Association between adherence to evidence-based guidelines for the prescription of non-steroidal anti-inflammatory drugs and the incidence of gastric mucosal lesions in Japanese patients

Objective  

Recently, guidelines for the treatment and prevention of ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs) were established. This study investigated the association between the current adherence to the guidelines and the incidence of gastric mucosal lesions caused by NSAIDs.     

Endoluminal MR imaging of porcine gastric structure in vivo

Background and aims

Recently, several new endoscopic instruments have been developed. However, even with the full use of current modalities, the safety of endoscopic surgery is not guaranteed. Information regarding factors such as fibrosis and the blood vessels under the mucosa is very important for avoiding procedure-related complications. The aim of this study was to define the detailed anatomy of the gastric wall structure in vivo using original endoluminal radiofrequency coils for safer endoscopic therapy.

Methods

Swine were used as the subjects and controlled with general anesthesia. Anatomical images were obtained with T1-weighted fast spin echo (T1FSE) and T2-weighted fast spin echo (T2FSE). Dynamic magnetic resonance (MR) angiography was also obtained with three-dimensional T1-weighted fast spoiled gradient recalled acquisition in the steady state (3D-DMRA) following the injection of hyaluronic acid sodium into the submucosal layer.

Results

Porcine gastric wall structure was visualized, and four layers were discriminated in the T1FSE and T2FSE images. The vascular structure was clearly recognized in the submucosa on 3D-DMRA.

Conclusion

Endoluminal MR imaging was able to visualize the porcine stomach with similar quality to endoscopic ultrasonography imaging. Additionally, it was possible to visualize the vascular structures in the submucosal layer. This is the first report to show that blood vessels under the gastric mucosa can be depicted in vivo.     

The Bi-Surface total knee arthroplasty: Minimum 10-year follow-up study

The Bi-Surface Knee System (Japan Medical Material, Kyoto, Japan), which has a unique ball-and-socket joint and whose femoral component is made from alumina ceramic, was designed to improve deep knee flexion and long-term durability after total knee arthroplasty. The purpose of this study was to review the clinical results of a minimum 10-year follow-up. Between 1989 and 1997, 507 total knee arthroplasties were carried out in 371 patients. Forty three patients (56 knees) were lost to follow-up. The mean age of the patients at operation was 68.5 years, and the patients were followed up for a mean of 11.7 years. The knees were evaluated on the basis of Knee Society knee score and functional score, radiographs, and Kaplan–Meier survivorship analysis. The knee score was improved from 38.9 ± 17.4 points preoperatively to 93.3 ± 7.8 points at the latest follow-up (p < 0.001). The functional score was improved from 34.9 ± 19.3 points to 52.7 ± 24.1 points (p < 0.001). The mean range of flexion was improved from 118.7 ± 21.7° to 124.2 ± 20.8° (p < 0.001). The critical angle, which means the border to gain more range of flexion postoperatively, was 130.1°. Kaplan–Meier survivorship at 10-year was 95.9% with any operation or radiographic failure as the end point. The corresponding rate was 97.4% with revision of any component as the end point. No ceramic component fracture occurred. The present study demonstrates that good range of flexion was maintained for a long time after total knee arthroplasty with excellent durability. The Bi-Surface Knee System appears to have achieved its design objectives.     

pH dependence and inhibition by extracellular calcium of proton currents via plasmalemmal vacuolar-type H+-ATPase in murine osteoclasts

The vacuolar-type H⁺-ATPase (V-ATPase) in the plasma membrane of a variety of cells serves as an acid-secreting pathway, and its activity is closely related to cellular functions. Massive proton secretion often leads to electrolyte disturbances in the vicinity of the cell and may in turn affect the activity of the V-ATPase. We characterized, for the first time, the proton currents mediated by plasmalemmal V-ATPase in murine osteoclast-like cells and investigated its activity over a wide range of pH gradients across the membrane (ΔpH = extracellular pH – intracellular pH). The V-ATPase currents were identified as outward H⁺ currents and were dependent on ATP and sensitive to the inhibitors bafilomycin A₁ and N , N '-dicyclohexylcarbodiimide. Although H⁺ was transported uphill, the electrochemical gradient for H⁺ affected the current. The currents were increased by elevating ΔpH and depolarization, and were reduced by lowering ΔpH and hyperpolarization. Elevation of extracellular Ca²⁺ (5–40 m m ) diminished the currents in a dose-dependent manner and made the voltage dependence more marked. Extracellular Mg²⁺ mimicked the inhibition. With 40 m m Ca²⁺, the currents decreased to < 40% at 0 mV and to < 10% at about −80 mV. Increases in the intracellular Ca²⁺ (0.5–5 μ m ) did not affect the current. The data suggest that acid secretion through the plasmalemmal V-ATPase is regulated by a combination of the pH gradient, the membrane potential and the extracellular divalent cations. In osteoclasts, the activity-dependent accumulation of acids and Ca²⁺ in the closed extracellular compartment might serve as negative feedback signals for regulating the V-ATPase.     

Antigen‐specific airway IL‐33 production depends on FcγR‐mediated incorporation of the antigen by alveolar macrophages in sensitized mice

Although interleukin (IL)‐33 is a candidate for the aggravation of asthma, the mechanisms underlying antigen‐specific IL‐33 production in the lung are unclear. Therefore, we analysed the mechanisms in mice. Intra‐tracheal administration of ovalbumin (OVA) evoked increases in IL‐33 and IL‐33 mRNA in the lungs of both non‐sensitized and OVA‐sensitized mice, and the increases in the sensitized mice were significantly higher than in the non‐sensitized mice. However, intra‐tracheal administration of bovine serum albumin did not increase the IL‐33 level in the OVA‐sensitized mice. Depletion of neither mast cells/basophils nor CD4⁺ cells abolished the OVA‐induced IL‐33 production in sensitized mice, suggesting that the antigen recognition leading to the IL‐33 production was not related with either antigen‐specific IgE‐bearing mast cells/basophils or memory CD4⁺ Th2 cells. When a fluorogenic substrate‐labelled OVA (DQ‐OVA) was intra‐tracheally administered, the lung cells of sensitized mice incorporated more DQ‐OVA than those of non‐sensitized mice. The lung cells incorporating DQ‐OVA included B‐cells and alveolar macrophages. The allergic IL‐33 production was significantly reduced by treatment with anti‐FcγRII/III mAb. Depletion of alveolar macrophages by clodronate liposomes significantly suppressed the allergic IL‐33 production, whereas depletion of B‐cells by anti‐CD20 mAb did not. These results suggest that the administered OVA in the lung bound antigen‐specific IgG Ab, and then alveolar macrophages incorporated the immune complex through FcγRII/III on the cell surface, resulting in IL‐33 production in sensitized mice. The mechanisms underlying the antigen‐specific IL‐33 production may aid in development of new pharmacotherapies.     

Isolation of vaccine-derived type 1 polioviruses displaying similar properties to virulent wild strain Mahoney from sewage in Japan

Type 1, 2, and 3 vaccine-derived polioviruses were isolated from a sewage disposal plant located downstream of the Oyabe River in Toyama Prefecture, Japan, between October 1993 and September 1995. Neurovirulence was analyzed in 13 type 1 vaccine-derived strains, using mutant analysis by polymerase chain reaction and restriction enzyme cleavage (MAPREC). Nine strains (69%) were estimated to have marked neurovirulence. Some of the neutralizing antigenic sites, temperature sensitivity, and plaque-forming ability of two virulent vaccine-derived poliovirus strains were similar to Mahoney strain. The neutralizing activity of human sera obtained after oral poliomyelitis vaccine (OPV) administration against one of the virulent vaccine-derived polioviruses was examined. Although all human sera showed sufficient neutralizing activity for the prevention of poliomyelitis by vaccine-derived poliovirus strains, a lower titer than that against Sabin type 1 strain was observed. Vaccination against virulent vaccine-derived poliovirus will be effective. However, the environmental presence of viruses that have properties similar to those Mahoney strain is a threat. The introduction of inactivated poliovirus vaccine (IPV), and well-maintained herd immunity, together with reinforced environmental surveillance is important for the final phase of the polio eradication program by the World Health Organization (WHO).     

Developing technologies for epigenomic analysis and clinical application of molecular diagnosis

Epigenetic alterations such as DNA methylation play a key role in silencing genes in carcinogenesis. DNA methylation leads to the silencing of a variety of genes involved in cell-cycle control, apoptosis, cell signaling and DNA repair in gastrointestinal cancer. The recent development of methylation analysis offers a quantitative, high sensitivity, high throughput and reliable method. This approach enabled us to apply methylation analysis in a clinical setting. The miR-34b/c gene is a tumor suppressor that is frequently silenced by DNA methylation in colorectal and gastric cancer (GC). Accurate preoperative diagnosis of invasiveness is essential for selecting appropriate therapeutic options for colorectal cancer, but the distinction between invasive and non-invasive colorectal tumor is often difficult. Methylation levels of miR-34b/c in colorectal washing fluid were highly discriminative between invasive and non-invasive tumors. Previous reports show that H. pylori infection, which plays an important role in gastric carcinogenesis, induces the methylation of various genes in the noncancerous gastric mucosae. These finding suggest that the accumulation of aberrant DNA methylation in noncancerous gastric mucosa is involved in the epigenetic field defect. Methylation of miR-34b/c was significantly elevated in noncancerous gastric mucosae of multiple GC patients compared with those of single GC patients and H. pylori-positive healthy individuals. These results suggest that methylation might be a useful marker for the diagnosis and risk assessment of cancer.     

CD22 serves as a receptor for soluble IgM

CD22 (Siglec-2) is a B-cell membrane-bound lectin that recognizes glycan ligands containing α2,6-linked sialic acid (α2,6Sia) and negatively regulates signaling through the B-cell Ag receptor (BCR). Although CD22 has been investigated extensively, its precise function remains unclear due to acting multiple phases. Here, we demonstrate that CD22 is efficiently activated in trans by complexes of Ag and soluble IgM (sIgM) due to the presence of glycan ligands on sIgM. This result strongly suggests sIgM as a natural trans ligand for CD22. Also, CD22 appears to serve as a receptor for sIgM, which induces a negative feedback loop for B-cell activation similar to the Fc receptor for IgG (FcγRIIB).     

Biventricular support using a centrifugal pump in a 6 year old with fulminant myocarditis

We experienced a case of ventricular assist with both a pulsatile-flow and a continuous-flow pump in a pediatric patient, and herein report the clinical course and characteristics of the pumps. A 6-year-old female was diagnosed with fulminant myocarditis and transferred to our hospital for mechanical support. After 12 days of extracorporeal membrane oxygenation, we implanted a left ventricular assist device (LVAD) and a right ventricular assist device (RVAD) using centrifugal Gyro pumps with a membrane oxygenator in a paracorporeal fashion. The membrane oxygenator was removed on postoperative day (POD) 4, and the patient was weaned from the respirator on POD 6. The LVAD was exchanged on POD 13 and 17, and the RVAD was exchanged on POD 14 because of thrombus formation inside the pumps. The RVAD was removed on POD 25. On POD 32, the patient experienced cerebral infarction and the centrifugal Gyro pump was switched to an extracorporeal pulsatile pump. No thromboembolic event occurred after pump conversion, although continuous administration of vasodilators was required to avoid hypertension. She underwent successfully heart transplantation in the USA after 8 months of ventricular support. A centrifugal pump is considered useful for pediatric patients, as pump flow and blood pressure can be relatively easily controlled in the postoperative acute phase compared with the pulsatile pump. However, special care should be taken to monitor for thrombus formation when support length becomes longer than 13 days, and a switch to a pulsatile pump should be considered once the hemodynamic status stabilizes.     

CT and MR imaging findings of xanthogranulomatous cholecystitis: correlation with pathologic findings

The aim of this study was to evaluate CT and MRI findings in xanthogranulomatous cholecystitis (XGC) and to correlate the imaging findings with various pathologic parameters. The study included 13 patients with histopathologically confirmed XGC. The CT (n=13) and MRI (n=5) obtained in these patients were evaluated retrospectively. On CT, low-attenuation areas in the wall of XGC correlated with foam and inflammatory cells or necrosis and/or abscess in XGC. Areas of iso- to slightly high signal intensity on T2-weighted images, showing slight enhancement at early phase and strong enhancement at last phase on dynamic study, corresponded with areas of abundant xanthogranulomas. Areas with very high signal intensity on T2-weighted images without enhancement corresponded with necrosis and/or abscesses. Luminal surface enhancement (LSE) of gallbladder wall represented preservation of the epithelial layer. The early-enhanced areas of the liver bed on dynamic CT and MR images corresponded with accumulation of inflammatory cells and abundant fibrosis. Our results indicate that CT and MRI findings correlate well with the histopathologic findings of XGC.