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Biomedical subjects

Kenneth D Brandt

Publications and source records attributed to Kenneth D Brandt.

35 records · Page 2Linked to original sources
PubMed2004

Neuromuscular aspects of osteoarthritis: a perspective.

Osteoarthritis (OA) represents failure of the diarthrodial joint and may be due to a primary abnormality in any of the tissues of the joint, e.g. articular cartilage, subchondral bone, synovium, periarticular muscle, or sensory nerves whose termini lie within the joint. Neuropathic arthropathy, due to severe sensory neuropathy, causes severe and rapid breakdown of joints. We have shown that interruption of sensory input from the ipsilateral hind limb strikingly accelerates progression of OA after anterior cruciate ligament transection in the dog; a clinical correlate exists in humans with diabetic neuropathy who sustain even minor joint trauma. Knee OA in humans is accompanied by defects in proprioception, although it is not clear whether the neurological abnormality is primary or a consequence of intra-articular pathology. The magnitude of the load on a joint and, especially, the rate of impulsive loading, influence development of OA. It is relevant, therefore, that quadriceps weakness may precede development of knee OA in some people, insofar as this may diminish the effectiveness of protective muscular reflexes and thereby increase deleterious joint loading. Individuals vary with respect to how they load their joints, perhaps because of genetic differences in central program generators.

Animals↗
PubMed2004

Hyaluronan injection affects neither osteoarthritis progression nor loading of the OA knee in dogs.

We previously reported that intraarticular injections of hyaluronan (HA), administered prophylactically to dogs in whom knee osteoarthritis had been induced by transection of the anterior cruicate ligament, did not significantly modify the intraarticular pathology but decreased the proteogylcan concentration of the articular cartilage by as much as 30%. Because the cartilage proteoglycan concentration is directly related to the stiffness of the tissue, these results raised the possibility that intraarticular HA therapy could exacerbate OA. In the present study, using a different HA formulation, with a longer interval between intraarticular HA injection and examination of joint tissues, we found that neither prophylactic nor therapeutic administration of HA had an effect on the severity of OA pathology, the magnitude of vertical ground reaction forces generated by the unstable hind limb (a surrogate for joint pain), or the cartilage proteoglycan concentration. The data suggest that the suppression of proteoglycan synthesis induced by HA is temporary and fully reversible and that HA injections do not result in overloading of the OA extremity. A significant correlation was noted between the severity of chondropathy and the magnitude of the vertical ground reaction forces generated by the unstable limb.

Animals↗
PubMed2003

Detection of radiographic joint space narrowing in subjects with knee osteoarthritis: longitudinal comparison of the metatarsophalangeal and semiflexed anteroposterior views.

OBJECTIVE: Although recent protocols for standardized knee radiography afford highly reproducible radioanatomic alignment of the joint and measurement of joint space width (JSW) in repeat radiographs acquired on the same day, the sensitivity of these techniques to joint space narrowing (JSN) over time in subjects with knee osteoarthritis (OA) is unknown. The present study was undertaken to compare the metatarsophalangeal (MTP) view and the semiflexed anteroposterior (AP) view with respect to sensitivity to JSN in knee OA. METHODS: In 49 subjects with definite knee OA, 2 MTP radiographs and 1 semiflexed AP radiograph were obtained at baseline. Each examination was repeated 14 months later. In MTP views, minimum JSW and the distance between the anterior and posterior margins of the medial tibial plateau (intermargin distance [IMD], an indicator of parallel alignment of the tibial plateau and the x-ray beam) were measured with a pair of calipers and a magnifying lens fitted with a graticule. JSW in semiflexed AP views was measured by digital image analysis. RESULTS: The mean of within-knee standard deviations of JSW in the baseline MTP examinations (n = 52 OA knees) was 0.24 mm (coefficient of variation 5.8%). Although IMDs in the 2 baseline MTP views were very highly correlated (+0.88), IMDs in the serial examinations were only moderately correlated (+0.45). Serial MTP views showed a small increase in mean JSW over 14 months that was not significantly greater than zero (mean +/- SD +0.09 +/- 0.66 mm; P not significant). In contrast, concurrent semiflexed AP examinations showed a marginally significant decrease in mean JSW (-0.09 +/- 0.31 mm; P = 0.10). CONCLUSION: These results demonstrate that evidence of the short-term reproducibility of a radiographic protocol is an insufficient basis on which to predict the quality of its longitudinal performance.

Aged↗
PubMed2003

Measurement of radiographic joint space width in the tibiofemoral compartment of the osteoarthritic knee: comparison of standing anteroposterior and Lyon schuss views.

OBJECTIVE: To evaluate progression of joint space narrowing in radiographs of osteoarthritic (OA) knees imaged in both the standing anteroposterior (AP) and the Lyon schuss positions, using alternative methods to measure joint space width (JSW). METHODS: Standing AP (extended view) and Lyon schuss (posteroanterior [PA] view, with 20-30 degrees of flexion) radiographic images of 58 OA knees were obtained twice (at baseline and 2 years later). With both methods, fluoroscopy was used to align the anterior and posterior margins of the medial or lateral tibial plateau with the central x-ray beam. Minimum JSW, mean JSW, and joint space area (JSA) of the medial or lateral femorotibial joint space were measured using a new digital image analysis system. The effects of knee flexion versus extension and parallel versus nonparallel tibial plateau alignment were evaluated with respect to the reproducibility of JSW in repeated examinations (intraclass correlation coefficient [ICC]), the mean of within-knee standard deviations of repeated measurements (SD(m)), and the sensitivity to changes in JSW in serial radiographs (standardized response mean [SRM]). RESULTS: The performance of the new software, as assessed by the reproducibility of repeated measurements of minimum JSW on the same image, was excellent in both the standing AP (ICC = 0.98) and Lyon schuss radiographs (2 SD(m) = 0.5 mm, ICC = 0.98). The reproducibility in different radiographs of the same knee was not evaluated. However, over 2 years, the mean (+/- SD) decrease in the minimum JSW of OA knees was 0.17 +/- 0.75 mm in standing AP radiographs (P not significant) and 0.24 +/- 0.50 mm in Lyon schuss views (P = 0.007), with SRMs of 0.23 and 0.48, respectively. The quality of alignment of the tibial plateau was satisfactory (<1 mm between anterior and posterior margins of the medial tibial plateau) in 66% of the pairs of Lyon schuss radiographs and in 57% of the pairs of standing AP radiographs. In the Lyon schuss radiographs, SRM was highly dependent on tibial plateau alignment. Minimum JSW was more sensitive to change than was mean JSW or JSA, in paired Lyon schuss radiographs that exhibited satisfactory alignment. CONCLUSION: Compared with the standing AP radiograph, PA imaging of the knee in 20-30 degrees flexion (the schuss position) increases the reproducibility of radiographic JSW measurements in OA knees and the sensitivity to change in JSW in serial radiographs. Sensitivity to change in minimum JSW is notably increased by aligning the medial tibial plateau with the central x-ray beam in the Lyon schuss radiograph.

Aged↗
PubMed2003

What is important in treating osteoarthritis? Whom should we treat and how should we treat them?

Most of the treatments used today for OA have a relatively weak evidence base to support their use, and their effect size is small. Many key questions about OA management remain unanswered, in part because of the strong bias toward research on single pharmaceutical agents rather than nonpharmacologic interventions and a comprehensive package of care involving pharmacologic and nonpharmacologic measures. Good management of OA involves the coordination of several different types of interventions provided by health care professionals; however, while a great deal of research is available on the use of individual treatments, there is a lack of information on how health services for patients who have OA should be organized. The problem is compounded by the fact that many people who have OA use complementary therapy as well as, or instead of, allopathic treatments despite the fact that most of the evidence suggests that many such interventions are no better than placebo [123], which might be because of the relatively small effects of most conventional nonsurgical treatment for OA and to the need for a more holistic, individualized approach to treatment than most conventional health professionals usually provide. For many people who have OA, the fear of side effects is a major barrier to the use of pharmacologic interventions [11]. The authors believe that future research in OA therapeutics should concentrate more on behavioral and physical interventions than on drugs, should examine packages of care involving combinations of treatment modalities, and should include a consideration of patient preferences. The authors also believe that the academic community striving to provide help for people who have OA should bear in mind the concept that there is "too much medicine" [37].

Complementary Therapies↗
PubMed2003

Is knee radiography useful for studying the efficacy of a disease-modifying osteoarthritis drug in humans?

Recent research on the radiographic imaging of knee OA has helped clarify the features of imaging protocols that contribute to accurate representation of disease severity--specifically, the thickness of articular cartilage--and to sensitive detection of disease progression. The absence of standards for reproducible positioning of the knee in the conventional standing AP view obscures the true rate and variability of JSN in knee OA. Moreover, the standing AP view is susceptible to systematic bias insofar as longitudinal changes in knee pain might lead to over- or underestimation of radiographic JSW depending on the direction of change in pain. More recent protocols for standardized knee radiography have been designed to achieve reproducible alignment of the medical tibial plateau and x-ray beam. As a group these protocols permit measurement of tibiofemoral JSW with remarkable precision--the sine qua non of sensitivity to change--however, only limited longitudinal data is available to permit a direct evaluation of the suitability of these protocols for use in clinical DMOAD trials. Longitudinal studies published to date suggest that fluoroscopic positioning methods are superior to nonfluoroscopic methods with respect to reproducing the position of the knee in serial examinations performed several years apart. Fluoroscopic methods also appear to be superior with respect to achieving parallel alignment of the medial tibial plateau and x-ray beam in serial radiographs, a positioning marker strongly associated with sensitive detection of JSN in knee OA. It is important to note that while the various standardization protocols described in this article perform with great success in short-term demonstrations of the reproducibility of positioning and radiographic JSW, differences clearly exist between protocols in the quality of performance over intervals relevant to clinical DMOAD trials. Over intervals of 2 to 3 years, changes in patient characteristics (e.g., severity of knee pain, body weight, load bearing, varus--valgus deformity) and uncontrollable events related to radiography (e.g., technologist turnover, equipment upgrades) have ample opportunity to affect the technical quality of a radiological knee examination. It is difficult, therefore, to conclude whether or not an apparent difference with respect to sensitivity to OA progression between specific radiographic protocols, implemented in separate locations with different cohorts, reflects a robust difference in technical quality or uncontrollable patient variables and events. The most informative recent studies have provided the results of head-to-head longitudinal comparisons of alternative standardization protocols or conventional examination methods performed concurrently in the same subjects [20,22]. Additional comparative studies of this nature are needed, however, to fully characterize the strengths and weaknesses of currently available alternatives in a way that will permit generalizable conclusions regarding the best radiographic methods for multicenter DMOAD trials.

Biomechanical Phenomena↗
PubMed2002

Tidal irrigation as treatment for knee osteoarthritis: a sham-controlled, randomized, double-blinded evaluation.

OBJECTIVE: To evaluate the effectiveness of tidal irrigation (TI) in comparison with a well-matched sham irrigation (SI) procedure as a treatment for knee osteoarthritis (OA). METHODS: One hundred eighty subjects with knee OA were randomized to receive TI or SI, with clinical followup over the ensuing 12 months. The primary outcomes of interest were change in pain and function, as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Subjects and the nurse assessor were blinded, and success of blinding was assessed. RESULTS: Although the study groups were otherwise comparable, the baseline WOMAC pain and physical functioning scores were higher (worse) in the SI group. After adjustment for baseline, there were no differences between the effects of

Aged↗
PubMed2002

Field test of the reproducibility of the semiflexed metatarsophalangeal view in repeated radiographic examinations of subjects with osteoarthritis of the knee.

OBJECTIVE: To estimate the reproducibility of the semiflexed metatarsophalangeal (MTP) view in repeat radiographic examinations of the knee of subjects with osteoarthritis (OA) with respect to radioanatomic alignment of the medial tibial plateau and the central x-ray beam and the precision of measurements of minimum medial tibiofemoral joint space width (JSW). METHODS: Thirty-eight subjects with definite knee OA underwent 2 semiflexed MTP examinations on the same day. Radioanatomic alignment of the medial tibial plateau and the x-ray beam (distance between anterior and posterior margins of the plateau) was measured manually (Lequesne method). Manual measurements of the JSW in repeat radiographs also were obtained. The reproducibility of JSW measurements was estimated by the method of Bland and Altman. RESULTS: Only 29% of the initial semiflexed MTP radiographs exhibited satisfactory radioanatomic alignment (intermargin distance < or =1 mm). However, intermargin distances in initial and repeat radiographs were highly correlated (r = 0.86, P < 0.01). In 89% of knees, the intermargin distance in the first examination was reproduced (+/- 1 mm) in the second examination. The standard error of measurement (mean of within-knee standard deviations of repeat JSW values) was 0.30 mm. The magnitude of discrepancy between repeat measurements of JSW was related positively to overall radiographic severity of knee OA (P < 0.05). CONCLUSION: The semiflexed MTP protocol affords highly reproducible radioanatomic positioning of the knee, although misalignment of the medial tibial plateau and the x-ray beam occurs in >70% of cases. Precision of measurement of JSW in the semiflexed MTP view approaches that associated with fluoroscopically assisted positioning protocols. However, the consequences of poor, albeit reproducible, alignment of the knee in serial semiflexed MTP radiographs in longitudinal studies of OA progression are currently unknown.

Aged↗
PubMed2002

Knee pain reduces joint space width in conventional standing anteroposterior radiographs of osteoarthritic knees.

OBJECTIVE: A suspected, but heretofore undemonstrated, limitation of the conventional weight-bearing anteroposterior (AP) knee radiograph, in which the joint is imaged in extension, for studies of progression of osteoarthritis (OA) is that changes in knee pain may affect extension, thereby altering the apparent thickness of the articular cartilage. The present study was undertaken to examine the effect of changes in knee pain of varying magnitudes on radiographic joint space width (JSW) in the weight-bearing extended and the semiflexed AP views, in which radioanatomic positioning of the knee was carefully standardized by fluoroscopy. METHODS: Fifteen patients with knee OA underwent a washout of their analgesic/nonsteroidal antiinflammatory drug (NSAID) agents (duration 5 half-lives), after which standing AP and semiflexed AP knee radiographs of both knees were obtained. Examinations were repeated 1-12 weeks later (median 4.5 weeks, mean 6.0 weeks), after resumption of analgesic/NSAID therapy. Knee pain was measured with the pain subscale of the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index (Likert scale). JSW was measured with a pair of calipers and a magnifying lens. Mixed model analyses of variance were used to test the significance of changes in pain and JSW within and between 2 groups of knees with mild-to-moderate radiographic severity of OA: (a) "flaring knees," in which the patient rated standing knee pain as severe or extreme after the washout and in which pain decreased to any degree after resumption of analgesics and/or NSAIDs (n = 12) and (b) "nonflaring knees," in which standing knee pain was absent, mild, or moderate after the washout or did not decrease after resumption of treatment (n = 15). RESULTS: After reinstitution of treatment, WOMAC pain scores decreased significantly in both flaring and nonflaring knees (-44%; P < 0.0001 and -18%; P < 0.01, respectively). After adjustment for the within-subject correlation between knees, mean JSW (+/-SEM) in the extended view of the flaring OA knee increased significantly from the first to second examination (0.20 +/- 0.06 mm; P = 0.005). In contrast, the change in adjusted mean JSW in the extended view of the nonflaring OA knee was negligible (-0.04 +/- 0.04 mm) and significantly smaller than that observed in flaring knees (P < 0.01). Mean JSW in the semiflexed AP view was unaffected by the severity or responsiveness of standing knee pain in flaring and nonflaring OA knees. CONCLUSION: JSW in weight-bearing extended-view radiographs of highly symptomatic OA knees can be altered significantly by changes in joint pain. In clinical trials and in epidemiologic studies of OA progression that use this radiographic technique, longitudinal variations in pain may confound changes in the apparent thickness of the articular cartilage.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Animal models of osteoarthritis.

Animal models have proved to be of considerable importance in elucidating mechanisms underlying joint damage in osteoarthritis (OA) and providing proof of concept in the development of pharmacologic and biologic agents that may modify structural damage in the OA joint. The utility of animal models in predicting the response to an intervention with a drug or biologic agent in humans, however, can be established only after evidence is obtained of a positive effect of the agent in humans. To date, no agent has been shown unequivocally to have such an effect, although diacerhein and glucosamine have recently been reported to lower the rate of loss of articular cartilage in patients with hip OA and knee OA, respectively, based on measurements of the rate of joint space narrowing in plain radiographs. Furthermore, the predominant manifestation of OA - and the feature that leads people with radiographic changes of the disease to decide to seek medical attention and contributes to the enormous medicoeconomic and socioeconomic burden imposed by the disease - is joint pain. Notably, none of the animal models of OA is a good indicator of the analgesic effects of pharmacologic agents. Indeed, it should not be assumed a priori that reduction in the rate of progression of joint damage in OA will be associated with a reduction in joint pain.

Animals↗