Eicosapentaenoic acid reduces the progression of carotid intima-media thickness in patients with type 2 diabetes

To investigate the effect of highly purified eicosapentaenoic acid (EPA) on the progression of diabetic macroangiopathy, we performed an open-label randomized prospective trial. A total of 81 Japanese type 2 diabetes were randomly assigned to the EPA (1800 mg/day) treated group or the control group. Carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV) were evaluated before and after treatment in both groups. Sixty patients (EPA group, n=30; control group, n=30) completed this study. During the study period of 2.1+/-0.2 years, the mean IMT and max IMT of the EPA treated group showed a significant annual decrease compared with that of the control group (mean IMT, -0.029+/-0.112 mm versus 0.016+/-0.109 mm, respectively, P=0.029; max IMT, -0.084+/-0.113 mm versus -0.005+/-0.108 mm, respectively, P=0.0008). The baPWV was also improved significantly in the EPA treated group compared with the control group (-22.1+/-127.9 cm/s versus 62.3+/-223 cm/s, respectively, P=0.021). Multiple regression analysis showed that the administration of EPA was a significant and independent factor associated with an annual improvement of mean IMT (R2=0.067). In summary, this is the first demonstration that administration of purified EPA improves the carotid IMT and the baPWV in patients with type 2 diabetes.     

Lacunar syndrome associated with paradoxical brain embolism

We report a patient who developed lacunar syndrome due to left upper pons infarction after performing leg exercises associated with paradoxical brain embolism. A 32-year-old man developed right arm weakness and moderate dysarthria following leg exercise. Brain MRI showed a paramedian pontine infarction of the left upper pons, and contrast transesophageal echocardiographic examination indicated that the patent foramen ovale was the embolic source. Simultaneous RI venography examination of the lower limbs identified deep venous thrombosis in the right leg as a paradoxical emboligenic source. We concluded that the presence of lacunar syndrome suggests that this mechanism was responsible for the paradoxical brain embolism.     

Preferable effect of pravastatin compared to atorvastatin on beta cell function in Japanese early-state type 2 diabetes with hypercholesterolemia

While a large numbers of clinical trials using various kinds of statins has been reported, a possible preventive effect on new onset of type 2 diabetes mellitus was shown only by the subanalysis of The West of Scotland Coronary Prevention Study (WOSCOPS) using pravastatin. The aim of this study was to investigate whether pravastatin has a preferable effect on glucose tolerance among statins. An open-label prospective cross-over trial was performed to compare the effect of pravastatin (10 mg/day) or atorvastatin (10 mg/day) in Japanese early-state type 2 diabetes mellitus with hypercholesterolemia. The analyzed study subjects were treated with pravastatin (10 mg/day, n = 12) or atorvastatin (10 mg/day, n = 12) for 12 weeks. After a 4-week-washout period, the drugs were switched and treatment was continued for another 12 weeks. Oral glucose tolerance test (OGTT) was performed to evaluate several parameters including the appropriateness of beta cell function for the individual insulin sensitivity (disposition index: product of a validated secretion parameter and sensitivity) at the end of each therapy. HbA(1c) and 2 h-glucose levels during OGTT in the pravastatin treatment were significantly lower than atorvastatin treatment. Disposition index after pravastatin treatment was significantly higher than after atorvastatin treatment. In conclusion, our study suggests that pravastatin has a favorable effect on pancreatic beta cell function compared with atorvastatin.     

Long-term effect of combination therapy with mitiglinide and once daily insulin glargine in patients who were successfully switched from intensive insulin therapy in short-term study

We have previously reported the therapeutic efficacy of mitiglinide combined with once daily insulin glargine (mitiglinide regimen) after switching from multiple daily insulin regimen of aspart insulin and glargine (intensive insulin regimen) in inpatients with type 2 diabetes mellitus in two consecutive days. In the present study, we followed up 9 of the 15 responsive patients with these novel regimens for 6 months after discharge. The data collected from these patients were compared to those of 15 randomly chosen patients who had well matched background and received intensive insulin regimen during hospitalization which was continued after discharge. The average HbA1c level of these 9 patients with mitiglinide regimen at 6 months was 6.7 +/- 0.8% and was comparable to that of the patients with intensive insulin regimen (HbA1c = 7.0 +/- 1.0%). In conclusion, mitiglinide and insulin glargine combination therapy maintained fair glycemic control for as long as 6 months in subpopulation of Japanese patients with type 2 diabetes.     

Phase I Trial of FLAGM with High Doses of Cytosine Arabinoside for Relapsed, Refractory Acute Myeloid Leukemia: Study of the Japan Adult Leukemia Study Group (JALSG)

This study was designed to determine the optimal high dose for cytosine arabinoside (ara-C) in combination with fludarabine, granulocyte colony-stimulating factor, and mitoxantrone (FLAGM) in adult patients with relapsed or refractory acute myeloid leukemia. Nine patients were enrolled at increasing dosage levels of ara-C (8, 12, and 16 g/m2 per dose level). Ara-C and fludarabine were administered once a day at level 1, once or twice a day at level 2, and twice a day at level 3. All patients had grade 4 hematologic toxicity. The most common adverse events were of grade 2 or less, with nausea and vomiting being the most common (6 events), followed by diarrhea (5 events), and rash (5 events). Of the 13 grade 3 nonhematologic toxicities reported, the 2 most common were febrile neutropenia (6 events) and disseminated intravascular coagulation (3 events). No early deaths were observed. FLAGM with high-dose ara-C was considered safe for patients, and the recommended dosage of ara-C in this study was 2 g/m2 every 12 hours for a total dose of 16 g/m2.     

Carotid intima-media thickness and risk of cardiovascular events in high-risk patients. Results of the Osaka Follow-Up Study for Carotid Atherosclerosis 2 (OSACA2 Study)

BACKGROUND AND PURPOSE: There is epidemiological evidence that increased carotid intima-media thickness (IMT) is a predictor of cardiovascular disease (CVD) events. However, the significance of carotid IMT in high-risk patients in whom risk factors are managed clinically has not been adequately investigated. The purpose of this study was to determine the usefulness of carotid IMT measurement in such patients. METHODS: The study comprised 900 outpatients with cardiovascular risk factors or established atherosclerosis. Carotid IMT was calculated as the mean bilateral IMT of the common carotid artery, bifurcation, and internal carotid artery. Baseline vascular risk factors, medications, and history of CVD were recorded at the time of enrollment. The incidence of CVD events was determined prospectively. RESULTS: During a mean follow-up period of 2.6 years, there were 64 CVD events. The relative risk (RR) of a CVD event increased with increased IMT. Association between CVD events and carotid IMT was significant after adjustment for risk factors and history of CVD, showing an increased risk per IMT tertile from the middle tertile (RR, 2.5; 95% confidence interval [CI]: 1.0-6.3) to the highest (RR, 3.6; 95% CI: 1.4-9.0). When patients with a history of CVD were excluded (n = 574), the predictive value of IMT was significant even after adjustment for risk factors (hazard ratio per 1 SD IMT increase was 1.57 [95% CI: 1.11-2.20]). CONCLUSIONS: Carotid IMT is an independent predictor of vascular events in high-risk patients in whom risk factors are managed clinically.     

A new molecular targeted therapeutic approach for renal cell carcinoma with a p16 functional peptide using a novel transporter system

Molecular targeting agents have become formidable anticancer weapons showing much promise against refractory tumors and functional peptides and are among the more desirable of these nanobio-tools. Intracellular delivery of multiple functional peptides forms the basis for a potent, non-invasive mode of delivery, providing distinctive therapeutic advantages. We examine the growth suppression efficiency of human renal cell carcinoma (RCC) by single-peptide targeting. We simultaneously introduced p16INK4a tumor suppressor peptides by Wr-T-mediated peptide delivery. Wr-T-mediated transport of p16INK4a functional peptide into 10 RCC lines, lacking expression of the p16INK4a molecule, reversed the specific loss of p16 function, thereby drastically inhibiting tumor growth in all but 3 lines by >95% within the first 96?h. In?vivo analysis using SK-RC-7 RCC xenografts in nude mice demonstrated tumor growth inhibition by the p16INK4a peptide alone, however, inoculation of Wr-T and the p16INK4a functional peptide mixture, via the heart resulted in complete tumor regression. Thus, restoration of tumor suppressor function with Wr-T peptide delivery represents a powerful approach, with mechanistic implications for the development of efficacious molecular targeting therapeutics against intractable RCC.     

Endoscopic examination for duodenal ulcer bleeding during transcatheter arterial embolization: analysis of two cases

Endoscopy is usually effective in treating duodenal ulcer bleeding, but depending on the lesion site and overall patient condition, hemostasis may be difficult to achieve with endoscopy alone. We described two patients with duodenal ulcer bleeding in whom endoscopic hemostasis was difficult. Immediately after transcatheter arterial embolization, endoscopic examination was used to confirm hemostasis and completing of the angiographic procedures.     

Proximal metatarsal osteotomy for hallux valgus: comparison of outcome for moderate and severe deformities

BACKGROUND: We compared the results of a distal soft-tissue procedure with a proximal crescentic osteotomy of the first metatarsal for moderate and severe hallux valgus. MATERIALS AND METHODS: The series consisted of 54 feet treated with this procedure. The average followup was 30 months. Fifty-four feet were divided into two groups including Group M (moderate) (24 feet, preoperative hallux valgus angle of 40 degrees or less and preoperative intermetatarsal angle of less than 18 degrees) and Group S (severe) (30 feet, preoperative hallux valgus angle of greater than 40 degrees or preoperative intermetatarsal angle of 18 degrees or greater). RESULTS: The difference between Group M and S was not significant with regard to the age of patients, duration of followup, or postoperative pain and function scores on the American Orthopaedic Foot and Ankle Society scale. However, postoperative alignment score in Group M was significantly greater than that in Group S (p = 0.038). Postoperative hallux valgus and intermetatarsal angles in Group S were significantly greater than those in Group M, respectively (p = 0.025, p = 0.001). The prevalence of recurrent hallux valgus (hallux valgus angle of 20 degrees or greater) in Group S was significantly higher than that in Group M (p = 0.013). CONCLUSION: This procedure is an effective method for relieving pain and improving function regardless of the severity of hallux valgus. However, the correction of moderate hallux valgus is likely to be better than that of severe hallux valgus.     

alpha4-Integrin(+) endothelium derived from primate embryonic stem cells generates primitive and definitive hematopoietic cells

The mechanism of commencement of hematopoiesis in blood islands of the yolk sac and the aorta-gonad-mesonephros (AGM) region during primate embryogenesis remains elusive. In this study, we demonstrated that VE-cadherin(+)CD45(-) endothelial cells derived from nonhuman primate embryonic stem cells are able to generate primitive and definitive hematopoietic cells sequentially, as revealed by immunostaining of floating erythrocytes and colony-forming assay in cultures. Single bipotential progenitors for hematopoietic and endothelial lineages are included in this endothelial cell population. Furthermore, hemogenic activity of these endothelial cells is observed exclusively in the alpha4-integrin(+) subpopulation; bipotential progenitors are 4-fold enriched in this subpopulation. The kinetics of this hemogenic subpopulation is similar to that of hemogenic endothelial cells previously reported in the yolk sac and the AGM region in vivo in that they emerge for only a limited time. We suggest that VE-cadherin(+)CD45(-)alpha4-integrin(+) endothelial cells are involved in primitive and definitive hematopoiesis during primate embryogenesis, though VE-cadherin(-)CD45(-)alpha4-integrin(+) cells are the primary sources for primitive hematopoiesis.