Repair of calvarial defects in rats by prefabricated hydroxyapatite cement implants.

The aim of the present study was to test the hypothesis that calvarial defects can be repaired by using preformed implants of calcium phosphate bone cement (CPBC) in rats. Sixty adult female Sprague-Dawley rats received full-thickness calvarial nonhealing defects with a diameter of 8 mm. Three different CPBCs were used: group 1: tetracalcium phosphate-based powder; group 2: a blend of amorphous and crystalline calcium phosphate precursors; and group 3: an alpha-tricalcium phosphate (alpha-TCP)-based powder. Implants were left to cure for 25-40 min at room temperature in a silicon mold of 7.9 mm and inserted press fit into the defects. Fifteen animals served as unfilled controls. After 13, 26, and 52 weeks, the material was analyzed qualitatively by using surface-stained undecalcified thick-section specimens and quantitatively by using semiautomated histometry. Kruskal-Wallis tests were applied to compare mean values of periimplant bone formation at a significance level of p < 0.05. Three implants of group 1 fractured during insertion. Resorption of CPBC without complementary bone formation was noticed in these implants. Unfractured implants were resorbed with simultaneous apposition of bone on the implant surface. After 52 weeks, the resorption rate varied between 23.1 and 39.3%. Periimplant bone formation increased continuously on average around all implant types, but it reached statistical significance only in group 2. The results showed that repair of calvarial defects can be achieved by preformed CPBC implants. The rate of resorption of preformed implants is, however, much lower than that reported for in vivo cured CPBC.

Biologic properties of a bispecific single-chain antibody directed against 17-1A (EpCAM) and CD3: tumor cell-dependent T cell stimulation and cytotoxic activity.

Anti-CD3 x anti-tumor-bispecific Abs have been used to redirect cytotoxic T cells to tumor cells in an MHC-unrestricted fashion and to induce their rejection in vivo. We have recently described a recombinant bispecific single-chain Ab that combines four different V regions of two Abs, anti-17-1A and anti-CD3, on one polypeptide chain. It folds correctly to a 60-kDa globular protein and is secreted in fully functional form by a high producer Chinese hamster ovary cell line. In this work, we report that its remarkable cytotoxicity against 17-1A+ tumor cells is exerted via T cells without an apparent engagement of a detectable costimulatory pathway. T cells are activated only by the bispecific Ab when coincubated with 17-1A+ target cells. In a chromium release assay, CD8+ T cells reach maximal tumor cell cytotoxicity within 4 h, while CD4+ T cells need about 20 h to reach similar levels of cytotoxicity. Addition of costimulatory CD28 Abs did not lead to a further increase in cytotoxicity. Its remarkable stability at 37 degrees in serum, the ease of production, and purification by affinity chromatography via polyhistidine tail make this smaller version of a bispecific Ab a promising candidate for a therapeutic trial in patients with solid tumor. Because adjuvant therapy with an intact, much less cytotoxic IgG2a Ab against the 17-1A target had already increased the 7-yr survival of colorectal cancer patients by 30%, the presented small bispecific construct lacking the immunogenic murine Fc region as well as autochthonous T lymphocyte stimulatory activity warrants a therapeutic trial in patients with minimal residual 17-1A+ cancer.

Epidemiologic research in an integrated regional medical care system: the Marshfield Epidemiologic Study Area.

To capitalize on Marshfield Clinic's advantages for population-based health research, we developed the Marshfield Epidemiologic Study Area (MESA). Marshfield Clinic is an integrated system consisting of a large multispecialty clinic and 23 affiliated clinics. Clinic physicians provide virtually all of the medical care, both inpatient and outpatient, for residents of the area. MESA consists of 14 ZIP codes in which over 95% of the 50,000 residents and most significant health events are captured in Marshfield Clinic databases, including all deaths, 94% of hospital discharges, and 92% of medical outpatient visits. MESA exemplifies the research potential of integrated medical care systems and the efforts required to realize that potential. Because it is representative of a defined population and provides an unselected sample of patients, MESA is well suited for epidemiologic research and research elucidating the clinical spectrum and natural history of diseases and the effectiveness of treatment.

The short nose.

Lengthening the short nose is arguably the most difficult operation in aesthetic rhinoplasty. Open and closed operative techniques can achieve absolute lengthening. In the open technique, maximum lengthening is achieved by releasing the mucoperichondrium, which has to be elevated bilaterally from the septum; releasing the soft tissue between the upper and lower lateral cartilages; and attaching a batten graft to the septum to project the tip cartilages caudally. The closed technique uses a hemitransfixion incision and elevation of the mucoperichondrium bilaterally, followed by attachment of a batten graft. The apparently short nose also can be treated by derotating the tip, correcting the columellar labial angle, and altering the location of the nasion as well as the nasofacial angle.