Showing papers by "Kenneth D. Brandt published in 1989"

Infectious complications of cyclophosphamide treatment for vasculitis

Abstract: Fifteen patients with Wegener's granulomatosis, polyarteritis nodosa, or isolated angiitis of the central nervous system were treated with cyclophosphamide according to a widely used regimen. Seventeen clinical episodes of infection were observed over 201 patient-months of cyclophosphamide therapy, and 2 patients died of pneumonia. Notably, neither the incidence of leukopenia nor the dosage or duration of cyclophosphamide or corticosteroid therapy correlated well with infection, which occurred most frequently in men over 60 years of age. Patients with Wegener's granulomatosis appeared to be at greater risk of infection than those with the other forms of vasculitis. These results suggest that this treatment regimen may not be as safe as was previously thought.

Gait alterations in dogs after transection of the anterior cruciate ligament

Abstract: We calculated mean peak vertical forces (MFz) of each limb of 9 adult mongrel dogs before and 2 weeks, 6 weeks, and 12 weeks after left anterior cruciate ligament transection (ACLT). Five additional dogs were studied before and 2 weeks and 6 weeks after sham ACLT. The gaits of 3 dogs that had undergone ACLT 2.5 years previously were also analyzed. Preoperatively, there were no differences in the MFz of the right and left hind limbs of the 9 dogs; we found that each limb exerted approximately 70% of the dog's static body weight on the force plate. Two weeks following ACLT, the MFz of the operated limbs decreased to 25% of the static body weight, while at 6 weeks and 12 weeks after surgery, the MFz generated by the operated limbs rose to about 32% and 37% of static body weight, respectively. No change was noted in the MFz of the contralateral hind limbs. In the 3 dogs that had undergone ACLT 2.5 years earlier, the MFz in the unstable stifle joint was 50% of static body weight. At both 2 weeks and 6 weeks after surgery, the MFz values for all 4 limbs of the animals subjected to sham ACLT were comparable with baseline values. These observations indicate that the osteoarthritic changes seen in the unstable limb are associated with decreased loading of that limb, without increased (compensatory) loading of the contralateral hind limb.

Lack of association between serum keratan sulfate concentrations and cartilage changes of osteoarthritis after transection of the anterior cruciate ligament in the dog.

Abstract: To determine whether the serum keratan sulfate (KS) concentration reflected the status of degenerating articular cartilage in a commonly used model of osteoarthritis (OA), serum KS levels were measured in 9 dogs prior to transection of the anterior cruciate ligament, 4 weeks later, and when the dogs were killed 8-14 weeks after surgery, at which time mild OA was present. In all cases, the serum KS levels were within the normal range. Values were not related to the cartilage uronic acid concentration, the rate of net 35SO4 glycosaminoglycan synthesis, or the histopathologic changes of OA. Although the serum KS concentration was not helpful as an indicator of the current status of the articular cartilage abnormality in the OA knee, serial samples from 6 dogs showed an increase of at least 10% over the baseline KS level at both timepoints following surgery (P = 0.031 and 0.027). This presumably reflects changes in proteoglycan metabolism in the unstable knee, although the possibility of a systemic change in proteoglycan metabolism following cruciate ligament transection cannot be excluded.

Cartilage matrix glycoprotein is present in serum in experimental canine osteoarthritis.

Abstract: We have described previously a disulfide-bonded 550,000-D cartilage matrix glycoprotein (CMGP), which is found in normal hyaline cartilage, fibrocartilage, and the vitreous of the eye, and consists of subunits with apparent molecular weights of 130,000 in 4% gels (116,000 in 9% gels). In osteoarthritic cartilage from dogs subjected to transection of the anterior cruciate ligament (ACL), CMGP is cleaved to major immunoreactive fragments with apparent molecular weights of 65,000 and 75,000 after reduction with 2-mercaptoethanol. In the present study, using immunolocation analysis, a monoclonal antibody to CMGP did not react with serum from 8 of 12 dogs before ACL transection but did react with serum from seven of these animals 4 wk after surgery and with serum from 10 dogs at sacrifice, 8-14 wk after ACL transection. Serum from four dogs reacted with the monoclonal antibody before ACL transection. Serum from two dogs was negative at all time points. Immunolocation studies using a polyclonal antiserum to CMGP were performed in seven of these dogs and produced results identical with the monoclonal antibody in four dogs. In contrast, analysis of serial serum samples from three dogs with cartilage atrophy revealed no evidence of CMGP at any time point. These data suggest that CMGP may be a serum marker for osteoarthritis in this canine model.

Suppression of glycosaminoglycan synthesis by articular cartilage, but not of hyaluronic acid synthesis by synovium, after exposure to radiation.

Abstract: We recently found that injection of 2 mCi of yttrium 90 (90Y; approximately 23,000 rads) into normal canine knees stimulated glycosaminoglycan (GAG) synthesis by femoral condylar cartilage. The present investigation was conducted to determine whether radiation affects cartilage metabolism directly. Rates of GAG synthesis and degradation in normal canine articular cartilage were studied following irradiation. Cultured synovium from the same knees was treated similarly, to determine the effects of irradiation on hyaluronic acid synthesis. Twenty-four hours after exposure to 1,000 rads, 10,000 rads, or 50,000 rads, 35S-GAG synthesis by the cartilage was 93%, 69%, and 37%, respectively, of that in control, nonirradiated cartilage. The effect was not rapidly reversible: 120 hours after exposure to 50,000 rads, GAG synthesis remained at only 28% of the control level. Autoradiography showed marked suppression of 35S uptake by chondrocytes after irradiation. Cartilage GAG degradation was also increased following irradiation: 4 hours and 8 hours after exposure to 50,000 rads, the cartilage GAG concentration was only 66% and 54%, respectively, of that at time 0, while corresponding values for control, nonirradiated cartilage were 90% and 87%. In contrast to its effects on cartilage GAG metabolism, radiation at these levels had no effect on synovial hyaluronicmore » acid synthesis.« less

Effects of salicylate on chondrocytes from osteoarthritic and contralateral knees of dogs with unilateral anterior cruciate ligament transection.

Abstract: Salicylates suppress net glycosaminoglycan synthesis in articular cartilage. The inhibitory effect is greater in osteoarthritic (OA) cartilage than in normal cartilage. Whether the isolated OA chondrocyte is inherently more susceptible to the effects of salicylate on glycosaminoglycan metabolism has not been determined. The results of this study show that, after isolation from the extracellular matrix, normal and OA chondrocytes in suspension culture are similarly susceptible to the metabolic effects of salicylate. However, chondrocytes from the contralateral knees of dogs with unilateral OA were notably resistant to the effects of salicylate.

Hereditary symphalangism. Association with osteoarthritis.

Abstract: A pedigree is described with 5 generations affected by hereditary symphalangism of the proximal interphalangeal joints of the hands. In the proposita, osteoarthritis was present proximal and distal to the symphalangitic segment, possibly due to altered mechanical forces in these joints.