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The present study aimed to retrospectively evaluate the efficacy and toxicities of adjuvant chemotherapy with paclitaxel and carboplatin (TC) following concurrent cisplatin-based chemoradiation (CCRT) in patients with cervical cancer with lymphadenopathy (N1). A total of 37 patients with FIGO stage IB2-IVA cervical carcinoma with N1 (median age 57 years, range 31-74 years) were enrolled. External beam radiation therapy was followed by high-dose-rate brachytherapy. In cases of suspected para-aortic lymphadenopathy or common iliac lymph node involvement, extended radiotherapy fields were applied. Positive lymph nodes were externally radiated. Cisplatin was administered weekly at a dose of 30 mg/m(2) during external beam radiation therapy. Adjuvant therapy was administered to 17 patients and comprised carboplatin (6 mg/ml/min) and paclitaxel (175 mg/m(2)) administered monthly after CCRT, and repeated every 4 weeks for 3-6 cycles. Over a median 21.5-month follow-up, no significant differences were found in the recurrence rate, progression-free survival, overall survival, or median interval to recurrence with N1 cervical cancer patients between the two groups. Patients with para-aortic lymphadenopathy who received CCRT and adjuvant chemotherapy had a more favorable overall and disease-free survival than those treated with CCRT alone. However, 16/17 patients developed grade 3-4 leukopenia and 14/17 patients developed severe hematologic toxicity during adjuvant chemotherapy. In conclusion, adjuvant chemotherapy consisting of full dose TC therapy after CCRT was not well tolerated in general and exhibited no benefit to N1 cervical cancer patients. However, it may be of therapeutic advantage over CCRT alone in cervical cancer patients with para-aortic lymphadenopathy.

Background: S100A12 is an endogenous ligand of the receptor for advanced glycation end products (RAGE). Plasma S100A12 levels are high in end-stage renal disease (ESRD) patients undergoing maintenance hemodialysis (HD). Peripheral arterial disease (PAD) is common in HD patients and is associated with increased cardiovascular morbidity and mortality rates in this population. To date, however, no study has specifically assessed the relationship between plasma S100A12 and PAD in HD patients. Methods: We conducted a cross-sectional study of 152 HD patients in our affiliated hospital. We investigated PAD history and patient characteristics and quantified plasma S100A12 levels in all participants. Results: HD patients with PAD (n = 26; 21.9 [13.6–33.4] ng/ml) showed significantly higher plasma S100A12 levels than HD patients without PAD (n = 126; 11.8 [7.5–17.6]ng/ml; p < 0.001). In multivariate logistic regression analysis, the plasma S100A12 level (odds ratio [OR] 5.71; 95% confidence interval [CI] 1.29–25.3; p = 0.022) was identified as an independent factor associated with PAD prevalence. Another factor associated with PAD prevalence was the ankle-brachial index (OR 0.54; 95% CI 0.40–0.74; p < 0.001). Conclusion: These results suggest that plasma S100A12 levels are strongly associated with PAD prevalence in ESRD patients undergoing HD.

Background and aims To compare the prognosis of chronic hemodialysis patients with or without parathyroidectomy. Methods Among 158 chronic hemodialysis patients who underwent total parathyroidectomy between July 1998 and April 2009, 88 patients were matched with 88 controls for sex, age, underlying disease and prior dialysis history. Then a retrospective evaluation of their prognosis was performed over a median observation period of 4.41 years. Results The overall survival rate was 90.4% in the parathyroidectomy group and 67.4% in the control group. The cardiovascular death-free survival rate was 94.6% in the parathyroidectomy group and 76.3% in the control group. During observation, intact parathyroid hormone was measured every 6 months, and its average serum level was 37 ± 92 ng/L in the total parathyroidectomy group versus 274 ± 233 ng/L in the control group (p=0.0001). The total parathyroidectomy group had a significantly lower corrected calcium level and higher serum albumin level. Multivariate analysis revealed that parathyroidectomy, atrial fibrillation and serum albumin were significant factors for both total and cardiovascular mortality. Conclusion Total parathyroidectomy was associated with better survival, probably due to decreased cardiovascular mortality.

Lean body mass decreases after a major operation such as open-heart surgery, which leads to postoperative complications, as a drastic loss of muscle mass is related to infections and longer hospital stays. The purpose of this study was to examine changes in lean body mass and muscle mass including body composition the perioperative phase until discharge in patients undergoing open-heart surgery. Body fluids, fat and lean body mass in 17 patients were determined before and 1 week after surgery, and at discharge using bioelectrical impedance analysis. In addition, the levels of hemoglobin, albumin, and C-reactive protein in blood were measured. Cardiac rehabilitation consisted of early mobilization and aerobic bicycle exercise was subsequently performed after confirmation of independent walking for 200 meters. Early mobilization after surgery was assisted by physical therapists experienced in cases of cardiovascular surgery. Early mobilization required no more than 3 delayed days and no major complications until discharge in any of the patients. Weight and body mass index were significantly lower at discharge than before and 1 week after surgery, while lean body mass, muscle mass, total body water, intracellular fluid, body protein, and body cell mass values were significantly lower at discharge than before surgery. The changes in body composition seen after cardiac surgery until discharge indicated continuous catabolic reactions in our patients and some cytokines have been suggested to influence this phenomenon. After receiving open-heart surgery, it is important for patients to receive nutritional therapy and begin resistance exercise as soon as possible. Aerobic exercise should produce muscle protein synthesis and increase muscle mass under adequate nutritional support including specific amino acid supplements. Our findings indicate that muscle mass and nutritional status should be monitored after discharge and followed consistently in patients after open-heart surgery.

Emerging evidence suggests that the Notch/Delta-like ligand 4 (Dll4) pathway may offer important new targets for antiangiogenesis approaches. In this study, we investigated the clinical and biological significance of Dll4 in ovarian cancer. Dll4 was overexpressed in 72% of tumors examined in which it was an independent predictor of poor survival. Patients with tumors responding to anti-VEGF therapy had lower levels of Dll4 than patients with stable or progressive disease. Under hypoxic conditions, VEGF increased Dll4 expression in the tumor vasculature. Immobilized Dll4 also downregulated VEGFR2 expression in endothelial cells directly through methylation of the VEGFR2 promoter. RNAi-mediated silencing of Dll4 in ovarian tumor cells and tumor-associated endothelial cells inhibited cell growth and angiogenesis, accompanied by induction of hypoxia in the tumor microenvironment. Combining Dll4-targeted siRNA with bevacizumab resulted in greater inhibition of tumor growth, compared with control or treatment with bevacizumab alone. Together, our findings establish that Dll4 plays a functionally important role in both the tumor and endothelial compartments of ovarian cancer and that targeting Dll4 in combination with anti-VEGF treatment might improve outcomes of ovarian cancer treatment. Cancer Res; 71(18); 6030–9. ©2011 AACR.

Human papillomavirus (HPV) DNA has been detected in the oral cavity of infants and breast cancer tissue, suggesting its vertical transmission through maternal milk. We determined whether HPV is detected in maternal milk and is vertically transmitted by breast-feeding. Informed consent was obtained, and maternal milk samples (n=80) were analysed for high-risk HPV DNA. In 43 women, this DNA was measured in the uterine cervix. In women with positive samples, this DNA was measured in the oral cavities of their children. The domain including HPV E6 and E7 was amplified by polymerase chain reaction using consensus primers, and HPV serotype determined by electrophoresis after restriction enzyme digestion. High-risk HPV-16 was detected in two of 80 samples (2.5%), and in these two cases, high-risk HPV was not detected in the uterine cervix or oral cavity of the child. It was concluded that the infection of HPV in maternal milk is rare (2/80); vertical transmission through maternal milk was not detected in this study (0/80). HPV infection through maternal milk may occur, but its likelihood is low.

Angiography is not always an accurate indicator of physiologically significant stenosis. We examined the usefulness of functional evaluation of coronary stenosis severity by determining the fractional flow reserve (FFR) using a pressure wire in patients who received hemodialysis with angiographically intermediate lesions. We recruited 44 patients with intermediate lesions; of these, 22 were undergoing hemodialysis while 22 were not. Quantitative coronary angiography (QCA) was performed to measure the minimal lumen diameter (MLD) and calculate the percent diameter stenosis (%DS). The FFR was calculated as the ratio of the coronary pressure at the distal stenotic site to the mean aortic pressure during maximum hyperemia. In each group, we investigated the relationship between the FFR and %DS and FFR and MLD. The patients in the hemodialysis group were significantly younger and had more calcified and type B2/C lesions than those in the non-dialysis group. Although the FFR was correlated with both %DS (r = 0.71, p

The incidence of cardiac death is higher among patients receiving dialysis compared with the general population. Although obstructive coronary artery disease is involved in cardiac deaths in the general population, deaths in hemodialysis patients occur in the apparent absence of obstructive coronary artery disease. To study this further, we prospectively enrolled 155 patients receiving hemodialysis after angiography had confirmed the absence of obstructive coronary lesions. All patients were examined by single-photon emission computed tomography using the iodinated fatty acid analog, BMIPP, the uptake of which was graded in 17 standard myocardial segments and assessed as summed scores. Insulin resistance was determined using the homeostasis model assessment index of insulin resistance (HOMA-IR). During a mean follow-up of 5.1 years, 42 patients died of cardiac events. Stepwise Cox hazard analysis associated cardiac death with reduced BMIPP uptake and increased insulin resistance. Patients were assigned to subgroups based on BMIPP summed scores and HOMA-IR cutoff values for cardiac death of 12 and 5.1, respectively, determined by receiver operating characteristic analysis. Cardiac death-free survival rates at 5 years were the lowest (32.2%) in the subgroup with both a summed score and assessment equal to or above the cutoff values compared with any other combination (52.9–98.7%) above, equal to, or below the thresholds. Thus, impaired myocardial fatty acid metabolism and insulin resistance may be associated with cardiac death among hemodialysis patients without obstructive coronary artery disease.

SUMMARY 1 Since endothelium-derived nitric oxide (NO) is a potent vasodilator and degraded into nitrous ions, we measured the serum nitrate ion (NO3−) and the amount of urinary excretions of NO3− as an index for endogenous NO to ascertain whether NO formation is augmented in patients with chronic liver diseases. 2 Using inpatients suffering from chronic liver diseases, serum levels and urinary excretions of NO3− were measured by using high-performance liquid chromatography with an anion exchange column. 3 Among the four patient groups of normal controls, and those with chronic liver diseases such as chronic active hepatitis, compensated cirrhosis, and decompensated cirrhosis the serum level of NO3− showed the highest level in a patient group with decompensated cirrhosis. The amount of urinary excretion of NO3− was significantly increased in both groups of patients with liver cirrhosis compared with the control group and patients with chronic active hepatitis. Patients with chronic active hepatitis did not show any difference between the normal control group. The amount of urinary excretion of NO3− correlated significantly and negatively with the level of serum albumin (P

EphB4 is a transmembrane receptor tyrosine kinase that plays an important role in neural plasticity and angiogenesis. EphB4 is overexpressed in ovarian cancer and is predictive of poor clinical outcome. However, the biological significance of EphB4 in ovarian cancer is not known and is the focus of the current study. Here, we examined the biological effects of two different methods of EphB4 targeting (a novel monoclonal antibody, EphB4-131 or siRNA) using several ovarian cancer models. EphB4 gene silencing significantly increased tumor cell apoptosis and decreased migration (P < 0.001) and invasion (P < 0.001). Compared with controls, EphB4 siRNA–1,2-dioleoyl-sn-glycero-3-phosphatidylcholine alone significantly reduced tumor growth in the A2780-cp20 (48%, P < 0.05) and IGROV-af1 (61%, P < 0.05) models. Combination therapy with EphB4 siRNA–1,2-dioleoyl-sn-glycero-3-phosphatidylcholine and docetaxel resulted in the greatest reduction in tumor weight in both A2780-cp20 and IGROV-af1 models (89–95% reduction versus controls; P < 0.05 for both groups). The EphB4-131 antibody, which reduced EphB4 protein levels, decreased tumor growth by 80% to 83% (P < 0.01 for both models) in A2780-cp20 and IGROV-af1 models. The combination of EphB4-131 and docetaxel resulted in the greatest tumor reduction in both A2780-cp20 and IGROV-af1 models (94–98% reduction versus controls; P < 0.05 for both groups). Compared with controls, EphB4 targeting resulted in reduced tumor angiogenesis (P < 0.001), proliferation (P < 0.001), and increased tumor cell apoptosis (P < 0.001), which likely occur through modulation of phosphoinositide 3-kinase signaling. Collectively, these data identify EphB4 as a valuable therapeutic target in ovarian cancer and offer two new strategies for further development. Mol Cancer Ther; 9(8); 2377–88. ©2010 AACR.

Endometrial cancer keeps increasing in Japan explosively. In endometrial cancer, the prognosis of serous carcinoma is very poor, because of early progression to abdominal cavity. Remedy for endometrial cancer is limited, so new therapy has been required for a long time. Immunotherapy is very promising in various cancers recently. PD-L1 (programmed cell death ligand 1) and B7-H3 are factors of immunoresponse between cancer cells and lymphcyte. Purpose: The purpose of this study is to investing the expression of PD-L1 and B7-H3, moreover, relationship with clinicopathological factors in serous carcinoma of endometrium. We immunohistochemically evaluated PD-L1 and B7-H3 expression in 21 serous carcinoma. The result was graded as positive in case stained more than 10% area. Result: 2/21(9.5%) for PD-L1 and 10/21(47.6%) for B7-H3 were positive. There was no correlation with tumor diameter, lymphnode metastasis, advanced stage and recurrence in PD-L1, however, B7-H3 expression had trend node metastasis, 3/10 in positive cases vs 0/11 in negative cases (p=0.05). In 4 recurrent cases treated with taxane and carboplatin as second line therapy, one case with B7-H3 negative got complete remission, however 3 cases with B7-H3 positive got partial improvement once, but finally got progression. Conclusion: PD-L1 expression was limited in serous carcinoma, so immunotherapy targeted for PD-1 and PD-L1 may be limited. The expression of B7-H3 is related to chemotherapy resistance. B7-H3 may be a biomarker for chemotherapy and target of new immunotherapy for serous carcinoma of endometrium. Citation Format: Masato Nishimura, Ayuka Mineda, Akiko Abe, Minoru Irahara. PD-L1 and B7-H3 expression in serous carcinoma of endometrium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4566.

Background We prospectively investigated whether cardiac autonomic imbalance is associated with sudden cardiac death (SCD) among a group of hemodialysis patients with left ventricular hypertrophy (LVH). Methods In a prospective cohort study, we enrolled 196 asymptomatic patients on chronic hemodialysis who had LVH as determined by echocardiography and had undergone twenty-four-hour ambulatory Holter electrocardiography between dialysis sessions (males/females, 114/82; mean age, 65±12 years) to analyze heart rate variability. We calculated the percentage difference between adjacent NN intervals more than 50 ms (pNN50) and high-frequency component (HF, 0.15–0.40 Hz) as parameters of cardiac parasympathetic activity, and the low-frequency component (LF, 0.04–0.15 Hz)/HF component ratio as a parameter of sympathetic activity. Results During 4.5±1.9-year follow-up, 21 patients who had undergone coronary revascularization within 60 days of enrollment were excluded from the analysis. Among the remaining 175 patients (male/female, 105/70; 66±12 years), SCD was recognized in 23 patients. On stepwise Cox hazard analysis, SCD was positively associated with age and LF/HF ratio, and tended to be inversely associated with pNN50. On Kaplan–Meier analysis, SCD-free survival rates at 5 years were 29.4% and 98.1% in patients with LF/HF ratios of 1.9 or more and below 1.9, respectively. Conclusions The presence of cardiac sympathetic overactivity may predict the occurrence of SCD in the asymptomatic hemodialysis patients with LVH.

Ovarian smooth muscle tumors are a very rare type of ovarian tumor. In this paper, we report the case of a 62-year-old woman who had a huge smooth muscle tumor of the right ovary. The values of all the serum tumor markers were within normal limit. The tumor measured 25 cm in diameter and weighed 6,200 g. Histological examination revealed that coagulative cellular atypia was modetare to severe, necrosis was not present and mitotic index was low. According to the criteria for the evaluation of the uterine smooth muscle tumors, this huge tumor was diagnosed as atypical leiomyoma. However, we finally made a diagnosis of this tumor as a smooth muscle tumor of uncertain malignant potential (STUMP) because of its huge size. Further information is required regarding the characteristics of ovarian smooth muscle tumor and the propriety to introduce uterine tumor histological criteria to ovarian tumors.

Cardiovascular disease is the leading cause of morbidity and mortality in patients undergoing hemodialysis. Such patients frequently develop complications such as asymptomatic coronary artery disease (CAD). Accordingly, CAD must ideally be diagnosed at an early stage to improve prognosis. Although myocardial perfusion single photon emission computed tomography (SPECT) is valuable for diagnosing CAD, the stress test is not always applicable to patients on hemodialysis. Thus, we proposed a multicenter, prospective cohort study called "B-SAFE" to investigate the applicability of resting (123)I-labeled beta-methyl-iodophenylpentadecanoic acid ((123)I-BMIPP)-SPECT will be used to diagnose cardiac disease and evaluate the prognosis of hemodialysis patients by imaging myocardial fatty acid metabolism. B-SAFE began enrolling patients from June 2006 at 48 facilities. We performed (123)I-BMIPP-SPECT on 702 hemodialysis patients with risk factors for CAD until 30 November 2007 and plan to follow up for three years. The primary endpoints will be cardiac death and sudden death. This study should end in 2010.

The prevalence of coronary artery disease (CAD) appears to be much higher in patients with end-stage renal disease (ESRD) undergoing dialysis than in a non-ESRD population. Cardiac death due to myocardial ischemia significantly contributes to the high mortality rate of ESRD patients. However, the method for screening for CAD in ESRD patients has not been established, because the frequency of silent myocardial ischemia is high and examinations requiring stress are often difficult to perform among this population. Myocardial fatty acid imaging may be a new modality to detect myocardial ischemia and identify the group at high risk for cardiac death among ESRD patients without adding any stress.

We prospectively evaluated if impaired myocardial fatty acid metabolism is involved in cardiac death after revascularization by percutaneous coronary artery intervention in dialysis patients. A cohort of hemodialysis patients was assessed by dual single-photon emission computed tomography using the radioiodinated fatty acid analogue BMIPP and radiolabeled thallium chloride. Tomography was done within one month before the first coronary intervention and at the last follow-up angiography at which neither restenosis nor de novo lesions were detected. Radiolabel uptake on tomography images was graded in segments and calculated as summed BMIPP or thallium scores. Among the 90 hemodialysis patients in the study, 19 died of cardiac events. Multivariate Cox hazard analysis found a significant association of cardiac death with the BMIPP summed scores at the last follow-up angiography. Kaplan–Meier analysis showed the cardiac death-free survival rates at 3 years of follow-up were significantly higher in patients with lower BMIPP summed scores. These results suggest that myocardial fatty acid imaging may be a useful test to identify high risk groups of cardiac death in hemodialysis patients.

Background/Aims: De novo coronary atherosclerosis may be involved in the poor prognosis after percutaneous coronary artery intervention (PCI) in hemodialysis patients. We aimed to clarify the factors associated with de novocoronary lesion in this population. Methods: We enrolled 106 patients on hemodialysis (72 men, 34 women; mean age, 65.4 ± 8.9 years), who had firstly received PCI with bare-metal stents for single coronary lesions and undergone follow-up coronary angiography (CAG) 6 months thereafter. Coronary lesion with stenosis of >50% diameter that was newly recognized at follow-up CAG was defined as de novo coronary stenosis. The values of biochemical parameters were determined as the means of several measurements between PCI and follow-up CAG. Results: Follow-up CAG revealed de novo coronary stenosis in 40 (37.7%) of the 106 hemodialysis patients who had received PCI. Stepwise multiple logistic regression analysis showed that de novo coronary lesions were strongly associated with homeostasis model assessment insulin resistance index (HOMA-IR; 1 mM× [µU/ml]: odds ratio, 7.312; p =0.001). This significant association of HOMA-IR with de novo coronary stenosis was recognized in the diabetic and nondiabetic subgroups. Conclusions: Insulin resistance may be involved in the progression of nonculprit coronary atherosclerosis after PCI in hemodialysis patients.

It is thought that area wide conservation of traditional townhouses is very important for the community planning. However, town takes always renewal. Therefore the conservation of traditional townhouses must have a concrete way of realization. I think that the methodology of the architectural typology in Italy, Tipologia' by Muratori School is useful for traditional townhouses in Japan. Because it is a method of dynamically understanding the form of construction in history. Here, I studied of an architectural typology on the traditional townhouses in Aboshi district, Himeji city. As a result, it is possible to divide into seven patterns. And, it is obvious that the way of improvement of each pattern is necessary for the area wide conservation.

新生児聴覚スクリーニング後当院耳鼻咽喉科小児難聴外来を受診した16例の精密聴力検査の結果及びその対応について検討した。初診時の月齢は平均1.5ヵ月で, スクリーニングの方法はOAEが大半であった。初回精査の結果は難聴11例, 聴力正常5例であった。新生児期のOAEによるスクリーニングで refer が多くなる原因として, 外耳道の狭さや中耳の滲出液による影響が指摘されている。初回精査時に難聴と判定した11例中6例はほぼ6ヵ月以内に閾値が改善し正常となった。閾値改善の要因として, 聴覚伝導路の髄鞘化が成長と共に完成していったものと考えられた。新生児の精密な聴力の評価には時間を要するため, 特定の医療機関に集中して紹介された場合には対応が困難となることが考えられる。偽陽性例を除外し難聴児を早期に発見するためには, 複数の医療機関でスクリーニング後の精査が可能となることが望ましいと考えられた。

Atrial fibrillation (AF) is common in dialysis patients. However, clinical characteristics and outcomes of dialysis patients with AF are poorly understood. The Fushimi AF Registry is a community-based prospective survey of AF patients in Japan. Follow-up data were available for 3713 patients with a median follow-up of 2.8 years. We compared clinical characteristics and outcomes between the dialysis group (n = 92; 2.5 %) and others. The dialysis group had more various co-morbidities, with a mean CHADS2 score of 2.5, and the rate of warfarin prescription was 38 %. The annual incidence rates of stroke or systemic embolism (SE), major bleeding, and all-cause death in the dialysis group were 4.0, 5.1, and 20.9 per 100 person-years, respectively. There was no significant difference in the incidence rate of stroke/SE between the dialysis group and the non-dialysis group [hazard ratio (HR) 1.74 (95 % confidence interval (CI) 0.74–3.42)]. The incidence rates of major bleeding, all-cause death, and the composite of stroke/SE and all-cause death in the dialysis group were higher than those in the non-dialysis group [major bleeding: HR 3.09 (95 % CI 1.46–5.72), all-cause death: HR 3.51 (95 % CI 2.48–4.81), the composite of stroke/SE and all-cause death: HR 2.99 (95 % CI 2.15–4.05)]. Among dialysis patients, warfarin did not affect major clinical events including stroke/SE, bleeding or all-cause death. Among AF patients, those receiving dialysis showed higher incidence of major bleeding and all-cause death compared with non-dialysis patients, but the risk of stroke/SE was not particularly high. URL: http://www.umin.ac.jp/ctr/index.htm .

We investigated whether chronic intravenous administration of l-carnitine could improve myocardial fatty acid imaging in patients on maintenance hemodialysis. We enrolled 72 hemodialysis patients who had impaired myocardial fatty acid imaging and left ventricular dysfunction not based on coronary lesion. l-Carnitine (1,000 mg) was intravenously administered after dialysis for 1 year to 36 participants (Carnitine group), while not in the other 36 participants (Control group). Single-photon emission computed tomography (SPECT) using an iodinated fatty acid analogue, BMIPP, was performed. Uptake on SPECT images was graded in 17 segments on a five-point scale (0, normal; 4, absent) and assessed as BMIPP summed scores. During follow-up, 19 participants were discontinued from the study, and 53 participants (65 ± 12 years: 27 carnitine, 26 control) were analyzed. The mean BMIPP summed scores 1 year after carnitine administration did not differ from that before in the carnitine group, nor from that in the control group. However, improved SPECT (Changes in BMIPP summed scores

Purpose We investigated whether impaired patterns of myocardial fatty acid imaging were associated with cardiac death in dialysis patients without coronary lesions. Methods We prospectively enrolled 155 hemodialysis patients without obstructive coronary artery disease, who had been examined by single-photon emission computed tomography (SPECT) using the iodinated fatty acid analogue BMIPP. Uptake of BMIPP on SPECT was graded in 17 segments on a five-point scale (0, normal; 4, absent) and assessed as BMIPP summed scores. Of the enrolled 155 participants, we analyzed 95 who had BMIPP summed scores ≥ 6 (52 men and 43 women, 65 ± 11 years). BMIPP scores ≥ 2 in ≥ 2 consecutive segments in SPECT were defined as focal, and the others as non-focal pattern. Results Of 95 participants analyzed, 42 (44.2 %) showed focal and 53 (55.8 %) non-focal type. During follow-up for 5.1 ± 2.0 years, 42 died of cardiac events. The occurrence of cardiac death was higher in the focal than in the non-focal group (30/42 [71.4 %] versus 12/53 [22.6 %], p = 0.001). In stepwise Cox hazard analysis, focal pattern was associated with cardiac death (hazard ratio 2.266), independent of impairment of BMIPP SPECT (BMIPP summed scores ≥ 12). The predictive potential of BMIPP SPECT for cardiac death was higher (p

Background Capillary pericytes (cPCs), the mural cells of microvessels, play an important role in the formation and maintenance of microvessels; however, little is known about the mechanisms of how cPCs regulate angiogenesis. To identify factors that modulate cPC function, genes whose levels were altered in cPCs during neovessel formation were identified through a microarray screen. Methods and results Ninjurin1 (nerve injury-induced protein, Ninj1) was selected as a candidate factor for angiogenesis regulation. Ninj1 was expressed in capillary cells including endothelial cells (cECs) and was expressed at a higher level in cPCs. Hypoxia induced the gene expression of Ninj1 in addition of vascular endothelial growth factor (VEGF) in cPCs. When cPCs were co-incubated with a thoracic aorta in a three-dimensional Matrigel system, the length of the EC-tubes sprouting from the aorta was increased. Small interfering RNA-mediated downregulation of Ninj1 in cPCs enhanced these cPCs-mediated angiogenic effects, whereas overexpression of Ninj1 attenuated their effects. The production of angiogenic growth factors, such as VEGF and angiopoietin 1, by cPCs was enhanced by the downregulation of Ninj1, and reduced by the overexpression of Ninj1. Conclusions Ninj1 is a novel regulator for the angiogenic effect of PCs. Specifically, Ninj1 negatively regulates the formation of neovessels, that is, the EC-tube, by reducing the trophic effects of cPCs.

Purpose To assess whether T1 relaxation time of tumors may be used to assess response to bevacizumab anti-angiogenic therapy. Procedures: 12 female nude mice bearing subcutaneous SKOV3ip1-LC ovarian tumors were administered bevacizumab (6.25ug/g, n=6) or PBS (control, n=6) therapy twice a week for two weeks. T1 maps of tumors were generated before, two days, and 2 weeks after initiating therapy. Tumor weight was assessed by MR and at necropsy. Histology for microvessel density, proliferation, and apoptosis was performed. Results Bevacizumab treatment resulted in tumor growth inhibition (p

We investigated whether insulin resistance is associated with impaired cardiac fatty acid metabolism in maintenance hemodialysis patients without coronary artery disease. We studied 55 nondiabetic (63±11 years old) and 51 diabetic (61±10 years old) hemodialysis patients with normal coronary arteries, using single-photon emission computed tomography (SPECT) with an iodinated fatty acid analogue, iodine-123- β -methyl iodophenyl-pentadecanoic acid ( 123 I-BMIPP), to evaluate cardiac fatty acid metabolism. SPECT imaging was graded regionally from 0 (normal) to 4 (absence of tracer) to calculate a summed score for 17 left ventricular segments. Insulin resistance was determined using the homeostasis model assessment index of insulin resistance (HOMA-IR). HOMA-IR correlated with summed BMIPP score in nondiabetic and diabetic patients. Stepwise multiple regression analysis showed that HOMA-IR was independently associated with BMIPP summed score in nondiabetic ( β =0.774, t =9.218, P= 0.0001) and diabetic patients ( β =0.792, t =9.079, P= 0.0001). Left ventricular ejection fraction was lower in nondiabetic subjects with BMIPP summed score of at least 6 plus HOMA-IR of at least 4 than in others with lower values for both assessments (53.1±13.8%, n =20 vs 67.7±9.1%, n =23, P =0.0002); this was also true in diabetic subjects (50.9±15.2%, n =24 vs 71.0±13.6%, n =11, P= 0.0007). Association between insulin resistance and impaired cardiac fatty acid metabolism may contribute to left ventricular dysfunction in patients with maintenance hemodialysis without coronary diseases.

Background Success of coronary stenting is limited by in-stent restenosis. We aimed to determine whether circulating levels of the cytokines, which have anti-inflammatory properties such as adiponectin or interleukin-10, could be associated with the occurrence of coronary in-stent restenosis in patients with end-stage renal disease (ESRD). Methods We enrolled 71 consecutive ESRD patients undergoing haemodialysis (mean age: 64.9+/-8.9 years; 19 women, 52 men; mean haemodialysis duration: 78.2+/-87.5 months), who received stenting for a single coronary lesion. Plasma concentrations of adiponectin and IL-10 were measured within one week before coronary stenting. Results Of the 71 patients who had received stenting, in-stent restenosis occurred in 37 patients (52.1%) within 6 months after stenting. In univariate logistic analysis, the homeostasis model assessment index of insulin resistance, blood haemoglobin, serum concentrations of high density lipoprotein-cholesterol or triglycerides and plasma concentrations of insulin or adiponectin were significantly associated with coronary in-stent restenosis. In a multiple logistic regression analysis among these variables, however, only the plasma adiponectin concentration was associated with the coronary in-stent restenosis: the odds ratio of the increase in 1 microg/ml of plasma adiponectin concentration for having restenosis was 0.651 (P = 0.001, 95% confidence interval: 0.506-0.839). Patients with restenosis had lower plasma adiponectin concentrations than those without [6.2+/-2.2 microg/ml (2.1-10.4 microg/ml; n = 37) vs 27.2+/-10.8 microg/ml (17.9-79.8 microg/ml; n = 34); P = 0.0001]. Conclusions Circulating adiponectin concentrations may be associated with the occurrence of coronary in-stent restenosis in ESRD patients undergoing maintenance haemodialysis.

Anthocyanins, which are responsible for a variety of bright colors (including red, blue, and purple) in fruits, vegetables, and flowers, are consumed as dietary polyphenols. Anthocyanin-containing fruits are thought to decrease coronary heart disease and are used in anti-diabetic preparations. Diabetes is associated with a variety of cardiovascular complications that may be mediated by endothelial dysfunction, and so this study was designed mainly to characterize the influence of a synthesized anthocyanidin derivative (HK-008) over acetylcholine (ACh)-induced relaxation in mesenteric arterial beds isolated from rats. In a glucose-tolerance test in intact rats, HK-008 (30 mg/kg) reduced the glucose level as effectively as the same dose of glibenclamide. The aortic relaxation induced by pinacidil (an ATP-sensitive potassium channel opener) was greatly inhibited by glibenclamide (10 microM), and also significantly inhibited by HK-008 (10 microM). Interestingly, the ACh-induced relaxation in the perfused, preconstricted mesenteric arterial bed was significantly enhanced by HK-008 (10 microM), and this enhancement was significantly attenuated by indomethacin (10 microM). The ACh-induced mesenteric relaxation was impaired by an increase in oxidative stress, viz. superoxide-generating treatment [xanthine oxidase (XO; 0.1 U/ml) plus hypoxanthine (HX; 10 microM)]. However, this impairment was strongly suppressed by HK-008 (10 microM). These results suggest that HK-008 increases endothelium-induced relaxation by suppressing oxidative stress or modulating prostanoids signaling. This compound may therefore be useful against certain cardiovascular disorders.

超軟弱粘土地盤の自重圧密中の強度特性を調べるために，遠心加速度場で自重圧密した模型粘土地盤に対してベーンせん断試験を行い，ベーンせん断強度と自重圧密解析より推定した有効応力および含水比との関係について検討した．その結果，自重圧密中の超軟弱粘土のせん断強度と含水比の間には，圧密の程度によらない固有な関係があることが分かった．また，遠心力除荷による応力解放が，自重圧密解析，ベーンせん断強度に及ぼす影響についても検討した．その結果，応力解放が解析結果に及ぼす影響は小さく，せん断強度と有効応力の関係については，等価有効応力を用いることで評価できることが分かった．

BACKGROUND Traditional risk factors of cardiovascular disease do not fully explain the accelerated atherosclerosis present in patients with end-stage renal disease (ESRD). The goal of this study was to identify the association of clinical and laboratory factors including seropositivity for Chlamydia pneumoniae determined by a specific enzyme-linked immunosorbent assay (ELISA) with the presence of coronary artery disease identified by coronary angiography in ESRD patients. METHODS We prospectively enrolled 161 consecutive ESRD patients undergoing haemodialysis for >6 months (106 men, 55 women; mean age 63.1+/-10.2 years; mean dialysis duration 91.3+/-90.1 months). All patients underwent coronary angiography within 1 week after blood sampling. The associations of coronary artery disease with clinical parameters including C. pneumoniae IgA and IgG seropositivity were analysed using multiple logistic regression models. RESULTS Coronary stenosis >50% was found in 102 of 161 haemodialysis patients (63.4%). Of the 102 patients, 75.5% were asymptomatic. Seropositivity for C. pneumoniae IgA was found in patients with coronary stenosis (77 out of 102, 75.5%) more frequently (P

Pure Al film with surface roughness, incompletely nitrided Al film (Al–N film), and transparent AlN film are deposited in turn on a glass substrate by an rf sputtering method. The Al film as the infrared reflector with optimized surface roughness is prepared by a method of two-step deposition of an Al layer at two different substrate temperatures. By coating with an Al–N film, the Al film reduces its diffuse reflectance while maintaining its characteristic low emittance. It is also confirmed that the top layer of the AlN film can perform the role of antireflector coating even if the surface is rough. As a result, an optimized AlN/Al–N/Al film with surface roughness on the glass substrate realizes the high performance of a solar selective absorber, e.g., high solar absorptance of 0.92 and low normal emittance of 0.06 at 373 K.

虚血性心疾患は血液透析患者の主要な死因の一つである. 冠動脈疾患の検出に心臓核医学検査は有用であるが運動・薬剤負荷を必要とし, 透析患者では, その実施・判定に困難を伴うことが多い. 正常心筋はエネルギー源の70%以上を効率のよい脂肪酸β酸化に依存しているが, 心筋虚血時には脂肪酸のβ酸化が抑制され, 代わってグルコースを利用した解糖系へ移行する. 透析患者の冠動脈病変検出における心筋脂肪酸代謝イメージング製剤である123I-BMIPPの安静時検査の有用性を検討した.慢性腎不全による維持血液透析患者130例 (平均透析期間88.5か月, 男性77例, 女性53例, 平均年齢63.8歳) に対し心筋血流製剤である塩化タリウム (201TI) ならびに123I-BMIPPのSPECT (single photon emission computed tomography) を施行し, その後60日以内に施行された冠動脈造影検査所見と対比した. 左室心筋を17分画し, TIおよびBMIPP SPECT所見を視覚的に判定, スコア化し (0: 正常-4: 欠損), その総計をTIならびにBMIPP summed scoreとした.冠動脈造影の結果, 対象患者の71.5%に75%以上の有意狭窄を認めた. BMIPP summed score 6以上を陽性とした場合, BMIPP-SPECTの冠動脈病変の総合正診率は90.0% (感度: 98.0%, 特異度: 65.6%) であった. 一方, TI-SPECTでは, TI summed score 1以上を陽性とした場合, 感度84.7%, 特異度46.9%, 総合正診率75.0%であった. ROC解析の結果, 冠動脈病変診断能を示すAUC (area under the curve) は, BMIPP SPECT 0.895, TI SPECT 0.727であった.BMIPP-SPECTはTI-SPECTに比して高い精度で冠動脈病変を検出できる. 慢性血液透析患者の冠動脈造影検査の適応判定ならびに冠動脈疾患合併の安全なスクリーニング検査として臨床的に有用である.

Background. The incidence of intracardiac thrombosis in haemodialysis patients has not been studied. Here we determined the incidence in end-stage renal disease patients on maintenance haemodialysis. Methods. Transoesophageal echocardiography was performed in 215 patients (125 males, 90 females; mean age 60 ± 9 years). Any potential candidate with current or past chronic or intermittent atrial fibrillation or with cardiovascular diseases was excluded from the study. Results. Thrombi were found in the left atrial appendages in 71 out of 215 subjects (33%). Based on multiple logistic regression analyses, the probability of finding a thrombus was found to be increased in patients on chronic antiplatelet therapy (odds ratio 4.268) and in those with diabetes mellitus and a low haematocrit (� 0.3; odds ratio 7.173). Other clinical parameters, including gender, age, duration of haemodialysis, blood pressure, left ventricular dimension, smoking habit or type of anticoagulation during dialysis, were not associated with the incidence of left atrial appendage thrombosis. Conclusions. Maintenance haemodialysis patients have a high incidence of left atrial appendage thrombosis. Either chronic use of antiplatelet drugs or the background conditions requiring antiplatelet therapy, and the concomitant presence of diabetes mellitus and a low haematocrit may be involved in left atrial appendage thrombosis.

1. Diabetes mellitus is significantly associated with the occurrence of congestive heart failure in end-stage renal disease patients undergoing maintenance haemodialysis. In the present study, we asked whether the left ventricular remodelling against sustained pressure and/or volume overload to the left ventricle may be different between diabetic and non-diabetic haemodialysis patients. 2. Left ventricular parameters, including left ventricular mass index (LVMI), interventricular septal wall thickness (IVST) and relative left ventricular wall thickness (rLVWT), were assessed in 486 patients receiving maintenance haemodialysis (145 diabetic and 341 non-diabetic patients) using transthoracic echocardiography. Plasma concentrations of B-type natriuretic peptide (BNP), measured with an immunoradiometric assay, were used as a humoral parameter indicating left ventricular wall stress. 3. In non-diabetic patients, the plasma BNP concentration correlated with LVMI (r = 0.245; P = 0.0001), IVST (r = 0.250; P = 0.0001) and rLVWT (r = 0.149; P = 0.006). Furthermore, LVMI was correlated with mean blood pressure and pulse pressure and IVST and rLVWT were correlated with pulse pressure. 4. In contrast, none of the measured factors was correlated with LVMI and IVST in diabetic patients. Plasma BNP concentrations were positively correlated with end-systolic and end-diastolic left intraventricular dimensions and were inversely correlated with rLVWT and left ventricular fractional shortening in diabetic patients, but not in non-diabetic patients. 5. In conclusion, a sustained increase in left ventricular wall stress is likely to elicit eccentric left ventricular remodelling in diabetic haemodialysis patients, whereas it causes concentric left ventricular remodelling in non-diabetic haemodialysis patients. This difference in left ventricular remodelling against left ventricular overload may be associated with the high incidence of congestive heart failure in diabetic haemodialysis patients.

Hydrophilic phosphine ligands possessing a carbohydrate side-chain, such as N -(4-diphenylphosphinophenyl)methyl gluconamide ( 9 ), N -[4-(2′-dicyclohexylphosphinobiphenyl)phenylmethyl] gluconamide ( 10 ), and N -[4-(2′-di- t -butylphosphinobiphenyl)]phenylmethyl gluconamide ( 11 ), were newly synthesized to carry out palladium-catalyzed biaryl coupling of arylboronic acids in a single aqueous medium. The catalyst prepared in situ from Pd(OAc) 2 and 10 exhibited a higher efficiency than that of 9 , 11 , Ph 2 P( m -C 6 H 4 SO 3 Na) (TPPMS) or P( m -C 6 H 4 SO 3 Na) 3 (TPPTS) for representative aryl bromides, chlorides, or triflates. The catalyst prepared in situ from Pd(OAc) 2 (0.001 mol%) and 10 (0.002 mol%) achieved 96,000 TON in the reaction of p -tolylboronic acid with 4-bromoacetophenone in water.

SUMMARY 1. The effect of vasodilatory β-adrenoceptor blockers on regional blood flow in the major organs of anaesthetized rats was investigated using radioactive microspheres. The administration of propranolol and saline was used as a control. 2. Intravenous injections of carvedilol (2 mg/rat), celiprolol (20 mg/rat) and bopindolol (1 mg/rat) equally decreased systemic blood pressure (SBP) by approximately 20 mmHg, whereas propranolol (1 mg/rat) decreased SBP only slightly but not significantly. 3. Heart rate was significantly decreased by carvedilol, celiprolol, bopindolol and propranolol. 4. Coronary blood flow was markedly increased by carvedilol, but not by the other three drugs. 5. Cardiac output tended to decrease following the administration of all four drugs. 6. Total peripheral vascular resistance was not significantly affected by carvedilol, celiprolol and bopindolol, but was markedly increased following propranolol. 7. Renal blood flow was markedly increased by carvedilol. 8. Blood flow in the brown fat was markedly increased by carvedilol and bopindolol, but not by celiprolol and propranolol. 9. These findings indicate that the newer vasodilatory beta-blockers, such as carvedilol and bopindolol, have a beneficial effect on the regional circulation in contrast with the classical beta-blocker propranolol. 10. The regional haemodynamic effects observed in the present study following intravenous injection of the beta-blockers may help explain the clinical experience that vasodilatory beta-blockers increase insulin sensitivity and decrease mortality in patients with congestive heart failure.

Al–N films are formed on a glass substrate by rf sputtering using Ar and N2 gas mixture. The concentration of partial N2 gas pressure (cN2) is changed from 0.0%N2 to 16.0%N2. Optical properties are measured in the wavelength range of 0.24 to 2.60 µm. When cN2 is varied at the same film thickness, the specimen with 7.3%N2 shows the highest solar energy absorptance (α) for the air mass one. Then, as the film becomes thicker at this cN2, α increases to 0.95, which is a promising characteristic for application as a solar absorber coating. It is also observed by atomic force microscopy that the surface roughness is enhanced as the film becomes thicker. The essential reason for the high value of α is the antireflection effect due to the gradient-refractive index caused by the enhanced surface roughness during film growth.

Nano-structured Ag layers with the thickness in a range of d Ag = 0.9-24 nm sandwiched between MgO layers are formed by rf sputtering. The morphology of nano-structured Ag is observed by the transmission electron microscope. Then the optical property is measured in a range of wavelength of 0.24-2.6 μm, which covers the solar energy spectrum. Several characteristics are recognized. For example, the nano-structured Ag layer having the intermediate morphology between the nano-particle and the continuous film shows the effective optical property in absorbing solar spectrum, such as large absorptance not only at visible region but also at near-infrared region. Moreover, it is found that the nano-structured Ag layers with d Ag ≤ 5.4 nm and with d Ag ≥ 24 nm are thermally stable at 673 K, but those with d Ag = 6.3-13.5 nm are thermally unstable. In order to utilize the advantageous characteristics of the nano-structured Ag layers for the solar absorber coating, the optical constant of each layer is experimentally evaluated. Then the selective solar absorber coating with functional graded structure made of all nano-structured Ag layers is designed. The fabricated coating shows the high-performance such as the photo-thermal conversion efficiency of 0.72 for air mass 1.5 at an operating temperature of 373 K, the thermal stability as well.

目的: 慢性腎不全による維持血液透析例の左室肥大の成因について, 糖尿病 (DM) 罹患の有無の観点から臨床的に検討した. 対象と方法: 維持血液透析患者486例 (DM145例, 非DM341例) を対象に, 透析前に心臓超音波検査を施行し, 心機能とともに心室中隔径 (IVST), 相対的左室壁厚 (rLVWT), 左室重量係数 (LVMI) を計測した. 透析施行直前のヘマトクリット値, 血漿BNP濃度, 血漿アルドステロン濃度を測定し, 左室肥大との関係を検討した. 結果: 非DM例では, 左室壁ストレスの指標である血漿BNP濃度は, LVMI (r=0.245, p=0.0001), IVST (r=0.250, p=0.0001), rLVWT (r=0.149, p=0.006) と正相関を示した. LVWIは, 透析前後の平均血圧および脈圧, IVSTならびにrLVWTは, 透析前後の脈圧と正相関を示した. DM例では, LVMI, IVST, rLVWTのいずれも血漿BNP濃度, 透析前後の血圧・脈圧値との関連はなかった. 非DM・DM例ともに, ヘマトクリット値, 血漿アルドステロン濃度は左室肥大の指標との関連を認めなかった. 結論: 非DM性透析患者では持続的な容量・圧負荷による左室壁ストレス増加に対して左室心筋リモデリングによる代償性の左室肥大を生じる. DM性透析患者では, 左室肥大は圧・容量負荷とは関係なく生じ, 左室壁ストレスに対する心筋リモデリング・代償性左室肥大の機構に障害がある可能性がある.

This study experimentally examined why subjective probability for delayed reward decays non-exponentially (“hyperbolically”, i.e., q ˂ 1 in the q-exponential discount function) in humans. Our results indicate that nonlinear psychophysical time causes hyperbolic time-decay of subjective probability for delayed reward. Implications for econophysics and neuroeconomics are discussed.

We have proposed γ-Al2O3 thin films as an epitaxial buffer layer on Si substrates for obtaining epitaxial Pb(Zr,Ti)O 3 (PZT) thin films and reported a 2-D ultrasonic image sensor and measurement and analysis of ultrasonic transmission using piezoelectric micromachined ultrasonic transducers (pMUTs) on γ-Al 2 O 3 /Si substrates. −6 dB beamwidth and sound pressure at 5 mm from surface of the 4 channel pMUT array were exbited 10 times larger than signle pMUT. These experimental results good agree with analysis results. It will be applied to design miniature 2-D pMUTs array ultrasonic probe.

SummaryOvarian cancer has a clear predilection for metastasis to the omentum, but the underlying mechanisms involved in ovarian cancer spread are not well understood. Here, we used a parabiosis model that demonstrates preferential hematogenous metastasis of ovarian cancer to the omentum. Our studies revealed that the ErbB3-neuregulin 1 (NRG1) axis is a dominant pathway responsible for hematogenous omental metastasis. Elevated levels of ErbB3 in ovarian cancer cells and NRG1 in the omentum allowed for tumor cell localization and growth in the omentum. Depletion of ErbB3 in ovarian cancer impaired omental metastasis. Our results highlight hematogenous metastasis as an important mode of ovarian cancer metastasis. These findings have implications for designing alternative strategies aimed at preventing and treating ovarian cancer metastasis.

A 57-year-old male who had been treated with hemodialysis due to end-stage chronic kidney disease for 3 years received arterio-venous bypass grafting with a polyurethane vascular access graft in his left upper arm. Two months later, he was diagnosed with hemolytic anemia with fragmented red blood cells (RBC). He had never shown clinical symptoms such as fever or neurological abnormalities characteristic of thrombotic thrombocytopenic purpura (TTP). Moreover, neither thrombocytopenia nor coagulation abnormality was found on routine laboratory examination. He received arterial banding to reduce the blood flow entering the artificial vascular access graft, which led to rapid recovery from hemolytic anemia, without recurrence. This was an extremely rare case of angiopathic hemolytic anemia with fragmented RBC caused by unfavorable bypass grafting, successfully treated with simple reoperation to reduce the blood flow entering the vascular access graft.

Vulvar cancer is an extremely rare complication during pregnancy, and its effect on pregnancy and survival is not well understood. A systematic literature review was conducted in order to examine the fetal and maternal outcomes and optimal management of pregnancy complicated by vulvar cancer. PubMed/MEDLINE were used to identify case reports with searching keywords "pregnancy" and "vulvar cancer" between January 1955 and February 2014 that identified 36 cases for analysis. Mean age was 30.7. The most common presenting symptom and gestational age were vulvar mass/swelling (75.0%) and the second trimester of pregnancy (54.8%), respectively. Vulvar biopsy at the time of initial presentation to care during pregnancy was performed in only 46.7% of cases. Among delayed cases for biopsy, mean duration of delay was 12.8 weeks and the majority had a delay for more than 8 weeks (62.5%). The majority of vulvar cancer was squamous histology (47.2%) and stage I disease (60.0%). Vulvectomy and inguinal-femoral lymphadenectomy were performed in 97.1% and 63.9%, respectively. Abdominal delivery was recorded in 46.2% of cases. Live birth and full term delivery rates were 96.3% and 74.0%, respectively. For survival analysis, delay in diagnosis and advanced stage disease were commonly associated with decreased disease-free survival (5-year rate, delay in diagnosis8 versus ≤8 weeks, 0% versus 69.1%, hazard ratio (HR) 7.86, 95% confidence interval (CI) 2.03-30.6, p=0.001; and stage III-IV versus stage I-II, 0% versus 59.8%, HR 3.35, 95% CI 1.16-9.68, p=0.011) and overall survival (5-year rate, delay in diagnosis8 versus ≤8 weeks, 0% versus 67.1%, hazard ratio (HR) 14.8, 95% CI 1.77-124, p=0.001; and stage III-IV versus stage I-II, 0% versus 86.4%, HR 8.22, 95% CI 2.06-33.2, p0.001). In conclusion, while the majority of cases resulted in good pregnancy outcomes, diagnosis of vulvar cancer during pregnancy is frequently delayed. Since delayed diagnosis is a significant prognosticator of decreased survival outcomes, early recognition is integral in the management of pregnancy complicated by vulvar cancer.

SUMMARY 1. The aim of the present study was to investigate whether long-term oral administration of eicosapentaenoic acid increases nitric oxide (NO) production and affects cardiac sympathetic activity in rats with diabetes mellitus. 2. We measured changes in urinary excretion of NO3–, a stable NO metabolite, and cardiac noradrenaline (NA) concentrations in non-diabetic rats and streptozotocin-induced diabetic rats treated with either ethyl icosapentate (EPA-E; 100 mg/kg per day; n = 10), a purified ethyl esterification product of eicosapentaenoic acid, or vehicle (distilled water; n = 10) for 6 weeks. The effects of NG-nitro- L-arginine ( L-NNA), a NO synthase inhibitor, on urinary NO3– excretion and cardiac NA concentrations were also investigated in diabetic rats treated with EPA-E. 3. Urinary NO3– excretion was higher at weeks 5 and 6 in diabetic rats treated with EPA-E than in diabetic rats treated with vehicle (week 5: 120±8 vs 51±11 μmol/g per day, respectively (P < 0.01); week 6: 279±83 vs 73±9 μmol/g per day, respectively (P < 0.01)). Cardiac NA concentrations were higher in diabetic rats than in non-diabetic rats and were decreased in the left atrium and both ventricles in diabetic rats treated with EPA-E compared with control. Systemic administration of L-NNA abolished the increase in urinary excretion of NO3– and the decrease in cardiac NA concentrations in diabetic rats treated with EPA-E. 4. Long-term oral administration of EPA-E may stimulate NO production and increased NO is likely to play a role in inhibiting enhanced cardiac sympathetic activity in diabetic rats.

Abstract —FMRFamide, a cardioexcitatory neuropeptide, directly activates a newly cloned amiloride-sensitive sodium channel that is expressed specifically in the brain and blocked by benzamil hydrochloride. In the present study, we investigated the effects of short- and long-term intracerebroventricular infusion of FMRFamide on arterial pressure, sympathetic activity, vasopressin release, and brain renin-angiotensin system genes in rats and studied the role of FMRFamide-activated brain sodium channels in salt-sensitive hypertension. The intracerebroventricular preinjection of FMRFamide and subsequent intracerebroventricular infusion of 0.15 mol/L NaCl increased mean arterial pressure (FMRFamide: 30 nmol/kg +13±2.6 mm Hg, P P −1 · d −1 ) for 5 days increased mean arterial pressure, heart rate, urinary excretion of vasopressin and norepinephrine, and mRNAs of renin, angiotensin I–converting enzyme, and angiotensin II type 1 receptor in hypothalamus and brain stem compared with vehicle. These increases were abolished by intracerebroventricular coinfusion of benzamil. In rats administered a low-salt diet (0.3% NaCl), however, increases in these variables were smaller than those in rats receiving a high-salt diet. Together, these findings suggest that brain FMRFamide-activated sodium channels may be involved in the mechanism of salt-sensitive hypertension through regulation of the brain renin-angiotensin system.

Clinical findings in 14 ears of 12 patients (7 females and 5 males) with inner ear damage due to acute otitis media were studied. The patients' ages ranged between 27 and 77 years (average 45 years). The patiens complained of otalgia, hearing loss, tinnitis, and vertigo at the time of their initial presentations. They were treated with antibiotics combined with steroids, vasodilators, and vitamins. Complete recovery of hearing was obtained in 6 ears. We recommend early auditory and vestibular testing for patients who were suspected to have sensorineural hearing loss, tinnitis or vertigo due to inner ear damage.