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We investigated the usefulness of one-stage urethroplasty by the parameatal foreskin flap method (OUPF procedure), which is useful for repairing all types of hypospadias. Between June 1992 and March 2001, the OUPF procedure was performed on 18 patients with hypospadias: 10 patients with distal and 8 with proximal hypospadias. The follow-up periods ranged from 33-75 months, with an average of 52 months. The duration of surgery, the catheter indwelling period, and the postoperative complications of each patient were analyzed. The median age of the patients at the time of surgery was 3 years and 8 months. The length of surgery for OUPF II ranged from 150-230 min (average 186 min), and from 190-365 min (average 267 min) for OUPF IV. Postoperative complications were confirmed in 3 of the 18 patients (16.6%). Two patients had fistulas, and one had a meatal regression. The fistulas were successfully closed by the simple multilayered closure method. After adopting DuoDerm dressings instead of elastic bandages for protection of the wound, no fistulization occurred. DuoDerm dressings are useful in the healing of wounds without complications. To date, the longest follow-up period has been 75 months, and during that time there have been no late complications such as urethral stenosis or penile curvature. OUPF is a useful method in the treatment of hypospadias with a low incidence of early and late complications.

Epstein-Barr virus (EBV) is usually maintained in an asymptomatic and latent form by the host immune system, and primarily by EBV-specific cytotoxic T cells (CTLs). However, EBV has been linked to several refractory diseases such as EBV-associated hemophagocytic syndrome(EBV-AHS) and chronic active EBV infection (CAEBV). In these ectopic diseases, EBV infects T/NK cells, causing severe immunodeficiency with a very high EBV load. In recent years, the laboratory procedure to assess these types of EBV infections has been improved. In particular, real-time polymerase chain reaction (PCR) has been used to quantify the EBV load, and the MHC: peptide tetramer assay has been used to quantitate EBV-specific CTLs; these tests have been employed for the management of the illnesses associated with EBV infection. Here, we have reviewed the recent progress in the clinical application of these assays. The pathogenesis of EBV-infected T/NK cells, and the host immune response to infection, including the roles carried out by innate immunity and inflammatory cytokines, are likely to be revealed in the future.

Thirteen previously untreated patients aged 70 and above with acute nonlymphocytic leukemia were treated with aclarubicin (ACR) alone. Among 10 cases (3, acute myelocytic leukemia; 4, acute myelomonocytic leukemia; 2, acute monocytic leukemia; and one, acute erythroleukemia) in which an evaluation was possible, 5 cases (3, acute myelomonocytic leukemia; and 2, acute monocytic leukemia) obtained complete remission (CR). The CR rate was 83% in 6 patients with acute myelomonocytic leukemia or acute monocytic leukemia. The median CR duration and survival was 7.5 and 10 + months, respectively. Although side effects of the drug on digestive system such as nausea, vomiting and anorexia were observed in all patients, they were controllable by conventional treatments. The results suggest that ACR is effective for the clinical management of elderly patients with acute nonlymphocytic leukemia, especially those with acute myelomonocytic leukemia or acute monocytic leukemia.

We investigated the impact of olmesartan and temocapril on pancreatic islet beta-cells during the development of diabetes mellitus using Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats. Four-week-old male OLETF rats were fed standard chow (untreated:n5), or chow containing either 0.005% olmesartan(n5) or 0.01% temocapril (n5) until being sacrificed at 35 weeks of age. Pancreas sections were double-stained with anti-insulin and anti-glucagon antibodies. The percent areas of beta-cells, alpha-cells and non-alpha-non-beta-cells were compared among groups. In untreated OLETF rats, the fasting plasma glucose (FPG) level was elevated at the 18th week and remained elevated until the 35th week. On the other hand, no significant elevation in FPG levels was observed in olmesartan- or temocapril-treated rats. Pancreatic islets from olmesartan-treated rats were significantly smaller in size as compared with those from untreated OLETF rats. Furthermore, the average area occupied by beta-cells as a fraction of the total area of an individual islet was significantly higher in olmesartan- or temocapril-treated rats than that in untreated OLETF rats. Olmesartan and temocapril both prevented the development of hyperglycemia, possibly through the prevention of islet beta-cell loss in spontaneously diabetic OLETF rats.

Angiotensin I-converting enzyme (ACE) inhibitory and hypotensive effects of 7 peptide fractions (Frs) of royal jelly protein hydrolysate (RJPH) were studied in comparison with those of RJPH alone. Fr 4 and Fr 5 were the highest in ACE inhibitory activity and yield, respectively. Molecular weights (MWs) of RJPH and Fr 1-Fr 7 were distributed from 100 to 5,000 and those of Fr 1-Fr 7 increased in order from Fr 1 to Fr 7. RJPH, Fr 3 and Fr 4 at doses of 10, 30 and 100mg/kg i.v. and Fr 5 and Fr 6 at doses of 30 and 100mg/kg i.v. caused transiently significant hypotensive effects in spontaneously hypertensive rats (SHR). Fr 3, Fr 4, Fr 5 and Fr 6 at a dose of 1,000mg/kg also caused significant hypotensive effects 3h, 4-5h, 7-8h and 8h after oral administration in SHR, respectively. RJPH caused a long-lasting hypotensive effect in proportion to the magnitude of the MWs of RJPH fractions. The hypotensive pattern of RJPH was similar to the combined pattern of Fr 3-Fr 6. From these results, it can be concluded that the long-lasting hypotensive effect of oral administration of RJPH is dependent on the MWs of its ACE inhibitory peptides and the time required to digest them.

Many studies have shown that a motif of 11 consecutive arginines (11R) is one of the most effective protein transduction domains (PTD) for introducing proteins into the cell membrane. By conjugating this "11R", all sorts of proteins can effectively and harmlessly be transferred into any kind of cell. We therefore examined the transduction efficiency of 11R in cerebral arteries and obtained results showing that 11R fused enhanced green fluorescent protein (11R-EGFP) immediately and effectively penetrated all layers of the rat basilar artery (BA), especially the tunica media. This method provides a revolutionary approach to cerebral arteries and ours is the first study to demonstrate the successful transductionof a PTD fused protein into the cerebral arteries. In this review, we present an outline of our studies and other key studies related to cerebral vasospasm and 11R, problems to be overcome, and predictions regarding future use of the 11R protein transduction method for cerebral vasospasm (CV).

A cross-sectional study was conducted to evaluate the association between dietary intake and depressivesymptoms in community-dwelling elderly persons. Five-hundred elderly persons aged 65 to 75 years were randomly selected from the population of O city in Okayama Prefecture, Japan. Among 401 respondents (response rate, 80.0%), data from 279 (133 males, 146 females) who completed the questionnaire concerning dietary intake and depressive state were analyzed using logistic regression. Each of 17 dietary intakes was classified into tertiles:high intake, moderate intake, and low intake. The Center for Epidemiology Studies Depression scale (CES-D) was used. Among males, the observed odds ratios (the 95% confidence intervals) for the depressive state were 0.36 (95% CI:0.13-0.98) in the highest tertile of carotene intake, 0.33 (95% CI:0.12-0.93) in the highest tertile of vitamin C intake, 0.29 (95% CI:0.10-0.85) in the highest tertile of carbohydrate intake, and 0.33 (95% CI:0.12-0.92) in the medium tertile of vitamin E intake. Among females, similar results were observed, but these results were not statistically significant. The results suggested that carbohydrate, carotene, and vitaminC intakes are associated with lowering depressive symptoms among elderly persons dwelling in communities in Japan.

To investigate the effect of exclusive breastfeeding on the likelihood of Japanese preschool children being overweight, population-based cross-sectional survey data from M town in Japan were used. Using the population registry of this town, all 616 preschool children were identified, and a self-administered questionnaire was sent to their parents. The exposure variable of interest was exclusive breastfeeding from birth to 6 months, and the outcome variable of interest was the children being overweight at preschool age. Statistical analyses used included logistic regression and sensitivity analyses. In the final analyses, we included 448 preschool children. Although all point estimates indicated a protective effect, logistic regression analyses showed no significant reduction in being overweight due to exclusive breastfeeding in the unadjusted model (odds ratio (OR)0.70, 95% confidence intervals:0.30-1.64), the model adjusted for birth weight (OR0.70, 95% CI:0.30-1.63), the model adjusted for child lifestyle (OR0.71, 95% CI:0.30-1.67), or the model adjusted for parental factors (OR0.46, 95% CI:0.15-1.37). In sensitivity analyses, point estimates were not significant, but a protective effect was observed. In conclusion, our results suggest that breastfeeding might have a protective effect on Japanese preschool children against being overweight, although statistical significance was not observed due to the limitation of the statistical power of the findings.

In 1957, Pavlik introduced the Pavlik harness as a useful treatment for developmental dislocation of the hip (DDH), and subsequent studies have documented favorable outcomes among patients treated with this device. However, there are only a few articles reporting how early radiographic measurements can be used to determine the prognosis after treatment with the Pavlik harness. In this study, 217 hips from 192 patients whose DDH treatment with the Pavlik harness was initiated before they were 6 months old and whose follow-up lasted at least 14 years (rate, 63.8%) were analyzed using measurements from radiographs taken immediately before and after harness treatment, and at 1, 2, and 3 years of age. Severin's classification at the final follow-up was I or II in 71.9% and III or IV in 28.1% of the hips, respectively. Avascular necrosis of the femoral head (AVN) was seen in 10% of the hips. Stepwise multiple regression analysis was performed to retrospectively determine whether any radiographic factors were related to the final classification as Severin I/II or III/IV. Receiver opera-ting characteristic (ROC) curves were drawn for these factors, and a Wiberg OE angle (Point O was the middle point of the proximal metaphyseal border of the femur) of 2 degrees on the 3-year radiographs was found to be the most useful screening value for judging the acetabular development of DDH cases after treatment with a Pavlik harness, with a sensitivity of 71% a specificity of 93%, and a likelihood ratio of 10.1.

Surgical treatment of metastatic spinal cord compression is controversial. The purpose of this study was to investigate the effectiveness of our current surgical treatments and the use of spinal instrumentation. In this retrospective study covering the years between 1990 and 2006, 100 patients with spinal metastases which were secondary to various cancers underwent posterior and/or anterior decompression with spinal stabilization for the purposes of reduction of pain, and/or to help correct or improve neurological deficits. The group was made up of 60 men and 40 women whose ages ranged from 16 to 83 years (average of 60 years), and the average follow-up period was 14 months. The effect of treatment upon pain relief and neural deficits was assessed, and the cumulative survival rate was calculated by the Kaplan-Meier method. The average surgical time was 185min. This was calculated based on the following times, listed here with the surgery type:178min for posterior surgery;245min for anterior surgery;465 min for combined surgery;and 475min for total en bloc spondylectomy. Average blood loss during surgery was 1,630 ml for posterior surgery, 1,760 ml for anterior surgery, 1,930 ml for combined surgery, and 3,640 ml for total en bloc spondylectomy. Preoperative pain and paralysis were improved by 88% and 53%, respectively. In regards to surgical complications, postoperative epidural hematoma was observed in 2 patients, and instrumentation-related infection was observed in 1. Only 2 patients died within 2 months of surgery. In conclusion, posterior and/or anterior decompression with spinal stabilization is a safe and effective treatment for patients with spinal metastases, and can improve their quality of life.

The present study was performed to clarify the effect of hypertonic saline infusion into the lung parenchyma on radiofrequency ablation (RFA) of the lungs. A total of 20 ablation zones were created in 3 pigs. The ablation zones were divided into 3 groups. Group 1 (n6) consisted of ablation zones created by applying smaller radiofrequency (RF) power without saline infusion;group 2 (n5) zones were created by applying greater RF power without saline infusion;and group 3 (n9) zones were created by applying greater RF power with saline infusion. The techniques of saline infusion included administration of hypertonic saline 1ml before RFA, followed by continuous administration at a rate of 1ml/min during the first 2min after the initiation of RFA. The ablation parameters and coagulation necrosis volumes were compared among the groups. Group 3 had a tendency toward smaller mean impedance than group 1 (p0.059) and group 2 (p0.053). Group 3 showed significantly longer RF application time than group 2 (p0.004) and significantly greater maximum RF power than group 1 (p0.001) and group 2 (p0.004). Group 3 showed significantly larger coagulation necrosis volume (mean, 1,421mm3) than group 2 (mean, 858mm3, p0.039) and had a tendency toward larger necrosis volume than group 1 (mean, 878mm3, p0.077). Although this small study had limited statistical power, hypertonic saline infusion during RFA appeared to enlarge coagulation necrosis of the lung parenchyma.

To determine health-related quality of life (HRQOL) after radical retropubic prostatectomy (RRP) or permanent prostate brachytherapy (BT), third party-conducted QOL surveys were prospectively compared. Between 2004 and 2005, 37 patients underwent RRP and 36 were treated with BT. A QOL survey consisting of the Medical Outcomes Study 36-Item Short Form (SF-36), the University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) and the International Prostate Symptoms Score (IPSS) was completed prospectively by a research coordinator at baseline, and at 1, 3, 6 and 12 months after treatment. The RRP patients scored well in general QOL except at 1 month after surgery, with their mental health better than at baseline by 6 months after surgery. Disease-specific QOL in RRP patients received a low score at 1 month for both urinary and sexual function, though urinary function rapidly recovered to baseline levels. BT patient QOL was not affected by the therapy except in the IPSS score. However, general and mental health scores in BT patients were inferior to those in RRP patients. This prospective study revealed differences in QOL after RRP and BT. These results will be helpful in making treatment decisions.

Angiogenesis involves complex processes mediated by several factors and is associated with inflammation and wound healing. High mobility group box 1 (HMGB1) is released from necrotic cells as well as macrophages and plays proinflammatory roles. In the present study, we examined whether HMGB1 would exhibit angiogenic activity in a matrigel plug assay in mice. HMGB1 in combination with heparin strongly induced angiogenesis, whereas neither HMGB1 nor heparin alone showed such angiogenic activity. The heparin-dependent induction of angiogenesis by HMGB1 was accompanied by increases in the expression of tumor necrosis factor-alpha (TNF-alpha) and vascular endothelial growth factor-A120 (VEGF-A120). It is likely that the dependence of the angiogenic activity of HMGB1 on heparin was due to the efficiency of the diffusion of the HMGB1-heparin complex from matrigel to the surrounding areas. VEGF-A165 possessing a heparin-binding domain showed a pattern of heparin-dependent angiogenic activity similar to that of HMGB1. The presence of heparin also inhibited the degradation of HMGB1 by plasmin in vitro. Taken together, these results suggested that HMGB1 in complex with heparin possesses remarkable angiogenic activity, probably through the induction of TNF-alpha and VEGF-A120.

We report 2 cases of small cell carcinoma (SmCC) of the stomach with distant metastasis that were treated with the same chemotherapeutic regimens as used to treat small cell lung cancer. Although the mean survival of patients with SmCC of the stomach is reported to be only 7 months, our patients survived for 15 and 14 months, respectively. In our experience, these chemotherapeutic regimens might provide a survival benefit for patients with SmCC of the stomach, although they demonstrated no remarkable antitumor effects.

For many years, surgery alone was the standard treatment for patients with stage I-IIIA non-small-cell lung cancer (NSCLC). However, recent studies have demonstrated that adjuvant chemotherapy provides a survival benefit. The first adjuvant chemotherapy for NSCLC was performed in the 1960s using a key drug known as cyclophosphamide. In the 1980s and early 1990s, a new anti-cancer drug, cisplatin, was developed. The first meta-analysis of this drug was conducted by the Non-small Cell Lung Cancer Collaborative Group in 1995. This analysis comparing surgery with surgery plus chemotherapy containing cisplatin produced a hazard ratio of 0.87 and suggested an absolute benefit of chemotherapy of 5% at 5 years;this difference was not statistically significant (p0.08). Several clinical trials of adjuvant chemotherapy were planned after the meta-analysis conducted in 1995, but the efficacy of adjuvant chemotherapy remained a matter of controversy. However, useful evidence was reported after 2003. The International Adjuvant Lung Cancer Collaborative Group Trial (IALT) demonstrated a 4.1% improvement in survival for patients with stage I to III NSCLC. The JBR. 10 trial demonstrated a 15% improvement in 5-year survival for the adjuvant chemotherapy arm in stage IB or II (excluding T3N0) patients. The Adjuvant Navelbine International Trialist Association (ANITA) trial reported that the overall survival at 5 years improved by 8.6% in the chemotherapy arm and that this survival rate was maintained at 7 years (8.4%) in stage II and IIIA patients. A meta-analysis based on collected and pooled individual patient data from the 5 largest randomized trials was conducted by the Lung Adjuvant Cisplatin Evaluation (LACE). This analysis demonstrated that cisplatin-based adjuvant chemotherapy improved survival in patients with stage II or III cancer. Alterna-tively, uracil-tegafur has been developed and tested in Japan. The Japan Lung Cancer Research Group (JLCRG) on Postsurgical Adjuvant Chemotherapy reported a 5-year overall survival advantage of 11% in the uracil-tegafur group patients with stage IB cancer. The efficacy of adjuvant chemotherapy with uracil-tegafur was confirmed in a meta-analysis. In conclusion, the results of phase III trials and a meta-analysis have confirmed the benefit of adjuvant chemotherapy for resected stage IB, II, and IIIA NSCLC.

The first operative procedure in sex reassignment surgery (SRS) for female-to-male transsexuals (FTMTS) is mastectomy. This procedure includes the removal of mammary tissue, removal of excess skin, and reduction and proper repositioning of the nipple and areola complex. We have performed mastectomies in over 120 patients since January 2001 and want to describe the operative procedures we have developed. We classified our patients into 3 groups according to the patient's breast volume and the degree of ptosis, and we selected the operative procedure that was suitable for each group. At present all costs for SRS are assumed by the patient in Japan. If the FTMTS patient undergoes the entire series of SRS operations, he has to pay more than 3,000,000 yen. Thus the surgeon should select the proper operative procedure so that the patient can avoid unnecessary additional operations. We describe herein the techniques and the strategy for performing mastectomy in FTMTS.

This study evaluated the effects of chronic hypoxia from birth on the resistance of rat hearts to global ischemia, with special emphasis on the duration of hypoxia. Male Wistar rats were housed from birth for 4 weeks or 8 weeks either in a hypoxic environment (FiO20.12) or in ambient air (8 animals for each group). Isolated rat hearts were perfused for 40 min with oxygenated Krebs-Henseleit buffer, subjected to 20 min global no-flow ischemia at 37, and then underwent 40 min of reperfusion. A non-elastic balloon was inserted into the left ventricle and inflated until the pre-ischemic LVEDP rose to 8mmHg. Cardiac function was measured before and after ischemia. The post-ischemic percent recovery of LVDP in hypoxic hearts was worse than in normoxic hearts (4 weeks:55+/-7 vs. 96+/-3%, p0.01;8 weeks:40+/-5 vs. 92+/-4%, p0.01), and was worst in the 8-week-hypoxic hearts. Similarly, the percent recovery of dP/dt in the hypoxic hearts was lower than in the normoxic hearts (4 weeks:51+/-5 vs. 96+/-7%, p0.01;8 weeks:31+/-6 vs. 92+/-7%, p0.01), and was lowest in the 8-week-hypoxic hearts. In conclusion, cyanotic myocardium revealed an age-dependent vulnerability to ischemia-reperfusion injury in a chronic hypoxic rat model.

Theophylline-associated convulsions have been observed most frequently in children with fever, but the mechanism is not fully understood. In this study, we investigated the basic mechanism of aminophylline [theophylline-2-ethylenediamine]-induced convulsions and the effects of Brewer's yeast-induced pyrexia in mice. Diazepam (5-10mg/kg, i.p.), a benzodiazepine receptor agonist, significantly prolonged the onset and significantly decreased the incidence of convulsions induced by aminophylline (350mg/kg, i.p.). However, the gamma aminobutyric acid (GABA)A receptor agonist muscimol (1-4mg/kg, i.p.), the GABAB receptor agonist baclofen (2-4mg/kg, i.p.) and the N-methyl-D-aspartic acid receptor antagonist dizocilpine (0.1-0.3mg/kg, i.p.) failed to protect against the convulsions. 20% Brewer's yeast (0.02ml/g, s.c.) increased body temperature by 1.03, and also significantly shortened the onset and significantly increased the incidence of convulsions induced by aminophylline. The anticonvulsant action of diazepam (2.5-10mg/kg, i.p.) on the convulsions induced by aminophylline was reduced by Brewer's yeast-induced pyrexia. The proconvulsant actions of the GABAA receptor antagonists picrotoxin (3-4mg/kg, i.p.) and pentylenetetrazol (40-60mg/kg, i.p.) were enhanced by Brewer's yeast. These results suggest that the anticonvulsant action of diazepam against aminophylline is reduced by Brewer's yeast-induced pyrexia, and that GABAA receptors are involved in the aggravation of the convulsions by Brewer's yeast in mice.

Urinary tract infections (UTIs) due to fluoroquinolone-insusceptible Escherichia coli have become increasingly common in recent years. We investigated the potential relationships between clinical measures to combat fluoroquinolone-insusceptible E. coli and experimental analyses on E. coli isolates. Over a 14-year period from 1994 through 2007, a total of 828 E. coli isolates were collected from patients (one isolate per patient) with UTI at the urology ward of Okayama University Hospital. We analyzed the mutations in quinolone resistance-determining regions of DNA gyrase (gyrA) and topoisomerase IV (parC). The production of biofilm by these isolates was also examined and the associated medical records were retrospectively reviewed. Seven of 189 (3.7%) strains from uncomplicated UTIs and 82 of 639 (12.8%) strains from complicated UTIs were insusceptible to fluoroquinolones. Amino acid replacements of type II topoisomerases were frequently observed at positions 83 and 87 in GyrA and at positions 80 and 84 in ParC. No significant difference in the biofilm-forming capabilities was observed between fluoroquinolone-susceptible and -insusceptible E. coli. Our study suggests that biofilm formation of fluoroquinolone-insusceptible E. coli isolates is not a major mechanism of resistance in patients with UTI.