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.

Background/Aims: Immune checkpoint blockade has recently been reported to be effective in treating microsatellite instability (MSI)-high tumors. Therefore, sufficient sampling of histological specimens is necessary in cases of unresectable pancreatic cancer (UR-PC). This multicenter study investigated the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen needle for MSI evaluation in patients with UR-PC. Methods: A total of 89 patients with UR-PC who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or EUS-FNB using 22-G needles at three hospitals in Japan (2018–2021) were enrolled. Fifty-six of these patients (FNB 23 and FNA 33) were followed up or evaluated for MSI. Patient characteristics, UR-PC data, and procedural outcomes were compared between patients who underwent EUS-FNB and those who underwent EUS-FNA. Results: No significant difference in terms of sufficient tissue acquisition for histology was observed between patients who underwent EUS-FNB and those who underwent EUS-FNA. MSI evaluation was possible significantly more with tissue samples obtained using EUS-FNB than with tissue samples obtained using EUS-FNA (82.6% [19/23] vs. 45.5% [15/33], respectively; p<0.01). In the multivariate analysis, EUS-FNB was the only significant factor influencing the possibility of MSI evaluation. Conclusions EUS-FNB using a Franseen needle is desirable for ensuring sufficient tissue acquisition for MSI evaluation.

Background/Aims: Intralesional steroid injections have been administered as prophylaxis for stenosis after esophageal endoscopic submucosal dissection. However, this method carries a risk of potential complications such as perforation because a fine needle is used to directly puncture the postoperative ulcer. We devised a new method of steroid intralesional infusion using a spray tube and evaluated its efficacy and safety. Methods: Intralesional steroid infusion using a spray tube was performed on 27 patients who underwent endoscopic submucosal dissection for superficial esophageal cancer with three-quarters or more of the lumen circumference resected. The presence or absence of stenosis, complications, and the number of endoscopic balloon dilations (EBDs) performed were evaluated after treatment. Results: Although stenosis was not observed in 22 of the 27 patients, five patients had stenosis and dysphagia requiring EBD. The stenosis in these five patients was relieved after four EBDs. No complications related to intralesional steroid infusion using the spray tube were observed. Conclusions Intralesional steroid infusion using a spray tube is a simple and safe technique that is adequately effective in preventing stenosis Clinical trial number (UMIN000037567).

PURPOSE: Small bowel obstruction (SBO) remains a common complication after pelvic or abdominal surgery. However, the risk factors for SBO in ulcerative colitis (UC) surgery are not well known. The aim of the present study was to clarify the risk factors associated with SBO after ileal pouch-anal anastomosis (IPAA) with a loop ileostomy for patients with UC. METHODS: The medical records of 96 patients who underwent IPAA for UC between 1999 and 2011 were reviewed. SBO was confirmed based on the presence of clinical symptoms and radiographic findings. The patients were divided into 2 groups: the SBO group and the non-SBO group. We also analyzed the relationship between SBO and computed tomography (CT) scan image parameters. RESULTS: The study included 49 male and 47 female patients. The median age was 35.5 years (range, 14–72 years). We performed a 2- or 3-stage procedure as a total proctocolectomy and IPAA for patients with UC. SBO in the pretakedown of the loop ileostomy after IPAA occurred in 22 patients (22.9%). Moreover, surgical intervention for SBO was required for 11 patients. In brief, closure of the loop ileostomy was performed earlier than expected. A multivariate logistic regression analysis revealed that the 2-stage procedure (odds ratio, 2.850; 95% confidence interval, 1.009–8.044; P = 0.048) was a significant independent risk factor associated with SBO. CT scan image parameters were not significant risk factors of SBO. CONCLUSION: The present study suggests that a 2-stage procedure is a significant risk factor associated with SBO after IPAA in patients with UC.
Colitis, Ulcerative* ; Female ; Humans ; Ileostomy* ; Logistic Models ; Male ; Medical Records ; Risk Factors ; Tomography, X-Ray Computed ; Ulcer*

Purpose

  The training for “Strengthening Human Resource Development for Nursing and Midwifery in Southeast Asia” was implemented in order to strengthen the nursing education system in Cambodia, Laos, Myanmar and Vietnam. The purpose of this study was to evaluate the training using the training evaluation guide suggested by WHO; and to explore factors for training program to be effective, issues, and lessons.

Methods

  The WHO training evaluation guide which has five evaluation levels was modified as a tool to evaluate the training. Data were collected from training evaluations questionnaire, meeting records during training, and records of interviews conducted during follow-up visits. The factors for training to be effective, issues, and lessons were inductively identified by methodological triangulation from the results of training evaluations, the summary of training feedback from participants and the results of action plan progress.

Results and Discussion

  The training was evaluated as effective that not only achieved “Level 1: Reaction and Satisfaction” and “Level 2: Learning”, but also “Level 3: Behavior”. The factors for training to be effective were (1) practical content through sharing experiences amongmulti-country participants in neighboring countries, (2) selection of suitable trainees by setting the training language as the native language of each participating country, (3)lecture documents in native language facilitated sharing of the learning with relevant people in one’s own country, (4) maintain trainees’ motivation to implement action plans following an agreement with trainees during the training to confirm action plan progress through follow-up visits, and (5) pre-visitingeach participating country to explain the training outline makes relevant people’s much understanding of the training and interest in the action plan. Lessons learned were the importance of the definitions of technical terminology in each country’s native language and the efficacy of follow-up visits. Future issues are: “Level 4: Results”, support for each participant’s needs and “Level 5: Impact”, the development of mechanisms for continued sharing of experiences.

Conclusions

  Our evaluation confirmed the effective factors　for training, issues, and lessons. These are needed to be considered for the future training.

A main symptom of chronic fatigue syndrome (CFS) is fatigue which continues for more than 6 months and does not improve with rest, leading to a marked decrease in quality of life. Other problems include fever, sleep disorder, and headache. Etiologically, a preceding viral infection, immunological disorder, and changes in the central nervous system, especially in hippocampus have been reported. However, the precise pathogenesis of CFS has not been elucidated, and neither diagnostic markers nor effective treatments have yet to be discovered. Here, we report a case of CFS, successfully treated with Kampo medicines.
The patient was a 16-year-old high school student, who had received medical therapy for one year under the diagnosis of CFS. His chief complaint was a continuing fever and strong malaise after influenza infection. At his visit to our outpatient clinic, we confirmed that his symptoms met the criteria for CFS. A combination treatment with Kampo medicine (sanoshashinto) and duloxetine improved his malaise and fatigue in 4 weeks, but fever and anorexia remained. The addition of hochuekkito to the combination dramatically ameliorated his symptoms. This case suggests that Kampo medicines would contribute to the effective treatment of CFS, which is refractory to Western medicines.

OBJECTIVE: Glycine transporter 1 (GlyT-1) is one of the most attractive therapeutic targets for schizophrenia. There is great interest in developing radioligands for in vivo imaging of GlyT-1 in the brain using positron emission tomography. Here, we report the properties of three novel non-sarcosine-based radioligands [11C]CHIBA-3007, [11C]CHIBA-3009, and [11C]CHIBA-3011, for GlyT-1 imaging in the mouse brain in vivo. METHODS: The three radioligands were synthesized by N-[11C] methylation of the corresponding desmethyl precursor. A pharmacological characterization of these radioligands for in vivo imaging of GlyT-1 in the brain was conducted using male ddY mice. RESULTS: [11C]CHIBA-3009 and [11C]CHIBA-3011 were scarcely incorporated into the brain, whereas [11C]CHIBA-3007 showed slight but considerable brain uptake. Regional brain uptake of [11C]CHIBA-3007 (medulla oblongata>cerebellum>cortex) was similar to the distribution of the GlyT-1 protein. However, pretreatment with CHIBA-3007 (1 mg/kg) or the GlyT-1 selective inhibitor ALX5407 (N-[(3R)-3-([1,1'-Biphenyl]-4-yloxy)-3-(4-fluorophenyl)propyl]-N-methylglycine) (30 mg/kg) did not significantly decrease brain uptake of [11C]CHIBA-3007, suggesting low specific binding to GlyT-1. Pretreatment with cyclosporin A significantly increased brain uptake of [11C]CHIBA-3009 and [11C]CHIBA-3011, suggesting a role for P-glycoprotein in the brain uptake of these ligands. All three radioligands were rapidly degraded intact forms were 3-18% in plasma and 15-74% in the brain at 15 min after injection. CONCLUSION: The results suggest that these three radioligands are not suitable for in vivo imaging of GlyT-1 in the brain because of low brain uptake and rapid metabolism. Further structural refinement is necessary to enhance brain uptake.
Animals ; Brain ; Cyclosporine ; Glycine ; Glycine Plasma Membrane Transport Proteins ; Humans ; Ligands ; Male ; Methylation ; Mice ; Niacinamide ; P-Glycoprotein ; Plasma ; Positron-Emission Tomography ; Schizophrenia ; Thiophenes

OBJECTIVE: Agonists of alpha7-nicotinic acetylcholine receptors (nAChRs) have been developed as potential therapeutic drugs for neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. Positron emission tomography (PET) is a noninvasive brain imaging technique to measure receptor occupancy in the living human brain. Although much effort has been expended to create specific PET radioligands for alpha7-nAChRs in the brain, only 4-[11C]methylphenyl-1,4-diazabicyclo[3.2.2.]nonane-4-carboxylate ([11C]CHIBA-1001) is currently available for clinical studies. In contrast, two 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, tropisetron and ondansetron, have been used to treat patients with chemotherapy-induced or postoperative nausea and vomiting. Furthermore, tropisetron, but not ondansetron, possesses high affinity for alpha7-nAChRs. In the present study, we evaluated the receptor occupancy in the human brain after a single oral administration of tropisetron and ondansetron using [11C]CHIBA-1001 and PET. METHODS: Two serial dynamic PET scans using [11C]CHIBA-1001 in healthy non-smoking male subjects were performed before and after receiving an oral administration of these medications. RESULTS: A single oral administration of tropisetron, but not ondansetron, decreased the total distribution volume of [11C]CHIBA-1001 in the human brain. CONCLUSION: This study shows that tropisetron, but not ondansetron, could bind to alpha7-nAChRs in the human brain after a single oral administration. Therefore, [11C]CHIBA-1001 may be a useful PET radioligand to measure the occupancy of alpha7-nAChRs in the human brain.
Administration, Oral ; Alzheimer Disease ; Brain ; Electrons ; Humans ; Indoles ; Male ; Neuroimaging ; Ondansetron ; Positron-Emission Tomography ; Postoperative Nausea and Vomiting ; Receptors, Cholinergic ; Receptors, Nicotinic ; Schizophrenia

We performed a survey to assess the positions and activities of Japanese women physicians in medical societies. In June 2000, questionnaires were sent to 92 medical societies of the Japanese Association of Medical Science. The response rate was 92.4%. Fifty-four societies (63.5%) failed to provide the number of women physicians. According to the questionnaires that were fully completed and returned, women physicians were more likely to belong to societies of internal medicine, pediatrics, ophthalmology and dermatology. Women physicians were less likely to hold board positions and were underrepresented in leadership positions, even in societies with high percentages of women members. Board positions failed to provide for maternity or child-care leave, and few societies offered childcare facilities at annual meetings. Gender-disaggregated data should be made readily available and additional surveys need to be made to identify obstacles to activities in medical societies.