Early bone changes in experimental osteoarthritis using microscopic computed tomography.

Alterations in trabecular subchondral bone have been measured using a microscopic computed tomography scanner in the guinea pig hind-limb myectomy model of osteoarthritis. These bone changes can be found as early as histologic changes in cartilage. To evaluate the influence of the myectomy on the animals, a gait study was performed. This data reveals an alteration in acceleration at the foot-flat phase of gait in the operated limb only, providing early quantification of the interaction between mechanics and biology.

Examination of subchondral bone architecture in experimental osteoarthritis by microscopic computed axial tomography.

Subchondral bone changes have been proposed as an early event in the pathogenesis of osteoarthritis. In this study, microscopic computed axial tomography was used to evaluate the subchondral bone structure in femoral heads from a guinea pig model of osteoarthritis. Examination of trabecular bone within the femoral head showed a highly significant increase in bone fraction in the experimental animals. This was due to the development of trabeculae that were thicker and closer together. We conclude that trabecular remodeling may be an early event in this model of osteoarthritis.

Pharmacokinetics of flurbiprofen in man. I. Area/dose relationships.

Flurbiprofen pharmacokinetics were studied in 15 normal male subjects after four oral doses. Plasma levels of total (bound + free) drug were monitored for 48 h and urine was collected for 96 h after the doses. All subjects demonstrated linear relationships between administered dose and total flurbiprofen AUC, indicating that oral clearance is independent of dose for the dose range evaluated in this study. Urinary recovery data indicated that the efficacy of absorption was dose independent.

Use of the guinea pig myectomy osteoarthritis model in the examination of cartilage-synovium interactions.

Synovium enhances the release of proteoglycan from articular cartilage in organ culture. Biomechanical stress-induced hip osteoarthritis (OA) was produced in guinea pigs by extra-articular myectomy and tendotomy. Organ culture experiments of control or OA cartilage with control or OA synovium were assayed for proteoglycan release. OA cartilage released more proteoglycan than control cartilage when cultured with either control or OA synovium. No significant difference in the effect of control or OA synovium in stimulating proteoglycan release from OA cartilage was detected, but the difference between control and OA cartilage release was significant.

Development of clinical criteria for osteoarthritis.

Clinical criteria for the classification of osteoarthritis (OA) in the knee have been developed and the use of algorithms has been proposed. Criteria for the classification of OA in the hand and hip are still being developed.

Experimental osteoarthritis induced by selective myectomy and tendotomy.

A new model of osteoarthritis has been developed that utilizes an extraarticular surgical technique to alter gait and weight-bearing capabilities in the hind limbs of experimental animals. Guinea pigs, averaging 650 gm in weight, were subjected to unilateral resection of a segment of the gluteal muscles at the sacral origin, to section of the infrapatellar ligament, or to both procedures. Progressive changes consistent with osteoarthritis developed over 10-24 weeks as judged by gross, radiologic, and microscopic findings. In addition, an increase in mean cartilage water content and 35SO4(-2) incorporation into proteoglycans by 10 and 14 weeks, respectively, were consistent with the chemical changes observed in early osteoarthritis. Abnormalities developed not only in the operated hind limb, but in the contralateral, unoperated hind limb at a slightly later time. Thus, this animal model provided the opportunity to evaluate a mild gait abnormality and other biomechanical influences on the evolution of osteoarthritis which is uninfluenced by any intraarticular joint trauma.

Pharmacokinetics of ibuprofen in man. I. Free and total area/dose relationships.

Ibuprofen kinetics were studied in 15 subjects after four oral doses. Plasma levels of both total and free ibuprofen were measured for 12 hr, and urine was collected for 48 hr after the doses. All subjects showed a nonlinear relationship between dose and total ibuprofen plasma AUC. Free ibuprofen plasma AUC, however, was linearly related to the dose, suggesting that oral clearance based on free drug was dose independent. Urinary recovery data indicated that efficiency of absorption was dose independent.

Capillary microscopy in eosinophilic fasciitis. A comparison with systemic sclerosis.

Capillary microscopy was performed on 19 patients with eosinophilic fasciitis. These patients were compared with 13 individuals with progressive systemic sclerosis (scleroderma). Capillary patterns were normal in 16 of 19 (84%) eosinophilic fasciitis patients; 3 exhibited either borderline or nonspecific changes, and none showed a definite scleroderma pattern. In contrast, characteristic nailfold capillary changes, consisting of both dilatation and loss of capillaries, were present in 11 of 13 (85%) scleroderma patients; the remaining 2 showed scleroderma-type abnormalities of only 1 finger and were, therefore, classified as borderline. These results suggest that capillary microscopy may help to distinguish these 2 disorders.

Appointment-keeping behavior and patient satisfaction: implications for health professionals.

This study examines patient satisfaction with care received in a subspecialty clinic, appointment-keeping behavior in that clinic, and the interrelationships between satisfaction and appointment-keeping compliance. The implications for health education and patient counselling are also discussed. The setting is an outpatient clinic of a large university hospital that serves both an urban and rural population. A mailed questionnaire was returned by 150/270 (56%) patients. While satisfaction and compliance were not significantly related, satisfaction was significantly related to the patient's perception of benefit received as a result of care provided by the clinic.

Frentizole therapy of active systemic lupus erythematosus.

Frentizole is a benzimidazoleurea that has immunosuppressive properties in mice. Eleven steroid-treated patients with active systemic lupus erythematosus received frentizole (150-350 mg/day) in combination with stable or decreasing doses of prednisone in an open label trial. Nine patients completed at least one 21- to 75-day course of therapy with this drug. Clinical parameters of disease improved in 8 of these 9 patients. Mean DNA binding decreased by 28%, mean CH50 increased by 20%, and mean absolute lymphocyte and T cell counts decreased by 25-26%. Granulocytopenia was not observed. Three patients developed reversible hepatic toxicity. Clinical and serologic improvement was noted in 3 patients who accepted a second 90-day course of frentizole therapy.

Acute nongonococcal infectious arthritis. Evaluation of risk factors, therapy, and outcome.

A retrospective analysis of 71 nongonococcal joint infections in 63 patients is reported. Staphylococcus aureus was isolated from 59% of the patients. Five patients died as a result of infections. The outcome in Gram-negative joint infections was similar to the overall outcome in the entire series of patients. All 11 joints with infected prostheses ultimately required removal of the prostheses. All patients were treated with appropriate parenteral antibiotics, and surgical intervention was used in 40 joints. Six patients underwent surgical treatment because of inability to sterilize the joint with antibiotics and because of repeated joint aspirations. The outcome with surgical intervention was good only in patients younger than 16 years of ages. Medical therapy (parenteral antibiotics and frequent joint aspirations) led to good results in 74% of the patients. Outcome of joint infection was also influenced by factors which contribute to impaired host resistance.

Evaluation of a continuing education program in rheumatoid arthritis.

A continuing medical education (CME) program in rheumatoid arthritis was implemented and evaluated in six community hospitals. It was targeted at primary care physicians and utilized physicians identified by their peers as being educationally influential for the dissemination of content knowledge. Although inpatient and outpatient audits of physician records demonstrated little change in three control communities, substantial improvement in the utilization of diagnostic procedures and patient management was documented in the three intervention communities utilizing the influential physicians. CME delivered through community-based educationally influential physicians is an effective way to change physician behavior in small communities with no prior ongoing educational programs. This approach should improve the primary care given to patients with rheumatoid arthritis and reduce the need for participation of academic faculty in traditional CME programs.

The relationship of dermatomyositis and polymyositis to internal malignancy.

The association of malignancy with dermatomyositis and polymyositis has been questioned. During the last 20 years (1956 to 1975), we have studied 58 cases of myositis that met predefined diagnostic criteria. These cases were analyzed for the frequency of malignancy, prognosis, and the value of a diagnostic test series for malignancy. A significantly greater frequency of malignancy was found with dermatomyositis than with polymyositis. The prognosis of dermatomyositis and polymyositis appears to be altered in the presence of malignancy. In the absence of malignancy, the prognosis is similar in the two forms of myositis. Lastly, the value of a screening laboratory and roentgenographic investigation for the presence of occult malignancy beyond a thorough history, physical examination, and the use of basic laboratory tests such as complete blood count, stool gualac test, urinalysis, multiphasic analysis, and chest roentgenogram was not documented by this study.