Serum soluble interleukin-2 receptor,interleukin-6, and tumor necrosis factor-alpha levels in children with celiac disease: response to treatment

OBJECTIVES: T-cell mediated immune response to dietary gluten and cytokines release are important for the enteropathy seen in celiac disease. We investigated the serum levels of soluble interleukin-2 receptor, interleukin-6, and tumor necrosis factor-alpha in celiac children before and after gluten exclusion. METHODS: Cytokine levels were determined using enzyme immunoassay in serum from 12 untreated celiac patients, 16 treated celiac patients on a gluten-free diet for at least two years, and from 26 control children. Eight of 12 untreated patients were also investigated at 6 and 12 months after gluten exclusion. Serum IgA antiendomysium antibodies were also assayed by indirect immunofluorescence. RESULTS: Soluble interleukin-2 receptor and interleukin-6 levels were significantly increased in untreated celiac patients compared with treated and control children. There was no difference in the tumor necrosis factor-alpha levels between the groups. Soluble interleukin-2 receptor levels were the only ones significantly decreased at 12 months after gluten exclusion. However, soluble interleukin-2 receptor and interleukin-6 levels at 12 months were significantly higher compared with controls. Antiendomysium antibodies had a diagnostic sensitivity of 100% and the titers decreased significantly after 12 months of gluten exclusion. A significant positive correlation was found between antiendomysium antibody titers with both soluble interleukin-2 receptor and interleukin-6 values. CONCLUSIONS: The serum soluble interleukin-2 receptor and interleukin-6 levels may be used as a noninvasive measure of celiac disease activity and response to treatment.     

Wanted: a national standard for early hearing detection and intervention outcomes data

The Joint Committee on Infant Hearing (JCIH, 2000) has presented principles and guidelines for universal newborn hearing screening and early hearing detection and intervention (EHDI). The guidelines describe the need for a national data set for early hearing detection and intervention. The guidelines fail to provide the specific constructs for such a data set. To the authors' knowledge, no nationally proposed uniform data structure exists to capture EHDI services' outcome metrics. This article presents a proposed newborn hearing screening and EHDI data model. This model was developed to record EHDI outcomes data from Military Health System birthing centers. The data are to be collected for tracking implementation of Healthy People 2010 goals related to newborn hearing screening and EHDI programs within the Military Health System. In this article, the authors use the T. Helfer, A. Shields, and K. Gates (2000) methods to model a uniform structure for collection of newborn hearing screening and EHDI data. They also discuss expansion of the data model for application to public health reporting of EHDI outcomes in the civilian sector to include integration of Census Bureau demographic data and geographic information system data to further enhance the research value of these EHDI outcomes data. They offer the data model with the intention of supporting national research efforts for studying the efficacy of EHDI programs and to help establish a national evidence-based practice database for such programs.     

Synthesis and biological activity of the penem antibiotic MEN 10700 and its orally absorbed ester MEN 11505

The synthesis and biological properties of the new penem antibiotic MEN 10700 (6) and of its selected oral prodrug MEN 11505 (8f) are described. MEN 10700 showed a broad spectrum of activity, with high potency both on Gram-positive and Gram-negative strains. It also exhibited good antibacterial activity toward anaerobes and on strains selected for their resistance to other antibacterial agents (cefotaxime- or ceftazidime-resistant Gram-negative strains, ciprofloxacin-resistant E. coli, extended spectrum beta-lactamase producing and cephalosporinase inducible enterobacteria). MEN 10700 showed a very high stability to enzymatic degradation by renal dehydropeptidase DHP-I. After oral administration in rats of the pivaloyloxymethyl ester prodrug MEN 11505, the relative bioavailability of MEN 10700 was calculated as F=43%.     

Third genome size category of avian paramyxovirus serotype 1 (Newcastle disease virus) and evolutionary implications

The goal of the study was to establish if there was a relationship between molecular patterns and virus evolution. Therefore the complete genome sequence of two distinct apathogenic Newcastle disease virus (NDV) strains was determined and a third genome size category, containing 15,198 nucleotides, was recognized. Phylogenetic analysis revealed that two major separations resulting in three genome size categories occurred during the history of NDV. An ancient division in the primordial reservoir (wild waterbird species) led to two basal sister clades, class I and II, with genome sizes 15,198 (due to a 12 nucleotide insert in the phosphoprotein gene) and 15,186 nucleotides, respectively. Ancestors of only class II viruses colonized chicken populations and subsequently converted to virulent forms. These took place more than once and resulted in an early lineage [including genotypes I–IV and H33(W)] with genome size of 15,186 nucleotides. A second division occurred in the 20th century in the secondary (chicken) host. This gave rise to the branching-off of a clade (including recent genotypes V–VIII consisting of only pathogenic viruses) with the concomitant insertion of six nucleotides into the 5′ non-coding region of the nucleoprotein gene thereby increasing the genome size to 15,192 nucleotides.     

Method for Simultaneous Determination of Free Concentration,Total Concentration,and Plasma Binding Capacity in Clinical Samples

Most quantitative research methods are based on measuring either the total or the free concentration of an analyte in a sample. However, this is often insufficient for the study of complex biological systems. The main objective of this research was to develop new methods for providing more information from samples: the free concentration (C_f), the total concentration (C_t), and the plasma binding capacity (PBC). Samples were processed using microextraction and ultrafiltration. For each of these techniques, two quantification procedures were used: addition of isotopically labeled standard and repeated analysis of the same sample. The new methods were validated by analyzing clinical samples and samples with known concentrations. Methods based on addition of labeled compound were found to be the fastest, and most reproducible. For analysis of clinical samples, methods based on microextraction were more sensitive and more accurate than those based on ultrafiltration. For analysis of pooled plasma samples, the overall accuracy of all approaches to determine PBC, testosterone C_f, and testosterone C_t was between 94 and 109%, 87–113%, and 94–122% respectively. The new approach goes beyond a simple concentration measurement, giving more information from clinical samples, with great potential for personalizing drug dosage and therapy to the needs of individual patients.     

Distamycin inhibits the binding of a nuclear factor to the -278/-256 upstream sequence of the human HLA-DR alpha gene

In this study we analyse the effects of the anti-tumor compound distamycin on the binding of nuclear factor(s) to a synthetic oligonucleotide (GTATA/IFN-gamma) mimicking a putative regulatory region of the human HLA-DR alpha gene. This region contains the sequence (GTATA), that is required for nuclear protein binding and is likely to interact with distamycin. The present results, by showing that distamycin inhibits the interaction between nuclear factors and the GTATA/IFN-gamma oligonucleotide, suggest that distamycin might alter the binding of transacting factors to cis-elements containing AT/TA sequences. Alterations of nuclear protein binding to specific target sequences could be one of the molecular mechanism(s) by which distamycin exerts its antiproliferative activity on living cells.     

Coagulation Contact Phase Factors and Inhibitors in β-Thalassemia Major Children

Selected hemostatic parameters of 23 children affected by β-thalassemia major were studied and compared to an age- and sex-matched group. Plasma prekallikrein level was reduced in all patients, splenectomized or not. In splenectomized patients, platelet count and in vitro platelet aggregability were significantly increased and Protein C was slightly increased. The activated partial thromboplastin time was prolonged and the normotest reduced. Finally, a reduction in the plasma levels of fibrinogen and of vitamin K-dependent proteins, including the antithrom-botic Protein C, was observed in nonsplenectomized patients. Our data indicate that the hemostatic system in patients with thalassemia major may be altered. The relationship between these laboratory changes and clinical manifestations remains to be established.     

Detection of extended-spectrum-beta-lactamase-positive Escherichia coli in bile isolates from two dogs with bacterial cholangiohepatitis

This is the first report of Escherichia coli isolates producing CTX-M-15, the predominant type of extended-spectrum β-lactamase (ESBL) associated with clinical disease in humans in the United Kingdom, in a United Kingdom pet dog. This report also describes the first isolation of CTX-M/Tem ESBL-positive E. coli from bile in dogs with hepatobiliary disease.