Objective: To evaluate the effect of arsenic (As) on the porphyrin biosynthetic pathway, urine samples from patients with endemic chronic arsenic poisoning were examined.Subjects and Methods: The subjects were 16 patients, who had been exposed to As from burning coal for 8 to 25 years, and-16 controls living in the same region in Guizhou Province in southwest China. Concentrations of urinary As, porphyrins and ALA were determined by induced coupled plasma mass spectrometry (ICP-MS), high performance liquid chromatography (HPLC) with a reversed-phase column and fluorescence detector, and colorimetric spectrophotometry, respectively.Results: Concentrations of As in patients and controls, 184.40 ± 200.04 and 86.82 ± 64.20 μ g/g creatinine (mean ± SD) respectively, were significantly different (p<0.05). The concentrations of various kinds of urinary porphyrins, including isomers I and III of coproporphyrin and pentacarboxylporphyrin, were determined. Positive correlations were observed between As and porphyrins (e.g. total porphyrins, hexacarboxylporphyrin and coproporphyrin III) or between As and ALA in male and female patients. However, porphyrin and ALA concentrations were not significantly different between the patients and the controls. Urinary porphyrin concentrations in females were higher than those in males.Conclusion: Exposure to As from burning coal may influence porphyrin biosynthesis.
Porphyrins ; g <3> ; Coal ; Urinary ; Chronic

Asthma is characterized by chronic airway inflammation with intense eosinophil and lymphocyte infiltration, mucus hyperproduction, and airway hyperresponsiveness. Accumulating evidence indicates that antigen-specific Th2 cells and their cytokines such as IL-4, IL-5, and IL-13 orchestrate these pathognomonic features of asthma. In addition, we and others have recently shown that IL-17-producing CD4+ T cells (Th17 cells) and IL-23, an IL-12-related cytokine that is essential for survival and functional maturation of Th17 cells, are involved in antigen-induced airway inflammation. In this review, our current understanding of the roles of IL-23 and Th17 cells in the pathogenesis of allergic airway inflammation will be summarized.
Asthma ; Cytokines ; Eosinophils ; Inflammation ; Interleukin-13 ; Interleukin-17 ; Interleukin-23 ; Interleukin-4 ; Interleukin-5 ; Lymphocytes ; Mucus ; Neutrophils ; T-Lymphocytes ; Th17 Cells ; Th2 Cells

Peripheral arterial disease (PAD) is a common complication of Diabetes Mellitus (DM) and often culminates in amputation of the affected foot. Pseudomonas aeruginosa infections associated with PAD are difficult to treat due to their multi-drug resistance. Herein we report a 38 year old male who reported with DM, chronic kidney disease (CKD) and rest pain of the right second toe in October 2011. He underwent percutaneous transluminal angioplasty (PTA) which was unsuccessful. The gangrene of the toes worsened and amputation of the right second toe was done. Bacteriological examination showed presence of P. aeruginosa which during the course of antibiotic therapy became multi-drug resistant. Gangrene and abscess of the foot worsened and amputation of the right third toe was performed. Then autologous peripheral blood mononuclear cell (PBMNC) therapy was performed but as infection control could not still be achieved, the fourth toe was amputated. A protocol of foot bath using carbonic water, local usage of antibiotics (Polymyxin-B), and basic fibroblast growth factor (b-FGF) spray was then employed after which the infection could be controlled and improvement in vascularity of the right foot could be observed in angiography. This combined approach after proper validation could be considered for similar cases.
Abscess ; Amputation ; Angiography ; Angioplasty ; Anti-Bacterial Agents ; Baths ; Carbon ; Cell- and Tissue-Based Therapy ; Diabetes Mellitus ; Drug Resistance, Multiple ; Fibroblast Growth Factor 2 ; Fibroblast Growth Factors* ; Foot ; Gangrene* ; Humans ; Infection Control* ; Kidney Failure, Chronic* ; Limb Salvage* ; Male ; Peripheral Arterial Disease ; Pseudomonas aeruginosa ; Renal Insufficiency, Chronic ; Toes* ; Water

A 48-year-old man complained of hemoptysis. Chest CT scan showed a large cardiac tumor invading the atrial septum and both atria, as well as multiple small nodules in bilateral lung fields. They were diagnosed as a malignant cardiac tumor and its lung metastases. As the tumor in the left atrium was extremely massive, operation was performed to prevent sudden death due to occlusion and to make a pathological diagnosis. The cardiac tumor invaded the atrial septum from the right atrium and occupied the left atrium. After the cardiac tumor was completely removed, the bilateral atria, the atrial septum, SVC, IVC and the right lower pulmonary vein were reconstructed with prosthetic pericardial patches. The tumor was angiosarcoma. During the postoperative period, Interleukin-2 was used as the treatment for angiosarcoma. Unfortunately the patient died of lung failure on the 107th postoperative day. Though IL-2 could not stop the development of lung metastasis in this case, the effectiveness of radiotherapy or IL-2 for angiosarcoma has recently been reported. In such cases where complete resection of the primary cardiac lesion is possible, postoperative radiotherapy or IL-2 administration seems to be effective for cardiac sarcoma.

Spinal cord injury after successful operation of the thoraco-abdominal aorta is an unpredictable complication which negatively affects the patient's quality of life. The main cause of spinal cord injury has been reported to be peroxidation of lipids. Edaravone, a free radical scavenger, has been used in the acute phase of cerebral infarction to ameliorate the brain damage. The aim of the present study was to evaluate the protective effect of edaravone on the neurological and histological outcome, and to examine the method of its administration so as to obtain the better effect, using animal models with ischemic spinal cord. Three groups of rabbits underwent surgical exposure of the abdominal aorta that was clamped for 20min to achieve spinal cord ischemia. Group A (n=6, control group) was given no medication. In group B (n=6), edaravone (3mg/ml saline/kg body weight) was administered intravenously 30min after reperfusion. In group C (n=6), the same dose of edaravone was administered at 30min, 24h and 48h after reperfusion. Neurological status was clinically assessed, using Tarlov's score, at 24h, 48h and 1week after reperfusion. Somatosensory evoked potential was measured preoperatively, at 20min after ischemia, at 30min after reperfusion, and at 24h, 48h and 1week after operation. Spinal cord sections were examined histologically to determine the degree of neuronal damage given by ischemic-reperfusion. Group A presented paraplegia with marked neuronal necrosis. Groups B and C maintained better neurogical function than Group A (p<0.001), and Group C was much better than Group B (p<0.05). In the model rabbits with 20min of ischemia-reperfusion, systemic repetitious administration of edaravone was found to have a more protective effect than a single administration on the spinal cord neurons and glia cells both neurologically and histologically.

Dopamine supersensitivity psychosis (DSP) is an unstable clinical condition observed in individuals with schizophrenia who have been treated with an antipsychotic medication at a high dosage and/or for a long period. An up-regulation of dopamine D2 receptors (DRD2) is thought to be involved in the essential pathology of DSP. An antipsychotic agent with both tight binding to DRD2 and a long half-life is generally effective for treating DSP, but a patient who meets the criteria of treatment-resistant schizophrenia sometimes needs treatment with clozapine. We report the case details of two patients whose DSP was not controlled with several antipsychotics but was successfully controlled with asenapine.Asenapine binds to a broad range of dopamine receptors and serotonin receptors, and it is thus distinct from other atypical antipsychotics. The unique profile of asenapine may contribute to the control of severe DSP symptoms in individuals with schizophrenia.

OBJECTIVE: The present study investigated long-term outcomes of medroxyprogesterone acetate (MPA) plus metformin therapy in terms of control of atypical endometrial hyperplasia (AEH) and endometrial cancer (EC), and post-treatment conception. METHODS: We retrospectively analyzed 63 patients (42 with EC; 21 with AEH) who underwent fertility-sparing management using MPA plus metformin. MPA (400 mg/day) and metformin (750–2,250 mg/day) were administered to achieve complete response (CR). Metformin was administered until conception, even after MPA discontinuation. RESULTS: Of the total patients, 48 (76%) had a body mass index (BMI) ≥25 kg/m² and 43 (68%) showed insulin resistance. Sixty-one patients (97%) achieved CR within 18 months. CR rates at 6, 8–9, and 12 months were 60%, 84%, and 90%, respectively. During a median follow-up period of 57 months (range, 13–115 months), relapse occurred in 8 of 61 patients (13.1%) who had achieved CR. Relapse-free survival (RFS) in all patients at 5 years was 84.8%. Upon univariate analysis, patients with BMI ≥25 kg/m² had significantly better prognoses than did those with BMI <25 kg/m2 (odds ratio=0.19; 95% confidence interval=0.05–0.66; p=0.009). Overall pregnancy and live birth rates per patient were 61% (19/31) and 45% (14/31), respectively. CONCLUSIONS: MPA plus metformin is efficacious in terms of RFS and post treatment conception. Moreover, metformin may be more efficacious for patients with BMI ≥25 kg/m².
Body Mass Index ; Endometrial Hyperplasia ; Endometrial Neoplasms ; Female ; Fertility Preservation ; Fertilization ; Follow-Up Studies ; Humans ; Insulin Resistance ; Live Birth ; Medroxyprogesterone Acetate ; Metformin ; Pregnancy ; Prognosis ; Recurrence ; Retrospective Studies

Introduction: During their clinical clerkship (CC), Japanese medical students’ literature searching skills were ambiguous. We conducted a questionnaire survey on students’ search processes to determine whether this skill improved after a lecture on conducting searches.　Method: This study was conducted from May to December 2019. The questionnaire survey was followed by a 90-minute lecture combining information and relevant activities. The questionnaire included students’ self-evaluation of their literature searching abilities, and references from their medical summaries and reports were compared to those of students from a 2018 group who did not attend the lecture.　Results: Sixty-seven students participated in the questionnaire survey and lecture. Questionnaire results demonstrated that the most frequently used search tool was PubMed. Regularly used types of literature were Japanese textbooks medical guidelines issued by the Japanese Medical Society, and English-language medical journal articles. The two major difficulties in conducting searches were the inability to critically appraise the literature and inadequate English reading skills.　The students’ satisfaction level regarding the lecture was found to be acceptable. After attending the lecture, students’ self-evaluation of their literature searching abilities improved significantly. Furthermore, compared to the 2018 group, references in students’ summaries and reports increased. Additionally, the number of English-language medical journal articles cited in reports was higher among students in the 2019 group than the 2018 group.　Conclusions: Although CC students can conduct literature searches, they struggle with critical appraisal and English-language comprehension. Interventions such as lectures may effectively improve their searching skills during CC.

Detection of the coronary artery is usually an easy procedure in the coronary artery surgery. However in cases with an intra-muscular and/or intra-fat coronary artery, it requires special skill and experience. Dissection of epicardial adipose tissue and/or muscle along the epicardial groove is a common procedure to reach such coronary artery in conventional CABG (C-CABG). Recently, off-pump CABG (OPCAB) has become a standard operation, and detection of such a coronary artery is difficult under the beating heart. Then conversion to the C-CABG becomes necessary to avoid ventricular rupture. We report a new procedure to easily detect such a coronary artery in OPCAB, using an ultrasonic Fowmeter used in neurosurgery. Because the tip of the probe is small (2mm in diameter) and flexible, its handling is quite similar to that of the micro-blade knife. Furthermore, audiable Doppler flow sound allows detection and dissection of the coronary artery without looking away from the operative field to check the coronary flow. In our case, use of the instrument enabled us to detect the anterior descending branch of the left coronary artery which was very deep in adipose tissue. Therefore, application of this ultrasound instrument is beneficial in OPCAB with an intra-muscular and/or intra-fat coronary artery.

Introduction: Vaccine policies have changed in recent years in Japan. In the present study, we assessed practices, recommendations, knowledge, and sources of information among primary care physicians (PCPs) regarding vaccinations in Japan. Methods: We conducted a nationwide cross-sectional study targeting PCPs in Japan. We used a web-based self-administered questionnaire targeting physicians that were members of the Japan Primary Care Association in 2019. We analyzed respondent administrations, recommendations, knowledge, and sources of information regarding vaccinations. Results: We received responses from 1,084 PCPs (20.1%) and invited 981 participants for the analysis. The rates at which physicians gave routine and voluntary vaccines in their own practices were 23.3-95.5% and 13.2-94.4%, respectively. The active recommendation rates for routine and voluntary vaccines were 41.6-92.0% and 13.6-75.5%, respectively. Furthermore, among routine vaccines, human papillomavirus vaccine was the least administered and recommended. PCPs working at clinics had the most accurate knowledge about vaccinations, and PCPs utilized academic organizations most readily as an information resource. Conclusion: We clarified practices, recommendations, knowledge, and sources of information regarding vaccinations among PCPs in Japan.