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Neutrophil-activating peptide-1/interleukin-8 (NAP-1/IL-8), secreted by monocytes, macrophages and a number of other cells, acts as a chemoattractant for neutrophil leukocytes and stimulates them to produce a series of responses such as shape change, adherence, exocytosis and respiratory burst, events that are of importance in inflammation. To study the release of NAP-1/IL-8, two human models of inflammation were chosen: transurethral resection of superficial bladder cancer and the subsequent instillation of bacillus Calmette-Guérin (BCG), performed in order to reduce the recurrence rate of papillary bladder tumors. As the secretions of the bladder wall are retained in the urine, patients' urine was collected during 4-hour periods. These urine samples were chromatographed on phosphocellulose. In the elution fractions NAP-1/IL-8 was quantified by a bioassay that measured the elastase release by human neutrophils. The neutrophil-stimulating activity was further purified by reverse phase high performance liquid chromatography. Although no NAP-1/IL-8 activity could be detected in normal individuals, formation of this inflammatory cytokine was observed in patients after transurethral resection and after BCG treatment. The significance and possible use of this secretion are discussed.

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Allogenic, demineralized bone powder (DBP) was implanted into rat rectus abdominis muscle to induce osteoneogenesis. The main induction steps are invasion of the implant by host mesenchyme cells, differentiation of cartilage, invasion by blood capillaries or angiogenesis, differentiation of osteoblasts and bone marrow. The result is the formation of a cancellous ossicle. Giant polykarions appear in the implant after calcification of the cartilage matrix. As the DBP particles are not resorbed in the implant, these polykarions could either be foreign body giant cells brought about in reaction to foreign matrix or chondroclasts which resorb the cartilage. The results obtained by histological and histochemical methods (McNeals-von Kossa stain, tartrate resistant acid phosphatase reaction), as well as ultrastructural studies, lead to the conclusion that these large polynucleated cells are chondroclasts.

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A 6 1/2-year-old child was admitted to the emergency ward for third degree burn injuries representing 40% of body surface. Shock therapy was first applied. After débridement and in a series of operating sessions hands were grafted with full-thickness skin and most other wounds were covered with mesh grafts. On the 14th day after admission a piece of approximately 5 cm2 split thickness scalp skin was used to expand the keratinocytes by cell culture techniques according to the method of Rheinwald and Green (7). After 20 days 4 sheets of cells of first subculture, each 10 cm in diameter, representing a surface of approximately 300 cm2, were implanted on the front of the left thigh, which was burnt third-degree deep. Light microscopy of punch biopsies from mesh grafted and keratinocyte implanted sites taken 5 months after grafting showed a well differentiated epidermis overlying scar tissue. The following conclusions were drawn: Autologous keratinocytes did take on a third degree wound. No basic difference was observed neither clinically nor histologically between mesh-grafted and keratinocyte-implanted sites. The epidermis formed by keratinocyte implantation lacked pigmentation but presented an aesthetically better appearance than the mesh-graft treated sites. Given the scarcity of donor sites and the results obtained by implanting keratinocyte cultures, this latter technique may be resorted to in any extended and deep burn injury.

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Under the influence of demineralized bone pieces L6 cells differentiate into chondrocytes. The cartilage formed is identifiable histologically. The results demonstrate that these myoblastic cells, which are committed to produce muscle, may still be influenced to express another potentiality of their genome.

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New bone tissue can be induced anywhere in the animal organism, i.e. even at a site distant from actual bone, by the implantation of demineralised bone powder (DBP). Basic implantation experiments were first carried out and tested in the rat (Bettex-Galland 1985). The results led us to use the experience gained to treat four patients with bone defects with DBP (one bone cyst, and 3 chronic skull defects). The DBP used was prepared aseptically from fresh cadaver bone. The results were assessed by means of x-ray films and/or CT-scan, and the preliminary evaluation is encouraging.

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The allogenic implantation of demineralized bone powder induces the formation of new bone tissue or osteoneogenesis. It is generally admitted that mesenchyme cells differentiate into chondroblasts and osteoblasts. In view of the clinical application of this principle, a series of experiments was performed on the animal. Demineralized bone powder of rat long bones was prepared and implanted in trephine defects of the skull or in the musculus rectus abdominis of young rats. The histologic results are described and illustrated. Very early the implant is invaded by poorly differentiated cells of the mesenchyme type and by blood vessels. It is also surrounded by a thin layer of fibroblasts. At day 10 of the implantation, the formation of cartilage is observed. This cartilage disappears in the following days. At day 20 islets of bone marrow are formed. This tissue is surrounded by osteoblasts in their activation phase. At day 30, these osteoblasts are in a highly active state and produce osteoid, in which osteocytes are enclosed. The osteoid is rapidly calcified. Given the primary localisation of the osteoblasts, the bone marrow lays in the center of newly formed ossicles. Osteoclasts can also be observed. At day 45, the different bone marrow centers tend to fuse laterally and to form larger ossicles. The osteoblasts are in a less active or totally inactive form. Many pieces of the implanted demineralized bone powder are still observable. Inflammatory reactions upon implantation are not observed and the bone tissue formation remains located inside the fibroblast layer surrounding the implant.(ABSTRACT TRUNCATED AT 250 WORDS)

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