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.

Estimation of the congestion area volume in potential living donor remnant livers.

BACKGROUND: Living donor liver transplantation is widely performed in adult patients. One of the problems in this setting is a small-for-size graft, which results in dysfunction and poor prognosis of a transplantation. A right liver graft was devised to overcome this problem; furthermore, inclusion of the middle hepatic vein (MHV) has been suggested to greatly improve recipient outcomes. However, extended right hepatectomy involves a surgical risk for the living donor in terms of congestion of the left paramedian sector. The volume of the venoocclusive region of a living donor liver possibly varies depending on the collateral patterns of veins draining the cranial part of segment 4 (S4). PATIENTS AND METHODS: We were analyzed the normal livers of 50 patients who underwent triphasic contrast-enhanced multidetector row computed tomography during preoperative and postoperative examinations. The patient pathologies consisted of gastric cancer (n = 25), colon cancer (n = 1), or renal cancer (n = 24). We calculated the volume of the entire liver as well as those of the right graft and left remnant lobes for comparison with the drainage volume of each hepatic vein and its branches. RESULTS: On the basis of the anatomic venous drainage of the cranial part of S4 (V4sup), we classified hepatic veins as group A (n = 31), the V4sup joined the left hepatic vein or the MHV distal to the vein draining S8 area (MV8), or group B (n = 19), V4sup joined the MHV proximal to MV8. The mean volume of the congested area was 6.9% in group A and 15.9% in group B. The venoocclusive areas in the remnant livers were estimated to be larger in group B (P < .001). CONCLUSION: The collateral pattern of V4sup and MV8 as well as preoperative volumetric analysis are important for graft selection to decide the line of transection.

Real-time monitoring of liver damage during experimental ischaemia-reperfusion using a nitric oxide sensor.

BACKGROUND: Hepatic ischaemia-reperfusion (IR) injury may lead to liver damage during liver surgery, and intrahepatic nitric oxide (NO) levels may play a role in this context. The aim of this study was to demonstrate real-time changes in intrahepatic NO concentration during IR and to correlate potential hepatic NO production with liver damage using a selective NO sensor. METHODS: Wistar rats were exposed to 15 min of hepatic ischaemia followed by reperfusion, after which changes in intrahepatic NO levels were measured using an NO sensor. Additionally, rats were exposed to five successive periods of IR, each consisting of 15 min ischaemia followed by 5 or 15 min reperfusion, and hepatic damage was evaluated by blood tests and histological examination. Hepatic expression of Akt, phosphorylated Akt, endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS was examined at different time points during and after IR by western blot and immunohistochemical analysis. RESULTS: During ischaemia, intrahepatic NO levels increased and reached a plateau at approximately 10 min. Repeated 15 min ischaemia-5 min reperfusion cycles reduced the maximum amount of NO produced during ischaemia gradually, and almost no NO production was observed during the fifth period of ischaemia. NO production following repeated ischaemia was proportional to the degree of hepatic viability. Phosphorylated eNOS was upregulated and correlated with the level of NO production during hepatic ischaemia. CONCLUSION: Intrahepatic NO levels decrease during repeated IR in rats. Real-time monitoring of intrahepatic NO levels is useful for the prediction of IR-related liver injury during experimental liver surgery.

CT colonography to detect rectosigmoid involvement in patients with primary ovarian cancer.

INTRODUCTION: We retrospectively evaluated the performance of preoperative computed tomographic (CT) colonography to detect tumor involvement of the rectosigmoid wall and predict the need for rectosigmoid resection in patients with primary ovarian cancer. METHODS: Thirty-three patients with primary ovarian cancer who underwent preoperative CT colonographic examination were evaluated. The images of the examination were analyzed and compared with the subsequent surgical findings. RESULTS: All abnormal findings (malignant infiltration of the rectosigmoid mucosa and extrinsic compression) revealed by conventional colonoscopy were correctly observed as extrinsic compression using CT colonography. The sensitivity, specificity, positive predictive value and negative predictive value of CT colonography for the prediction of rectosigmoid resection were 100%, 64.7%, 72.7%, and 100%, respectively. Though conventional colonoscopic examinations could not be completed in five patients because of the presence of extrinsic stenosis and occlusion at the sigmoid colon, CT colonography enabled the entire large bowel to be examined in these patients. CONCLUSIONS: This preliminary study showed that the CT colonographic examination is feasible and safe. CT colonography seems to have several advantages over conventional colonoscopy for the detection of rectosigmoid involvement in patients with advanced ovarian cancer. For confirmation of the efficacy of CT colonography, further large prospective studies are needed.

Medications used to treat Parkinson's disease and the risk of gambling.

Recent case-series studies indicated that a medication used to treat Parkinson's disease (PD), in particular Pramipexole, is associated with gambling. A case-series study cannot test this hypothesis; therefore, we need to design a case-control or cohort study to test the aforementioned hypothesis. Typical of a case-control design, we sampled on the dependent variable, which we defined as incident gambling in PD. A research neurologist, who was kept uninformed of the case-control status, retrospectively measured the exposure of interest (i.e. medications used to treat PD) by using the medical database system of Mayo Clinic Jacksonville. Eleven patients with PD without history of gambling, but had newly developed gambling, were matched by age and sex to the control group of 37 PD patients without gambling at a ratio of one case to at least three controls. Disease duration, age, and sex did not differ between cases and controls. Combined therapy with Pramipexole and levodopa did not increase the risk of gambling as compared to monotherapy with Pramipexole (OR, 0.15; 95% CI, 0.01-1.26). Treatment with Pramipexole was associated with increased risk of gambling and this association approached significance (OR, 3.6; 95% CI, 0.9-14.9). Patients with PD who newly developed gambling behavior were more likely to have been taking Pramipexole than other anti-PD medication. However, the association between Pramipexole and gambling behavior is not necessarily etiologic.

Serial MR imaging and 1H-MR spectroscopy in monozygotic twins with Tay-Sachs disease.

Four-year-old monozygotic female twins with early onset Tay-Sachs disease are described. The sisters showed similar slowly progressive clinical symptoms and deterioration, however the younger sister also demonstrated intractable myoclonus in the right leg. The serial MR images and (1)H-MR spectroscopy of the brain were obtained in both twins. MR images showed high intensity on T (2)-weighted image in the bilateral white matter, however there were no signal changes in the basal ganglia and thalamus during any of the phases. The ratio of N-acetylaspartate (NAA)/creatine (Cr) was decreased in the both white matter lesions and the corpus striatum, and that of myoinositol (mI)/Cr was increased in the damaged white matter on MR spectroscopy. The elevation of the lactate peak was clearly demonstrated in the left basal ganglia of the younger sister; however it was not shown in cerebral lesions of the elder sister. Changes in metabolites on MR spectroscopy were closely linked to the respective clinical features of each twin. Follow-up examination by (1)H-MR spectroscopy is useful for the evaluation of neuronal changes in children with Tay-Sachs disease.

The correlation between 1H-MR spectroscopy and clinical manifestation with tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disease. Cortical tubers are one of the standard intracranial hallmarks of TSC, they comprise subependymal hamartomas protruding into the ventricles, cortical and white matter hamartomas, and giant cell tumors. The clinical course of TSC varies from asymptomatic to severe, with epileptic seizures and psychomotor retardation. We discuss here the correlation between clinical manifestation and features on 1H-MR spectroscopy ( 1H-MRS) of the white matter involving cortical tubers in patients with TSC. Statistical analysis of the N-acetylaspartate (NAA), choline (Cho) and myoinositol (mI)/creatinine (Cr) ratios between tubers and normal controls showed decreased NAA/Cr and increased mI/Cr ratios (P<0.05) in tubers, but no significance difference in Cho/Cr. The significance of the clinical appearance is associated with a decreased ratio of NAA/Cr in tubers with TSC. An elevated ratio of mI/Cr in tuber does not parallel the severity of the clinical features of TSC. These findings suggest that 1H-MRS may be useful for the evaluation of the clinical severity and prognostic diagnosis of TSC.

Safety of ofloxacin (OFLX) and fosfomycin sodium (FOM) ear drops.

OBJECTIVE: The objective of this study is to evaluate the safety of two ear drops, Ofloxacin (OFLX: Taribid Otic Solution, Daiichi Seiyaku) and Fosfomycin sodium (FOM: Fosmicin S, Meiji Seiyaku). METHODS: Albino guinea pigs were used as experimental animals, and the ototoxicity was evaluated by means of threshold changes in the compound action potentials (CAP), when topically applied to the middle ear cavity of the guinea pig. The sound stimuli applied were; click sound, with tone bursts of 8 kHz, 4 kHz, and 2 kHz. In one group of animals, after one application of the ear drops in the right middle ear cavity, the change in CAP was compared with a contralateral saline control at 24h, one week, and four weeks. In other group of animals, the ear drops were applied into the middle ear cavity for seven consecutive days and the CAP was measured at 24h. RESULTS: At 24h the CAP threshold for click, 8 and 4 kHz elevated significantly for both the saline and ear drop treatment, but the threshold returned to normal when measured at 7 days and 28 days. Seven consecutive days of ear drops administration resulted in no reduction in the CAP for either ear drops. CONCLUSIONS: Based on the lack of changes in the CAP, these two ear drops studied did not show any significant ototoxicities.

Gene expression changes in a patient presenting nonleukaemic nasal granulocytic sarcoma to acute myelogenous leukaemia using 40 K cDNA microarray.

This is a case report of granulocytic sarcoma occurring as a nasal lesion prior to the onset of acute myelogenous leukaemia (AML). To understand this case in more detail, we used 40,000 human cDNA microarray to identify the gene expression patterns of nonleukaemic stage bone marrow (BM), AML stage BM and AML stage peripheral blood cells and subsequently define the molecular basis of this disease progression. Of significance, we have tracked the expression profile of BM samples during the course of nonleukaemic to leukaemic progression, and identified a number of genes that may account for the growth potential of leukaemia cells and indicate poor prognosis of this case.

Disease-specific expression of VEGF and its receptors in AML cells: possible autocrine pathway of VEGF/type1 receptor of VEGF in t(15;17) AML and VEGF/type2 receptor of VEGF in t(8;21) AML.

Various angiogenic factors, such as vascular endothelial growth factor (VEGF) and an associated molecule, placenta growth factor (PlGF), are thought to be important for normal and malignant hematopoiesis. This study examined mRNA expression of VEGF, PlGF and receptors for these molecules in AML cells and identified the disease-specific patterns of expression. AML M3 having t(15;17) abnormality showed highest expression of VEGF and VEGF receptor type 1 (VEGFR1), suggesting the autocrine pathway of VEGF-VEGFR1. Then, t(8;21) AML demonstrated augmented expression of VEGF and VEGF receptor type 2 (VEGFR2), suggesting VEGF-VEGFR2 autocrine pathway. Then, addition of VEGFR2 kinase inhibitor in Kasumi-1, a t(8;21) AML cell line, resulted in marked inhibition of cell growth, although growth inhibitory effect of R2 kinase inhibitor to HL-60 was marginal. In addition, cell cycle analysis study showed S-phase cell population reduction by R2 kinase inhibitor in Kasumi-1, but not in HL-60. This observation is thought to be the rationale for novel molecular target therapy directed to angiogenic molecules.

Inflammatory gene signature in ulcerative colitis with cDNA macroarray analysis.

BACKGROUND: Most array analyses of ulcerative colitis have focused on identifying susceptibility genes for ulcerative colitis. AIM: To clarify the changes in gene expression during inflammation in ulcerative colitis colon mucosa using cDNA macroarray. METHODS: From 23 ulcerative colitis patients, 16 each of inflamed and non-inflamed specimens (total 32 samples for individual analysis) were obtained by colonoscopic biopsy. Eighteen of the 32 samples, used for pairwise analysis, consisted of nine sample pairs, each pair being from the same patient. We examined expression profiles of approximately 1300 genes with cDNA macroarray. Comparisons were made using two kinds of statistics, t-test and significance analysis of microarray in both analyses. The reproducibility of significant genes from the macroarray analysis was confirmed by real-time ploymerase chain reaction. RESULTS: We detected five upregulated genes, categorized into proinflammatory genes (MRP14, GRO gamma and SAA1) and anti-inflammatory genes (TIMP1 and Elafin) in inflamed mucosa, and one upregulated gene (L-FABP) in non-inflamed mucosa. CONCLUSIONS: As the cDNA macroarray analysis in this study exactly reflects the total profile of gene expression in the clinical setting of ulcerative colitis, the genes identified will be directly applicable to diagnostics or as novel therapeutic targets in active ulcerative colitis.

Present characteristics of symptomatic Entamoeba histolytica infection in the big cities of Japan.

Medical records, for 2000 and 2001, of symptomatic amoebic patients who were treated at our hospitals in Tokyo, Yokohama and Osaka were studied retrospectively for the purpose of gathering epidemiological data on symptomatic Entamoeba histolytica infection. A total of 58 patients were treated. Fifty-five of them were male, and 96% of the male patients were Japanese. The mean age of patients was 44.9 years old, and 91% of patients contracted the disease in Japan. Fifty-six per cent of the male patients indicated that they were practising homosexuals, and 44% of the male patients denied these practices or left the question unanswered. The serum Treponema pallidum haemagglutination test was positive in 45% of the patients, and antibody to human immunodeficiency virus (HIV) was positive in 45%. Our study revealed that recent symptomatic E. histolytica infection almost exclusively afflicted middle-aged males in the big cities of Japan, that a majority of the patients were probably exposed to the causative organism during homosexual activity, and that an increasing number of patients will be co-infected with HIV.

Clinicopathologic evaluation after resection for ductal adenocarcinoma of the pancreas: a retrospective, single-institution experience.

INTRODUCTION: Between April 1992 and December 2000, 167 patients with pancreatic carcinoma were evaluated and treated in our department. One hundred eight patients (64.7%) with pancreatic carcinoma underwent pancreatectomy. Of these patients, 94 had histologically proven ductal adenocarcinoma. The overall postoperative mortality rate was 3.2% (3 patients), and the morbidity rate was 35.1% (33 patients). The estimated 1-, 2-, 3-, and 5-year survival rates were 43.6%, 28.7%, 21.8%, and 12.9%, respectively. There were only six long-term survivors who survived >5 years after surgery. METHODOLOGY AND AIMS: Institutional experience with 94 consecutive patients with ductal adenocarcinoma who underwent pancreatectomy was reviewed to clarify the influence of 29 prognostic factors (5 host, 17 tumor, and 7 treatment factors). Special reference was made to determine whether these significant factors have an effect on long-term survival. Univariate and multivariate models were used to analyze the effect of prognostic factors on survival. RESULTS: Univariate analysis indicated that blood loss, operative time, postoperative complications, histopathologic lymphatic and venous permeation, lymph node metastasis, conclusive stage, conclusive curability, resection margins, serosal invasion, size of tumor, retroperitoneal invasion, major arterial invasion, and mode of histologic infiltration were associated with significantly longer survival (p < 0.05). By Cox proportional hazards survival analysis, the most powerful predictors of outcome were venous permeation, lymph node metastasis, tumor diameter, and conclusive curability. The longest-term survivor had the most advanced stage (stage IV(b)) of disease and curability C. No long-term survivors had all of the good prognostic factors (according to multivariate analysis). CONCLUSIONS: The prognosis after surgical resection of pancreatic carcinoma mostly depends on tumor factors. In this study, it was difficult to identify the determinants of long-term survival in patients with resectable tumors.

Expression of endothelial cell-associated molecules in AML cells.

Recently, it has been clarified that interaction between hematopoietic cells and endothelial cells is important in normal hematopoiesis and leukemogenesis. In this study, we examined the relationship between AML cells and endothelial cells by analyzing the expression profile of angiogenic factors, angiopoietin-1 (Ang-1), Ang-2, Tie-2 (a receptor for angiopoietins) and vascular endothelial growth factor (VEGF). Our results demonstrated that CD7(+)AML expressed Ang-2 mRNA frequently and integrin-family adhesion molecules (CD11c and CD18) intensively, suggesting the close correlation with endothelial cells. On the other hand, in t(8;21) AML cells, expression of Ang-2 was infrequent and expression of integrin-family adhesion molecules (CD11b, CD11c and CD18) was weak, suggesting the sparse association with endothelial cells. As for CD7(+)AML cells, despite the frequent and intense expression of endothelial cell-associated molecules (such as Ang-2, CD11c and CD18), intensity of Tie-2 expression was quite low (P < 0.05). Ang-2 expressed in CD7(+)AML cells is not considered to act in an autocrine fashion, but to work on endothelial cells to "feed" leukemic cells. Although Ang-2 is recognized as a natural antagonist for Tie-2, our data presented here suggested the alternative role of Ang-2 in the relationship between endothelial cells and leukemia cells, at least in a subset of leukemia such as CD7(+)AML. These results were supported by the study using AML cell lines, KG-1 (CD7 negative) and its subline KG-1a (CD7 positive); KG-1 had mRNA expression profile of Ang-1(+)Ang-2(-)Tie-2(+), while KG-1a showed Ang-1(+)Ang-2(+)Tie-2(-). These difference in the expression profile of angiogenic factors between CD7(+)AML and t(8;21)AML may explain the characteristic morphological features of these leukemias (CD7(+)AML as blastic type and t(8;21)AML as differentiative type).

Cellular localization of the signaling components of Arabidopsis His-to-Asp phosphorelay.

In the higher plant, Arabidopsis thaliana, histidine-to-aspartate (His-to-Asp) phosphorelay signal transduction systems play crucial roles in propagation of environmental stimuli, including plant hormones. This plant has 11 sensor His-kinases, 5 histidine-containing phosphotransfer (HPt) factors (AHPs), and 20 response regulators (ARRs). To gain new insight into the functions of these phosphorelay components, their intracellular localization was examined with use of GFP-fusion proteins, constructed for certain representatives of HPt factors (AHP2) and type-A and type-B ARRs (ARR6/ARR7 and ARR10, respectively). The results showed that AHP2 is mainly located in the cytoplasmic space, while both the types of ARRs have an ability to enter preferentially into the nuclei, if not exclusively. Together with the results from an in vitro phosphorelay assay with AHP2 and ARRs, these results are discussed, in terms of a geneal framework of the Arabidopsis His-to-Asp phosphorelay network.

Phenotype-genotype relationships in peroxisome biogenesis disorders of PEX1-defective complementation group 1 are defined by Pex1p-Pex6p interaction.

The peroxisome biogenesis disorders (PBDs), including Zellweger syndrome (ZS), neonatal adrenoleucodystrophy (NALD) and infantile Refsum disease (IRD), are fatal autosomal recessive diseases caused by impaired peroxisome biogenesis, of which 12 genotypes have been reported. ZS patients manifest the severest clinical and biochemical abnormalities, whereas those with NALD and IRD show less severity and the mildest features respectively. We have reported previously that temperature-sensitive peroxisome assembly is responsible for the mildness of the clinical features of IRD. PEX1 is the causative gene for PBDs of complementation group E (CG-E, CG1 in the U.S.A. and Europe), the PBDs of highest incidence, encoding the peroxin Pex1p of the AAA ATPase family. It has been also reported that Pex1p and Pex6p interact with each other. In the present study we investigated phenotype-genotype relationships of CG1 PBDs. Pex1p from IRD such as Pex1p with the most frequently identified mutation at G843D was largely degraded in vivo at 37 degrees C, whereas a normal level of Pex1p was detectable at the permissive temperature. In contrast, PEX1 proteins derived from ZS patients, including proteins with a mutation at L664P or the deletion of residues 634-690, were stably present at both temperatures. Pex1p-G843D interacted with Pex6p at approx. 50% of the level of normal Pex1p, whereas Pex1p from ZS patients mostly showing non-temperature-sensitive peroxisome biogenesis hardly bound to Pex6p. Taking these results together, we consider it most likely that the stability of Pex1p reflects temperature-sensitive peroxisome assembly in IRD fibroblasts. Failure in Pex1p-Pex6p interaction gives rise to more severe abnormalities, such as those manifested by patients with ZS.

Malignant lymphoma of the bone associated with systemic sarcoidosis.

A 57-year-old woman was hospitalized with malignant lymphoma of the right talus. After treatment, complete remission was obtained. Gallium-67 scintigraphy to confirm the remission demonstrated increased uptake in the whole body skeletal muscle, especially in her thighs. Biopsy of right gastrocnemius muscle showed epithelioid granuloma. Serum angiotensin-converting enzyme activity (ACE) and lysozyme had increased to several times the normal range. We diagnosed her disease as bone-associated sarcoidosis-lymphoma syndrome. Human herpes virus 8 (HHV-8) genome was examined in the bone marrow specimen, and the relationship between sarcoidosis-lymphoma syndrome and HHV-8 was discussed.