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  • 1
    ISSN: 0340-1855
    Keywords: Schlüsselwörter Diclofenac ; in vitro ; Osteoblasten ; stromale Knochenmarkzellen ; Hüftprothektik ; Key words Diclofenac ; in-vitro ; osteoblasts ; bone marrow cells ; hip arthroplasty
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Introduction: Results of animal experiments have demonstrated that the osseous integration of non-cemented prostheses can, at the very least temporarily, be impaired by the application of non-steroidal antiphlogistic agents (such as diclofenac). It is the objective of this study to examine whether there is a direct influence of diclofenac used in usual clinical dosages (3 times 50 mg daily) on bone cells and their progenitor cells which would explain the observed slow integration of the prostheses. Methods: To investigate this, cultivated human in vitro osteoblasts and stromal bone marrow cells were incubated with increasing doses of the medications. Our study focused on the effect of diclofenac application on proliferation and functional metabolism in both cell lines. The measurable maximal plasma concentration 2h after the application of one tablet Voltaren 50® reached 1.6μg/ml. This correlated with diclofenac concentrations between 1 and 10 ml found in our experiments. The detected values were correlated to the control group (0 μg/ml diclofenac). Results: The drug effect upon osteoblasts was higher than on progenitor cells. The proliferation of in vitro stromal bone marrow cells, compared to untreated cells, was found to be decreased. We observed a decrease to 82% at a diclofenac concentration of 1 μg/ml, Osteoblasts exhibited a decrease to 97,5% at the same concentration. The DNA synthesis increased to 118% in stromal bone marrow cells, in osteoblasts to 144%. In contrast, we detected a neglectible decrease to 92% in the collagen synthesis of osteoblasts compared to untreated cells. The synthesis of osteocalcin by osteoblasts increased to 119%. The alkaline phosphatase activity was found to be decreased to 88% in stromal bone marrow cells and increased in osteoblasts to 111%. Conclusion: Temporary inhibiting effects on osseous integration in non-cemented prosthesis by diclofenac could be caused by a disturbance in the anabolic bone metabolism, exhibited by an increase of osteoblastic osteocalcin expression. Osteocalcin as a known negative regulator of the osteoneogenesis is most likely inhibiting the collagen matrix deposition.
    Notes: Zusammenfassung Einleitung: Nichtsteroidale Antiphlogistika (NSAR, z.B. Diclofenac) können das knöcherne Einwachsen nicht zementierter Prothesen zumindest vorübergehend beeinträchtigen. Es wird untersucht, ob ein direkter Einfluß von Diclofenac, in üblicher klinischer Dosierung (3×50 mg), bzw. der dadurch maximal erreichbaren Plasmakonzentration auf Knochenzellen und ihre Progenitoren besteht. Methoden: In-vitro kultivierte humane Osteoblasten und stromale Knochenmarkzellen wurden mit steigenden Medikamentendosierungen inkubiert und deren Wirkung auf das Proliferationsverhalten sowie Funktionsstoffwechsel gemessen. Die, durch Einnahme eines Dragees Voltaren 50®(Diclofenac) im Mittel nach 2 Stunden meßbare maximale Plasmakonzentration beträgt 1,6 μg/ml (26). Dies entspricht Diclofenackonzentrationen von etwa 1 μg/ml in unseren Experimenten. Die ermittelten Werte werden auf die Kontrollgruppe (0 μg/ml Diclofenac) bezogen. Ergebnisse: Die Wirkung von Diclofenac auf Osteoblasten ist bei allen Versuchen ausgeprägter als auf Vorläuferzellen. Die Proliferation stromaler Knochenmarkzellen wird bei Diclofenackonzentrationen von 1μg/ml auf 82%, bei Osteoblasten auf 97,5% reduziert. Die DNA-Synthese stromaler Knochenmarkzellen erhöht sich bei 1 μg/ml Diclofenac auf 118%, bei Osteoblasten auf 144%. Die Kollagensynthese der Osteoblasten wird auf 92% gesenkt. Die Osteocalcinsynthese der Osteoblasten steigt auf 119%. Die Aktivität der Alkalischen Phosphatase sinkt bei stromalen Knochenmarkzellen auf 88%, bei Osteoblasten steigt sie auf 111%. Schlußfolgerungen: Die zumindest während der Medikamentengabe verminderte Implantat-Knochen-Haftung könnte in einer Störung des anabolen Knochenstoffwechsels begründet sein, was sich in einer signifikanten Zunahme der spezifischen Osteocalcinexpression zeigt. Osteocalcin inhibiert als Negativ-Regulator der Osteogenese vermutlich die kollagene Matrixablage.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0827
    Keywords: Key words: Heterotopic osteoblast-like cells — Colony formation — Differentiation — Alkaline phosphatase — Osteocalcin.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. In this study, a characterization of human bone-forming cells responsible for heterotopic ossification was carried out in vitro. The biological and biochemical cell characteristics of the heterotopic osteoblast-like (HOB) cells were compared with those of orthotopic osteoblast-like (OB) cells from normal bone and stromal bone marrow cells believed to contain a subpopulation of osteogenic precursor cells. We found that HOB's from the spongiosa of heterotopic ossification required less time until the beginning of migration and the achievement of confluence in vitro compared with OBs from femoral shaft spongiosa. The fraction of mitotically active cells assessed by a clonogenic assay was higher as well in HOB cells. The in vitro studies of mitogenesis and the efficiency of colony formation of osteogenic cells indicate that with increasing differentiation and relative age they become more dependent on growth factors in the medium, otherwise the morphology of osteoblast-like cells changes and they pass irreversibly into the postmitotic stage of the cell cycle. The activity of the alkaline phosphatase is distinctly higher in the HOB than in the OB cells, HOB cells exhibit a lower level of osteocalcin expression compared with OB cells. No significant difference was found between OB and HOB cells in the amount of procollagen of type I sequestered by the cells. After 30 days, HOB and OB cells formed a mineralized matrix on exposure to 2 mM β-glycerophosphate. Since HOBs were isolated from heterotopic bone that had developed within 3–6 months after hip surgery, the differences in cellular behavior compared with OBs may be attributed to the relatively young age of HOB cells.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1433-044X
    Keywords: Key words Diagnosis-related billing • Payment for special procedures • Health maintenance law • Computer-assisted documentation ; Schlüsselwörter Fallpauschalen • Sonderentgelte • Bundespflegesatzverordnung • Krankenhausinformationssystem • Computergestützte Codierung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Nach dem Gesundheitsstrukturgesetz besteht für alle deutschen Kliniken seit dem 01. 01. 1995 die Verpflichtung zur Dokumentation und Kodierung von Einweisungs-, Aufnahme- und Entlaßdiagnose in die ICD-9 und die Dokumentation und Verschlüsselung zumeist operativ erbrachter Leistungen in die ICPM. Seit dem 01. 01. 1996 besteht zudem die Verpflichtung zur Abrechnung nach leistungsabhängigen vollpauschalierten Entgeltformen (Fallpauschalen und Sonderentgelte), wobei sich der Abrechnungsentscheid auf die erhobenen Daten stützt. In der Berufsgenossenschaftlichen Unfallklinik Tübingen wurden während des gesamten Jahres 1996 alle Diagnosen und Therapien handschriftlich dokumentiert und mit Hilfe zweier Handbücher kodiert. Seit 01. 01. 1997 wird ausschließlich rechnergestützt dokumentiert und kodiert. Die Entscheidung über die Abrechnungsform wird anhand der eingegebenen Daten vom Klinikinformationssystem vorgeschlagen. Retrospektiv wurden anhand von Krankenakten und Abrechnungsbelegen jeweils die Monate Januar bis April der Jahre 1996 und 1997 auf die Anzahl der abgerechneten Fallpauschalen und Sonderentgelte hin verglichen. Hierbei zeigt sich, daß durch eine rechnergestützte Kodierung und Dokumentation die Anzahl der erkannten und tatsächlich abgerechneten Fallpauschalen und Sonderentgelte im Vergleich zum Vorjahr deutlich zugenommen hat.
    Notes: Summary Since 1995 German health maintenance laws require hospitals to document and code all referals, admissions and discharges using the 4-digit ICD. Operative procedures are documented and coded using the ICPM. Beginning in January 1996, reimbursement for health services requires a diagnosis-related billing and payment for special procedures. The decision for billing is based on documented diagnosis and therapy. This extended request for documentation makes an online access to diagnosis and therapy with a computer-assisted coding system advisable. In 1996 in our hospital each diagnosis and operation was manually documented and coded on a form. Since the beginning of 1997, documentation and coding has been exclusively computer-assisted. On the basis of documented diagnosis and therapy the computer provides the route of reimbursement. Retrospectively we evaluated the number of charged diagnosis-related billings and payments for special procedures from January to April of 1996 and 1997. It became evident that with computer-assisted documentation and coding the number of detected and charged diagnosis-related billings and payments for special procedures was significantly increased in comparison with the previous year.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1434-3916
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The histological and enzymatic effects of single-dose irradiation of 7 Gray (Gy) versus fractionated irradiation of 5 × 2 Gy on the suppression of heterotopic ossification were examined over a period of 60 days in adult male Wistar rats (n = 57). The standardized osteogenesis model system in rats [9, 10, 11, 16, 19] was used for this purpose. The course of developing ossifications was documented quantitatively and qualitatively by means of quantitative computed tomography/osteodensitometry and digital luminescence radiography. Assessment of the activities of the enzymes alkaline and acid phosphatase throughout the experiment as well as characterization of the isoenzyme of alkaline phosphatase (AP) in connection with histological observations displayed a metaplasia of the ingrowing connective tissue into bone-typical cells during osteoinduction. Thus, the increase of AP is the first sign of a functional transformation of mesenchymal stem cells into chondroid bone cells. The increase in the acid phosphatase level with a maximum of acitivity between the 15th and 30th day (according to the respective treatment group) is highly suggestive of a remodeling process paralleling incipient chondroclast and osteoclast activity. In the animal groups undergoing irradiation, the above-mentioned increase of enzymes occurred after a delay. Furthermore, the maximum values observed were lower than those in the group not undergoing irradiation. Both findings were more manifest in the animal group which underwent 5 × 2 Gy of radiation than in the group which underwent single-dose irradiation of 7 Gy. Radiation suppresses matrix-induced osteogenesis. The histological and enzymatic course of this process was unchanged in the animals which did not undergo irradiation. However, it was quantitatively reduced and accompanied by a retardation of osteogenesis. Both effects were again reduced with fractionated irradiation of 5 × 2 Gy, which is theoretically dose-equivalent to a 1 × 7 Gy application. Histological examinations revealed damage to the migratory, proliferating mesenchymal stem cell population by irradiation doses which had relatively small effects on preosteoblasts, osteoblasts, chondroblasts and other specialized cell forms. Therefore, it may be concluded that the smaller degree of heterotopic ossification in the irradiated groups was due to damage of and a decrease in the number of mesenchymal stem cells at the implant site. Our results stress the necessity of instituting postoperative irradiation therapy as early as possible to prevent heterotopic ossification. In view of experimentally proven better effects, fractionated irradiation has to be preferred to a dose-equivalent single-dose radiation, especially considering the fewer side-effects noted with fractionated irradiation.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    International orthopaedics 23 (1999), S. 253-259 
    ISSN: 1432-5195
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé  La présence de facteurs de croissance a été montrée dans la consolidation osseuse mais pas encore établie dans les cals par distraction. Nous avons étudié les cytokines durant la distraction chez 3 patients. Des examens immuno-histo-chimiques ont été faits à partir de biopsie pour étudier les facteurs TGF-β, IGF-I, récepteurs TGF-β II, récepteurs IGF et l’antigène nucléaire de prolifération (PCNA). Histologiquement, nous avons trouvé de l’os immature dans la zone médiane du cal et, dans la zone de remodelage une calcification avec os lamellaire. Les ostéoblastes en général et les cellules fibroblastes-like de la zone médiane ont été positives pour le facteur TGF-β et son récepteur. Il existe une corrélation entre la quantité de cellules positives et l’activité proliferative trouvée par la PCNA et par la densité radiologique. Le facteur IGF-I a été détecté ubiquitairement. En conclusion, les facteurs de croissance sont présents dans l’os en formation et en remodelage des cals par extension. La correlation entre l’activité proliferative cellulaire et la densité radiographique, souligne leur rôle dans le processus ostéogénique.
    Notes: Abstract  Although growth factors have been demonstrated during bone healing, their presence has not yet been confirmed in callus distraction. Therefore, in 3 patients we searched for cytokines during callus distraction. Bone biopsies were immuno-histochemically stained for TGF-β1, IGF-I, TGF-β type II receptor, IGF receptor, and proliferating cell nuclear antigen (PCNA). Histologically we found immature woven bone in the middle of the callus zone and increasing calcification and lamellar bone in the re-modelling zone. Osteoblasts and fibroblast-like cells in the middle zone, and osteoblasts in all zones stained for TGF-β and its receptor. The number of positive staining cells related to proliferous activity as assessed both by PCNA, and by bone density in radiographs. IGF-I could be detected everywhere. In conclusion, growth factors are present in bone formation and in areas of re-modelling during callotasis. Their relation to proliferous activity and radiographic density supports their involvement in osteogenesis.
    Type of Medium: Electronic Resource
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