Methicillin-resistant Staphylococcus aureus: A public health issue with economic consequences

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has become endemic worldwide in hospitals, and community-associated MRSA is spreading into the community at large. OBJECTIVES: To estimate the current cost of MRSA in Canada and to assess the magnitude of this public health issue. METHODS: An extensive review of the literature was conducted to gather epidemiology, health care resource utilization and cost data for MRSA in Canadian settings. The current MRSA burden was estimated using available cost data and the most recent epidemiology data. RESULTS: The rate of MRSA in Canadian hospitals increased from 0.46 to 5.90 per 1000 admissions between 1995 and 2004, while community-associated MRSA continued to spread into the community. Patients harbouring MRSA required prolonged hospitalization (average 26 days of isolation per patient), special control measures, expensive treatments and extensive surveillance. Total cost per infected MRSA patient averaged $12,216, with hospitalization being the major cost driver (81%), followed by barrier precautions (13%), antimicrobial therapy (4%) and laboratory investigations (2%). The most recent epidemiological data, combined with available cost data, suggest that direct health care cost attributable to MRSA in Canada, including cost for management of MRSA-infected and-colonized patients and MRSA infrastructure, averaged $82 million in 2004 and could reach $129 million in 2010. CONCLUSION: MRSA is a costly public health issue that needs to be tackled if the growing burden of this disease in Canadian hospitals and in the community is to be limited.     

Influence of HLA-DR genes on the production of rheumatoid arthritis-specific autoantibodies to citrullinated fibrinogen

OBJECTIVE: Antibodies directed against citrullinated fibrinogen are highly specific for rheumatoid arthritis (RA). This study was undertaken to test whether RA-associated HLA-DR alleles are associated with anti-citrullinated fibrinogen in RA patient sera and whether replacement of arginyl by citrullyl residues on fibrinogen peptides modifies their binding to HLA-DR molecules and their recognition by T cells. METHODS: Antikeratin, antifilaggrin, and anti-citrullinated fibrinogen antibodies were assayed in RA patients who had undergone HLA-DR typing. Direct assays were performed to investigate binding of citrullinated or native fibrinogen peptides (encompassing the entire alpha- and beta-chains of fibrinogen) to purified HLA-DR molecules. T cell proliferative responses to citrullinated or native fibrinogen peptides were measured in RA patients and controls. RESULTS: HLA-DRB1*0404 was associated with anti-citrullinated fibrinogen in RA sera (P = 0.002). For the RA-associated alleles HLA-DRB1*0401 and HLA-DR1, there was a nonsignificant trend toward association (P = 0.07). Multiple peptides from the alpha- and beta-chains of fibrinogen bound many HLA-DR alleles; DRB1*0404 was the best fibrinogen peptide binder. Citrullination did not influence fibrinogen peptide binding to HLA-DR or fibrinogen peptide recognition by T cells. Peripheral blood T cells that recognized native or citrullinated fibrinogen peptides were common in RA patients but not in healthy controls. CONCLUSION: The RA-associated HLA-DRB1*0404 allele is also associated with production of antibodies to citrullinated fibrinogen. DRB1*0401 and DRB1*01 tend to be associated with anti-citrullinated fibrinogen, but this is not statistically significant. Citrullination of fibrinogen peptide does not influence peptide-DR-T cell interaction. Finally, T cell proliferation in response to citrullinated or uncitrullinated fibrinogen peptides is frequent in RA patients and very infrequent in controls.     

Immunocytochemical detection of apoptosis in human odontoblasts

Pulpal chamber size decreases on ageing due to primary and secondary dentin deposition. This work was designed to find out the consequences of this pulp chamber reduction on odontoblast number and distribution. Twenty-one healthy human premolars were equally divided into three groups from 11-, 12.5- and 14-yr-old adolescents, respectively). The external and the internal perimeters of dentin were recorded on vestibulo-lingual sections, from buccal to lingual cemento-enamel junction using an image analysis system. Nuclei of the odontoblasts were recorded on 12 automatically selected fields. On nine erupted premolars (3 teeth from each 11-, 12.5- and 14-yr-old patients), apoptosis was detected by confocal microscopy using a modification of the original TUNEL method. Apoptotic cells were labeled in central pulp fibroblasts, perivascular endothelial cells, and in odontoblasts. When the pulp volume decreases due to primary dentin production, the decrease of the surface available for odontoblasts is compensated for by a multilayer distribution of cells. Secondary dentin deposition, associated with odontoblasts reorganization in a single layer, results in a hyperbolic decrease of the odontoblasts number. This decrease seems to result from a programmed cell death, which eliminates half of the odontoblasts over a 4-yr period.     

Daily and photoperiodic 2- 125I-melatonin binding changes in the pars tuberalis of the Syrian hamster (Mesocricetus auratus): Effect of constant light exposure and pinealectomy

Abstract: Using quantitative autoradiography, 2¹²⁵I-melatonin binding was investigated throughout the light/dark cycle in the pars tuberalis (PT) of the pituitary of adult Syrian hamsters kept for 8 weeks either in long or short photoperiod (LP or SP, respectively). Melatonin receptor density in the PT displayed photoperiod dependent daily variations (maximal values in LP). Indeed, in LP, melatonin receptor density underwent strong daily variations with maximal values during the first half of the light period and minimal values at the end of the night. These variations depended on changes in the maximal binding (B_max) without differences in the dissociation constant (K_d). In contrast, PT melatonin receptor density was constant and at a very low level throughout the 1ight:dark cycle in SP exposed animals. Daily PT melatonin receptor density variations of LP exposed animals were abolished by pinealectomy or continuous light exposure. These results show clearly that both at the daily and at the seasonal level the regulation of PT melatonin receptors is strongly dependent on circulating melatonin concentrations in the Syrian hamster, but that other regulatory factors, yet unclarified, might also play a role.     

Differential Seasonal Regulation of Melatonin Receptor Density in the Pars Tuberalis and the Suprachiasmatic Nuclei: A Study in the Hedgehog (Erinaceus europaeus, L.)

Using quantitative autoradiography, we have studied the seasonal changes of high affinity melatonin receptor density in both the SCN and PT of the hedgehog, a seasonal breeder and an hibernator. Animals in 3 different physiological states were studied: sexually active animals, and sexually inactive animals during the hibernation period, being then either euthermic or hypothermic. In sexually active animals, B_maax were 75.8 ± 7.1 fmol/mg protein in PT and 9.1 ± 0.5 fmol/mg protein in SCN; and Kd values were: 94 ± 22 pM in the PT and 101 ± 15 pM in the SCN. This specific binding was strongly decreased in the PT of sexually inactive animals. Moreover, this decrease was significantly stronger in hypothermic than in euthermic hedgehogs. Saturation studies and Scatchard analysis revealed that the observed decrease in the PT resulted from change in the B_max but not in the Kd, B_max values being respectively 56.4 ± 5.9 and 29.5 ± 1.9 fmol/mg protein in euthermic and hypothermic sexually at rest animals. In none of the different physiological states, did the density of melatonin receptors of the SCN show any changes, B_maax values being respectively 9.8 ± 0.5 and 9.8 ± 0.4 fmol/mg protein in euthermic and hypothermic sexually at rest animals. This shows for the first time a tissue-specific regulation of melatonin receptor density occurring in the PT but not in the SCN. Furthermore, this decrease of binding in the PT is correlated with both sexual inactivity and hibernation period. This strongly suggests that the mediation of the photoperiodic effect on seasonal functions like seasonal hypothermia and reproduction involves an effect of melatonin on the PT rather than on the SCN.     

Evidence of the presence in normal serum of a carrier of the serum thymic factor (FTS)

Chromatography of normal human or mouse serum on Sephadex G-150 revealed the presence of two peaks of activity in the rosette assay used for the characterization of the serum thymic factor (FTS). one peak corresponded to the elution volume of FTS (mol. wt. 867), the other to molecules with mol. wts. of 40000–60000. Both peaks were absent in serum of thymectomized (Tx) mice but could be induced in such Tx mice by injection of synthetic FTS. Study of the biological half-life of both peaks (assessed by the rosette assay) and demonstration of their specific retention on anti- FTS immunosorbent indicate, altogether with direct binding experiments, that FTS is transported in serum by a molecule with a mol. wt. of the order of that of albumin or prealbumin. It is apparent that FTS bound to this molecule is responsible for the biological FTS-like activity associated with large mol. wt. fractions of normal serum.