Effects on intact femora of dogs of the application and removal of metal plates. A metabolic and structural study comparing stiffer and more flexible plates.

Studies of flexible plates made of plastic have shown that less osteoporosis develops beneath them than beneath rigid metal plates. However, to date plastic plates of appropriate physical properties and biocompatibility are not available for use in humans. To determine if a similar beneficial effect could be obtained using metal plates, the effects of thick chromium cobalt plates were contrasted in experiments in dogs with the effects of thinner plates of similar design made of titanium, 6-aluminum, 4-vandium. A significant reduction in the osteoporosis was obtained by use of the more flexible plates. Following plate application a delayed, massive, transient stimulus to bone formation occurred endosteally, periosteally, and intracortically. Despite this, a substantial decrease in bone mass occurred, primarily mediated by endosteal bone resorption. Intracortical porosity played little or no role in net bone loss. The major effects subsided by six months. Recovery after plate removal was predominantly the result of endosteal new-bone formation.

Plaque assay for Rickettsia rickettsii.

A plaque technique for the assay of Rickettsia rickettsii is described. The method employs primary chick or green monkey kidney monolayer cell cultures with either an agarose or special Noble agar overlay. Plaques were counted in 6 days and resultant titers correlated well with ld(50) end points obtained by a standard assay in embryonated eggs. Identification of the plaque-forming organisms was accomplished by direct observation of rickettsiae-like bodies in the monolayer lesions, inhibition of plaques by antibiotics, sensitivity of plaques to specific immune serum, and failure to cultivate other microorganisms from the infected cells. Versatility of the test was demonstrated by assaying samples of rickettsiae from several different sources commonly used in our laboratory. These included infected yolk sacs, various cell cultures, and infected guinea pig tissue. Sufficient numbers of viable rickettsiae were present in the cells of a single lesion to permit direct recovery.

Bony ingrowth fixation of the acetabular component in canine hip joint arthroplasty.

Five mature dogs were studied five to eight months after insertion of a newly designed acetabular component that eliminates the use of bone cement in total hip arthroplasty (THA). The component was hemispheric, with a layer of porous metal on its outside surface. It initially was fixed to the innominate bone by screws passed through projections from the edge of the metal substrate. When the dogs were killed five or eight months after implantation, all components were fixed rigidly to the bone. Bony ingrowth covered an average of 53% of the porous surface of the implant, penetrating three layers of balls.

Preclinical toxicologic studies of netilmicin.

1-N-Ethylsisomicin (netilmicin), a semisynthetic aminoglycoside antibiotic, was given parenterally to mice, rats, guinea pigs, rabbits, and dogs for toxicological evaluation. Acute signs of toxicity were consistent with neuromuscular blockade. Results of teratological studies in rats and rabbits were negative; the only effect observed was wavy ribs, a minor developmental variation, in rats. No effects were found on fertility, reproduction, or development of offspring. Single daily doses of 60 mg/kg s.c. for 10 weeks in young rats and 30 days in young dogs were non-toxic. No indication of toxicity was found in rats and dogs given single daily doses of 7.5 mg/kg i.v. for 2 weeks. Daily i.m. doses caused signs of neuromuscular blockade in rats after 2 weeks at 100 mg/kg and after 1 month at 50 mg/kg, and in dogs after 2 months at 75 mg/kg; dose levels of 150 mg/kg did not cause renal failure. No ocular changes or impairment of vestibular or auditory function were evident at any dose studied. Comparison with tobramycin, gentamicin, and kanamycin at s.c. doses of 50 or 150 mg/kg per day for 4 weeks showed netilmicin to be less nephrotoxic in rats than tobramycin or gentamicin and only slightly more nephrotoxic than kanamycin. Only mild changes were seen microscopically in kidneys of dogs given netilmicin at daily doses of 75 mg/kg i.m. for 3 months. The renal effects of netilmicin given at high multiples of the human therapeutic dose were one-half to one-third less that those of gentamicin and were not severe at any dosage.

Stimulation of bone formation in vivo by phosphate supplementation.

The effect of phosphate supplementation on bone remodeling was assessed in six mature, healthy beagle dogs. The phosphate supplement was given in divided doses orally, daily for 12 weeks in the form of a neutral potassium phosphate preparation. The dose averaged 108 mg P/kg per day, which is double the normal canine phosphorus intake. Bone remodeling was assessed by measurement, at sacrifice, of areas of cortical bone containing different color-coded tetracyclines which had been continuously administered during 12-week control and treatment periods; remodeling was assessed kinetically during the control and treatment periods by replicate studies employing 47Ca intravenously. Both techniques demonstrated that the principal effect of phosphate supplementation was a significant stimulation of bone formation. Within cortical bone, formation was doubled, from an average of 2.7% to 5.3% per year. The major location of new bone deposits was endosteal. Whole skeletal mineral accretion, measured kinetically, increased 45% above an average control value of 0.154 g/day. These studies suggest that, in the adult dog, "normal" plasma phosphate levels are suboptimal for new bone formation. Even with this short duration of administration, phosphate produced microscopic calcification of the renal parenchyma. However, there was no biochemical evidence of renal functional impairment.