OBJECTIVE: To test the hypothesis that textural changes in the carotid intima-media complex (IMC) detected by B-mode ultrasound are associated with the difference of remodeling process in earlier atherosclerotic involvement in patients with Kawasaki disease (KD) and coronary artery lesions (CALs). METHODS: Eighteen patients with KD and CALs (mean age 17.2 years), 17 patients with heterozygous familial hypercholesterolemia (FH)(mean age 16.9 years) and 15 age-matched healthy controls (Cont) were assessed and compared for carotid intima-media thickness (CIMT), elastic property (E(p)), and first- and second-order statistics. RESULTS: KD showed significantly higher gray scale median (GSM) than FH and Cont. KD and FH showed significantly higher CIMT, entropy and lower angular second moment than Cont, but no significant difference was found between KD and FH. CONCLUSION: Higher GSM in KD may indicate alteration of tissue components and heterogeneity of IMC, suggesting the development of arteriosclerotic vascular remodeling after vasculitis. This is distinct from that of atherosclerosis with lower GSM often observed in FH.

PURPOSE: Unresectable T4 tumors of the breast are usually treated with systemic therapies, while the role of local therapies remains debatable. This study aims to evaluate the effectiveness of chemoradiotherapy as a part of T4 breast cancer treatment, and to assess the role of local radiotherapies in patients with unresectable T4 breast tumors. MATERIALS/METHODS: Between February 1998 and June 2010, 39 unresectable T4 breast tumors were treated with chemoradiotherapy at our institutes. Clinical stages included stage IIIB (n = 15), stage IIIC (n = 3), and stage IV (n = 21). Twenty-one cases had undergone previous systemic therapies, whereas the remaining 18 cases reported no history of previous treatment. Radiation doses of 59-66 Gy (median 60 Gy) were administered to the breast in addition to concurrent chemotherapies. Acute adverse effects were assessed on a weekly basis during treatment to 2 weeks after completion of treatment, and were scored by the Common Terminology Criteria for Adverse Events v3.0. Treatment response was assessed at 1 month after completion of chemoradiotherapy. Statistical analysis of survival was calculated using the Kaplan-Meier method. RESULTS: Chemoradiotherapy was completed in all cases. Greater than grade 3 hematological toxicities were observed with regard to lymphocytes (33%), platelets (8%), neutrophils (3%), and hemoglobin (3%). Greater than grade 3 nonhematologic toxicities included chemoradiation dermatitis (23%) and pneumonitis (5%). Sixteen T4 tumors (41%) achieved complete response, whereas 23 (59%) achieved partial response. All patients were treated with chemotherapy and/or endocrine therapy following chemoradiotherapy. The median follow-up period was 20 months (range 3-96 months). Nineteen patients died because of progressive breast cancer. Infield recurrence or relapse was observed in 11 cases during the course of treatment, but only 3 cases were symptomatic. The 2-year overall local control rate was 73.6%, and the survival rate was 65.9%. CONCLUSION: Chemoradiotherapy represents a viable option for local treatment of unresectable T4 breast tumors.

We have previously reported the efficacy of the Patient Oriented Clerkship (POC) in the clinical clerkship in Showa University Hospitals, by a trial with old four-year pharmacy program students. In the unique clerkship, each student has a patient in charge, and follows his/her clinical conditions throughout the rotation. The aim of the POC is that having the students learn spontaneously (Active Learning) and actively (Adult Learning) promoted by student's commitment and responsibility by communicating with patients and health professionals in a team. As the POC requires students both Active Learning and Adult Learning, we define the POC as Active Adult Learning (AAL). Having a patient in charge for each student gives them many opportunities to participate in the medical team and foster their problem solving skills. Our previous study eventually showed positive results of the POC in the one-month short clerkship in the four-year program. On the other hand, the effect of the unique hospital clerkship in the new six-year program is not known. We conducted a student survey to clarify the learning effect in the new six-year education system which was revised and 2.5 month clinical clerkship was scheduled according to the model core clerkship curriculum. This report is the first report to show a challenge of the AAL/POC clerkship in the new six-year pharmacy education program.

PURPOSE: To retrospectively analyze results of concurrent chemoradiotherapy (CCRT) using gemcitabine (GEM) for unresectable pancreatic adenocarcinoma. METHODS AND MATERIALS: Records of 108 patients treated with concurrent external beam radiotherapy (EBRT) and GEM were reviewed. The median dose of EBRT in all 108 patients was 50.4 Gy (range, 3.6-60.8 Gy), usually administered in conventional fractionations (1.8-2 Gy/day). During radiotherapy, most patients received GEM at a dosage of 250 to 350 mg/m(2) intravenously weekly for approximately 6 weeks. After CCRT, 59 patients (54.6%) were treated with adjuvant chemotherapy (AC), mainly with GEM. The median follow-up for all 108 patients was 11.0 months (range, 0.4-37.9 months). RESULTS: Initial responses after CCRT for 85 patients were partial response: 26 patients, no change: 51 patients and progressive disease: 8 patients. Local progression was observed in 35 patients (32.4%), and the 2-year local control (LC) rate in all patients was 41.9%. Patients treated with total doses of 50 Gy or more had significantly more favorable LC rates (2-year LC rate, 42.9%) than patients treated with total doses of less than 50 Gy (2-year LC rate, 29.6%). Regional lymph node recurrence was found in only 1 patient, and none of the 57 patients with clinical N0 disease had regional lymph node recurrence. The 2-year overall survival (OS) rate and the median survival time in all patients were 23.5% and 11.6 months, respectively. Patients treated with AC had significantly more favorable OS rates (2-year OS, 31.8%) than those treated without AC (2-year OS, 12.4%; p < 0.0001). On multivariate analysis, AC use and clinical T stage were significant prognostic factors for OS. CONCLUSIONS: CCRT using GEM yields a relatively favorable LC rate for unresectable pancreatic adenocarcinoma, and CCRT with AC conferred a survival benefit compared to CCRT without AC..

The immunomodulatory effects of a hot water extract from matured fruit of the date palm tree (<i>Phoenix dactylifera</i> L.) were investigated in comparison to those of prune and fig fruit in mice. The number of spleen IFN-γ⁺CD4⁺, IFN-γ⁺CD49b⁺ and IL-12⁺CD11b⁺ cells was highest in mice given the date extract-added diet. Polyphenols identified in the date extract, such as chlorogenic acid, caffeic acid, pelargonin and ferulic acid, stimulated IFN-γ mRNA expression significantly in mouse Peyer's patch cell cultures. Chlorogenic acid and caffeic acid also increased the number of IFN-γ⁺CD4⁺ cells significantly, while some polyphenols increased the number of IFN-γ⁺CD49b⁺ and IL-12⁺CD11b⁺ cells significantly. On the other hand, a 70% ethanol-insoluble date extract treated with trypsin increased the number of IFN-γ⁺CD49b⁺ and IL-12⁺CD11b⁺ cells significantly. These results indicate that some polyphenols and polysaccharides present in date fruit stimulate the cellular immune system in mice.

Glucocorticoid (GC) administration with or without other chemotherapeutic reagents is a commonly used option in the treatment of mast cell malignancies. However, the responsiveness of mast cell tumors to GC treatment varies in individuals, and the regulatory mechanisms determining the GC sensitivity of malignant mast cells remain unclear. Since the expression of the GC receptor (GR) has been reported to be associated with GC sensitivity in human neoplastic lymphocytes, we attempted to investigate the relationship between GR levels and GC sensitivity by using neoplastic mast cells derived from canine mast cell tumors (MCTs). To elucidate the regulatory mechanisms involved in GC responsiveness, we analyzed various canine MCT cell lines and tissue samples from dogs with MCT. While the proliferation of canine MCT cells was suppressed by the addition of GC to the culture, we found that MCT cells derived from humans and rodents, as well as canine lymphoma cells, responded poorly to GC. However, there were also some variations in responsiveness to GC treatment among canine MCT cell lines used in this study. Using real-time polymerase chain reaction and Western blot analysis, we elucidated the relationship between GR expression and responsiveness to GC in canine MCT cells. Furthermore, to assess the involvement of GR expression in GC sensitivity in vivo, clinical investigations were conducted on dogs with cutaneous MCT. Written informed consent was obtained from owners, and the affected dogs were treated with prednisolone (0.5-2.0mgkg(-1)day(-1), administered orally) 1 or 2 weeks prior to the surgical removal of the tumors. Tumor volume was measured according to WHO criteria both before and after prednisolone treatment, and the GC sensitivity of each MCT was determined on the basis of the reduction in tumor volume. Of the 15 dogs with MCT, 11 responded to treatment with prednisolone completely or partially, whereas 4 dogs showed no response. Examination of clinical samples obtained by surgical removal revealed that GR expression levels were significantly lower in GC-resistant MCT tissues than in GC-sensitive MCT tissues. Thus, these results strongly indicate that GR expression may contribute to GC sensitivity in canine MCT.

The positive effects of wearing a mouthguard have been indicated in various epidemiological surveys and experiments, and their usage appears to be increasing in many sports. However, many preventable sports-related dental injuries still occur even with the use of a conventional mouthguard. We have developed a mouthguard (the Hard & Space mouthguard) with sufficient injury prevention ability (more than 95% shock absorption ability against impact with a steel ball carrying 15.2 kg m(2) S(-2) potential energy) and ease of clinical application. This mouthguard consists of an outer and an inner EVA layer and a middle layer of acrylic resin (hard insert), with a space to prevent contact between the inner surface of the mouthguard and the buccal surfaces of the maxillary front teeth or teeth already weakened through prior damage or treatment. The purpose of this article is to describe the method by which the Hard & Space mouthguard may easily be fabricated. We believe that this new type of mouthguard has the potential to reduce sports-related dental injuries.

AIMS Intermittent claudication (IC) is one of the serious symptoms of peripheral arterial disease (PAD) and is characterized by pain in the legs or buttocks that worsens with exercise and subsides with rest. The concept of 'therapeutic angiogenesis' for PAD has been widely proposed; however, the methodology, including cell transplantation, is still unclear. In this study, we examined the clinical efficacy of silencing the int6 gene, which encodes a protein that stabilizes hypoxia-inducible factor (HIF)-2α, on angiogenesis in PAD. METHODS AND RESULTS An animal model for IC was established in Sprague-Dawley rats by external iliac artery ligation and evaluated by quantitative analysis of gait disturbance. Next, we explored the therapeutic effects of int6 siRNA injected into the adductor magnus muscle on IC. Recovery of hindlimb function occurred in the early stages after int6 siRNA injection. The number of blood vessels showed an obvious increase in the int6 siRNA-treated muscles. Angiography revealed the recovery of peripheral circulation at the affected sites. Early up-regulation of HIF-2α and other angiogenic factors, including basic fibroblast growth factor and hepatocyte growth factor, was also apparent in the int6 siRNA-treated sites. We also confirmed the up-regulation of HIF-2α and its translocation to the nucleus in the int6 siRNA-injected muscle. CONCLUSION A single injection of int6 siRNA promoted angiogenesis via up-regulation of HIF-2α-related angiogenic factors in the muscles of the affected hindlimb and reduced gait disturbance. The int6 gene may be a novel therapeutic target for the treatment of IC in patients with PAD.

OBJECT The objective of the present study was analysis of results of the prospective clinical trial directed toward the evaluation of therapeutic efficacy of the administration of autologous formalin-fixed tumor vaccine (AFTV) concomitant with fractionated radiotherapy in cases of newly diagnosed glioblastoma multiforme. METHODS Twenty-four patients were enrolled into the clinical trial, while 2 cases were excluded from the final analysis of results. The treatment protocol included aggressive tumor resection, fractionated radiotherapy up to a total dose of 60 Gy, and 3 concomitant courses of AFTV administered with an interval of one week at the late stage of irradiation. Two delayed-type hypersensitivity (DTH) tests were done--one 48 hours before the initial course of vaccination (DTH-1) and one 2 weeks after the third (DTH-2). All but one of the patients received salvage therapy at the time of tumor progression. The defined primary end point was overall survival; secondary end points were progression-free survival and safety of concomitant treatment. RESULTS The median duration of overall survival was 21.4 months (95% CI 13.8-31.3 months). The actuarial 2-year survival rate was 40%. The median duration of progression-free survival was 7.6 months (95% CI 4.3-13.6 months). Overall survival showed a statistically significant association with recursive partitioning analysis class (p < 0.05); progression-free survival showed a statistically significant association with p53 staining index (p < 0.05) and size of DTH-2 response (p < 0.001). AFTV injection concomitant with fractionated radiotherapy was well tolerated by all patients and in no case did treatment-related adverse effects exceed Grade 1 toxicity; adverse effects were limited to local erythema, induration, and swelling at the site of injection. CONCLUSIONS The results of this study demonstrate that AFTV treatment concomitant with fractionated radiotherapy may be effective in patients with newly diagnosed glioblastoma. Further clinical testing is warranted.