Purpose：Methadone is an opioid used in Japan for the treatment of cancer pain. A thorough consideration of complex pharmacokinetics with individual differences and of serious adverse effects is necessary before switching to methadone; therefore, methadone is not yet widely used. We examined the analgesic and adverse effects of methadone through clinical cases and considered the clinical significance of methadone as an opioid analgesic for the treatment of cancer pain. Methods：The clinical course of 44 patients with cancer pain who were switched to methadone from other opioids was analyzed. Results：Out of the 44 cases investigated, 37 cases （84.1％） were successful. In the successful cases, pain intensity before and after methadone administration was reduced from an average of 7.5 to 2.8, respectively, on the numerical rating scale. Strong drowsiness （six cases） and nausea （three cases） were observed as adverse effects. However, no serious effects, such as QT prolongation and respiratory depression, were recognized. Conclusion：For patients with refractory cancer pain who require a high opioid dose, methadone is considered to be one of the alternatives in pain therapeutics.

Background: Methadone can only be administered orally in Japan. However, it is unclear how to treat pain when patients become unable to take methadone orally because of the progression of the disease. Aims: To assess retrospectively end-of-life pain control management after patients become unable to take methadone orally. Methods: Twenty-eight patients with cancer pain undergoing treatment with oral methadone died at a palliative care unit between April 2013 and September 2014. All patients died of cancer and were unable to swallow before death. We assessed pain control approaches after the patients became unable to take methadone orally. Results: Twenty-one patients survived 1 day or longer after becoming unable to swallow. Methadone was switched to another opioid because of pain. Of these 21 patients, 10 patients survived for 1 week or longer after being switched to another opioid. At this point, methadone would be mostly eliminated from the blood circulation. Among these 10 patients, seven patients were treated with subcutaneous morphine, and three patients were excluded because their pain could not be evaluated. The conversion ratio from final oral methadone dosage to oral morphine equivalent dose of opioids used on the seventh day was 6.1. Conclusion: Even when patients become unable to ingest methadone, switching to other opioids may not always be necessary because of the long half-life of methadone when pain is absent at the end of life. If necessary, pain could be managed by switching to other opioids with a conversion ratio of 6.1.

Introduction: Paroxysmal atrial fibrillation (Paf) occurred in an inpatient who has been prescribed methadone for cancer pain in our palliative care unit, but oral administration of aprindine (antiarrhythmic agent) succeeded in defibrillation and methadone administration could be continued. Case: A 75-year-old man had developed multiple bone metastases after resection of thyroid cancer. Due to refractory cancer pain, switching from oxycodone to methadone was performed. Pain relief was achieved with methadone 40 mg/day and without QT interval prolongation. After methadone administration about 9 months, there suddenly became loss of appetite in the morning of one day. ECG examination revealed Paf onset. Aprindine 20 mg was orally administered for the purpose of defibrillation. After about 2 hours sinus rhythm was gained and later without recurrence. Conclusion: This case was considered to have the coincidental complication of paroxysmal atrial fibrillation in the course of methadone administration. If administration of antiarrhythmic agents is performed in a patient whom has been prescribed methadone, it is feared to lead to result in QT interval prolongation due to drug interactions. It is important to carefully select an agent that rarely leads to QT prolongation.

Allergic rhinitis a chronic inflammatory disease of the upper airways that has a major impact on the quality of life of patients and is a socio-economic burden. Understanding the underlying immune mechanisms is central to developing better and more targeted therapies. The inflammatory response in the nasal mucosa includes an immediate IgE-mediated mast cell response as well as a latephase response characterized by recruitment of eosinophils, basophils, and T cells expressing Th2 cytokines including interleukin (IL)-4, a switch factor for IgE synthesis, and IL-5, an eosinophil growth factor and on-going allergic inflammation. Recent advances have suggested new pathways like local synthesis of IgE, the IgE-IgE receptor mast cell cascade in on-going allergic inflammation and the epithelial expression of cytokines that regulate Th2 cytokine responses (i.e., thymic stromal lymphopoietin, IL-25, and IL-33). In this review, we briefly review the conventional pathways in the pathophysiology of allergic rhinitis and then elaborate on the recent advances in the pathophysiology of allergic rhinitis. An improved understanding of the immune mechanisms of allergic rhinitis can provide a better insight on novel therapeutic targets.
Basophils ; Chemokines ; Cytokines ; Eosinophils ; Epithelial Cells ; Humans ; Immunoglobulin E ; Inflammation ; Interleukin-5 ; Interleukins ; Mast Cells ; Nasal Mucosa ; Quality of Life ; Rhinitis, Allergic ; T-Lymphocytes

PURPOSE: Nasal polyposis is a chronic inflammatory disease of the upper airways often associated with asthma and characterized by markedly increased numbers of eosinophils, Th2 type lymphocytes, fibroblasts, goblet cells and mast cells. Previous studies have shown elevated levels of thymic stromal lymphopoietin (TSLP) in atopic diseases like asthma, atopic dermatitis and mainly in animal models of allergic rhinitis (AR). Here, we investigated the expression of TSLP in nasal polyps from atopics and non-atopics in comparison with the nasal mucosa and its potential role in nasal polyposis. METHODS: Messenger RNA expression for TSLP, thymus and activation-regulated chemokine (TARC) and macrophage derived chemokine (MDC) in nasal polyps and nasal mucosa of atopics and non-atopics was analyzed by real time PCR. Immunoreactivity for TSLP in nasal polyps and in the nasal mucosa of patients with AR and non-allergic rhinitis (NAR) was analyzed by immunohistochemistry. Eosinophil counts was analyzed by Wright-Giemsa staining and nasal polyp tissue IgE, by ELISA. RESULTS: Messenger RNA expression for TSLP,TARC and MDC was markedly higher in nasal polyps as compared to the allergic nasal mucosa. Immunoreactivity for TSLP was detected in epithelial cells, endothelial cells, fibroblasts and inflammatory cells of the nasal mucosa and nasal polyps. The number of TSLP+ cells was significantly greater in the nasal mucosa of AR than NAR patients. The number of TSLP+ cells in nasal polyps from atopics was significantly greater than that of non-atopics and that in the allergic nasal mucosa. The number of TSLP+ cells correlated well with the number of eosinophils and the levels of IgE in nasal polyps. CONCLUSIONS: The high expression of TSLP in nasal polyps and its strong correlation to eosinophils and IgE suggest a potential role for TSLP in the pathogenesis of nasal polyps by regulating the Th2 type and eosinophilic inflammation.
Asthma ; Chemokine CCL17 ; Chemokine CCL22 ; Cytokines ; Dermatitis, Atopic ; Endothelial Cells ; Eosinophils ; Epithelial Cells ; Fibroblasts ; Goblet Cells ; Humans ; Immunoglobulin E ; Immunohistochemistry ; Inflammation ; Lymphocytes ; Mast Cells ; Models, Animal ; Nasal Mucosa ; Nasal Polyps ; Real-Time Polymerase Chain Reaction ; Rhinitis ; Rhinitis, Allergic, Perennial ; RNA, Messenger

PURPOSE: The pathogenesis of nasal polyposis (NP) is unclear. Eosinophils and mast cells are considered to play important roles in this process. In addition, the levels of Th2-type cells are increased, irrespective of the atopic status of the patient with NP. In this context, we and others have shown high levels of thymus and activation-related chemokine/CCL17, macrophage-derived chemokine, eotaxin, and RANTES in patients with NP. Forkhead box P3 (FOXP3) plays a key role in CD4+CD25+ regulatory T-cell function and represents a specific marker for regulatory T cells (Tregs). Decreased expression of FOXP3 has been reported in allergic diseases. The present study was designed to evaluate the presence and potential roles of Tregs, defined by the expression of FOXP3 protein, in NP. METHODS: Using immunohistochemistry, we estimated the numbers of FOXP3+ cells in the epithelium and lamina propria of the NPs of 17 patients with chronic rhinosinusitis with NP and the nasal mucosa of 15 patients with allergic rhinitis (AR). The number of FOXP3+ cells in NPs was compared with that in the nasal mucosa of patients with AR, and the numbers of FOXP3+ cells in atopic and non-atopic NP were also compared. RESULTS: The number of FOXP3+ cells in the lamina propria of patients with NP was significantly lower than that in the nasal mucosa of the AR patients (2.79 vs. 5.99, P=0.008). There was no statistically significant difference noted for the numbers of FOXP3+ cells between the epithelium of the NP and the nasal mucosa (3.60 vs. 2.39, P=0.180). Furthermore, the numbers of CD4+FOXP3+ cells were lower in NPs than in the allergic nasal mucosa. There was no difference in the number of FOXP3+ cells between the atopic and non-atopic NP patients. CONCLUSIONS: Fewer Tregs (i.e., decreased FOXP3 expression) are found in NPs than in the nasal mucosa of AR patients. As the severity of eosinophilic, Th2-type inflammation and the levels of inflammatory mediators are much higher in NPs than in the nasal mucosa of AR patients, an inverse co-relationship may exist between these parameters and the number of Tregs. The deficiency of Tregs in NP may account for the more pronounced Th2-type inflammation seen in these patients.
Chemokine CCL22 ; Chemokine CCL5 ; Eosinophils ; Epithelium ; Humans ; Immunoglobulin E ; Immunohistochemistry ; Inflammation ; Mast Cells ; Mucous Membrane ; Nasal Mucosa ; Rhinitis ; Rhinitis, Allergic, Perennial ; T-Lymphocytes ; T-Lymphocytes, Regulatory ; Thymus Gland

A study was conducted to clarify the effect of hyperoxia (HO) on exercise tolerance andhemodynamics in patients with ischemic heart disease (IHD) . The subjects were 10 patients with serious IHD who showed ischemic ST depression during low-intensity exercise testing. In all subjects, cardiopulmonary exercise testing (CPX) was performed using two types of inhalation : normoxia (NO) and HO (O₂: 60%, N₂: 40%) . Heart rate (HR), blood pressure (BP), rating of perceived exertion (RPE), elapsed exercise duration and pressure rate product (PRP) were measured, and ECG was recorded during CPX according to the Bruce protocol. The peak oxygen uptake (VO₂peak) was calculated using the appropriate formula. These data were compared between the NO and HO groups, and the following results were obtained.
ST depressions on ECG, BP, HR and PRP after 20 min of rest showed no changes under NO. The other hand, only ST depression was improved after 20 min of rest under HO. The exercise duration in HO group was longer than in the NO group, and the VO₂peak in the HO group was higher than in the NO group. However, peak RPE showed no significant difference between the HO and NO groups. The incidence of ST depression as an endpoint of CPX showed no significant difference between the two groups. BP, HR and PRP at the CPX endpoint showed no significant differences between the HO and NO groups. In patients whose exercise duration was prolonged beyond the mean value by HO, peak HR and PRP were increased significantly. However, this tendency was not seen in patients whose exercise was prolonged for less than the mean value.
In conclusion, these results suggest that an increase in the oxygen supply to peripheral working muscles may play an important role in increasing exercise tolerance under HO in IHD patients.

Purpose: The objective of this study was to investigate whether body fat rate (BFR) and triceps skinfold thickness (TSF) are associated with estimated fentanyl absorption in patients treated with the fentanyl transdermal matrix patch for moderate to severe cancer pain, by measuring the residual content of fentanyl in used matrix patches. Methods: Adult Japanese inpatients experiencing chronic cancer-related pain and receiving treatment for the first time with a transdermal fentanyl matrix patch (Durotep®MT patch) were included in the present study. During the initial application period, BFR was measured using a body fat scale, and TSF was measured by an experienced nurse with an adipometer. One patch was collected from each patient. The residual fentanyl content in used matrix patch was determined by high-performance liquid chromatography. The transdermal fentanyl delivery efficiency was estimated based on the fentanyl content of the used matrix patches. Results: Fifteen adult patients (5 males and 10 females) were included in this study. Nine patches with a release rate of 12.5μg/h and 6 patches with a release rate of 25μg/h were collected. The application site was the chest or upper arm. BFR and TSF both showed a significant positive correlation with delivery efficiency. Conclusion: In malnourished or low-body fat patients receiving DMP, pain intensity should be more carefully monitored, and fentanyl dose adjustment may be required. Additional parameters, such as nutritional status including body fat change, the degree of dry skin, and plasma fentanyl concentration, also require detailed evaluation. Palliat Care Res 2010; 5(2): 206-212

The extent to which students’ experiences are enriched by incorporating anthropology into clinical education in undergraduate medical education has not been adequately examined. The authors have collaborated to integrate anthropological fieldwork with clinical education in a clinical clerkship course. Reflection on the course has highlighted that the principles of anthropological fieldwork have stimulated changes in the roles of both faculty and students, as well as their interpersonal dynamics. These changes have the potential to promote an ‘education emerged from serendipity in the field’ approach, which tends to be undervalued in the current clinical training driven by the prevailing outcome-based medical education paradigm.