Monotherapy with enoxaparin for the prevention of recurrent venous thromboembolism.

This study aimed to determine whether a weight-adjusted dose of subcutaneous enoxaparin is as effective and safe as oral acenocoumarol for the secondary prophylaxis of pulmonary embolism. Three hundred and eighty consecutive noncancer outpatients hospitalized with an episode of symptomatic pulmonary embolism selected treatment with acenocoumarol or enoxaparin at a dose of 1 mg/kg once daily after being informed of the type of administration and expected frequency of laboratory monitoring for both medicinal products. Endpoints were symptomatic recurrent thromboembolic events evaluated by standard objective testing, and a composite endpoint of recurrent venous thromboembolism, major bleeding, and death from any cause. One hundred and ninety-nine patients (52%) chose acenocoumarol therapy and 181 chose enoxaparin monotherapy. Four patients in the enoxaparin group (2.2%) and six patients in the acenocoumarol group (3%) had an objective thromboembolic recurrence (hazard ratio, 1.35; 95% confidence interval, 0.38-4.79; P = 0.64). Nine patients in the enoxaparin group (5.0%) had a hemorrhagic complication compared with 11 in the acenocoumarol group (5.5%) (P = 0.81). The hospital length of stay was shorter with enoxaparin compared with acenocoumarol (11 versus 16 days, P = 0.0001). Enoxaparin is as effective and safe as acenocoumarol in the secondary prevention of recurrent thromboembolic disease and is associated with shorter hospitalization.     

Downregulation of osteoblast markers and induction of the glial fibrillary acidic protein by oncostatin M in osteosarcoma cells require PKCdelta and STAT3.

The effects of OSM on proliferation and differentiation of osteosarcoma and nontransformed osteoblasts were analyzed. OSM downregulates osteoblast markers but induces the glial fibrillary acidic protein by the combined activation of PKCdelta and STAT3, offering new lines of therapeutic investigations. INTRODUCTION: Oncostatin M (OSM) is a multifunctional cytokine of the interleukin-6 family implicated in embryonic development, differentiation, inflammation, and regeneration of various tissues, mainly the liver, bone, and the central nervous and hematopoietic systems. One particularity of OSM relies on its growth inhibitory and pro-differentiating effects on a variety of tumor cell lines such as melanoma, providing arguments for a therapeutic application of OSM. The objective of this study was to analyze the effects of OSM on osteosarcoma cell lines proliferation and differentiation. MATERIALS AND METHODS: Proliferation was analyzed by 3H thymidine incorporation. Differentiation was analyzed by semiquantitative RT-PCR and immunocytochemistry for various markers. Alizarin red S staining was used to evaluate bone nodule formation. Morphological changes were studied by confocal and electron microscopy. Western blotting, kinases inhibitors, and dominant negative STAT3 were used to identified the signaling pathways implicated. RESULTS: OSM inhibits the growth of rat osteosarcoma cell lines as well as normal osteoblasts, in correlation with induction of the cyclin-dependent kinases inhibitor p21WAF1. However, OSM reduces osteoblast markers such as alkaline phosphatase, osteocalcin, and bone sialoprotein, leading to strong inhibition of mineralized nodule formation. This inhibitory effect is restricted to mature osteoblasts and differentiated osteosarcoma because OSM effectively stimulates osteoblast markers and bone nodule formation in early, but not late, bone marrow mesenchymal stem cell (BMSC) cultures. In osteosarcoma cells or BMSC, OSM induces expression of the glial fibrillary acidic protein (GFAP) as well as morphological and ultrastructural changes, for example, elongated shape and bundles of microfilaments in cell processes. Rottlerin (PKCdelta inhibitor), and to a lesser degree UO126 (MEK/ERK inhibitor), prevents the loss of osteoblastic markers by OSM, whereas dominant negative STAT3 prevents GFAP induction. CONCLUSIONS: These results highlight the particular gene expression profile of OSM-treated osteosarcoma cells and BMSCs, suggesting either a osteocytic or a glial-like phenotype. Together with the implication of PKCdelta, ERK1/2, and STAT3, these results offer new lines of investigations for neural cell transplantation and osteosarcoma therapy.     

Dynamics of bacterial hand contamination during routine neonatal care.

OBJECTIVE: To evaluate the dynamics of bacterial contamination of healthcare workers' (HCWs) hands during neonatal care. SETTING: The 20-bed neonatal unit of a large acute care teaching hospital in Geneva, Switzerland. METHODS: Structured observation sessions were conducted. A sequence of care began when the HCW performed hand hygiene and ended when the activity changed or hand hygiene was performed again. Alcohol-based handrub was the standard procedure for hand hygiene. An imprint of the five fingertips of the dominant hand was obtained before and after hand hygiene and at the end of a sequence of care. Regression methods were used to model the final bacterial count according to the type and duration of care and the use of gloves. RESULTS: One hundred forty-nine sequences of care were observed. Commensal skin flora comprised 72.4% of all culture-positive specimens (n = 360). Other microorganisms identified were Enterobacteriaceae (n = 55, 13.8%); Staphylococcus aureus (n = 10, 2.5%); and fungi (n = 7, 1.8%). Skin contact, respiratory care, and diaper change were independently associated with an increased bacterial count; the use of gloves did not fully protect HCWs' hands from bacterial contamination. CONCLUSIONS: These data confirm that hands become progressively contaminated with commensal flora and potential pathogens during neonatal care, and identify activities at higher risk for hand contamination. They also reinforce the need for hand hygiene after a sequence of care, before starting a different task, and after glove removal.     

The population distribution of the Met allele at the PRNP129 polymorphism (a high risk factor for Creutzfeldt-Jakob disease) in various regions of France and in West Europe.

The present study has been conducted to ascertain the level of allelic variation at codon 129 of the prion protein gene in France. Six French populations have been studied (Paris, Lille, Rennes, Chambéry, Grasse and Perpignan), totalling 1374 normal subjects. Mean heterozygosity in France is 46.5%, and the mean Met 129 allele (a high risk susceptibility factor for Creutzfeldt-Jakob disease) is 0.674. There is a genetic heterogeneity (chi(2)=38.44, p<0.001) between the six populations compared, and Met allele frequencies are inversely correlated with latitude (r=-0.93, p<0.01). Such an inverse correlation with latitude (r=-0.78, p=0.01) is also found when Met allele frequencies in France are compared to those already published in five other European countries and in Turkey. We hypothesise that high Met 129 frequencies populations may be at higher risk for Creutzfeldt-Jakob disease.     

Medizinische Beurteilungskriterien zu bandscheibenbedingten Berufskrankheiten der Lendenwirbelsäule (II)

The first part of this serial paper dealt with the medical criteria used in evaluation of the clinical picture caused by physical stress and the evaluation of other candidate causes and was published in issue no. 3/2005 (pp. 711–752) of Trauma and Berufskrankheit. This follow-up paper (II) presents criteria to be used in the evaluation of whether it is necessary to give up the occupations putting the spine at risk and in estimation of the degree of disability.