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G Delling

Publications and source records attributed to G Delling.

At least 127 records · Page 7Linked to original sources
PubMed1994

[Apoptosis: bcl-2 as a key protein for programmed cell death].

The realization that malignant tumors may grow not only due to proliferation but also because cells don't die when they should provides absolute new directions in basic and clinical tumor research. Thus, apoptosis, the programmed cell death is very hot now in the scientific community. In the center of interest are the regulation mechanisms of apoptosis and its significance in different tumor entities. Recently, numerous studies on apoptosis during embryogenesis, different stages of tissue development and in epithelial and hormone dependent tumors have been published. The data suggested an important role of bcl-2 in regulation of apoptosis. In this view the demonstration of bcl-2 oncogene expression in osteosarcoma, a mesenchymal tumor, is of potential great interest.

Animals↗
PubMed1994

[Osteosarcoma--apoptosis and proliferation. Study of bcl-2 expression].

The relationship between the growth of tumors and the expression of the protooncogene Bcl-2 could be shown in epithelial tumors. A bcl-2 expression leads to a prolonged cell survival due to an inhibition of apoptosis. The potential meaning of bcl-2 expression in mesenchymal tumors remains still unknown. The fact, that the heterogenous group of osteosarcoma is not sufficiently characterized at present, suggested to investigate the bcl-2 expression in osteosarcoma. Thus, immunohistochemistry was used to analyze 47 specimens of different osteosarcomas of 36 patients. Sixteen cases (46%) showed a strong expression of bcl-2 and 13 cases (35%) were moderately positive for bcl-2. Seven cases (19%) were negative for bcl-2. The heterogenous, negative up to strong expression of bcl-2 yield clues, that the Bcl-2 controlled regulation of programmed cell death could be an important factor of cellular kinetics. Additionally the cellular proliferation rate was determined with the monoclonal antibody MIB 1, directed against the Ki-67 epitope. The data of bcl-2 expression and cellular proliferation rate lead to a classification correlating with the histological classification. To verify the importance of apoptosis in the genesis of mesenchymal tumors and whether Bcl-2 may play an important role as a predictive factor for the prognosis of osteosarcoma, further investigations will be needed.

Adolescent↗
PubMed1994

Polyostotic heterogeneity of the spine in osteoporosis. Quantitative analysis and three-dimensional morphology.

It was the aim of this study to record quantitatively and qualitatively the distribution of the three-dimensional microarchitecture throughout the human spine in osteoporosis. Bone biopsies of the iliac crest and the complete spine of 26 autopsy cases without skeletal disease and 11 female patients with proven osteoporosis were removed. Grindings of all vertebrae by a technique which we developed allowed two- and three-dimensional measurements simultaneously. The analysis included an evaluation of trabecular bone volume, trabecular interconnection, and trabecular thickness, as well as a qualitative investigation of the structure of cancellous bone. The bone loss in osteoporosis is a loss of structure. The relative loss of the trabecular microarchitecture is greater in the iliac crest than in the lumbar spine. It is a gradual change from normal bone to osteoporosis. Transformation from plates to rods and the loss of whole trabeculae are caused by perforations. The polyostotic heterogeneity in osteoporosis is remarkable. Adjacent vertebrae may show differences of up to 100% in bone structure and bone volume. This explains the difficulties in early diagnosis of osteoporosis. Due to the polyostotic heterogeneity it is impossible to define a threshold mineral content for osteoporotic fractures.

Aged↗
PubMed1994

3D computed X-ray tomography of human cancellous bone at 8 microns spatial and 10(-4) energy resolution.

Human cancellous bone was imaged and its absorptive density accurately measured in three dimensions (3D), nondestructively and at high spatial resolution by means of computerized microtomography (microCT). Essential for achieving the resolution and accuracy was the use of monoenergetic synchrotron radiation (SR) which avoided beam hardening effects, secured excellent contrast conditions including the option of energy-modulated contrast, and yet provided high intensity. To verify the resolution, we selected objects of approximately 8 micron size that could be observed on tomograms and correlated them in a unique manner to their counter images seen in histological sections prepared from the same specimen volume. Thus we have shown that the resolution expected from the voxel size of 8 microns used in the microCT process is in effect also attained in our results. In achieving the present results no X-ray-optical magnification was used. From microCT studies of composites (Bonse et al., X-ray tomographic microscopy (XTM) applied to carbon-fibre composites. In: Materlik G, ed. HASYLAB Jahresbericht 1990. Hamburg: DESY, 1990; 567-568) we know that by including X-ray magnification a resolution below 2 microns is obtained. Therefore, with foreseeable development of our microCT method, the 3D and nondestructive investigation of structures in mineralized bone on the 2 micron level is feasible. For example, it should be possible to study tomographically the 3D distribution and amount of osteoclastic resorption in the surrounding bone structure.

Aged↗
PubMed1994

Three-dimensional analysis of the spine in autopsy cases with renal osteodystrophy.

The spinal column was removed from nine autopsy cases with chronic maintenance dialysis and sectioned in the sagittal plane to a thickness of 1 millimeter using a surface-stained block grinding technique. A combination of two- and three-dimensional analysis included an evaluation of the spine deformity index (SDI), the bone volume (BV/TV), the trabecular interconnection (TBPf), the trabecular thickness (Tb.Th), the trabecular number (Tb.N) as well as a qualitative investigation of the structure of cancellous bone. The control group consisted of 26 autopsy cases with intact skeletons. An iliac crest biopsy made a direct comparison of the diagnostic biopsy location and the spinal column possible. The SDI showed vertebral fractures in renal osteodystrophy (ROD) of types I and II, in spite of a trabecular bone volume within normal limits. The trabecular bone volume showed mean values and a distribution throughout the spinal column familiar in the skeletally-intact control group. Those cases with a longer history of hemodialysis showed higher BV/TV values regardless of age and sex. A trabecular volume within normal limits did not mean physiological trabecular interconnection. Perforations were commonly observed with ROD. Classical, hidden and tunnelling perforations were distinguished. Microcallus formations were frequently seen in the periphery of vertebrae at rod nodes, rods and plate intersections. Three-dimensional analysis in ROD shows a greater alteration in architecture than can be assumed from the two-dimensional histological sections.

Autopsy↗
PubMed1994

The microarchitecture of the axis as the predisposing factor for fracture of the base of the odontoid process. A histomorphometric analysis of twenty-two autopsy specimens.

The axis from twenty-two cadavera was removed at autopsy and was sectioned in the sagittal plane to a thickness of one millimeter with use of a surface-stained block-grinding technique. Combined two and three-dimensional analysis included an evaluation of the volume of the trabecular bone, the trabecular interconnection, and the cortical thickness as well as qualitative investigation of the structure of the cancellous bone. The body of the axis, the base of the odontoid process, and the odontoid process were analyzed separately. The base of the odontoid process is a region of least resistance for fractures because of its unique microarchitecture. The mean volume of trabecular bone of the base of the odontoid process is 55 per cent less than that of the axis and the odontoid process. The base also has a markedly poorer trabecular interconnection and a cortical thickness that is one-third that of the odontoid process. In all of the specimens, trabeculae that were disconnected from the trabecular lattice (trabeculae with free ends) were demonstrated in the base of the odontoid process. The formation of microcallus in six (27 per cent) of the specimens supports the hypothesis that microfractures occur as a result of stress peaks, mechanical fatigue, and the relative insufficiency of bone in the static condition. Therefore, the base of the odontoid process can be considered as a site of predilection for fractures.

Adolescent↗
PubMed1994

Bone densitometry and histomorphometry in patients with hairy cell leukemia.

Tumor necrosis factor alpha, the cytokine that participates in the autocrine growth control of hairy cell leukemia has strong bone resorptive properties. This prompted us to look for bone involvement in HCL. Bone mineral density (BMD) was not decreased in 14 HCL patients who did not have radiographic evidence of bone destruction. Osteopenia was found in only two HCL patients with skeletal complications of the disease and bone pain preceded diagnosis in both cases. Lymphomatous infiltration of the vertebral bodies T 12/L1 was confirmed histologically in the female patient while bilateral necrosis of the femoral head preceded the diagnosis of HCL in the male patient. Histomorphometry of bone biopsy samples was performed in another 12, previously untreated male HCL patients. Trabecular bone volume was found to be reduced in 11, greatly reduced in 5 of them, while osteosclerosis was found in only one patient. The increase of trabecular bone pattern factor, a new parameter for simple quantification of trabecular interconnection indicated a poorly connected trabecular lattice in eight of these 12 patients.

Adult↗
PubMed1994

[Structure of the axis--key to the etiology of the dens fracture].

Fractures of the dens are seen especially in young adolescents but also in individuals after the sixth decade of life. The etiology of these fractures and the occurrence of non-union after initial treatment is still discussed controversially. To address these issues, the axis was removed from thirty-seven autopsy cases for histomorphometric analysis. The base of the dens is a region of least resistance for fractures due to its reduced trabecular bone volume, a poorer trabecular interconnection and a cortical thickness one third that of the axis. In all of the cases, trabeculae disconnected from the trabecular lattice, and in 30% microcallus formations were demonstrated in the base of the dens. In osteoporotics the microarchitectural differences of cancellous bone between the base of the dens and the other regions of the axis are increased markedly. The obtained data suggest that the bone structure of the axis is responsible for the location, the distribution and the frequency of fractures of the odontoid process. The deficiency of bone mass within the base also offers a new explantation for the occurrence of non-unions even after treatment of fractures of the base of the dens.

Adolescent↗
PubMed1994

[Possibilities for preoperative determination of transplant quality using an osteoporosis index].

Preprosthetic procedures and reconstructive measurements are typically performed in elder patients. In this age group osteoporotic changes of the skeleton are common. The facial bones are persistently envolved within this process. Preoperative assessment of bone height and width are nowadays routine procedures in preprosthetic surgery, little attention is paid towards the bone quality at the recipient site of dental implants and the donor and recipient sites of bone-grafts. This study is performed to investigate the possibility to evaluate the bone quality prior to preprosthetic and reconstructive operations. The amount of the mineralization of the skeleton was determined in 17 patients which were scheduled for preprosthetic and reconstructive surgery with the help of Dual Energy X-Ray Absorptiometry (DEXA). The amount of mineralization of the skeleton and the osteoporosis-index, which were determined with the help of DPX-scans, are representative also for the facial skeleton. In our preliminary study patients with a low skeletal mineralization have a tendency towards increased complications after preprosthetic and bone-graft surgery. In addition the preoperative assessment of bone quality serves the basis for a accompanying osteoporosis therapy.

Adult↗
PubMed1993

Treatment of osteosarcoma: experience of the Cooperative Osteosarcoma Study Group (COSS).

Using high-dose methotrexate, doxorubicin, and cisplatinum (or BCD) for adjuvant chemotherapy in osteosarcoma of the extremities, we achieved 8-year metastasis-free survival rates of 60-70%. No relapse has been observed after that time. A dose of 12 g/m2 of high-dose methotrexate seems superior to 6 g; doxorubicin was found to be indispensable for efficient therapy and administering ifosfamide in addition seemed to be beneficial. Primary chemotherapy appeared to be safe and to facilitate surgery. The response on chemotherapy provided valuable prognostic information. Salvage of poor responders by alternative postsurgical chemotherapy was unsuccessful. Intraarterial, as opposed to intravenous, use of cisplatinum, in addition to systemic three-drug chemotherapy, did not improve the local tumor response rate. The local failure rate was low (4.7%); it was higher, however, after limb-salvage procedures than after amputation and rotationplasty (11.1% vs. 2.2%, p < 0.05). The outcome after local failure was almost universally fatal. The most intriguing late sequelae of chemotherapy were cardiomyopathy due to doxorubicin and hearing loss due to cisplatinum. Given the limited number of effective drugs, it might be difficult to further improve the cure rate and also to diminish late toxicity. Exploration of the most effective but least toxic mode of drug administration might be one possibility. Another might be reduction of the cumulative doses and therapy duration, while simultaneously increasing the dose rate.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Selenium deficiency and fulvic acid supplementation induces fibrosis of cartilage and disturbs subchondral ossification in knee joints of mice: an animal model study of Kashin-Beck disease.

Kashin-Beck disease is an acquired, chronic and degenerative osteoarticular disorder. Selenium deficiency and fulvic acid in drinking water have been implicated in the cause of this disease. Pathologically, chondronecrosis of the growth plate and articular cartilage and subconsequent disturbance of ossification were observed in the joints. In this animal model study, mice were fed with a selenium deficient diet and fulvic acid supplemented drinking water for two generations. In undecalcified histological preparations of bone we carried out histological staining to detect mineralized and unmineralized bone and cartilage. The results revealed that selenium deficiency and fulvic acid supplementation induced degeneration of the articular cartilage in the knee joints of mice. Dynamic fluorescent labelling of ossification, enzyme histochemical detection of alkaline phosphatase activity in osteoblasts and a typical immunohistochemical localization of collagens type I and II indicated the development of fibrocartilage at the articular surface of knee joints, resembling the early stages of osteoarthrosis. This became obvious by disturbed development of the articular space and meniscus, markedly impaired formation of subchondral bone and early differentiation failure during enchondral ossification. This animal model provides an approach to study the molecular pathogenesis of Kashin-Beck disease.

Animals↗
PubMed1993

High spatial resolution imaging of bone mineral using computed microtomography. Comparison with microradiography and undecalcified histologic sections.

RATIONALE AND OBJECTIVES: The application of various high-resolution (< 100 microns) imaging techniques for in vitro bone mineral analysis is explored. METHODS: The techniques of contact microradiography and microtomography, using the x-ray spectrum filtered out of synchrotron radiation (SR) and conventional staining techniques, are compared to each other by presenting a variety of different samples. The relationship between radiation exposure and spatial resolution micro-computed tomography (CT) images of a finger bone is explored. The relevant properties of SR are explained. RESULTS: In CT images, a spatial resolution of 100 microns was obtained. New bone mineral induced by mechanical periosteal irritation in a rabbit tibia was quantified. In one case a microradiogram and a microtomogram of the same slice were taken for comparison. Histologic sections and microradiograms taken from a specimen of a human femur for comparison are presented. CONCLUSIONS: Microradiography and staining techniques require rather sophisticated sample preparation; quantitative image analysis is more difficult as the resulting image must be digitized. The CT technique requires almost no sample preparation and allows for accurate bone mineral quantification. However, CT images with a resolution of several microns limit the sample size to a few mm. Micro-CT and microradiography can be performed with conventional x-ray sources, but the use of SR is of particular interest in high resolution imaging, because its white spectrum allows for optimum x-ray energy selection and its high intensity for short scan times.

Absorptiometry, Photon↗
PubMed1993

[Pathophysiology of osteoporosis].

3-dimensional analyses of trabecular bone structure in osteoporosis reveal that perforations of individual trabeculae are common. They result in a reduction of the stability of the trabecular network by inducing mechanically incompetent trabeculae. Reparative mechanisms, like microcallus formations, may also lead to errors when measuring trabecular bone density.

Adult↗
PubMed1992

Bone metal content in patients with chronic renal failure.

Bone accumulation of metals, other than aluminum (Al), in patients with chronic renal failure (CRF) has rarely been studied. We report the bone and blood levels of iron (Fe), vanadium (V), lead (Pb), Al and calcium (Ca) in 18 CRF patients on long-term hemodialysis and in 14 controls (C). Significant increments in mean blood Al (1,300%), V (160%) and Fe (60%) and decrease in blood Pb (-50%) were found in the patients with CRF. Renal subjects had higher bone concentrations (mean +/- S.E.M.; microgram/g of bone) of Al (CRF = 129.1 +/- 16.9; C = 12.6 +/- 2.9; P < 0.0001), Fe (CRF = 940.4 +/- 133.4; C = 263.4 +/- 49.0; P < 0.0001) and V (CRF = 2.55 +/- 0.43; C = 1.39 +/- 0.36; P = 0.0308) and lower Ca (CRF = 268.2 +/- 11.1 mg/g; C = 377.2 +/- 28.1; P = 0.0017). A positive correlation was found between bone Al and V (r = 0.355, P < 0.05). Results indicated that a significant bone accumulation of Al, Fe and V, but not Pb, occurred in the hemodialyzed azotemic individuals.

Adult↗
PubMed1992

Enzyme and immunohistochemistry on undecalcified bone and bone marrow biopsies after embedding in plastic: a new embedding method for routine application.

A simplified method of low temperature methyl and butyl methacrylate embedding (up -20 degrees to -15 degrees C) is demonstrated using a proper redox system of benzoyl peroxide and aromatic amine. This method combines the morphological superiority of plastic-embedded bone tissue and bone marrow sections with the advantages of specific enzyme histochemical and immunochemical markers. The method permits good preservation of morphological details, the survival of antigenic determinants and the retention of enzyme activities. The specimens were fixed in 1.6% formaldehyde and 5% sucrose in 0.02 M phosphate buffer at pH 7.4, washed in 0.02 M phosphate buffer and 5% sucrose, dehydrated with acetone and impregnated with monomers of embedding medium. All these steps were carried out at +4 degrees C. The method presented is especially suitable for enzyme histological and immunohistological diagnosis of primary and secondary bone tumours, soft tissue tumours, as well as myelo- and lymphoproliferative disorders of bone marrow biopsies. Examples are demonstrated with mono- and polyclonal antibodies and reaction products of hydrolytic enzymes.

Biopsy↗
PubMed1992

Trabecular bone pattern factor--a new parameter for simple quantification of bone microarchitecture.

The stability of trabecular bone depends not only on the amount of bone tissue, but also on the three-dimensional orientation and connectedness of trabeculae, which is summarized as trabecular microarchitecture. In previous studies we could demonstrate that in three-dimensional bone tissue the relation of trabecular plates to rods is reflected in the ratio of concave to convex surfaces of the bone pattern in two-dimensional bone sections. For the quantification of the connectedness of these bone patterns we developed a new histomorphometric parameter called Trabecular Bone Pattern factor (TBPf). The basic idea is that the connectedness of structures can be described by the relation of convex to concave surfaces. A lot of concave surfaces represent a well connected spongy lattice, whereas a lot of convex surfaces indicate a badly connected trabecular lattice in two-dimensional sections. By means of an automatic image analysis system we measure trabecular bone area (A1) and perimeter (P1). A second measurement of these two parameters (now A2 and P2) is done after a simulated dilatation of trabeculae on the screen. This dilatation results in a characteristic change of bone area and perimeter depending on the relation of convex to concave surfaces. TBPf is defined as a quotient of the difference of the first and the second measurement: TBPf = (P1 - P2)/(A1 - A2). First measurements of TBPf in 192 iliac crest bone biopsies of autopsy cases show that there is not only age-related loss of bone volume, but also a decrease of trabecular connectedness. By means of TBPf we can demonstrate a significant difference in the age-related loss of trabecular connectivity between male and female individuals.

Autoanalysis↗
PubMed1992

[Renal osteodystrophy in Maracaibo].

In the present work we report the bone histologies obtained from the iliac crest of 49 patients on chronic hemodialysis in Maracaibo. All of them were dialyzed thrice weekly with untreated tap water containing high aluminum (Al) levels. Their mean blood Al levels were found to be higher than 100 micrograms/L. Histomorphometry was used for the diagnosis of the underlying renal osteodystrophic type. Al-staining techniques (Aluminum) were applied for detection of bone Al deposits. Additionally, bone Al content was determined quantitatively by means of graphite furnace atomic absorption spectroscopy. A mixed type of osteodystrophy (type III according to Delling's classification) consisting in the simultaneous presence of hyperparathyroid bone lesions (osteitis fibrosa, OF) and a hyperosteoidosis (osteomalacia, OM) was found in 63.3% of the studied patients. The other patients (37.7%) exhibited a pure osteomalacia (OM). Bone Al deposits at the mineralization front were observed in 70% of cases and were frequently associated with bone pain, spontaneous fractures and skeletal deformities. We conclude that bone biopsy should be performed in all patients presenting bone pain and high blood Al levels.

Adolescent↗