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Biomedical subjects

R Kotz

Publications and source records attributed to R Kotz.

175 records · Page 10Linked to original sources

[The incidence of recurrence of intra- and extra-lesional operated metastases of long tubular bones].

Using a collective of 54 patients with 76 operated metastases of long bones in carcinoma of the breast and kidney the frequency of local recurrence after intralesional and extralesional (marginal, wide, radical) resection was investigated. 57 operations were done intralesional, 19 extralesional. Local recurrence was seen in 50.8% in the intralesional group on the other hand in only 15% in the extralesional group (p 0.007). Relief of pain was similar in both groups. The postoperative range of motion had worse results after extralesional resection and endoprosthetic replacement. There was no difference between both groups in the manifestation of further metastases.

Adult↗

[Experiences with ventral stabilization in vertebral metastases in the area of the thoracic and lumbar spine].

43 cases of tumor resection followed by ventral stabilisation are reported in 42 patients with metastases in the spine. Indications for surgery were beginning or incomplete transversal lesion of the spinal cord, bedrest for at least 3 weeks, unsusceible pain caused by instability, or unsuccessful conservative and radiotherapeutic treatment. 46.5% of the cases can be rated as good considering the time of survival and life quality, 18.5% can be judged as a partial success. 7 patients hat to be reoperated in the same level, most of them because of local recurrence. Complications occurred in 40% of the cases. These operations should be performed by a "term of specialists". Postoperative treatment with isotope-, hormone- or radiotherapy is decisive to obtain good results.

Adult↗

Exposure of oncologic nurses to methotrexate in the treatment of osteosarcoma.

Methotrexate is a therapeutic agent used widely for osteosarcoma. We used an extremely sensitive high-performance liquid-chromatography assay to evaluate 112 urine samples obtained from 28 hospital employees during high-dose therapy with methotrexate and during routine care of patients. The highest cumulative urinary excretion was observed when methotrexate infusions were handled in a workbench from which a portion of filtered air was emitted into the room. Remarkable urine contaminations were identified for personnel, including 1 administrative employee who had "stood by" for 2 h in the room where infusions were prepared. Lower methotrexate concentrations were detected in the urine of nurses whose exclusive function was to care for patients. The urine burden in oncologic nurses decreased after a central pharmacy unit was installed. Methotrexate was excreted in the sweat of patients who were under high-dose therapy, and its elimination half-life was 11.1 h (mean maximal concentration = 1.7 micrograms/ml [n = 51). The maximal burden in spontaneous vomit from these patients was 441.5 micrograms/ml, and it declined to 0.24 micrograms/ml 19.5 h after infusion was completed. No methotrexate was detected in personnel who prepared 20-g methotrexate infusions in the central pharmacy unit. We demonstrated that occupational safety depended not only on technical precautions, but on the skills of specifically trained personnel.

Antimetabolites, Antineoplastic↗

Reversible downregulation of telomerase activity by hyperthermia in osteosarcoma cells.

Telomerase, a ribonucleoprotein enzyme, maintains telomere length and is expressed by the majority of malignant tumours, but not in normal tissue. Telomerase facilitates the division of tumour cells and its activity has been suggested as a prognostic indicator, but so far the regulation or modulation of telomerase activity has not been described. Hyperthermia has been shown to decrease tumour growth by inhibition of proliferation. Therefore, the effect of hyperthermia on telomerase activity in human osteosarcoma cells was studied. Telomerase activity was measured by the Telomeric Repeat Amplification Protocol (TRAP) assay in three different osteosarcoma cell lines subjected to hyperthermia (42.5 degrees C, 90 min) and in controls cultured under basal conditions (37 degrees C). Telomerase activity was strongly inhibited by hyperthermia and decreased in all cell lines tested after a recovery time of 2 h under basal conditions (37 degrees C) to an activity of approximately 85%, after 12 h approximately 60% and with lowest activity approximately 55% compared to activity of control cells. Telomerase activity then increased and reached the same, i.e. basal, level as before hyperthermia, after 112 h. These results show that hyperthermia results in a reversible downregulation of telomerase activity in osteosarcoma cells. This effect facilities studies on the regulation of telomerase activity and detailed information might lead to new therapeutic strategies.

Cell Division↗

Heat-shock protein 72 in human osteosarcoma: T-lymphocyte reactivity and cytotoxicity.

Heat-shock proteins (hsp) have been shown to be involved in tumor immunity. The expression of hsp72, the inducible form of the 70-kDa family, is increased in human osteosarcoma and correlates with a good response to neoadjuvant chemotherapy. It is selectively expressed on the surface of osteosarcoma cell lines where it acts as a target molecule for natural killer cells. Because hsps are strongly immunogenic, this study investigates the role of hsps as antigens in human osteosarcoma. Osteosarcoma cells and infiltrating T lymphocytes were isolated from osteosarcoma specimens from 3 patients with high-grade osteosarcoma. Two of the tumors immunohistochemically expressed hsp72, whereas one did not. T-cell lines isolated from both hsp72-positive osteosarcomas had a significantly proliferative response upon stimulation with recombinant human hsp72, whereas the T lymphocytes from the hsp72-negative osteosarcoma did not recognize hsp72. The lines had a significantly proliferative response upon stimulation with autologous osteosarcoma cells and exerted cytotoxicity. Cytotoxicity and proliferation could be increased by heat treatment of the target cell in the hsp72 responsive lines. These results demonstrate that hsp72 is involved in the interaction of T lymphocytes and osteosarcoma cells in a specific group of osteosarcomas expressing hsp72. Because of the cytotoxic potential of these T lymphocytes, induction of hsp72 in osteosarcomas might lead to an increased immune response and rejection of the osteosarcoma.

Coculture Techniques↗

In vivo and in vitro cellular ingrowth into a new generation of artificial ligaments.

Artificial ligaments are a useful tool in ligament reconstruction. Although the new generation of artificial ligaments shows encouraging clinical results, in contrast to earlier generations studies on the biological properties are lacking. Biopsies were taken from a ligament advancement reinforcement system (LARS) 6 months after implantation and investigated by histochemistry. An in vitro study seeding human fibroblasts or osteoblast-like cells (up to 10(6) cells for 21 days) on ligament pieces (5 x 5 mm) was conducted and analyzed by histochemistry. The biopsies showed complete cellular and connective tissue ingrowth in the LARS ligament. In vitro fibroblasts and osteoblast-like cells encapsulated the fibers by building a cellular net around them. To our knowledge, these findings demonstrate for the first time the cellular ingrowth into the LARS ligament. This mechanism might explain the strength and the inert behavior of the ligament without the synovialitis shown in clinical studies.

Adult↗

Hyperthermia increases the susceptibility of chondro- and osteosarcoma cells to natural killer cell-mediated lysis.

As an adjuvant to chemotherapy hyperthermia has proven to be successful as a treatment for osteo- and chondrosarcoma patients. The aim of this study was to investigate whether hyperthermia could increase cellular expression of heat-shock-protein 72 in human osteo- and chondrosarcoma cells and how heat treatment would affect their susceptibility to natural killer cell (NK-cell)-mediated lysis. About 5-10% of the peripheral mononuclear blood cells (PBMC) in the human peripheral blood are natural killer cells (NK-cells). Natural cytotoxicity, mediated by NK-cells, is believed to play an important role in host defense against cancer. The exact mechanisms of recognition of target cells and subsequent NK-cell activation are not yet known. NK-cells, isolated from the peripheral blood of healthy donors, were enriched by magnetic cell-separation to a purity of 85-97%, assessed by FACS-analysis. The susceptibility of heat-treated (42.5 degrees C, 90 minutes) and untreated osteosarcoma (MG63) and chondrosarcoma (HTB94) cell lines to NK-killing was determined by a release assay of lactate dehydrogenase (LDH). Lysis by NK-cells was increased by heat treatment of the target cells from 16.6% + 4.5% to 33% + 15%, p=0.035, for osteosarcoma cells, (E/T ratio of 5:1) and from 13.7% + 3.1% to 27.9% + 16.9%, p=0.021, (E/T ratio of 20:1) for chondrosarcoma cells. An increased expression of HSP72 of chondro- and osteosarcoma cells after heat treatment was detected by the Western blot technique. The results of this study show that hyperthermia increases HSP72 expression in osteo- and chondrosarcoma cells and their susceptibility to NK-cell-mediated lysis. These findings may lead to new therapeutic strategies, using hyperthermia to improve immunological defense against chondro- and osteosarcoma cells.

Bone Neoplasms↗

Serum concentrations of APO-1/Fas and interleukin-1beta-converting enzyme in osteosarcoma correlate with response to chemotherapy.

BACKGROUND: Cytotoxic drugs used in neoadjuvant chemotherapy may exert their effect by activation of apoptosis. Both APO-1/Fas and Interleukin-1beta-converting (ICE)/caspase-1 are believed to act as mediators of apoptotic cell death. PATIENTS AND METHODS: The sera of 21 patients with high-grade osteosarcoma were tested at the time of diagnosis by ELISA and compared with clinical data. RESULTS: The mean APO-1 serum levels were 844 +/- 344 pg ml(-1) and the mean ICE serum levels were 212 pg ml(-1) +/- 155 pg ml(-1) for all patients. Furthermore, both serum levels were found to be statistically significantly higher in patients with good regression grades compared to those in patients with bad regression grades. CONCLUSION: In highly-malignant osteosarcoma elevated serum levels of both APO-1 and ICE seem to be predictive of good response to chemotherapy.

Adolescent↗

Serum levels of TNF-beta and sTNF-R in patients with malignant bone tumours.

OBJECTIVE: To determine serum levels of TNF-beta and soluble TNF-R in patients with primary highly malignant bone tumours. PATIENTS AND METHODS: Sera of 27 patients with highly malignant osteosarcoma and Ewing sarcoma were taken at the time of diagnosis and analysed by ELISA. RESULTS: Both TNF-beta and sTNF-R levels were lower in sera from osteosarcoma patients as compared to those from Ewing sarcoma. In patients with high-grade osteosarcoma, but not Ewing sarcoma, high levels of TNF-beta correlated with bad response to neoadjuvant chemotherapy. CONCLUSION: In patients with high-grade osteosarcoma TNF-beta levels seem to be of predictive value and both TNF-beta and sTNF-R seem to be of diagnostic value for differentiation between high-grade osteosarcoma and Ewing sarcoma.

Adolescent↗

[Incidence of recurrence of aneurysmal bone cysts following surgical treatment and adjuvant therapy with phenol].

Between 1966 and 1991, at the Department of Orthopaedics 34 patients with a mean age of 15.7 years (range 7-46 years) underwent surgery because of aneurysmatic bone cysts. Mean follow-up was 11 years (range 1-26.3 years). We observed a total rate of recurrence of 11.8%. In a group of 9 patients who received local phenol therapy after curettage and bone transplantation no recurrence was observed. The different surgical and conservative methods of treatment are discussed also with respect to rates of recurrence stated in the literature.

Adolescent↗

Patellar resurfacing in tumor endoprosthesis: a study in regard to power transmission.

Relation between quadriceps muscle mass and knee extension strength was investigated after resection of malignant bone tumor and endoprosthetic replacement of the distal femur in 19 patients with patellar resurfacing (Group A) and 16 patients without resurfacing (Group B). In all cases, a modular cementless, hinged prosthesis had been used. Age and follow-up period were comparable in the 2 groups. Muscle mass was measured ultrasonographically and strength was evaluated isokinetically. All the data on the operated side are given as percentage of the non-operated side. There was a positive correlation between muscle mass and strength in both groups. By linear regression analysis, a slightly lower value of strength was predicted in the unresurfaced group than in the resurfaced group. Analysis of covariance revealed that the influence of patellar resurfacing on strength was significant. This factor should also be considered in making a decision about patellar resurfacing with a tumor endoprosthesis.

Adolescent↗

Chronic lower back pain due to sarcoma.

We describe a 74-year-old woman with extensive pelvic leiomyosarcoma presenting with uncharacteristic musculoskeletal pain of the lumbosacral region and left lower extremity. Hemipelvectomy was considered the treatment of choice, and a model for a pelvic prosthesis was constructed based on imaging analysis. However, the tumour (and the complaints) responded surprisingly well to a combined treatment regimen including superselective arterial catheter embolization, which led to tumour regression to such a degree that aggressive surgical treatment became unnecessary.

Aged↗