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C Gaissmaier

Publications and source records attributed to C Gaissmaier.

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Effects of single-dose versus fractionated irradiation on the suppression of heterotopic bone formation--an animal model-based follow-up study in rats.

The histological and enzymatic effects of single-dose irradiation of 7 Gray (Gy) versus fractionated irradiation of 5 x 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 19, 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 activity 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 x 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 x 2 Gy, which is theoretically dose-equivalent to a 1 x 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.

Acid Phosphatase↗

Carney complex.

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Chondroma↗

[Computer-assisted performance documentation. Effects in orthopedics and trauma surgery on budgets and reimbursement].

Since 1995 German health maintenance laws require hospitals to document and code all referrals, 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.

Budgets↗

Growth factors in distraction osteogenesis. Immuno-histological pattern of TGF-beta1 and IGF-I in human callus induced by distraction osteogenesis.

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-beta1, IGF-I, TGF-beta 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-beta 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.

Adult↗

[Effect of diclofenac on human osteoblasts and their stromal precursors in vitro in relation to arthroplasty].

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 2 h after the application of one tablet Voltaren 50 reached 1.6 micrograms/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 microgram/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 microgram/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.

Aged↗

Different behavior of human osteoblast-like cells isolated from normal and heterotopic bone In vitro.

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 beta-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.

Alkaline Phosphatase↗

The suppression of heterotopic ossifications: radiation versus NSAID therapy--a prospective study.

This prospective, randomized study compares the effect of postoperative irradiation and nonsteroidal anti-inflammatory drug (NSAID) therapy on the prevention of heterotopic ossifications after the implantation of a total hip endoprosthesis. A total of 154 operations were performed; one group of patients underwent radiation treatment of 3 x 3.3 Gy, and the other group took 3 x 50 mg of diclofenac per day over a period of 3 weeks. Average age, sex, preoperative diagnosis, and risk factors were similar in both groups. Postoperative radiation began on average 2.9 days after operation, and the radiation therapy was finished on average within 3.8 days. NSAID prophylaxis was begun on the first postoperative day. Heterotopic ossifications occurred in two of the patients who had undergone postoperative prophylaxis by radiation. In both cases, the ossification was Brooker I, and there was no functional impairment. There were no ossifications of Brooker II-IV in this group. One patient had a Staphylococcus epidermidis infection, and fistula revision had to be carried out; the prosthesis could be left in place. In the group treated with NSAID, 16 heterotopic ossifications stage Brooker I and 2 stage Brooker II could be detected. Eleven patients stopped the treatment because of gastrointestinal problems. Both postoperative radiation and NSAID therapy have proved to be effective prophylactic methods. In direct comparison, radiation prophylaxis by 3 x 3.3 Gy proved to be slightly more successful than NSAID prophylaxis.

Anti-Inflammatory Agents, Non-Steroidal↗

Monoclonal rat antibodies directed against Toxoplasma gondii suitable for studying tachyzoite-bradyzoite interconversion in vivo.

We previously reported the in vitro analysis of stage differentiation of Toxoplasma gondii in murine bone marrow-derived macrophages. The purpose of this study was to generate monoclonal rat antibodies that might be suitable for investigating tachyzoite-bradyzoite interconversion in vivo with the murine model. Immunization of Fischer rats with cysts of T. gondii NTE resulted in the generation of seven monoclonal antibodies of the immunoglobulin G2a, G2b, or M isotype, which were further characterized by the immunoblot technique, immunofluorescence assay, immunohistology, and immunoelectron microscopy. Immunoblots demonstrated specific reactivity of five monoclonal antibodies with proteins with molecular masses of 40, 52, 55, 60, 64, 65, and 115 kDa. One antibody (CC2) appeared to recognize a differently expressed antigen depending on the parasite stage, reacting with a 40-kDa molecule in tachyzoites and a 115-kDa antigen in bradyzoites and oocysts. Several other monoclonal antibodies were shown to be stage specific and to react in immunofluorescence assays or in immunoblots with either tachyzoites or bradyzoites. Kinetics of stage conversion in vitro could be monitored by immunofluorescence with two of these monoclonal antibodies. Preliminary immunohistological investigations of tissue sections from infected mice demonstrated the possible usefulness of these monoclonal antibodies for future in vivo studies on stage differentiation of T. gondii in the murine system.

Animals↗

[Osteogenesis in exposure to ionizing radiation in vitro].

Irradiation is a well established therapeutical concept to prevent heterotopic ossification after joint replacement. The influence of irradiation on proliferation of mature osteoblasts and their potential osteoprogenitors, matrix formation and mineralization are not well known in this setting. We therefore studied the effect of different doses of ionizing irradiation on the several steps of osteogenesis in vitro, using cells isolated from the juvenile rat. A colony forming test, the MTT-viability assay, a cell count, measurement of the cellular protein content and alkaline phosphatase activity, as well as determination of in vitro mineralisation have been applied to calvarian osteoblasts, fibroblasts and stromal bone marrow cells. Irradiation results in a dose-dependent suppression of clonogenic activity in all mitotically active cells, but metabolic activity and matrix synthesis were not impaired. In dense cultures alkaline phosphatase expression and in vitro mineralisation were not significantly affected by irradiation. Our experimental in vitro data suggest that irradiation inhibits the initial phase of in vivo osteogenesis due to the cytostatic effect. Postoperative irradiation after THR must therefore take place as early as possible. The homoeostasis of normal, orthotopic bone does not seem to be severely affected by local low-dose irradiation.

Alkaline Phosphatase↗

[Ultrasound imaging of the patellar tendon--an experimental study].

QUESTION: The accuracy of ultrasound in the detection of histological changes is a point of discussion. METHOD: In an experimental study we examined on 58 explanted human patellar tendons the correlation between histological and sonographic changes. RESULTS: Ultrasonographic measurements of length, width, thickness and circumference of the ligaments correlated highly to the explants' macroscopic evaluated dimensions. The sonographic lesions were distinguished in changes in form and echogenicity. Macroscopic visible changes in the explanted ligaments could be detected ultrasonographically. In histological aspect 2 tendons and in ultrasonographical aspect 16 tendons were found to be normal in the whole course of the tendons. 14 ligaments showed histological but not ultrasonographical abnormalities. 42 ligaments were conspicuous in both methods of examination. In the course of the tendons a very high correlation (up to 92%) between sonographical and histological findings was detected. At the insertion are of the patellar ligament the correlation was low. CONCLUSION: The performed study shows that ultrasonographically detected lesions of the patellar ligament point to histological changes but no conclusions to the kind of histological changes can be taken. However ultrasonographically found abnormalities correlate in a high proportion to histologically detectable changes in the ligaments. Ultrasonography is a good method to evaluate degenerative symptoms in the patellar ligament.

Adult↗

[Prevention of heterotopic ossification following cementless hip replacement using 5 x 2 Gy fractionated irradiation. A prospective study].

97 patients were treated with cementless custom-made total hip replacement of the Aldinger type for osteoarthritis of the hip. All were prophylactically treated by radiotherapy with 5 x 2 Gy. 10.3% showed heterotopic ossification. 8 patients showed ossification grade I by the Arcq scale and 2 of grade II. Clinical results according to the Merle d'Aubigné score were good or very good in over 90% at one year postoperatively. One patient showed loosening of the femoral stem caused by sinking-in of the custom-made implant. During the revision procedure there were no signs of radiation induced damage to the implant bed. Negative sequelae to the bony implant bed by prophylactic radiotherapy cannot be detected on radiological assessment. Side effects like delayed wound healing or alteration of local immune status with subsequent infection which are commonly discussed, were not seen. Fractionated irradiation is an effective means of prophylaxis of heterotopic ossification.

Adult↗

[Suppression of heterotopic ossification: single-dose versus fractionated irradiation--animal study].

Periarticular ossification is one of the main problems of total hip replacement. Irradiation with megavolt photons is known to be a well recognized means of prevention of heterotopic ossification. So far only little scientific basis exists about the most favourable way of radiotherapy for prevention of ectopic ossification. In this study two theoretically equivalent doses are compared. Allogeneic bone matrix was implanted into both thighs of 50 adult male Wistar rats for experimental induction of heterotopic ossification. Immediately after operation the thigh implants were irradiated with a single dose of 7 Gy or a total dose of 10 Gy given in 5 fractions of 2 Gy each. In the model of matrix-induced osteogenesis in rats fractionated irradiation by 5 x 2 Gy leaded to a highly-significant (p = 0.001) better suppression of ectopic ossification compared to irradiation by 1 x 7 Gy. Once-only irradiation with 1 x 7 Gy leads to a reduction of the calcium contents by 27.5%, split irradiation by 5 x 2 Gy obtained a reduction by 66.9% compared to the calcium contents of thigh implants not exposed to radiation. In view of experimentally proven better effects, fractionated irradiation has to be preferred to single dose radiation also considering less side effects in split radiation.

Animals↗