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Biomedical subjects

Thomas Bardin

Publications and source records attributed to Thomas Bardin.

7 recordsLinked to original sources

Prognostic value of early computed tomography in radiculopathy due to lumbar intervertebral disk herniation. A prospective study.

OBJECTIVE: To prospectively evaluate the relationship between the early computerized tomography (CT) features of disk herniation and the clinical outcome in patients with recent-onset sciatic or femoral neuralgia treated conservatively. Early CT is often used, despite the absence of data on usefulness for predicting outcomes. METHODS: Of 78 patients with sciatica or femoral neuralgia of less than 1 month's duration, presumably due to a disk herniation, 75 were found by CT to have a disk herniation at the expected level. All patients were treated conservatively. The 60 patients who were reassessed clinically after 3 months were included in the study. Based on the results of the clinical assessment, the patients were classified as having a good outcome (complete or partial recovery) or a poor outcome. CT findings were compared in these two groups. RESULTS: None of the features of disk herniation studied on the CT scans were significantly correlated with the clinical outcome. A larger herniation or presence of a free fragment was more common in the good outcome group, but the differences were not statistically significant (P= 0.07). CONCLUSION: In this study, early CT scan did not predict the clinical outcome of patients with nerve root pain from lumbar disk herniation. None of the CT criteria was associated with a poor clinical outcome. Early CT scan has no prognostic value in this setting.

Adolescent↗

Estrogens, cartilage, and osteoarthritis.

A role for estrogens in osteoarthritis is consistent with the larger increases in women than in men in the incidence and prevalence of hip, knee, and finger osteoarthritis after 50 years of age. Furthermore, hormone replacement therapy for the menopause seems to be associated with a decrease in the prevalence of symptoms and radiological alterations related to hip and knee osteoarthritis. The two estrogen receptors alpha and beta (ERalpha and Erbeta) have been identified in normal and osteoarthritic cartilage, indicating that cartilage can respond to estrogens. Finally, in vivo experiments in animals and in vitro studies have shed light on the mechanisms by which estrogens may influence chondrocyte metabolism.

Animals↗

Gonococcal arthritis.

Gonococcal arthritis results from blood dissemination of Neisseria gonorrhoeae from primary sexually acquired mucosal infection. The disease has become rare in Western countries since the introduction of effective control programmes, but it still needs to be recognized promptly to avoid systemic, potentially life-threatening involvement, destructive changes associated with chronic arthritis and spread of the infection. Sexually active women are predominantly affected. Clinical features include polyarthralgia, sometimes migratory, tenosynovitis, arthritis, constitutional symptoms and skin lesions, which are mild and easily unnoticed. True arthritis occurs in less than 50% of cases. Primary mucosal infection may be asymptomatic.N. gonorrhoeae is a fragile micro-organism which is difficult to culture. Sampling of blood, synovial fluid, skin lesion, genito-urinary tract, pharynx and rectum must be performed before starting antibiotics. Samples should be plated immediately on fresh, pre-warmed appropriate media and sent quickly to the laboratory. Culture of N. gonorrhoeae is of tremendous importance not only for definite diagnosis but also for determination of drug susceptibility. When culture is negative, rapid response to antimicrobial treatment will allow a probable diagnosis. Penicillin resistance has developed worldwide in recent years, and penicillin is no longer the initially recommended antibiotic for gonococcal arthritis. Patients should be started on a third-generation cephalosporin and later switched to ampicillin or penicillin only when sensitivity to these antimicrobials has been demonstrated. Oral therapy substitutes the intravenous or intramuscular route after signs and symptoms have improved, in order to complete 7 days of antimicrobial therapy. Effusions should be aspirated until disappearance. Purulent effusions are rare but may require longer antibiotic treatment. The patient's sexual partner must be examined and treated. Patients should be tested and eventually treated for Chlamydia, syphilis and HIV, and educated about the sexual mode of transmission and means of preventing sexually transmitted diseases.

Anti-Bacterial Agents↗

Musculoskeletal manifestations of chronic renal failure.

Musculoskeletal problems remain among the main limitations of the quality of life of renal failure patients, in particular of those treated with long-term maintenance dialysis. Renal osteodystrophy continues to receive great attention. The mechanisms of uremic skeletal resistance to parathormone (PTH) are further investigated. The assay used for the dosage of "intact PTH" has been found to detect 7-84 fragments with an inhibitory effect on the action of the whole hormone. A decrease in the density of PTH receptor on osteoblasts is another recently evidenced factor. Investigations of the recently described RANK-RANKL system have demonstrated an increase in serum osteprotegerin levels, which, together with the two above-mentioned abnormalities, may explain bone resistance to PTH. These are important advances in the understanding of renal osteodystrophy as skeletal resistance to PTH appears to play an important part in the pathophysiology of secondary hyperparathyroidism and of adynamic bone disease. Because of this skeletal resistance, it has been recommended for several years that serum PTH level be monitored and kept twofold to threefold above the upper value of the normal level to maintain normal bone turnover in dialysis patients. Relative hypoparathyroidism has recently been found to be associated with increased spontaneous fracture rate and mortality, so this recommendation appears to hold adequate, despite the demonstration that serum PTH levels in this range are a poor predictor of bone turnover and that chronic parathyroid gland hyperplasia is likely to favor parathyroid gland autonomization. Recent publications have insisted on the role that hyperphosphatemia plays not only in the development of secondary hyperparathyroidism, but also of vascular, especially coronary, calcification and as a predictor of mortality. This "silent killer" of uremic patients is one of the main targets for therapeutic intervention. Extensive use of calcium-containing phosphate binders has been recently criticized as calcium overload appears to favor vascular calcification. Sevelaner (RenaGel) is a calcium- and aluminum-free phosphate binder that is an important advance in the management of renal osteodystrophy, especially in patients with extraskeletal calcification and hypercalcemia. The use of vitamin D derivatives has also raised concern because they enhance calcium and phosphorus absorption and reduce bone turnover. New metabolites with fewer hypercalcemic effects have been developed. Calcium-sensing receptor agonists are stimulating interest and are likely to take an important place in the future management of renal osteodystrophy. Uremic myopathy has received recent attention. Impaired muscle capillary oxygen transfer has been identified as a pathophysiologic factor, and progressive resistance training has been shown to improve the condition. Finally, a new entity, nephrogenic fibrosing dermopathy, has been described, which must be distinguished from calciphylaxis and scleromyxedema.

Clinical Trials as Topic↗

Association between tumor necrosis factor receptor II and familial, but not sporadic, rheumatoid arthritis: evidence for genetic heterogeneity.

OBJECTIVE: Tumor necrosis factor alpha (TNFalpha) binds the receptors TNFRI and TNFRII. Results of genome scans have suggested that TNFR2 is a candidate rheumatoid arthritis (RA) locus. A case-control study in a UK Caucasian population has shown an association between a TNFR2 genotype (196R/R in exon 6) and familial, but not sporadic, RA. The present study was undertaken to test this association in the French Caucasian population. METHODS: To test for an association in sporadic RA, 100 families were genotyped for the 196M/R polymorphism and analyzed using the transmission disequilibrium test and haplotype relative risk. To test for an association in familial RA, RA index cases from 100 affected sibpair (ASP) families were genotyped for 196M/R. Linkage analysis was performed with 3 TNFR2 microsatellite markers. RESULTS: The TNFR2 196R/R genotype was not associated with sporadic RA (odds ratio [OR] 0.59, P = 0.72), but was associated with familial RA (OR 4.0, P = 0.026). The association was most marked in the context of TNFR2 "twin-like" RA sibs (affected sibs sharing both TNFR2 haplotypes) (OR 9.2, P = 0.0017). Linkage analysis results were consistent with the association; most of the TNFR2 linkage evidence was found in the subgroup of families with 196R/R ASP index cases. CONCLUSION: This study is the first to replicate evidence of the involvement of TNFR2 in RA genetic heterogeneity. Our data refine the initial hypothesis, to suggest that a TNFR2 recessive factor, in linkage disequilibrium with the 196R allele, plays a major role in a subset of families with multiple cases of RA.

Adult↗

Effect of cryoglobulin and crystalcryoglobulin on TNF-alpha production by normal human monocytes.

OBJECTIVES: We recovered an IgG1-kappa cryocrystalglobulin in synovial fluid and membrane specimens from a patient with destructive arthropathy. In the present study, we investigated its proinflammatory properties by measuring its effects on TNF-alpha production by normal human monocytes. MATERIALS AND METHODS: Normal human monocytes isolated by plastic adhesion were cultured in microtiter plates. Adherent monocytes were cultured for 6, 8, and 24 hours with sterile cryocrystalglobulin (150 microg/mL and 2 mg/mL), type I noncrystallised cryoglobulin (same concentrations), monosodium urate (MSU) crystals (2 mg/mL), LPS (10 microg/mL), or medium alone. Supernatant TNF-a concentrations were assayed using an ELISA. RESULTS: Cryocrystalglobulin had no effect on TNF-alpha production by normal human monocytes. Noncrystallised cryoglobulin increased TNF-alpha levels in supernatants in a time-dependent and concentration-dependent fashion. This increase was significantly less marked than the increases achieved with MSU crystals or LPS. CONCLUSION: IgG1kappa cryocrystalglobulin has no effect on TNF-alpha production by normal human monocytes. Fc region changes within the cryocrystalglobulin molecule may explain this finding.

Cells, Cultured↗

Cytokine and chemokine mRNA produced in synovial tissue chronically infected with Chlamydia trachomatis and C. pneumoniae.

OBJECTIVE: We used a highly quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) assay system to define the steady-state levels of mRNA encoding a large panel of soluble mediators of inflammation in synovial tissues from patients with chronic arthritis infected with Chlamydia trachomatis versus C. pneumoniae. METHODS: RNA/cDNA was prepared from synovial biopsies of 4 patients with chronic arthritis and joint infection with C. trachomatis, 6 with C. pneumoniae at that site, 3 uninfected healthy controls, and 3 patients with undifferentiated oligoarthritis (UO) who were PCR negative for all organisms assayed. Real-time RT-PCR was used to assess relative mRNA levels from 12 cytokine and 2 chemokine genes (IL-1alpha, IL-1beta, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p35, IL-12p40, IL-15, IFN-gamma, TNF-alpha, MCP-1, RANTES). Input loading was normalized to 18S rRNA. Data were obtained for each mRNA from each sample in triplicate in comparison to the same mRNA level in the controls. RESULTS: In most C. trachomatis infected synovial tissue samples, high levels of IL-10 mRNA were present, with less mRNA for IL-8, IL-15, IFN-gamma, and TNF-alpha. Synovial tissues from chronic arthritis patients with synovial C. pneumoniae showed significant levels of mRNA solely for IL-8 and IL-1beta. All other cytokine messengers assessed in each sample from each patient group were at or near control level. One patient with C. pneumoniae showed a high transcript level for RANTES, and one patient with C. trachomatis showed a high transcript level for MCP-1. No patient with UO showed elevated messenger level for any cytokines assayed, but RANTES mRNA was elevated in each. CONCLUSION: Our data suggest that while both C. trachomatis and C. pneumoniae have been associated with inflammatory joint disease, each elicits a somewhat different steady-state profile of mRNA encoding relevant cytokines and chemokines during chronic infection of synovial tissue. Precisely how these differing profiles relate to clinical aspects of synovial inflammation will require further study, but the observations confirm and extend data indicating potentially important differences in the pathobiology of these 2 bacterial species.

Adult↗