This study did not demonstrate a true long-term benefit of internal fixation, compared with nonoperative treatment, for acute nondisplaced or minimally displaced scaphoid fractures. The long-term risks of surgery should be considered when recommending operative treatment.

Connective tissue remodeling provides mammals with a rapid mechanism to repair wounds after injury. Inappropriate activation of this reparative process leads to scarring and fibrosis. Here, we studied the effects of platelet-derived growth factor receptor-␤ blockade in vivo using the platelet-derived growth factor receptor (PDGFR)-␤ inhibitor imatinib mesylate on tissue repair. After 7 days, healing of wounds was delayed with significantly reduced wound closure and concomitant reduction in myofibroblast frequency, expression of fibronectin ED-A, and collagen type I. Using a collagen type I transgenic reporter mouse, we showed that inhibiting PDGFR-␤ activation restricted the distribution of collagen-synthesizing cells to wound margins and dramatically reduced cell proliferation in vivo. By 14 days, treated wounds were fully closed. Blocking PDGFR-␤ signaling did not prevent the differentiation of myofibroblasts in vitro but potently inhibited fibroblast proliferation and migration. In addition, PDGFR-␤ inhibition in vivo was accompanied by abnormal microvascular morphogenesis reminiscent of that observed in PDGFR-␤ ؊/؊ mice with significantly reduced immunostaining of the pericyte marker NG2. Imatinib treatment also inhibited pericyte proliferation and migration in vitro. This study highlights the significance of PDGFR-␤ signaling for the recruitment, proliferation, and functional activities of fibroblasts and pericytes during the early phases of wound healing.

The variable clinical response seen with most cancer immunotherapy suggests that there is a large interindividual variation in immunologic response to tumors. One of the key functional parameters of an immune response is the local production of cytokines. As a method to survey the immune status of tumor-infiltrating cells, we have investigated the constitutive expression of cytokine mRNA in biopsies from epithelial ovarian carcinomas by using a PCR-assisted mRNA amplification assay. Using a set of cytokine-specific primers for 10 different cytokines, we have found selective expression of interleukin 10 (IL-10), granulocyte-macrophage colony-stimulating factor, and interferon gamma mRNA in ovarian tumor tissue as compared to normal ovaries and ovarian tumor cell lines. Such differences could not be explained by the extent of T-cell infiltration, since comparing samples with the same intensity of T-cell receptor (TCR) constant region alpha-chain product from the tumor and normal biopsies demonstrated different cytokine patterns. No IL-2 gene expression was detected in the tumor biopsies. IL-2 mRNA, however, became expressed after stimulation of the tumor-derived cells via the CD3 molecule but not after growth in recombinant IL-2 alone. Using the same methodology, we also analyzed the TCR variable region beta-chain gene repertoire. No restriction or biased expression of these genes was observed.

Gerdin B, Hällgren R (University Hospital, Uppsala, Sweden). Dynamic role of hyaluronan (HYA) in connective tissue activation and inflammation (Minisymposium: Hyaluronan). J Intern Med 1997; 242: 49–55. An increased tissue accumulation of HYA occurs in several human and experimental inflammatory conditions. Such is the case in sarcoidosis, idiopathic pulmonary fibrosis and farmer's lung in man, and experimental bleomycin‐induced lung damage in rats. Graft rejection in man and rats, experimental myocarditis in mice and myocardial infarction in rats follow the same pattern. Increased amounts of HYA also appear in gut luminal perfusion fluid in human inflammatory bowel disease. A transient accumulation of HYA is seen in wound healing, which is more sustained in fetuses. An increased accumulation of water and presentation of ligands for receptors on inflammatory cells are two consequences of the HYA accumulation.

No abstract

The BSHS-B is a valid but shorter alternative to the previously described BSHS-A. Important domains of postburn distress are captured better in the BSHS-B than in the BSHS-R.

By using biotin-labeled proteoglycan core protein and an avidin-enzyme system, hyaluronic acid (HA) was visualized in rat kidney. In the normal kidney, HA was localized in the extracellular space of the inner medulla and increased markedly towards the papillary tip. No staining for HA was seen in the interstitial tissue of the cortex or the outer medulla. During the development of rejection of allogeneic renal grafts, a progressive increase in accumulated HA was seen in the interstitial tissue of the cortex and outer medulla. The extractable amounts of HA increased, on average, 40 times in the cortex and outer medulla; no increase was measured in the inner medulla and papilla. The relative water content of the cortex and outer medulla also increased progressively and correlated with the HA accumulation. The extractable amounts of HA in syngeneic grafts increased by day 2 and then leveled off, indicating that surgical trauma may induce some transient HA accumulation after transplantation. Interstitial accumulation of HA, a glycosaminoglycan with unique water-binding qualities, would presumably influence water transport and osmotic activity and should thereby be implicated in the normal papillary function, but also in the development of the interstitial edema of the cortex and outer medulla during rejection of renal grafts.

The expression and localization of PDGF f8 receptors and PDGF-AB/BB in human healing wounds was evaluated by immunohistochemical techniques and in situ hybridization. Expression of PDGF ft receptor protein and PDGF-AB/BB were analyzed in wound margin biopsies using the PDGFR-B2 and PDGF 007 antibodies. PDGF ft receptor expression was minor in normal skin. An increased expression of PDGF f receptor protein was prominent in vessels in the proliferating tissue zone in wounds as early as 1 d after surgery and was apparent c 4 wk after surgery. There was also a concordant increase in PDGF , receptor mRNA detected by in situ hybridization. PDGF-AB/ BB was present in healing wounds as well as in normal skin. In normal skin, expression of PDGF-AB /BB was confined to peripheral nerve fibers and to solitary cells of the epidermis and of the superficial dermis. In wounds, infiltrating mononuclear cells also stained for PDGF-AB/BB. To identify cell types expressing PDGF AB/BB and PDGF f receptors, respectively, we performed double immunofluorescence stainings.PDGF ft receptors were expressed by vascular smooth muscle cells and cells in capillary walls; the receptor protein could not be detected in neurofilament containing structures, T lymphocytes, or CD68 expressing macrophages. PDGF-AB/BB colcalized with neurofilaments, it was present in Langerhans cells of the epidermis and in HLA-DR positive cells located in the epidermal/dermal junction area. Of the macrophages infiltrating the wound, 43±18% stained positively for PDGF AB/BB. Since PDGF-AB/BB and PDGF 13 receptors are expressed in the healing wound, two essential prerequisites for a role of PDGF in wound healing are fulfilled. (J. Clin. Invest. 1993.