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Biomedical subjects

R Schenk

Publications and source records attributed to R Schenk.

At least 19 recordsLinked to original sources

[Experiences with 216 manual esophageal anastomoses and with mechanical single and double row suture technique (SPTU, EEA, ILS) in stomach cancers].

From 1973 to 1990 we have performed 216 anastomoses of the oesophagus after resection of gastric malignancy. Both resection due to a carcinoma of the oesophagus and subtotal gastric resection due to distal carcinoma of the stomach have not been considered. In a retrospective study we present the results of our oesophageal anastomoses performed by hand-suture and stapling. The perioperative complications are shown with special regard to the insufficiency rate of the oesophageal anastomosis and the resulting mortality. In 70 by hand suturing performed anastomoses (1973-80) we have seen 3 (4.4%) leaks of the oesophagojejuno-/oesophagogastrostomy, in 146 stapled anastomoses (1980-90) 6 (4.2%) insufficiencies were seen. Two of 3 dehiscences in the hand-sewn group and one of the 6 leaks in the stapler group had a lethal outcome. The overall hospital mortality could be reduced from 18.5% to 6.9%.

Anastomosis, Surgical

Establishment and characterization of two immortalized cell lines of the osteoblastic lineage.

Osteoblastic cells were cloned by culturing rat calvariae cells in agarose in the presence of TGF-beta and EGF. Two bone cell lines were established by immortalizing such an osteoblastic clonal cell population by the introduction of the avian v-mycOK10 gene in the form of a mouse ecotropic retrovirus. Although originating from the same clonal cell population, the two lines exhibited somewhat differing properties. IRC10/30-myc1 expressed alkaline phosphatase (AP), showed PTH- and PGE2-induced cAMP production, synthesized mainly collagen type I and a minor fraction of type III, and produced mRNA for the bone-specific protein osteocalcin. IRC10/30-myc3 did not express AP, showed no PTH responsiveness, and synthesized only about one-third as much collagen as IRC10/30-myc1 (4 versus 12% of total protein synthesis). However, the cell line IRC10/30-myc3 was induced to synthesize cAMP by PGE2 and produced osteocalcin mRNA. When cultured in vivo in diffusion chambers, both lines proved to be osteogenic. Besides bone, both lines also formed cartilage and fibrous tissue. Thus, by immortalizing a clonal cell population of the osteoblastic phenotype, cell lines expressing varying properties can emerge. Furthermore, the expression of alkaline phosphatase and PTH-inducible adenylate cyclase are not prerequisites for a cell to form bone in vivo. Finally, cells expressing the phenotype of differentiated osteoblasts, including osteocalcin synthesis, still have a multipotential differentiation capacity and form bone and cartilage in vivo.

Adenylyl Cyclases

BM 21.0955, a potent new bisphosphonate to inhibit bone resorption.

A total of 300 new bisphosphonates were screened for their effect on bone resorption in the rat. Among these, 1-hydroxy-3-(methylpentylamino)propylidenebisphosphonate (BM 21.0955) was selected for detailed investigation. It inhibited arotinoid-stimulated bone resorption as assessed by calcemia in thyroparathyroidectomized rats at a SC dose as low as 0.001 mg P (0.016 mumol) per kg body weight per day. The compound was thus about 2, 10, 50, and 500 times more potent than risedronate, alendronate, pamidronate, and clodronate, respectively. Intravenous administration was as effective as subcutaneous, and oral administration was 100 times less effective. The effect after one administration decreased with time but was still measurable after 2 weeks. Nonstimulated bone resorption assayed by the urinary excretion of radiolabeled tetracycline from lifelong prelabeled animals was also inhibited. This effect started 3 days after a single dose and was still maximal after 7 days. Histomorphometric analysis of the tibial metaphysis in growing intact rats also showed an inhibition of bone resorption along with an increase in bone mass. The number of osteoclasts increased in animals treated with 0.01 and 0.1 mg P per kg (0.16 and 1.6 mumol/kg) body weight SC but decreased in animals given 1 mg P per kg (16.1 mumol/kg), showing that the inhibition of bone resorption was not due to an inhibition of osteoclast recruitment. No inhibition of mineralization occurred. This new bisphosphonate appears to have great potential for use in human bone disease.

Alendronate

[Histology of the implant-bone interface in cemented and uncemented endoprostheses].

The introduction of bone cement into endoprosthetic surgery was a significant step forward from the 'pre-cement' era. Nonetheless, its disadvantages soon stimulated the search for better means of anchoring implants without cement. Interest focuses on the so-called interface zone, which is the area between bone and foreign body. On the basis of light-microscopical findings our understanding of the biological and biomechanical interactions has influenced the principles of prosthetic design and the implant materials selected for use. The present article gives a synopsis of the histomorphology of the interface, with special reference to stability, tissue reactions, wear products, and implant fixation at bone surfaces (concerning bony ingrowth, osseointegration, and bonding). In all, 127 histological specimens of total hip and knee revisions were reviewed, in addition to a total of 24 non-cemented polyethylene cups retrieved at autopsy.

Bone Cements

Effect of halogenmethylenebisphosphonates on bone cells in culture and on bone resorption in vivo.

Dihalogenmethylenebisphosphonates increase alkaline phosphatase activity and fatty acid oxidation in calvaria cells in culture (Cl2MBP greater than Br2MBP approximately equal to F2MBP). The monohalogen ClMBP and the non-halogenated analogues are less active on phosphatase and inactive on or inhibitory towards fatty acid oxidation. The three dihalogenbisphosphonates and ClMBP inhibit bone resorption in vivo, Cl2MBP most strongly.

Alkaline Phosphatase

Quantitative morphometric evaluation of the inhibitory activity of new aminobisphosphonates on bone resorption in the rat.

Three new bisphosphonates of various chain length, namely, 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (AHBuBP), 5-amino-1-hydroxypentylidene-1,1-bisphosphonate (AHPeBP), and 6-amino-1-hydroxyhexylidene-1,1-bisphosphonate (AHHexBP) were compared with 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP), and dichloromethylene bisphosphonate as to their effect on metaphyseal bone remodeling in the rat. The parameters assessed were growth in length, mineralization, metaphyseal density, mean trabecular diameter, and number of trabeculae. Both metaphyseal density, an index of metaphyseal Ca balance, and number of trabeculae, an index of bone resorption, showed the following sequence of potency: AHBuBP greater than AHPrBP = AHPeBP = AHHexBP greater than Cl2MBP. All compounds decreased trabecular diameter somewhat, an index of bone formation, with AHBuBP decreasing the least. AHBuBP and possibly AHHexBP appear to be interesting new bisphosphonates for future clinical use.

Animals

[Immunohistochemistry: theoretical potentials and practical application].

Immunhistochemical methods are increasingly used and their application in surgical pathology is obvious. Nine different immunohistochemical techniques are compared in this review article. The peroxidase anti-peroxidase method of Sternberger et al. (1970), the avidin biotin complex method of Hsu et al. (1981) and the labeled avidin biotin technique of Guesdon et al. (1979) are to be preferred. Two step methods using labeled antibodies such as alkaline phosphatase or peroxidase-labeled second antibodies are less sensitive. However, two-step methods using alkaline phosphatase-labeled antibodies offer the advantage of double staining procedures since alkaline phosphatase reacts with different azo dyes and results in a wide spectrum of colours in the final reaction product. At present, the major problems of immunohistochemistry in daily work are the selection of the fixative and of appropriate controls. Though both problems remain unresolved, immunohistochemical methods should be used for special problems in surgical pathology.

Alkaline Phosphatase

Relation between bone mineralization, Ca absorption, and plasma Ca in phosphonate-treated rats.

Disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) is known to inhibit the crystallization of calcium phosphate salts in vitro. Large doses of EHDP administered in vivo inhibit skeletal mineralization, decrease intestinal calcium absorption, and produce hypercalcemia. In the present study, EHDP or one of 13 other phosphonates were given to rats at 10 mg P/kg-day sc for 7 days in order to better define the nature of the relationship between bone mineralization, intestinal absorption, and plasma calcium in the regulation of calcium homeostasis. Each of the phosphonates which inhibited skeletal mineralization in vivo also inhibited crystallization in vitro, but the converse was not true. A very close correlation was found between inhibition of skeletal mineralization, decreased intestinal calcium absorption, and slight hypercalcemia. A dose-response study with two compounds also revealed the same close correlation. It is argued that the impairment of intestinal calcium absorption in phosphonate-treated rats may represent a secondary homeostatic response to the primary effect of the drugs on bone mineralization. This response may be mediated by an elevation of a fraction of plasma calcium.

Animals

[Treatment of 10 cases of symptomatic Paget's disease with etidronate (EHDP)].

10 patients with active symptomatic Paget's disease of bone have been treated for 6 months with disodium etidronate (EHDP) at a dose of 20 mg/kg/day. A statistically significant fall in the serum levels of alkaline phosphatase and urinary hydroxyproline was observed. However, only 2 patients experienced a significant reduction of bone pain. 6 patients were partially improved and 2 patients showed no change. Iliac crest biopsies after treatment demonstrated dimunution of the abnormal structure of the pagetic bone, but also a considerable increase in unmineralized osteoid borders. The future potentialities for treatment of Paget's disease are discussed.

Aged

The comparative effects of vitamin d deficiency and ethane-1-hydroxy-1,1-diphosphonate administration on the histology and glycolysis of chick epiphyseal and articular cartilage.

A comparison has been made between the effect of a vitamin D--deficient diet and treatment with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) on the morphology of chick epiphyseal cartilage and on the production of lactate in vitro by epiphyseal and articular cartilage. The cell populations in the growth plate were different following the two treatments. Vitamin D deficiency was characterized by an increase in proliferating cells, with a relative paucity of hypertrophic cells; EHDP treatment was characterized by an increase in hypertrophic cells. When similar cell types were compared, neither treatment changed lactate production from the control value. This stresses the need to correlate the morphology of cell types with their metabolic function. The present results indicate that the major effect of vitamin D deficiency in the chick is to block the differentiation of proliferating to hypertrophic cells. In contrast, EHDP may act by inhibiting calcification directly. Even though EHDP at the doses used is known to interfere with the production of 1,25-dihydroxycholecalciferol there is no block to cell differentiation under EHDP similar to that seen in dietary deficiency of vitamin D.

Animals

[Treatment of Paget's disease with phosphonates].

A group of 22 patients with Paget's disease of bone was treated with a diphosphonate (sodium etidronate; EHDP), a stable synthetic analogue of inorganic pyrophosphate. This substance was given during 3 months at the dose of 20 mg/kg body weight per day, and proved effective by reducing the raised urinary excretion of total hydroxyproline and by lowering the concentration of serum alcaline phosphatase. It also improved the disease-related osteo-articular pain in 60% of the patients. A rise in serum phosphate under EHDP therapy is due to the increase in renal tubular reabsorption of phosphate. Bone histology showed regression of disease activity and the appearance of lamellar structure in newly formed bone. Because of a transient increase of the amount of uncalcified osteoid, it is advisable to give the diphosphonate in courses not over 3 months or at a reduced daily dose.

Adult

Action of 1,25-dihydroxyvitamin D3 and a diphosphonate on calcium metabolism in rats.

The effect of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) on Ca balance, 45Ca kinetics, and bone morphology has been studied in control rats and rats given disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP), 10 mg P/kg sc per day. This large dose of EHDP is known to inhibit bone mineralization and intestinal calcium absorption and to depress the endogenous production of 1,25-(OH)2D3. In conctrol rats, 1,25-(OH)2D3 increased intestinal calcium absorption. However, in contrast to the enhanced calcium absorption that results from an augmentation of dietary calcium, the 1,25(OH)2D3-induced augmentation of calcium absorption does not lead to a rise in calcium retention, the intestinal effect being matched by an increased excretion of urinary calcium. The EHDP-induced decrease of intestinal calcium absorption could be completely prevented by the concomitant administration of 1,25-(OH)2D3 but not the inhibition of bone mineralization. Therefore, in contrast to the impairment of calcium absorption, that of bone mineralization brought about by large doses of EHDP cannot be merely attributed to a decreased production of 1,25-(OH)2D3.

Animals