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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.

Vitis coignetiae Pulliat (Yamabudo) is used as a health juice and wine based on the abundant polyphenols and anthocyanins in its fruit. However, it is not known whether the leaves of this plant confer similar benefits. This study investigated the hepatoprotective effects of aqueous extracts from Vitis coignetiae Pulliat leaves (VCPL) in an animal model of nonalcoholic steatohepatitis (NASH). Rats were fed a choline-deficient high-fat diet for four weeks to generate fatty livers. NASH was induced by oxidative stress loading. Ten weeks later, blood and liver samples were collected from anesthetized animals and assessed biochemically, histologically, and histochemically to determine the extent of oxidative stress injury and the overall effects of VCPL. Six-week VCPL extract supplementation reduced serum levels of liver enzymes, decreased CYP2E1 induction, increased plasma antioxidant activities and delayed the progression of liver fibrosis. The findings suggested that VCPL has strong radical-scavenging activity and may be beneficial in preventing NASH progression.

Reportedly, thyroid mucosa-associated lymphoid tissue (MALT) lymphoma is closely associated with Hashimoto's thyroiditis. However, it remains unknown which antigen is closely associated with thyroid MALT lymphoma. We examined whether B cell response to thyroglobulin (Tg), which is a common thyroid-specific autoantigen, is related etiologically to the pathogenesis of thyroid MALT lymphoma. Expression of human Tg antigens and Cluster of differentiation (CD) 35 was examined immunohistochemically in 15 cases of thyroid MALT lymphoma using paraffin-embedded, formalin-fixed tissue specimens. In all cases of thyroid MALT lymphoma, human Tg was detected immunohistochemically in the follicular epithelial cells and follicular dendritic cells (FDCs). These FDCs were positive by double immunostaining for anti-human Tg rabbit polyclonal antibody (Ab) and for CD35. Results showed that the Tg, a thyroid autoantigen, had immunostained the germinal center of the thyroid MALT lymphoma. The Tg was present in the FDCs, as revealed by the staining pattern of the germinal center;this fact was confirmed by double immunostaining of anti-human Tg mouse monoclonal Ab and anti-CD35 mouse monoclonal Ab. The results of our study suggest that Tg is an autoantigen that is recognized by thyroid MALT lymphoma cells.

The present study aimed to investigate the status of physical activity and the differences in psychological factors associated with physical activity from the perspective of transtheoretical model stages between prime- and middle-aged Japanese. The study involved 375 prime-aged volunteers (175 men, 200 women) and 557 middle-aged volunteers (247 men, 310 women) living in Kuse, a town in Okayama Prefecture, Japan. We found that the prime-aged men at the preparation stage had significantly higher self-efficacy scores than at the contemplation stage (p<0.01). Middle-aged men had significantly higher self-efficacy scores at the contemplation stage than at the precontemplation stage (p<0.001). Middle-aged women, meanwhile, had significantly higher self-efficacy scores at the maintenance stage than at the action stage (p<0.01), and at the contemplation stage than at the precontemplation stage (p<0.001). The present findings provide valuable information about the differences in psychological factors affecting physical activity between prime-aged and middle-aged community-dwelling Japanese. This information may be useful to health professionals as they develop effective community-based intervention programs for target populations.

Little information is available on the mechanism of diastolic left ventricular (LV) dysfunction in patients with chronic respiratory disease complicated by hypoxia. The purpose of this study was to investigate how chronic hypoxia impairs LV diastolic function in an hypoxic animal model. Thirty-six male Wistar rats 8 weeks old were assigned to normoxia (N), chronic hypoxia (CH), and re-normoxia (RN) groups, 12 rats per group. The N group rats were kept in ambient air for 8 weeks, while the CH group was kept hypoxic for 8 weeks. After 8 weeks of hypoxia the RN group rats were kept for a further 8 weeks in ambient air. LV systolic and diastolic functions, as well as right ventricular (RV) function, were analyzed using Doppler echocardiography;we also measured the hematocrit, and weighed the LV and RV. Hematocrit, RV weight/body weight, and RV weight/LV weight were higher in the CH group than in the other 2 groups. However, most of these parameters returned to normoxia levels after re-normoxia. In the CH group, LV dimension and area were smaller than in the other 2 groups. LV systolic function was preserved in all groups;however, in the CH group, mitral flow showed a restrictive pattern, while pulmonary flow demonstrated a pulmonary hypertensive pattern with prolonged RV ejection time. In conclusion, chronic hypoxia induced pulmonary hypertension and RV hypertrophy. Although LV systolic function was preserved, diastolic function was impaired in hypoxia. Ventricular interaction may impair LV diastolic function.

ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is an inflammatory-induced gene. We have previously reported that ADAMTS1 was strongly but transiently expressed in the infarcted heart. In this study, we investigated whether a 3'-untranslated region (UTR) affects the mRNA stability of this gene. When stimulated with tissue necrosis factor (TNF)-alpha, the expression level of ADAMTS1 mRNA rapidly increased, but the induction of ADAMTS1 mRNA peaked at 6h after stimulation, after which the expression levels of ADAMTS1 mRNA decreased. The 3'-UTR ADAMTS1 mRNA contains multiple adenine and uridine-rich elements, suggesting that the 3'-UTR may regulate gene stability. The addition of actinomycin D, an RNA synthesis inhibitor, demonstrated the decay of induced ADAMTS1 mRNA by TNF-alpha. Furthermore, a region containing multiple AUUUA motifs within the ADAMTS1 3'-UTR destabilized transfected Enhanced Green Fluorescence Protein (EGFP) mRNA expression. These results demonstrated that the ADAMTS1 3'-UTR may regulate the expression of ADAMTS1 mRNA.

The authors previously developed a mobile ecological momentary assessment (EMA) system as a real-time data collection device using a mobile phone. In this study, a real-time advice function and real-time reporting function were added to the previous system as a supportive intervention. The improved system was found to work effectively and was applied to several clinical cases, including patients with depressive disorder, dizziness, smoking habit, and bronchial asthma. The average patient compliance rate was high (89%) without the real-time advice and higher (93%) with the advice. The trends in clinical data for patients using a mobile EMA with/without the new function were analyzed for up to several months. In the case of dizziness, an improving trend in its clinical data was observed after applying the real-time advice, and in the case of depressive disorder, a stabilizing trend was observed. The mobile EMA system with the real-time advice function could be useful as a supportive intervention in behavior modification and for motivating patients in self-management of their disease.

Serum des-gamma-carboxy prothrombin (DCP) is commonly used to detect hepatocellular carcinoma (HCC). This review focuses on the clinical features of DCP-positive HCC and the molecular function of DCP in HCC. DCP-positive HCC demonstrates more aggressive clinicopathological features than DCP-negative HCC. Analysis of the biological effects of DCP revealed that DCP acts as a growth factor in both an autocrine and paracrine manner. DCP stimulates HCC cell proliferation through the Met-Janus kinase 1-signal transducer and activator of transcription 3 signaling pathway, whereas for vascular endothelial cells, it stimulates cell proliferation and migration through the kinase insert domain receptor-phospholipase C-gamma-mitogen-activated protein kinase signaling pathway.

Scoliosis is a common clinical manifestation of Rett syndrome, a neurodevelopmental disorder that almost exclusively affects females. The spinal curve in patients with Rett syndrome is typically a long C curve of a neuromuscular type. As the onset of the scoliosis is very early and shows rapid progression, early surgical intervention has been recommended to prevent a life-threatening collapsing spine syndrome. However, there are high perioperative risks in Rett syndrome patients who undergo spinal surgery, such as neurological compromise and respiratory dysfunction due to rigid spinal curve. We herein report the surgical result of treating severe rapid progressive thoracic scoliosis in a 16-year-old girl with Rett syndrome. Posterior segmental pedicle screw fixation was performed from T1 to L3 using a computer-assisted technique. Post-operative radiography demonstrated a good correction of the curve in both the sagittal and coronal alignment. There were no postoperative complications such as neurological compromise. The patient had maintained satisfactory spinal balance as of the 3-year follow-up examination.

Amphiphysin I, known as a major dynamin-binding partner localized on the collars of nascent vesicles, plays a key role in clathrin-mediated endocytosis (CME) of synaptic vesicles. Amphiphysin I mediates the invagination and fission steps of synaptic vesicles by sensing or facilitating membrane curvature and stimulating the GTPase activity of dynamin. Amphiphysin I may form a homodimer by itself or a heterodimer with amphiphysin II in vivo. Both amphiphysin I and II function as multilinker proteins in the clathrin-coated complex. Under normal physiological conditions, the functions of amphiphysin I and some other endocytic proteins are known to be regulated by phosphorylation and dephosphorylation. During hyperexcited conditions, the most recent data showed that amphiphysin I is truncated by the ca2-dependent protease calpain. Overexpression of the truncated form of amphi-physin I inhibited transferrin uptake and synaptic vesicle endocytosis (SVE). This suggests that amphi-physin I may be an important regulator for SVE when massive amounts of Ca2 flow into presynaptic terminals, a phenomenon observed in neurodegenerative disorders such as ischemia/anoxia, epilepsy, stroke, trauma and Alzheimer's disease. This review describes current knowledge regarding the general properties and functions of amphiphysin I as well as the functional regulations such as phosphorylation and proteolysis in nerve terminals.