[Experimental application of calcium phosphate granulate for the substitution of conventional bone transplants (author's transl)]. / Experimentelle Anwendung von Kalziumphosphatgranulat zur Substitution von konventionellen Knochentransplantaten.

Autologous spongiosa, a calcium phosphate ceramic and Kiel bone chips were implanted in the tibiae of dogs and compared with respect to tissue compatibility and osteogenetic effect. After the ceramic implants and the autologous spongiosa had been left in the tibial fat marrow for six weeks, bone tissue and bone marrow had formed to the same extent around both materials. Their stimulating effect on osteogenesis was comparable. In contrast to the ceramic material, together with which they had been implanted in active bone marrow, the Kiel bone chips were surrounded by fibrous tissue in addition to bone tissue. All of the three types of implant proved to be tissue compatible. On the whole, the calcium phosphate ceramic was found to be equal to autologous and superior to heterologous spongiosa from a biological point of view. In technical terms the ceramic implant was superior also to the autologous graft.

[Significance of coagulation disorders and inflammatory immune reaction in an infectious model of rheumatoid arthritis. I. Systemic, shock-like coagulopathy and fibrin incorporation as indicators of rheumatoid manifestations in the erysipelas model]. / Zur Bedeutung von Gerinnungsstörungen und entzündlicher Abwehr einer infektiös verursachten rheumatoiden Modellkrankheit. I. Systemische, schockartige Koagulopathie und Fibrininkorporation als Indikatoren der rheumatoiden Organmanifestation im Rotlaufmodell

A combined study employing plethysmographical, scintillation counting and coagulation methods indicates that a coagulation crisis in combination with fibrin overproduction may be an indicator of a beginning arthritis of rheumatoid character. Rats which received a single subcutaneous infection with erysipelas bacteria exhibit a shock resembling crisis two days post inoculation as substantiated by the consumption of coagulation factors II, V, VIII, XII and decrease of platelets. This consumption of coagulation factors is characterized by a rapid compensatory increase of platelets, antihaemophilic factor VIII and fibrin, 5 times more in the pig and 3 1/2 times more in the rat than in control animals. In adult rats the overproduction of fibrin is combined with an intense concealed consumption of fibrin in all organs of manifestation. Only in young rats an absolute consumption of fibrin is observed. The incorporation of fibrin into connective tissue is accompanied by fibrin consumption as demonstrated by immunofluorescence, by oedema of the paw, and by mesenchymal proliferation as substantiated by scintillation counting of incorporated 35SO4 and 3H-Proline, as markers for the beginning synthesis of ground substances and collagen. This model supports the importance of an initial vascular phase for the subsequent phase of manifestation in chronic rheumatoid diseases. It is discussed whether the organ specific permeability of the affected organs (joints, heart, arteries and eyes) may be a localizing factor of organ manifestation, parallel to the hormonal mesenchymal reaction.

[The significance of coagulation disorders and the inflammatory reaction in an infectious model of rheumatoid arthritis. II. Inhibition trials with antirheumatic drugs in the inflammatory reaction phase of erysipelas polyarthritis in rats]. / Zur Bedeutung von Gerinnungsstörungen und entzündlicher Abwehr bei einer infektiös verursachten rheumatoiden Modellkrankheit. II. Inhibitionsversuche mit Antirheumatika in der entzündlichen Abwehrphase der Rotlaufpolyarthritis bei Ratten

The arthritic activity in the initial phase and during manifestation of experimental erysipelas in rats, an animal model for human rheumatoid arthritis, was studied by plethysmometrical methods. The development of body weight and specific pathologic alterations peculiar to the model such as keratitis, thrombosis of the aorta and gangrene of the tip of the tail served as additional parameters. In the volumetric analysis it could be shown that the first arthritic swelling on both hind legs develops symmetrically up to day 6 post infection in rats with about 200 g of body weight-and in contrast-on the 2nd p.i. in younger animals with about 120 g. The first maximal paw volume was measured on day 9 p. i., the greatest decrease in body weight-a reduction of 25%-on day 10 p. i. In addition the reaction of the animal model following the application of steroid and non-steroid symptomatically as well as cytostatically acting antirheumatic drugs was tested. Daily treatment with acetylsalicylic acid, indomethacine or hydrocortisone provoked more or less significant inhibition of arthritic swelling in the paw. Only at the onset of arthritis acetylsalicylic acid was more effective than the other antiphlogistic drugs. No measurable increase of paw volume during cyclophosphamide treatment could be evaluated. None of the antirheumatics used had a positive effect on body weight developement. In hydrocortisone and also in cyclophosphamide treated rats a greater decrease was obtained than in the infected controls. No thrombosis developed after cytostasis with cyclophosphamide. The advantages of this systemic connective tissue disease with regard to its comparability with human rheumatoid arthritis and due to the course of its arthritic manifestation are discussed, together with the disadvantages specific to the model and the experimental conditions.

[Studies of the toxic components of Erysipelothrix rhusiopathiae. 2. Communication: Detailed characterization of an extracted endotoxin (author's transl)]. / Untersuchungen über toxische Bestandteile von Rotlaufbakterien (Erysipelothrix rhusiopathiae). 2. Mitteilung: Nähere Charakterisierung eines extrahierten Endotoxins

The endotoxins of different Erysipelothrix rhusiopathiae strains were examined in various biological systems, since in earlier investigations (Leimbeck and Böhm, 1975) the lethal effect for 10 day old chick embryos had been found to be highly dependent upon the virulence of the strains. The lethal effect for mice and rats was found to be much less. The toxin of the strain T28 proved to be highly pyrogenic for rabbits and inducing acute shock-effects in swine SCHULZ et al. (1961) already suggested that a shock-like pathogenesis existed in the swine erysipelas infection. Furthermore the endotoxic nature was confirmed by the typical course of temperature after i.v. application of the toxin, the ability to cause the Sanarelli-Schwartzman-reaction (both in rabbits), the protection against toxicity by cortisones, and heat stability. An erysipelas antiserum did not neutralize the toxin. It was found to have low antigenic and apparantly no immunogenic properties and an allergic skin-reaction in experimentally infected swine could not be induced. The toxins of various strains were tested by the macrophagemigration-inhibition test. In respect to a preliminary classification the toxin could be identified as a complexed water-soluble and heat-stable glucoproteid with an estimated molecular weight of 31.700. The polysaccharides were found to be the presumable carriers of toxicity.

[Experimental erysipelas in different species as a model for systemic connective tissue disease. II. The chronic phase with special reference to polyarthritis (author's transl)]. / Experimenteller Rotlauf bei verschiedenen Spezies als Modell einer systemischen Bindegewebskrankheit II. Chronische Phase mit besonderer Berücksichtigung der Polyarthritis

INTRODUCTION: In part I of this paper (Schulz et al., 1975) it was shown that in the initial phase of experimental erysipelas a transition from the vascular processes to a systemic connective tissue reaction can be demonstrated in different species. It is the purpose of this paper to describe the chronic phase of the disease with special emphasis on polyarthritis. MATERIALS AND METHODS: 12 spontaneously diseased and 22 experimentally infected pigs were used in experiments to study the pathogenesis of the disease. In addition, 74 Wistar rats and 148 Sprague-Dawley rats were used in the experiments. All experimental animals were specific-pathogen-free and were parenterally infected with the standardized E. insidiosa serotype B strain T 28. The observation period for the pigs was up to 2 years, for the rats up to 11 months. The methods used for pathohistological and electron microscopical studies are described in part I. Immunihistological studies were carried out on synovial tissue with peroxidase-conjugates of goat-anti-pig-IgG, goat-anti-pig-IgM, pig-collagen, E. insidiosa-homogenate and heat-aggregated-pig-IgG. Furthermore, goat-anti-pig-IgG and rabbit-anti-pig-C3 conjugated with FITC were used. Passive hemagglutination tests and Latex agglutination test (Singer and Plotz) were performed to demonstrate rheumatoid factors and collagen antibodies. RESULTS: Polyarthritis occurred in pigs between the 4th and 10th day p.i. and between the 4th and 8th day p.i. in nearly 100% of the infected rats. Fibrinous exudation, proliferation and destruction with pannus formation are marked in most of the joints examined during the first three months. Fibrosis begins 30 days p.i. in the rats' joints and is most severe in both species between the 5th and 8th month. 3 types of lining cells may be differentiated electron microscopically: A (M) cells, B (F) cells and an intermediate form which is found in both species most frequently. Swelling of the endothelial cells together with constriction of the lumen and thickening of the basal membrane occurs in the capillaries. DISCUSSION: A comparison of chronic erysipelas polyarthritis in pigs and rats with rheumatoid arthritis of men reveals many morphological and immunological similarities between the two diseases. Systemic connective tissue activation manifests itself in organs predilected for rheumatic changes, such as heart valves, endocardium and joints. The possible prepetuation of the processes by specific or nonspecific immunomechanisms or by deposits of fibrin is discussed. In addition, experimental erysipelas is reproducible in nearly 100% of the animals given one single subcutaneous application of one defined bacteria strain. Therefore too, erysipelas is suited as an animal model for human rheumatic diseases.

[Experimental erysipelas in different species as a model for systemic connective tissue disease. I. Systemic vascular processes during organ manifestation (author's transl)]. / Experimenteller Rotlauf bei verschiedenen Spezies als Modell einer systemischen Bindegewebskrankheit. I. Systemische vaskuläre prozesse bei der Organmanifestation

INTRODUCTION: The similarities between erysipelas in animals and rheumatic diseases in man have been discussed since the work of Nieberle (1931). The present work sets out to investigate the course of organ manifestations in pigs, rats, and mice using germ-free or specific pathogen-free experimental animals. Particular consideration will be given to the initial systemic vascular processes as well as to the significance of the erysipelas antigen. MATERIAL AND METHODS: In several experiments, a total of 166 pigs--partly gnotobiotic or specific pathogen-free animals--37 specific pathogen free Wistar rats and 57 albino mice were orally and/or parenterally infected with standardized erysipelas strains of serotype B. Clinical examination post infection were carried out with the EKG and by x-raying the joints of the extremities. All large parenchymatous organs, as well as heart valves, aorta and synovia were examined histologically in paraffin sections. In mice and rats, joints of the extremities were embedded in toto in metracrylate. Besides various histological staining methods, histochemical reactions were used to demonstrate mucopolysaccharides and fibrin. The myocardium, central nervous system and synovia of several joints were examined with the electron microscope. In the pig, immunohistological methods demonstrating the presence of fibrin, complement and IgG, as described by Seidler et al. (1971) and Trautwein et al. (1972), were used. RESULTS: The most important changes in joints, heart valves heart musculature and blood vessels occur during the early bacteriemic phase. A distinct sticking effect develops in the mouse 3.5 hours p.i., in the rat 24 hours p.i., and in the pig 36 hours p.i. Simultaneously, hyaline thrombi occur in capillaries and venules; these are seen as parallel, loosely-packed fibrin fibers in the electron microscope. With the aid of immunofluorescence fibrin, IgG and complement C3 can also be demonstrated here. Exudates rich in fibrin develop parallel to the microthrombosis. In pigs and rats vascular and myocardial necroses develop to 3 days p.i. The mice do not survive the 3rd p.i. 39% of the pigs showed edema and mesenchymal activation of varying intensity in the heart valves between the 3rd and 8th day p.i. Besides the insudation of the valves, endocardial thromboses developed in 80% of the mice. Endocarditis, aand in addition large aortic thromboses were recognized in more than 50% of the rats. As early as the 4th day p.i., coagulopathy, angionecrosis and exudation led to acute arthritic symptoms..