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In applying amorphous silica and talc in the site of solid Sarcoma 180 implants, the authors found a suppression and delay of tumor growth which was proveked by peritumoral foreign-body granulomas. Correlating these findings which those experiments which resulted in granulomas of hypersensitivity type, it may be suggested that any kind of peritumoral chronic inflammation enables an anti-tumor effect.
BCG administered by the multiple-puncture technique has been used in a prospective, randomized study of the adjuvant treatment of patients with osteogenic sarcoma. Pulmonary granulomas were found in the lungs of four of five patients receiving BCG, that underwent thoracotomy for the diagnosis of pulmonary nodules within three weeks of the last BCG injection. Except for a single, foreign-body granuloma no pulmonary granulomas were seen in seven randomized patients who did not receive BCG. In addition, two patients receiving BCG had evidence of granulomas in bone marrow and in a mediastinal lymph node. BCG administered by the multiple-puncture technique is capable of causing granulomas at sites distant from that of the BCG application. BCG can cause pulmonary granulomas and these granulomas may be confused with pulmonary metastatic disease.
In human beings there have been no observations of heterogenous sarcoma after application of macromolecular artificial implants although such materials have been applied for the last 25 years. Only benign granulomas and inflammatory processes have been described. This paper describes the appearance of double-refraction artificial particles in macrophages and in granulomas encapsulated in the neighborhood of Dacron arterial prosthesis and synthetic suture materials. These processes are possibly an expression of a biological discharge of the implants.
Observation of two patients with hair-spray induced lung disease have prompted us to study the ultrastructure of the lung lesion. We have compared the results with experimental lesions in animals injected with hair-spray extracts and with human monocyte cell cultures exposed to hair-spray. The lungs show a chronic alveolitis with a striking granulomatous reaction including macrophages and multinucleated giant cells of the foreign body type. The intraalveolar and interstitial macrophages and the giant cells all contain PAS-positive material. Ultrastructurally distinct lamellar inclusions are found in the secondary lysosomes of the macrophages and giant cells. Identical structures can be produced in animals injected with hair-spray extracts and with polyvinyl-pyrrolidone and -acetate (PVP/PVA), which are regular ingredients of hair-sprays. Large, presumeably polymeric particles (PVP/PVA) are ingested by giant cells. This "gigantophagocytosis" is associated with the fusion of mononuclear phagocytes and leads to the genesis of giant cells. In cell cultures of human blood monocytes hair-spray extracts and PVP/PVA induce maturation and aggregation of these cells, with PAS-positive cytoplasmatic inclusions. The development of multinuclear giant cells in these monocyte cell cultures is also seen. These observations suggest that hair-spray induced lung disease is caused by the prolonged and extensive body response of the local mononuclear phagocyte system (MPS). Overstimulation of the MPS leads to a quantitative and qualitative change which is followed by a partial blockade of this system. The alveolitis is a consequence of the foreign body response to inhaled hair-spray substances.
Three cases are reported in which pseudotumours developed in the hand following injury by oil palm thorns. In one patient there was a periosteal reaction of the proximal phalanx adjoining the site of injury. The lesions were excised, and the embedded oil palm thorn was identified in all three. The clinical and pathological features of the lesions and problems in their diagnosis are described. In every case the local tissue reaction was out of proportion to the size of the foreign body, raising the possibility that a toxic substance might have been released by the thorn.
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A case is presented of chronic systemic Dacron and Teflon embolism arising from a Beall Model 103 mitral valve prosthesis installed 11 years earlier. The emboli induced intense foreign body reaction resulting in numerous microgranulomas throughout the body. Multiple microinfarctions in the brain accounted for repeated episodes of transient ischemic attacks. Wearing of the prosthesis with consequent embolic complications seems to be the inevitable terminal fate of such early models of the Beall valve. Regular assessment of the functional status of such prostheses, particularly those in place for more than 5 years, is strongly recommended.
The basis for the glucocorticoid-mediated decrease in tissue collagen was studied in mouse granulomas and in primary granuloma fibroblast cultures. Injection of mice for 12 days with dexamethasone (0.35 mg/kg body weight) resulted in a 50--70% inhibition of collagen synthesis and accumulation in polyvinyl sponge-induced granulomas whereas total protein synthesis was inhibited by only about 25%. The decreased collagen content of the granuloma was accounted for by both a reduced fibroblast number and diminished synthesis per cell. Growth rates, total protein synthesis and collagen synthesis were the same in granuloma fibroblast cultures derived from control or steroid-treated mice. However, addition of 3.10(-7) M hydrocortisone to the culture medium caused a 30--50% inhibition of both collagen and non-collagen protein synthesis in firbroblasts from either source. These inhibitory effects were dose- and time-dependent with a lag time of 12--24 h. Prolyl hydroxylase activity was reduced both in sponge granulomas from glucocorticoid-treated mice and in hydrocortisone-treated fibroblast cultures. However, protein synthesis was inhibited to the same extent as the inhibition of prolyl hydroxylase activity and there was no effect on peptidyl prolyl hydroxylation. These results indicate that the glucocorticoid-induced reduction of collagen synthesis and accumulation observed in mouse granulomas and primary granuloma fibroblast cultures is not specific for this protein. Furthermore, glucocorticoid-induced inhibition of collagen synthesis cannot be attributed to underhydroxylation of collagen prolyl residues.
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Examination of a great number of tissue samples taken from the newly formed capsules surrounding artificial joints reveals small particles of prosthetic material. Abraded from the joint by wear and tear, these particles of plastic, metal, and acrylic cement initiate a foreign-body reaction and result in the formation of granulation tissue, including macrophages and foreign-body giant cells. Typical features of tissue reactions exist for each of the materials from which prostheses are made. The consequent formation of scar tissue produces a thickening of the capsule, which, in turn, may cause a reduction in the mobility of the joint. In small amounts, the foreign-body particles are eliminated via the perivascular lymph spaces. Where this transport system is insufficient to handle the volume, however, the foreign-body response may extend to the whole environment surrounding the joint. In such cases, there may be loosening of the cemented prosthetic parts because of deterioration of contiguous bone anchors by the tissue membrane lining the bone cement.
Quantitative histopathologic and biochemical comparisons were made between polyvinyl sponge capsular and sponge tissue in the rabbit on different days after subcutaneous implantation. Up to 9 days the predominant cell type in the capsular tissue is the fibroblast and in the sponge it is the neutrophil. During this time period the sponge tissue shows lower rates of (14C) proline and (14C) cytidine incorporation and lower rates of total (14C) collagen synthesis than the surrounding capsule. Different gel electrophoretic patterns of isolated radioactive proteins are found in sponge and capsule at 6 days. These biochemical differences appear to be related to the small number of fibroblasts, relative to granulocytes present in sponges during the first 9 days after implantation. It is suggested that future biochemical investigations of the early phase of connective tissue reactions (first 9 days) in this model utilize sponge capsular tissue within 1 cm of the sponge edge instead of the sponge and its contents.
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Multinucleated giant cells were examined with electron microscopy from (1) four peripheral giant cell granulomas of the jaws, (2) a central giant cell tumor of the maxilla, (3) five giant cell tumors of tendon sheath, (4) experimentally induced foreign body granulomas in rats, (5) a virus-induced sarcoma, and (6) osteoclasts from the mandibles of rats and (7) the femurs of hamsters. The purpose of the study was (1) to examine the location and arrangement of the nuclei and the centrioles of the multinuclueated cells and compare them with the osteoclast which has previously been thought to have a unique arrangement and (2) to observe whether the physical location of the centrioles and the nuclei were such that the nuclei could undergo mitosis within the cytoplasm. All of the multinucleated cells were found to have a similar arragnement of nuclear concentration areas and nucleus-free areas. A giant centrosphere containing multiple pairs of centrioles was found in the nucleus-free areas, unassociated with any particular nucleus. In the case of the foreign body giant cell and the osteoclast, this giant centrosphere was located very close to the foreign material or bone. When occasional single pairs of centrioles were found, they were located in the area of nuclear concentration, closely associated with a particular nucleus at the periphery. These findings have shown that a common centrosphere containing multiple centrioles is not an exclusive feature of the osteoclast as was previously thought. The findings suggest that a mononuclear cell containing a centriole pair fuses to the larger cell and maintains its centriole pair in close proximity to its nucleus for a short period of time, during which it may undergo mitotic activity. Eventually, the centrioles proceed to a common centrosphere whereas the nuclei aggregate in another area making further mitotic activity an unlikely possibility.
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A study was carried out on the pathology of trichinosis in human muscle biopsy sample and comparatively in experimental trichinosis in the rat, by current microscopic techniques and Troitsky's method of block silver impregnation of the nerve endings. Stress is laid upon the incipient changes in the parasitized muscle fibers, the sarcolemmic origin of the parasite capsule, the myogenic nature of certain periparasitary but intracapsular clear cells of precocious appearance and other associated, non-specific lesions, such as common myositis changes or giant myogenic foreign-body cells. The intimate relationships between parasitized muscle fibres, cellular interstitial reactions, local new-growth vessels and proliferation of the nerve endings are also described. The morpho-functional significance of such morphological synergic manifestations is discussed as an adaptation to the new local conditions brought about by the appearance of the peculiar muscle fibre-parasite unit in trichinosis.
These investigations delineate the recently described suppression of a form of cellular hypersensitivity in mice with streptozotocin-induced diabetes mellitus using a variety of cell-mediated immunologic responses in animals with several different forms of diabetes. Streptozotocin- and alloxan-induced diabetic mice and db/db genetically determined diabetic mice showed reductions in the areas of inflammation around Schistosoma mansoni eggs injected into the pulmonary vasculature of 68, 70, 77%, respectively. In contrast, streptozotocin-induced diabetes had no effect on the nonimmunologic foreign body granuloma around divinyl benzene copolymer beads injected into the pulmonary arterioles. Animals protected from diabetes by treatment with nicotinamide before streptozotocin administration did not develop hyperglycemia and had normal areas of immunologic granuloma formation around schistosome eggs. Treatment with insulin reversed the suppression of schistosome egg granuloma formation in both streptozotocin- and alloxan-diabetic animals. Two additional in vivo parameters of cellular immunologic reactivity were examined in streptozotocin-induced diabetes: delayed footpad swelling was essentially eliminated; skin graft survival across the H-2 area was significantly prolonged from 10.2 days in the controls to 14.4 days in moderately diabetic A/J mice. These observations suggest that diabetes mellitus is associated with suppression of cell-mediated reactions in vivo and that the defect is reversible with insulin treatment.
Histological, histochemical and ultrastructural studies were done on soft tissue surrounding alloarthroplastic joints. In 38 cases a prosthesis of the hip joint and in 2 cases of the knee had to be exchanged and replaced. In most of the cases the reoperation became necessary because the anchoring of the prosthetic parts in the bone loosened. Up to 18 months after the first operation infection was responsible for the malfunctioning in some cases. Other complications were luxation and material faults. The morphological changes are determined by the tissue reaction to the different alloplastic materials used and by the time interval they remained in the organism. The large polymerized acrylic cement particles are phagozytosed by multinucleated foreign body giant cells. About 12 months following the implantation of the artificial joints small double refractile particles appear and evoke characteristic morphological changes. The particles are abraded by the continuous friction of the moving alloplastic or metallic surfaces of the prostheses. Usually they are phagozytosed by histiocytes, which form large granulomas and undergo degenerative changes as is indicated by the ultrastructural and histochemical findings. These alterations are more pronounced and occur sooner in prosthesis with parts (rotation ball or cup.) fabricated by polyester than in those made by polyethylene. The abraded particles not only are transported to the inguinal lymphnodes, but also to the tissue between prostheses and bone, where they induce the same morphological changes as in the capsule. Hence the fibrous membrane separating bone and prostheses increases in width, and the spongy bone is partially destroyed by the proliferating histiocytes. It is assumed that by impairing the anchoring this foreign body reaction to the abraded alloplastic particles is the leading cause of the loosening of this kind of artificial joints.