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Biomedical subjects

J Dequeker

Publications and source records attributed to J Dequeker.

At least 199 records · Page 11Linked to original sources

Pharmacokinetics of rimexolone after intra-articular administration.

The pharmacokinetics of rimexolone were investigated after intra-articular injection into the knee joints of patients with rheumatoid arthritis. After a single dose of 40 mg rimexolone the drug could be detected in plasma over 3 months. The suspension dissolves in the synovia very slowly and provides a sustained release of the steroid in the joint. Pharmacokinetic analysis was performed on the assumption that the disposition of rimexolone after intra-articular administration is absorption limited ("flip-flop-case"). Dose linearity was studied in a range from 40 to 200 mg. Total body clearance averaged 106 L/h and was independent of dose. The mean residence time of rimexolone in the knee joint is very long and averaged 25 days. It could be shown that the mean residence time of different glucocorticoids correlates well with the duration of their clinical effectiveness.

Arthritis, Rheumatoid↗

Depressed T-cell reactivity to recall antigens in rheumatoid arthritis.

Reactivity toward soluble recall antigens (Candida albicans, cytomegalovirus, herpes simplex, streptokinase-streptodornase, and influenza) was determined in cultures of peripheral blood mononuclear cells from 41 rheumatoid arthritis patients (with clinically active as well as inactive disease) and from 28 controls. In the group with clinically active rheumatoid arthritis we found an increased incidence of "anergy," defined as nonreactivity to three or more antigens. In an attempt to explain this decreased antigen reactivity, the latter was correlated with peripheral blood lymphocyte subsets, as defined by two-color immunofluorescence with a panel of eight monoclonal antibodies. We found a significantly lower number of memory T4 cells (CD4+CD45RA-) and a significantly higher number of the CD3-CD57+ (nonspecific suppressor) cells and of CD3-CD56+/CD16+ (natural killer) cells in anergic RA patients. In the total group of rheumatoid arthritis patients, the antigen reactivity correlated positively with the percentage of memory T4 cells. Antigen reactivity was negatively correlated with the percentage of CD3-CD57+ cells and of the CD3- natural killer cells in peripheral blood. Our data suggest that a decrease in memory T4 cells and an increase in nonspecific suppressor cells may contribute to the impaired cellular immune function in peripheral blood of rheumatoid arthritis patients.

Aged↗

Sex- and age-related changes in bone and serum osteocalcin.

We measured bone osteocalcin concentrations in EDTA extracts from iliac crest cortical bone specimens obtained postmortem from 63 men and 71 women (age range 19-90 years), and serum osteocalcin levels in healthy blood donors, 49 men and 49 women (age range 21-65 years). Bone and serum osteocalcin concentrations were higher in men than in women, and an age-related decline was observed in both sexes. In women, however, a temporary increase in serum (P less than 0.05) osteocalcin was seen in the sixth decade. This study shows sex- and age-related changes in bone osteocalcin consistent with changes in serum osteocalcin, confirming that serum measurement of osteocalcin reflects bone levels. As osteocalcin reflects osteoblastic activity and thus bone formation, the overall decline in bone and serum osteocalcin in men and women, and the increase in serum osteocalcin in the sixth decade in women, indicate that aging is associated with a decrease in bone formation and turnover and that osteoblastic activity and bone turnover are stimulated at the menopause.

Adult↗

Effect of ovariectomy and prednisolone on bone mineral content in rats: evaluation by single photon absorptiometry and radiogrammetry.

The effects of ovariectomy and prednisolone were studied for 9 months in 3-month-old rats on a moderately low calcium diet. Measurements were made by single photon absorptiometry of the femur at cortical and trabecular bone sites. Radiogrammetry was performed at the midshaft of the femur. During growth, body weight, bone size, and bone mineral content (BMC) increased in male rats more than in females. After ovariectomy, body weight increase was more pronounced, but bone mineral increase was lower than in controls. At the distal end of the femur, bone mineral density decreased after 3 months, and at the midshaft of the femur, medullary width increased significantly from 6 months on. Prednisolone in a dose of 0.5 mg/kg/day did not influence BMC. However, prednisolone treatment after ovariectomy induced a more pronounced effect on bone than ovariectomy alone. BMC increase was lower than in ovariectomy, and bone mineral density decreased significantly, especially at the distal end of the femur. After correction for differences in body weight, globally the same results were found. We conclude that (1) the combination of single photon absorptiometry and radiogrammetry allows the evaluation of growth and the effect of ovariectomy and prednisolone treatment in rats; (2) ovariectomy results in bone loss first at the distal end and later in the midshaft of the femur; (3) prednisolone in a dose of 0.5 mg/kg/day alone did not affect bone mass; and (4) prednisolone profoundly enhanced the effects of ovariectomy.

Absorptiometry, Photon↗

OM-8980 and D-penicillamine in the treatment of rheumatoid arthritis. A 12-month double-blind randomized study.

Forty patients with active rheumatoid arthritis were included in this monocentre double-blind study comparing the therapeutic efficacy and safety of the immunomodulator OM-8980 with that of D-penicillamine. After 12 months of treatment, the parameters of Ritchie index, duration of morning stiffness, pain assessed by a visual analogue scale and categories, number of swollen joints, grip strength and erythrocyte sedimentation rate (ESR) were all significantly improved with OM-8980, as was the case for the Ritchie index, number of swollen joints and ESR with D-penicillamine. Significant intergroup differences were recorded for pain categories in favour of OM-8980 and for the Ritchie index and number of swollen joints in favour of D-penicillamine. The need for concomitant anti-inflammatory therapies and the assessment of efficacy by physicians and patients did not differ significantly between the two groups. OM-8980 was significantly better tolerated than D-penicillamine (5 patients with 5 side effects as compared with 12 patients with 16 side effects). OM-8980 can thus be regarded as an efficient and well-tolerated slow-acting drug for the treatment of rheumatoid arthritis.

Adjuvants, Immunologic↗

Soft tissue involvement, mediastinal pseudotumor, and venous thrombosis in pustulotic arthro-osteitis. A study of eight new cases.

A syndrome of hyperostosis of the thoracic wall, nonspecific signs of inflammatory disease, and palmar and plantar pustulosis is described in eight patients (Table 1). Seven had intersternocostoclavicular ossification, and one had chronic recurrent multifocal osteomyelitis. This complex of findings has been called "pustulotic arthro-osteitis". This report emphasizes the periosseous soft tissue inflammation and the unexplained subclavian and mediastinal vein thrombosis seen in two patients. Inflammatory periosseous and mediastinal lesions were seen on plain films in all eight patients and on computed tomographic (CT) scans in seven. Radiographs of the spine showed a spondyloarthropathy in three patients. This was characterized by ossification of the vertebral ligaments and sclerosis of the vertebral bodies. Awareness of the radiologic features of pustulotic arthro-osteitis is important because the clinical, biochemical and pathologic findings are often nonspecific and misleading.

Adult↗

Physical and histomorphological characteristics of iliac crest bone differ according to the grade of osteoarthritis at the hand.

The amount of cortical and trabecular bone was studied in 32 iliac crest necropsy specimens from women 60-75 years of age and examined according to the grade of osteoarthritis. Three different methods to evaluate bone mass were used: dual photon absorptiometry, physical assessment according to Archimedes' principle, and histomorphometry. Patients were divided into groups--with or without osteoarthritis--according to the presence of osteoarthritis on hand x rays. A significantly increased amount of cortical and trabecular bone mass was found in those who had osteoarthritis at the hands. Percent pure/crude bone volume and trabecular width were found to be increased with osteoarthritic grade, indicating that primary osteoarthritis is probably part of a generalized bone disease.

Absorptiometry, Photon↗

Pulmonary function and maximal transrespiratory pressures in ankylosing spondylitis.

Clinical measurements and pulmonary functions, including maximal transrespiratory pressures, were studied in 30 patients (age 43 (SD 10) years) with ankylosing spondylitis. Vital capacity (VC) was slightly reduced to 79 (16)% and forced expiratory volume in one second (FEV1) was similarly reduced to 82 (20)% such that the average FEV1/VC ratio was 77.8 (6.65). Total lung capacity was slightly reduced to 85 (13)%. Transfer factor of the lung for carbon monoxide (TLCO) averaged 88 (17)% and TLCO per unit lung volume was 114 (26)%. Reductions in lung volumes correlated well with clinical measurements. Both maximal expiratory pressures (PEmax) and inspiratory pressures (PImax) were clearly reduced to 56 (17)% and 76 (28)% respectively. This suggests that spirometrically determined volumes were better preserved than respiratory muscle strength in ankylosing spondylitis. It is speculated that the reduction in respiratory muscle strength may be due to intercostal muscle atrophy.

Adult↗

Collagen and non-collagenous proteins in different mineralization stages of human femur.

Mineralized tissues exhibit varying degrees of mineralization in different areas within the same bone. Using the technique of density gradient fractionation, bone powder from the diaphysis of human femur has been separated in different fractions corresponding to the degree of mineralization. Isolated bone fractions were analysed for their content in collagen and non-collagenous proteins. The results showed marked differences between compact and spongy bones, this latter containing higher proportions of little mineralized bone particles than the former (p less than 0.01). The ethylenediaminetetra-acetic acid (EDTA) extractability and the bone matrix size decreased relative to the decrease in specific gravity of bone particles. Among the matrix components of different fractions, sialoprotein consistently increased with the increase in specific gravity while proteoglycan decreased in reverse manner to the increase in collagen. However, in the most mineralized fraction (specific gravity: 2.33 g/cm3), the proteoglycan amount increased while collagen decreased. In conclusion, this study of bone maturation in human femur confirms the suitability of the technique of density gradient fractionation in the studies of bone matrix-mineral interactions. Apart from the fraction with the highest specific gravity, the analytical results obtained in fractions are similar to those observed in age-related bone changes, suggesting that the increase in mineralization degree of bone particles may be related to their age.

Aging↗

Bone mineral homeostasis in spontaneously diabetic BB rats. II. Impaired bone turnover and decreased osteocalcin synthesis.

Bone morphology and function were studied in male spontaneously diabetic BB rats after 3-4 weeks of diabetes. The tibia and lumbar vertebrae weights were decreased, but the bone calcium percentage remained normal. Bone volumes in the tibial metaphysis and the first lumbar vertebra were normal on quantitative histomorphometry. Osteoclast, osteoblast, and osteoid surface percentages, however, and the calculated daily mineral apposition rate in the tibia (1.0 +/- 0.4 vs. 5.6 +/- 0.6 microns/day) and vertebra (0.2 +/- 0.1 vs. 2.3 +/- 0.2 microns/day) were all severely decreased in diabetic rats. Plasma osteocalcin concentrations were also markedly decreased in diabetic rats (24 +/- 2 vs. 108 +/- 10 ng/ml); the half-times of [125I]osteocalcin were similar in diabetic and nondiabetic rats, indicating that decreased plasma osteocalcin was due to decreased synthesis. Plasma osteocalcin levels were more decreased than expected from their suppressed 1,25-dihydroxyvitamin D3 levels, and 1,25-dihydroxyvitamin D3 injections did not increase plasma osteocalcin in diabetic rats as they did in nondiabetic rats. Bone osteocalcin content was normal in diabetic rats. Photon absorptiometry of tibiae showed a similar bone mineral content in diabetic and nondiabetic rats. Biomechanical properties of diabetic rat femora were all in the normal range. Nondiabetic semistarved rats with the same body weight as diabetic rats exhibited a similar delay in bone growth as diabetic rats, but the osteoblast and osteoid surfaces were normal, and the mineral apposition rate was normal (tibia) or slightly decreased (vertebra). Plasma osteocalcin concentrations were also normal in semistarved rats. Thus, the number and/or function of osteoblasts are severely suppressed in diabetes, and this results in decreased osteoid surface, mineral apposition rate, and plasma osteocalcin levels; moreover, these changes cannot be explained by simple weight loss.

Animals↗

Biomechanical characteristics of iliac crest bone in elderly women according to osteoarthritis grade at the hand joints.

Postmortem iliac crest trabecular bone specimens were tested in compression to determine their mechanical characteristics. Trabecular bone volume and width were evaluated by histomorphometry and radiographic grading of osteoarthritis (OA) of hand joints was also done. Patients were divided into 2 groups: no or low grade OA (Group 1) and manifest OA Grades II-IV (Group 2). From the 27 specimens tested (women 56-80 years old), 17 were in Group 1 and 10 in Group 2. Significant differences in stiffness (E), compressive strength, trabecular bone volume and trabecular width between the 2 groups were found. In the group with manifest OA, bone was significantly stiffer, had a significantly increased compressive strength value, a significantly higher trabecular bone volume and trabecular width, compared to the group with no or low OA grade. Significant correlations were found between elastic modulus and trabecular bone volume and width, and also between compressive strength and trabecular bone volume and width. Our findings support the hypothesis that the primary defect in OA is not in the articular cartilage but in the subchondral bone and that primary OA is part of a more general bone disease.

Aged↗

[The risk of developing osteoporosis in rheumatic diseases].

Although osteoporosis is frequently associated with rheumatic diseases, at present it is not clear if osteoporosis is due to local factors as for example disease and inflammation, or to a systemic factor related to the rheumatic condition. In this review the present stage of knowledge on the inverse relationship between primary osteoarthritis and primary osteoporosis, bone metabolism in rheumatoid arthritis, the effect of corticosteroids on bone in rheumatoid arthritis, and preventive and curative therapy for osteoporosis is discussed.

Adrenal Cortex Hormones↗