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Oral care is important for patients with head and neck cancer who undergo radiotherapy because these patients encounter various symptoms, which decrease their quality of life(QOL). Oral mucositis is considered the major side effect of radiation, and the dose-volume parameters can serve as predictors of the occurrence of severe oral mucositis. Therefore, understanding radiation treatment planning(e. g., prescription dose and irradiated volumes of the organs at risk)and providing oral healthcare before, during, and after radiotherapy are essential for maintaining patients' QOL., Methods: An RT viewer (Climb Medical Systems) was installed into the inhouse hospital information system to provide education regarding radiation treatment planning to medical staff members (dentists and nurses) by medical physicists., Results: Patients can undertake appropriate oral care before radiotherapy, and this intervention has potential for reducing the radiation-related side effect., Conclusion: Education regarding radiation treatment planning by medical physicists using the RT viewer could improve the knowledge of medical staffs regarding the predictors of radiation-induced side effects for. By introducing the appropriate intervention of oral care before radiotherapy, it may be feasible to maintain patients' QOL.

The spread of COVID-19 has re-affirmed the crucial importance of the pharmaceuticals industry in improving the level of citizens' health and medical care, as well as the industry's importance in terms of contribution to economic growth and tax revenues. Although some time has passed since the importance of industry-academia collaboration was first raised in relation to the creation of innovative new drugs and the continuation of global competitiveness, conflicts between academia and companies have also been highlighted as barriers that hinder efforts to promote the practical realization of academia-initiated seeds. The authors have hypothesized that conflicts between academia and companies can be attributed to the vulnerability of innovation creation environments, including drug discovery, on the academia side, insufficient awareness concerning human resources that will undertake industry-academia operations, and inadequate development of structures. Consequently, we implemented fact-finding investigations in relation to universities and public research institutions in Japan, with the objective of ascertaining the actual status of innovation creation environments, including drug discovery, on the academia side. From the results of these investigations, we will clarify the issues that may present barriers to innovation creation, and consider policies, etc. for the enhancement of innovation creation environments.

Patients who contract severe renal infections often suffer from urosepsis. Therefore, early diagnosis and treatment are required. Sometimes, the treatment with antibiotics is not enough for control of the infections. Most of the patients also require surgical interventions including transurethral drainage and nephrectomy. Twenty-two patients with severe renal infections treated between April 2010 and October 2019 at our institute were evaluated retrospectively. Eleven patients had undergone nephrectomy. Open nephrectomy was performed on 10 patients. Laparoscopic nephrectomy was attempted in the other patient but was converted to open nephrectomy because severe adhesion was found around the tissues. Nephrectomy was performed by the retroperitoneal approach on 9 patients and by the transperitoneal approach on 2 patients. The reteroperitoneal approach was used on two patients who suffered postoperative colon perforation. Inflammatory involvement of renal pelvis, hilum and adjacent structures leads to dense fibrotic reaction and obliteration of tissue planes, which makes the nephrectomy procedure challenging. Therefore, it is important to choose the most appropriate nephrectomy procedure for each patient when they have contracted severe renal infections.

Japanese pharmaceutical products continue to experience a trade deficit, since import values exceed export values. In drug discovery development, given the pace of technological innovations, there has been a major shift from low-molecular-weight compounds to biomedicine. It is anticipated that industry, academia and government will work more closely together in support of the pharmaceutical industry. Drug discovery requires much time and vast resources before the results can be put to practical use, and evidence suggests that many newly approved drugs derive from university-sourced technology. Pharmaceutical companies keep a close eye on technology evolving in universities. However, some reports state that there is a substantial difference compared to the development costs of the major Japanese pharmaceutical companies. Therefore, the authors hypothesized that there may be some issues hindering industrial-academic partnerships in drug discovery. In order to understand the actual situation and barriers to promoting industrial-academic collaboration, the Japan Pharmaceutical Manufacturers Association (JPMA), Japan Agency for Medical Research and Development (AMED), and the Medical Industry-Academia Collaboration Network (medU-net) Council will work together in issuing questionnaires and conducting an awareness survey. This survey sought the personal opinions of individuals belonging to JPMA and medU-net. Based on the results of this survey, we will introduce the issues related to industrial-academic collaboration and partnerships, and any gaps between industry and academia. Furthermore, we suggest solutions to promoting drug discovery innovation in Japan.

Herein, we describe a case of an elderly patient with muscular dystrophy for whom control of the plasma vancomycin (VCM) concentration proved difficult when he developed a catheter-related bloodstream infection. The pharmacist initially carried out therapeutic drug monitoring using an estimate of the creatinine clearance (CL cr ) level, which was based on the serum creatinine (SCr) and serum cystatin-C (CysC) levels, but was ultimately unable to control the plasma VCM concentration. Therefore, the plasma VCM concentration was predicted ex post facto using population pharmacokinetic parameters as a covariate; that is, directly including the glomerular filtration rate (GFR CysC ) estimated from the CysC level, which is not affected by the muscle mass. As a result, the estimated VCM concentration was closer to the actual concentration than that predicted using CL cr . Furthermore, the results of examining the predictive accuracy according to the assessment of renal function at the time of initial VCM administration suggested that estimation of the trough concentration using GFR CysC might be useful in elderly patients with muscular dystrophy.

Multiple myeloma has been known as an incurable disease; however, since the approval of bortezomib in Japan in 2006 as the treatment for relapsed and refractory multiple myeloma, novel agents such as immunomodulatory drugs (IMIDs) and antibodies have been introduced one after another. Hence, progression-free survival and overall survival rates have markedly improved, regardless of the transplantation indication, and we have entered an era of a possible cure. Now that long-term survival can be expected, some clinical issues exist: 1) when to start treatment, 2) what regimen to choose for initial treatment, 3) how to continue treatment including maintenance therapy, 4) what to do for supportive care, and 5) what to choose for relapse treatment. The answers to these questions should be revised year-by-year according to the evidence from new clinical trials. This paper will discuss the current state of knowledge based on the latest evidence on treatment strategies for patients with myeloma who are ineligible for transplantation.

Priapism is defined as a full or partial erection for >4 hours without sexual stimulation or orgasm. Ischemic priapism is an emergency disease that urgently requires surgery to reduce pressure in the corpora cavernosa. We encountered a case of severe ischemic priapism that required a proximal shunt. The patient was a 71-year-old man who had been diagnosed with benign prostatic hyperplasia ; hence, oral administration of tamsulosin had been initiated at a local hospital. His penis became gradually rigid and presented with prolonged erection. Then he consulted our hospital. Penile aspiration was impossible, and phenylephrine injection was not effective. He was subsequently transferred to our hospital. He did not have severe pain but had complete erection. We could not correctly evaluate blood gas from the corpora cavernosa and color Doppler ultrasonography showed little blood flow in the corpora cavernosa. We judged that the patient had ischemic priapism. The erection could not be controlled by distal shunt plastic surgery performed using the T shunt and Al-Ghorab methods. Therefore, a proximal shunt plastic surgery as described by Sacher was performed. The surgery was effective, but it caused erectile dysfunction.

Here, we report the case of an 82-year-old woman with sclerosing mesenteritis diagnosed using needle biopsy under the guidance of computed tomography (CT) and ultrasound (US). The patient manifested appetite loss, weight loss, and epigastric pain. CT of the abdomen and pelvis revealed increased density of the mesentery adjacent to the small bowel along with enlarged lymph nodes. Hence, we suspected sclerosing mesenteritis but also considered malignancies, such as lymphoma. We then performed CT- and US-guided needle biopsy with coaxial technique. We inserted an introducer needle by verifying its location using CT and extracted multiple specimens using a finer needle that passed through the introducer without incident. The collected specimens were adequate and histological diagnosis revealed sclerosing mesenteritis. We treated the patient with corticosteroids, and her symptoms and radiographic findings improved. Thus, the coaxial technique was a useful and minimally invasive tool for the diagnosis of sclerosing mesenteritis.

We describe our experience with two cases of acute gastric dilation after radiofrequency catheter ablation (RFCA) for supraventricular arrhythmia. After the RFCA procedure, patients experienced epigastric pain, abdominal distension, and vomiting. Computed tomography showed marked dilation of their stomachs, but without apparent obstruction of the gastric antrum or the duodenum. Esophagogastroduodenoscopy and upper gastrointestinal series revealed significant gastroparesis. We considered that gastric hypomotility had been induced by vagus nerve injury after RFCA. Peristaltic stimulants effectively improved the patients' symptoms by improving gastric motility. There have been few reports of acute gastric dilation after RFCA in Japan to date, but the possibility of encountering this condition is expected to increase in parallel with the recent increased use of RFCA. Therefore, gastroenterologists should be alert to this rare complication.

The safety and effective dose of chemotherapy in treating non-Hodgkin lymphoma in elderly patients is yet to be established. In this study, we assessed the prognosis of diffuse large B-cell lymphoma (DLBCL) in elderly patients (≥75 years) treated with an optimal dose of R-CHOP. No significant differences were observed in progression-free survival between elderly patients and patients aged <74 years with DLBCL. Furthermore, no differences were observed between full-dose R-CHOP and 80% dose R-CHOP groups. Median relative dose intensity was 0.80 in elderly patients with DLBCL. Thus, our data suggested that 80% dose R-CHOP is tolerable and effective in these patients.

A 10-year-old girl was referred to our hospital with left preauricular adenopathy and gingival swelling. She was diagnosed with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) based on being positive for expressions of CD10, CD19, TdT and HLA-DR. She showed no CD20 expression at the time of diagnosis. Based on the initial diagnosis of BCP-ALL, induction chemotherapy for BCP-ALL was initiated. However, the blasts did not disappear from her peripheral blood. Bone marrow examination on day 33 identified 81.3% residual blasts with positive expressions of CD19, 20 and HLA-DR and negative CD10 and TdT expressions; these cells were morphologically and phenotypically different from those at the initial diagnosis. Based on cytogenetic studies, the final diagnosis was double-hit lymphoma/leukemia (DHL) with IgH-BCL2 and Igλ-MYC. Although dose intensive chemotherapy, including rituximab, led to complete remission, bone marrow and central nervous system relapse occurred. At relapse, blasts expressed CD10, CD19 and HLA-DR, but not CD20, findings the same as those at the onset. The patient died of the disease 44 days after cord blood transplantation with non-remission status. DHL in childhood is extremely rare and its prognosis is poor. The establishment of an effective treatment for DHL is highly anticipated.

A previously healthy 44-year-old male presented with fever, abdominal pain, liver dysfunction and lymphadenopathy. He was diagnosed as having acute cytomegalovirus (CMV) infection with elevated CMV-IgG and IgM, and observed with supportive therapy. He was admitted to our hospital with prolonged fever lasting for a month. Enhanced CT revealed multiple thromboses in the right pulmonary artery and superior mesenteric vein. Follow-up CT after one week revealed new-onset thromboses in the left pulmonary artery and common iliac vein. Screening tests for thrombophilia were negative. His symptoms were improved with anticoagulant therapy with intravenous heparin, followed by oral warfarin. He was discharged on admission day 28 with good condition. Follow-up CT after 6 months revealed complete resolution of the thromboses. Anticoagulant therapy was stopped after 9 months, and he has been well without recurrence. Though vascular thrombosis is a rare complication, we must be alert to the signs and symptoms of thrombosis in patients with acute CMV infection.

Monoclonal antibodies (mAbs) with new mechanisms of action are emerging as promising agents for patients with multiple myeloma (MM). Of these, anti-CD38 antibodies and anti-signaling lymphocytic activation molecule F7 (SLAMF7) antibody have demonstrated efficacy for relapsed and refractory myeloma (RRMM). Two CD38-targeting antibodies, daratumumab and isatuximab had significant activity as single agents, whereas the SLAMF7-targeting antibody, elotuzumab, did not. Patients with RRMM treated with 16 mg/kg daratumumab achieved at least PR of 36% and 29% in two distinct phase 2 studies. More favorable results of phase 3 study of 16 mg/kg daratumumab with lenalidomide and dexamethasone revealed that 92.9% of patients with RRMM achieved at least partial response (PR), with a 43.1% complete response (CR) rate. The median PFS was better in daratumumab arm (Not Reached) than control arm (18.4 months). When combined with lenalidomide plus dexamethasone, elotuzumab, at a dose of 10 mg/kg, improved the median PFS from 14.9 months to 19.4 months in a phase 3 study named ELOQUENT-2. In addition to IMiDs, bortezomib was a hopeful partner. Regarding toxicity, these mAbs are tolerable even in elderly patients. The most common adverse event is an infusion-related reaction. Based on several published reports, we suggest that mAbs combined with standard agents could be successfully adapted for the treatment of newly diagnosed patients with MM.

In October 2014, the varicella vaccination policy in Japan was changed from a single voluntary inoculation to two routine inoculations. This paper reports the results of booster vaccination in children who did not show seroconversion after initial vaccination (i.e., primary vaccine failure : PVF) over a 7-year period prior to the introduction of routine varicella vaccination. Between November 2007 and May 2014, 273 healthy children aged between 1.1 and 14.5 years (median : 1.7 years) underwent varicella vaccination. Before and 4 to 6 weeks after vaccination, the antibody titers were measured using an immune adherence hemagglutination (IAHA) assay and a glycoprotein-based enzyme-linked immunosorbent assay (gpELISA). In addition, side reactions were examined during the four-week period after vaccination. Children who did not show IAHA seroconversion (PVF) were recommended to receive a booster vaccination, and the measurement of antibody titers and an assessment of side reactions were performed after the booster dose. In May 2015, a questionnaire was mailed to each of the 273 participants to investigate whether they had developed varicella and/or herpes zoster after vaccination. After initial vaccination, the IAHA seroconversion rate was 75% and the mean antibody titer (Log2) with seroconversion was 4.7, while the gpELISA seroconversion rate was 84% and the mean antibody titer (Log10) with seroconversion was 2.4. Among children with PVF, 54 received booster vaccination within 81 to 714 days (median : 139 days) after the initial vaccination. After booster vaccination, the IAHA seroconversion rate was 98% and the mean antibody titer (Log2) with seroconversion was 5.8. Both the seroconversion rate and the antibody titer were higher compared with the values after the initial vaccination (p < 0.01). After booster vaccination, the gpELISA seropositive rate was 100% and the mean positive antibody titer (Log 10) was 3.6 ; similar results were obtained for the IAHA assay, with a significantly higher, antibody response than that after the initial vaccination (p < 0.01). Side reactions were generally minor, including fever (≥ 37.5 degrees C), rash at the injection site, and rash at other sites. There were no significant differences in the incidences of side reactions between the initial and booster vaccinations. A total of 185 participants responded to the questionnaire (response rate : 68%), and the period between receiving the initial vaccination and their response to the questionnaire ranged from 1.0 to 7.5 years (median : 4.0 years). The prevalence of breakthrough varicella after the initial vaccination was 17% among seroconverters who did not receive booster vaccination and 14% among non-seroconverters who received booster vaccination, showing no significant difference between the two groups. In conclusion, there are no safety issues regarding the administration of a booster vaccination to children with PVF after an initial varicella vaccination, and,a good antibody response can be expected.

Dietary intake of radioactive substances ((134)Cs, (137)Cs, (40)K) from food in fiscal 2011--2014 was surveyed using the duplicate diet method. 1,612 diet samples were collected from general households of 18 prefectures. (134)Cs and (137)Cs were detected in samples from Fukushima Prefecture, Miyagi Prefecture and Tokyo Prefecture. (134)Cs and (137)Cs were detected in 11 samples in fiscal 2011, 12 samples in fiscal 2012, and 7 samples in fiscal 2013, but none was detected in fiscal 2014. The largest radioactivity in a sample was 12 Bq/kg in Fukushima Prefecture in fiscal 2011. The detected levels gradually decreased and were less than 1.0 Bq/kg in fiscal 2014. The maximum estimated dose of radioactive cecium was 0.14 mSv/year in fiscal 2011. Radioactive potassium was detected in every meal, and showed little change through the four years (median around 30 Bq/kg).

Streptococcus suis is a major swine pathogen. It has recently been recognized as an emerging zoonosis that causes mainly meningitis and sepsis in human. In particular, toxic shock-like syndrome (TSLS) caused by this pathogen has a high mortality rate. However, misidentification of S. suis by conventional biochemical and commercial identification tests is not rare. The patient was a 71-year-old man who worked as a pig farmer who was admitted for fever, oliguria and subcutaneous hemorrhage. He was diagnosed as having septic shock and blood culture was positive for Gram-positive cocci, mainly diplococcus. This pathogen was identified with S. suis with using MALDI-TOF MS analysis, though a commercial Gram-Positive bacteria identification kit revealed viridans streptococci. His clinical features met the diagnostic criteria of TSLS, and ceftriaxone and clindamycin were administered. On admission day 28, he was discharged in good condition.

Objective: Administration of vitamin B12 and folic acid for 7 days prior to the administration of the first dose of pemetrexed is recommended. However, vitamin supplementation rarely is initiated less than 7 days prior to the first dose of pemetrexed. Therefore, we analyzed the safety of pemetrexed with vitamin supplementation for less than 7 days prior to the first dose of pemetrexed., Methods: Patients were classified into 2 groups according to the duration of vitamin supplementation prior to the first dose of pemetrexed: group A received vitamin supplementation for 7 days or more, and group B received vitamin supplementation for less than 7 days. We analyzed adverse effects, such as myelosuppression, rash, and diarrhea, after 1 cycle of pemetrexed therapy., Results: A total of 70 patients were administered pemetrexed; 40 patients were men and 30 were women with a median age of 64.5 years(range, 43-86 years). A total of 57 patients were classified into group A and 13 into group B; 33 patients were administered pemetrexed as a first-line treatment. Neutropenia of Grade 3 or more was observed in 4/49(8.2%)patients in group A and 2/13(15.4%)patients in group B(p=0.60). There were no significant differences in the rates of occurrence of neutropenia, rash, and diarrhea., Conclusion: This retrospective study indicated that patients could be safely treated with pemetrexed if vitamin supplementation is initiated for less than 7 days prior to the first administration of pemetrexed. However, further studies are needed because of a lack of statistical power and adjustment for confounding factors.

A 79-year-old man was referred to our hospital complaining of weight loss. Esophagogastroduodenoscopy revealed a flat, elevated lesion of 30-mm diameter located on the posterior wall of the upper gastric body. The lesion was histologically diagnosed as a well-differentiated adenocarcinoma. Endosonography showed a submucosal tumor under the carcinoma, which was highly suspicious of a gastrointestinal tumor derived from the muscle layer. Adenocarcinoma was diagnosed as an intramucosal lesion, but laparoscopic fundectomy was performed because of the submucosal tumor. Pathological diagnosis was U, less, pType 0-IIa, 18×30 mm, pT1b (SM1), tub2, int, INFa, ly0, v0, pN0, H0, P0, CYX, M0, pStage IA, gastrointestinal stromal tumors, prognostic group 1.

We developed an assay for rapid, specific detection of Shigella, Salmonella, and verotoxin-producing Escherichia coli O157 using the direct PCR analysis of mixed human fecal specimens. In this study, the sensitivity of the direct PCR assay for 50 mixed human fecal specimen was found to be 1.3, 0.42, and 0.76 colony-forming units/kit for Shigella sonnei, Salmonella Typhimurium, and verotoxin-producing E. coli O157, respectively. We compared the efficiency of the direct PCR method with the conventional direct agar plate method for 5000 fecal specimens from food handlers. The 50 mixed fecal specimens were concentrated to approximately 2.5% in distilled water and were heated to 95 degrees C for 5min. Then, 5 μL of the specimen supernatant was added to 45 μL of the PCR mixture. Direct PCR results were evaluated by melting curve analysis. Among the 5000 fecal specimens from food handlers, Salmonella Infantis was isolated from 1 specimen using the direct agar plate method, and it was positive for the Salmonella gene (stn), as confirmed with the direct PCR method. Shigella, Salmonella, or verotoxin-producing E. coli O157 were not detected in the remaining 4999 fecal specimens with the direct agar plate method. However, Salmonella Enteritidis isolated by the enrichment culture method from 1 fecal specimen was positive for stn. Non-O157 verotoxin-producing E. coli isolated using direct horse blood agar from another fecal specimen was positive for stx. Moreover, enteroinvasive E. coli isolated using direct BTB agar from one fecal specimen was positive for ipaH. We conclude that the direct PCR assay can be applied as a new rapid screening method for personal hygiene among food handlers.

A 79-year-old woman suffering from double vision after a 4-year history of MGUS was referred to our hospital. MRI revealed that she had three intracranial plasmacytoma masses and one spinal plasmacytoma mass. Bone marrow aspirates showed 52.4% plasma cell infiltration and immunoelectrophoresis identified serum IgG-M protein, leading to a diagnosis of IgG-type multiple myeloma. IgG was elevated to 3,355 mg/dl and urine type Bence-Jones protein was positive. KL-6, a membrane-bound glycoprotein encoded by Mucin 1 and a marker of interstitial pneumonia, was also elevated to 1,409 mg/dl, but computed tomography of the lungs revealed no obvious pulmonary lesions. Previously reported studies showing that myeloma patients with elevated KL-6 might have a poor prognosis prompted us to treat this patient with a three-drug (bortezomib, cyclophosphamide, and dexamethasone: VCD) combination regimen. When 6 cycles of the regimen had been completed, no M-protein was detectable in her serum. Furthermore, κ free light chain had significantly decreased from 12,700 to 24.8 mg/l. In addition, (18)F-FDG PET/CT revealed reduced mass sizes and no (18)F-FDG uptakes by plasmacytomas. Thus, she was defined as having achieved a stringent complete remission (sCR). We therefore concluded that the VCD combination regimen was highly effective in this multiple myeloma patient with KL-6 elevation.

Additional varicella vaccination was carried out targeting 16 subjects who had immune adherence hemagglutination (IAHA) seroconversion following the initial varicella vaccination and did not contract breakthrough varicella after the initial vaccination. The median ages at the initial and additional vaccination were 2.1 (1.1-6.9) years old and 6.1 (4.4-10.5) years old, respectively. The mean interval between the initial and additional vaccination was 4.0 (3.2-5.2) years. IAHA and glycoprotein-based enzyme-linked immunosorbent assay (gpELISA) antibody titers were measured just before and 4-6 weeks after the additional vaccination. Side reaction was surveyed at four weeks after the additional vaccination, and compared with the results at the initial vaccination. IAHA and gpELISA seroconversion rates at the initial vaccination were 100% and 88% respectively. Prior to the additional vaccination, IAHA antibody titers significantly decreased in 50% of the subjects, and became negative in 38% of the subjects. On the other hand, a significant increase in IAHA antibody titers was observed in 25% of the subjects, and this is assumed to be the result of a subclinical infection after the initial vaccination. The positive rate of both antibodies after the additional vaccination was 100%, the mean IAHA antibody titer (Log2) after the initial/additional vaccination in seropositive subjects was 4.6/6.5, and the mean gpELISA antibody titer (Log10) was 2.3/4.0. The mean IAHA and gpELISA antibody titers were higher after the additional vaccination than after the initial vaccination (p < 0.01, p < 0.01). This is considered to be the booster effect due to the additional vaccination. At 0-2 days after the additional vaccination, a rash at the injection site was observed in 56% of the subjects, higher than the incidence after the initial vaccination (13%) (p < 0.05), but no severe systemic side reactions were observed at either the initial or the additional vaccination. In conclusion, an additional varicella vaccination 3-5 years after the initial vaccination is thought to have greater immunogenicity and is considered effective.

A 14-year-old girl weighing 32 kg was diagnosed with suprasellar tumor causing hydrocephalus, hypothyroidism, adrenal dysfunction and central diabetes insipidus. She was treated with levothyroxine and hydrocortisone and urged to take fluid to replace urine. She was scheduled to undergo ventricular drainage to relieve hydrocephalus prior to tumor resection. For the first surgery, desmopressin was not started and urine output reached 4,000 to 6,000 ml x day(-1), urine osmolality 64 mOsm x l(-1) and urine specific gravity 1.002. Anesthesia was induced with sevoflurane and maintained with propofol and remifentanil. Maintenance fluid was with acetated Ringer's solution and urine loss was replaced with 5% dextrose. Bradycardia and hypotension occurred after intubation, which was treated with volume load. Infusion volume was 750 ml and urine output was 1100 ml during 133 min of anesthesia. Postoperative day 1 nasal desmopressin was started. Ten days later, partial tumor resection was performed. Anesthesia was induced with propofol and fentanyl and maintained with sevoflurane and remifentanil. Infusion volume was 610 ml, urine output 380 ml, and blood loss 151 ml during 344 min of anesthesia. Hemodynamic parameters were stable throughout the procedure. Pathology of the tumor was revealed to be germinoma. Bradycardia and hypotension experienced during the first surgery was suspected to be caused by preoperative hypovolemia brought by polyuria. Desmopressin was proved to be effective to treat excessive urine output and to maintain good perioperative water balance.

Recently available varicella vaccine titers are several dozen times higher than the formulation standard in accompanying information, i.e., > or = 1,000 PFU/dose. We investigated changes in immunogenicity associated with vaccination using a reduced dose whose virus titer was close to that used when the vaccine was developed, and examined the need for the virus titer presently used. In a non blinded study of 43 children with no history of varicella infection, we administered 0.1 mL of varicella vaccine (1/5 of the normal dose) to 20 children 1 year 0 month to 4 years 5 months old (median: 1 year 5 months) and the standard 0.5mL dose to 23 children 1 year 2 months to 3 years 7 months old (median: 1 year 9 months). We measured IAHA and gpELISA antibody titer before vaccination and 4 to 6 weeks after vaccination. We defined "positive" as > or = 2 fold of IAHA titer and > or = 50 U of gpELISA antibody titer. We administered an additional 0.5mL of varicella vaccine to children whose IAHA titer failed to show seroconversion and remeasured antibody titer 4 to 6 weeks after revaccination. IAHA seroconversion was 25.0% (5/20) and gpELISA seroconversion 55.0% (11/20) in the 0.1 mL vaccination group, which was lower than that of 76.2% (16/21) and 87.0% (20/23), IAHA p < 0.01, gpELISA p < 0.05, in the 0.5 mL vaccination group. We administered an additional vaccination to 19 children--15 in the 0.1 mL vaccination group and 4 in the 0.5 mL vaccination group-with 100% seroconversion for both methods. Mean antibody titer after revaccination in the 0.1 mL vaccination group (IAHA 2 (6.0), gpELISA 10 (3.7)) was higher than those in the 0.5mL vaccination group who seroconverted following initial vaccination (IAHA 2(4.5), gpELISA 10(2.6)) (p < 0.01). We also measured virus titer in the remaining vaccine following vaccination of 0.1 mL (n = 20), and estimated virus titer administered to the 0.1 mL vaccination group to be 2,600-6,400 PFU/ dose. Varicella vaccine immunogenicity decreased if dosage was reduced to 1/5 of the standard dose, indicating that the present virus titer is necessary to maintain adequate immunogenicity. An additional administration of the standard dose to children who failed to seroconvert after initial 0.1 mL administration produced high antibody titers thought to constitute a booster effect.

Mixed human feces were evaluated for simultaneous direct PCR detection of 3 food-borne bacteria--verotoxin-producing bacteria, Salmonella, and Shigella. Mixed feces concentrated approximately 2.5% in distilled water, were heated at 95 degrees C for 5 min. The heated suspension was then centrifuged and 5 microL of the supernatant poured into a 45 microL PCR mixture prepared to neutralize PCR inhibitors originating in biological samples. As a result of PCR under the above conditions followed by melting curve analysis (MCA), one positive fecal sample containing food-borne bacteria was detected from among 50 mixed fecal samples, showing the same sensitivity as individual cultivation. Results thus indicate that this method enables rapid, reliable, highly sensitive testing of many fecal samples--especially those of personnel handling food, which requires the simultaneous testing of many samples.

Surveillance is very important for preventing the nosocomial spread of methicillin-resistant Staphylococcus aureus (MRSA), and the pulsed-field gel electrophoresis (PFGE) method has long been used to identify the infection source and route as a molecular and epidemiological genotyping method. However, the use of the method in routine clinical laboratory measurements is difficult due to its complicated procedures. Since a molecular and epidemiological genotyping kit based on the POT (Phage Open-reading Frames Typing) method has been developed, we examined 192 MRSA isolates newly detected from inpatients in our hospital in 2010 in order to investigate the usefulness of POT for surveying outbreaks of MRSA. Among the 192 isolates 118 were suspected of nosocomial spread by the previous method, which defined a MRSA detection at more than 48 hours after admission as a nosocomial spread. The POT method was introduced at our laboratory in 2010, and we were able to recognize 38 patients as having strongly suspected nosocomial MRSA infection with the POT method taking into consideration the infection situation, such as places (wards and transfer) and time (date of admission and date of collected samples). Our Infection Control Division was confidently able to demonstrate the current condition of the nosocomial spread by providing the results to the clinical staff, who were also able to practice infection control confidently. We concluded that the POT method was very useful and convenient for investigating MRSA isolates and evaluating collected data because no particular analysis other than the digitizing electrophoretic pattern method was necessary.

A two-phase combined measles-rubella vaccine (MR) immunization schedule was introduced for age 1 and prior to primary school entry in Japan in April 2006. Further immunization was also introduced for 13 (Phase 3) and 18-year-old (Phase 4) cohorts for the 5-year period from April 2008 to March 2013. We surveyed Phases 3 and 4 MR immunization immunogenicity and safety. From August 2007 to December 2009, we conducted 3 Phase 3 and 15 Phase 4 immunizations. We then took paired serum samples (pre- and 4-6 weeks post-immunization), and measured measles antibody titers using hemagglutination inhibition (HI) and neutralizing test (NT), and rubella antibody titers using HI. Pre-positive measles HI antibody titer (> or = 8) was 72% (13/18) and pre-positive measles NT antibody titer (> or = 2) was 100% (18/18). Post-positive measles HI and NT antibody titers were 94% (17/18) and 100% (18/18). Mean post-immunization measles HI and NT antibody titers were significantly higher than pre-titers, with four-fold or greater increases seen in 9 (50%) and 6 (33%) subjects. Pre-positive rubella HI antibody titer (> or = 8) was 94% (17/18), and post-positive rubella HI antibody titer 100% (18/18). Mean post-immunization rubella HI antibody titer was significantly higher than pre-titer, with four-fold or greater increases seen in 8 subjects (44%). Paired HI antibody titers were measured in pre- and post-Phase 1 immunization for measles in 3 subjects and for rubella in 2 subjects. Those with post-Phase 1 measles HI antibody titers of 32, 64, and 128 yielded titers of 16, 8, and < 8 pre-Phase 3 or Phase 4 immunization, showing antibody reduction or seronegative conversion. Those with post-Phase 1 rubella HI antibody titers of 128 and 256 yielded titers of 64 and 32 in pre-Phase 4 immunization, showing antibody reduction. Seroconversion or four-fold or greater increases in titer were seen post-immunization in 60% (3/5) of these subjects. A clinical reaction survey of all subjects 4 weeks post-immunization, showed only 1 case of mild fever and no local or systemic adverse reactions such as generalized urticaria or anaphylaxis. In conclusion, Phases 3 and 4 MR immunogenicity was satisfactory.

A 24-year-old man was admitted with a 7-month history of non-productive cough, and recent onset of fever and progressive dyspnea. A chest X-ray film and computed tomography (CT) scan showed bilateral infiltrates that indicated pneumocystis pneumonia (PCP). A transbronchial lung biopsy specimen demonstrated Pneumocystis jirovecii infection on Grocott staining, and was positive for acid-fast bacilli without necrotizing granuloma, which indicated coinfection with both Pneumocystis jirovecii and Mycobacterium tuberculosis. A test for human immunodeficiency virus (HIV) infection was positive, and his CD4 + T-lymphocyte count was 92 cells per cubic millimeter. Chest CT findings and pathological findings.were atypical for active tuberculosis (TB). It is important that clinicians should be aware that HIV-infected patients may have concurrent pulmonary TB and PCP, because the diagnosis is difficult.

A total of 100 patients with benign prostatic hyperplasia (BPH) and overactive bladder (OAB) symptoms (BPH/OAB), enrolled between June 2006 to March 2008, were randomly divided into 2 groups of morning medication (M) and evening medication (E) groups, then 50 mg of naftopidil was given once a day after breakfast or supper for 8 weeks. Data were available for efficacy analysis on 80 patients (M group ; 43, E group ; 37). Naftopidil significantly improved the overall international prostatic symptom score ; from 19.2±7.9 to 11.7±5.8 in the M group and from 19.4±6.4 to 12.3±6.8 in the E group (p<0.0001), QOL score from 4.9±0.8 to 3.2±1.4 in the M group and from 5.0±0.8 to 3.6±1.3 in the E group (p<0.0001), and OAB symptom score from 7.8±2.6 to 5.0±2.5 in the M group (p<0.0001) and from 8.6±2.9 to 5.8± 3.3 in the E group (p<0.0001). There was no significant difference in the incidence of adverse effects between the M group (6.1%) and E group (2.2%). These results suggest that naftopidil improves storage symptoms as well as voiding symptoms regardless of timing of administration.

A case was presented of a 5-year-old girl who suffered an accidental dural puncture during placement of an epidural catheter under general anesthesia for orthopedic surgery. She complained of headache 4 days after the operation, which was relieved on supine position but became worse on sitting position. Her symptoms failed to respond to conservative management. An epidural blood patch was performed under general anesthesia and completely resolved her symptoms. The reported incidence of epidural blood patch for post dural puncture headache following accidental dural puncture in children is low. We outline this case and the consideration for management for epidural blood patch in pediatric patients.

The recovery support system of the drug addiction in Japan is inadequate. It causes because of having part in the problem by the concept that each field of the medical model, justice model and welfare model is different. Each organization should wrestle with new cooperation of the recovery support. It will be necessary for there to make the support system which mainly on a social-welfare model in future. It is necessary to let service provider of the welfare fill up more. I introduced the organization which participated in drug addiction and explained the present conditions and problems.

Double-balloon endoscopy (DBE) was developed as a new technique for visualization and intervention of the entire small intestine. It has been world-widely reported that DBE is very useful for not only diagnosis but also endoscopic therapy. In this paper, the principle of the DBE system and indication for DBE are described introductory. DBE should be performed considering differential diagnosis based on clinical information such as episode of bleeding, detailed case history and CT findings for making diagnosis efficiently.

Squamous cell carcinoma antigen (SCCA) is a diagnostic tumor marker for the advanced uterine, cervix and lung tumor. Although SCCA is a prognostic indicator for some tumors, recent progress of this marker has shown that the SCCA could also be found in the serum of nonmalignant disease such as renal failure and others. Here, we report a case of spuriously high level of SCCA in patient without carcinoma, renal failure, head-and-neck disease and lung disease. An early fifties female who had been undergone the diagnostic conization for high-grade cervical intraepithelial neoplasia ten years ago and observed without special treatment with around 20ng/ml level of SCCA. She has no signs of tumor, renal failure, head-and-neck disease or lung disease until now. The high performance liquid chromatography with Superdex 200 showed the molecular weight of the major part of SCCA of the patient is more than 160 kDa and the part of 45 kDa, the same molecular weight as lung tumor, is trace amount. Moreover, the ultrafiltration analysis showed the SCCA of the present case did not penetrate the 100 kDa cut-filter, but SCCAs with other patients with uterine, cervix, lung tumor and renal failure did penetrate the filter. In this case, the analysis of molecular weight of SCCA using HPLC gel filtration and ultrafiltration is useful to rule out spuriously elevated SCCA.

The Tokyo metropolitan hospital society of chief medical technologist has carried out a staining survey once a year since 1992. This staining survey is performed to plan improvements of the staining technology at each hospital and reduction of differences among hospitals. This report describes the examination results for PAS stain, Papanicolaou stain, and PAM stain.

Background: Invasive pulmonary aspergillosis (IPA) occurs predominantly in immunocompromised hosts, however increasing numbers of cases of IPA have been reported among basically immunocompetent patients who have some pulmonary abnormalities such as lung cancer and chronic obstructive pulmonary disease (COPD)., Case: Case 1. A 67-year-old man was admitted because of hemoptysis and purpura. He had COPD and small cell lung cancer and had finished chemotherapy 5 years previously. Chest X-ray showed pneumonia-like infiltration in his right lower lung field, and marked thrombocytopenia was pointed out. We started antibiotics and corticosteroids for community-acquired pneumonia (CAP) and idiopathic thrombocytopenic purpura. During treatment, we found Aspergillus fumigatus in his sputum culture and therefore added antifungal agents to his treatment. Despite intensive care, he died due to multi-organ dysfunction. Case 2. An 80-year-old man was admitted with fever and productive cough. He had COPD and non-small cell lung cancer and finished chemotherapy 2 months previously. Chest X-ray showed pneumonia-like infiltration in his right upper lung field. We started antibiotics and corticosteroids for acute exacerbation of COPD because of CAP. Several weeks later, after we observed initial improvement of his condition, pneumonia-like infiltration re-developed and Aspergillus fumigatus was detected in his sputum. We started antifungal agents and the treatment of IPA was successful, but he died because of idiopathic perforation of the sigmoid colon., Conclusion: In patients without myelosuppression, IPA could develop pneumonia-like pulmonary infiltrations.

A traditional Chinese herbal medicine, Kampo medicine, maoto, has been widely used in the treatment of febrile symptoms caused by viral infection. This herbal extract granule for oral use, however, is not well accepted by infants or young children due to its unpleasant taste and odor. Therefore, we prepared Kampo medicine, maoto, suppository and investigated the pharmaceutical and clinical efficacy of the suppository. Kampo medicine, maoto, granules were micro-pulverized and homogeneously dispersed into Hosco-H15 to prepare suppositories containing 0.25 to 1.0 g herbal extract by the conventional fusion method. Content of l-ephedrine, an index compound of Kampo medicine, maoto, in the extract granules and suppositories was determined by using a high performance liquid chromatographic method. Physicochemical experiments revealed that the suppository containing 0.5 g herbal extract had the most suitable melting point of 34 degrees C. Contents of l-ephedrine in the suppository were constant, 93-96% of those in the same amount of the extract granules in different three lots. Upper and lower portions of the suppository had the same content of l-ephedrine. The suppository maintained more than 95% of l-ephedrine content through 6 months at 4 degrees C, room temperature and 40 degrees C, although maldistribution of the extract constituent was observed after storage at 40 degrees C. The suppository was administered to 21 pediatric febrile patients at a dose of 1/3 to 2 full pieces depending on their body weight and physical status. Significant reduction (p<0.001) of body temperature from 39.5 to 37.5 degrees C without serious adverse effects was observed in 17 patients who were monitored the clinical effects on the febrile symptoms. In conclusion, Kampo medicine, maoto, suppository was found to satisfy the physicochemical quality and quantity standards as well as to be clinically applicable to neonates, infants and children with viral febrile symptoms without any adverse effects.

Severe advanced head and neck carcinoma which can not be removed via surgical procedure combined with a large lymph node metastasis has a poor prognosis. We administered concurrent chemoradiotherapy with S-1 for a lower gingival carcinoma. As a direct result, we discovered that the treatment greatly reduced the size of tumor, and we consider that this treatment prolonged the patient.s life. The treatment results suggest that the so-called dormancy state of the tumor was continued. In this case study, radiotherapy with S-1 showed a highly effective response from the viewpoint of QOL improvement.

Background: Many drugs and the combinations of drugs are recommended for each treatment step in bronchial asthma. However, there are few issues examined about the optimal drug and combination of drugs in a long term prognosis. In this study, we investigated the optimal drugs and combinations of drugs from a point of view of prognosis., Methods: One hundred and ninety four patients who visited our hospital for treatment from November, 2003 to October, 2004 and were managed according to GINA guideline were surveyed retrospectively. We compared the rate of step up and the frequency of urgent visit and urgent hospitalization in one year between drug groups in each treatment step., Results: The rate of step up was significantly higher in leukotriene receptor antagonist (LTRA) group than in inhalation corticosteroid (ICS) group and theophylline group in Step 2. The frequency of urgent visit and urgent hospitalization was significantly higher in ICS+LTRA group than in ICS+theophylline group and ICS+long-acting beta 2-agonist (LABA) group in Step 3., Conclusion: There is a possibility that the prognosis becomes bad when we use LTRA in the practical treatment according to GINA guideline.

Irinotecan hydrochloride shows much different responses in each patient, and it has severe adverse effects. Therefore, a sensitive marker for the side effect of irinotecan on immunotoxicity may be able to prevent the severe complications by the early detection. We have recently developed a method to assess the immunotoxicity by measuring the productivity of TNF-alpha from whole blood containing monocytes when stimulated by lipopolysaccharide. By using this method, the effects of continuous low-dose irinotecan therapy on immunotoxicity were assessed in 10 patients with advanced gastric or colon cancer. When compared this method with the others such as white blood cell count, lymphocyte blastoid transformation by phytohem agglutinin (PHA), and natural killer cell activity in terms of the sensitivity, immunotoxicity by this method was found earlier than the other methods. Because our original method is easy to perform and sensitive as compared to the conventional methods, it can be widely used as one of the laboratory tests useful for patients treated with immunosuppressive agents.

Sho-saiko-to (Xiao-Chai-Hu-Tang), one of the major traditional Chinese medicines, has been frequently prescribed with other synthetic or biotechnological drugs for the treatment of various acute or chronic diseases in Japan, and thus it is important to understand the interactions between Sho-saiko-to and coadministered drugs. This paper reviews the effects of Sho-saiko-to on the pharmacokinetics and pharmacodynamics of concomitant drugs in the gastrointestinal tract. Sho-saiko-to slightly hastens the gastrointestinal absorption of the sulfonylurea compound tolbutamide. Furthermore, it is considered that the increase in the gastrointestinal absorption rate by Sho-saiko-to may potentiate the hypoglycemic effects of tolbutamide in the early period after oral administration. Sho-saiko-to can facilitate the epithelial membrane permeability of tolbutamide at an early phase across the rat jejunum in situ and Caco-2 cell monolayers. It is also suggested that Sho-saiko-to enhances the energy-dependent transport of tolbutamide and has an inhibitory effect on the passive paracellular transport of tolbutamide in Caco-2 cells. This result might be related to the accelerated in vivo absorption rate of tolbutamide by concomitant dosing with Sho-saiko-to in rats. In addition, Sho-saiko-to has inhibitory effects on the efflux pump mediated by MDR1, and it appears that the crude constituents in Glycyrrhizae radix, glycyrrhizic acid and liquiritin, contribute to MDR1 suppression.

We treated a patient with lung adenocarcinoma who responded to chemotherapy with vinorelbine (VNR) plus carboplatin (CBDCA) on an outpatient basis. The patient was a 68-year-old man. He visited a local physician complaining of wet coughing, headache and general fatigne. The symptoms remained unchanged and the patient was admitted to our department for treatment in June 2000. A massive shadow in the right upper lobe and multiple cerebral metastases were found. Based on this, the diagnosis was lung adenocarcinoma (T3N2M1, clinical stage IV). Whole-brain irradiation and systemic chemotherapy were initiated from July 2000. The patient received 1 course of systemic chemotherapy with vindesine (VDS) plus cisplatin (CDDP) on an inpatient basis. This regimen was replaced with combination therapy of paclitaxel (TXL) plus CBDCA in the outpatient setting, along with VNR plus CBDCA due to side effects caused by TXL. The cerebral metastases almost disappeared due to whole-brain irradiation. Chest CT after 3 courses revealed a reduction in primary tumor size. The VNR plus CBDCA combination therapy was continued for a further 6 courses. As the result, neither the primary tumor nor the cerebral metastases enlarged. The combination therapy with VNR plus CBDCA seems to be a useful regimen that can maintain high QOL and be conducted for a long term on an outpatient basis.

A 64-year-old man was scheduled for resection of brain tumor in the prone position. He had been on hemodialysis for three years. Anesthesia was induced using propofol, fentanyl, and vecuronium, and maintained with isoflurane and nitrous oxide in oxygen. Transesophagial echocardiography (TEE) was useful for maintaining fluid balance. To prevent bleeding tendency and to maintain electrolyte balance, continuous hemodiafiltration (CHDF) without anti-coagulant drugs was utilized for fluid management. Surgery was performed in the lateral position since the application of CHDF was impossible in the prone position. Approximately 3500 ml of blood was lost and 18 units of packed blood cells and 18 units of flesh frozen plasma were administered. We occasionally checked activated clotting time and platelet count during surgery, but they were kept in normal ranges. In this case, we were able to achieve proper intraoperative fluid management using TEE and CHDF.

Hypercalcemia of malignancy is a common problem for cancer clinicians. Treatment of hypercalcemia of malignancy with pamidronate in a patient with advanced recurrent oral cancer is reported herein. The patient was a 36-year-old man who had neck lymph node metastases due to recurrence of squamous cell carcinoma of the buccal mucosa and complained of cloudiness of consciousness due to hypercalcemia. The patient was administered pamidronate. A fine reduction in serum calcium was observed and cloudiness of consciousness was also alleviated. Although treatment of hypercalcemia with pamidronate is palliative, it is effective against the deterioration of quality of life.

In June 2001, we joined the regional anesthesia & Pain Medicine Delegation to the People's Republic of China. We visited 10 large hospitals in Beijing, Shanghai and Guiyang. We observed clinical anesthesia in operating theater and TCM (Traditional Chinese Medicine) in out-patient clinics. Acupuncture anesthesia was not popular and less frequently used for clinical anesthesia ranging 0 to 10%. Many surgical cases were done by Western medicine similar to Japan and USA. General anesthesia machines were imported from Germany and USA. All endo-tracheal tubes and catheters were made in China. But they lack the organization of anesthesia societies and system of specialization in the field of anesthesia.

Cervi Parvum Cornu has been widely used as an agent in commercially available tonic medicines. The establishment of the method for the identification of each agent, especially crude drugs in formulations, is very important from the viewpoint of the quality control of drugs. In this paper, we reported the examination on the extraction method of DNA from the formulations, and also on the PCR method using four sets of primers, amplifying the DNA fragments of the regions of 12S rRNA and/or cytochrome b genes. The same size of DNA fragments as in the Cervi Parvum Cornu reference sample were found in all PCR products obtained from four commercial tonic medicines investigated. Therefore, it was confirmed that Cervi Parvum Cornu was contained in all the tonic medicines used. The PCR method was found to be a useful method for the identification of Cervi Parvum Cornu in tonic medicines and the DNA fragments amplified by the PCR method was clarified to be also helpful materials as index constituents for Cervi Parvum Cornu.