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Biomedical subjects

B Krempien

Publications and source records attributed to B Krempien.

At least 37 records · Page 2Linked to original sources

Iliac crest needle biopsy as a method for determining estrogen receptors in bone metastases from breast cancer.

The purpose of our study was to clarify whether the amount of tissue extracted by means of iliac crest needle biopsy (ICNB) would suffice for a quantitative determination of estrogen receptors (ER) in bone metastases, and to see if the method currently used for determining ER in primary tumors could also be successfully utilized in ICNB. 22 of 31 breast cancer patients examined could be evaluated. ER was positive in 7 (31.8%). Reasonable data are to be expected when the biopsy weight exceeds 0.1 g. Our study confirms that the necessary amount of tissue for ER analysis can indeed be extracted by ICNB. Our results justify further studies on a larger group of patients, since we cannot make conclusive statements concerning the value of this method for predicting the ultimate success of an endocrine treatment.

Adult↗

Value of bilateral iliac crest needle biopsy for pretherapeutic tumor staging of bronchogenic carcinomas.

Two hundred and forty-three patients with lung cancer were biopsied pretherapeutically and bilaterally on the anterior iliac crest. Tumor infiltration into the bone marrow could be demonstrated in 7 patients. No tumor-positive biopsies were found in the 163 patients with non-small cell lung cancer (NSCLC). In small cell lung cancer (SCLC), however, the infiltration rate was 9% (7/80). In 3 of the 7 patients (43%) only 1 of the 2 sides biopsied had been infiltrated. All 7 patients with tumor-positive bone marrow samples were found to have additional metastases elsewhere (stage IV, 7/26; 27%). Therefore, according to our results, we cannot recommend iliac crest biopsy as a routine pretherapeutic procedure to aid in the staging of SCLC and NSCLC.

Adult↗

Cellular basis of inflammation-induced osteopenia in growing rats.

Local nonosseous inflammation provoked by four subcutaneous talc powder injections induced a marked trabecular bone loss in rats within 7 days. The disturbance included suppression of bone elongation, inefficiency and decreased number of trabecular osteoblasts, decreased osteoprogenitor cell number in tibial metaphyses, and bone marrow expansion. Neither the appearance and function of osteoblasts in the vicinity of the cortical bone nor the number of osteoclasts in the metaphysis were found to be altered. The loss of trabecular bone in granulomatosis was based on a suppression of bone elongation and a failure of osteoblasts to form normal secondary spongiosa.

Animals↗

The value of bone marrow examination for tumor staging in breast cancer.

The purpose of our study was to investigate the value of cytokeratin antibodies for identifying bone marrow involvement in breast cancer patients who showed no evidence of distant metastases using noninvasive tumor staging procedures. Bone marrow for histological (biopsy) and immunocytochemical (aspiration) evaluation was obtained from the anterior iliac crest from 50 unselected consecutive women during surgical treatment of the primary tumor. The histological examination was done on nondecalcified bone sections. The immunocytochemical studies were carried out on interface smears of the bone marrow aspirates. For staining, cytokeratin antibodies (PKK 1) and the immune alkaline phosphatase method was used. Cytokeratin-positive cells were found in 4 of the 50 cases (8%). Of those 4 patients, however, 2 also showed evidence of neoplastic bone marrow infiltration histologically. We thus were able to prove that immunocytochemistry on aspirates is superior to conventional histology in identifying tumor in bone marrow. Nonetheless, our results clearly fell below the rate found in previous studies where epithelial membrane antigen antibodies were used.

Bone Marrow↗

Protective effects of a prophylactic treatment with the bisphosphonate 3-amino-1-hydroxypropane-1,1-bisphosphonic acid on the development of tumor osteopathies in the rat: experimental studies with the Walker carcinosarcoma 256.

The present report primarily describes protective effects of a long-term prophylactic treatment with 3-amino-1-hydroxypropane-1,1-bisphosphonic acid (APD) on the development of tumor-induced osteolytic bone destructions. Pretreatment with daily intravenous doses of APD 9.5 mg/kg for 1 week resulted in a significant reduction of Walker carcinosarcoma 256-induced bone destruction, when Walker cells were transplanted intraosseously (2 x 10(6) tumor cells/rat) 7 weeks later. Shorter pretreatment periods (4, 2 or 1 week prior to tumor inocculation) resulted in a nearly total inhibition of bone destruction as well as tumor-induced hypercalcemia. Tumor growth itself was not inhibited by APD pretreatment. Histological and microradiographical findings are reported. Consistent to our experiments and with regard to new immunocytological methods to detect single metastatic tumor cells in the bone marrow, potential risk groups may be defined which may profit from the prophylactic APD treatment to inhibit tumor-induced bone destructions.

Animals↗

Talc granulomatosis in the rat: the relationship between osteoblast insufficiency and adjacent bone marrow hyperplasia.

Bone loss in talc granulomatosis is paralleled by hyperplasia of bone marrow in the rat. To test the hypothetical relation between those two phenomena, bone matrix osteoinduction was employed as a model in which bone formation and bone marrow appearance are separated in time. Implantation of demineralized bone matrix to normal rats was followed by three talc injections (one weekly), starting 1 week after matrix implantation. Implants of demineralized bone and [3H]thymidine-labeled tibial metaphyses from talc-injected and normal rats were analyzed histologically and evaluated for alkaline and tartrate-resistant acid phosphatase activity on days 7, 14, 21, and 30 after matrix implantation. Analysis of tibial autoradiographs showed a marked growth arrest and bone marrow hyperplasia in talc-injected rats 7 days after first talc injection. Alkaline phosphatase activity in homogenates of bone implants was low in talc-injected rats on day 14 after implantation. Moreover, histology of the bone implants showed numerical and functional inhibition of osteoblasts on the same day, causing marked growth delay. Bone marrow appeared as late as day 21 after bone matrix implantation. We conclude that hyperplasia of the adjacent bone marrow is not the cause of bone loss in talc granulomatosis, but rather its compensatory consequence.

Animals↗

Effects of 1 alpha,25- and 24R,25-dihydroxyvitamin D3 on aluminum-induced rickets in growing uremic rats.

Rats were subjected to a two-stage subtotal nephrectomy or sham operation, and treated with aluminum (Al) or both aluminum and vitamin D3 metabolites for 5 weeks with a cumulative dose of 13.6 mg aluminum. Animals were injected with 3H-thymidine and 3H-proline. The following analyses were performed: quantitative histology of tibial metaphyses and cytomorphometric electron microscopy of osteoclasts, quantitative (ICP-spectroscopy) and qualitative determination (histochemical staining) of aluminum within organs, and serum biochemistry (Ca, P, Mg, vitamin D3 metabolites, alkaline phosphatase, urea). The following new facts of the aluminum-related bone disease became evident: (a) Application of aluminum to growing uremic rats induced rickets, whose major epiphyseal growth plate changes were 1 alpha,25(OH)2D3-dependent. Addition of 1 alpha,25(OH)2D3 prevented the formation of rachitic metaphysis, but failed to prevent osteoid accumulation on epiphyseal and metaphyseal trabecular surfaces. Moreover, calcitriol produced hyperosteoidosis and osteosclerosis in the same rats. Aluminum did not alter the function of osteoblasts, while osteoclasts seemed inactivated. (b) The development of rickets was associated with suppressed serum levels of 1,25(OH)2D3, reduced phosphorus level and the high content of aluminum in the bone, kidney, and liver. The addition of 24R,25(OH)2D3 markedly exaggerated the reduction of serum levels of calcitriol. We suggested that aluminum induces rickets in growing uremic rats, which consists of two components: vitamin D refractory osteomalacia and 1 alpha,25(OH)2D3-dependent epiphyseal growth plate changes.

24,25-Dihydroxyvitamin D 3↗

Effects of new bisphosphonic acids on tumor-induced bone destruction in the rat.

This report is concerned with therapeutic studies utilizing new bisphosphonic acids on tumor-induced osteolytic metastases. The bone metastases on SD rats were induced by intraarterial and intraosseous transplantation of Walker carcinosarcoma 256 B ascites cells. The treatment was carried out using disodium-3-amino-1-hydroxypropylidene-1,1-bisphosphonate (ADP), diglycidyl-[3-(3, 3-bisphosphono-3-hydroxy-propylamino)-2-hydroxypropyl-]urazol++ +-Na2 (DDU) and 1,2,4-triglycidylurazol (TGU). The extent of bone metastases was determined by X-ray on the 5th and 10th days following tumor inoculation, as well as both microradiographically and histologically upon termination of the experiment. High dose DDU produced a clear reduction of the tumor osteolysis, but these positive results were surpassed using APD. The best results were achieved by pretreatment with APD 24 h prior to tumor inoculation.

Animals↗

Iodine-131-labeled diphosphonates for the palliative treatment of bone metastases--III. Considerations of interaction, binding and absorbed dose.

General considerations about the possible mechanisms of action of rather low dose ionizing radiation with bone metastases and stimulated nerve fibers reveal that only minute amounts of chemicals are produced by direct interaction of energetic electrons. Thus changes of the chemical milieu due to direct interaction must be ruled out in favour of a radiation-induced trigger reaction which may then initiate a cascade of cellular responses. Organ distribution studies of a series of radioiodinated benzylidenediphosphonates with H-, HO- and H2N- in the alpha- and p-position revealed best results for pHO-NH2 (BDP3). The microscopic distribution of 131I-DBP3 in bone tissue was monitored by autoradiography. Elevated uptake in normal (tibia) and neoplastic bone (experimental osteosarcoma) corresponded with the degree of vascularization and formation of new hydroxylapatite. Unlike the uptake in human osteoblastic bone metastases the experimental osteosarcoma of SD-rats accumulated 131I-BDP3 less than normal bone. This was due to the short volume doubling time, the delay of hydroxyl-apatite deposition and the formation of necroses. Theoretical replacement of 131I in iodinated BDP3 with radioisotopes emitting higher energy electrons yielded best bone metastasis/organ ratios for 32P labeled BDP3. The bone metastasis/bone marrow dose ratio by comparison with 131I labeled BDP3 is, however, almost equal. The isotopes 130I and 133I are not suited to the achievement of higher tumor/background doses although they are higher energy beta- -emitters than 131I. Because of their short physical half life and absence of different kinetics in normal and neoplastic bone no dose enhancement in bone metastases can be attained.

Animals↗

The influence of 1 alpha,25- and 24(R),25-dihydroxyvitamin D3 on bone constituents during early mineralization in the rat.

The influence of vitamin D metabolites on intramuscular implants of bone matrix in rachitic rats was investigated. Recipient rats with rickets were injected daily with 1 alpha,25(OH)2D3,24(R),25(OH)2D3 or a combination of both metabolites. The presence of 1 alpha,25(OH)2D3 increased significantly the alkaline phosphatase activity, and slightly increased the activity of acid phosphatase. 24(R),25(OH)2D3 had no effect on the activity of the measured enzymes. The results of inductively coupled plasma emission spectrometric determination of bone elements revealed that: (a) 1 alpha,25(OH)2D3 stimulated the incorporation of magnesium and decreased the phosphorus content of bone implants when compared with rats given both vitamin D metabolites; (b) 1 alpha,25(OH)2D3 as well as 24(R),25(OH)2D3 had antagonistic effects on bone carbonate content. The values for 1 alpha,25(OH)2D3 treated animals were significantly higher, and 24(R),25(OH)2D3 treated rats had a significantly lower carbonate content of implants when compared to the controls. Time-dependent CO2-liberation diagrams indicated a differently bound bone carbonate in 1 alpha,25(OH)2D3 treated rats; (c) when plotted against time, the diagrams for both the values for zinc and the activity distribution of the measured enzymes had a similar appearance, indicating zinc incorporation into bone enzymes during early mineralization. It is concluded that 24(R),25(OH)2D3 should not be compared to 1,25(OH)2D3 on the basis of the same effects, since other effects of 24(R),25(OH)2D3 on the developing bone exist, opposite to those of 1,25(OH)2D3; and these could be important for protecting bone from different agents and in determining the nature of early mineral deposited.

24,25-Dihydroxyvitamin D 3↗

Inflammation-mediated osteopenia in the rat: the effects of artificial granuloma and sham operation on cortical and trabecular bone.

Recent studies have established that generalized loss of trabecular bone occurs in the growing rat following day-to-day inflammatory irritation for a period of 3 wk. We can now demonstrate that there are similar effects on bone in milder but more prolonged chronic inflammation (14 wk). Thus, there were significant decreases in trabecular bone mass as well as in cortical bone after weekly subcutaneous injections or implantations of nonspecific irritants. Osteopenia, induced by a single but extensive inflammatory lesion, remained apparent even 14 wk after induction. This indicates that inflammation-mediated osteopenia is at least incompletely reversible. A less pronounced but similar reduction of cortical and trabecular bone was observed in rats following sham operation. This might be of importance in all animal studies on bone metabolism that include surgical procedures.

Animals↗

Inflammation-mediated osteopenia in the rat: a new animal model for pathological loss of bone mass.

We have developed a rat model of inflammation-mediated osteopenia. Generalized loss of trabecular bone occurs in the rat after sc injection of nonspecific irritants such as talcum (magnesium silicate) and cotton wool (Cellulose). Although it appears likely that a systemic mediator of bone resorption is responsible for these effects, the loss of bone was not due to increased PTH secretion, since it occurred in parathyroidectomized rats, nor due to excessive 1,25-dihydroxyvitamin-D3 production. In parathyroidectomized rats, this inflammation was associated with significant increase in serum calcium within 4-7 days independent of its cause. Identification and characterization of this mechanism may provide insight into the bone loss associated with chronic inflammatory diseases such as rheumatoid arthritis and periodontal disease.

Animals↗

Foreign body giant cell reaction in lungs, liver and spleen. A complication of long term haemodialysis.

Accumulation of a foreign material in grotesque quantities was observed in the macrophages of lung, liver and spleen of a patient on maintenance haemodialysis. The material appeared in macrophages which were found either in groups or singly, without causing epitheloid cell reaction, necrosis or fibrosis. The material was non-isotropic, non-crystalline and did not stain with routine staining procedures. Transmission electron microscopy showed its presence within lysosomal membranes. The nature of the material and the mechanism of its incorporation into the patient remain unclear, but it is conceivable that incorporation is a consequence of longterm interaction of blood and foreign material during haemodialysis. The clinical consequences of such incorporation have to established.

Female↗

Bone cell kinetics and function during experimental uremia.

Bone cell kinetics and function and chondrocyte kinetics were evaluated in uremic rats and their pair-fed controls using quantitative histology and 3H-thymidine labeling. The principle histologic abnormality in the proximal tibial metaphysis of uremic rats was a relative abundance of proliferating and differentiated bone cells. No mineralization abnormalities were observed. There was increased proliferation of bone cells and an increased rate of differentiation of osteoblasts and osteoclast nuclei in uremic animals. There was no change in chondrocyte kinetics, indicating a dissociation of the normal bone elongation and bone maturation processes. The data on osteoclast number and hard tissue suggest individual osteoclasts in uremic animals have sub-normal resorbing efficiency. It is proposed that the cell kinetic alterations are due to secondary hyperparathyroidism. The cause of osteoclast inefficiency is uncertain, but may be related to (1) deficiency of active products of vitamin D; (2) chronic uremia; and/or (3) chronic secondary hyperparathyroidism.

Animals↗