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Biomedical subjects

G Delling

Publications and source records attributed to G Delling.

At least 199 records · Page 11Linked to original sources

Nuclear polymorphism in osteosarcomas as a prognostic factor for the effect of chemotherapy. A quantitative study.

A current strategy for osteosarcoma treatment is neo-adjuvant chemotherapy prior to the resection of the tumour. It appears that some tumours respond very well to the cytostatic therapy, while others show little or no effect. It is desirable to be able predict the response of the tumour before starting chemotherapy. 16 biopsy specimens from patients with osteosarcoma who had been treated according to the protocol of the study COSS-80 and COSS-82 were examined. 100 tumour cells from each biopsy have been measured by an electronic interactive image analysis system (IBAS II; Kontron/ZEISS). After completion of chemotherapy en bloc resection of the tumour was performed. The entire surgical specimen was completely examined at two levels by means of undecalcified sections, and assigned a grade for the effect of chemotherapy analogous to the grading of Salzer-Kuntschik et al. (1983). The quantitative analysis of tumour cell nuclei revealed two different patterns of nuclear sizes, which were correlated significantly with the chemotherapy response (P less than 0.002). Tumour cell nuclei of well responders were significantly larger and showed a greater variance in size (mean value 66 + 41 micron 2), than those of poor responders (mean value 38 + 18 micron 2). We conclude from our results that quantitative analysis and classification of nuclear size of osteosarcoma cells may be useful for predicting chemotherapy response in patients with osteosarcoma.

Adolescent↗

Osteosarcomas and Ewing's sarcomas. Comparative immunocytochemical investigation of filamentous proteins and cell membrane determinants.

Primary malignant bone tumors, osteosarcomas (9 cases), and Ewing's sarcomas (10 cases) were examined for their reactivities with monoclonal and polyclonal antibodies against filamentous proteins and cell membrane determinants of the lymphoid and macrophage marker series. The reactivity of antibodies was studied on snap-frozen tissue probes by using a triple layer immunoperoxidase method. Osteosarcomas were positive for vimentin and, in part, for HLA-DR. Other types of intermediate-sized filaments were not detected in tumour cells. In a small number of cases (2/9) tumour cells were reactive with antibodies of the macrophage series (Leu M2). In Ewing's sarcomas, vimentin and HLA-DR was also demonstrated. It was particularly interesting that Leu M2 staining was found in the majority of cases (8/10). The staining pattern supports the assumption that this peculiar tumour is of mesenchymal (monocyte/macrophage) histogenesis. It was evident from the present study that, in primary osteogenic tumors, none of the examined tumour "markers" were as distinctive as they are for bone metastases. Nevertheless, the reactivity of Ewing's sarcoma cells with monoclonal antibodies of the Leu M2 type throws some highlights on the, as yet, obscure histogenesis of the neoplasm and may be of diagnostic value in conjunction with the known light and electron microscope features of the tumour.

Adolescent↗

[Comparison of x-ray and histological findings in osteosarcomas following preoperative chemotherapy].

Since the introduction of pre-operative chemotherapy, osteosarcomas have shown a more favourable prognosis. Reaction of the tumour due to chemotherapy is judged pre-operative primarily by radiology (plain films, angiography, CT, scintigraphy). There is little evidence concerning the radiological appearances after pre-operative chemotherapy and morphological changes, particularly in respect of tumour regression. Specific radiological changes were therefore compared with pathological findings following chemotherapy and operation in 17 patients with osteosarcomas. Tumours were examined which showed radiological evidence of intra-and extra-osseous sclerosis or lysis and which still were classified as vital tumour tissue. Tumour planes were reconstructed from large histological sections of the operative specimen and compared with the radiological appearances. Sclerosis was found to be due to reactive new bone formation or to mineralisation of the osteosarcomatous tissue. Lysis correlated with persistent vital tumour, or in connective tissue. Nine out of ten cases, regarded as vital on radiological evidence, showed vital tumour cells on histological section. Lyses and scleroses were not reliable indications of the pre-operative state of the osteosarcoma following chemotherapy. On the other hand, combined qualitative radiological criteria for assessing tumour vitality, proved to be helpful.

Adolescent↗

[Bone scintigraphy in assessing the success of chemotherapy in osteosarcoma].

During preoperative chemotherapy regional 99mTc-MDP clearance by tumor and healthy bone as well as tumor blood flow were determined in 13 patients with osteosarcoma. The results were compared to histologic regression grades. After good response (tumor vitality less than 10%) tumor blood flow normalized and regional 99mTc-MDP clearance decreased by 66% (range 56-82%). After poor response to chemotherapy (tumor vitality greater than 10%) tumor blood flow remained increased, whereas regional 99mTc-MDP clearance was unchanged or increased except in one patient. After 4-7 weeks of chemotherapy tumor viability was accurately assessed in 8 of 9 patients (89%) by means of regional 99mTc-MDP clearance. Tumor viability could be evaluated also by simple tumor/non-tumor ratios. A decrease of 99mTc-MDP clearance by more than 20% indicated an effective chemotherapy with a specificity of 80%. After 10-13 weeks of chemotherapy the specificity was improved including the results of tumor blood flow determination.

Adolescent↗

Influence of prostaglandins on electrolyte metabolism of human trabecular bone in vitro.

A procedure was developed to investigate the electrolyte metabolism of human trabecular bone and its regulation in vitro, in particular the influence of prostaglandins. Trabecular bone was prepared from femoral heads of patients who had undergone hip replacement surgery for coxarthrosis. 500 mg samples were incubated in modified EAGLE's minimal essential medium. Net electrolyte movements between bone and incubation medium were measured. During 6 hours of incubation PGE2 caused an increase in the release of calcium and magnesium from bone into incubation medium as compared to controls. The effect of PGE2 was dose-dependent and comparable to that of human parathyroid hormone 1-34 (hPTH 1-34) whereas hPTH 3-34 had no effect. Human calcitonin (hCT) caused a decrease in the release of calcium and magnesium. PGE2 was found to be the most potent prostaglandin. PGE1 and PGF2 alpha had about 50% and PGF1 alpha about 40% of the potency of PGE2. PGA1 and PGA2 had no effect. The effect of PGE2 could be completely inhibited by hCT and was not further enhanced by hPTH 1-34. Magnesium movement was affected in the same way as calcium movement, while phosphate movement and release of alkaline phosphatase and hydroxyproline from bone into incubation medium were not affected by prostaglandins.

Aged↗

Computerized simulation of bone remodeling: graphic demonstration of dynamic processes.

A computerized simulation model has been developed to study the histologic patterns of dynamic remodeling processes in trabecular bone. The osteoid seam thickness and the distance between the tetracycline labels are calculated based on (partly hypothesized) parameter values, such as matrix appositional rate, mineralization rate, number and life span of the osteoclasts, resorption rate, and mineralization lag time. The results of a simulation run are demonstrated using computer graphics. Such simulation results cast doubts on the validity of some approaches that attempt to infer details of remodeling processes from histologic measurements. For example, the distance between the tetracycline labels obtained by simulation illustrates the difficulty of over-or underestimating the matrix appositional rate by measuring it from a histologic section.

Bone Resorption↗

Clinical, biochemical and histological results of a double-blind trial with 1,25-dihydroxyvitamin D3, estradiol and placebo in post-menopausal osteoporosis.

Twenty-eight women with postmenopausal osteoporosis were studied in a double-blind trial aimed to compare the effects of a one-year treatment with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), estradiol valerate (E2) and placebo. Patients were divided into 4 groups: group 1 was given 1,25(OH)2D3 alone, group 2 was given E2 alone, group 3 was given 1,25(OH)2D3 + E2, group 4 received a placebo. The evaluation of the effects of the treatments included clinical examination of patients, the measurement of a number of biochemical parameters, such as plasma and urinary calcium and phosphate, urinary hydroxyproline, serum alkaline phosphatase, the measurement of intestinal calcium absorption and bone mineral content (BMC) and a histomorphometric study of bone biopsies from the iliac crest. The best clinical results were obtained in the patients who were given 1,25(OH)2D3 alone; appreciable results were also noticed in the patients who were given E2 alone or in combination with 1,25(OH)2D3, while patients in the placebo group worsened. BMC decreased in the placebo group and increased, although non significantly, in the patients treated with 1,25(OH)2D3 or E2 or both. The histomorphometric study showed a significant increase in the mean trabecular diameter in patients treated with 1,25(OH)2D3 alone or in combination with E2. Changes in the volume density of trabecular bone paralleled those in BMC. The results of the trial indicate that 1,25(OH)2D3 is an effective therapeutic agent in postmenopausal osteoporosis.

Aged↗

[Etidronic acid therapy in Paget's disease of bone].

Treatment of Paget's disease of bone was done in 32 patients using monotherapy with disodium etidronate (Diphos). A further 19 patients underwent combined treatment with etidronate and human calcitonin. Both monotherapy and combined treatment led to marked regression of disease activity in most patients as measured be decreased activity of alkaline phosphatase. In most cases this coincided with improvement of complaints. In two cases with initial monotherapy and in six with combined treatment success of treatment remained unsatisfactory. The latter group comprised patients with very serious illness. Our experience suggests that etidronic acid is an effective and well tolerated drug relatively free of side-effects for the treatment of Paget's disease of bone.

Alkaline Phosphatase↗

Morphological grades of regression in osteosarcoma after polychemotherapy - study COSS 80.

The histologic grade of regression of 50 osteosarcomas after polychemotherapy - according to the protocol study, COSS 80 - was classified on a six-stage regression scale; 56% of all patients responded well to chemotherapy regression grades I, II, and III and no significant difference between BCD- and CPL-treated patients could be found. Tumors under 10 cm in length responded better to chemotherapy than those of greater length and there was a good correlation between the clinical estimation of tumor regression and progression and the histologic grade of regression.

Antineoplastic Agents↗

Morphological changes in osteosarcoma after chemotherapy--COSS 80.

Forty-five osteosarcomas were investigated by special methods such as preparation of undecalcified bone tumor tissue, imprint cytology, histochemistry, and quantitative analysis. The morphological regression grades and their relation to chemotherapy are reported by Salzer-Kuntschik et al. (1983). The results presented demonstrate that smaller osteosarcomas respond more favorably than larger tumors. The function of bone-tumor cells, e.g., osteoid production, trabecular tumor bone formation, and mineralization, seems to be more important for the sensitivity to chemotherapy than the cell polymorphism. The estimation of bone-tumor morphology in at least two total areas of the bone tumor is essential in borderline cases (grade III/grade IV). Imprint cytology is very helpful for rapid estimation of the effect of therapy and the demonstration of cellular polymorphism. At the moment, we are not able to determine the effect of chemotherapy from the first biopsy before starting chemotherapy.

Alkaline Phosphatase↗

[Spondylosclerosis hemispherica. Roentgenmorphologic and histomorphologic contribution to this syndrome].

We have observed 87 cases of spondylosclerosis hemispherica. This lesion has a multiple aetiology, including bacterial causes (florid or low grade infections), stress due to scoliosis, ankylosing spondylitis, dorsal disc prolapse or diffuse disc degeneration. In the majority of cases it is possible to ascertain the aetiology from a consideration of the clinical and serological findings, together with ordinary radiography, conventional tomography or computed tomography. Appropriate treatment can then be given.

Adult↗

[Osteopenia. A problem of long-term dialysis].

Hemodialysis induced osteopenia represents one of the serious late complications of long-term treatment with hemodialysis. The incidence of osteopenia in our hemodialysis-patients ranges between 5 and 10 percent (Atkinson et al. 1973; Delling et al. 1976; Heidler et al. 1976; Parfitt 1976; Fuchs et al. 1977a; Henning et al. 1977; Schulz 1978, 1979; Madsen 1979; Schulz et al. 1980, 1981). Well timed variation of the conventional electrolytecomposition of dialysate can prevent osteopenia in many cases successfully. Precise histological classification of bone (histomorphometrical evaluation of bone-biopsy) and determination of parathormon- and fluor-level are the obligatoric precondition of adequate osteopenia-treatment. Therapy of osteopenia comprises--beside decrease of dialysate calcium and -magnesium--stepwise increase of NaF--and 1,25(OH)2D3-application. Surveillance during therapy should include monitoring of calcium, phosphate and fluor-metabolism, microradioscopy of hand skeleton, rebiopsy of bone (iliac crest) and determination of iPTH.

Adolescent↗