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The patient is a 39-year-old woman. At the age of 34, she recognized a 22 mm sized mass in the upper outer quadrant of her right breast, which was diagnosed as a fibroadenoma. 5 years later, the mass increased to 45 mm. We performed lumpectomy which led to a diagnosis of a malignant phyllodes tumor with osteogenic sarcoma. Since the resection margins were positive, we performed mastectomy in addition. Nine months after surgery, a 23 mm large mass appeared on the right fifth costal. Recurrence of malignant phyllodes was suspicious from cytological diagnosis and since thoracoabdominal CT showed no metastasis to other organs, we performed resection. Histological results were the same as the primary tumor. Two months more later, an 11 mm large mass revealed in the right anterior thoracic region. We performed resection again, which showed the same histological features as the primary tumor. Since malignant phyllodes tumors often recur in the early postoperative period, a close follow-up is recommended.

Recent changes in the environment surrounding community pharmacists include "follow-up after dispensing" becoming mandatory, initiation of "certified pharmacy system with specific functions," with the discussions on post-graduate training, lifelong training and specialization, refill of prescriptions, as well as pros and cons of hospital pharmacies in preparation for the 2022 dispensing fee revision. In this regard, since 2019, I have been receiving training at The Cancer Institute Hospital of Japanese Foundation for Cancer Research (JFCR). In addition, to implementing community pharmacists' perspectives into collaboration between community pharmacists and hospital pharmacists, a tracing report model incorporating the Common Terminology Criteria for Adverse Events (CTCAE) ver. 5.0 has been created. And, a regimen of drugs and operation describing necessary supportive care has been published in The Cancer Institute Hospital of JFCR website. As a practice of patient safety management at pharmacies, we are working on the standardization of questionnaire criteria to assess the severity of adverse medication reactions in cancer patients and the measurement of health-related quality of life using EuroQol 5 dimensions 5-level (EQ-5D-5L), introduced with cooperation of universities, hospitals, and pharmacies. As medical care is advancing day by day, especially in cancer medication therapy, patient safety management by pharmacists becomes essential, when dealing with the complexity of administration schedule and the wide variety of side effects. For patient safety management, community pharmacists need to practice with pharmaceutical and medical knowledge, and have skills to acquire and convey information, with a researcher's perspective.

A woman in the 60s. She was referred to our hospital because the fecal occult blood test was positive. Colonoscopy was performed. Cancer is found in the transverse colon. There were no metastases in the lungs and liver. Laparoscopic left hemicolectomy was performed. Histopathological examination was adenocarcinoma(tub1>tub2>muc), pT1b, pN2, ly2, v1, pPM0, pDM0, pRM0, budding(0, Grade 1), fStage Ⅲb. After postoperative adjuvant chemotherapy, she visited an outpatient clinic 8 months after surgery with a complaint of swelling of both inguinal lymph nodes. The swollen inguinal lymph node was relatively soft and there was no evidence of infection. A biopsy of the bilateral lymph nodes was performed. Histopathological examination revealed adenocarcinoma containing mucus components. These findings were consistent with histological findings in transverse colon cancer. Based on these results, we diagnosed metastatic recurrence from transverse colon cancer to both inguinal lymph nodes.

Here we report a case of a 41-year-old male patient who underwent resection of a desmoid tumor originating from the greater omentum with no history of open surgery. An elastic hard mass was palpated in the left upper abdomen, but there were no abnormalities on serum chemical tests, including tumor markers. Computed tomography showed a parenchymal tumor located near the descending colon. Integrated positron-emission tomography and computed tomography revealed moderate accumulation of tracer in the tumor. An intra-abdominal malignant mesenchymoma was suspected and surgery was performed. The tumor was located in the anterior portion of the greater omentum. It partially invaded the diaphragm, and the affected regions were concurrently resected. The resected specimen measured 80 mm at longest diameter. The cut surface was grayish white and parenchymal. The histopathological findings showed the atypical spindle shaped tumor cells grown with collagen fiber progression. Immunohistochemical staining for β-catenin showed strong staining in the nuclei and cytoplasm of tumor cells. The patient was diagnosed with desmoid tumor originating from the greater omentum. The desmoid tumor with no history of open surgery was rare. We report this rare case, along with a discussion of the literature.

To determine the relationship between seasons and regions and aflatoxin M 1 (AFM 1 ) contamination of milk distributed in Fukuyama City, we conducted a survey once during the summer and once during the winter between June 2018 and January 2019. We compared the AFM 1 contamination levels in milk drinks available in Fukuyama City during the same period, to provide more about the factors causing AFM 1 contamination. All milk samples examined exhibited AFM 1 contamination levels below the standard AFM 1 contamination level (0.5 μg/kg). For the comparison based on seasons, one milk sample collected in the summer (0.07 μg/kg) exceeded the EU limit (heat-treated milk: 0.050 μg/kg). However, there was no significant difference in the AFM 1 contamination level (p>0.05). For the comparison based on regions, the AFM 1 contamination level in the milk sample from the Chugoku Region was significantly higher in the winter and significantly lower in the summer compared to those from other regions. AFM 1 contamination of milk did not have a direct relationship with seasons or regions, but was instead influenced by the type, amount, and management of feed supplied to dairy cattle. For the comparison between milk and milk drinks, the AFM 1 contamination levels in milk drinks were significantly lower (p<0.01). The highest AFM 1 concentration (0.08 μg/kg) was detected in one sample of milk drink sampled during the summer. The AFM 1 contamination of milk drinks is likely affected by the level of contamination in raw materials, the proportion of such raw materials in the drinks, and the process type. An increase in non-fat milk solids was assumed to be a factor that increases AFM 1 contamination.

The Japan Environment Health and Children's Study (JECS) is an ongoing cohort study designed to evaluate the impact of various environmental factors on children's health. In this study, more than 100,000 pregnant women were recruited in 15 regional centers throughout Japan. Within the University of Occupational and Environmental Health, the departments of Pediatrics, Obstetrics and Gynecology, Environmental Health, and the School of Health Sciences collaborate with the JECS University of Occupational and Environmental Health Subunit Center in advancing research in this study. Several original articles based on JECS and written by our unit members were published in recent years. The aim of this review is to summarize these studies by JECS and University of Occupational and Environmental Health Subunit Center based on the data from JECS. We introduce research articles covering the following categories; environmental health, occupational health, and maternal and child health. Studies found associations between concentrations of metals and maternal health, such as premature birth, placenta previa and placenta accrete, associations between metals and IgE, dietary differences among occupational groups, associations between work-related factors and dietary behaviors, associations between job changes and pregnancy/delivery, mental and physical stress among pregnant women and influence on work, associations between sleep and gestational diabetes, and associations between an ability to push up in the prone position and infant development. This review may promote the development of new research, such as collaborative research projects, including clinical and social medicine, epidemiological studies and laboratory investigations.

A 44-year-old woman in the first remission phase of mixed-phenotype acute leukemia (T-lymphoid and myeloid lineages) suddenly exhibited thrombocytopenia (1.1×10 4 /µl) with generalized petechiae approximately 150 days after bone marrow transplantation (BMT) from a one-locus (HLA-B) mismatched unrelated donor. Until then, the donor bone marrow had smoothly engrafted, and the platelet count had promptly normalized. Despite extensively searching for the triggering agent such as GVHD, graft failure, relapsed leukemia, or adverse drug effects, it could not be determined. Suspecting immune thrombocytopenia secondary to BMT, prednisolone (1 mg/kg/2 days) therapy was initiated, but its effects were unsatisfactory. Next, eltrombopag, a thrombopoietin receptor agonist (TPO-RA), was administered, which exhibited a marked effect on thrombocytopenia, resulting in the withdrawal of prednisolone. Even though the efficacy of eltrombopag against immune thrombocytopenia is well established, limited studies have reported the efficacy and safety of eltrombopag against immune thrombocytopenia after allogeneic stem cell transplantation. Herein we report a case in which thrombocytopenia occurred late after transplantation but was successfully treated with a TPO-RA. In addition, we discuss suspected causative mechanisms and review the literature.

A 39-year-old woman with very sever obesity was admitted to our hospital for a right breast redness and hardness. Her height, weight and BMI were 166 cm, 145 kg and 52.6 kg/m2. Her breast had peau d'orange. CT scan showed swelling of whole right breast and Level I , II lymph node. We performed core needle biopsy and diagnosed as the inflammatory breast cancer with ER and HER2 positive. We introduced chemotherapy(pertuzumab, trastuzumab and paclitaxel)and nutrition counseling in order to reduce her body weight. After 4 courses of chemotherapy, the clinical complete response was obtained and her body weight decreased to 125 kg. We performed mastectomy and axillary node resection and confirmed pathological complete response. Adjuvant chemotherapy(5-FU, epirubicin and cyclophosphamide), adjuvant trastuzumab therapy, postmastectomy radiation therapy and adjuvant hormonal therapy were administered. There have been no signs of recurrence as of 2 years after the operation.

Echocardiography revealed 2 aneurysms in the mitral valve with mitral regurgitation and aortic regurgitation,in a 42-years-old man. He had had infective endocarditis due to Streptococcus 9 months before. A prolapse in the right coronary cusp without vegetation and 2 aneurysms in the anterior mitral leaflet were found intraoperatively. Aortic valve was replaced, and then mitral aneurysms were resected and repaired using his own pericardium. There has been almost no regurgitation or recurrence of infection over 3 years.

Purpose: To elucidate the distribution of improved pain and numbness after cervical decompression surgery in patients with cervical spine disorders., Methods: This study included 4 men and 5 women aged 45 to 71 years(mean 58 years)presenting with radiculopathy and 50 men and 17 women aged 35 to 88 years(mean 66 years)presenting with myelopathy., Results: All 9 patients with radiculopathy presented with neck pain, and 3 presented with cervical angina. Among the patients with myelopathy, 2 presented with headache, 2 with onion-skin facial pain, 29 with neck pain, 8 with truncal pain, 7 with low back pain, 4 with numbness below the T4 dermatomal area, 1 with penile pain, 61 with arm pain, 49 with leg pain, and 2 without pain or numbness. Patients with myelopathy presenting with preoperative neck and arm pain had significantly better recovery rates compared to patients without such pain., Conclusion: Patients with cervical spine disorders present with pain and numbness in various areas. Preoperative neck pain and arm pain are indicators for better recovery in patients with myelopathy.

Objective: Assessing the degree of problems related to drug abuse is important in each treatment setting. The Drug Abuse Screening Test-20 (DAST-20) is a brief, simple 20-item instrument to measure the degree of problems related to drug use. The objective of the present study is to examine the reliability and validity of the Japanese version of the DAST-20., Methods: We translated the DAST-20 into Japanese using back translation. The anonymous self-administered questionnaire was completed by 310 drug users at the Drug Addiction Rehabilitation Centers (DARC group, n = 113) and at HIV/AIDS regional hospitals (HIV group, n = 197) in Japan., Results: The average DAST-20 score was 7.6 (DARC group = 14.7, HIV group = 2.8). Each item score was highly correlated with the total score (r = 0.45-0.88). A high internal consistency (Cronbach's α = 0.95) was observed (men = 0.95, women = 0.84). Overall test-retest reliability was 0.86 (men = 0.85, women = 0.90). The total DAST-20 score was strongly positively correlated with the Severity of Dependence Scale-J score (r = 0.85), but moderately positively correlated with the Alcohol Use Disorders Identification Test score (r = 0.41). In addition, confirmatory factor analysis indicated an acceptable fit to the data (goodness-of-fit index [GFI] = 0.893, adjusted goodness-of-fit index [AGFI] = 0.854, comparative fit index [CFI] = 0.948, root mean square residual [RMR] = 0.008, root mean square error of approximation [RMSEA] = 0.073)., Conclusion: Our results clearly suggest that the Japanese version of the DAST-20 has sufficient internal consistency and acceptable levels of concurrent validity and construct validity.

A 81-old-woman underwent a transurethral resection of bladder tumor (TURBT) at a nearby hospital in April 2011. The diagnosis was invasive urothelial carcinoma, G3 with a component of bladder small cell carcinoma, T1 or more. She was recommended to visit our hospital for combined modality therapy of bladder cancer, but she refused the treatment for over one year. In May 2012, she came to our hospital with the chief complaint of pain at urination. Cystoscopy revealed non-papillary sessile tumor in the top of the bladder, and CT scan demonstrated the presence of the right obturator lymph nodes swollen up to 1.2 cm in size. The second TURBT was performed and the diagnosis was bladder small cell carcinoma (pT3N2M0) according to urothelial cancer guidelines of the Japanese Urological Association (JUA). Because she strongly refused hospitalization anymore, we started daily oral intake of low dose Tegafur-Uracil (100 mg) for the treatment. After one month, the serum Neuron-Specific Enolase (NSE; tumor maker of small cell cancer) level was elevated to 27.6 ng/ml and the right obturator lymph node was enlarged up to 1.9 cm. Therefore, the Trgafur-Uracil dose was increased to 200 mg daily. After then, the serum NSE level was decreased to 15.5 ng/ml following reduction in size of the obturator lymph nodes with partial response in December 2013. After two years of follow-up period, her regular urine test showed normal findings, and no apparent recurrence was detected on urinary bladder with MRI and Cystoscopy. This is a case of advanced bladder small cell carcinoma significantly improved by oral administration of Tegafur-Uracil 200 mg/day for over 2 years.

A 45-year-old man experienced dyspnea on effort and was hospitalized due to severe mitral valve regurgitation and atrial fibrillation. He also had alcoholic cirrhosis. After he was stabilized, mitral valve plasty and Maze procedure were performed. The postoperative clinical course was satisfactory. During the follow-up period, he began to suffer from persistent left pleural effusion, which amounted to about 2,500 to 3,000 ml, and required intercostal tube drainage weekly. Therefore a pleuro-peritoneal shunt was implanted. The pleural effusion decreased, and he obtained significant relief from dyspnea. After one year, we confirmed that pleural effusion had not reoccurred, and removed the pleuro-peritoneal shunt.

This report describes a 41-year-old patient, who developed herpes simplex virus type 2 (HSV-2)-hepatitis after umbilical cord blood transplantation (CBT). The patient had received allogeneic bone marrow transplantation from an unrelated donor for acute myeloid leukemia (AML) not in remission. AML relapsed 18 months after the first transplantation, and CBT was performed. AML relapsed again 5 months later and the patient was given chemotherapy. Although there was no active chronic graft-versus-host disease, liver dysfunction appeared, and one week later, progressed to acute liver failure. Viral screening of blood by PCR including hepatitis B and C viruses, human immunodeficiency virus, Epstein-Barr virus, cytomegalovirus, herpes simplex virus type 1 and HSV-2 revealed elevation of HSV-2 (2.34 × 10⁴ copies/ml). We diagnosed the patient as having HSV-2 acute hepatitis, and initiated treatment with antiviral drugs (acyclovir, foscarnet) and plasma exchange. However, liver functions deteriorated rapidly, and the patient died on day 6 after the onset of acute liver failure. Although HSV hepatitis is very rare after allogeneic stem cell transplantation, it is rapidly progressive and associated with a high mortality rate. Thus, early diagnosis with prompt antiviral intervention is recommended.

Objective: To examine the factors related to fatigue accumulation by irregular shift workers after the late-night shift., Method: We studied employees of a company in the transportation industry in Fukushima prefecture. The company transports passengers, and many employees, including the crew, engage in irregular shift work. We performed the investigation by using a self-administered questionnaire which was sent to 89 employees in October, 2011. Of the 89 who were given the survey, 84 replied, and 52 of those employees had worked the late-night shift (straddling midnight) at least once during September. In answer to the question "How long does it take you to recover after working the late-night-shift?" choices were "I don't feel tired ", "I recover the next day", "I recover in two or three days", and "It takes more than three days". We classified the choices into two groups of: 1) "I don't feel tired" and "I recover the next day", and 2) "I recover in two or three days" and "It takes more than three days". Other questions were asked about age, BMI, weekday average duration of sleep, whether or not a nap was taken before the late-night shift, risk of lifestyle-related diseases (hypertension, dyslipidemia, and diabetes), awareness of life stress accumulation, and exercise habits., Results: Thirty-two employees answered that they recovered from the late-night shift by the next day, whereas 20 employees answered that it took more than 2 days to recover after the late-night-shift. The group who answered that recovery time after the late-night shift took more than 2 days significantly (p=0.035) felt that their stress management was insufficient. Age, BMI, weekday average duration of sleep, whether or not a nap was taken before the late-night shifts, risk of lifestyle-related diseases, and exercise habits showed no significant association with fatigue accumulation. The group who answered that their stress management was insufficient significantly chose liquor (p=0.045) and cigarettes (p=0.030) for stress reduction., Discussion: In this study, a relationship was recognized between degree of awareness of daily stress relief and fatigue recovery period. In addition, various means of stress relief had different effects, suggesting the need for individualized mental health care.

A low birthrate and aging society have led to a decrease in the Japanese work force. Therefore, maintaining the environment surrounding working women has become an important priority of the occupational physician. As for laws on women's healthcare, revision allows adaptation to fit changes in the times. In 2012, a revision of the "Labour Standards for Women" included the addition of several harmful chemical substances and acceptable safety levels were established according to current toxicology study. In this report, we examine the effect on women's health of three laws; "Labour Standards Act", "Labour Standards for Women" and "Act on Securing, Etc. of Equal Opportunity and Treatment between Men and Women in Employment". Finally, the details of the 2012 revision of "Labour Standards for Women" are described.

This article aims to introduce biological monitoring, which has been carried out in Japan for 25 years. Biological monitoring in occupational health is an assessment of the overall exposure to chemicals that are present in the workplace through measurement of the appropriate determinants in biological specimens in workers. Lead in blood and urinary δ-aminolevulinic acid in the urine of workers who handle lead, and urinary metabolites of workers who handle 8 kinds of organic solvents, are mandatory measurements. In 2013, insium and compounds, etheylbenzene (only coating workers), and cobalt and inorganic compounds were added to biological monitoring subjects, alongside the ordinal ones of specified chemical substances. Occupational physicians are required to carry out biological monitoring according to standardized protocols in order to correctly utilize biological monitoring results for occupational health management.

We report on an 8-year-old boy with non-paraneoplastic anti-NMDA receptor (NMDAR) encephalitis, who presented with psychotic symptoms and involuntary movement following an intractable seizure. His serum and CSF tested positive for anti-NMDAR antibodies. He received an initial immunotherapy consisting of methylprednisolone pulse therapy (mPSL) and intravenous immunoglobulin therapy (IVIg), without any clinical improvement. He had three cycles of monthly cyclophosphamide pulse therapy (500 mg/m2), and his clinical condition started to improve gradually two weeks after the first cycle, without any side effects. Six months after onset, he tested normal upon standard neurological examination. Cyclophosphamide therapy should be considered for children with anti-NMDAR encephalitis, as well as mPSL and IVIg.

Objectives: Ever since the Fukushima Daiichi nuclear power plant (NPP) accident, every day about 3,000 workers have been working to repair the situation. The frequent occurrence of heat disorders has been a concern for the workers wearing protective clothing with poor ventilation. We have been analyzing the heat disorder problem since the accident in order to come up with a solution to prevent future heat disorder incidents among Fukushima Daiichi NPP accident clean-up workers., Methods: From March 22 to September 16, 2011, the Fukushima Labor Bureau assessed 43 cases of nuclear power plant workers with heat disorders. Age of subject, month and time of occurrence, temperature, and humidity were examined for each case, as well as the severity of heat disorders. The grade of severity was divided into Grade I and Grade II or higher. Then, age, temperature, and humidity were analyzed using the Mann-Whitney Utest, and age, temperature, humidity, and presence or absence of a cool-vest were analyzed using the χ(2) test and logistic regression analysis. SPSS version 17.0 statistical software was used with a level of significance of p< 0.05., Results: Heat disorders occurred most frequently in subjects in their 40s (30.2%), followed by those in their 30s (25.6%), mostly in July (46.5%) between 7 am and 12 pm (69.8%). Heat disorders occurred most frequently in environments with temperatures more than 25°C (76.7%) and humidity of 70-80% (39.5%). Heat disorders of Grade II or higher occurred in 10 cases, 5 of which were in June. According to statistical analysis, there were no significant differences in difference of severity for all factors., Conclusions: Heat disorders usually occur in workers aged 45-60; however, cases of heat disorders at the Fukushima Daiichi NPP occurred in clean-up workers at the relatively younger ages of 30-40, suggesting the need for heat disorder prevention measures for these younger workers. Heat disorder cases primarily occurred in the morning, necessitating preventive measures for the early hours of the day. In addition, because heat disorders of Grade II or higher occurred in June in 5 of 10 cases, we believe heat disorder precautions should be implemented from June. The lack of significant difference in severity difference may be attributable to the small number of cases or other factors. We think Fukushima Daiichi NPP accident clean-up workers need heat disorder prevention measures for their safety, based on the results of this study.

This study evaluated the in vitro activity of doripenem (DRPM) against 200 Streptococcus pneumoniae and 197 Haemophilus influenzae from children and adults in 2007, 50 H. influenzae type b in 2006, 20 Listeria monocytogenes in 1990-2005, 23 Neisseria meningitidis in 2007-2009 and 83 Bordetella pertussis in 1989-2003. All strains were isolated from Japanese clinical facilities. We also investigated in vitro activity of other carbapenems (meropenem, imipenem, panipenem, biapenem), cephems (ceftriaxone, cefotaxime), ampicillin and clarithromycin. The all MICs were determined by a broth micro dilution method or an agar dilution method according to CLSI. The MIC90(s) of DRPM against S. pneumoniae and H. influenzae from children were 0.25 microg/mL, 1 microg/mL, respectively, which were similar to strains from adults. These results suggested that antibacterial activity of DRPM is not variable by patient's age. DRPM also showed excellent activities against H. influenzae type b, L. monocytogenes and N. meningitidis, which cause purulent meningitis, and B. pertussis causing whooping cough more than the other carbapenems. DRPM showed superior activities against serious strains of pediatric infection diseases.

Recent research has demonstrated that complex 'epigenetic' mechanisms, which regulate gene transcription without altering the DNA code, could play a critical role in the pathophysiology of psychiatric disorders. We previously reported that pretreatment of mice with 5-HT(1A) receptor agonists 24 hr before testing suppressed the decrease in emotional behaviors induced by exposure to acute restraint stress. In addition, DNA microarray analysis showed that such a pretreatment with 5-HT(1A) receptor agonist produces changes in several gene transcriptions in the hippocampus including the reduction of histone deacetylase 10. Based on these findings, we recently carried out studies focused on the relationship between the development of emotional resistance to stress and histone acetylation induced by a 5-HT(1A) receptor agonist as well as a histone deacetylase inhibitor. The findings suggest that 5-HT(1A) receptor agonists may be useful for preventing mental illnesses that arise due to a decreased resistance and adaptability to stress. Moreover, the notion that chromatin remodeling is an important mechanism in mediating emotionality under stressful situations is further supported.

A growing body of evidence suggests that the brain serotonin (5-HT) nervous system is an important component related to the etiology as well as the treatment of stress-related psychiatric disorders. Molecular cloning studies have revealed the existence of 14 different genes, each encoding a distinct 5-HT receptor subtype. The 5-HT7 receptor is the most recently identified member of the 5-HT receptor subtypes, and the physiological role of this receptor is still unknown. Recently, either selective agonists or antagonists for 5-HT7 receptors, as well as 5-HT7 receptor knockout mice, have been developed, and these have recently been used as the experimental tools for determining the actual function of 5-HT7 receptors. The first half of the present article introduces the reports that have examined the role of the 5-HT7 receptor on emotional regulation. On the other hand, it has been indicated that the ability to adapt to stress is an important defensive function of a living body, and impairment of this ability may contribute to some stress-related disorders. Thus, the examination of brain mechanisms involved in stress adaptation could help to pave the way for new therapeutic strategies for stress-related psychiatric disorders. The second half of the present article introduces our recent studies focusing on the relationship between brain 5-HT7 receptors and the mechanisms of stress adaptation.

Treatment periods for bacterial meningitis are often very long, and often this prolonged treatment is based on the judgment of its effectiveness by the degree of enhancement on brain magnetic resonance imaging (MRI). In this study, we analyzed the contrast MRI in the acute and recovery phases of bacterial meningitis in twelve patients, and graded the contrast level of the subdural space and subarachnoid space separately. While the contrast level of the subarachnoid space increased with time in 4 cases, that of the subdural space increased in 10 cases, and 9 of them revealed a good prognosis without continuation of the treatment. These findings indicate that increased contrast level of the subdural space is common in the recovery phase of bacterial meningitis, and that repetitive MRI investigation is not valuable to determine the duration of treatment.

MALDI-imaging MS (IMS) with MSMS analysis is a new powerful tool for the identification of not only disease-related proteins in formalin-fixed paraffin-embedded (FFPE) tissue sections but also protein/peptides/drugs/medicine in fresh-frozen tissues. IMS is used to reveal the mass profiles and spatial distribution of proteins in tissue sections and/or digested peptides derived from deposited protein in pathologic organs and then MSMS analysis identifies the amino acid sequence of the detected proteins in the tissue section. Moreover, on-tissue digestion combined with the MALDI-IM-TOF-IMS approach allows a proteomics "bottom-up" strategy with clinical samples, especially perioperative isolated tissues and FFPE tissues conserved for a long time in a clinical sample bank. The mass barcode-like image (MBI) on a longitudinal sliced hair by IMS is used in the selected reaction monitoring mode for serially chronological monitoring and traceability every few hours after drug and medicine intake. The advances of quantitative MBI for sliced sections of hair allow a new universal standardized assessment of drugs and medicines throughout the drug history.

A 31-year-old man visited another hospital with a chief complaint of a solid mass in the left scrotum. The diagnosis was a skin cancer of the scrotum, and he was referred to our hospital. We performed surgical resection of the mass, left testis, and bilateral superfical inguinal nodes. Histopathological findings revealed leiomyosarcoma of the scrotum. He is free of disease at 16 months after the operation.

We report 12 cases of acute encephalopathy associated with influenza H1N1-2009 treated according to Japanese guideline (2009). In all 12 cases, electroencephalogram presented diffuse or localized high-amplitude slow waves. Brain CT and MRI showed abnormalities in 4 and 6 cases, respectively. We used hypothermia therapy for 5 patients. One patient showed impairment in short term memory, while the rest of the patients showed no sequelae. These 12 cases presented here suggest the early recognition and therapy according to the newly proposed guideline may reduce severe sequelae and mortality by acute encephalopathy associated with influenza H1N1-2009.

A 71-year-old man underwent left nephrectomy for metastasis from renal cell carcinoma (RCC) of the small intestine. In spite of post-operative therapy (interferon-alpha or interleukin-2), multiple lung metastases and intestinal hemorrhage by metastatic tumor of small intestine appeared 9 years after the operation. To control the bleeding from the small intestine, the small intestine was partially excised and the histopathological diagnosis was metastasis of RCC. He died 10 months later because of disease progression. Metastasis of RCC to the small intestine is rare. To our knowledge, this is the 40th case of small intestinal metastasis from RCC reported in the literature.

This study evaluated the in vitro activity of combinations of doripenem (DRPM) with aminoglycosides (tobramycin or amikacin) or fluoroquinolone (ciprofloxacin) against 92 isolates of Pseudomonas aeruginosa from 16 clinical facilities in 2004 in Japan. We also tested combination effect of other carbapenems (imipenem (IPM), meropenem, biapenem) with aminoglycosides or fluoroquinolone by checkerboard dilution methods. DRPM showed synergistic or additive effects with the aminoglycosides or the fluoroquinolone against 90% of the isolates. The combination of DRPM and aminoglycosides showed the strongest synergistic effects against IPM-intermediate resistant and IPM resistant strains among the tested combinations. These results suggested that combination of DRPM with aminoglycosides would be useful for the treatment of infections caused by P aeruginosa including IPM-resistant strains.

To investigate the effectiveness and safety of GVHD prophylaxis using FK506 alone as a continuous infusion, 104 patients who underwent reduced-intensity cord blood transplantation were retrospectively reviewed. The respective incidence of acute GVHD was 25 grade 1(24. 1%), 19 grade2(18. 3%), 15 grade3(14. 4%), and 4 grade4(3. 8%), which are comparable to that in the literature. The incidences of grade 2 and greater acute GVHD were 32 out of 69(46. 4%)for those whose wholeblood concentration of FK506 werele ss than 13 ng/mL, whereas 6 out of 35(17. 1%)for those FK5 06 were greater than 13 ng/mL. The differenceies between above and below 13 ng/mL were statistically significant(p=0. 008). There were 19 cases(18. 3%)of renal dysfunction, although none required hemodialysis. There were only 4 patients who discontinued FK506, which further confirmed the safety of FK506 alone. Together with our previous report on the upper limit of FK506(17 ng/mL)and these results, we recommend the optimal serum concentration of FK506 to range from 13 to 17 ng/ mL.

We investigated attempted suicide cases, both successful and failed involving patients, accepted by public health care institutions in Shiga Prefecture, whose population is about 1. 4 million, from the 12th January 2010 to 14th February 2010. Prefectural emergency hospitals, fire stations, and pathologists cooperated in the investigation, and the cases were reported with the age and sex as well as the means and results of the attempts. How these institutions cooperated in the cases was also reported. A total number of 104 people attempted suicide, in which 40 people (38.5%) succeeded, 54 people (51.9%) failed, and the outcome was unknown in 10 people (9.6%). Forty-one people (39.4%) were in their 30s, being the most common age group. Successful suicides were most prominent among elderly males, and failed attempts were most prominent among young females. Hanging and poisonous gassing were the common means of suicide among the successful cases, and overdose, drinking, and wrist -cutting were the common means among the failed attempts. Sixty-four people (61.5%) were admitted to public emergency hospitals, 51 people (49.0%) were rescued by fire workers, and 34 people (32.7%) were sent for autopsy following police reports on fatal cases as suicide. Successful suicides and males were mostly sent for pathological examination without any coordinated care from different medical institutions, whereas, failed cases and females were often taken care of by several institutions. Five people (4.8%) were referred for psychiatric help. Suicide intervention needs to take account of differences in the sex, age, means, and other characteristics of those who attempt suicide. Each institution plays an important role, and they need to cooperate in order to establish an effective intervention.

Recent research has demonstrated that complex 'epigenetic' mechanisms, which regulate gene transcription without altering the DNA code, could play a critical role in the pathophysiology of psychiatric disorders. The present review summarizes recent evidence for the existence of sustained epigenetic mechanisms of gene regulation in several psychiatric disorders such as depression, schizophrenia and Rett syndrome. The gene transcriptions of the key molecules such as brain-derived neurotrophic factor (BDNF) or Reelin that play a role in on psychiatric disorders are regulated with histone modification or DNA methylation. Furthermore, one potential mechanism whereby stress can disrupt prenatal and/or neonatal development is through epigenetics, because the key issue of epigenetics is its long-term influence. In addition, we also found in the recent research that the epigenetic mechanism of gene regulation, especially histonedeacetylase, in the brain may be involved in the development of emotional resistance to stress stimuli. A better understanding of epigenetic regulation might provide new therapeutic avenues for disorders such as depression, schizophrenia, Rett syndrome and neurodevelopmental diseases.

A case of neuroendocrine (NE) differentiated prostate cancer is reported herein, which was progressed with NE differentiation during hormonal treatment in adenocarcinoma of the prostate. A 65-year-old man was admitted to our department with increased serum prostate specific antigen (PSA) (150 ng/ml). A prostate biopsy was performed and histological examinations indicated poorly differentiated adenocarcinoma with a Gleason score of 5 + 4 = 9. Further examinations showed metastases to systemic bones. The clinical stage was T3bN0M1b and hormonal therapy using leuprorelin was started. Eighteen months after hormonal therapy, the serum PSA level declined to 1.702 ng/ml. He subsequently experienced edema in his legs. Computed tomography (CT) demonstrated enlargement of the prostate and swelling of multiple pelvic lymph nodes. Immunohistochemical examination of a re-biopsy specimen revealed a neuroendocrine carcinoma. The neuron-specific enolase (NSE) level was 50.9 ng/ml. The treatment measure was changed from hormonal therapy to combination chemotherapy comprising cisplatin (CDDP) and irinotecan (CPT-11). Pelvic radiotherapy (50 Gy) was then performed. Two courses of the chemotherapy resulted in a great reduction of the tumor volume. However, he had liver metastases 3 months later. His condition worsened rapidly and he died at 8 months after definite diagnosis.

Recently, patients with myopathies who had not previously been able to survive after adolescence required long-term follow-up and treatment. We here discussed medical practice after adolescence in child neurology for these patients with myopathies, such as muscular dystrophies, Pompe disease and juvenile dermatomyositis. Major issues encountered in such practice included inpatient facilities and community medical networks, especially for patients who receive long-term home mechanical ventilation, management for cardiomyopathy and/or gastrogavage. A full information transfer system between child specialists and adult specialists is needed for the benefit of maturing patients.

A 70-year-old man was diagnosed as having rheumatoid arthritis (RA) in 2005. He was treated with 1 g salazosulfapyridine (SASP) daily for two years. Hematological investigations conducted since 2005 demonstrated hemoglobin concentrations of 8 approximately 9 g/dl, which then dropped to 4.9 g/dl on November 21, 2007, following which he was admitted to our hospital. Megaloblastic anemia associated with SASP treatment and anemia of chronic disorders were diagnosed on the basis of folate deficiency and bone marrow examination. This report describes a case of megaloblastic anemia, which developed two years after starting SASP and promptly recovered after its withdrawal and treatment with folic acid and prednisolone. The doses of SASP prescribed for RA in Japan are less than those prescribed abroad. Megaloblastic anemia associated with SASP treatment for RA is not usually detected in Japan. Currently, SASP is widely used and one of the key drugs in the treatment of RA. This case suggests that SASP therapy in RA might result in megaloblastic anemia.

The leaves of Perilla frutescens Britton var. acuta Kudo (Perillae Herba) are commonly found in traditional oriental herbal medicines, which are primarily used to treat depression and anxiety-related disorders. We have recently identified rosmarinic acid as well as its major metabolite caffeic acid as novel antidepressive and/or anxiolytic-like substances from components within Perillae Herba. The present article will review our previous findings and also provide a view of future studies. Behavioral as well as analytical studies have demonstrated that first, the extracts from Perillae Herba, which produced an antidepressive-like effect in the forced swimming test, contained abundant rosmarinic acid; second, the extracts from another species of Perillae Herba, which contains only low levels of rosmarinic acid, did not have an antidepressive-activity; third, rosmarinic acid and caffeic acid themselves also produced an antidepressive-like effect; finally, both compounds showed an anxiolytic-like activity in the conditioned fear stress test. Neurochemical studies have also revealed that neither rosmarinic acid nor caffeic acid affects the uptake of monoamines or monoamine oxidase activity, which may underlie the therapeutic value of existing clinically effective antidepressants. Furthermore, it has been found in the recent study that caffeic acid produces antidepressive- and/or anxiolytic-like effects through the modulation of the alpha1A-adrenoceptor-mediated signal transductions and also attenuates the down-regulation of BDNF transcription that results from the exposure to forced swimming stress. These results suggest that rosmarinic acid and caffeic acid may produce antidepressive- and/or anxiolytic-like effects via some mechanism(s) other than those of drugs that now clinically used. Therefore, further studies on the mechanisms involved in the antidepressive- and/or anxiolytic-like properties of both substances could help to explain the pathophysiology underlying depression and anxiety disorders, and pave the way for the development of new therapeutic drugs.

We report a case of port-site metastasis of bladder cancer after left retroperitoneoscopy-assisted nephroureterectomy and cystectomy. The patient was a 73-year-old man with a chief complaint of gross hematuria. The diagnosis was invasive bladder cancer with bone metastasis. He received two courses of chemotherapy (methotrexate, vinblastine, adriamycin, cisplatin), and this resulted in resolution of the bone metastases. Two months later, abdominal and pelvic computed tomography showed a bladder tumor invading the left lower ureter with hydronephrosis. Left retroperitoneoscopy-assisted nephroureterectomy and cystectomy were performed. The patient was unable to undergo systemic chemotherapy because of renal dysfunction. Four months later, a lateral abdominal wall tumor was found at a port-site, and needle biopsy confirmed this to be metastatic urothelial carcinoma. Clinicians need to be aware of port-site metastasis, particularly in patients with UC, and take steps to prevent it during laparoscopic procedures.

Prostatic stromal sarcoma (PSS) is an unusual lesion that is reported only occasionally. Here we describe a case of prostatic stromal sarcoma in a 33-year-old man who had complained of perineal pain. The serum prostate-specific antigen (PSA) level was above the normal limit at 5.8 ng/ml, and abdominal computed tomography (CT) revealed a giant mass in the retrovesical region. Chest CT demonstrated lung metastases. Specimens obtained by transrectal needle biopsy of the prostate suggested a mesenchymal tumor, but a precise diagnosis required a larger specimen. Palliative transurethral resection (TUR-P) was performed because of obstruction of the urogenital tract, and the final diagnosis was made from this specimen. The tumor contained yellowish gelatinous materials, and the stromal element appeared histologically malignant, with increased cellularity, mitotic figures and pleomorphism. The histological diagnosis was PSS, and the patient received VIP (etoposide, ifosfamide, cisplatin) chemotherapy regimen. However, the pelvic mass continued to increase in size, and the patient's condition rapidly deteriorated and he died. Sarcoma of the prostate gland showing aggressive behavior is quite rare. The detailed histological and immunohistochemical findings in this case are reported, together with a review of the literature.

We report a case of adrenal metastasis from renal cell carcinoma. A 52-year-old man was referred to our hospital for a left renal mass. A computed tomography revealed a left renal tumor. Liver cirrhosis and splenomegaly were observed. Blood tests revealed pancytopenia; platelet count was 2.5 x 10(4)/mm3. The patient was treated by partial splenic embolization (PSE) in an attempt to ensure a safe nephrectomy. After the embolization, his platelet count increased to 6.1 x 10(4)/mm3, and left nephrectomy was performed successfully. Histopathological finding was renal cell carcinoma (RCC). We concluded that PSE before surgery was useful for the patients with thrombocytopenia due to hypersplenism. Four years after surgery, computed tomography revealed the presence of a mass on the right adrenal gland. He was suspected of having a non-functioning adrenal tumor. Metastasis of the RCC was suspected and right adrenalectomy was performed by a laparoscopic procedure. Histologically, the mass was identified as a RCC metastasis. It is clinically rare for an RCC metastasis to the contralateral adrenal gland to occur.

Luteinizing hormone-releasing hormone agonist (LH-RH analogue) therapy, is one of the most widely used hormonal therapies. Recently, subcutaneous injection of a new long acting 3-month LHRH analogue depot has been developed. We investigated the adverse events induced by injection of an LH-RH analogue in 82 patients (median age was 75 year old, 59-87) using our questionnaire. Forty-eight and 34 cases had been administered leuprorelin acetate (LSR) and goserelin acetate (ZLA). The presentation rate of skin reaction was 8.8% (3/34) in the ZLA group and 14.6% (7/48) in the LSR group. There was no significant difference in rate of skin reaction between the LSR and ZLA group (p = 0.5113). Eight patients had induration (6 in LSR 2 in ZLA). We also present a case of subcutaneous granuloma formation at the injection site after using the three-month type preparation of leuprorelin acetate. We should be aware of the risk of skin reactions at the injection site and monitor carefully when using an LH-RH analogue.

A 20-year-old man complained of fever, general lymphadenopathy, severe lumbago, and gynecomastia in January 2003. The diagnosis of Hodgkin lymphoma was confirmed by biopsy specimens of the right supraclavicular lymph node. The clinical stage was IIIB, and the prognostic score was 3. Plasma levels of interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) were elevated to 446 pg/mL, and 1,710 pg/mL,respectively. Six-course combination chemotherapy with the ABVD regimen was initiated,and a complete response (CR) was achieved. Clinical signs disappeared and plasma levels of IL-6 and VEGF decreased to 5.0 pg/mL and 100 pg/mL, respectively. The patient remained in CR as of December 2006. Elevated IL-6 and VEGF may be appropriate tumor markers for patients with Hodgkin lymphoma.