[Ligament repair with PDS (polydioxanone) in chronic insufficiency of the fibular ligament of the upper ankle joint: experimental and clinical experiences]. / Die Bandplastik mit PDS (Polydioxanon) bei der chronischen fibularen Bandinsuffizienz am oberen Sprunggelenk: Experimentelle und klinische Erfahrungen.

From September 1988 till February 1989, 14 patients with chronic ligamentous rupture of the ankle had been operated on using PDS-plasty. Of 12 patients checked in follow-up examination (mean postoperative period 45 weeks), only two showed good or very good results. Most patients had the same signs of chronic instability as preoperatively. Two patients had been reoperated on. Intraoperatively we did not find a biological substitute along the PDS guide line. In an experiment on the rat we examined histological changes and tensile strength at appointed times. Histological data showed no biological substitute of PDS. We also found residues of PDS even after 300 days. After a short time loss of tensile strength occurred. In view of an aseptical necrosis that occurred in our experiments, we must point out the risk of foreign body granulomas.

Protective influence of oxypurinol on the trinitrobenzene sulfonic acid(TNB) model of inflammatory bowel disease in rats.

Chronic inflammation of the colon and the rectum was induced by intracolonic administration of 25 mg trinitrobenzoic sulfonic acid (TNB) in 0.25 ml 30% ethanol. Three weeks after TNB administration the colon and the rectum showed transmural, granulomatous inflammation which had many similarities to Crohn's disease and furthermore to the morphological and functional changes which occur in early phases of postischemic intestinal damage. In the colon of TNB-treated animals the ATP and GTP levels were markedly decreased. The accumulation of thiobarbituric acid-reactive substances (TBA-RS) demonstrated a free radical-mediated component of the tissue damage. Treatment with oxypurinol radical scavenger and xanthine oxidoreductase inhibitor diminished the morphological changes, the loss of energy-rich nucleotides and the TBA-RS accumulation.

Aortocoronary vascular prosthesis made of siliconized homologous vein or bovine sacral artery.

The purpose of our study was to develop and prepare aortocoronary prostheses, test them experimentally in multivascular and coronary reoperations in case of missing autologous grafts and to use them for shunt operations in cardiac surgery. Human vein or bovine sacral artery were used for preparing aortocoronary prostheses. As for metrics of 9-14 Charr. and a length of 20-30 cm were obtained. Aortocoronary prostheses were preformed according to the coronary configuration for left descending artery, circumflex artery and right coronary artery. Aortocoronary prostheses meet the conditions of desantigenicity, sterility, athrombogenicity, tightness and high tensile strength, tear propagation strength, bursting pressure and shrinkage temperature. Experimental testing was performed in dogs in aortofemoral and aortocoronary positions. Infections did not occur. The healing process and structural changes of aortocoronary vascular prostheses (grafts) were examined histologically and evaluated by means of scanning electron microscopic examinations. Athrombogenicity and healing-in without inflammation and calcification were proved.

[Effect of an angiogenesis-promoting dipeptide on microcirculation in experimental chronic stomach ulcer in the rat]. / Die Wirkung eines die Angiogenese fördernden Dipeptids auf die Mikrozirkulation beim experimentellen chronischen Ulcus ventriculi der Ratte.

The influence of an angiogenesis stimulating dipeptide (Lys-Pro-derivative) on the blood flow rate of the stomach was tested in rats suffering from ulcus ventriculi by microspheres technique. 21 days after operation (acetic acid model by Takagi) the ulcers in the group treated with the dipeptide were healed completely, but not in the control group. The higher blood flow in the ulcer area of the dipeptide group radiometrically gained, was not changed significantly (U-test by Man-Whitney). These results demonstrate, that the process of rapid wound healing promoted by the dipeptide cannot entirely be explained by a higher blood flow of the stomach.

The linoleic acid metabolite 9DS-hydroxy-10,12(E,Z)-octadecadienoic acid is a strong proinflammatory mediator in an experimental wound healing model of the rat.

Locally administered 9Ds-hydroxy-10,12(E,Z)-octadecadienoic acid (9-HODE) caused a drastic inflammatory response in the experimental model of granulation tissue formation of the rat according to RUDAS (Arzneimittelforsch. 10,226-229, 1960). Three days after implantation of the polyvinyl chloride rings the granulation tissue became inhomogeneous with proliferation islets surrounded by edematous regions containing a diminished number of cells. The number of polymorphonuclear leukocytes and of macrophages was greatly enhanced in the whole tissue, whereas the number of lymphocytes was reduced. After seven days the whole granulation tissue was loosened, and its mass was twice as high as in the control animals. The number of fibroblasts per area unit and the hydroxyproline content were diminished. Linoleic acid and 13Ls-hydroxy-9,11(Z,E)-octadecadienoic acid (13-HODE) caused also some changes in the formation of granulation tissue, but in a different manner, in particular, without accumulation of polymorphonuclear leukocytes and macrophages, indicating the specificity of the effect of 9-HODE. The recruitment of leukocytes was not due to a direct chemotactic action of 9-HODE as shown in an agarose diffusion test comparing the effects of 9-HODE and leukotriene B4. The possible biological importance of the proinflammatory effect of 9-HODE is discussed.

[Monoiodoacetic acid-induced arthropathy of the rabbit knee--a contribution to the pathogenesis of arthrosis]. / Die Monojodazetat-induzierte Arthropathie am Kaninchenknie--Ein Beitrag zur Pathogenese der Arthrose.

A chemically-induced joint degeneration was produced by an one-time intraarticular injection of the glycolysis inhibitor monoiodic acetate into the rabbit knee joint (32 joints of 16 rabbits + 4 control animals). The investigation is founded on Kalbhen's animal model of osteoarthrosis and on Salter's and Moskowitz' experiments. Histomorphological examinations were done in intervals of 1 day to 12 weeks. The results raise several open questions in experimental as well as clinical aspects. On that account these results were discussed pathogenetically in the view of the own pathophysiological and biocybernetical conception of osteoarthrosis development.

[Morphometric and histologic studies after transplantation of avital xenogenic tissues]. / Morphometrische und histologische Untersuchungen nach Transplantation avitaler xenogener Gewebe.

The reaction of subcutaneous soft tissue on xenogenic grafts was studied by means of morphometric and histological methods. Xenogenic grafts of human dura and bovine vessels were prepared with fibrin tissue adhesives and with a Lys-Pro-derivative which is an angiogenic factor in other animal models. The best results could be demonstrated in the animal group in which the Lys-Pro-derivative was used, 7, 28, and 87 d after operation.

[The effect of the peptide dalargin on wound healing]. / Untersuchungen zur Wirkung des Peptides Dalargin auf die Wundheilung.

The wound-healing agent Dalargin, a hexapeptide and varios of its cleavage products were tested in a wound-healing model on the basis of granulation in rat. Three days after wounding (p.op.) an increase in granulation was observed at Dalargin concentrations of 10 micrograms/ml and 50 micrograms/ml. Seven days p.op. an increase was observed already at a Dalargin concentration of 5 micrograms/ml. The cleavage products of Dalargin had no stimulating effect on granulation. A histologic differentiation of the different cell parts in the granulation tissue led to an increased total number of cells. The concentration of 5 micrograms/ml induced both an increase in the number of endothelial cells and fibroblasts, the concentration of 50 micrograms/ml induced just an increase of the number of endothelial cells. The possible bases of the mode of operation are being discussed. The stimulating effect on wound healing as described could be confirmed by the results obtained in our animal experiments.

The dipeptide Lys-Pro restores the diminished wound healing following treatment with anti-T-helper cell monoclonal antibody.

To determine the role of T-cell subsets in wound healing, we studied the granulation tissue proliferation after depletion of CD4 or CD8 positive cells. Granulation tissue proliferation in CD8-diminished AB mice was significantly higher than in the control group as a result of depleted suppressor cell activity. The CD4-depleted mice produced granulation tissue in less than 30% of the control group. To investigate the role of dipeptidylpeptidase IV on CD4 positive cells in wound healing we used Lys-[Z(NO2)]-Pro, a chemically modified dipeptide which may result by degradation of polypeptides by this peptidase. It was possible to restore the diminished capability of granulation tissue proliferation in CD4-depleted mice by a single treatment with the dipeptide Lys-[Z(NO2)]-Pro. Our results suggest that: (i) the CD4 positive T-helper subset regulates wound healing, and (ii) products of degradation by dipeptidylpeptidase IV may bypass T-helper cell function.

[Comparative animal experiments of different tissue adhesives. I. Tensile strength studies. II. Histologic and morphometric studies]. / Vergleichende tierexperimentelle Untersuchungen verschiedener Gewebeklebstoffe. Teil I: Zerreissfestigkeitsuntersuchungen. Teil II: Histologische und morphometrische Untersuchungen.

This paper for the first time presents the results of extensive histological and histomorphometric studies investigating the tensile strength of tissue adhesives in model experiments on animals. The material used in comparative studies were TISSEEL, a human adhesive based on fibrinogen, HISTOACRYL-blue, a cyanoacrylate, and KL-3, a type of urethane adhesive. All the materials used in these studies were shown to be principally suitable as tissue adhesives. TISSEEL, the biological adhesive, was obviously superior to all the other adhesives whereas the two synthetic adhesives HISTOACRYL-blue and KL-3 were found to be roughly equal in their properties. The animal model described in the present paper is recommended for use as a standard technique for testing the suitability of new tissue adhesives.

[Experimental chronic stomach ulcer]. / Das experimentelle chronische Ulcus ventriculi.

A survey of different methods for the production of experimental gastric ulcer in rats is given. 20 male Wistarrats got a chronic gastric ulcer after the injection of 0.05 ml acetic acid (30%) under the serosa. We documented the developing of the ulcer in phases by means of histology. In contrast to other models the Acetic Acid Injection Ulcer (by Takagi et al. 1969) shows similar histology and chronicity to human histology and chronicity.

[Preparation and experimental studies with an allogenic tissue adhesive during the addition of a dipeptide which promotes wound healing]. / Präparation und experimentelle Untersuchungen mit einem allogenen Gewebekleber unter Zusatz eines wundheilungsfördernden Dipeptides.

The indication for application of tissue sealants in operative medicine was extended in the last years. With an allogenic fibrin adhesive system produced from coagulation plasma-fractions COHN I and cryoprecipitate an effective tissue glue system is introduced which is comparable to international known preparations. By addition of a wound healing compound to this tissue glue the revascularisation and connective tissue organisation of the wound area can be accelerated. Experimental data with this combined sealant prove the excellent sealing of the wound surfaces and an increased tension strength of the sealed wound.

[Animal experiment research on the application of a human bone collagen substance]. / Tierexperimentelle Untersuchungen zum Einsatz einer Human-Knochen-Kollagen-Substanz.

The possibility of the application demineralised human cortical substance with a particle size of 315 micron was investigated on the filling of artificial defects at the tibial diaphysis in rabbit. A clear induction of the bone healing was observed histologically on the transplant side already after 4 weeks and the absence of a periosseous callus formation radiologically.

Pancreatic endocrine tumours: histological, immuncytochemical and electronmicroscopical investigations.

Fifteen endocrine pancreatic tumours (8 insulinomas, 3 gastrinomas, 1 vipoma, 3 tumours without hormonal activity) and two cases with dysplasia of the endocrine pancreas are reported. Immunohistochemical and electronmicroscopical investigations produced evidence of multihormonality in adenomas that clinically appeared to be monohormonal. The S-phase fraction of such tumours is below 1% which indicates their low proliferative potential. The malignancy of endocrine pancreatic tumours cannot be seen from cytochemical or histological symptoms; it can be established with certainty only from the presence of metastases. Multiple endocrine adenomas should suggest the possibility of hereditary endocrine polyadenomatosis. Hyperplasia and distribution disorder of the endocrine tissue as well as pathologically increased nesidioblastic activity represent the morphologic substrate of dysplasia of the endocrine pancreas as a potential cause of hyperinsulinaemic hypoglycaemia in infancy.

Histological studies into rat liver following long-term application of aminophenazone, phenazone, and propyphenazone.

Morphological studies by means of light microscopy are important for toxicological drug testing. More complete information on potential damage can be obtained only by combination of pharmacological, biochemical, hepatofunctional, and morphological tests and studies. No systematic tests had been applied to rats, in the past. Therefore, aminophenazone, phenazone, and propyphenazone were tested for periods up to 16 weeks. Long-term application of the three pyrazolone derivatives resulted in the following dose-dependent and time-dependent alterations: hepatocyte enlargement, fatty degeneration and reactive-inflammatory changes along with single-cell necrosis, round cellular infiltration of periportal fields, and Kupffer cell activation. The alterations differed in intensity by the following order: aminophenazone greater than phenazone greater than propyphenazone.

[Immunohistological determination of beta-endorphin in chromophobe, clinically hormone-nonproducing hypophyseal adenomas]. / Immunhistologischer Nachweis von beta-Endorphin in chromophoben, klinisch hormonell inaktiven Hypophysenadenomen.

Pituitary adenomas are usually classified according to the nature of their proper hormonal production. Silent adenomas of the pituitary are tumors without clinical and biochemical evidence of overproduction of any known adenohypophyseal hormones. The proportion of such seemingly nonfunctioning tumors is 20 to 30%. Silent corticotropic adenomas are able to synthesize some normal or abnormal sequences of proopiomelanocortin precursor without any signs of hypercorticism. These tumors were divided into basophilic adenomas with strong periodic acid-Schiff (PAS) positivity and chromophobic adenomas with moderate or no PAS positivity. All of our cases were chromophobic adenomas. Two of the cases were positive for beta-endorphin by immunofluorescence. ACTH immunoreactivity was not present in the cells. Electron microscopic study of the adenoma cells showed small secretory granules with a halo. The diameter of these granules varied from 50 to 250 nm. Automated morphometric and densitometric investigations of silent corticotropic adenomas and adenomas from patients with Cushing's disease gave different karyometric results. The most important practical problem arising from the present investigation was the high frequency of recurrence of silent corticotropic tumors.