Showing papers by "Kenneth D. Brandt published in 1994"

A randomized, double blind, placebo controlled trial of intravenous loading with S-adenosylmethionine (SAM) followed by oral SAM therapy in patients with knee osteoarthritis.

Abstract: OBJECTIVE: We evaluated the effectiveness and rapidity of onset of S-adenosylmethionine (SAM), administered as daily intravenous boluses of 400 mg for 5 days, followed by oral tablets, 200 mg thrice daily for 23 days, versus a matching placebo regimen, in the treatment of 81 patients with symptomatic knee osteoarthritis (OA). METHODS: The study was bicentric, randomized, double blinded, and placebo controlled. Patients underwent a 7-day washout of arthritis medications prior to initiation of this study treatment. Major outcome measures were the Stanford Health Assessment Questionnaire disability and pain scales, and supplemental visual analog scales for rest and walking pain. RESULTS: At one site, patients had milder OA, the baseline characteristics of the treatment groups were well matched, and the SAM treated group showed significantly greater reduction in overall pain and rest pain (p < 0.05) than the placebo treated group. At the other site, the patients had more severe OA, randomization yielded markedly different treatment groups, and the response to treatment did not differ between groups. Onset of SAM effect was seen as early as 14 days after the start of treatment. CONCLUSION: SAM may be an effective treatment for some patients with symptomatic knee OA, and merits further study. Intravenous loading before oral maintenance therapy may be advantageous.

Distribution and predictors of depressive symptoms in osteoarthritis

Abstract: Objective To determine the prevalence and correlates of depressive symptoms in a sample of elderly persons with osteoarthritis (OA). Methods Secondary analysis of cross sectional interview data from 108 community living persons age 50 or over who met American College of Rheumatology clinical criteria for OA of the hip and/or knee. Results The prevalence of substantial depressive symptomatology appeared to be no greater than would be expected in the general population for this age group. However, persons currently under a physician's care for OA were significantly more depressed than those not under care, and, with the exception of those who had post-high school education, depression was a better predictor of being under care than OA symptoms. The direct and interactive effects of 3 variables--education, age and self-perceived impact of the OA problem--were found to explain 40% of variance in depression scores in the total sample and 50% among those currently receiving care. Younger and less educated subjects had relatively more depressive symptoms and, furthermore, in this subgroup the correlation between OA impact and depression was high. Conclusions The importance of assessing depression in persons who seek care for OA is supported. Furthermore, our results suggest that the observed relationship between education and arthritis outcomes could be mediated, at least in part, by depression.

Procollagenase is reduced to inactive fragments upon activation in the presence of doxycycline.

Abstract: Tetracyclines have been shown to inhibit matrix destruction and metalloproteinase activity in a number of pathologic conditions.' We showed that oral doxycycline administration slows the progression of cartilage destruction in osteoarthritis induced in dogs by anterior cruciate ligament t r a n s e c t i ~ n . ~ ~ ~ Articular cartilage collagenase was strikingly reduced in treated dogs, and inhibition of total collagenase was more pronounced than was inhibition of active enzyme. This observation and the variability in reported levels of enzyme inhibition by the tetracyclines led us to examine the effect of doxycycline on proenzyme activation. For this purpose, we activated recombinant human neutrophil procollagenase in vitro in the presence or absence of doxycycline and assayed activity and the molecular weight changes that accompany activation. Procollagenase was activated with trypsin or APMA, and collagenase activity was assayed on either collagen fibers4 or a small peptolide ~ubs t ra te .~ When the enzyme was activated before the addition of doxycycline, approximately 50% inhibition of enzyme activity was noted in the presence of 30 pM doxycycline with either substrate or mode of activation. By contrast, when latent enzyme was activated in the presence of doxycycline, 30 pM doxycycline inhibited almost all of the activity, and 50% inhibition was obtained with 5-12 FM doxycycline depending on the conditions of activation (TABLE 1). When trypsin was used to activate latent enzyme, the extent of inhibition was related to the rate of activation. At higher trypsin concentrations, when activation was rapid, inhibition was less than that at lower trypsin concentrations, when activation required extended incubation. For the data shown in TABLE 1, ICs0 at the lower trypsin concentration (6 pM) was half that obtained at the higher trypsin concentration. Similar results were obtained with APMA activation. Upon examination by Western blotting of the molecular weight changes that accompany activation, the basis for the foregoing observation became apparent (FIG. 1). In the absence of doxycycline, most of the proenzyme (55 kDa) was converted to active enzyme (46 kDa with trypsin, 45 kDa with APMA). In the presence of doxycycline, however, little active enzyme accumulated. Instead, trypsin cleaved the

Current practices for monitoring ocular toxicity related to hydroxychloroquine (Plaquenil) therapy.

Abstract: OBJECTIVE Growing interest in aggressive early management of rheumatoid arthritis (RA) with hydroxychloroquine (alone or in combination with other immunomodulating drugs) is reason to review current practices for monitoring ocular toxicity in patients who take antimalarial therapy METHODS We surveyed by mail all ophthalmologists and rheumatologists in the State of Indiana about their practices in this regard RESULTS Twenty-nine of 31 rheumatologists (94%) responded All but one recommended ophthalmologic examinations every 6 months and 41% would leave the choice of testing procedures to the ophthalmologist Fifty percent had discontinued hydroxychloroquine because of a patient's failure to make and/or keep an appointment with the ophthalmologist Of 213 ophthalmologists surveyed, 150 (70%) responded Seventy-nine percent recommended semiannual examinations Funduscopy, visual acuity, and color vision tests were reported to be performed routinely Eleven of 13 retina specialists (85%), but only 25% of 127 general ophthalmologists, would obtain macular photographs (p < 0001) Forty-two percent of general ophthalmologists, compared with 8% of retina specialists, would perform computerized perimetry (p < 0001) Recognition of retinal hyperpigmentation as a classic sign was surprisingly low in both groups Concurrent review of the medical records of 24 patients with RA or systemic lupus erythematosus showed extremely variable followup intervals for ophthalmologic examination; 7 of the 24 patients had no record of an ophthalmologic evaluation CONCLUSION As interest in the early, aggressive management of RA continues to grow, significant education needs to be devoted to the monitoring and diagnosis of ocular toxicity of hydroxychloroquine by both rheumatologists and ophthalmologists

Serial kinematic analysis of the canine knee after L4-S1 dorsal root ganglionectomy: implications for the cruciate deficiency model of osteoarthritis.

Abstract: OBJECTIVE To characterize knee movements before and after unilateral hindlimb deafferentation in dogs with stable joints. METHODS High speed cinematography and frame by frame analysis were used to analyze knee kinematics of 6 dogs serially for 26 weeks following L4-S1 dorsal root ganglionectomy, which was performed to deafferentate one hindlimb. RESULTS Overall knee movements were not reduced, but knee extension increased during most of the gait cycle. Few changes occurred in knee velocity, and none at touchdown or during weight acceptance. CONCLUSION We previously showed that unilateral hindlimb deafferentiation does not cause osteoarthritis or reduce ipsilateral peak vertical forces in dogs with stable knee joints over an observational period of 16 months. We now show that joint protection in the deafferented stable joint occurs, paradoxically, in the presence of increased knee extension. We conclude that whereas sensory nerves may limit knee extension during ambulation, the health of the joint is not dependent upon this "extension limiting" function.

CLINICAL RHEUMATOLOGY TRAINING IN AN UNCERTAIN FUTURE. Opinions of Recent and Current Rheumatology Fellows About an Extended Fellowship in Musculoskeletal Medicine

Abstract: OBJECTIVE To estimate among recent and current rheumatology fellows the appeal of a 3-year rheumatology fellowship emphasizing musculoskeletal medicine. METHODS A survey of 348 trainee members of the American College of Rheumatology during 1990-1993, by mailed questionnaire. RESULTS The response rate was 77.8% (n = 271). Both recent and current fellows indicated that they desired more experience in musculoskeletal medicine. Most notably, 50% of current fellows, and a significantly higher proportion of recent fellows (70%; P < 0.005), indicated that they would have opted for a 3-year fellowship in musculoskeletal medicine had one been available to them at the completion of their residency. CONCLUSION Expertise in musculoskeletal medicine is desired by a sufficient proportion of recent and current rheumatology fellows to warrant the investment in another year of training.