上原 由紀

This cross-sectional study from January 2012 to December 2012 aimed to examine the sex-specific association between serum uric acid (SUA) levels/hyperuricemia and hypertension among Japanese patients. SUA level, medical histories, and lifestyle-related items were collected from 85,286 of 136,770 participants. Among those with hyperuricemia, the median age was 46 years and 97% were men, which was significantly different than those without hyperurecemia (44 years and 56%, respectively; P<.01). Hyperuricemia was 1.79 times more likely in hypertensive men than normotensive men and almost six times more likely in hypertensive women (odds ratio=5.92 and adjusted odds ratio=1.33 for men and adjusted odds ratio=1.81 for women) after multivariate analysis. SUA quartiles positively correlated with systolic and diastolic blood pressures in both sexes. Hyperuricemia and SUA levels were significantly associated with hypertension in both sexes. These findings underscore the importance of maintaining normal SUA levels to manage and prevent hypertension. Better management of SUA as well as blood pressure may have potential in preventing future cardiovascular disorders.

Abacavir/lamivudine (ABC/3TC) is a nucleoside reverse transcriptase inhibitor used for treating human immunodeficiency viral (HIV) infections. Hypersensitivity reactions such as skin eruptions caused by ABC are well-known, but rarely occur in Asians. Raltegravir (RAL) is an integrase strand transfer inhibitor, that is now increasingly, used for treating HIV infections because it has few adverse effects. This retrospective analysis assessed the efficacy and safety of combined ABC/3TC and RAL in both treatment-naïve and -experienced Japanese patients with HIV infections. In all 11 treatment-naïve patients (100%), virological suppression to undetectable level was achieved. Liver transaminases, renal function, and serum lipid profiles showed no exacerbations up to 48 weeks of treatment. In 12 patients who were switched from previous regimens to ABC/3TC and RAL, HIV viral load was undetectable in 11 patients (91.6%), but remained detectable in 1 patient with poor adherence. Major reasons for switching regimens to ABC/3TC and RAL were hyperlipidemia and nausea. After switching, these adverse effects improved, and no new adverse effects were observed. Despite the small number of participants in this study, the results support the combination of ABC/3TC and RAL as a possible treatment choice in Japanese individuals with HIV-infection.

We report the case of a 58-year-old man presenting with chest pain who underwent percutaneous coronary intervention (PCI). The patient subsequently developed a fever over 38°C, pain on micturition, and cloudy urine 3 days following PCI. Urine cultures were positive for Escherichia coli and Enterococcus faecalis, whereas blood cultures were negative. Arthritis occurred two weeks following urinary tract infection (UTI). We herein present a rare case of reactive arthritis caused by UTI following PCI.

Streptococcus agalactiae (S. agalactiae) is a major cause of invasive disease in neonates and pregnant women, but has also recently been observed among non-pregnant adults, especially elderly persons or persons with underlying chronic disease. S. agalactiae is also a rare cause of infective endocarditis, and most cases require early surgery. We report the case of a 43-year-old previously healthy man who experienced rapid progressive culture-negative infective endocarditis with aortic valve vegetation and severe aortic regurgitation, which was complicated by lumbar spondylodiscitis. Emergency aortic valve replacement was performed on the day of his admission, which revealed a congenital bicuspid aortic valve was ruptured by the vegetation. The resected aortic valve specimen was submitted for 16S ribosomal RNA gene sequencing, which revealed that the pathogen was S. agalactiae. Therefore, S. agalactiae should be considered a potentially causative pathogen in cases of rapid progressive infective endocarditis, even if it occurs in a non-pregnant immunocompetent adult.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is one of the worldwide concerns of antimicrobial chemotherapy. An accumulation of ten patients in five families (A-E) suffering from skin and soft tissue infection (SSTI) of CA-MRSA was experienced in 2012, in Fuchu-shi, Tokyo, Japan. Molecular epidemiological investigation was performed for the 10 MRSA strains obtained from 8 children and 2 of their parents to assess endemic patterns of CA-MRSA in the community. Results of molecular typing, presence of toxin genes and antimicrobial susceptibilities were analyzed combined with the patients' clinical information. Each family had its own unique MRSA strain: A, ST30-SCCmec IVd; B, ST8-SCCmec IVd; C, ST8-SCCmec IVa; D, ST8-SCCmec IVl; E, ST8-SCCmec IVl and ST858-SCCmec IVl. Seven strains from the families A-C carried Panton-Valentine leukocidin gene. Three strains from the families D and E carried toxic shock syndrome toxin gene. Strains belonged to the same family demonstrated genetically related banding patterns of pulsed-filed gel electrophoresis. The family C experienced intrafamilial transmission of USA300-0114. Our data showed the MRSA clones disseminating in this community were highly diverse. They contained USA300-0114 clone, the rapidly distributing clone in the world, as well as MRSA clones identified in Japan. Our results suggested intrafamilial transmission of MRSA could be initial phenomenon of wide transmission in a community, therefore CA-MRSA SSTI in children and their family members should be monitored closely in order to notice the spread of highly pathogenic and transmittable strains.

OBJECTIVE: To evaluate the diagnostic accuracy of the rapid influenza antigen detection test (RIADT) and determine which symptoms are relevant to results. DESIGN: Single-centre, cross-sectional study. SETTING: Primary care centre, Tokyo, Japan. PARTICIPANTS: 82 consecutive outpatients presenting with upper respiratory symptoms and fever ≥37°C at any time from symptom onset, between December 2010 and April 2011. MAIN OUTCOME MEASURES: Results of history and physical examination including age, sex, temperature, time of test from symptom onset, vaccination record and current symptoms (sore throat, arthralgia and/or myalgia, headache, chills, cough and/or throat phlegm, nasal discharge) were recorded. The RIADT and a fully automated respiratory virus nucleic acid test (Verigene Respiratory Virus Plus; VRV), the latter being the gold standard, were performed. Patients were divided into four groups: false negative (FN), RIADT- and VRV+; true positive (TP), RIADT+ and VRV+; true negative (TN), RIADT- and VRV-; and false positive, RIADT+ and VRV-. Groups were compared regarding age, sex, temperature, time of test from symptom onset, vaccination record and symptoms. RESULTS: RIADT sensitivity, specificity, positive predictive value and negative predictive value were 72.9% (95% CI 61.5% to 84.2%), 91.3% (79.7% to 102.8%), 95.6% (89.5% to 101.6%) and 56.8% (40.8% to 72.7%), respectively. Time from symptom onset to test was shorter for the FN group than the TP group (p=0.009). No significant differences were detected for the other factors assessed. Results revealed higher temperatures for FN than TN patients (p=0.043), and more FN than TN patients had chills (p=0.058). CONCLUSIONS: The RIADT sensitivity was low, due to early administration of the test. In the epidemic season, the RIADT should not be used for suspected influenza until 12 h after symptom onset. A positive RIADT firmly supports the influenza diagnosis; a negative result does not confirm its absence. High fever and chills might indicate influenza, but additional tests are sometimes necessary.

Methicillin-susceptible S. aureus (MSSA) changes to methicillin-resistant S. aureus upon the acquisition of Staphylococcal Cassette Chromosome mec (SCCmec), a genomic island that encodes methicillin resistance. All SCCmec elements reported to date share four common characteristics: (1) carrying the mec gene complex (mec); (2) carrying the ccr gene complex (ccr); (3) being flanked by characteristic nucleotide sequences, inverted repeats, and direct repeats, at both ends; and (4) being integrated at the integration site sequence (ISS) for SCC, which is located at the 3'-end of orfX or at the extremity of the SCC element. SCCmec elements in S. aureus are classified into different types based on the combination of mec and ccr, which share variations, five classes in mec and eight in ccr. To date, at least 11 types of SCCmec elements have been identified. Regions other than mec and ccr within the SCCmec element are designated as "joining regions" (J-regions), which are classified into three subgroups, J1-3. Many J-region variants have been identified among the SCCmec elements of types I-V. We herein describe PCR methods to type SCCmec elements by first identifying the mec and ccr type, and then identifying genes in the J-regions.

OBJECTIVE: The causes of fever of unknown origin (FUO) vary depending on the region and time period. We herein present a study of patients with classic FUO where we investigated differences based on patient background factors, such as age and causative diseases, and changes that have occurred over time. METHODS: We extracted and analyzed data from the medical records of 256 patients ≥18 years old who met the criteria for classic FUO and were hospitalized between August, 1994 and December, 2012. RESULTS: The median age of the patients was 55 years (range: 18-94 years). The cause of FUO was infection in 27.7% of the patients (n=71), non-infectious inflammatory disease (NIID) in 18.4% (47), malignancy in 10.2% (26), other in 14.8% (38), and unknown in 28.9% (74). The most common single cause was human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (n=17). NIID and malignancy were more common in patients ≥65 years old than in patients <65 years old. During 2004-2012, compared to 1994-2003, infections and "other" causes were decreased, whereas NIID, malignancy, and unknown causes were increased. CONCLUSION: FUO associated with HIV/AIDS is increasing in Japan. In addition, as in previous studies in Japan and overseas, our study showed that the number of patients in whom the cause of FUO remains unknown is increasing and exceeds 20% of all cases. The present study identified diseases that should be considered in the differential diagnosis of FUO, providing useful information for the future diagnosis and treatment of FUO.

Hospital-wide active surveillance for methicillin-resistant Staphylococcus aureus (MRSA) targeted to adult patients with a history of MRSA carriage within the past 5 years was performed in Juntendo University Hospital (JUH) over a 2-year period. In the first year, MRSA screening culture was ordered by physicians in charge. In the second year, infection-control practitioners (ICPs) took samples for active surveillance culture. The average monthly transmission rate of MRSA in JUH was 0.35 per 1,000 bed-days in the first year and decreased significantly to 0.26 per 1,000 bed-days in the second year (P < 0.05). In the second year, more active commitment of ICPs to MRSA screening was effective in improving the performance rate of screening, shortening turn-around time of screening results, and decreasing transmission rate. Increasing compliance with active MRSA surveillance by involvement of ICPs, targeting patients with a previous history of MRSA carriage in the previous 5 years, was effective to control nosocomial MRSA transmission.

We performed a cross-sectional study that included 100 HIV-infected Japanese men without hemophilia to examine the influence of smoking on HIV infection. History of smoking was obtained using a questionnaire. The percentage of current smokers was 40 % and was the highest (50 %) among men in their forties. The mean Brinkman index (BI, number of cigarettes smoked per day multiplied by years of smoking) was 450. The percentage of patients with a BI ≥600 was significantly higher in patients with an AIDS-defining event than in those without an AIDS-defining event. A BI ≥600 was associated with an AIDS-defining event. Reducing smoking appears to be critical to enhancing disease management efforts in Japanese men with HIV.

Patients and healthcare workers in a Japanese haemodialysis clinic were investigated for nasal carriage of meticillin-resistant Staphylococcus aureus (MRSA). MRSA carriage was found in 10 (8.9%) of 112 patients in the first year and four (3.9%) of 103 patients in the second year. All isolated MRSA samples carried staphylococcal cassette chromosome mec type II or III and classified as clonal complex 5, which were common as healthcare-associated strains. Pulsed-field gel electrophoresis indicated horizontal transmission limited to two pairs of patients in one session. One of 54 healthcare workers carried MRSA genetically unrelated to patients' strains. Infection control measures based on the US Centers for Disease Control and Prevention's recommendation showed limited spread of MRSA in a haemodialysis room. © 2013 The Healthcare Infection Society.

Although coagulase-negative staphylococci (CoNS) is a frequent cause of prosthetic valve endocarditis, native valve endocarditis (NVE) caused by CoNS is not commonly seen. Its high mortality is well known; however, there are no systematic reports published in Japan. We herein report the cases of two Japanese patients with CoNS NVE who were admitted to our hospital located in Tokyo and conduct literature searches on CoNS NVE in Japan from 1983 to March 2012 using PubMed and ICHUSHI WEB (Japan Medical Abstract Society). We also summarize the features of 22 Japanese patients with CoNS NVE, including our patients.

Background: Innate immunity is generally impaired in chronic renal failure (CRF). Mannose-binding lectin (MBL) has an important role in first-line host defense against pathogens via the lectin pathway. We recently reported that functional MBL was significantly lower in CRF patients than in healthy subjects. In this study, we aimed to determine whether functional MBL would be improved following hemodialysis (HD) therapy. Methods: This study included 22 patients with end-stage renal disease (ESRD) on maintenance HD. Functional MBL was measured every 6 months for 1 year after HD using an enzyme-linked immunosorbent assay. Results: Median serum functional MBL levels of ESRD patients were significantly higher after 6 and 12 months than at the start of HD therapy (p &lt; 0.05 and p &lt; 0,01, respectively). Furthermore, median functional MBL levels at 12 months were significantly higher than those at 6 months (p &lt; 0.05). Conclusions: We found significant increases in serum functional MBL levels in patients on HD. Our results indicated that HD tailored to remove uremic toxins could improve functional MBL levels in these patients. Copyright (C) 2012 S. Karger AG, Basel

INTRODUCTION: Lactococcus garvieae is a well-recognized fish pathogen, and it is considered a rare pathogen with low virulence in human infection. We describe the 11th case of L. garvieae infective endocarditis reported in the literature, and the first reported case in Japan. CASE PRESENTATION: We report a case of a 55-year-old Japanese woman who had native valve endocarditis with L. garvieae. The case was complicated by renal infarction, cerebral infarction, and mycotic aneurysms. After anti-microbial treatment, she was discharged from the hospital and is now well while being monitored in the out-patient clinic. CONCLUSION: We encountered a case of L. garvieae endocarditis that occurred in a native valve of a healthy woman. The 16S ribosomal RNA gene sequencing was useful for the identification of this pathogen. Although infective endocarditis with L. garvieae is uncommon, it is possible to treat high virulence clinically.

We assessed the utility of reporting direct blood Gram stain results compared with the results of positive blood cultures in 482 episodes, and monitored the impact on the selection of antimicrobial treatment. We found that the groups: "Staphylococcus species (spp.)", "Pseudomonas spp. and related organisms", and "Yeasts" identified in this way perfectly matched those on later culture identification. When the report indicated "Staphylococcus spp." or "Pseudomonas spp. and related organisms", the physicians started or changed antimicrobials suitable for these bacteria more frequently than "Other streptococci" and "family Enterobacteriaceae" (p < 0.05). The incorrect recognition of Acinetobacter spp. and Pseudomonas spp. as "family Enterobacteriaceae" is still the most challenging problem in this context, but these microorganisms seemed to be cultured from patients in some special departments and clinical conditions, including malignant diseases and chemotherapy. In conclusion, Gram-stain results that definitively identify "Staphylococcus spp.", "Pseudomonas spp. and related organisms", and "Yeasts" can be reliably and rapidly provided by clinical laboratories, and this has a significant impact on the early selection of effective antimicrobials. In case of patients at a high risk of non-fermentative gram-negative rod infection, we have to consider the selection of anti-pseudomonal agents while awaiting culture identification and susceptibility tests. Further investigation is needed to assess the clinical impact of reporting Gram-stain results in the presence of bacteremia.

We had encountered a 74-year-old woman on hemodialysis therapy suffering from liver abscess of Actinomyces israelii. Percutaneous drainage of the abscess before starting antimicrobial therapy followed by correct microbiological identification and susceptibility test led us to determine long treatment with ampicillin and to a successful outcome. Periodontitis was thought to be a possible entry of actinomyces. Hepatic actinomycosis should be recognized as one of the important infectious diseases among patients of end-stage renal disease.

We assessed the usefulness of reporting direct blood Gram stain results compared with the results of positive blood cultures in 482 episodes and monitored impact on selection of antimicrobial treatment. We found that the reporting groups "Staphylococcus spp," "Pseudomonas spp and related organisms, and "yeasts" identified in this way matched perfectly with later culture identification. When the report indicated Staphylococcus spp or Pseudomonas spp and related organisms, physicians started or changed antimicrobials suitable for these bacteria more frequently than when "other streptococci " and "family Enterobacteriaceae " were reported (P &lt; .05). Incorrect recognition of Acinetobacter spp as Enterobacteriaceae family is still the most challenging problem in this context. Gram stain results that definitively identify Staphylococcus spp, Pseudomonas spp and related organisms, and yeasts reliably can be rapidly provided by clinical laboratories; this information has a significant impact on early selection of effective antimicrobials. Further investigation is needed to assess the clinical impact of reporting Gram stain results in bacteremia.

Background/Aims: Seasonal variations in laboratory test results have been pointed out in dialysis patients. Although the mechanism for this phenomenon is not clear, this could result in changes in dialysis and medication prescriptions. We investigated the effect of the circannual rhythm on laboratory test parameters in chronic haemodialysis patients. Methods: Data of 38 laboratory test parameters were collected every month and analyzed for 150 stable haemodialysis patients, with non-linear sine wave regression and paired t test between data of peak and trough months. Results: Serum urea nitrogen, unsaturated iron binding capacity, lactate dehydrogenase, alkaline phosphatase, amylase, and neutrophil count showed significant circannual rhythms with high amplitudes. Additionally, serum creatinine, uric acid, chloride, calcium, phosphate, magnesium, total cholesterol, total protein, leucocyte count, mean corpuscular haemoglobin level, mean corpuscular haemoglobin concentration, and platelet count showed significant circannual rhythms with little amplitudes. Conclusions: The circannual rhythm of laboratory test parameters could be attributed to seasonal variations in food intake. Awareness of these variations should be taken into account in the interpretation of laboratory results. Copyright (c) 2008 S. Karger AG, Basel.

Disseminated trichosporonosis is known to be a severe opportunistic mycosis and has a high mortality rate. In autopsy cases, it is often difficult to diagnose as trichosporonosis because the causative Trichosporon species are pathologically similar to other fungi, especially the Candida species. Immunohistochemical analysis is essential for the differential diagnosis, but an antibody to Trichosporon is not available commercially. In the present study, we investigated the supplemental utility of nested polymerase chain reaction (PCR) for the pathological diagnosis of trichosporonosis from formalin-fixed and paraffin-embedded tissues. Total DNA was purified from 30 major organs in three autopsy cases, and Trichosporon DNA was specifically amplified by nested PCR using three sets of primers. Of 22 organs in which Grocott's stain was positive for fungal infection, 170- and 259-bp PCR products were detected in 20 (91%) and 12 (55%) organs, respectively. In short-term fixation (about 1 day), these bands were highly detected in ten (100%) and nine (90%) organs, whereas the detection efficiency tended to decrease after long-term fixation and decalcification. No PCR product of 412 bp was detected in any organs. These findings suggest that nested PCR from short-term-fixed tissues is useful for supportive pathological diagnosis of disseminated trichosporonosis.

Patients receiving hemodialysis are generally considered to be at increased risk of developing tuberculosis. In the current study, in order to evaluate the usefulness of serological tests in dialysis patients, serum antibodies for tuberculous glycolipids antigen (TBGL) and for lipoarabinomannan (LAM) were measured in hemodialysis patients. The present study included 243 hemodialysis patients. Serum antibodies for TBGL and LAM were measured. Tuberculin skin tests were carried out and chest X-rays evaluated at the same time. There were no patients with active tuberculosis at the time of blood sampling. Thirty-six patients (14.8%) and 25 patients (10.3%) were positive for anti-TBGL antibody and anti-LAM antibody, respectively. One hundred and fifty-five patients (63.8%) were positive for tuberculin skin testing and 123 patients (50.6%) had old pulmonary tuberculosis on their chest X-ray. There was no significant correlation between the results of anti-TBGL antibody and anti-LAM antibody. There were no relationships among the results of tuberculin skin test and the two serological tests. However, positivity of anti-TBGL antibody and anti-LAM antibody was significantly higher in patients with findings of old tuberculosis on the chest X-ray than those without findings. The current results show that these serological tests are positive more frequently in hemodialysis patients without any proof of active tuberculosis than in healthy subjects (2%) and careful interpretation is necessary for relevant results.

As there is a high risk of indirect and direct transmission of infectious agents in chronic hemodialysis, infection control procedures should be established in dialysis units. This paper presents the findings of a questionnaire designed to survey the current status of infection control procedures in hemodialysis settings. Two hundred and forty-three hemodialysis units in Japan were surveyed. Nearly 90% of hemodialysis units reported compliance with each procedure recommended by the Center for Disease Control and Prevention in the United States, including use of disposable gloves, handling of non-disposable or non-single-use items, and routine serological testing of blood-borne viruses. However, more than 50% of units reported that they did not comply with recommendations concerning some procedures, such as places for preparing medications and their delivery, clean areas in the units, vaccination for hepatitis B, and additional measures for hepatitis B surface antigen (HBs-Ag) positive patients. Especially, the concept of universal precautions seemed to be misunderstood in units with a high prevalence of anti-hepatitis C antibody-positive (anti-HCV Ab-positive) patients. In conclusion, further intensive education and training will be necessary to establish infection control procedures.

It is reported that urinary ATP concentration analysis is useful for determining urinary tract infection and renal damage caused by drugs. By means of the firefly luciferin-luciferase method, we determined the reference value of urinary free ATP and evaluated the effects of urine sediments and conditions of storage. The reference value was established as 1.77 × 10 -10∼7.70 × 10-9M using urine samples obtained from 63 outpatients who seemed to have no renal disease. There was no significant difference in ATP concentration between 33 males and 30 females. No significant changes were observed in 11 healthy volunteers during a 1-year period. Within-run reproducibility of ATP was satisfying (8.28% and 11.4% of coefficient value in low and high concentration samples, respectively). ATP concentration was significantly decreased after centrifugation (p &lt 0.05) and after filtration (p &lt 0.01). The amounts of the red blood cells (RBC) and white blood cells (WBC) in samples whose ATP concentration was decreased after centrifugation or filtration were significantly higher than those in samples whose concentration did not decrease (p &lt 0.05). Urine containing many RBCs and/or WBCs might show an artificially higher ATP concentration if no preparations has been performed. There were significant positive correlations between the ATP concentrations before and after refrigeration, but no correlations before and after freezing. It is concluded that the reference value of urinary free ATP concentration was 1.77 × 10-10∼7.70 × 10-9 M and that care is required in the estimation of urinary ATP concentrations in samples containing many sediments, especially with WBC and RBC.