL (+3.9%, +2.8%). Conclusions: D-PTH and W-PTH comparably increased Ct.Th, the primary endpoint. D-PTH had a strong effect on trabecular bone. Although D-PTH decreased Ct.vTMD, it increased Ct.Th and total bone strength. W-PTH had a moderate effect on trabecular bone, maintained Ct.vTMD, and increased Ct.Th and total bone strength to the same extent as D-PTH., Bone, 160, art. no. 116416; 2022

Patients with ST-elevation myocardial infarction (STEMI) who arrive at a hospital via self-transport reportedly have a delayed door-to-balloon time (DBT). However, the clinical impacts of delayed DBT on in-hospital mortality among such patients are not well known.Methods and Results:In total, 1,172 STEMI patients who underwent primary percutaneous coronary intervention between January 2009 and December 2013 from the Acute Myocardial Infarction (AMI) Kyoto Registry were analyzed. Compared with the emergency medical service (EMS) group (n=804), the self-transport group (n=368) was younger and had a significantly longer DBT (115 min vs. 90 min, P0.01), with fewer patients having a Killip classification of 2 or higher. The in-hospital mortality rate was lower in the self-transport group than in the EMS group (3.3% vs. 7.1%, P0.01). A DBT90 min was an independent predictor of in-hospital mortality in EMS patients (odds ratio (OR)=2.43, P=0.01) but not in self-transport patients (OR=0.89, P=0.87).The present study demonstrated that there was no relationship between in-hospital prognosis and DBT ≤90 min in STEMI patients using self-transport. The prognosis of these patients cannot be improved by focusing only on DBT. Treatment strategies based on means of transport should also be considered.

A J-shaped or U-shaped curve phenomenon might exist between systolic blood pressure (SBP) or pulse pressure (PP) at admission and in-hospital mortality in Japanese patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI). However, data regarding a relationship between mean blood pressure (MBP) at admission and in-hospital outcome in AMI patients undergoing primary PCI are still lacking in Japan.A total of 1,413 primary PCI-treated AMI patients were classified into quintiles based on admission MBP (< 79 n = 283, 79-91 n = 285, 92-103 n = 285, 104-115 n = 279, and ≥ 116 mmHg n = 281). Patients with MBP < 79 mmHg had a significantly higher in-hospital mortality, while mortality was not significantly different among the other quintiles: 16.6% (< 79), 4.9% (79-91), 3.9% (92-103), 3.2% (104-115), and 5.0% (≥ 116 mmHg). On multivariate analysis, Killip class ≥ 3 at admission, LMT or multivessels as culprit lesions, admission MBP < 79 mmHg, and age were independent positive predictors of in-hospital mortality, whereas hypercholesterolemia and TIMI 3 flow before/after PCI were negative predictors, while the other MBP categories were not.These results suggest that admission MBP < 79 mmHg might be associated with in-hospital death, and the in-hospital prognostic effects of MBP, the steady component of blood pressure, at admission might be different from those of SBP or PP, the pulsatile component of blood pressure, at admission in Japanese AMI patients undergoing primary PCI.

Acute myocardial infarction (AMI) at left main trunk (LMT) is a deteriorated condition with high in-hospital morbidity and mortality; however, detailed data regarding AMI patients with LMT as culprit lesion (LMT-AMI patients) undergoing primary percutaneous coronary intervention (PCI) has been still limited. Using the AMI-Kyoto Multi-Center Risk Study database, clinical background, angiographic findings and results of primary PCI were retrospectively compared between primary PCI-treated LMT-AMI patients without in-hospital death (survivors, n = 21) and those with in-hospital death (non-survivors, n = 19). The survivors had higher values of estimated glomerular filtration rate (eGFR) and systolic blood pressure at admission and lower prevalence of Killip grade 4 than the non-survivors. Pre-procedural thrombolysis in myocardial infarction (TIMI) flow grade ≥2 at the initial coronary angiography (CAG) and post-procedural TIMI flow grade 3 at the final CAG were more frequent in the survivors, compared with the non-survivors. In contrast, age and gender did not differ significantly between the two groups. On multivariate analysis, higher eGFR and Killip grade 4 at admission were found to be independent in-hospital prognostic factors in the LMT-AMI patients. Admission eGFR and Killip grade 4 are tightly associated with in-hospital prognosis in LMT-AMI patients undergoing primary PCI.

Data regarding clinical efficacy of thrombectomy in patients with acute myocardial infarction (AMI) have been still limited in Japan. Using the AMI-Kyoto Multi-Center Risk Study database, the clinical background characteristics, angiographic findings, primary percutaneous coronary intervention (PCI) results and in-hospital prognoses were retrospectively compared between AMI patients with totally occluded infarct-related artery (IRA) (TIMI flow grade 0) undergoing thrombus aspiration during primary PCI (with-aspiration patients, n = 568) and those without thrombus aspiration (without-aspiration patients, n = 266). The with-aspiration patients were more likely to have higher TIMI grade in the IRA immediately after primary PCI, and had a lower in-hospital mortality rate than the without-aspiration patients. According to a multivariate analysis, thrombectomy as well as stent usage was found to be independent predictor of final TIMI flow grade ≥2 in the IRA, and the final TIMI flow grade ≥2 in the IRA was found to be an independent factor for in-hospital survival. These results suggest that among real-world, unselected Japanese AMI patients with totally occluded IRA on initial coronary angiography, thrombus aspiration is an effective adjunctive therapy during primary PCI to improve final epicardial coronary flow in the IRA, which might lead to better in-hospital prognosis.

Background Many mortality risk scoring tools exist among patients with ST-elevation Myocardial Infarction (STEMI). A risk stratification model that evaluates STEMI prognosis more simply and rapidly is preferred in clinical practice. Methods and Findings We developed a simple stratification model for blood examination by using the STEMI data of AMI-Kyoto registry in the derivation set (n = 1,060) and assessed its utility for mortality prediction in the validation set (n = 521). We selected five variables that significantly worsen in-hospital mortality: white blood cell count, hemoglobin, C-reactive protein, creatinine, and blood sugar levels at >10,000/μL, 1.0 mg/dL, >1.0 mg/dL, and >200 mg/dL, respectively. In the derivation set, each of the five variables significantly worsened in-hospital mortality (p < 0.01). We developed the risk stratification model by combining laboratory variables that were scored based on each beta coefficient obtained using multivariate analysis and divided three laboratory groups. We also found a significant trend in the in-hospital mortality rate for three laboratory groups. Therefore, we assessed the utility of this model in the validation set. The prognostic discriminatory capacity of our laboratory stratification model was comparable to that of the full multivariable model (c-statistic: derivation set vs validation set, 0.81 vs 0.74). In addition, we divided all cases (n = 1,581) into three thrombolysis in myocardial infarction (TIMI) risk index groups based on an In TIME II substudy; the cases were further subdivided based on this laboratory model. The high laboratory group had significantly high in-hospital mortality rate in each TIMI risk index group (trend of in-hospital mortality; p < 0.01). Conclusions This laboratory stratification model can predict in-hospital mortality of STEMI simply and rapidly and might be useful for predicting in-hospital mortality of STEMI by further subdividing the TIMI risk index.

Data regarding relationship between pulse pressure (PP) at admission and in-hospital outcome in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) are still lacking. A total of 1413 primary PCI-treated AMI patients were classified into quintiles based on admission PP (

SummaryBackgroundData regarding the relationship between systolic blood pressure (SBP) at admission and in-hospital outcome in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) are still lacking in Japan.Methods and resultsA total of 1475 primary PCI-treated AMI patients were classified into quintiles based on admission SBP (

SummaryBackgroundSeveral clinical studies have demonstrated an inverse relationship between systolic blood pressure (SBP) at admission and in-hospital mortality in patients hospitalized for acute myocardial infarction (AMI). However, data on the relation between admission SBP and in-hospital prognosis in AMI patients are still lacking in Japan.Methods and resultsA total of 1211 AMI patients were classified into quintiles based on SBP at hospital admission (

【はじめに】橈骨頭周囲の骨化をきたした小児亜急性期Monteggia骨折の1例を経験したので報告する．【症例】7歳，女児．左手をついて転倒し受傷．近医受診するも橈骨頭脱臼に気づかれず，シーネ固定のみ受けた．受傷後25日目に左橈骨頭脱臼および橈骨頭周囲の骨化像を指摘され当科外来初診．左肘の著明な可動域制限および単純X線で左尺骨の塑性変形を認め，小児Monteggia骨折と診断した．受傷後33日目に手術施行．橈骨頭脱臼の整復は尺骨の可及的徒手矯正のみでは困難で，観血的な骨化巣の全切除を要した．術後5日目に橈骨頭の再脱臼を認めたため，同日再手術施行．尺骨骨切りや輪状靱帯再建には家族の同意が得られず，近位橈尺関節の経皮ピンニングを行った．再手術後の経過は良好で術後1カ月で抜線し可動域訓練を行った．最終観察時，軽度の回内制限が残存するが，ADL障害はなく，再脱臼，骨化は認めなかった．

Summary Background Prolonged pre-hospital time for acute myocardial infarction (AMI) is associated with decreased indication for primary percutaneous coronary intervention (PCI). However, the efficacy of primary PCI in AMI patients with prolonged pre-hospital time has not been fully investigated in Japan. Methods and results A total of 3010 consecutive AMI patients admitted to AMI-Kyoto Multi-Center Risk Study Group hospitals were retrospectively analyzed, and the clinical characteristics and in-hospital prognosis of these patients were reviewed. Patients with pre-hospital delay [elapsed time (ET) > 12 h] had a lower frequency of Killip ≥ 3 (9.3%) and less frequently received primary PCI (77.7%) compared with patients with ET ≤ 12 h. In the ET > 12 h group, older patients or patients with MI history tended to be complicated by heart failure. Primary PCI was performed for patients with ET > 12 h, irrespective of the severity of heart failure [Killip 1 (78.7%) vs Killip ≥ 2 (74.0%); p = 0.3827]. On multivariate logistic regression analysis, age [odds ratio (OR) 1.053], MI history (OR 2.860), Killip ≥ 2 (OR 10.235), and multi-vessels or left main coronary artery as culprit (OR 11.712) were significant independent positive predictors of in-hospital mortality for patients with ET > 12 h. Practice of primary PCI was not a significant negative predictor for patients with ET > 12 h (OR 0.812), but it was for patients with ET ≤ 12 h (OR 0.425). Conclusions These findings indicate that patients with ET > 12 h have a less severe condition and less frequently receive primary PCI compared with patients with ET ≤ 12 h. Although primary PCI is often performed for these patients irrespective of the severity of heart failure, no preferable effect of primary PCI on the in-hospital mortality is demonstrated. In contrary, practice of primary PCI is a significant negative predictor of in-hospital mortality for patients with ET ≤ 12 h.

Background: Erythropoietin (EPO) enhances re-endothelialization and anti-apoptotic action. Larger clinical studies to examine the effects of high-dose EPO are in progress in patients with acute myocardial infarction (AMI). Methods and Results: The aim of this multi-center pilot study was to investigate the effect of `low-dose EPO' (6,000 IU during percutaneous coronary intervention (PCI), 24 h and 48 h) in 35 patients with a first ST-elevated AMI undergoing PCI who was randomly assigned to EPO or placebo (saline) treatment. Neointimal volume, cardiac function and infarct size were examined in the acute phase and 6 months later (ClinicalTrials.gov identifier: NCT00423020). No significant regression in in-stent neointimal volume was observed, whereas left ventricular (LV) ejection fraction was significantly improved (49.2% to 55.7%, P=0.003) and LV end-systolic volume was decreased in the EPO group (47.7 ml to 39.0 ml, P=0.036). LV end-diastolic volume tended to be reduced from 90.2% to 84.5% (P=0.159), whereas in the control group it was inversely increased (91.7% to 93.7%, P=0.385). Infarction sizes were significantly reduced by 38.5% (P=0.003) but not in the control group (23.7%, P=0.051). Hemoglobin, peak creatine kinase values, and CD34+/CD133+/CD45dim endothelial progenitors showed no significant changes. No adverse events were observed during study periods. Conclusions: This is a first study demonstrating that short-term `low-dose' EPO to PCI-treated AMI patients did not prevent neointimal hyperplasia but rather improved cardiac function and infarct size without any clinical adverse effects. (Circ J 2010; 74: 2365-2371)

［はじめに］頚椎に発生し脊髄症状を呈した骨軟骨腫の一例を経験したので報告する．［症例］13歳女性．多発性骨軟骨腫の既往があり3度の摘出術（右前腕，右手，両膝）を施行されている．入院2ヶ月前より右上腕から前腕にかけてしびれ，脱力感が出現．入院1ヶ月より箸の保持困難を自覚．歩行時につまずくようになり近医受診．頚部脊柱管を狭窄する椎弓由来の腫瘍を指摘され当科入院となった．腫瘍はC5椎弓より発生，脊柱管内に達し硬膜を圧迫していた為，これによる脊髄症状と診断．腫瘍摘出術を行い，症状の著明な改善を得た．病理診断は骨軟骨腫であった．［考察］骨軟骨腫は長管骨骨幹端部に好発する良性骨腫瘍としてよく知られているが，脊椎発生はまれである．今回我々は，頚椎に発生し脊髄症状を呈した骨軟骨腫の1例を経験したので若干の文献的考察を加えて報告する．

Single-strand elbow medial collateral ligament reconstruction strength was evaluated by use of double-docking and interference screw methods with either a palmaris longus tendon or GraftJacket as the reconstruction material. Thirteen upper extremities were mounted in 90 degrees of valgus orientation and subjected to cyclic valgus loading that increased progressively until failure occurred. The double-docking reconstructions outperformed the interference screw reconstructions (P.05), whereas the palmaris longus and GraftJacket performed comparably (P.05). The favorable initial strength of the GraftJacket make it a potentially viable alternative to the use of autogenous palmaris longus tendons; however, further studies are required to evaluate graft strength during healing. The clinical use of the double-docking technique of single-strand medial collateral ligament reconstruction should be considered because of its simplicity and initial strength.

To investigate the molecular mechanism underlying the differentiation of osteoblasts and chondroblasts, we established a clonal cell lines, RD-C6, from Runx2-deficient mouse embryos. RD-C6 cells expressed almost undetectable levels of phenotypes related to osteoblast and chondroblast differentiation at basal culture condition, whereas treatment with recombinant human bone morphogenetic protein-2 (rhBMP-2) or transduction of BMP-2 by adenovirus effectively induced this cell line to express mRNA related to the differentiation of osteoblasts and chondroblasts including alkaline phosphatase, osteocalcin, and osterix. Transduction of Runx2 also induced the expression of these mRNA in RD-C6 cells. BMP-2 transduction increased expression levels of mRNA for Msx2 and Dlx5, but Runx2 transduction induced no significant increases in expression levels of these mRNA. Microarray analysis using RD-C6 cells with or without rhBMP-2 treatment demonstrated that BMP-2 upregulated 66 genes including 13 transcription-related molecules such as Id1, Id2, Id4, Hey1, Smad6, Smad7, and Msx2. To confirm bone and cartilage formation ability of RD-C6 cells, we transplanted RD-C6 cells into the peritoneal cavity of athymic mice using diffusion chambers with rhBMP-2. RD-C6 cells generated unmineralized cartilage but not bone. These results indicate that BMP-2 induces Runx2-deficient cells to express markers related to osteoblast and chondroblast differentiation using a Runx2-independent pathway, but it failed to induce these cells to differentiate into bone-forming osteoblasts and mature chondrocytes.

症例は29歳男性．14ヶ月前より頸背部痛，腰痛が出現．近医外来にて加療したが症状軽快せず，総合病院入院．頸椎から仙椎にかけての多発する溶骨性変化，Th1/2，3/4，7の硬膜外膿瘍および腸骨，肋骨に溶骨性変化を認めた．骨生検にて乾酪性肉芽腫，ラングハンス巨細胞，抗酸菌を認めたことから多発性骨結核と診断され，抗結核薬の内服を開始したが，内服加療開始後よりTh4以下のしびれが出現し，両下肢不全麻痺を呈した．約6ヶ月間の抗結核薬内服と臥位安静加療を行ったが麻痺の十分な改善が得られなかったため当科入院．Th3，4に認めた膿瘍が硬膜管を圧排しており，後方よりインストゥルメンテーションを使用した7椎間におよぶ脊椎固定術，骨移植術を施行し，症状の著明な改善を得た．術後4ヶ月で再発兆候はなく，独歩も可能となった．今回我々は，病変が極めて広範囲である稀な骨結核の1例を経験したので若干の文献的考察を加えて報告する．

【目的】2001年5月より外傷性肩関節前方不安定症に対して行った鏡視下Bankart法の短期成績を報告する．【対象と方法】術後8ヵ月以上経過した21例22肩を対象とした．性別は男性15例，女性7例，患側は右側13例，左側9例である．手術時平均年齢は23歳，術後平均経過観察期間は20ヵ月であった．手術方法は鏡視下にアンカーを平均3個用いて，剥離した関節唇を関節窩に修復した．臨床評価はJOA Score，JSS Shoulder Instability Scoreを用いて調べ，再脱臼，スポーツ復帰の程度について検討した．【結果】臨床評価ではJOA Scoreが平均74.8点から98.1点，JSS Shoulder Instability Scoreが平均54.8点から97.5点と，主に疼痛，関節安定性の改善を認めた．スポーツ復帰は全例で可能であったが，ラグビー選手1例にタックル時再脱臼を認めた．【考察】鏡視下Bankart法の短期成績は良好であったが，ラグビーなどコンタクトスポーツでは，さらなる長期観察が必要と考える．

We describe a case of neuro-Behcet's disease (NBD) characterized by recurrent attacks of neurologic deficit. T2-weighted images showed a high signal intensity lesion with extensive edema in the right thalamolenticular region, midbrain, and pons as well as the cerebral white matter. After a relapse of the disease, MRI demonstrated a high signal intensity in the left thalamus, internal capsule, and midbrain. These MRI abnormalities showed marked resolution with steroid treatment. We observed sequential MRI findings in a patient with a relapsing–remitting form of NBD who had parenchymal CNS involvement, and we examined the correlation among the MRI findings and clinical features during the clinical course.

We investigated the osteogenic potential of skin fibroblasts that overexpressed BMP-2 or Runx2 by using adenoviral vectors. In in vitro experiments, skin fibroblasts infected with adenovirus vector encoding BMP-2 (AdBMP-2) released substantial levels of BMP-2 proteins into culture media, and those infected with adenovirus vector encoding Runx2 (AdRunx2) produced its protein. Transduction of BMP-2 or Runx2, respectively, increased alkaline phosphatase (ALP) activity and induced expression of mRNAs of ALP, osteocalcin, and osterix in skin fibroblasts. In in vivo experiments, we investigated the bone induction activity by transplantation of a complex composed of carrier [poly-D,L-lactic-co-glycolic acid/gelatin sponge (PGS)] and skin fibroblasts (PGS/SF complex). Transplantation of PGS/SF complexes composed of skin fibroblasts transduced with AdBMP-2-induced ectopic bone formation when transplanted into the subfascia of back muscle, unlike those infected with AdRunx2. Transplantation of PGS/SF complexes composed of skin fibroblasts transduced with AdBMP-2 into craniotomy defects induced bone formation from 2 weeks after transplantation, and almost all PGS was replaced by newly synthesized bone at 6 weeks. To investigate the fate of the transplanted cells, we transplanted skin fibroblasts isolated from green fluorescence protein transgenic mice into craniotomy defects. Transplantation of these skin fibroblasts transfected with AdBMP-2 generated green fluorescence protein-positive osteoblasts and osteocytes, indicating that the transplanted skin fibroblasts differentiated into osteoblastic lineage cells during bone repair. In contrast, transplantation of PGS/SF complexes composed of skin fibroblasts transduced with AdRunx2 induced a few ALP-positive cells at 1 week after transplantation, but their number decreased depending on time after transplantation. In addition, transplantation of these complexes was insufficient to induce bone repair. Taken together, our results suggest that skin fibroblasts expressing BMP-2 are more suitable for cell-mediated therapy of bone repair than those expressing Runx2.

Background: Cart1 encodes the paired-like homeodomain in the central portion of the gene, and plays a crucial role in the developmental lineage of bone and cartilage, especially in head formation. However, its transactivation mechanism is still poorly understood, including the target gene. Here, we report biochemical dissections of Cart1 functional domains and a relationship between dimerization and transcription activity. Results: Deletion studies of GAL4-fused Cart1 indicated that the transactivation domain is located in the middle portion of the C-terminal domain, but the N-terminal is also required for a full activation of the consensus palindromic binding site (TAATNNNATTA). Analysis of the basic amino acid residues at both ends of the homeodomain revealed that both sides act as nuclear localization signals, and are necessary for the cooperative binding to the palindromic sequence. In this study, two additional Cart1 isoforms that behave as dominant negatives were identified from rat chondrosarcoma cells. These isoforms suppressed the transcription activity of the wild-type, despite loss of DNA binding ability, and could interact with the wild-type in yeast. Finally, we demonstrated that wild-type Cart1 forms a DNA-independent homodimer in in vivo conditions, and that the transactivation of wild-type Cart1 was suppressed by the N- or C-terminal domain which was expressed in the nucleus. Conclusion: These results revealed that homodimerization through direct interaction is necessary for the potent transcription activity of Cart1.

Cardiorenal anemia syndrome has recently been receiving greater attention; however, data regarding the relationship between chronic kidney disease (CKD)/anemia on presentation and in-hospital outcome in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) are still limited in Japan.A total of 1,447 primary PCI-treated AMI patients were classified into 4 groups according to the presence of CKD and/or anemia on hospital admission (with CKD/with anemia n = 222, with CKD/without anemia n = 299, without CKD/with anemia n = 151, without CKD/without anemia n = 775). Angiographic acute results of primary PCI were similar among the 4 groups. The patients with CKD had a significantly higher in-hospital overall mortality rate than the patients without CKD, and in the presence or absence of CKD, patients with anemia tended to have a higher in-hospital mortality rate than the patients without anemia. According to a multivariate analysis, anemia on admission was found to be an independent predictor of in-hospital mortality, whereas admission CKD and admission eGFR were statistically not independent predictors. Moreover, the multivariable adjusted odds ratio of in-hospital death in AMI patients with CKD alone was 1.855 (95% CI 0.929-3.706), and that in AMI patients with CKD/with anemia was 3.384 (95% CI 1.697-6.748).These results suggest that among real-world, unselected Japanese AMI patients undergoing primary PCI, the combination of CKD and anemia on admission confers significant adverse effects on in-hospital mortality.

Objective The predictors of in-hospital outcomes after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) complicated with heart failure or cardiogenic shock at presentation remain unclear. Methods Using the AMI-Kyoto Multi-Center Risk Study database, the clinical background characteristics, angiographic findings, primary PCI results, and in-hospital prognoses were retrospectively compared between primary PCI-treated AMI patients with a Killip class status of ≥2 (Killip 2-4 patients, n=390) and those with a Killip class 1 status (Killip 1 patients, n=1,057). Results The Killip 2-4 patients were more likely to have a higher age and proportion of women and exhibited a higher prevalence of previous myocardial infarction, diabetes mellitus and chronic kidney disease or anemia on admission, lower systolic blood pressure (SBP) values on admission, a higher rate of multivessels or left main trunk as the culprit artery, a larger number of diseased vessels, a lower Thrombolysis In Myocardial Infarction (TIMI) grade in the infarct-related artery (IRA) before/after primary PCI and a significantly higher in-hospital mortality rate than the Killip 1 patients. According to a multivariate analysis, age was found to be an independent positive predictor of in-hospital mortality, while admission SBP was an independent positive predictor of in-hospital survival in both groups. In contrast, anemia on admission was found to be an independent predictor of in-hospital death, while the TIMI 3 flow in the IRA after PCI was found to be an independent factor for survival in the Killip 2-4 patients, but not the Killip 1 patients. Conclusion Anemia on admission and the final TIMI 3 flow in the IRA are critical determinants of in-hospital death in AMI patients with a Killip class status of ≥2 undergoing primary PCI.

Lithium-ion batteries have exclusively employed an ethylene carbonate (EC)-based electrolyte to ensure the reversibility of the graphite negative electrode reaction. Because of the limitation of electrolyte compositions, there has been no remarkable progress in commercial lithium-ion batteries despite active research on positive electrode materials. Herein, we present a salt-superconcentrating strategy as a simple and effective method of universalizing a graphite negative electrode reaction in various organic solvents. A dilute electrolyte (e.g., 1 mol dm(-3)) of sulfoxide, ether, and sulfone results in solvent cointercalation and/or severe electrolyte decomposition at a graphite electrode, whereas their superconcentrated electrolyte (e.g.,3 mol dm(-3)) allows for highly reversible lithium intercalation into graphite. We have found a unique coordination structure in the superconcentrated solution and an anion-based inorganic SEI film on the cycled graphite electrode, which would be the origin of the reversible graphite negative electrode reaction without EC. Our salt-superconcentrating strategy, expanding the graphite negative electrode reaction in various organic solvents other than EC, will contribute to the development of advanced lithium-ion batteries with high-voltage and fast-charging characters based on new EC-free functional electrolytes.

The development of a stable, functional electrolyte is urgently required for fast-charging and high-voltage lithium-ion batteries as well as next-generation advanced batteries (e.g., Li-O2 systems). Acetonitrile (AN) solutions are one of the most promising electrolytes with remarkably high chemical and oxidative stability as well as high ionic conductivity, but its low stability against reduction is a critical problem that hinders its extensive applications. Herein, we report enhanced reductive stability of a superconcentrated AN solution (4 mol dm(-3)). Applying it to a battery electrolyte, we demonstrate, for the first time, reversible lithium intercalation into a graphite electrode in a reduction-vulnerable AN solvent. Moreover, the reaction kinetics is much faster than in a currently used commercial electrolyte. First-principle calculations combined with spectroscopic analyses reveal that the peculiar reductive stability arises from modified frontier orbital characters unique to such superconcentrated solutions, in which all solvents and anions coordinate to Li(+) cations to form a fluid polymeric network of anions and Li(+) cations.

We investigated the independent change in pulmonary diffusing capacity (DLCO) as one manifestation of pulmonary microangiopathy and to analyze the correlation between DLCO and serum ACE. We also examined the association between DLCO and the ACE genes. We examined pulmonary functions, especially %DLCO/VA (DLCO corrected by alveolar volume, percent predicted) in 54 NIDDM patients and 34 age-matched normal control subjects. Subjects were subdivided according to the degree of retinopathy. Serum ACE level was assayed by a colorimetric method in 54 patients and an insertion/deletion polymorphism in the ACE gene was amplified using the polymerase chain reaction in 52 of the 54 patients. There was a significant reduction of %DLCO/VA (percent predicted P0.05) in diabetic patients. In the proliferative retinopathy (PDR) group. %DLCO/VA was significantly (P0.05) lower than in the no diabetic retinopathy (NDR) and simple diabetic retinopathy (SDR) groups. Although the levels of serum ACE were within normal ranges in all diabetic groups, %DLCO/VA was negatively correlated with serum ACE values (r = 0.49, P0.0002, y = -1.4x + 109.3). Differences among DD, ID and II type of the ACE gene, with respect to the incidence of abnormal values of each clinical parameter, were not significant. DLCO was significantly reduced in patients with PDR and the serum ACE was significantly related to impaired DLCO. Our study suggests the existence of microangiopathic involvement of pulmonary vessels in NIDDM patients.

【目的】動揺性肩関節は女性に多く，全身の関節弛緩を伴うことが多い．今回はホルモン療法を行った患者の経過を報告する．【症例】女性4例．現在年齢はA38，B53，C28，D25歳で，全例II型の骨頭下降率を有し，他の関節にも不安定性を認めた．ホルモン療法の期間は4カ月～5年でBは閉経のため，Cは副作用のため現在治療中止している．Cのみ手術の既往はないが，他の3例は両肩のthermal shrinkageやcapsular shiftなどが行われている．【結果と考察】関節の不安定性にはプロゲステロンが関与しており，その働きを抑制するEP合剤（ピル）の投与や偽閉経療法などに効果が期待される．全例とも治療中は関節の安定性が得られ，自覚的な脱臼の程度や回数が減少した．関節の不安定性が完全に消失するわけではなく副作用もあるが，適応を選べば効果は期待でき，手術療法を行う前に一度試みてよい方法ではないかと考える．

Mutation in the mitochondrial gene at position 3243 was recently identified in a large pedigree of diabetes mellitus and deafness. As the mitochondria play an important role in glucose-stimulated insulin secretion in pancreatic beta-cells, we therefore searched for such mutations to detect a candidate gene for diabetes. We screened 10 diabetic subjects with clinical features suggesting mitochondrial DNA mutations. An adenine to guanine point mutation in tRNA(Lys) in at position 8296 (the 8296 mutation) was newly identified. Subsequently, we screened 1216 diabetic subjects, 44 patients with sensorineural deafness subjects and 300 non-diabetic control subjects for this mutation. We identified the mutation in 11 (0.90%) unrelated diabetic subjects, one (2.3%) patient with deafness and no non-diabetic control subject. Seven of these 12 subjects showed maternal inheritance. Deafness was seen in 7 of 12 probands. Four family pedigrees showed maternal inheritance of diabetes over two or three generations. Subjects carrying the 8296 mutation may develop diabetes and the mutation can explain as high as ca. 1% of the causes of diabetes.

We report a 17-year-old girl with short stature, external ophthalmoplegia, atypical retinal pigmentary degeneration, sensorineural hearing loss, and cardiac conduction defect (Kearns-Sayre syndrome). A large-scale deletion (6741 base pairs) in mitochondrial DNA was found in her muscle specimen. She also had insulin-dependent diabetes mellitus (IDDM). On admission, her plasma glucose level was elevated at 31.0mmol/l with mild ketoacidosis, and haemoglobinA1c elevated at 16.5%. After improvement of diabetic ketoacidosis, she was placed on insulin 24-30 units/day despite her small body weight of 25 kg. There was reduced excretion of urinary C-peptide at 3.97 nmol/day. In addition, she had idiopathic hypoparathyroidism with a serum calcium level of 2.15 mmol/l, phosphate 1.7 mmol/l, and intact PTH below 10 ng/l. Human leucocyte associated antigen typing showed A24, A26; B54, B61; CW1, CW3; DR8, DR14; DQ1 and DQ3, suggesting that the presence of HLA-A24 and CW3 antigen contributed to the association of IDDM and hypoparathyroidism, similar to Japanese patients with polyglandular autoimmune syndrome, complicated by hypoparathyroidism and IDDM. We suggest that a genetic linkage, as well as mitochondrial dysfunction, may be responsible for the association of the two disease states. This is an extremely rare case of Kearns-Sayre syndrome, presenting in association with IDDM and idiopathic hypoparathyroidism.

We report a 3-year-old girl with permanent dislocation of the patella due to distal femoral epiphyseolysis in the perinatal period.This distal femoral epiphyseolysis may have occurred from a trial of external cephalic version.Radiogram showed genu valgum in the right knee when aged two months.Presently, the patient has a permanent lateral dislocation of the patella.The etiology of patellar dislocation is discussed.

We investigated the clinical results and prognosis following the use of prosthetic arthroplasty of the proximal humerus. 12 shoulders of 11 patients were investigated. Preoperative diagnosis was dislocation fracture in 6 shoulders, non-union caused by fracture in 2 shuolders, and avascular necrosis of the humeral head in 4 shoulders. The mean age at operation was 56.3 years (range; 34-84 years) . The mean follow-up period was 3 years 7 months (7 months-17 years 9 months). Operative results were evaluated according to the Japanese Orthopaedic Association (JOA) score.The average postoperative JOA score for 6 cases with complications was 56.0 points (48-67 points). On the other hand in 6 cases without complications this was 84.7 points (74-97 points) . In four cases without complications, those who had their shoulder immobilized in an elevated position, the JOA score was higher (88.0 points) compared to the remaining two without immobilization (78.0 points).From the results of this study, it can be concluded that the prognosis is poor in patients with complications. Also, after prosthetic arthroplasty, if the shoulder is immobilized in an elevated position, better results can be obtained.

1) 原発性悪性骨腫瘍94例において, 骨格発育異常の合併を検索した.2) Ewing 肉腫1例に Down 症候群が合併し, 骨肉腫2例には Marfan 症候群, 低身長が合併していた.3) これら骨格発育異常と悪性骨腫瘍の合併は, 共通の遺伝子異常にもとつく可能性を示唆していた.

Purpose In previous reports, it was demonstrated that bone marrow adipocytes were related to steroid osteoporosis through osteoclastogenesis induced by Receptor Activator of Nuclear factor κ-B Ligand (RANKL) expression. The purpose of this study was to evaluate the effect of Tumor necrosis factor-alpha (TNF-α) on RANKL expression in bone marrow adipocytes, and osteoclast differentiation supported by human bone marrow adipocytes. Methods RANKL, osteoprotegerin (OPG), and macrophage-colony stimulating factor (M-CSF) mRNA expression in bone marrow adipocytes and their regulation by TNF-α treatment were measured by real-time RT-PCR. Co-cultures of bone marrow adipocytes and osteoclast precursors were performed with or without TNF-α, and osteoclast differentiation was evaluated morphologically and functionally. Results RANKL expression and an increase in the RANKL/OPG ratio in bone marrow adipocytes were stimulated by TNF-α treatment. In co-culture of bone marrow adipocytes and osteoclast precursors with TNF-α, the number of TRAP-positive multinuclear cells and resorption cavity formations of calcium phosphate film were increased. Osteoclast differentiation was suppressed by anti-RANKL antibody treatment. In co-culture with non-cell-contact conditions, no TRAP-positive cells or resorption cavity formations were observed. Conclusions TNF-α increased RANKL expression in primary human bone marrow adipocytes. TNF-α induced the ability of bone marrow adipocytes to promote osteoclast differentiation and activity in a manner directly related to RANKL expression.

SummaryA 54-year-old woman visited our hospital because of palpitation and dizziness. Systolic ejection murmur, Levine IV/VI, was heard at the left sternal border and atrial gallop was auscultated at apex. Echocardiogram demonstrated diffuse hypertrophy of the left ventricular walls extending to the apex. The left ventricular walls increased symmetrically; the septal and the posterior wall measured approximately 26mm and 30mm in thickness, respectively. Apical two-chamber views revealed a narrow outflow of the left ventricular cavity at apex with a distinct convergence zone, where color flow Doppler imaging showed turbulent jet flow from mid to late systole. The leukocyte α-galactosidase A activity was lower than normal. Percutaneous endomyocardial biopsy showed specific change for Fabry's disease by electron microscopy. On cardiac catheterization, mid-ventricular resting pressure gradient of approximately 90mmHg was shown. This pressure gradient dramatically disappeared after intravenous administration of 70mg of cibenzoline. We describe a rare case of Fabry's disease that revealed diffuse hypertrophy having dynamic obstruction at mid-left ventricle, like mid-ventricular obstruction, and the administration of cibenzoline had beneficial effects on pressure gradient of mid-left ventricle.

Erythropoietin (EPO) enhances re-endothelialization and anti-apoptotic action. Larger clinical studies to examine the effects of high-dose EPO are in progress in patients with acute myocardial infarction (AMI).The aim of this multi-center pilot study was to investigate the effect of `low-dose EPO' (6,000 IU during percutaneous coronary intervention (PCI), 24 h and 48 h) in 35 patients with a first ST-elevated AMI undergoing PCI who was randomly assigned to EPO or placebo (saline) treatment. Neointimal volume, cardiac function and infarct size were examined in the acute phase and 6 months later (ClinicalTrials.gov identifier: NCT00423020). No significant regression in in-stent neointimal volume was observed, whereas left ventricular (LV) ejection fraction was significantly improved (49.2% to 55.7%, P=0.003) and LV end-systolic volume was decreased in the EPO group (47.7 ml to 39.0 ml, P=0.036). LV end-diastolic volume tended to be reduced from 90.2% to 84.5% (P=0.159), whereas in the control group it was inversely increased (91.7% to 93.7%, P=0.385). Infarction sizes were significantly reduced by 38.5% (P=0.003) but not in the control group (23.7%, P=0.051). Hemoglobin, peak creatine kinase values, and CD34(+)/CD133(+)/CD45(dim) endothelial progenitors showed no significant changes. No adverse events were observed during study periods.This is a first study demonstrating that short-term `low-dose' EPO to PCI-treated AMI patients did not prevent neointimal hyperplasia but rather improved cardiac function and infarct size without any clinical adverse effects.

The mortality of heart failure patients with renal insufficiency is high, and these patients tend to develop diuretic resistance. Under these conditions, continuous hemodiafiltration (CHDF) is a possible alternative volume reduction therapy to diuretics. However, its efficacy and safety are not clear. Between April 2005 and March 2008, 248 patients with acute decompensated heart failure were admitted to the CCU of Kyoto City Hospital. Of those patients, 31 (20 volume overloaded heart failure, 11 cardiogenic shock) received CHDF therapy, and their weight loss, acute hemodynamic changes, and clinical outcome were assessed to evaluate the efficacy and safety of CHDF therapy. CHDF was performed for 6.5 +/- 6.5 days. There was no significant change in acute hemodynamics after CHDF initiation. In the volume overloaded heart failure (VH) group, significant weight loss was observed at 24 hours and 48 hours after CHDF initiation (P < 0.001). In-hospital mortality of the VH group and cardiogenic shock (CS) group were 10.0% and 54.5%, respectively. CHDF for acute decompensated heart failure (ADHF) is a safe, effective, and reliable volume reduction therapy for volume overloaded heart failure. Further investigation is required to assess the effectiveness of CHDF for cardiogenic shock.

Background: Predictors of in-hospital outcome after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) requiring mechanical support devices such as intra-aortic balloon pumping (IABP) and/or percutaneous cardiopulmonary support (PCPS) remain unclear. Methods and Results: Using the AMI-Kyoto Multi-Center Risk Study database, clinical background, angiographic findings, results of primary PCI, and in-hospital prognosis were retrospectively compared between primary PCI-treated AMI patients requiring mechanical assist devices (with-IABP/PCPS patients, n=275) and those without (without-IABP/PCPS patients, n=1,510). The with-IABP/PCPS patients were more likely to have a larger number of diseased vessels, lower Thrombolysis In Myocardial Infarction (TIMI) grade in the infarct-related artery (IRA) before/after primary PCI, and a significantly higher in-hospital mortality rate than the without-IABP/PCPS patients. On multivariate analysis, the number of diseased vessels ≥2 or diseased left main trunk (LMT) at initial coronary angiography (CAG) was the independent positive predictor of the in-hospital mortality in the with-IABP/PCPS patients, not in the without-IABP/PCPS patients, whereas acquisition of TIMI 3 flow in the IRA immediately after primary PCI was the negative predictor in the without-IABP/PCPS patients, not in the with-IABP/PCPS patients. Conclusions: The number of diseased vessels ≥2 or diseased LMT at initial CAG is an independent risk factor of in-hospital death in primary PCI-treated AMI patients requiring mechanical support devices. (Circ J 2010; 74: 1152 - 1157)