Objective To monitor the systemic gene expression profile in a murine model of li-popolysaccharide (LPS)-induced acute lung injury by the recently modified long serial analysis of gene expression (SAGE) so as to discuss the molecular mechanism of acute lung injury. Methods Acute lung injury was induced by intra-tracheal injection of LPS (25 mg/kg). Control mice were given normal saline in same volume. Animals were killed at 24 hours after the administration of LPS and lungs were harvested en bloc for SAGE study. Results A total of 24 670 tags representing 12 168 transcripts in the control mice and 26 378 tags representing 13 397 transcripts in the mice with lung injury were identified respectively. There were 11 transcripts increased more than 10 folds, 107 transcripts 5-10 folds and 2 121 transcripts 2-5 folds in the LPS-treated mice. But seven transcripts decreased to 1/10, 87 transcripts to 1/10-1/5 and 1 571 transcripts to 1/5-1/2. The most overexpressed genes in the lung injury mice mainly included serum amyloid A 3, metallothionein 2, lipocalin 2, cyclin-dependent kinase inhibitor 1A, lactate dehydrogenase 1 , melatonin receptor, SI00 calcium-binding protein A9 and natriuretic pep-tide precursor. Mitogen activated protein kinase 3, serum albumin, complement component 1 inhibitor, and ATP synthase were underexpressed in the lung injury mice. Conclusion The changes of various genes as well as some unreported genes have been confirmed in the LPS-induced acute lung injury. Further studies of these unreported genes are beneficial to better understanding the mechanism of acute lung injury and may provide useful markers for clinical diagnosis.

Renal damage caused by hemolysis during cardiopulmonary bypass (CPB) was investigated, and the preventive effects of haptoglobin in regard to this condition was also evaluated. Nineteen patients who underwent open heart surgery were divided into two groups: a control group (n=11) and a haptoglobin group (n=8). In the control group, the level of plasma-free hemoglobin increased significantly after CPB (p<0.01), and this level was strongly correlated with renal tubular leaking enzymes: NAG (r=0.76) and γ-GTP (r=0.81), in the Intensive Care Unit or on the first day after surgery. On the contrary, in the haptoglobin group, in which 4, 000 units of haptoglobin was added in the priming solution of CPB, no increased level of plasma free hemoglobin was observed. Furthermore, leak age of renal tubular enzymes were statistically less (p<0.05). It was concluded that free hemoglobin was a cause of renal damage during CPB and the damage was preventable by the administration of haptoglobin.

Objective: The effect of antipsychotic drugs on quantitative electroencephalography (EEG) has been mainly examined by the administration of a single test dose or among patients using combinations of other psychotropic drugs. We therefore investigated the effects of strict monotherapy with antipsychotic drugs on quantitative EEG among schizophrenia patients. Methods: Data from 2,364 medical reports with EEG results from psychiatric patients admitted to the Hokkaido University Hospital were used. We extracted EEG records of patients who were diagnosed with schizophrenia spectrum disorders and who were either undergoing strict antipsychotic monotherapy or were completely free of psychotropic drugs. The spectral power was compared between drug-free patients and patients using antipsychotic drugs. We also performed multiple regression analysis to evaluate the relationship between spectral power and the chlorpromazine equivalent daily dose of antipsychotics in all the patients. Results: We included 31 monotherapy and 20 drug-free patients. Compared with drug-free patients, patients receiving antipsychotic drugs demonstrated significant increases in theta, alpha and beta power. When patients taking different types of antipsychotics were compared with drug-free patients, we found no significant change in any spectrum power for the aripiprazole or blonanserin groups. Patients taking risperidone demonstrated significant increases in alpha and beta power. Patients taking clozapine and olanzapine demonstrated significant slow wave increases. Multiple regression analysis revealed that the chlorpromazine equivalent dose was positively associated with theta power. Conclusion Use of any antipsychotic drug by patients was associated with a dose-dependent increase in theta power. However, each type of antipsychotic demonstrated different spectral power changes.

Objective: The effect of antipsychotic drugs on quantitative electroencephalography (EEG) has been mainly examined by the administration of a single test dose or among patients using combinations of other psychotropic drugs. We therefore investigated the effects of strict monotherapy with antipsychotic drugs on quantitative EEG among schizophrenia patients. Methods: Data from 2,364 medical reports with EEG results from psychiatric patients admitted to the Hokkaido University Hospital were used. We extracted EEG records of patients who were diagnosed with schizophrenia spectrum disorders and who were either undergoing strict antipsychotic monotherapy or were completely free of psychotropic drugs. The spectral power was compared between drug-free patients and patients using antipsychotic drugs. We also performed multiple regression analysis to evaluate the relationship between spectral power and the chlorpromazine equivalent daily dose of antipsychotics in all the patients. Results: We included 31 monotherapy and 20 drug-free patients. Compared with drug-free patients, patients receiving antipsychotic drugs demonstrated significant increases in theta, alpha and beta power. When patients taking different types of antipsychotics were compared with drug-free patients, we found no significant change in any spectrum power for the aripiprazole or blonanserin groups. Patients taking risperidone demonstrated significant increases in alpha and beta power. Patients taking clozapine and olanzapine demonstrated significant slow wave increases. Multiple regression analysis revealed that the chlorpromazine equivalent dose was positively associated with theta power. Conclusion Use of any antipsychotic drug by patients was associated with a dose-dependent increase in theta power. However, each type of antipsychotic demonstrated different spectral power changes.

PURPOSE: We conducted a prospective single-center study to evaluate the possibility of discontinuation of dutasteride after combination therapy with an alpha blocker for benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We prospectively treated BPH patients with an alpha blocker and dutasteride (0.5 mg/d). Patients who had been treated with alpha blockers against BPH for more than 2 months were eligible, and 20 patients were included in the study. After 6 months of combination therapy, dutasteride was discontinued. Patients were followed for 12 months after cessation. Prostate volume, intraprostatic architecture determined by transrectal ultrasound, peak urinary flow rate, postvoid residual urine volume, and the serum prostate-specific antigen level were evaluated every 6 months, and the International Prostate Symptom Score and overactive bladder symptom score (OABSS) every 3 months. Patients were allowed to restart dutasteride during the follow-up period according to their desire. RESULTS: Twelve patients (12/20, 60%) restarted the combination therapy from 6 to 12 months into the follow-up period. For patients who restarted dutasteride, the prostate volume and OABSS had increased and worsened after discontinuation, respectively. A visible transition zone with a clear border on transrectal ultrasound at baseline and regrowth of the prostate after discontinuation of dutasteride were risk factors for restarting the therapy (Mann-Whitney U test: p=0.008, p=0.017). CONCLUSIONS: Prostatic enlargement after discontinuation of dutasteride differs among patients. Rapid regrowth of the prostate leads to deterioration of storage symptoms and a tendency to restart dutasteride. Baseline intraprostatic architecture may be a predictive factor for whether the patient is a good candidate for discontinuation.
5-alpha Reductase Inhibitors/administration & dosage/adverse effects ; *Adrenergic alpha-Antagonists/administration & dosage/adverse effects ; Aged ; Drug Monitoring ; Drug Therapy, Combination/methods ; *Dutasteride/administration & dosage/adverse effects ; Follow-Up Studies ; Humans ; Japan ; Male ; Middle Aged ; Organ Size ; Prospective Studies ; *Prostate/drug effects/pathology/ultrasonography ; Prostate-Specific Antigen/analysis ; *Prostatic Hyperplasia/drug therapy/pathology ; Secondary Prevention/methods/statistics & numerical data ; Treatment Outcome ; Withholding Treatment

PURPOSE: Mumps vaccine has not been included in the routine national immunization program in Japan, leading to low vaccine coverage rates and periodic epidemics approximately every 5 years. Our hospital (a secondary community hospital in Japan) experienced an increased number of mumps-related complications with a nationwide epidemic in 2016. Using previously reported data and mumps-related cases in our hospital, we estimated the cost-effectiveness of routine mumps vaccination in Japan with a static model using current epidemiologic data. MATERIALS AND METHODS: With a decision tree flowchart of mumps infection and adverse events, we estimated the burden of mumps-related complications in our hospital for 5 years, and calculated the current annual national burden. Finally, we compared the current burden and assumptive burden of the stable state after routine vaccination in Japan using a static model. RESULTS: The cost-benefit ratios with sensitivity analysis were 3.69 (1.08-9.52) and 6.84 (1.51-23.73) in independent inoculation and simultaneous inoculation, respectively, from a social perspective in addition to an annual gain of 9,487 (3,227-14,659) quality adjusted life years. CONCLUSION: We contributed additional evidence in terms of cost-effectiveness that routine mumps vaccination should be introduced in Japan with simultaneous inoculation.
Asian Continental Ancestry Group* ; Cost-Benefit Analysis ; Decision Trees ; Hospitals, Community* ; Humans ; Immunization Programs ; Japan* ; Mumps Vaccine ; Mumps* ; Quality-Adjusted Life Years ; Software Design ; Vaccination*

Kinki University School of Medicine introduced clerkships for undergraduate clinical training in 1999. Clinical clerkships are performed for the first 8 weeks of the sixth academic year. In 1999 and 2000 we conducted questionnaire surveys asking students about this system. The teaching staff encourages students to participate extensively in clinical situations, which reflects the consensus about this system. We also performed similar surveys of nurses and teaching staff. Clinical clerkships did not increase the incidence of problems between patients and medical staff. Many students felt their motivation to be a physician was increased. Although the findings of these questionnaire surveys indicate that our clerkship system works successfully, they also revealed some problems for sixth-year students. Although we recognize the significance of this system for undergraduate clinical training, further improvement is required.

Purpose: Despite widespread adoption of open abdominal management (OAM), there is currently no threshold criterion for OAM duration for non-trauma patients. Moreover, there is a positive relationship between morbidity and the duration of OAM, but an uncertain relationship with patients’ age. Therefore, a novel clinical index for the duration of open abdominal management (IDOM) was developed based on the patient’s age and risk of severe complications following OAM to indicate the maximum tolerable number of days of OAM based on the individual’s age. The utility of this new index was evaluated. Methods: This retrospective study included 65 non-trauma patients managed with an open abdomen (OA) from August 2015 to August 2018. The IDOM was developed based on the patient’s age. The result indicated the maximum number of OA days. Patients’ demographic and operative variables were examined and patient data was assigned to one of two groups according to whether the actual number of OA days was above or below the calculated IDOM. Prevalence of complications between these groups was compared. Measures of validity were employed to assess the utility of the IDOM for patient complications. Results: Sixty-five patients were included. The above-the calculated IDOM group exhibited a significantly longer OA and higher rates of wound complications and postoperative respiratory complications compared with the below the calculated IDOM group. The IDOM predicted the incidence of OA-related complications with a sensitivity of 72.4%, and a specificity of 80.6%. Conclusion The IDOM is a potentially useful tool for appropriate duration at the outset of OA.

Overactive bladder (OAB) is a symptom-based syndrome defined by urinary urgency, frequency, and nocturia with or without urge incontinence. The causative pathology is diverse; including bladder outlet obstruction (BOO), bladder ischemia, aging, metabolic syndrome, psychological stress, affective disorder, urinary microbiome, localized and systemic inflammatory responses, etc. Several hypotheses have been suggested as mechanisms of OAB generation; among them, neurogenic, myogenic, and urothelial mechanisms are well-known hypotheses. Also, a series of local signals called autonomous myogenic contraction, micromotion, or afferent noises, which can occur during bladder filling, may be induced by the leak of acetylcholine (ACh) or urothelial release of adenosine triphosphate (ATP). They can be transmitted to the central nervous system through afferent fibers to trigger coordinated urgency-related detrusor contractions. Antimuscarinics, commonly known to induce smooth muscle relaxation by competitive blockage of muscarinic receptors in the parasympathetic postganglionic nerve, have a minimal effect on detrusor contraction within therapeutic doses. In fact, they have a predominant role in preventing signals in the afferent nerve transmission process. β3-adrenergic receptor (AR) agonists inhibit afferent signals by predominant inhibition of mechanosensitive Aδ-fibers in the normal bladder. However, in pathologic conditions such as spinal cord injury, it seems to inhibit capsaicin-sensitive C-fibers. Particularly, mirabegron, a β3-agonist, prevents ACh release in the BOO-induced detrusor overactivity model by parasympathetic prejunctional mechanisms. A recent study also revealed that vibegron may have 2 mechanisms of action: inhibition of ACh from cholinergic efferent nerves in the detrusor and afferent inhibition via urothelial β3-AR.

Purpose: Accelerated atherosclerosis is a major complication in patients with end-stage renal disease and it plays an important role in the pathogenesis of erectile dysfunction (ED). However, the association between aortic calcification burden and the severity of ED remains unclear. The aim of the present study was to investigate this association in men undergoing dialysis. Materials and Methods: This cross-sectional study included 71 men undergoing peritoneal dialysis and/or hemodialysis between July 2016 and May 2018 at Mutsu General Hospital. ED was assessed with the Sexual Health Inventory for Men (SHIM). Patients were divided into the mild/moderate (SHIM score ≥8) and severe ED groups (SHIM score ≤7). Aortic calcification index (ACI) was examined as a clinical indicator of abdominal aortic calcification. Multivariable logistic regression analysis was performed to identify the significant factors associated with severe ED. Results: The median age of the study participants was 64 years; all had ED, with 64.8% having severe ED. In the multivariable analyses, a slight association was observed between ankle-brachial index and severe ED (odds ratio [OR], 0.058; p=0.072), whereas ACI was significantly associated with severe ED (OR, 1.022; p=0.022). Conclusions Aortic calcification burden was independently associated with severe ED.