Adherence to clinical practice guidelines for the management of Clostridium difficile infection in Japan: a multicenter retrospective study.

This study was conducted to investigate the adherence to clinical practice guidelines (CPGs) for Clostridium difficile infection (CDI). A retrospective multicenter observational study was conducted via chart review at four teaching hospitals in Japan from April 2012 through September 2013. CDI was diagnosed based on positive identification of CD toxin by enzyme immunoassay testing. CDI patients were divided into non-severe and severe groups according to the severity criteria of four published guidelines (SHEA/IDSA 2010, ACG 2013, ESCMID 2009, HPA/DH 2008). Three parameters were assessed in association with disease severity: adherence to treatment guidelines, prognosis, and relapse rate. In total, 170 patients were diagnosed with CDI (1.04 cases per 10,000 patient-days). The 30-day all-cause mortality and recurrence rates were 13% and 14%, respectively. CPGs adherence ranged from 52% to 70% in the non-severe group and from 8.5 to 23% in the severe group (P < 0.01). Among severe CDI patients, no significant difference in mortality or recurrence was found between the patients whose treatments adhered and did not adhere to the CPGs. CPGs adherence was low, especially for patients with severe CDI. Improved guideline adherence and more accurate definitions of severity based on prognosis are needed for appropriate CDI management.

Hydroxyurea-induced foot ulcer in a case of essential thrombocythaemia.

OBJECTIVE: To illustrate the association between hydroxyurea and the development of ulcers. METHOD: A case study is presented, in which histological changes, mean corpuscular volume (MCV) and transcutaneous oxygen tension (TcPO2) were all measured and analysed, both during hydroxyurea treatment and following it's discontinuation. RESULTS: Two months following the cessation of hydroxyurea therapy, the patient's ulcer had healed completely. Biopsy specimens taken before and after its discontinuation showed a considerable improvement in vascularity, with a capillary density 6.28 times higher after discontinuation of the drug. TcPO2 was just 8mmHg at the first measurement, and this increased to 65mmHg at the second. CONCLUSION: These findings suggest deficient neovascularisation and circulation during hydroxyurea treatment. Changes in MCV also appeared to have an effect on the progress of wound healing, which supports the hypothesis that macroerythrocytosis may be involved in the development of these rare ulcers, via impairment of the microcirculatory rheology.

Fluoroquinolones versus trimethoprim-sulfamethoxazole for the treatment of Stenotrophomonas maltophilia infections: a systematic review and meta-analysis.

BACKGROUND: Fluoroquinolones are a popular alternative to trimethoprim-sulfamethoxazole for Stenotrophomonas maltophilia infections. OBJECTIVES: To compare the effects of fluoroquinolones and trimethoprim-sulfamethoxazole on mortality of S. maltophilia infections. DATA SOURCES: PubMed and EMBASE. STUDY ELIGIBILITY CRITERIA: Clinical studies reporting mortality outcomes of S. maltophilia infections. PARTICIPANTS: Patients with clinical infections caused by S. maltophilia. INTERVENTIONS: Fluoroquinolone monotherapy in comparison with trimethoprim-sulfamethoxazole monotherapy. METHODS: Systematic review with meta-analysis technique. RESULTS: Seven retrospective cohort and seven case-control studies were included. Three cohort studies were designed to compare the two drugs, whereas others had other purposes. A total of 663 patients were identified, 332 of which were treated with trimethoprim-sulfamethoxazole (50.1%) and 331 with fluoroquinolones (49.9%). Three cohort studies were designed to compare the effect of the two drugs, whereas the others had other purposes. Levofloxacin was most frequently used among fluoroquinolones (187/331, 56.5%), followed by ciprofloxacin (114/331, 34.4%). The overall mortality rate was 29.6%. Using pooled ORs for the mortality of each study, fluoroquinolone treatment (OR 0.62, 95% CI 0.39-0.99) was associated with survival benefit over trimethoprim-sulfamethoxazole treatment, with low heterogeneity (I2 = 18%). Specific fluoroquinolones such as ciprofloxacin (OR 0.44, 95% CI 0.17-1.12) and levofloxacin (OR 0.78, 95% CI 0.48-1.26) did not show a significant difference in comparison with trimethoprim-sulfamethoxazole. In the sub-group analyses of adult and bacteraemic patients, significant differences in mortality were not observed between fluoroquinolones and trimethoprim-sulfamethoxazole. CONCLUSIONS: Based on a meta-analysis of non-randomized studies, fluoroquinolones demonstrated comparable effects on mortality of S. maltophilia infection to trimethoprim-sulfamethoxazole, supporting the use of fluoroquinolones in clinical S. maltophilia infections. Although the pooled analysis of overall studies favoured fluoroquinolones over trimethoprim-sulfamethoxazole, the studies included were observational, and sub-group analyses of certain fluoroquinolone agents did not show statistical differences with trimethoprim-sulfamethoxazole. Randomized clinical studies are needed to address these issues.

Unique characteristics of community-onset healthcare- associated bloodstream infections: a multi-centre prospective surveillance study of bloodstream infections in Japan.

BACKGROUND: Analysis of bloodstream infections (BSIs) is valuable for their diagnosis, treatment and prevention. However, limited data are available in Japan. AIM: To investigate the characteristics of patients with bacteraemia in Japan. METHODS: This study was conducted in five hospitals from October 2012 to September 2013. Clinical, demographic, microbiological and outcome data for all blood-culture-positive cases were analysed. FINDINGS: In total, 3206 cases of BSI were analysed: 551 community-onset healthcare-associated (CHA)-BSIs, 1891 hospital-acquired (HA)-BSIs and 764 community-acquired (CA)-BSIs. The seven- and 30-day mortality rates were higher in patients with CHA- and HA-BSIs than in patients with CA-BSIs. The odds ratios (ORs) for seven-day mortality were 2.56 [95% confidence interval (CI) 1.48-4.41] and 2.63 (95% CI 1.64-4.19) for CHA- and HA-BSIs, respectively. The ORs for 30-day mortality were 2.41 (95% CI 1.63-3.57) and 3.31 (95% CI 2.39-4.59) for CHA- and HA-BSIs, respectively. There were 499 cases (15.2%) of central-line-associated BSI and 163 cases (5.0%) of peripheral-line-associated BSI. Major pathogens included coagulase-negative staphylococci (N = 736, 23.0%), Escherichia coli (N = 581, 18.1%), Staphylococcus aureus (N = 294, 9.2%) and Klebsiella pneumoniae (N = 263, 8.2%). E. coli exhibited a higher 30-day mortality rate among patients with HA-BSIs (22.3%) compared with patients with CHA-BSIs (12.3%) and CA-BSIs (3.4%). K. pneumoniae exhibited higher 30-day mortality rates in patients with HA-BSIs (22.0%) and CHA-BSIs (22.7%) compared with patients with CA-BSIs (7.8%). CONCLUSION: CHA- and HA-BSIs had higher mortality rates than CA-BSIs. The prognoses of E. coli- and K. pneumonia-related BSIs differed according to the category of bacteraemia.

4-Hydroxyretinal, a new visual pigment chromophore found in the bioluminescent squid, Watasenia scintillans.

The bioluminescent squid, Watasenia scintillans has three visual pigments. The major pigment, based on retinal (lambda max 484 nm), is distributed over the whole retina. Another pigment based on 3-dehydroretinal (lambda max approximately 500 nm) and the third pigment (lambda max approximately 470 nm) are localized in the specific area of the ventral retina just receiving the downwelling light. Visual pigment was extracted and purified from the dissected retina. The chromophores were then extracted and analyzed with HPLC, NMR, infrared and mass spectroscopy, being compared with the synthetic 4-hydroxyretinal. A new retinal derivative, 11-cis-4-hydroxyretinal, is identified as the chromophore of the third visual pigment of the squid.

O-H stretching vibration in Fourier transform difference infrared spectra of bacteriorhodopsin.

FTIR difference spectroscopic studies of M intermediate and LA bacteriorhodopsin in the O-H stretching region show bands at 3671 and 3641 cm-1, respectively. The O-H stretching bands in this region may reflect protonation-deprotonation changes or environmental change in the tyrosine residues in bR.

Fourier transform infrared spectroscopic study on retinochrome and its primary photoproduct, lumiretinochrome.

Structural studies of retinochrome, and its photoproduct, lumiretinochrome, were done by Fourier transform infrared difference spectroscopy. The absorption bands in the carbonyl stretching region which shift in D2O show the changes in the protein part during the photoreaction. Strong absorption bands in the finger-print region show that the all-trans-retinal chromophore in retinochrome isomerizes to the 11-cis-retinal chromophore in lumiretinochrome upon illumination with yellow-green light at 83K.

Effect of modification of the chromophore in retinochrome.

14-Methyl-, 14-chloro-, 14-fluoro-retinals have been incorporated into apo-retinochrome to investigate the effect of the electronegativities of C-14 substituents on the protonation of the Schiff base. The extent of protonation decreased in going from 14-methyl- to 14-chloro- to 14-fluoro-retinal. There was usually no protonation in the case of the 14-fluoro analogue. The chromophore-protein interactions are also discussed.

The absorbance spectrum and photosensitivity of a new synthetic "visual pigment" based on 4-hydroxyretinal.

The firefly squid, Watasenia scintillans, is the only animal known to possess a visual pigment in which the chromophore is 4-hydroxyretinal. This paper describes the absorbance spectrum and some properties of a synthetic "A4" visual pigment generated from bovine opsin and 4-hydroxyretinal. The absorbance spectrum of this pigment is compared with (a) bovine rhodopsin and (b) a rhodopsin template with the same lambda max as the synthetic visual pigment. The A4 pigment is shown to have an absorbance spectrum that is almost identical to that of a rhodopsin template. It is also shown that the photosensitivity and thermal stability of the A4 pigment, dispersed in detergent micelles, is essentially similar to that of rhodopsin.

Optimal walking in terms of variability in step length.

The optimal condition in speed, step rate, and step length of human walking has been reported in terms of temporal consistency, energy cost, and attentional demand. No study, however, has been conducted on the optimal condition in terms of spatial variability of walking. This study examined whether there is an optimal walking speed with minimum intrasubject variability in step length and step width during free walk (experiment 1) and whether there is an optimal step rate with minimum step length variability during walking with imposed step rates (experiment 2). Wearing shoes with ink-applied felt squares attached to the heels, healthy students walked on a flat walkway (0.6 x 16 m) at five different speeds with a freely chosen step rate in experiment 1 and walked at three different speeds with five different step rates in experiment 2. Free walk was found to have the fewest variable errors (VEs) in step length approximately at preferred walking speed. Variable error in step width increased linearly with an increase in walking speed. Under imposed step rates, VEs in step length were the fewest when walking with step rates close to those in free walk. Our everyday walking is performed most frequently at preferred speed and/or with freely chosen step rate, thereby optimizing the consistency of gait performance. Intrasubject variability in step length may be a useful measure for evaluation of walking.

Effect of Uncariae ramulus et Uncus on endothelium in spontaneously hypertensive rats.

The protective effect of the extract of Uncariae ramulus et Uncus (URE) against endothelium disorder due to hypertension was investigated. We administered low (150 mg/kg/day) and high (450 mg/kg/day) doses of URE orally to spontaneously hypertensive rats for 8 weeks. Endothelium dependent vasodilatation by acetylcholine increased significantly in the high URE group compared with the control group. Endothelium dependent vasocontraction by xanthine oxidase decreased significantly in the high URE group compared with the control group. Serum NO2-/NO3- were tended to increase in the high URE group. It is suggested that URE may have a protective effect for the endothelium against the influence of hypertension.

Elastic plasma protein film blended with platelet releasate accelerates healing of diabetic mouse skin wounds.

BACKGROUND AND OBJECTIVES: The growth factors derived from platelets and plasma proteins mediate the wound-healing process that is characterized by the sequential migration and differentiation of several cell populations that give rise to angiogenesis, collagen synthesis, wound contraction, and re-epithelialization. To evaluate the efficacy of the blood-derived factors in wound healing, we examined a novel wound dressing consisting of concentrated human plasma proteins and platelet releasate (CPPP). MATERIALS AND METHODS: To generate CPPP, plasma proteins and platelets in the peripheral blood (n = 5) were concentrated with the cold ethanol precipitation method. The thrombin obtained from the same blood unit and calcium chloride (CaCl(2)) were mixed to a concentrate. The CPPP has enough strength to dress cutaneous wounds and contains large amounts of cytokines and fibronectin. We applied the CPPP to excisional skin wounds in genetically healing-impaired model mice (n= 5) and the wounds were evaluated 10 days after the operation. RESULTS: The area of CPPP-treated wounds decreased significantly compared with that of the control wounds (65% vs. 94% of the original size, respectively, P= 0.032). The immunostained section revealed a striking effect of CPPP on vascularization compared with the control wounds (13.2 vs. 2.7 vessels per mm(2) as mean vascular density observed in the sections, respectively, P= 0.013). CONCLUSIONS: Our results suggest that CPPP is a promising biologically active dressing for full-thickness skin wounds. CPPP can be an entirely autologous biological dressing, suggesting that it is free from the risk of transmission of pathogens through blood products.

The effect of Juzen-taiho-to/TJ-48 on the expression of killer-cell immunoglobulin-like receptors (CD158a/b) on peripheral lymphocytes in vitro experiment.

Juzen-taiho-to (TJ-48), a mixture of extracts from 10 medicinal herbs, has been used traditionally to treat patients with anemia, anorexia or fatigue. It is well known that the treatment of TJ-48 result in the decrease of patient's complaints, as well as the increase of NK cytolytic activity (NK activity) although its augmentation is not clear in the other kampo formula from the clinical viewpoint. To investigate its biological activities, such as the augmentation of NK activity, we analyzed the effects of TJ-48 on the expression of killer-cell immunoglobulin-like receptors (KIRs) in vitro experiment. The peripheral lymphocytes were incubated in medium alone, or medium containing TJ-48 or interleukin-2 (IL-2) plus TJ-48 at several concentrations for 48 h. After each incubation, cells were collected and their KIRs were detected by flow cytometry using monoclonal antibodies CD158a and CD158b. TJ-48 increased the populations of CD16+CD158a+ and CD16+CD158b+ cells in a dose-dependent manner. In contrast, CD16-CD158a/b+ cells did not increase. Additionally, the extract of TJ-48 enhanced the increase of KIRs expression induced by IL-2. These actions contribute to the augmentation of NK cytolytic activity by TJ-48, and might explain, in part, its antitumor effects which has been observed in vivo.

Enhancement effect of an ethanol/Panasate 800 binary vehicle on anti-inflammatory drug permeation across excised hairless mouse skin.

The novel binary vehicle system consisting of ethanol (EtOH) and Panasate 800 as tricaprylin was applied to five types of nonsteroidal anti-inflammatory drugs, and its enhancing effect on drug permeation across hairless mouse skin in vitro was assessed. The permeability of all drugs was remarkably increased by the treatment of skin with EtOH/Panasate 800 binary systems compared with either EtOH or Panasate 800 alone, and the effect reached a maximum in EtOH/Panasate 800 (40/60) system. With regard to this binary system, the skin permeation ratio or flux of the drug increased in the following order: salicyluric acid (SU) > salicylic acid (SA) > alclofenac (ALC) > ketoprofen (KP) > ibuprofen (IBU). The one-layer skin model was applied concerning the above skin permeation profiles of the five drugs. Diffusion parameter (D'), partition parameter (K'), and permeation constant (Kp = D' x K') were calculated using the Laplace-transformed equations with the aid of MULTI (FILT). It was well demonstrated that the reduction of lag time and the increase of flux caused by EtOH/Panasate 800 binary vehicle systems was due to an increase of D' value by Panasate 800 and K' value by EtOH, respectively, in the skin. Especially, the EtOH/Panasate 800 (40/60) binary vehicle system produced the largest Kp value in each drug. In relation to all the EtOH/Panasate 800 binary vehicle systems, the logarithms of calculated Kp were found to be in inverse proportion to the logarithms of a n-octanol/water partition coefficient (P) of the drug which appeared in previous literature.

Reproducibility of the walking patterns of normal young adults: test-retest reliability of the walk ratio(step-length/step-rate).

The walk ratio, step-length divided by step-rate, is a speed-independent index of walking patterns. This study reports on the reproducibility of the walk ratio in repeated tests. A total of 25 healthy young subjects walked on a flat floor at five different speeds and the test was repeated on the same day and after 3 months. The walk ratio did not vary in the tests. Intraclass correlation coefficients of the walk ratio between the tests were 0.6-0.8 except for walking at extreme speeds. These results suggest that the walk ratio is a reliable measure for evaluating pathological and aging walking patterns. Copyright 1998 Elsevier Science B.V. All rights reserved

Establishment of monoclonal antibodies reactive with epithelial and myoepithelial cells in the breast.

Monoclonal antibodies which are considered to be able to differentiate epithelial and myoepithelial cells in the breast have been developed. Human mammary carcinoma cell line (HBC-4W) was used for immunization. Monoclonal antibodies-B4B2F10 (epi-1), E9E8B7 (myo-1)-with IgM was examined using tissues from diseased breast by avidin-biotin-peroxidase assay. Epi-1 antibody reacted with epithelial cells while myo-1 antibody reacted with myoepithelial cells in the mammary glands, respectively. The reaction was markedly visible, in particular, in fibroadenoma, mastopathy, and papilloma, which showed clear two-cell-type structures. In the infiltrating ductal carcinoma, epi-1 antibody reacted with carcinoma cells, while myo-1 antibody reacted with stromal cells rather than carcinoma cells suggesting that infiltrating ductal carcinoma was mainly of epithelial origin. In the infiltrating lobular carcinoma, however, myo-1 as well as epi-1 antibodies reacted with carcinoma cells. It is suggested that infiltrating lobular carcinoma was of a mixture of epithelial and myoepithelial cell origin.

The effects of a herbal medicine (Mao-to) in patients with chronic hepatitis C after injection of IFN-beta.

We found that a herbal medicine (Mao-to) relieves the side effects of interferon (IFN)-beta and the combination therapy improves the biochemical response rate. However, the exact mechanism by which Mao-to is effective remains to be established. We conducted a controlled trial to clarify the effects of Mao-to. The study was carried out in 18 patients with chronic hepatitis C, and we examined subjective symptoms, body temperature and cytokines such as interleukin (IL)-beta, IL-1receptor antagonist (ra), IL-6 and TNF-alpha. Each patient received 6 million units of IFN-beta intravenously. Mao-to was given orally just before, just after, and 1 hour after IFN administration. The control study was carried out 6 months after the combination therapy of Mao-to and IFN-beta. The scores for general malaise, arthralgia and discomfort were significantly lower in the combination group than in control group. Body temperature did not significantly differ between the two groups. Plasma IL-6 level and IL-1ra were significantly elevated in the combination group compared to control (P = 0.0057 and 0.0003, respectively). Mao-to did not affect plasma concentrations of IL-1beta and TNF-alpha. We considered the increment of IL-1ra caused by Mao-to is to be one of the key factors involved in reducing the flu-like symptoms accompanying IFN-beta and improving the biochemical response rate.

Comparative efficacy of Keishi-bukuryo-gan and pentoxifylline on RBC deformability in patients with "oketsu" syndrome.

Keishi-bukuryo-gan (Gui-Zhi-Fu-Ling-Wan) (KBG) is one of the prescriptions in Japanese traditional medicine for improving the "oketsu" syndrome, so-called blood stasis syndrome. "Oketsu" syndrome is an important pathological conception in Japanese traditional medicine and often accompanies cerebro-vascular disorders. Previously, we were able to reveal a deterioration of RBC (Red blood cell) deformability and viscoelasticity in patients with "oketsu" syndrome. The purpose of the present study was to evaluate whether KBG has an effect on RBC deformability in comparison with pentoxifylline (PXF). The subjects were 30 male patients with multiple lacunar infarctions. Eighteen patients (44-79 yrs, mean +/- SD, 66.1 +/- 10.7 yrs) were treated with 12 g of KBG daily for 4 weeks (KBG group). Twelve patients (59-78 yrs, 70.7 +/- 6.4 yrs) were treated with 300 mg of PXF daily for 4 weeks (PXF group). Based on the "oketsu" score, the patients of each group were divided into two subgroups, a non-"oketsu" group ("oketsu" score 20 points or less) and an "oketsu" group ("oketsu" score 21 points or higher). KBG had significant effects on RBC deformability as evaluated by filtration method. KBG also significantly increased intracellular ATP content, as did PXF. Moreover, KBG was more effective for patients with a more severe "oketsu" state. However, PXF was effective only in patients with "oketsu" syndrome, who might have deteriorated RBC deformability. In conclusion, the effect of KBG on RBC deformability was by no means inferior to PXF.

Growth and protective potentials of attenuated strains of equid herpesvirus 1 in the lungs of mice.

Attenuated equid herpesvirus 1 (EHV-1) strains with different passage histories in bovine kidney cells (BKC), i.e. BK77, BK161, BK271 and BK343, were examined for their growth in mouse lungs after intranasal inoculation. BK77 and BK161 were recovered from lungs with almost the same titres, and were found to be about 100 times lower than that of the parent HH1 strain. The growth abilities of high-passaged BK271 and BK343 were markedly reduced. Although partial growth of BK343 in the lungs of athymic nude mice was observed, the virus was almost eradicated from their lungs within 1 week. By contrast, the parent HH1 persisted in the lungs of nude mice for at least 1 week. The mice immunized with the BKC-passaged viruses were partially protected against subsequent challenge with the parent HH1. Antibodies were detected by ELISA. These results demonstrate that, although serial BKC-passage lowered the growth ability of the parent HH1, the descendant viruses still have a partial protective potential in mice.