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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.

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.

Ausgehend von der aus der Literatur bekannten guten Einheilung allogener nichtbe- handelter und formaldehydkonservierter Gefase als Gefastransplantate (1, 2) entwickelten wir Ende der 70er Jahre eine Gefasprothese, die insbesondere den Anfderungen an ein AV-Interponat fur Punktionen entsprechen sollte. Diese Prothese ist gekennzeichnet durch Verfugbarkeit verschiedener, insbesondere weiter Lumina, optimale Durchstromungseigenschaften bei Glattwandigkeit durch Formfixierung und primare Athrombogenitat durch selektive Silkonierung der Innenflachen.

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.

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.

Summary In rats with polyvinyl rings implanted under the dorsal skin, the formation of granulation tissue was found to be stimulated by application of brain extract with fibroblast growth factor (FGF) S3 activity which had been obtained from cattle. This stimulating effect on wound healing proved to depend on doses and was detectable in rats aged two and six months on the third and seventh postoperative days. The desired action could be induced only by repetitive administration of FGF S3 or by coupling of the latter to SYSpur-derm®, a synthetic dermatoplastic material. More fractions with potential agtion upon formation of granulation tissue proved to be obtainable from further biochemical separation of FGF S3. One of such fractions was successfully concentrated to a potentiality by which one tenth of the normal dose hielded the same effect as the full dose. Hexosamine and hydroxyproline levels were measured, at the same time, and found to stimulate fibroblasts. The findings are discussed.

Summary Reported in this paper are studies by which evidence was produced to increased formation of granulation tissue in rats, aged two and six months, seven days after repeated localised administration of brain extract from cattle with FGF activity (fibroblast growth factor). Such increased formation of granulation tissue was attributable to the formation in the same granulation tissue of larger amounts of capillaries, which actually provided conditions for better blood supply. The above increase was associated with stimulation of the synthetic function of fibroblasts and myofibroblasts in the granulation tissue. Comprehensive morphometric tests, including differential counting, appeared to show that additional effects had to be assumed, in particular on macrophages and lymphocytes. Such increase in angiogenesis seemed to suggest that in the in vivo model studied FGF proved to be, first of all, a factor of angiogenesis rather than a factor of fibroblast growth. The above results, as obtained from rats which differed in age, exhibited a certain variation in response to FGF. This seems to underline the importance of age-dependent examination also in the context of pharmacological studies.

A bovine brain fraction with FGF activity (fibroblast growth factor) increased the formation of granulation tissue of rats in an experimental wound healing model. It was characterised by intensified formation of new capillaries, stimulation of the synthesis function of fibroblasts and myofibroblasts, and proliferation of freshly developed granulation tissue. The results obtained from light microscopy and autoradiographic electron microscopy with 3H-thymidine suggested significant increase in the labelling of activated, undifferentiated endothelial cells in vascular sprouts and of differentiated endothelial cells in developed capillaries. FGF S3 appeared to speed up the differentiation of freshly formed endothelial cells. Also labelled were pericytes and other fibroblastoid cells, undifferentiated mesenchymal cells, juvenile undifferentiated fibroblasts, mature fibroblasts, myofibroblasts, and macrophages. Pericytes are presumed to be preferential precursors of myofibroblasts, on account of their occurrence in time and similar ultrastructural parameters. Close neighbourhood of lymphocytes and labelled fibroblasts gave rise to the assumption of specific effects, such as stimulation by lymphokines.

Summary From bovine brains a fraction with fibroblast growth factor activity was prepared according to the method given by Gospodarowicz et al. (1978) and tested regarding to its biological effectiveness on articular cartilage regeneration in rabbits the cartilage in one knee-joint of those had been injured in a defined manner. The intraarticular administration of the brain fraction supported the healing process of the intrachondral lesions by conspicuously increasing the chondrocyte proliferation starting from preexisting cartilage tissue. In the case of subchondral lesions the neodifferentiation of chondrocytes out of the simple connective tissue that primarily filled the defect was promoted significantly.

Malakoplakia which was found in the kidney if a man aged 55 years is described. This rare granulomatous lesion was extirpated together with a renal cyst. So-called Hansemann-cells with inclusion bodies and ring structures were found by light and electronmicroscopic examinations. These concentrically arranged ring like structures were not typical Michaelis-Gutmann-bodies, and they consisted of microfibrils and small granula. Using X-ray microprobe analysis could be detected calcium. These findings were considered to be an early stage of malakoplakia.

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.

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.

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.

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.

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.

5 types of fibroblasts were characterized by histomorphometrical and ultrastructural examinations of the wound healing of rats, 3, 7, 14 and 21 days p. op. These cells were undifferentiated mesenchymal cells, immature fibroblasts, mature fibroblasts, myofibroblasts and fibroclasts. The functions of these cells were discussed with respect to cell proliferation, synthesis, and degradation of collagen.

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.

Extended trials were carried out on the purpose of finding optimal silicone rubber materials for endotheses, among others macroscopical and microscopical examinations of local compatibility after implantation in rats and dogs. Short-term experiments on 7 kinds of silicone rubber (VEB Chemiewerk Nünchritz) showed that subcutaneous and intramuscular implantation was well tolerated by rats. Optimal terms for removal were the 7th and the 28th day. Long-term trials of 4 kinds of silicone rubber in rats and dogs up to 1 year yielded no significantly different results compared with control materials from the Dow Corning Corporation. After comparing trials for biostability, 2 silicone rubbers were recommended for clinical use. Optimal terms for removing in long-term experiments were the 3rd, 6th, and 12th month. In the rat experiments after 6 months the thickness of the capsule remained constant, as morphometrically determined. This might be crucial in the assessment of long-term compatibility.

Known liver function tests (activities of ASAT = L-Aspartate: 2-oxoglutarate aminotransferase, ALAT = L-Alanine: 2-oxoglutarate aminotransferase, GLDH = Glutamate-dehydrogenase, LDH = Lactate-dehydrogenase in serum) are not qualified for detecting minimal histopathological liver alterations induced by aminophenazon.

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.

Die experimentelle Lymphstauung bewirkt am isolierten, arbeitenden Rattenherzen trotz konstantem Koronarfluss eine progressive Abnahme der Auswurfleistung des linken Ventrikels, die morphologisch unter anderem mit einem intersititiellen und intrazellularen Odem, insbesondere der Herzmuskelzellen und Kapillarendothelien sowie mit partiellen Herzmuskelzellnekrosen einhergeht.

A bovine brain fraction with fibroblast growth factor (FGF) activity was prepared according to the method described by Gospodarowicz et al. and its influence on the healing process of experimentally produced intrachondral lesions in the knee-joint of rabbits was studied. Intraarticular administration of this preparation resulted in a substantial stimulation of the proliferation of "cluster cells", a special kind of chondrocytes which accumulate and form clusters.

After oral application of aminophenazone to animals (170 and 340 mg/kg daily, over up to 17 weeks), the authors investigated the effect of this drug on some liver functions and performed also a morphological study. They found that aminophenazone produces an increase of the smooth ER, peripheral fatty degradation and reactive-inflammatory responses of the liver, the intensity of these phenomena being dependent upon the dose and time of application. The increase of the smooth ER is the expression of the inductive effect which persists throughout the whole experimental period and manifests itself by accelerated degradation of hexobarbital, increased N-demethylation, increased ascorbic acid synthesis and increased liver weight. The increase in body weight is reduced in the animals treated. The enzyme activities in the plasma lie within the range observed with control animals; they are no indicator of the slight live changes stated. Reactive metabolites and/or the impairment of other metabolic reactions may be considered to be the cause of the hepatotoxic effect of aminophenazone.

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.

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.

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.

Reported in this paper are studies by which evidence was produced to increased formation of granulation tissue in rats, aged two and six months, seven days after repeated localised administration of brain extract from cattle with FGF activity (fibroblast growth factor). Such increased formation of granulation tissue was attributable to the formation in the same granulation tissue of larger amounts of capillaries, which actually provided conditions for better blood supply. The above increase was associated with stimulation of the synthetic function of fibroblasts and myofibroblasts in the granulation tissue. Comprehensive morphometric tests, including differential counting, appeared to show that additional effects had to be assumed, in particular on macrophages and lymphocytes. Such increase in angiogenesis seemed to suggest that in the in vivo model studied FGF proved to be, first of all, a factor of angiogenesis rather than a factor of fibroblast growth. The above results, as obtained from rats which differed in age, exhibited a certain variation in response to FGF. This seems to underline the importance of age-dependent examination also in the context of pharmacological studies.

In female rats the administration of 1,5 mmol/kg of, respectively, propyphenazone and phenazone over a period of 12 weeks produces a histologically detectable fatty degeneration and reactive-inflammatory changes of the liver, presumably caused by reactive metabolites. These slight morphological alterations do not lead to an increase in plasma enzyme activities. Only in case of phenazone administration, reduced increases in body weight are indicative of a toxic effect. The acceleration of hexobarbital degradation and N-demethylation and the increase in liver weight testify to the inductive activity of both these compounds.

A bovine brain fraction with FGF activity (fibroblast growth factor) increased the formation of granulation tissue of rats in an experimental wound healing model. It was characterised by intensified formation of new capillaries, stimulation of the synthesis function of fibroblasts and myofibroblasts, and proliferation of freshly developed granulation tissue. The results obtained from light microscopy and autoradiographic electron microscopy with 3H-thymidine suggested significant increase in the labelling of activated, undifferentiated endothelial cells in vascular sprouts and of differentiated endothelial cells in developed capillaries. FGF S3 appeared to speed up the differentiation of freshly formed endothelial cells. Also labelled were pericytes and other fibroblastoid cells, undifferentiated mesenchymal cells, juvenile undifferentiated fibroblasts, mature fibroblasts, myofibroblasts, and macrophages. Pericytes are presumed to be preferential precursors of myofibroblasts, on account of their occurrence in time and similar ultrastructural parameters. Close neighbourhood of lymphocytes and labelled fibroblasts gave rise to the assumption of specific effects, such as stimulation by lymphokines.

Known liver function tests (activities of ASAT = L-Aspartate: 2-oxoglutarate aminotransferase, ALAT = L-Alanine: 2-oxoglutarate aminotransferase, GLDH = Glutamate-dehydrogenase, LDH = Lactate-dehydrogenase in serum) are not qualified for detecting minimal histopathological liver alterations induced by aminophenazon.

In rats with polyvinyl rings implanted under the dorsal skin, the formation of granulation tissue was found to be stimulated by application of brain extract with fibroblast growth factor (FGF) S3 activity which had been obtained from cattle. This stimulating effect on wound healing proved to depend on doses and was detectable in rats aged two and six months on the third and seventh postoperative days. The desired action could be induced only by repetitive administration of FGF S3 or by coupling of the latter to SYSpur-derm, a synthetic dermatoplastic material. More fractions with potential action upon formation of granulation tissue proved to be obtainable from further biochemical separation of FGF S3. One of such fractions was successfully concentrated to a potentiality by which one tenth of the normal dose yielded the same effect as the full dose. Hexosamine and hydroxyproline levels were measured, at the same time, and found to stimulate fibroblasts. The findings are discussed.

The carbohydrate binding glycoprotein Anti-AHP binds to the plasma membrane of the (transformed) L-cell both in agglutination reactions and by the immunofluorescence technique. On the surface of (normal) mouse embryo fibroblast cells Anti-AHP receptors were not detectable. Anti-AHP is suitable as another marker for L cells. The random distribution of the binding sites at 4 degrees C changes with elevated temperatures (clustering, capping of sites). Anti-AHP inhibits the growth of L cells much more than that of fibroblasts. It does not act as a mitogen for the investigated cells.