Spraying of phenol red dye as a screening test for <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection in surgically resected stomach specimens

Background Endoscopic spraying of phenol red dye and urea (phenol red test) has recently been used to assess the distribution of Helicobacter pylori in the gastric mucosa. We examined whether the phenol red test could be used to detect H. pylori in surgically resected stomachs.Methods A total of 82 surgically resected stomachs, obtained from 82 patients (mean age, 60.1 years; range, 33–84 years) with early gastric carcinomas were examined. Phenol red solution and urea were sprayed over the entire mucosa of each resected stomach. A color change from yellow to red was considered as a positive reaction for H. pylori. Gastric mucosal specimens taken from positively stained and negatively stained areas on the phenol red test were then examined immunohistochemically to determine the degree of H. pylori colonization.Results Diffusely positive reactions were seen in 16 resected stomachs (19%), and regionally positive reactions were seen in 36 (44%). The other 30 stomachs (37%) showed no color change (negative reaction). H. pylori was detected immunohistochemically significantly more frequently in positively stained than in negatively stained areas (P 0.0001). Specificity, sensitivity, and predictive values for positive and negative results of the phenol red test, determined on the basis of H. pylori immunostaining, were 100%, 74.3%, 100%, and 72.7%, respectively.Conclusions The phenol red test is a specific, relatively sensitive, rapid, easy-to-use, and repeatable method that can be used to diagnose H. pylori infection in surgically resected material. It enables pathologists as well as gastroenterologists with no microbiological expertise to easily diagnose H. pylori infection.     

Prognostic significance of PRAME expression based on immunohistochemistry for diffuse large B-cell lymphoma patients treated with R-CHOP therapy

The preferentially expressed antigen of melanoma (PRAME), a tumor-associated antigen, is considered a prognostic marker for various human malignancies. The prognostic significance of PRAME expression for diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab-containing chemotherapy has not been evaluated to date, and the ability of immunohistochemistry (IHC) to detect PRAME expression in these patients has not yet been studied, although IHC is simple to perform in clinical practice. We evaluated the prognostic significance of PRAME expression based on IHC analysis in 160 DLBCL patients treated with R-CHOP therapy. There was a significant association between higher PRAME expression and shorter progression-free survival (PFS), and a trend toward shorter overall survival (OS) in patients with higher PRAME expression than that in patients with lower PRAME expression (5-year PFS, 48.1 vs. 61.1 %; 5-year OS, 65.6 vs. 79.1 %). Patients with high PRAME expression tended to have lower chemotherapeutic responses. Thus, IHC is useful for detecting and assessing PRAME expression in DLBCL. Further, we found a positive correlation between IHC and quantitative real-time RT-PCR measurements of PRAME expression. Our findings indicate that IHC results of PRAME expression can be a novel prognostic maker in DLBCL patients treated with R-CHOP therapy.     

Loss of Amino Acids Into Dialysate During Hemodialysis Using Hydrophilic and Nonhydrophilic Polyester–Polymer Alloy and Polyacrylonitrile Membrane Dialyzers

During hemodialysis, amino acid loss through the dialysate remained a significant problem and was not clear in some dialyzers; therefore, we investigated amino acid loss with hydrophilic and nonhydrophilic polyester–polymer alloy membranes and polyacrylonitrile membranes. Nine maintenance hemodialysis patients were studied to assess amino acid loss during hemodialysis with the three membranes. Total amino acid losses were 85.7 ± 27.2 mg/L, 83.3 ± 16.1 mg/L, and 72.1 ± 22.5 mg/L with the hydrophilic, nonhydrophilic polyester–polymer alloy, and polyacrylonitrile membranes, respectively. Amino acid losses were greater with the hydrophilic membrane compared with the polyacrylonitrile membrane for ornithine (2.0 ± 0.6 vs. 1.4 ± 0.4 mg/L, P = 0.025), phenylalanine (2.4 ± 0.9 vs. 1.8 ± 0.8 mg/L, P = 0.012), and tryptophan (0.6 ± 0.2 vs. 0.4 ± 0.2 mg/L, P = 0.023). Amino acid losses were greater with the nonhydrophilic membrane than with the polyacrylonitrile membrane for ornithine (2.0 ± 0.4 vs. 1.4 ± 0.4 mg/L, P = 0.017), phenylalanine (2.3 ± 0.5 vs. 1.8 ± 0.8 mg/L, P = 0.018), tryptophan (0.7 ± 0.2 vs. 0.4 ± 0.2 mg/L, P = 0.003), and cystine (3.2 ± 0.7 vs. 2.0 ± 0.7 mg/L, P = 0.005). In conclusion, greater losses of ornithine, phenylalanine, tryptophan, and cystine were observed with polyester–polymer alloy than with polyacrylonitrile membranes during hemodialysis. Constant attention should be paid to the amino acid loss profile to improve nutritional control in hemodialysis patients.     

In vitro and in vivo antibacterial activities of K-4619, a new semisynthetic aminoglycoside

The antibacterial activities of K-4619 (3-de-O-methylsporaricin A sulfate) were compared with those of sporaricin A, amikacin, dibekacin, and gentamicin. K-4619 exhibited a high order of activity against gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. Its activity against Providencia species and Serratia marcescens was the highest of all drugs tested. K-4619 was highly effective against bacteria that produce various aminoglycoside-inactivating enzymes, except for 3-acetyltransferase I. The bactericidal activity of K-4619 was somewhat greater than that of amikacin. The activity of K-4619 against gram-negative bacteria increased at alkaline pH and was hardly affected by inoculum size, addition of horse serum, and composition of the medium. The in vivo protective effect of K-4619 against infections with Klebsiella pneumoniae, S. marcescens, and P. aeruginosa in mice was greater than that of sporaricin A. K-4619 was also active in mice infected with gentamicin- or amikacin-resistant strains bearing some of the aminoglycoside-inactivating enzymes.     

Amlodipine, but not MDR1 polymorphisms, alters the pharmacokinetics of cyclosporine A in Japanese kidney transplant recipients

BACKGROUND: Cyclosporine A (CsA) is a critical immunosuppressive drug with a narrow therapeutic range and wide interindividual variation in its pharmacokinetics. Many factors, including P-glycoprotein (PGP), influence the oral bioavailability and interpatient variability of CsA. A number of polymorphisms have been identified in the human MDR1 gene, and some of them have been found to be associated with an altered expression of PGP. We have investigated the role of these polymorphisms in CsA absorption from kidney transplant recipients. In addition, we also investigated the effect of amlodipine on CsA absorption. METHODS: The area under the time-concentration curve from 0 to 2 hr (AUC(0-2)) estimated by the trapezoidal rule was used for the evaluation of extent of CsA absorption. The genotypes were identified by a polymerase chain reaction, restriction fragment length polymorphism analysis. RESULTS: No association was found between polymorphisms in the MDR1 and CsA AUC(0-2)/dose/kg. In contrast, the combination of amlodipine significantly increased CsA AUC(0-2)/dose/kg (706.2 microg x hr/L to 819.2 microg x hr/L, P<0.05). Furthermore, we attempted to compare MDR1 polymorphisms and the absorption of CsA again without patients receiving amlodipine, but there was still no significant difference. CONCLUSIONS: There is no relationship between polymorphisms for MDR1 and CsA absorption, suggesting polymorphisms for MDR1 cannot account for the interpatient variability of CsA. Amlodipine, which is the substrate of PGP, significantly increased CsA absorption. These results indicate that PGP plays a significant role in CsA absorption, but its polymorphisms could not influence the CsA absorption.     

Excessive inflammation but decreased immunological response renders liver susceptible to infection in bile duct ligated mice

BACKGROUND/AIMS: Obstructive jaundice (OJ) is associated with increased surgical morbidity and infectious complication. The aim of the current study was to clarify the mechanism of excessive inflammation and susceptibility to infection in OJ. METHODS: C57/BL6 mice were subjected to bile duct ligation (BDL) or sham surgery. Expression tumor necrosis factor-alpha, macrophage inflammatory protein-2, monocyte chemoattractant protein-1, inducible protein-10, and interleukin (IL)-10, activation of nuclear factor kappa B, fluorescence activated cell sorter analysis, serum alanine aminotransferase levels, and histology were examined. Survival after lipopolysaccharide (LPS) administration or cecal ligation and puncture 3 or 14 d after surgery was determined. IL-1beta and interferon-gamma expression was examined after LPS administration. RESULTS: OJ induced nuclear factor kappa B activation and increased expression of macrophage inflammatory protein-2, which caused significant increases in neutrophil recruitment. Serum alanine aminotransferase levels increased consistent with histological observations in OJ. Mononuclear cells were recruited in the liver after BDL associated with monocyte chemoattractant protein-1 up-regulation. The recruitment of NK and T cells was varied, consistent with IP-10 expression during the time course of OJ. IL-10 expression was significantly up-regulated 14 d after BDL. After LPS administration, the mice at 3 d after BDL and at 3 and 14 d after sham surgery were all still alive, but all mice at 14 d after BDL died. After LPS administration, IL-1beta significantly increased in the mice at 14 d after BDL. CONCLUSIONS: Immune response such as expression of pro- and anti-inflammatory mediators and recruitment of immune cells may thus differ over the time course of OJ. Prolonged OJ may cause excessive inflammation, thus result in susceptibility to infection.     

Eldecalcitol reduces the risk of severe vertebral fractures and improves the health-related quality of life in patients with osteoporosis

Eldecalcitol reduces the risk of vertebral fractures in comparison to alfacalcidol in osteoporotic patients under vitamin D repletion. The aim of this study was to evaluate the effects of eldecalcitol on the spinal location of incident vertebral fractures, the severity of the fractures, and the changes in health-related quality of life (HRQOL) compared with those of alfacalcidol. The post hoc analysis has been performed on the data from the three-year, double-blind, randomized, head-to-head clinical trial of eldecalcitol versus alfacalcidol conducted in Japan. A total of 1054 patients were enrolled and randomized to take 0.75 μg eldecalcitol or 1.0 μg alfacalcidol daily for 3 years. The incidence of vertebral fractures was re-evaluated based on the location on the spine (upper T4–T10; lower T11–L4). The severity of vertebral fractures was determined by the semi-quantitative method, and the change in HRQOL was analyzed by using the Medical Outcomes Study Short Form 36-item questionnaire. The incidence of vertebral fracture at the lower spine was less in the eldecalcitol group than in the alfacalcidol group (p = 0.029). The incidence of severe vertebral fracture (Grade 3) was 3.8 % in the eldecalcitol group and 6.7 % in the alfacalcidol group, demonstrated a significant difference between the 2 groups (p = 0.036). Both eldecalcitol and alfacalcidol improved HRQOL in osteoporotic patients. Although no significant differences in each HRQOL scores were observed between eldecalcitol and alfacalcidol during the observational period, overall improvement from baseline of HRQOL scores were clearly observed in the eldecalcitol group. In conclusion, the incidences of lower spinal vertebral fractures and severe vertebral fractures were reduced further by eldecalcitol compared to alfacalcidol in the 3-year clinical trial. Daily treatment with eldecalcitol is effective in improving HRQOL, possibly owing to the reduced risk of lower spinal vertebral fractures and/or severe vertebral fractures.