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101.
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While attempts are being made to improve health promotion by following a linear Evidence-Based (EB) approach, the actors involved are aware that the quality of health promotion is not just a matter of supplying 'evidence-based' interventions to local practitioners, but the result of a situated coproduction process that depends on many factors. This paper explores what constitutes an intervention that works from the perspective of health promotion professionals (HPP), and how, according to them, the development and implementation of interventions should be improved. We interviewed 81 HPPs about the use of 10 health promotion interventions at 30 Municipality Health Services in The Netherlands. The HPPs described an intervention that works as something that produces its intended effects after being realized in a local situation. Interventions are realized by combining elements of a supplied intervention (e.g. a theory, artefacts) with elements that are situated in the local context (e.g. funding, local network). Interventions that are transferred contain implicit assumptions about local contexts, but it is often unclear what precisely constitutes an intervention and what is assumed of local contexts. An intervention that works is a situated configuration of aligned elements. A linear EB approach depends on the realization of the local circumstances in which 'evidence based' interventions can work. Various strategies are possible for approximating such circumstances, but the core assumption that the configuration that is realized in practice is similar to the 'evidence based' intervention seems unrealistic for most health promotion in The Netherlands. Under such circumstances, attention should shift from central quality assurance to the system of actors and the distributed actions and heterogeneous learning processes that together add up to interventions that work. 相似文献
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Studies on levamisole--induced agranulocytosis 总被引:1,自引:0,他引:1
Thompson JS; Herbick JM; Klassen LW; Severson CD; Overlin VL; Blaschke JW; Silverman MA; Vogel CL 《Blood》1980,56(3):388-396
Widespread clinical trials of leavo-tetramisole (levamisole) as an immunopotentiating agent in rheumatoid arthritis, metastatic carcinoma, and immunodeficiency states have been complicated by agranulocytosis (AGC) in 2.5%-13% of patients. Other than a relationship with prolonged high dosage, very little is known regarding the pathogenesis of levamisole-induced AGC. Whereas leukoagglutination was negative, fluorochromatic microgranulocytotoxicity (GCY) tests were positive with serum from 10 of 10 acutely neutropenic patients. The antibody was IgM, reacted with 100% of unrelated granulocytes, but not with T or B lymphocytes. Some sera also reacted with monocytes and the myeloid cell line, K-562. Tests for antigen-antibody complexes or cold autoantibodies were negative. Although clinical evidence strongly suggests a haptene (drug) mechanism, in vitro mixing experiments were also negative. An alternative choice parallels the model of aldomet- induced Coombs'-positive hemolytic anemia. Finally, GCY first became positive 2-3 mo prior to the onset of AGC on two patients, suggesting the possibility of identifying those at risk well before the onset of neutropenia. 相似文献
105.
Enhancement of erythrocyte superoxide dismutase activity: effects on cellular oxidant defense 总被引:3,自引:0,他引:3
To delineate further the role of superoxide dismutase (SOD) in red blood cell (RBC) oxidant defense, normal human erythrocytes were osmotically lysed and resealed in the presence of varying concentrations of exogenous SOD. This resulted in a dose-dependent increase in SOD activity in the resealed erythrocytes while maintaining nearly normal RBC hemoglobin concentration (less than 10% decrease from the control value), cell volume, and cellular deformability. Surprisingly, a five- or ninefold increase in SOD activity yielded no additional protection against superoxide-generating drugs (phenazine methosulfate or menadione sodium bisulfite). No significant differences were observed between the control and SOD-loaded RBCs in O2-driven methemoglobin formation or generation of thiobarbituric acid-reactive substances. In contrast, RBCs with elevated SOD activity pretreated with sodium azide (to block catalase activity) or 1-chloro-2,4- dinitrobenzene (to deplete reduced glutathione, GSH) showed significantly enhanced methemoglobin generation in response to superoxide generating drugs. No differential response was noted between the control, control-resealed, and SOD-loaded RBCs to oxidants other than superoxide. Based on our results and other data, we conclude that elevated SOD activity may imbalance cellular oxidant defense, resulting in enhanced oxidation due to the accelerated generation of H2O2, the product of O2- dismutation. This effect is significantly exacerbated under conditions in which H2O2 catabolism is altered. 相似文献
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108.
Clonality in myelodysplastic syndromes (MDS) has been studied with various techniques including glucose-6-phosphate dehydrogenase (G6PD) isoenzyme and cytogenetic analyses, and with molecular techniques such as gene deletion studies and the analysis of restriction fragment- length polymorphisms (RFLP) of X-linked genes. In this study, we investigated the use of fluorescence in situ hybridization (FISH) with a chromosome-specific probe to examine cytogenetic clonality in peripheral blood (PB) cells from three patients with MDS. In each case, trisomy 8 was shown by conventional cytogenetic analysis at the time of the initial diagnosis. By using FISH with a probe for the centromere of chromosome 8, we identified the trisomy in individual PB cells from Wright-stained smears. With this technique, we could determine the cell lineage involved by the trisomy, and through serial analyses we could assess the response of the clonal and nonclonal cells to growth-factor therapy, and the expansion of the trisomic clone over time. In each of the three cases, various proportions of granulocytes, monocytes, eosinophils, and basophils showed trisomy 8 by FISH analysis. In none of the cases did we detect trisomy 8 in lymphocytes. By analysis of PB cells before and during therapy with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF), we found that GM-CSF stimulated both trisomic and disomic cells. During a 1-year period of sequential study, we detected an abrupt increase in the percentage of trisomic cells in one patient, a stable percentage in another, and a slowly increasing percentage in the third. The abrupt increase in the first patient preceded a transformation to a more acute phase by 2 months. We conclude that FISH analysis of PB cells of patients with MDS offers an additional approach to the study of clonality in this disorder. In some cases this analysis may provide a useful and simple means of assessing response to therapy and progression of disease. 相似文献
109.
Molecular cloning, chromosomal location, and tissue-specific expression of the murine cathepsin G gene 总被引:5,自引:1,他引:5
Heusel JW; Scarpati EM; Jenkins NA; Gilbert DJ; Copeland NG; Shapiro SD; Ley TJ 《Blood》1993,81(6):1614-1623
We previously have characterized a cluster of genes encoding cathepsin G (CG) and two other CG-like hematopoietic serine proteases, CGL-1 and CGL-2, on human chromosome 14. In this report, we clone and characterize a novel, related murine hematopoietic serine protease gene using human CG (hCG) cDNA as the probe. This murine gene spans approximately 2.5 kb of genomic DNA, is organized into five exons and four introns, and bears a high degree of homology to hCG at both nucleic acid (73%) and deduced amino acid (66%) levels. The predicted cDNA contains an open reading frame of 783 nucleotides that encodes a nascent protein of 261 amino acids. Processing of a putative signal (pre) peptide of 18 residues and an activation (pro) dipeptide would generate a mature enzyme of approximately 27 Kd that has an estimated pI of 12.0. Conserved residues at His44, Asp88, and Ser181 form the characteristic catalytic triad of the serine protease superfamily. The gene is tightly linked to the CTLA-1 locus on murine chromosome 14, where the serine protease genes mCCP1-4 are clustered. Expression of this gene is detected only in the bone marrow and is restricted to a small population of early myeloid cells. These findings are consistent with the identification of the gene encoding murine CG. 相似文献
110.
von der Mohlen MA; van Deventer SJ; Levi M; van den Ende B; Wedel NI; Nelson BJ; Friedmann N; ten Cate JW 《Blood》1995,85(12):3437-3443
A recombinant endotoxin-neutralizing protein, rBPI23, was shown to partially prevent endotoxin-induced activation of the fibrinolytic and coagulation systems in experimental endotoxemia in humans. In a placebo- controlled, blinded crossover study, eight volunteers were challenged twice with an intravenous bolus injection of endotoxin (40 EU/kg of body weight) and concurrently received either rBPI23 (1 mg/kg) or placebo (human serum albumin, 0.2 mg/kg). rBPI23 treatment significantly lowered the endotoxin-induced fibrinolytic response, ie, reduced the release of tissue-type plasminogen activator, urokinase- type plasminogen activator, plasminogen activator inhibitor antigen, and complex formation of plasmin alpha 2-antiplasmin (P = .0078 for each). Plasminogen activator inhibitor activity was also reduced, but not significantly according to the Hochberg method (P = .0304). The endotoxin-induced activation of the procoagulant state as reflected by increase in F1 + 2 fragments and TAT complexes was blunted by rBPI23 infusion (P = .0391 [not significant according to the Hochberg method] and .0078, respectively). These results indicate that rBPI23 is capable of reducing both the activation of the fibrinolytic and the coagulation systems after low-dose endotoxin infusion in humans. 相似文献