Low-Dose Erythropoietin in Patients With ST-Segment Elevation Myocardial Infarction (EPO-AMI-II) - A Randomized Controlled Clinical Trial.

Background: Erythropoietin (EPO) has antiapoptotic and tissue-protective effects, but previous clinical studies using high-dose EPO have not shown cardioprotective effects, probably because of platelet activation and a lack of knowledge regarding the optimal dose. In contrast, a small pilot study using low-dose EPO has shown improvement in left ventricular function without adverse cardiovascular events.

Methods and results: We performed a multicenter (25 hospitals), prospective, randomized, double-blind, placebo-controlled, dose-finding study to clarify the efficacy and safety of low-dose EPO in patients with ST-segment elevation myocardial infarction (STEMI) under the Evaluation System of Investigational Medical Care of the Ministry of Health, Labor and Welfare of Japan.

Manifestations of fulminant CD8 T-cell post-transplant lymphoproliferative disorder following the administration of rituximab for lymphadenopathy with a high level of Epstein-Barr Virus (EBV) replication after allogeneic hematopoietic stem cell transplantation.

We herein report the case of a 22-year-old woman with severe aplastic anemia who underwent allogeneic hematopoietic stem cell transplantation (HSCT). After HSCT, the Epstein-Barr virus (EBV)-DNA load in the peripheral blood gradually increased, and the patient presented with a fever and lymphadenopathy on day 56 post-HSCT. Although we administered rituximab, her clinical condition worsened.

Safety and clinical outcome of erythropoiesis-stimulating agents in patients with ST-elevation myocardial infarction: a meta-analysis of individual patient data.

Background: Erythropoiesis-stimulating agents (ESAs) have been investigated in small studies in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Erythropoiesis-stimulating agents did not show a clear effect on left ventricular function or clinical outcome, but some studies suggested an increased risk of thromboembolic events.

Methods: A systematic literature search in MEDLINE was performed, until December 2012.

Long-term PT-INR levels and the clinical events in the patients with non-valvular atrial fibrillation: a special reference to low-intensity warfarin therapy.

Background: Anticoagulation therapy is essential in atrial fibrillation (AF), and in Japan, less intense control is popular.

Purpose: To assess the efficacy and safety with a special reference to low intensity warfarin therapy.

Subjects And Methods: In 488 out of 508 patients with non-valvular AF, prothrombin time-international normalized ratio (PT-INR) was kept at 1.

Involvement of cross-linked ribosomal protein S19 oligomers and C5a receptor in definitive erythropoiesis.

We performed a series of experiments under a working hypothesis that cross-linked oligomers of ribosomal protein S19 (RP S19) play an essential role in definitive erythropoiesis as a ligand of the C5a receptor of erythroblasts and macrophages. We found molecules functionally and immunologically indistinguishable from RP S19 oligomers in the extracellular fluid of porcine and guinea pig bone marrow. When an increased hematopoietic state was induced in guinea pigs by bloodletting, the bone marrow RP S19 oligomer concentration was concomitantly increased.

Successful treatment of severe newly diagnosed immune thrombocytopenia involving an alveolar hemorrhage with combination therapy consisting of romiplostim, rituximab and vincristine.

A 51-year-old man was admitted due to a severe bleeding tendency. After he was diagnosed with immune thrombocytopenia (ITP), several therapies, including steroids, steroid pulse, vincristine and rituximab, were administered; however, the patient's bleeding symptoms were not sufficiently controllable with these treatments. Subsequently, a diffuse alveolar hemorrhage was observed.

Asialoerythropoietin exerts stronger angiogenic activity than erythropoietin via its binding affinity to tissue.

Purpose: Although erythropoietin (EPO) is known to express angiogenic and cardioprotective effects, it also induces hypertension, polycythemia, and platelet activation, which may cause serious adverse effects in patients with cardiovascular diseases. We compared the angiogenic effects of EPO and its nonerythropoietic derivative, asialo-EPO (AEPO).

Methods: Lower limb ischemia was induced in ICR and C57/BL mice.

Design and rationale of low-dose erythropoietin in patients with ST-segment elevation myocardial infarction (EPO-AMI-II study): a randomized controlled clinical trial.

Purpose: The development of novel pharmaceutical interventions to improve the clinical outcomes of patients with acute ST-segment elevation myocardial infarction (STEMI) is an unmet medical need worldwide. In animal models, a single intravenous administration of erythropoietin (EPO) during reperfusion improves left ventricular (LV) function in the chronic stage. However, the results of recent proof-of-concept trials using high-dose EPO in patients with STEMI are inconsistent.

A novel synthetic derivative of human erythropoietin designed to bind to glycosaminoglycans.

To synthesize long-acting and antiangiogenic erythropoietin to be clinically applied for treatment of patients with solid tumors, we synthesized a hybrid molecule of human erythropoietin added onto the C-terminus with a heparin-binding motif of human PLGF-2 to develop a novel derivative of long-acting and antiangiogenic erythropoietin: heparin-binding erythropoietin (HEPO), and studied the characteristics of this novel erythropoietin derivative. HEPO cDNA was synthesized, expressed in insect cells, and the protein was purified using a heparin-sepharose affinity column. The erythropoietic and angiogenic effects of the partially purified protein were analyzed in vitro and in vivo.

Erythropoietin, but not asialoerythropoietin or carbamyl-erythropoietin, attenuates monocrotaline-induced pulmonary hypertension in rats.

Erythropoietin (EPO) has long been utilized for the treatment of renal anemia. The erythropoietin receptor (EPOR) is also expressed in the cardiovascular and central nervous systems in addition to an erythroid lineage, to provide an organoprotective role against several types of cellular stress. Pulmonary hypertension (PH) is a poor prognostic disease caused by primary and secondary pulmonary vascular injury.

Features of Japanese patients with myelodysplastic syndrome in an aging population of Sado Island.

Myelodysplastic syndrome (MDS) is relatively common in the elderly, and aging of populations is progressing in developed nations, notably so in Japan. The major age group in Japan and Sado Island are distributed between 30 and 60 and between 50 and 80, respectively. The aim of this study was to analyze the features of MDS in the population of Sado Island to anticipate the characteristics of the disease in the near future.

Japanese case of Budd-Chiari syndrome due to hepatic vein thrombosis successfully treated with liver transplantation.

A 22-year-old Japanese woman was found to have severe esophageal varices and then suffered from hepatic encephalopathy. She was diagnosed with Budd-Chiari syndrome (BCS) due to hepatic vein (HV) thrombosis accompanied by portal vein thrombosis without inferior vena cava (IVC) obstruction. Latent myeloproliferative neoplasm (MPN) lacking the JAK2-V617F mutation was considered to be the underlying disease.

Characteristics of electrocardiographic repolarization in acute myocardial infarction complicated by ventricular fibrillation.

Background And Purpose: Some de- and re-polarization patterns can reflect an increased risk of ventricular tachyarrhythmias. We studied whether some electrocardiographic (ECG) patterns are able to predict the development of ventricular fibrillation (VF) during acute myocardial infarction (MI).

Methods: We compared the patterns of ST-T segment of 78 patients who developed VF during acute MI (patient with VF) vs 170 comparable patients with acute MI but with no VF complications.

Free heme is a danger signal inducing expression of proinflammatory proteins in cultured cells derived from normal rat hearts.

Endogenous molecules from damaged tissue act as danger signals to trigger or amplify the immune/inflammatory response. In this study, we examined whether free heme induced pro-inflammatory proteins in cultured cells derived from normal hearts and investigated the cells targeted by heme, together with its mechanism of action in these cells. We cultured collagenase-isolated heart-derived cells from normal rats and examined whether free heme induced pro-inflammatory proteins, reactive oxygen species (ROS) production and NF-κB activation, by quantitative RT-PCR, ELISA and flow cytometry.

Successful remission of Evans syndrome associated with Graves' disease by using propylthiouracil monotherapy.

A 46-year-old woman with Graves' disease was admitted for anemia and thrombocytopenia. She had previously been treated with methimazole but she self-discontinued the treatment 6 months prior to admission. She was diagnosed with Evans syndrome associated with Graves' disease and treated with propylthiouracil without corticosteroids, which normalized her thyroglobulin level.

Hypocellularity and insufficient expression of angiogenic factors in implanted autologous bone marrow in patients with chronic critical limb ischemia.

The aim of this study was to identify the clinical parameters of absolutely poor-prognosis patients with chronic critical limb ischemia (AP-CLI). Sixteen no-option CLI patients with arteriosclerosis obliterans: ASO (nine) and non-ASO patients (seven) treated with bone marrow-mononuclear cell implantation (BMI) were analyzed. There were three AP-CLI patients (all ASO).