Five-year point prevalence survey of healthcare-associated infections and antimicrobial use in a Japanese university hospital.

BACKGROUND: Periodic point prevalence surveys (PPSs) provide a method for assessing changes in healthcare-associated infections (HAIs) and antimicrobial use over time. Following the introduction of an antimicrobial stewardship programme at Nagoya University Hospital (Aichi, Japan) a five-year PPS study was performed to highlight any epidemiological changes. METHODS: One-day PPSs were performed annually in July at Nagoya University Hospital. Data on patient characteristics, medical devices, active HAIs and antimicrobial use were collected using a standard data-collection form. RESULTS: A total of 4339 patients were included. Over the five-year study period the median patient age was 62 years, median duration of hospital admission was nine days, 9% of patients had an HAI and 35.2% received at least one antimicrobial. Overall there were 406 HAIs (95% confidence interval, 369-447) with surgical site infection, pneumonia and febrile neutropenia occurring most frequently. Enterobacterales were the most common pathogens (N = 78, 28.6%) and 32.1% were third-generation cephalosporin-resistant. Meropenem was the most frequently prescribed antimicrobial for HAIs. Surgical antimicrobial prophylaxis changed drastically, with shorter durations and a marked reduction in oral cephalosporin use. However, antimicrobials for medical prophylaxis gradually increased. CONCLUSIONS: This five-year PPS study shows consistent data for patient background, HAIs and causative pathogens and highlights changes in antimicrobial use during the era of the National Action Plan on Antimicrobial Resistance. To describe the epidemiology of Japanese hospitals by PPS, multicentre PPSs including in community hospitals should be performed annually.

Determination of contrast medium dose for hepatic CT enhancement with improved body size dependency using a non-linear analysis based on pharmacokinetic principles.

AIM: To propose a pharmacokinetic non-linear analysis method to determine contrast medium (CM) dose for computed tomography (CT) hepatic enhancement to improve body size dependency and validate the proposed CM dose determination method through a clinical study. MATERIALS AND METHODS: Enhancement data of 105 patients who underwent hepatic dynamic CT with a fixed CM dose were analysed. From the analysis results, CM doses as a function of each of four body size indices (body weight [BW], lean body weight [LBW], blood volume [BV], and body surface area [BSA]) for achieving improved body size dependency were determined (proposed method), and the body size dependencies were simulated using the enhancement data from 105 patients. The proposed method was validated with a two-arm clinical study on BW. Body size dependency was evaluated using p-value of correlation coefficient between Body size indices and enhancements (p<0.05: significant dependency) and mean absolute error (MAE). RESULTS: The simulation showed that significant body size dependencies not considered by the conventional method can be improved by the proposed method. MAEs of BW, LBW, and BV were also significantly reduced (p<0.05). The clinical study with BW demonstrated a similar improvement to that in the simulation result. MAE was also significantly reduced (p<0.001). CONCLUSION: The proposed method demonstrated more improved BW, LBW, and BV dependence compared to the conventional method. Through the two-arm clinical study, the proposed method using BW only, without height information, is a suitable index for improving body size dependency.

Spectroscopy of Pionic Atoms in

We observed the atomic 1s and 2p states of π^{-} bound to ^{121}Sn nuclei as distinct peak structures in the missing mass spectra of the ^{122}Sn(d,^{3}He) nuclear reaction. A very intense deuteron beam and a spectrometer with a large angular acceptance let us achieve a potential of discovery, which includes the capability of determining the angle-dependent cross sections with high statistics. The 2p state in a Sn nucleus was observed for the first time. The binding energies and widths of the pionic states are determined and found to be consistent with previous experimental results of other Sn isotopes. The spectrum is measured at finite reaction angles for the first time. The formation cross sections at the reaction angles between 0° and 2° are determined. The observed reaction-angle dependence of each state is reproduced by theoretical calculations. However, the quantitative comparison with our high-precision data reveals a significant discrepancy between the measured and calculated formation cross sections of the pionic 1s state.

Gender and Age Analyses of NIRS/STAI Pearson Correlation Coefficients at Resting State.

According to the valence asymmetry hypothesis, the left/right asymmetry of PFC activity is correlated with specific emotional responses to mental stress and personality traits. In a previous study we measured spontaneous oscillation of oxy-Hb concentrations in the bilateral PFC at rest in normal adults employing two-channel portable NIRS and computed the laterality index at rest (LIR). We investigated the Pearson correlation coefficient between the LIR and anxiety levels evaluated by the State-Trait Anxiety Inventory (STAI) test. We found that subjects with right-dominant activity at rest showed higher STAI scores, while those with left dominant oxy-Hb changes at rest showed lower STAI scores such that the Pearson correlation coefficient between LIR and STAI was positive. This study performed Bootstrap analysis on the data and showed the following statistics of the target correlation coefficient: mean=0.4925 and lower confidence limit=0.177 with confidence level 0.05. Using the KS-test, we demonstrated that the correlation did not depend on age, whereas it did depend on gender.

[Diffusion studies of redox-sensitive nitroxyl spin probes through bilayer lipid membranes using 300 MHz electron spin resonance spectrometer].

Electron spin resonance (ESR) studies were carried out for 14N-labeled deuterated 3-methoxy-carbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl (MC-PROXYL) and 3-carboxy-2,2,5,5-tetramethyl-1-pyrrolidin-1-oxyl (carboxy-PROXYL) in pure water and various concentrations of liposomal solutions by using 300 MHz ESR spectrometer. The ESR parameters such as the line width, hyperfine coupling constant, rotational correlation time, g-factor, partition parameter and permeability were reported for the samples. The line width broadening was observed for MC-PROXYL and carboxy-PROXYL in liposomal solution. The hyperfine coupling constant was observed for both nitroxyl spin probes. The permeable and impermeable nature of nitroxyl spin probes was demonstrated. The rotational correlation time increases with increasing concentration of liposome. The partition parameter increases with increasing concentration of liposome for MC-PROXYL, which indicates that the nitroxyl spin probes diffuse into lipid membrane. The permeability value decreases with increasing concentration of liposome, which reveals an increase in membrane permeability. The peaks corresponding to the lipid phase were observed for MC-PROXYL in liposomal solution, but not resolved for carboxy-PROXYL. These results confirm the permeable and impermeable nature of nitroxyl spin probes.

Anti-tumor necrosis factor therapy in patients with difficult-to-treat lupus nephritis: a prospective series of nine patients.

OBJECTIVE: To clarify the efficacy and safety of anti-TNF-alpha therapy for intractable lupus nephritis. METHODS: In nine patients with systemic erythematosus who presented with lupus nephritis resistant to steroids and immunosuppressants, 200 mg/body of infliximab was drip-infused three times. No changes were made to other treatments for three months after the start of anti-TNF-alpha therapy, and urinary findings, renal function, serum complement, anti-DNA antibody, SLE activity, and adverse events were examined for six months after the start of anti-TNF-alpha therapy. RESULTS: One of the nine patients developed pyelonephritis after the first infliximab injection and received no further injections. The remaining eight patients received 3 infliximab injections. Of the eight patients, urinary protein decreased after anti-TNF-alpha therapy in six patients, and the SLEDAI improved in five patients. Urinary findings and/or SLE activity improved in six patients. Of the patients whose urinary protein levels decreased after anti-TNF-alpha therapy, proteinuria recurred six months after anti-TNF-alpha therapy in one patient. After anti-TNF-alpha therapy, proteinuria and the SLEDAI improved significantly. With respect to adverse events, therapy was discontinued in one patient who developed pyelonephritis, and one patient developed decreased blood pressure due to infusion reactions. In one patient in whom the steroid dosage was increased due to poor response to anti-TNF-alpha therapy, brainstem infarction occurred four months later. In one patient, anti-DNA antibody levels increased after therapy, but none of the patients had decreased serum complement levels or increased SLE activity. CONCLUSION: In intractable lupus nephritis, anti-TNF-alpha therapy improved urinary protein levels and SLE activity. Although adverse events must be monitored cautiously, it may be possible to use anti-TNF-alpha therapy as a third-line treatment.

Expression profiling of genes related to asthma exacerbations.

BACKGROUND: Asthma is a chronic airway inflammatory disease; however, the molecular mechanisms that underlie asthma exacerbation are only partially understood. OBJECTIVE: To identify gene expression signatures that reflect the acute exacerbation of asthma, we examined the differential expression of genes during asthma exacerbation and stable condition by using microarray analysis. METHODS: The subjects were mite-sensitive asthmatic children and non-asthmatic control children. The children were divided into four groups (AE: asthma exacerbation, n=12; SA: stable asthma, n=11; IC: infected control, n=6; and NC: non-infected control, n=5). Total RNA was extracted from peripheral blood mononuclear cells and subjected to microarray analysis with Illumina Human Ref8 BeadChip arrays. Welch's t-test was performed to identify genes whose expression was altered during asthma exacerbation. Quantitative real-time RT-PCR was performed on samples collected from 43 asthmatic children and 11 control children to verify the microarray results. RESULTS: The expression of 137/16 genes was significantly up/down-regulated during asthma exacerbation assessed by microarray analysis. Of the genes, 62 were also differentially expressed during upper respiratory infection. Many of the asthma exacerbation related genes were involved in defence responses and responses to external stimuli, but these associations disappeared after excluding the infection-related genes. Quantitative real-time RT-PCR confirmed that the genes related (S100A8 and GAS6) and unrelated to infections (CD200 and RBP7) were differentially expressed during asthma exacerbation (P<0.01). CONCLUSIONS: Previously unidentified immune responses during asthma exacerbation may provide further clarification of the molecular mechanisms underlying asthma.

Involvement of REG Ialpha protein in the regeneration of ductal epithelial cells in the minor salivary glands of patients with Sjögren's syndrome.

The regenerating gene (Reg) was originally isolated from regenerating rat pancreatic islets and revealed recently to constitute a multi-gene family in humans. REG Ialpha protein is known to be overexpressed not only in various human inflammatory diseases but also in various experimental models of inflammation in animal tissues. However, its involvement in pathophysiology of the minor salivary gland (MSG) is not clear. We investigated REG Ialpha expression in the MSG of patients with primary Sjögren's syndrome (SS) and assessed its role in ductal epithelial cell proliferation in such tissues. Lip biopsy specimens were obtained from 40 patients with primary SS and examined using immunohistochemistry for REG Ialpha protein, Ki67 and single-strand DNA (ssDNA). The relationships among clinicopathological factors and expression of REG Ialpha protein, Ki67 and ssDNA in the MSG were then analysed. REG Ialpha protein was expressed rarely in ductal epithelial cells of the normal MSG but was apparently overexpressed in those of patients with SS. The labelling indices for both Ki67 and ssDNA in the ductal cells of the MSGs were significantly higher in SS patients than in controls. Moreover, these labelling indices were significantly higher in REG Ialpha-positive than in negative SS patients. REG Ialpha protein may play a role in the regeneration of ductal epithelial cells in the MSGs of patients with SS.

Role of Necl-5 in the pathophysiology of colorectal lesions induced by dimethylhydrazine and/or dextran sodium sulphate.

Necl-5 is an immunoglobulin-like molecule that was originally identified as a poliovirus receptor. Although Necl-5 expression is often up-regulated in cancer cells, its pathophysiological significance in the development of cancer remains unclear. We investigated the roles of Necl-5 in the development of colitis-associated neoplasia. Necl-5-deficient mice were generated and treated with dimethylhydrazine (DMH) and/or dextran sodium sulphate (DSS) to induce colitis and its associated neoplasias. Colon tissues were examined for histology, Ki-67 expression by immunohistochemistry and K-ras gene mutation. Colon tumours occurred significantly less frequently in heterozygous (Necl-5(+/-)) or homozygous Necl-5-deficient (Necl-5(-/-)) mice than in wild-type (WT) mice with DMH/DSS treatment. Total ulcer index and inflammatory cell infiltration were significantly lower in Necl-5(-/-) mice than in WT mice with DSS alone or DMH/DSS treatment. Colon tumours in both WT and Necl-5(-/-) mice showed high cell proliferation ability but lacked K-ras mutation. The total Ki-67 labelling index in non-neoplastic colon epithelium was significantly higher in WT (45.9 +/- 0.94) than in Necl-5(+/-) (34.3 +/- 1.40) or Necl-5(-/-) (27.7 +/- 1.15) mice with DMH/DSS treatment (p < 0.001). Necl-5 plays a role in the development of colitis-associated cancer by up-regulating colonic mucosal cell proliferation.

Expression of SDF-1 alpha and nuclear CXCR4 predicts lymph node metastasis in colorectal cancer.

Although stromal cell-derived factor (SDF)-1 alpha and its receptor CXCR4 are experimentally suggested to be involved in tumorigenicity, the clinicopathological significance of their expression in human disease is not fully understood. We examined SDF-1 alpha and CXCR4 expression in colorectal cancers (CRCs) and their related lymph nodes (LNs), and investigated its relationship to clinicopathological features. Specimens of 60 primary CRCs and 27 related LNs were examined immunohistochemically for not only positivity but also immunostaining patterns for SDF-1 alpha and CXCR4. The relationships between clinicopathological features and SDF-1 alpha or CXCR4 expression were then analysed. Stromal cell-derived factor-1 alpha and CXCR4 expression were significantly associated with LN metastasis, tumour stage, and survival of CRC patients. Twenty-nine of 47 CXCR4-positive CRCs (61.7%) showed clear CXCR4 immunoreactivity in the nucleus and a weak signal in the cytoplasm (nuclear type), whereas others showed no nuclear immunoreactivity but a diffuse signal in the cytoplasm and at the plasma membrane (cytomembrane type). Colorectal cancer patients with nuclear CXCR4 expression showed significantly more frequent LN metastasis than did those with cytomembrane expression. Colorectal cancer patients with nuclear CXCR4 expression in the primary lesion frequently had cytomembrane CXCR4-positive tumours in their LNs. In conclusion, expression of SDF-1 alpha and nuclear CXCR4 predicts LN metastasis in CRCs.

A novel humanized anti-human death receptor 5 antibody CS-1008 induces apoptosis in tumor cells without toxicity in hepatocytes.

BACKGROUND: The antitumor activity of CS-1008, a humanized agonistic anti-human death receptor (DR) 5 antibody, was investigated in preclinical models. MATERIALS AND METHODS: Cytotoxicity of CS-1008 was evaluated in a several human tumor cell lines as well as primary human hepatocytes in vitro. To evaluate antitumor efficacy, athymic nude mice were inoculated with human colorectal tumor COLO 205, pancreatic tumor MIA PaCa-2 or non-small-cell lung carcinoma NCI-H2122 and CS-1008 was i.v. administered. The combination effects of CS-1008 with gemcitabine or docetaxel (Taxotere) against MIA PaCa-2 or NCI-H2122 were evaluated in vivo, respectively. RESULTS: CS-1008 inhibited the growth of tumor cell lines with DR5 expression, including COLO 205, NCI-H2122, MIA PaCa-2 and renal cell adenocarcinoma ACHN in vitro with antibody cross-linkage. Using COLO 205, apoptosis induction was confirmed by annexin V staining. Weekly administration of CS-1008 resulted in the inhibition of COLO 205 tumor growth as well as MIA PaCa-2 in vivo. CS-1008 in combination with gemcitabine or docetaxel demonstrated enhanced antitumor activity against MIA PaCa-2 or NCI-H2122 cells, respectively. Unlike tumor necrosis factor-related apoptosis-inducing ligand, CS-1008 did not induce cell death in human primary hepatocytes. CONCLUSION: CS-1008 has a selective toxicity toward tumor cells expressing DR5 and the potential for antitumor efficacy in human malignancies.

Human monoclonal antibodies against the complex of phosphatidylserine and prothrombin from patients with the antiphospholipid antibodies.

The presence of antibodies against the complex of prothrombin and phosphatidylserine (aPS/PT) more significantly correlates with manifestations of antiphospholipid syndrome (APS) and with the presence of lupus anticoagulants (LA) than antibodies against prothrombin bound to oxygenated polystyrene (aPT-A). To investigate immunological specificities and functional activities of aPS/PT, four monoclonal aPS/PT, designated as HG-4, KE-6, KF-5 and KF-6, from two patients with antiphospholipid antibodies (aPL) were established and characterized. Three of these antibodies (HG-4, KF-5 and KF-6) recognized the complex of phosphatidylserine and prothrombin, but did not react to prothrombin directly coated on oxygenated plates. KE-6 bound not only to the complex of phosphatidylserine and prothrombin but also to prothrombin on oxygenated plates. None of them showed the binding activity to prothrombin directly coated on non-oxygenated plates. HG-4, KE-6 and KF-5 had LA-like activity. The findings support the hypothesis that autoimmune aPS/PT recognize the cryptic epitopes or neoepitopes exposed upon interaction between prothrombin and phosphatidylserine, and that aPS/PT are, at least in part, responsible for LA activity.

Enhanced desensitization efficacy by liposomal conjugation of a specific antigen.

Since liposomes are known as strong adjuvants, we attempted to use liposomes in immunotherapy as adjuvants, and to achieve desensitization in pre-sensitized mice. At first, we sensitized mice with intraperitoneal injection of model antigen, 100 microg ovalbumin (OVA), with Alum and treated them with liposome composed of distearoylphosphatidylcholine (DSPC) and cholesterol (2:1 as a molar ratio), which was coupled with a small amount of OVA (10 microg OVA in 400 nmol DSPC and 200 nmol cholesterol-liposome was injected into 20 g mouse). It is well known that antigen-specific immunotherapy increases IgG blocking antibodies and decreases in IgE antibodies. The treatment with i.v. injection of OVA-liposome at days 8, 10, and 12 after sensitization strongly suppressed OVA-specific IgE production without affecting IgG level after the boost (100 microg OVA with Alum). Moreover, the treatment with high-density OVA-liposome (10 microg OVA in 80 nmol DSPC and 40 nmol cholesterol-liposome/20 g mouse) not only strongly suppressed IgE levels but also reduced IgG production after the boost of OVA-sensitized mice suggesting the importance of liposomal characteristic in desensitization immunotherapy. Next we reduced the dose of OVA-liposome and the desensitization effect was also observed at the dose of as low as 1 microg OVA on OVA-liposome/mouse. On the contrary, free OVA did not affect the production of both IgG and IgE levels. Biodistribution study indicated that OVA-liposome was highly accumulated in spleen of OVA-sensitized mice compared to control liposome at 3 h after i.v. injection. These results suggest that the liposomal OVA effectively interacts with and desensitizes immune cells, therefore, liposomes coupling with a certain antigen may be effective in allergy immunotherapy.

MR Imaging of Hippocampal Sulcus Remnant: Age-Related Differences.

The hippocampal sulcus remnant (HSR) is often observed at the medial temporal lobe on MR images. In the present study, we made a retrospective assessment of the frequency and age-related differences in HSR in routine brain MR examinations of 1000 patients, 494 females and 506 males. Cases with one or several spots that were hypointense on T1-weighted and FLAIR images and hyperintense on T2-weighted images were defined as positive for HSR. Abnormal spots with the same intensity as cerebrospinal fluid were observed in 210 out of 506 males and in 193 out of 494 females. No significant sex-related differences were observed in the frequency of HSR. The HSR was seen more frequently with age in both males and females. Patients with hypertension had a significantly higher frequency of HSR.

Laparoscopic incisional hernia repair. A new mesh fixation method without stapling.

BACKGROUND: Recent advances in laparoscopic surgery have made various abdominal surgeries possible. To avoid wound infection, mesh repair of abdominal incisional hernias is performed laparoscopically. Here we present a new procedure to fix mesh to the abdominal wall. SURGICAL TECHNIQUE: Four anchoring sutures are made using a suture-grasping device; the additional transabdominal sutures are then made with a modified double-needle device. Additional circumferential fixation with tacks is not necessary. CONCLUSIONS: This new mesh fixation method involves simple suturing techniques and is less time consuming than the conventional procedure.

Prevalence and risk factor analysis of microalbuminuria in Japanese general population: the Takahata study.

Microalbuminuria, an indicator of glomerular injury, is associated with increased risk of progressive renal deterioration, cardiovascular disease, and mortality. However, the prevalence of microalbuminuria in Japanese general population is less certain. Thus, we examined the prevalence of microalbuminuria and its associated risk factors in Japan. Subjects of this cross-sectional study were asymptomatic individuals over 40 years in Takahata, Japan. Urine albumin-creatinine ratio was calculated from a single-spot urine specimen collected in the morning. Creatinine clearance (CCr) was obtained by Cockcroft-Gault equation. Multivariate logistic regression analysis was used to determine which risk factors (i.e., age, hypertension, diabetes, obesity, and salt intake) might predict the presence of microalbuminuria. A total of 2321 subjects (mean age, 64 years; men, 1034; women, 1287) were entered into the final analysis. Among them, the prevalence of microalbuminuria, macroalbuminuria, and proteinuria by dipstick test (> or = 1+) were 317 (13.7%), 39 (1.7%), and 103 (4.4%), respectively. Age, hypertension, and diabetes were independently associated with microalbuminuria in men. In addition to the classical risk factors detected in men, estimated 24-h urinary sodium excretion and uric acid were also independently associated with microalbuminuria in women. Among the 668 subjects with renal insufficiency (CCr <60 ml/min/1.73 m(2)), the prevalence of microalbuminuria and macroalbuminuria were 119 (17.8%) and 18 (2.7%), respectively. In conclusion, microalbuminuria is prevalent across all age groups and is associated with lifestyle-related risk factors in Japanese general population. However, there are a substantial number of subjects with renal insufficiency accompanying no microalbuminuria.