An adapter for stapling of a colorectal anastomosis

A technique involving the use of an end-to-end anastomosing stapler for low anterior resection has been modified to allow for a low colorectal anastomosis with an anus-pushing rubber adapter. The facility and safety of this procedure, under direct vision, has been confirmed.     

Increased intracellular activity of matrix metalloproteinases in neutrophils may be associated with delayed healing of infection without neutropenia in myelodysplastic syndromes

To investigate the influence of the intracellular activity of type II and type IV collagenases [matrix metalloproteinases (MMP)-2, MMP-8, and MMP-9] in neutrophils from patients with myelodysplastic syndromes (MDS), we tried to measure intracellular activity using flow cytometric techniques. We also studied the clinical features of patients showing high activity. The intracellular collagenase activity, expressed as a ratio to the standardized fluorescence intensity, in patients with MDS was significantly higher than normal volunteers (19.5±14.8 vs 13.3±6.8, p=0.024). The difference among subcategories of MDS according to the French-American-British (FAB) and WHO classifications was not significant. No significant influence of three variables of the International Prognostic Scoring System (IPSS) was seen on activity. Of 8 patients with activity of more than 26.9 (mean+2 standard deviations of normal controls), 5 experienced an episode of delayed healing of infection without neutropenia, while 1 of 43 patients with activity of less than 26.9 experienced such an episode (p=0.0002). The average collagenase activity of six patients with delayed healing of infection without neutropenia (44.7±28.9) was significantly higher than that of other MDS patients (16.0±7.1, p=0.005) (Fig. 4). It was also significantly higher than the activity of the control group (13.3±6.8, p=0.011). Our report suggests that increased collagenase activity in neutrophils may delay healing of infection. In addition, we suggest that increased collagenase activity may be an independent prognostic factor for the susceptibility to severe infection in MDS.     

Long-term efficacy and safety of rabeprazole in patients taking low-dose aspirin with a history of peptic ulcers: a phase 2/3, randomized,parallel-group, multicenter,extension clinical trial

A 24-week, double-blind, clinical trial of rabeprazole for the prevention of recurrent peptic ulcers caused by low-dose aspirin (LDA) has been reported, but trials for longer than 24 weeks have not been reported. The aim of this study is to assess the long-term efficacy and safety of rabeprazole for preventing peptic ulcer recurrence on LDA therapy. Eligible patients had a history of peptic ulcers on long-term LDA (81 or 100 mg/day) therapy. Patients with no recurrence of peptic ulcers at the end of the 24-week double-blind phase with rabeprazole (10- or 5-mg once daily) or teprenone (50 mg three times daily) entered the extension phase. Rabeprazole doses were maintained for a maximum of 76 weeks, including the double-blind 24-week period and the extension phase period (long-term rabeprazole 10- and 5-mg groups). Teprenone was randomly switched to rabeprazole 10 or 5 mg for a maximum of 52 weeks in the extension phase (newly-initiated rabeprazole 10- and 5-mg groups). The full analysis set consisted of 151 and 150 subjects in the long-term rabeprazole 10- and 5-mg groups, respectively, and the cumulative recurrence rates of peptic ulcers were 2.2 and 3.7%, respectively. Recurrent peptic ulcers were not observed in the newly-initiated rabeprazole 10- and 5-mg groups. No bleeding ulcers were reported. No clinically significant safety findings, including cardiovascular events, emerged. The use of long-term rabeprazole 10- and 5-mg once daily prevents the recurrence of peptic ulcers in subjects on low-dose aspirin therapy, and both were well-tolerated.     

Correction to: Quantitative evaluation of anti-resorptive agent-related osteonecrosis of the jaw using bone single photon emission computed tomography in clinical settings: relationship between clinical stage and imaging

Annals of Nuclear Medicine -     

In Vitro Potentiation of Carbapenems with ME1071, a Novel Metallo-β-Lactamase Inhibitor,against Metallo-β-Lactamase- Producing Pseudomonas aeruginosa Clinical Isolates

ME1071, a maleic acid derivative, is a novel specific inhibitor for metallo-β-lactamases (MBL). In this study, the potentiation of ME1071 in combination with several β-lactams was evaluated using MBL-producing Pseudomonas aeruginosa isolates. The rates of susceptibility of MBL producers to carbapenems (imipenem, biapenem, and doripenem) and ceftazidime were increased by 8 to 27% in the presence of 32 μg/ml of ME1071. The corresponding resistance rates were decreased by 13 to 46%, respectively. On the other hand, ME1071 showed weaker or no potentiation with non-MBL producers. The K_i value of ME1071 for IMP-1 was 0.4 μM, significantly lower than the K_m values of carbapenems for the IMP-1 enzyme. On the other hand, the K_i value of ME1071 for VIM-2 was 120 μM, higher than the K_m values of carbapenems for the VIM-2 enzyme. Results of this study indicate that ME1071 can potentiate the activity of ceftazidime and carbapenems against MBL-producing strains of P. aeruginosa.Carbapenem use has increased during the past 2 decades. This is due, in part, to carbapenems'' broad spectrum of antibacterial activity and their resistance to hydrolysis by extended-spectrum β-lactamases. However, the emergence of carbapenemases and other carbapenem resistance mechanisms is threatening this antibiotic class (18, 20). In a recent survey, 12.4% of Pseudomonas aeruginosa isolates from clinical specimens showed resistance to imipenem (8). In P. aeruginosa, carbapenem resistance has been attributed to two main mechanisms: (i) the loss of the OprD outer membrane porin channel and/or overexpression of some efflux pumps, possibly in combination with high-level production of the resident AmpC β-lactamase, and (ii) the production of carbapenem-hydrolyzing class A or class B β-lactamases (9, 18).Class B β-lactamases are metallo-β-lactamases (MBLs) that require zinc ions for their activity (5, 18). Although clinically significant, MBLs remain rare, though their frequency has been increasing in P. aereuginosa (3, 8). Most MBLs hydrolyze most β-lactams, including carbapenems such as imipenem, meropenem, biapenem, and doripenem. In Japan, the IMP-1 subgroup is the most prevalent MBL (8, 10). In Japan, nationwide surveillance studies have reported MBL producers to represent 2 to 3% of P. aeruginosa isolates from clinical specimens (8).The majority of MBL producers exhibit a multidrug-resistant (MDR) phenotype, including also resistance to aminoglycosides and fluoroquinolones (8, 10). For these reasons, there is interest in the administration of β-lactams together with an MBL inhibitor as therapy for infection by MBL-producing multidrug-resistant organisms.ME1071 (Fig. ​(Fig.1)1) is a novel specific inhibitor for MBLs discovered by Meiji Seika Kaisha Ltd. (Tokyo, Japan). The aim of this study was to evaluate the MBL-inhibitory activity of ME1071 by using 174 nonduplicate clinical isolates of MBL-producing P. aeruginosa and 16 nonduplicate non-MBL-producing P. aeruginosa isolates. The kinetic parameters of IMP-1 and VIM-2 for 5 carbapenems and ME1071 were also determined using purified enzymes.Open in a separate windowFIG. 1.Chemical structure of ME1071.(Part of this work was presented at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, September 2007.)     

Estimation of the duration after methamphetamine injection using a pharmacokinetic model in suspects who caused fatal traffic accidents

When the population parameters of drug pharmacokinetics in the human body system are known, the time-course of a certain drug in an individual can generally be estimated by pharmacokinetics. In the present two cases where methamphetamine abusers were suspected to have inflicted mortalities in traffic accidents, the time-elapse or duration immediately after methamphetamine injection to the time when the accidents occurred became points of contention. In each case, we estimated the time-course of blood methamphetamine after the self-administration in the suspects using a 2-compartment pharmacokinetic model with known pharmacokinetic parameters from the literatures. If the injected amount can be determined to a certain extent, it is easy to calculate the average time-elapse after injection by referring to reference values. However, there is considerable individual variability in the elimination rate based on genetic polymorphism and a considerably large error range in the estimated time-elapse results. To minimize estimation errors in such cases, we also analyzed genotype of CYP2D6, which influenced methamphetamine metabolism. Estimation based on two time-point blood samples would usefully benefit legal authorities in passing ruling sentences in cases involving similar personalities and circumstances as those involved in the present study.