Maintenance treatment with esomeprazole following initial relief of non-steroidal anti-inflammatory drug-associated upper gastrointestinal symptoms: the NASA2 and SPACE2 studies

Non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclo-oxygenase-2 (COX-2) inhibitors, cause upper gastrointestinal (GI) symptoms that are relieved by treatment with esomeprazole. We assessed esomeprazole for maintaining long-term relief of such symptoms. Six hundred and ten patients with a chronic condition requiring anti-inflammatory therapy who achieved relief of NSAID-associated symptoms of pain, discomfort, or burning in the upper abdomen during two previous studies were enrolled and randomly assigned into two identical, multicentre, parallel-group, placebo-controlled studies of esomeprazole 20 mg or 40 mg treatment (NASA2 [Nexium Anti-inflammatory Symptom Amelioration] and SPACE2 [Symptom Prevention by Acid Control with Esomeprazole] studies; ClinicalTrials.gov identifiers NCT00241514 and NCT00241553, respectively) performed at various rheumatology, gastroenterology, and primary care clinics. Four hundred and twenty-six patients completed the 6-month treatment period. The primary measure was the proportion of patients with relapse of upper GI symptoms, recorded in daily diary cards, after 6 months. Relapse was defined as moderate-to-severe upper GI symptoms (a score of more than or equal to 3 on a 7-grade scale) for 3 days or more in any 7-day period. Esomeprazole was significantly more effective than placebo in maintaining relief of upper GI symptoms throughout 6 months of treatment. Life-table estimates (95% confidence intervals) of the proportion of patients with relapse at 6 months (pooled population) were placebo, 39.1% (32.2% to 46.0%); esomeprazole 20 mg, 29.3% (22.3% to 36.2%) (p = 0.006 versus placebo); and esomeprazole 40 mg, 26.1% (19.4% to 32.9%) (p = 0.001 versus placebo). Patients on either non-selective NSAIDs or selective COX-2 inhibitors appeared to benefit. The frequency of adverse events was similar in the three groups. Esomeprazole maintains relief of NSAID-associated upper GI symptoms in patients taking continuous NSAIDs, including selective COX-2 inhibitors.     

BeeDoctor,a Versatile MLPA-Based Diagnostic Tool for Screening Bee Viruses

The long-term decline of managed honeybee hives in the world has drawn significant attention to the scientific community and bee-keeping industry. A high pathogen load is believed to play a crucial role in this phenomenon, with the bee viruses being key players. Most of the currently characterized honeybee viruses (around twenty) are positive stranded RNA viruses. Techniques based on RNA signatures are widely used to determine the viral load in honeybee colonies. High throughput screening for viral loads necessitates the development of a multiplex polymerase chain reaction approach in which different viruses can be targeted simultaneously. A new multiparameter assay, called “BeeDoctor”, was developed based on multiplex-ligation probe dependent amplification (MLPA) technology. This assay detects 10 honeybee viruses in one reaction. “BeeDoctor” is also able to screen selectively for either the positive strand of the targeted RNA bee viruses or the negative strand, which is indicative for active viral replication. Due to its sensitivity and specificity, the MLPA assay is a useful tool for rapid diagnosis, pathogen characterization, and epidemiology of viruses in honeybee populations. “BeeDoctor” was used for screening 363 samples from apiaries located throughout Flanders; the northern half of Belgium. Using the “BeeDoctor”, virus infections were detected in almost eighty percent of the colonies, with deformed wing virus by far the most frequently detected virus and multiple virus infections were found in 26 percent of the colonies.     

Bone marrow suppression and severe anaemia associated with persistent Plasmodium falciparum infection in African children with microscopically undetectable parasitaemia

In sub-Saharan Africa the highest overlap between malaria and HIV infections occurs in female adolescents. Yet control activities for these infections are directed to different target groups, using disparate channels. This reflects the lack of priority given to adolescents and the absence of an accepted framework for delivering health and health-related interventions to this high-risk group. In this paper it is argued that female adolescents require a continuum of care for malaria and HIV – prior to conception, during and after pregnancy and that this should be provided through adolescent services. The evidence for this conclusion is presented. A number of African countries are commencing to formulate and implement adolescent-friendly policies and services and disease control programs for malaria and HIV will need to locate their interventions within such programs to ensure widespread coverage of this important target group. Failure to prioritize adolescent health in this way will seriously limit the success of disease control programs for malaria and HIV prevention.     

Accelerated net efflux of 3-O-[14C]methylglucose in isolated fat cells

A flow-tube apparatus suited for measurement of rapid efflux of sugars from adipocytes is described. Due to heterogeneity of fat cell populations, a conventional analysis of the time-course of net efflux of 3-O-methylglucose based on the integrated rate equation can produce gross errors in estimates of kinetic parameters. The half-saturation constant and maximum transport capacity for 3-O-methylglucose transport were found to be about 3-fold higher for net efflux than for equilibrium exchange flux, both in insulin-stimulated and non-stimulated adipocytes. This suggests asymmetric kinetic parameters for 3-O-methylglucose transport.     

Recognition of glycoconjugates by Helicobacter pylori. Comparison of two sialic acid-dependent specificities based on haemagglutination and binding to human erythrocyte glycoconjugates

Helicobacter pylori expresses separate binding characteristics depending on growth conditions, as documented by binding to human erythrocyte glycoconjugates. Cells grown in Ham's F12 liquid medium exhibited a selective sialic acid-dependent binding to polyglycosylceramides, PGCs (Miller-Podraza et al. (1996) Glycoconjugate J 13:453–60). There was no binding to traditional sialylated glycoconjugates like shorter-chain gangliosides, glycophorin or fetuin. However, cells grown on Brucella agar bound both to PGCs and other sialylated glycoconjugates. Fetuin was an effective inhibitor of haemagglutination caused by agar-grown cells, but had no or a very weak inhibitory effect on haemagglutination by F12-grown bacteria. PGCs were strong inhibitors in both cases, while asialofetuin was completely ineffective. The results indicate that H. pylori is able to express two separate sialic acid-dependent specificities, one represented by binding to fetuin, as described before, and another represented by a selective binding to PGCs. Abbreviations: PGCs, polyglycosylceramides; TLC, thin-layer chromatography; SDS PAGE, sodium dodecylsulfate polyacrylamide gel electrophoresis; BSA, bovine serum albumin; C, chloroform; M, methanol. The carbohydrate and glycosphingolipid nomenclatures are according to recommendations of IUPAC-IUB Commission on Biochemical Nomenclature (Lipids (1977) 12:455–68; J Biol Chem (1982) 257:3347–51 and J Biol Chem (1987) 262:13–18). This revised version was published online in November 2006 with corrections to the Cover Date.     

Increased lymphocytic aminopeptidase N/CD13 promoter activity after cell‐cell contact

Aminopeptidase N (APN)/CD13 is a transmembrane ectoenzyme expressed on a wide variety of cells. With respect to haematopoietic cells, APN/CD13 has been considered specific for the myeloid lineage, because granulocytes and monocytes/macrophages, but not lymphocytes of peripheral blood, show a surface expression of CD13 antigen. However, we could recently show that cell‐cell contact of lymphocytes with endothelial cells, monocytes, and fibroblast‐like synoviocytes (SFCs) results in an increase of steady‐state APN/CD13 mRNA and a rapid expression of cell‐surface protein on the lymphocytes. In this study using the Dual‐Luciferase reporter assay, we demonstrate that interaction of the T‐cell line Jurkat with SFCs results in a higher activity of the APN/CD13 myeloid promoter in T cells. An enhancer located between the myeloid and epithelial APN/CD13 promoter increases the response of the promoter to the cell‐cell contact‐induced expression of APN/CD13 in lymphocytes. Adhesion of lymphocytes to extracellular matrix did not result in increased promoter activity. The lymphocytic promoter response induced by direct cell‐cell contact with SFCs is not affected by mutations of a proximal promoter element (nucleotides −48 to −35), which has a possible functional role in the basal APN/CD13 gene expression in lymphocytes. Upregulated peptidase‐promoter activity via cell‐cell contact shown in this study for the first time is discussed as a general mechanism in peptidase induction. J. Cell. Biochem. 80:115–123, 2000. © 2000 Wiley‐Liss, Inc.     

Composition of bryozoan assemblages related to depth in Svalbard fjords and sounds

Svalbard bryozoan communities were investigated along a depth range from the surface to 296 m between the inner glacial fronts and fjord mouths during 2001 and 2002. The main study area was Kongsfjorden (79°N, 12°E). A total of 137 taxa of bryozoans were identified: 108 to species, 24 to genus, 3 to family, 1 to order and 1 to phylum level. Cluster and multidimensional scaling analyses revealed four distinct assemblages of bryozoans: shallow (0–40 m; 68 taxa), deep (40–296 m; 80 taxa), inner fjordic (three taxa) and an assemblage found on small stones in shallow waters (nine taxa). The inner fjordic assemblage was recorded from the front of tidal glaciers extending about 10 km out into the fjord. In terms of abundance, Celleporella hyalina Linnaeus dominated in shallow areas (18%), Hippothoa arctica Kluge (55%) in deep water, Alcyonidium disciforme Smitt (86%) proximate to glaciers fronts and Electra arctica Borg on small stones (98%). The species were classified according to their depth range as a stenobathic-shallow (46 taxa), stenobathic-deep (57 taxa) and eurybathic-generalist (21 taxa). Mean diversity measures did not show any significant differences between the shallow and deep communities. The bryozoan assemblages seem to be structured primarily by processes related to depth and sediment characteristics.     

Reliability of international normalised ratios from two point of care test systems: comparison with conventional methods

Objective To find out how accurately two point of care test systems—CoaguChek Mini and TAS PT-NC (RapidPointCoag)—display international normalised ratios (INRs).Design Comparison of the INRs from the two systems with a “true” INR on a conventional manual test from the same sample of blood.Setting 10 European Concerted Action on Anticoagulation centres.Participants 600 patients on long term dosage of warfarin.Main outcome measures Comparable results between the different methods.Results The mean displayed INR differed by 21.3% between the two point of care test monitoring systems. The INR on one system was 15.2% higher, on average, than the true INR, but on the other system the INR was 7.1% lower. The percentage difference between the mean displayed INR and the true INR at individual centres varied considerably with both systems.Conclusions Improved international sensitivity index calibration of point of care test monitors by their manufacturers is needed, and better methods of quality control of individual instruments by their users are also needed.