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Biomedical subjects

K D Brandt

Publications and source records attributed to K D Brandt.

At least 19 recordsLinked to original sources
PubMed1992

Impairment of osteophyte formation in hyperglycemic patients with type II diabetes mellitus and knee osteoarthritis.

OBJECTIVE: Since insulin is a potent growth factor for connective tissue, the present study was designed to investigate whether radiographic features of knee osteoarthritis (OA) in patients with poorly controlled, insulin-resistant type II diabetes mellitus differ from those in nondiabetic controls with knee OA. METHODS: Radiographs from 25 female patients with diabetes and knee OA were compared with those from 48 female controls who were similar with respect to age, weight, and duration of OA symptoms. RESULTS: Although the 2 groups were similar with respect to the frequency and severity of joint space narrowing, subchondral sclerosis, and geodes, osteophytes were less common in the patients with diabetes (P = 0.044), and spurring, when present, tended to be "marked" less often in the diabetic patients than in the controls. CONCLUSION: The data suggest that diminished availability of insulin at the cellular level or diabetic microvascular disease attenuates the chondro- and osteogenesis required for osteophyte formation in the joints of patients with OA.

Adult↗
PubMed1992

Reduction of joint pain in patients with knee osteoarthritis who have received monthly telephone calls from lay personnel and whose medical treatment regimens have remained stable.

OBJECTIVE: We previously reported that monthly telephone contact by lay personnel, to promote self-care for patients with osteoarthritis (OA), was associated with improved joint pain and physical function after 1 year of followup. The present study was a secondary analysis to determine whether improvement was contingent on intensified medical treatment. METHODS: We reanalyzed control/treatment group differences in all 40 subjects with radiographically confirmed knee OA who had had no changes in antirheumatic drug therapy or institution of physical therapy during the period of observation. RESULTS: Group differences in measured pain remained significant (effect size [ES] = 0.65 SD, P less than 0.01). The same trend was observed for physical function (ES = 0.53 SD, P not significant). CONCLUSION: The findings in this reanalysis suggest that periodic telephone support interventions are effective enough to be regarded as an adjunctive treatment for OA.

Aged↗
PubMed1992

Reduction of the severity of canine osteoarthritis by prophylactic treatment with oral doxycycline.

OBJECTIVE: In vitro studies have indicated that levels of neutral metalloproteinases in osteoarthritic (OA) cartilage are elevated and that doxycycline (doxy) inhibits collagenolytic and gelatinolytic activity in extracts of OA cartilage. The purpose of the present study was to test the effect of oral doxy administration on the severity of cartilage degeneration in OA. METHODS: OA was induced in 12 adult mongrel dogs by transection of the anterior cruciate ligament (ACL) 2 weeks after dorsal root ganglionectomy. Six dogs received doxy orally from the day after ACL transection until they were killed 8 weeks later; the other 6 served as untreated OA controls. RESULTS: The unstable knee of each untreated dog exhibited extensive full-thickness cartilage ulceration of the medial femoral condyle. In sharp contrast, cartilage on the distal aspect of the femoral condyle of the unstable knee was grossly normal in 2 doxy-treated dogs, and exhibited only thinning and/or surface irregularity in the others. Degenerative cartilage lesions on the medial trochlear ridge, superficial fibrillation of the medial tibial plateau, and osteophytosis were, however, unaffected by doxy treatment. Collagenolytic activity and gelatinolytic activity in cartilage extracts from OA knees of untreated dogs were 5-fold and 4-fold greater, respectively, than in extracts from dogs given doxy. CONCLUSION: Prophylactic administration of doxy markedly reduced the severity of OA in weight-bearing regions of the medial femoral condyle. It remains to be determined whether administration of doxy after OA changes have developed is also effective.

Administration, Oral↗
PubMed1992

Treatment of knee osteoarthritis: relationship of clinical features of joint inflammation to the response to a nonsteroidal antiinflammatory drug or pure analgesic.

Our randomized double blinded comparison of acetaminophen versus analgesic and antiinflammatory doses of ibuprofen in the treatment of 182 subjects with knee osteoarthritis (OA) systematically evaluated soft tissue tenderness and joint swelling. Improvement in these signs of joint inflammation was associated with lessening of disability (p = 0.02), and reduction in rest pain (p = 0.07), but not with the drug treatment regimen. Thus, joint tenderness and swelling, presumptive evidence of synovitis, may not be a priori indications for use of an antiinflammatory drug, or predict greater responsiveness to treatment with an antiinflammatory drug than to a pure analgesic, in symptomatic treatment of patients with knee OA.

Acetaminophen↗
PubMed1992

A radiographic comparison of erosive osteoarthritis and idiopathic nodal osteoarthritis.

Clinical, radiographic and histologic features suggest that inflammation is central to the pathogenesis of erosive osteoarthritis (OA). Since mediators of inflammation may activate osteoclasts and stimulate release of metalloproteinases in joint cartilage, we hypothesized that patients with erosive OA may have more joint space narrowing and less proliferative bone response (osteophytes, sclerosis) than those with idiopathic nodal OA. Hand radiographs of 33 patients with erosive OA and 33 age and sex matched patients with nodal OA were evaluated for prevalence and severity of joint space narrowing, osteophytes, subchondral sclerosis, subchondral cysts, erosions and subchondral collapse. While the prevalence and severity of OA was greater at each joint in erosive OA than in nodal OA, significant differences (p less than 0.05) were confined largely to the interphalangeal joints. Among patients with erosive OA, radiographic features of OA were more severe in joints with erosive changes than in joints that did not show erosive change (p less than 0.01 in most cases). Notably, when joints with erosive change were excluded, only joint space narrowing was more severe in patients with erosive OA than in the corresponding joints of patients with nodal OA (p less than 0.001). Our analysis did not support the hypothesis that inflammatory mediators modify chondro or osteoneogenesis in erosive OA.

Adult↗
PubMed1992

Prevalence of cartilage shards in synovium and their association with synovitis in patients with early and endstage osteoarthritis.

It has been suggested that incorporation of shards of fibrillated cartilage into the synovium is a cause of synovitis in osteoarthritis (OA). We examined the prevalence with which fragments of cartilage are seen in synovium, and their association with synovitis, in patients with endstage OA and early OA of the knee. Samples of synovium were obtained from 12 patients with endstage OA who were undergoing knee joint replacement and 30 with only mild/moderate radiographic changes of OA who exhibited articular cartilage changes of OA at arthroscopy. The presence of cartilage shards was sought in synovium from the medial and lateral tibiofemoral compartments and the suprapatellar pouch of each patient. Comparable volumes of the synovial lining from patients with endstage and early OA were examined, and tissue mononuclear cell infiltration was graded as an indicator of synovitis. Cartilage shards were seen in synovium from 7 of 12 patients with endstage OA, all of whom had synovitis. No topographic relationship was found between shards and mononuclear cell infiltration. In contrast, cartilage fragments were not seen in synovium from any of the 30 patients with early OA, although 9 of them had full thickness cartilage ulcers and 17 had evidence of synovitis.

Adult↗
PubMed1992

Neurogenic acceleration of osteoarthrosis. The effects of previous neurectomy of the articular nerves on the development of osteoarthrosis after transection of the anterior cruciate ligament in dogs.

The development of osteoarthrosis in unstable knee joints of dogs after transection of the anterior cruciate ligament is greatly accelerated when the afferent nerve fibers from the ipsilateral hindlimb have been interrupted by dorsal root ganglionectomy before transection. The purpose of the current study was to determine whether partial loss of the afferent fibers from the knee joints of dogs, accomplished by neurectomy of the primary articular nerves before transection of the ligament, also accelerates the development of osteoarthrosis. Osteoarthrosis did not develop in dogs that had had transection of the medial, posterior, and lateral articular nerves to the left knee joint but had an intact anterior cruciate ligament. Osteoarthrosis developed in all dogs that had had transection of the anterior cruciate ligament. However, the osteoarthrotic lesions, as gauged by histological and macroscopic criteria, were more frequent and severe in dogs that had had neurectomy before transection than in those that had intact sensory nerves and an unstable joint (p less than or equal to 0.05). A subchondral fracture occurred in three dogs that had had neurectomy and had an unstable joint but in none of the dogs that had intact sensory nerves and an unstable joint.

Animals↗
PubMed1992

Correlation of serum concentrations of ibuprofen stereoisomers with clinical response in the treatment of hip and knee osteoarthritis.

Stereoselective pharmacokinetic measurements of the active enantiomer, S-ibuprofen, were correlated with clinical response in 45 participants in a randomized double blinded 4 week comparison of ibuprofen, 1200 or 2400 mg/day, for treatment of hip or knee osteoarthritis. Ibuprofen dose correlated with S-ibuprofen area under the serum concentration curve (AUC), trough and average concentration, but not with clinical outcome. AUC of S-ibuprofen correlated with improvement in disability, rest pain and in the physician's global assessment (p = 0.02, 0.08, and 0.10, respectively), and negatively with the subject's weight and creatinine clearance (p = 0.09 and 0.07, respectively). Some individual variation in responsiveness to ibuprofen (and other nonsteroidal antiinflammatory drugs) may be attributed to pharmacokinetic differences.

Adult↗
PubMed1992

Hypothesis: can type IX collagen "glue" together intersecting type II fibers in articular cartilage matrix? A proposed mechanism.

Type IX collagen is crosslinked to the surface of type II collagen molecules, and has been proposed as the glue that binds the collagen network of cartilage matrix. However, there is as yet no evidence that the crosslinks that have been described to date provide interfibrillar connections, and the only mechanism proposed for such connections between intersecting fibers is unlikely on stereochemical grounds. We propose that both type IX collagen and an intermediary molecule are necessary for network stabilization and that proteoglycans are likely candidates for the role of intermediary.

Animals↗
PubMed1991

Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee.

BACKGROUND: The optimal short-term, symptomatic therapy for osteoarthritis of the knee has not been fully determined. Accordingly, we compared the efficacy of a nonsteroidal antiinflammatory drug, ibuprofen, given in either an antiinflammatory dose (high dose) or an analgesic dose (low dose), with that of acetaminophen, a pure analgesic. METHODS: In a randomized, double-blind trial, 184 patients with chronic knee pain due to osteoarthritis were given either 2400 or 1200 mg of ibuprofen per day or 4000 mg of acetaminophen per day. They were evaluated after a washout period of three to seven days before the beginning of the study, and again after four weeks of treatment. The major measures of outcome included scores on the pain and disability scales of the Stanford Health Assessment Questionnaire (range of possible scores, 0 to 3), scores on the visual-analogue scales for pain at rest and pain while walking, the time needed to walk 50 ft (15 m), and the physician's global assessment of the patient's arthritis. RESULTS: Seventy-eight percent of the patients completed four weeks of therapy. No significant differences were noted among the three treatment groups with respect to failure to complete the trial because of noncompliance or adverse events. All three groups had improvement in all major outcome variables, and the groups did not differ significantly in the magnitude of improvement in most variables. The mean improvement (change) in the scores on the pain scale of the Health Assessment Questionnaire was 0.33 with acetaminophen (95 percent confidence interval, 0.14 to 0.52), 0.30 with the low dose of ibuprofen (95 percent confidence interval, 0.09 to 0.51), and 0.35 with the high dose of ibuprofen (95 percent confidence interval, 0.13 to 0.57). Side effects were minor and similar in all three groups. CONCLUSIONS: In short-term, symptomatic treatment of osteoarthritis of the knee, the efficacy of acetaminophen was similar to that of ibuprofen, whether the latter was administered in an analgesic or an antiinflammatory dose.

Acetaminophen↗
PubMed1991

Relationship between arthroscopic evidence of cartilage damage and radiographic evidence of joint space narrowing in early osteoarthritis of the knee.

We examined the relationship between articular cartilage degeneration, as visualized arthroscopically, and joint space narrowing (JSN) in standing anteroposterior knee radiographs of 161 patients with chronic knee pain. The majority of these patients had radiographic findings of mild osteoarthritis. Twenty-five (33%) of the 76 patients in the series whose radiographs showed tibiofemoral JSN had grossly normal articular cartilage in both tibiofemoral compartments at arthroscopy (false-positive). The specificity of medial JSN for the presence of medial compartment articular cartilage degeneration was 0.61, i.e., only 61% of patients with normal (grade 0) medial compartment cartilage had a normal medial joint space. Of 22 patients with greater than 50% medial JSN, 9 (41%) had normal articular cartilage in the medial compartment at arthroscopy. Of 6 patients with greater than 50% lateral JSN, 3 (50%) had normal lateral compartment articular cartilage at arthroscopy. Among 36 patients with greater than 25% JSN who had neither medial nor lateral compartment articular cartilage degeneration, JSN was associated with articular cartilage degeneration in the patellofemoral compartment in 8 (22%), with meniscus degeneration in 18 (50%), and with both in 8 (22%). Thus, in these patients with chronic knee pain, radiographic evidence of JSN in the tibiofemoral compartment did not permit confident prediction of the status of the articular cartilage.

Adolescent↗
PubMed1991

Radiographic grading of the severity of knee osteoarthritis: relation of the Kellgren and Lawrence grade to a grade based on joint space narrowing, and correlation with arthroscopic evidence of articular cartilage degeneration.

We examined standing knee radiographs of 92 patients who had chronic knee pain and radiographic evidence of mild or moderate osteoarthritis (OA) according to the Kellgren and Lawrence (K/L) criteria. Because the K/L criteria overemphasize osteophytosis relative to joint space narrowing (JSN), we graded OA severity also with a scoring system that placed greater emphasis on JSN than on osteophytes. In each case, the articular cartilage was visualized directly at arthroscopy. Of 17 patients whose radiographic findings were normal by both the K/L criteria and our JSN-weighted criteria, 7 had advanced tibiofemoral and/or patellofemoral compartment changes of OA seen at arthroscopy, emphasizing the insensitivity of the radiograph for detecting early articular cartilage loss. In addition, tibiofemoral JSN was common in the presence of normal articular cartilage. The JSN-weighted scale provided no advantage over the K/L criteria for assessing the severity of articular cartilage changes of OA.

Adult↗
PubMed1991

Osteoarthritic changes in canine articular cartilage, subchondral bone, and synovium fifty-four months after transection of the anterior cruciate ligament.

Anterior cruciate ligament transection (ACLT) in the dog results in osteophyte formation and in morphologic, metabolic, biochemical, and biomechanical changes in the articular cartilage of the unstable knee that mimic those of human osteoarthritis (OA). However, in dogs studied up to 2 years after ACLT, the changes have appeared to be self-limiting, which has led to the suggestion that this is a model of cartilage damage and repair, rather than of OA. To ascertain whether changes in articular cartilage and subchondral bone of dogs subjected to ACLT lead to progressive changes of OA, we studied 3 dogs for 54 months after ACLT. Arthrotomy was performed in the dogs to visualize and then transect the anterior cruciate ligament. When the dogs were killed, full-thickness ulceration of the articular cartilage was seen on the medial femoral condyle and tibial plateau of the unstable knee, while cartilage in other regions was thicker than that of the contralateral knee, consistent with hypertrophic cartilage repair. Synovial infiltration by mononuclear cells was not more severe than that seen in dogs killed at earlier intervals after ACLT, although gross fibrotic thickening of the capsule was apparent in each dog. Histomorphometric studies revealed a marked increase in subchondral bone volume and active bone formation. These findings show that the changes that develop in the canine knee joint after ACLT are progressive and are unambiguously those of OA.

Animals↗
PubMed1991

Transection of the anterior cruciate ligament in the dog: a model of osteoarthritis.

Study of the early stages of osteoarthritis (OA) in humans presents numerous difficulties, since the patient commonly does not seek medical attention until pathologic changes are far advanced and articular cartilage has already been extensively lost. Investigators have, therefore, used animal models to obtain information about the early changes in articular cartilage, bone, and synovium. Among the most widely studied of these models is the cruciate-deficient dog. This report validates the cruciate-deficient dog as a model of progressive OA and emphasizes that, before full-thickness loss of articular cartilage, OA is marked by a phase of cartilage hypertrophy associated with a striking increase in synthesis of matrix macromolecules by the chondrocyte (compensatory repair). It reviews evidence that some nonsteroidal antiinflammatory drugs (NSAIDs) and deafferentation of the unstable limb may accelerate cartilage loss in OA, and examines the relationship of synovitis and of changes in subchondral bone to the changes in articular cartilage.

Animals↗
PubMed1991

Cleavage of type XI collagen fibers by gelatinase and by extracts of osteoarthritic canine cartilage.

Gelatinase (matrix metalloproteinase 2) purified from culture medium of MDCK cells by affinity chromatography on gelatin-sepharose was tested against type XI collagen. The purified enzyme-digested native type XI collagen in solution, and as reconstituted fibers, at 30, 34, and 37 degrees C. Both substrates yielded the same digestion products, as characterized by SDS-polyacrylamide gel electrophoresis, but the soluble collagen was cleaved at a higher rate. The first major product seen was an 87-kDa peptide, which was usually associated with one or two peptides migrating between it and alpha 3(XI). With time, a second group of 3 peptides appeared at 78, 75, and 73 kDa. After continued digestion, a third group of peptides was detected with prominent 69- and 67-kDa peptides and minor peptides at 71, 65, and 62 kDa. In overnight (20 hour) digestions, the 60-kDa digestion product accumulated and most of the larger digestion products could no longer be detected. Minor products at 71, 55, and 50 kDa were also noted in these limited digestions. Under the same conditions, denatured type XI was digested to fragments smaller than 13.5 kDa. The enzyme was inhibited by 1,10-phenanthroline or EDTA. Two purified components of cartilage matrix, type II collagen and proteoglycan subunit, as well as crude cartilage homogenates, were not effective inhibitors of the purified enzyme. Similar activity was extracted from canine articular cartilage, and the activity was much stronger in cartilage from osteoarthritic joints than from control joints.

Animals↗