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Biomedical subjects

G Delling

Publications and source records attributed to G Delling.

At least 181 records · Page 10Linked to original sources

Histomorphometric changes of osteosarcoma after chemotherapy. Correlation with 99mTc methylene diphosphonate functional imaging.

An investigation to correlate histologic changes in 12 osteosarcoma specimens from patients undergoing chemotherapy was performed using functional images of regional 99mTc methylene diphosphonate (MDP) plasma clearance rates assessed from dynamic bone scintigraphies taken during chemotherapy. Residual tumor cell viability was determined by microscopic examination of multiple thin sections from surgical specimens and quantitated by histomorphometry. Regions that showed decreases in 99mTc MDP plasma clearance of more than 20% were associated with areas of necrotic tumor, and regions that showed absent decline or increasing clearance rates were associated with high residual cell viability and incomplete response to chemotherapy. Therefore, functional bone scintigraphy allows an objective presurgical assessment of tumor response to chemotherapy.

Adolescent↗

Comparison of quantitative ground substance analysis in biopsy and resected tumour in osteosarcomas.

Osteosarcomas may show variable differentiation. They are divided into osteoblastic, chondroblastic and fibroblastic subgroups depending on their dominant histological differentiation. The pattern of histological differentiation of osteosarcoma is supposed to have an influence on the response to chemotherapy and in this study the relationship between the differentiation of the tumours and response to chemotherapy was examined in 22 osteosarcomas. For this purpose the nuclear size of tumour cells was determined on imprints and the area of the different ground substances on tumour sections after undecalcified preparation. Tumours with little nuclear polymorphism and those with an area of chondroblastic ground substance of more than 20% in the biopsy showed a poor response to chemotherapy. We conclude from our results that lack of nuclear polymorphism and in particular a large area of chondroblastic ground substances in the biopsy, can be regarded as an unfavourable prognostic factor in the response to primary chemotherapy. A comparison of the area of chondroblastic ground substance in biopsy and resection material proves that the biopsy delivers a representative view of the total area of chondroblastic ground substance for the groups of responder and non-responder. Patients with a large amount of chondroblastic ground substance in the biopsy probably require more aggressive chemotherapy.

Adolescent↗

[Bone cement containing cytostatic drugs: new aspects in the treatment of malignant bone tumors. I. Experimental studies].

Radical surgery in malignant bone tumors can either be limited by anatomical structures or seems inadequate in the palliative stabilization of bone metastases. Incomplete removal of the tumor and stabilization by compound osteosynthesis or endoprosthesis contains two problems: 1) the wide spread of malignant cells by manipulation in the tumor bearing area; 2) progressive destruction of bone due to remaining tumor. To overcome these problems we developed methotrexate bone cement (MTX-Palacos) with the aim to obtain high local concentrations of methotrexate in order to destroy remaining tumor cells and avoid systemic side effects. In vitro studies showed that methotrexate is released continuously from this cement without relevant changes of its biomechanical properties. Animal studies with transplanted osteosarcomas and mamma carcinomas in mice showed a considerable decrease of tumor growth when a plug of MTX-Palacos was inserted in the center of the tumor. Histological findings showed that in the surroundings of the plug the tumor was destroyed considerably contrary to normal bone cement which had no effect on the tumor at all. The results are discussed with regard to clinical application of MTX-Palacos.

Animals↗

[Preparation of hip joint endoprostheses for qualitative and quantitative morphologic assessment].

The morphological investigation of endoprostheses and the evaluation of the reaction with the surrounding bone tissue require the use of new preparation techniques. A standardized procedure of preparation is suggested to enable a comparison among various study groups. After removing the specimens (at autopsy), x-rays are taken, followed by separation into horizontal and longitudinal sections. These sections are undecalcified embedded retaining the implant/bone interface and grounded to thickness of 5-10 mu. First results of a quantitative analysis of bone loss are presented.

Bone Resorption↗

Bone morphology in primary hyperparathyroidism--a qualitative and quantitative study of 391 cases.

The changes of trabecular bone in primary hyperparathyroidism were studied in 391 iliac crest bone biopsies. In 60 unselected cases a histomorphometric analysis was performed. The classical osteoitis fibrosa is very rare in our material (4%). Only 49% of the cases developed specific endosteal fibrosis, 46% had increased remodelling surfaces and in 1% it was not possible to detect any difference in comparison to age-related controls. For diagnostic purposes the investigation is not helpful in nearly 50%.

Biopsy↗

The angiographic response of osteosarcoma following pre-operative chemotherapy.

The prognosis of osteosarcoma has improved significantly with recent advances in chemotherapy. Evaluation of the effect of chemotherapy is important for optimal timing of surgery, for selecting an alternative drug regimen in instances of poor response to chemotherapy and for testing combinations of new drugs. The purpose of this paper is to define the value of plain radiographs and angiography in assessing tumor response to chemotherapy. Studies were obtained before and after chemotherapy. The radiographic results were correlated with histologic evaluation of the resected specimen. Patients with less than 10% residual viable tumor in the resected bone were designated "responders" and patients with more than 10% of remaining viable tumor were "nonresponders". Angiographic appearances correctly separated 15 patients with good response to chemotherapy from seven patients who were not responsive. Conversely, comparison of plain radiographs obtained before and after chemotherapy did not allow a reliable differentiation between patients with good, poor, or no response to chemotherapy. The current role of angiography in the management of patients with osteosarcoma is discussed. It is concluded that - in contrast to plain film radiography - angiography is an accurate method for assessing the response of osteosarcoma to chemotherapy.

Adolescent↗

Bone metastases of differentiated and medullary thyroid gland carcinomas. Usefulness and limitations of immunohistology performed on undecalcified plastic-embedded tissue specimens.

Undecalcified methylmethacrylate(MMA)-embedded biopsies and surgical specimens from 20 bone metastases of differentiated or medullary thyroid carcinomas or prostate carcinomas were investigated immunohistologically for the presence of thyroglobulin, cytokeratin, vimentin, and CEA. The immunoreactions on MMA-sections revealed the same staining patterns as those demonstrated using paraffin sections of the primary lesions. Conversely, immunohistological examination of decalcified paraffin-embedded specimens of the same metastases yielded either false-negative results or results that did not allow an exact evaluation. The findings demonstrate the usefulness and limitations of immunohistology when performed on undecalcified plastic-embedded material.

Adult↗

Histomorphometric analysis of osteoclastic bone resorption in metastatic bone disease from various primary malignomas.

The present study deals with qualitative und quantitative analysis of osteoclastic bone resorption in metastatic bone disease. 267 cases were examined histomorphologically and divided into three developmental stages. In the first 'phase of early appearance' no bone resorption takes place. The stimulation of osteoclastic resorption in the surroundings of tumour tissue is typical in the second 'phase of interaction'. Pressure atrophy, aseptic necrosis and osteolysis by the tumour cells themselves are other mechanisms of bone destruction in the last 'phase of carcinomatosis'. Because osteoclasts are exclusively responsible for the loss of bone tissue in the 'phase of interaction', this stage is suited for precise quantitative analysis of osteoclastic resorption. 24 pure osteolytic secondary bone tumours of various primary lesions were examined histomorphometrically. The numerical values were compared with each other and with standard values of healthy individuals. In contrast with normal bone tissue the fractional resorption surfaces und osteoclast indices increase in metastases. Activated osteoclasts are larger and have more nuclei. The numbers of osteoclast index and nuclei per osteoclast are significantly higher in renal than in breast carcinoma. Osteoclasts can be activated in distances of more than 500 micron from tumour tissue. The mean stimulation distance in metastasis from squamous cell carcinoma is markedly higher than in secondary bone tumours of breast carcinoma. Several osteoclast activating substances and divers mechanisms of stimulation might be responsible for different numerical values of morphometric parameters in metastases from various primary malignancies.

Bone Neoplasms↗

[Alloplastic replacement of the anterior cruciate ligament by a polytetrafluoroethylene ligament. Animal experiment study].

4 sheep knees received an implant of polytetrafluorethylene. 18 month after implantation the clinical and histological investigation showed two cases of anterior instability and rupture of parts of the prosthesis. We sw severe degenerative lesions intraarticular with chronic inflammation characterized by the proliferation of immature fibroblasts, the accumulation of macrophages and the formation of multinucleated giant cells. The transfer of our results to the human knee is discussed.

Animals↗

Renal osteodystrophy in asymptomatic hemodialysis patients: evidence of a sex-dependent distribution and predictive value of serum aluminum measurements.

Bone histologies and serum concentrations of calcium, phosphate, alkaline phosphatase, iPTH, 25 OHD, 1,25(OH)2D3, and aluminum were obtained from 113 chronically hemodialyzed patients free of symptoms and signs of renal osteodystrophy. All patients had a pathologic bone histology; in 69.0%, a mixed form with predominant osteitis fibrosa and concomitant osteoidosis. In 30.1%, we found pure hyperosteoidosis, nearly half of these cases showing osseous aluminum deposits. Hyperosteoidosis was much more frequent in women (35.7%) than in men (20.9%), although the prescribed intake of aluminum-containing phosphate binders was the same. It is possible that female hemodialysis patients were more prone to aluminum accumulation or that they had a better compliance in taking the aluminum hydroxide. Serum parameters alone were not very helpful in predicting the underlying bone disease. Mean iPTH concentrations tended to be lower in the patients with hyperosteoidosis than in those with the mixed lesion, but there was wide variation. Serum aluminum was only predictive for aluminum deposits in the bone when concentrations exceeded 100 micrograms/L.

Adult↗

[Comparative x-ray and nuclear medical studies of osteosarcomas to evaluate the effectiveness of preoperative chemotherapy].

In 16 patients with a long bone osteosarcoma treated after the therapy regimen of COSS 80/82 (Cooperative Osteosarcoma Study) the tumour response to preoperative chemotherapy was assessed by conventional roentgenograms (plain films, tomograms, angiograms). The histological grade of regression determined in the operative specimen was used as a reference for the extent of tumour devitalisation. By their different typical roentgenological course the osteosarcomas with a very good and those with a rather poor response could be correctly identified (100%). On following the clinically used differentiation between "good responders" (histological grades I to III) and "poor responders" (grades IV to VI) the corresponding classification of these tumours by roentgenograms and functional scintigraphic imaging was found to be correct in 94% of the cases. The coincidence of the correct as well as the false results in both radiological methods was as high as 100% if those osteosarcomas showing only a "medium response" in their roentgenograms were added to the clinical group of good responders. There were no fundamentally discrepant results obtained by each of the two radiological techniques. With the combined workup of the roentgenological and the scintigraphic material any incorrect preoperative estimation of tumour regression with a harmful influence on therapy (date and type of surgery, mode of postoperative chemotherapy) could be avoided.

Adolescent↗

Scanning electron microscopy in bone pathology: review of methods, potential and applications.

This article reviews the applications of SEM methods to human bone pathologies referring to studies made at UCL. We consider the methods which may be most suitable; these prove to be not "routine" in the context of most bio-medical applications of SEM. Valuable information can be obtained from a bone sample if its edges are ground flat, before making either a matrix surface preparation by washing away all the cells or a mineralizing front preparation, by also dissolving the osteoid-for which hydrogen peroxide is recommended to produce a robust specimen. BSE contrast from a cut block surface can be used to measure bone phase volume. SE contrasts from natural surfaces (trabeculae, canals and lacunae) can be used to study forming, resting and resorbing surfaces both qualitatively and quantitatively (except in the case of histological osteomalacia, where the existence of osteoid will go undetected and reversal lines will be difficult to distinguish from recently resorbed surfaces). We also recommend the use of PMMA embedded bone blocks, which can be used as obtained from the pathologist, but are better embedded by a more rigorous procedure. BSE image analysis can be used to quantitate bone density fractions opening up a completely new investigative method for the future. Osteoid can be measured automatically using CL if the bone sample is block stained with brilliant sulphaflavine before embedding or if a scintillant is added to the embeddant. We give examples of observations made from a number of bone diseases: vitamin D resistant rickets, osteogenesis imperfecta; osteomalacia; osteoporosis; hyperparathyroidism; fluorosis; Paget's disease; tumour metastasis to bone.

Adolescent↗

[Iatrogenic aluminum osteopathy in a uremic infant].

An infant with uremia due to congenital renal hypoplasia was treated with oral aluminum hydroxide for 9 months in an attempt to reduce hyperphosphatemia. An increasingly painful osteopathy with pathological fractures ensued with loss of thoracic wall stability and respiratory failure. Increased serum aluminium levels and histochemically proved deposits of aluminium at the mineralisation front between calcified and noncalcified osteoid were demonstrated. In the context of recent findings concerning aluminium bone toxicity it is beyond doubt that this phosphate binding agent was detrimental for this child. Though a low phosphate diet normalized hyperphosphatemia after aluminium hydroxide treatment had been stopped, no effect on the progressive osteopathy was observed. Since aluminium hydroxide as a phosphate binder can be replaced by calcium carbonate or a low phosphate diet at least in young children, it should not be further recommended in this age group. This seems especially important in nondialyzed patients.

Aluminum↗

[The morphology of generalized osteopathies].

New findings in the morphology of generalized bone disorders are described in this report. The structure of the skeleton is the result of defined activity of the cellular units (osteoclasts and osteoblasts). The use of iliac crest bone biopsies and decalcified preparation procedures demonstrates the influence of cellular units on the skeleton as well as bone mineralization disturbances. The morphological results represent the basis for treatment as well as new therapeutical principles.

Biopsy↗

[Unusual course of renal osteopathy with Paget's disease and aluminum deposits].

In a woman with chronic renal failure due to interstitial nephritis after chronic analgesic abuse, secondary hyperparathyroidism was at first the predominant feature during a one-year period of dialysis. After parathyroidectomy severe aluminium-induced osteomalacia dominated the picture in the final phase. Surprisingly hyperparathyroidism recurred despite removal of all glandular tissue, and there also developed--previously undescribed--Paget's disease.

Aluminum↗