Effect of recombinant human bone morphogenetic protein-2 on fracture healing in a goat tibial fracture model.

Bone morphogenetic proteins (BMPs) are considered to have important regulatory roles in skeletal embryogenesis and bone healing. Recombinant human BMPs (rhBMPs) have been shown to heal critical size defects and promote spinal fusion. We studied the effects of rhBMP-2 in an absorbable collagen sponge (ACS) on bone healing in a large animal tibial fracture model. Bilateral closed tibial fractures were created in 16 skeletally mature goats and reduced and stabilized using external fixation. In each animal, one tibia received the study device (0.86 mg of rhBMP-2/ACS or buffer/ACS), and the contralateral fracture served as control. The device was implanted as a folded onlay or wrapped circumferentially around the fracture. Six weeks following fracture, the animals were sacrificed and the tibiae harvested for torsional testing and histomorphologic evaluation. Radiographs indicated increased callus at 3 weeks in the rhBMP-2/ACS treated tibiae. At 6 weeks, the rhBMP-2/ACS wrapped fractures had superior radiographic healing scores compared with buffer groups and controls. The rhBMP-2/ACS produced a significant increase in torsional toughness (p = 0.02), and trends of increased torsional strength and stiffness (p = 0.09) compared with fracture controls. The device placed in a wrapped fashion around the fracture produced significantly tougher callus (p = 0.02) compared with the onlay application. Total callus new bone volume was significantly increased (p = 0.02) in the rhBMP-2/ACS fractures compared with buffer groups and controls regardless of the method of device application. The rhBMP-2/ACS did not alter the timing of onset of periosteal/endosteal callus formation compared with controls. Neither the mineral apposition rates nor bone formation rates were affected by rhBMP-2/ACS treatment. The increased callus volume associated with rhBMP-2 treatment produced only moderate increases in strength and stiffness.

In vitro strength comparison of hydroxyapatite cement and polymethylmethacrylate in subchondral defects in caprine femora.

Hydroxyapatite cement was investigated in situ for the reconstruction of juxta-articular defects. Polymethylmethacrylate is currently the most commonly used material for the reconstruction of bone defects following the exteriorization and curettage of aggressive benign tumors. In vitro, we compared the effects of hydroxyapatite cement and polymethylmethacrylate in restoring the stiffness of the subchondral plate in a caprine femoral defect model. Ten matched pairs of caprine femora underwent nondestructive compression testing normal to the load-bearing surface. A standardized subchondral defect 12 mm in diameter was created in the medial femoral condyle. Compression testing was repeated to determine the reduction in stiffness caused by the defect. Each femur from each pair was randomly assigned to one of two groups (n=9), and the defects were augmented with either polymethylmethacrylate or hydroxyapatite cement. After 12 hours, compression testing was repeated to determine the subchondral stiffness after augmentation. Compared with intact femora, the defect specimens that were later treated with either polymethylmethacrylate or hydroxyapatite cement exhibited stiffness values of 70 (386+/-107 N/mm) and 59% (343+/-94 N/mm) respectively, which represented a significant reduction in stiffness (p=0.05). Augmentation with polymethylmethacrylate or hydroxyapatite cement restored stiffness by 81 (450+/-111 N/mm) and 71% (413+/-115 N/mm), respectively, of the values of intact specimens. Hydroxyapatite cement restored stiffness significantly (p=0.05) over the stiffness of the nonaugmented defect compared with the stiffness after augmentation with polymethylmethacrylate (p=0.12). Neither polymethylmethacrylate nor hydroxyapatite cement restored stiffness to that of intact femora (p=0.05). In the current detect model, hydroxyapatite cement was comparable with polymethylmethacrylate in restoring subchondral stiffness. Unlike polymethylmethacrylate, however, hydroxyapatite cement has the following advantages: it is osteoconductive, is replaced by host bone, and avoids the potential for thermal necrosis. Hydroxyapatite cement may therefore provide a viable alternative to polymethylmethacrylate for augmentation of juxta-articular and other bone defects.

Effects of pneumolysin on human polymorphonuclear leukocytes and platelets.

Pneumolysin was bound by human polymorphonuclear leukocytes in a reaction which occurred very rapidly at 0 degrees C. Low concentrations of pneumolysin were found to stimulate leukocyte migration and lysosomal enzyme secretion. At increasing lysin levels, inhibition of spontaneous migration and chemotaxis, cell death, and lysis were observed. Pneumolysin was also found to lyse platelets and to activate serum to become chemotactic.

Additional evidence that a new virulence-associated antigen of Neisseria gonorrhoeae is not of pilus origin.

Triton-X-100-treated pilus suspensions prepared from Neisseria gonorrhoeae produced a single line of precipitate in immunodiffusion tests. This line was distinct from that of the virulence-associated antigen.

Strain-specific virulence-associated antigen of Neisseria gonorrhoeae.

A strain-specific virulence-associated antigen has been found in Neisseria gonorrhoeae strain F-62. Using immunodiffusion in agar gel, it has been shown that the antigen is distinguishable from endotoxin and the virulence-associated toxic protein. It does not appear to be derived from pili. The antigen was not detected in T1 and/or T2 colony type cultures of 10 other isolates. It exhibited a possible partial immunological relationship with an antigen found in one additional strain. It was susceptible to digestion with Pronase and trypsin.