[Biological autoimmune syndrome with antiphospholipid antibodies in occupational asbestosis].
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Biomedical subjects
Publications and source records attributed to J Dehais.
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The etiology of scleroderma remains unknown. Although a genetic susceptibility seems to play a role, some environmental and iatrogenic factors have been suggested to trigger the disease. Contact for many months or years with natural or synthetic "toxic" products (by inhalation, cutaneous contact, injection, swallowing or surgical implant) could be implicated in the development of typical scleroderma or pseudo-scleroderma. These products are either occupational or non occupational like those used at home in daily life. We will sum up the knowledges about this subject.
The objective was to investigate the presence of mycoplasmas in rheumatoid arthritis (RA) and other chronic arthritides. Samples of synovial fluid (SF) were systematically collected from all patients presenting with an articular effusion. Each sample was divided into three parts. The first was kept for cytological count and culture on standard media for pyogens and mycobacteria, the second was cultivated on specific media for mycoplasmas and the third frozen for subsequent study by polymerase chain reaction (PCR). A total of 209 samples were studied. Half of the patients had inflammatory rheumatic diseases: RA (27), spondyloarthropathy (28), connective tissue disease (5), unclassified arthritis (45). The remaining suffered from other conditions, including osteoarthritis (60), gouty arthritis (19), haemarthrosis (5), post-traumatic effusion (2). Eight samples were positive by culture, two for Mycoplasma hominis; three for M. fermentans, one for M. salivarium, one for M. orale and one for Ureaplasma urealyticum. All the patients concerned had an inflammatory rheumatic disease: five had RA, one had psoriatic arthritis and two had unclassified arthritis. These results were confirmed by PCR in two cases (one M. fermentans, one U. urealyticum). The lack of sensitivity of the conventional PCR assay on SF is discussed. Mycoplasmas were mainly detected in SF of RA patients. These results raise the question of the possible role of mycoplasmas in the triggering and maintenance of inflammatory rheumatic diseases, especially RA.
Rheumatoid arthritis and other autoimmune diseases might be triggered by infectious agents. We have reviewed the evidence suggesting that mycoplasmas may play a role in the genesis of arthritis. Mycoplasmas are a common cause of spontaneous arthritis in many animal species. Numerous experimental models of mycoplasma-induced arthritis have been developed, some with mycoplasmas known to cause disease in humans. Mycoplasmas entertain complex relationships with the immune system of their hosts and frequently induce autoimmune events such as rheumatoid factor production. However, the potential role of mycoplasmas in human joint disease remains unknown. Mycoplasmas can be responsible for septic arthritis in patients with immune deficiencies, especially hypogammaglobulinemia. Whether mycoplasmas can incite or perpetuate inflammatory joint diseases such as rheumatoid arthritis remains controversial. Advances in molecular biology techniques for detecting infectious agents can be expected to settle this issue in the near future.
Penetration of prednisolone across the blood-brain barrier was studied in 17 patients (ten women and seven men) with a mean age of 64 +/- 17 years admitted for nerve root pain warranting a lumbar puncture. One blood sample and one cerebrospinal fluid sample were obtained concomitantly from each patient, two hours (n = 7), four hours (n = 5) or six hours (n = 5) after an oral dose of 40 mg of prednisone. Prednisolone was assayed in all samples using high performance liquid chromatography and its binding to plasma proteins was determined using ultrafiltration. Total plasma prednisolone levels declined over time from 597 +/- 174 ng/ml two hours post-dose to 422 +/- 106 ng/ml four hours post-dose and 250 +/- 85 ng/ml six hours post-dose. Plasma levels of free prednisolone were 95 +/- 21 ng/ml, 59 +/- 17 ng/ml, and 18 +/- 14 ng/ml, respectively, at the same time points. Prednisolone was detectable in all cerebrospinal fluid samples, in levels of 14 +/- 2 ng/ml after two hours, 29 +/- 9 ng/ml after four hours and 17 +/- 7 ng/ml after six hours. These data demonstrate that equilibration of plasma and cerebrospinal fluid levels is achieved after six hours.
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Hairy cell leukemia can be responsible for polyarthritis due either to leukemic infiltration or to immunity-drive inflammation. The second variant can antedate or post-date the clinical onset of leukemic symptoms and usually presents as rheumatoid arthritis, more rarely as lupus or scleroderma. The presence of hairy cells in the joint fluid does not rule out autoimmune polyarthritis. The main differential diagnoses are Felty's syndrome and large granular lymphocyte leukemia. We report a case of hairy cell leukemia with seropositive rheumatoid arthritis.
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Fibrogenesis imperfecta ossium (FIO) is an extremely rare, acquired, metabolic bone disease related to a collagen defect in bone matrix inducing spontaneous fractures. Among the 17 cases of FIO reported to date, four patients exhibited a monoclonal gammopathy (MCG) and one, treated with melphalan, was the first patient to present clinical and histological remission of the bone and plasma cell manifestations. We report the case of a 56-year-old woman who suffered spontaneous fractures of both patellae and olecranons. Skeletal X-rays showed generalized coarse, ill-defined trabeculae. The following biological parameters were abnormal: ESR: 50 mm/hour, alkaline phosphatase (AP) 256 IU/liter [normal (N): 40-110], serum IgG kappa light chain 11 g/liter, bone marrow aspirate 9% atypical plasma cells. Iliac crest biopsy showed the features of FIO including evidence of osteomalacia and nonbirefringent osteoid seams under polarized light. Eroded surfaces were increased, and trabecular bone volume was decreased. Melphalan (4 mg/day) was given in 1988 and was interrupted 1 year later because of leucopenia. Clinical status worsened. A second bone biopsy in 1989 showed identical features of FIO. In November 1990, an X-ray film showed several fractures, and coarser trabeculae. The patient died in December 1991. Regarding the prevalence of MCG and FIO, their association is unlikely accidental. The collagen defect might be related to a plasma cell-induced osteoblast impairment.
AIM/BACKGROUND: Mycoplasmas, especially Mycoplasma fermentans, were suggested more than 20 years ago as a possible cause of rheumatoid arthritis but this hypothesis was never substantiated. In view of the superior sensitivity of the polymerase chain reaction (PCR) assay over culture, the aim was to use this method to seek M fermentans and M penetrans in synovial samples from patients with various arthritides. METHODS: Synovial fluid samples (n = 154) and synovial biopsy specimens (n = 20) from 133 patients with various rheumatic disorders were stored at -80 degrees C for between one and 40 months. Aliquots (500 microliters) of the synovial fluid samples were centrifuged and the deposit, and also the synovial biopsy specimens (approximately 1 g) were placed in lysis buffer with proteinase K for DNA extraction. The DNA was tested by using a semi-nested PCR assay for M fermentans and a single-round PCR for M penetrans. RESULTS: M fermentans was detected in the joints of eight (21%) of 38 patients with rheumatoid arthritis, two (20%) of 10 patients with spondyloarthropathy with peripheral arthritis, one (20%) of five patients with psoriatic arthritis, and four (13%) of 31 patients with unclassified arthritis. M fermentans was not found in the joints of the seven patients with reactive arthritis, the 29 with osteoarthritis or post-traumatic hydrarthrosis, the nine with gouty arthritis, nor the four with chronic juvenile arthritis. M penetrans was not detected in any sample. CONCLUSIONS: These findings show that the presence of M fermentans in the joint is associated with inflammatory rheumatic disorders of unknown cause, including rheumatoid arthritis. However, whether this organism triggers or perpetuates disease of behaves as a passenger remains conjectural.
Low-dose pulse methotrexate has emerged as one of the most frequently used slow-acting, symptom-modifying antirheumatic drugs in patients with rheumatoid arthritis (RA) because of its favourable risk-benefit profile. Methotrexate is a weak bicarboxylic acid structurally related to folic acid. The most widely used methods for the analysis of methotrexate are immunoassays, particularly fluorescence polarisation immunoassay. After oral administration, the drug is rapidly but incompletely absorbed. Since food does not significantly affect the bioavailability of oral methotrexate in adult patients, the drug may be taken regardless of meals. There is a marked interindividual variability in the extent of absorption of oral methotrexate. Conversely, the intraindividual variability is moderate even over a long time period. Intramuscular and subcutaneous injections of methotrexate result in comparable pharmacokinetics, suggesting that these routes of administration are interchangeable. A mean protein binding to serum albumin of 42 to 57% is usually reported. Again, the unbound fraction exhibits a large interindividual variability. The steady-state volume of distribution is approximately 1 L/kg. Methotrexate distributes to extravascular compartments, including synovial fluid, and to different tissues, especially kidney, liver and joint tissues. Finally, the drug is transported into cells, mainly by a carrier-mediated active transport process. Methotrexate is partly oxidised by hepatic aldehyde oxidase to 7-hydroxymethotrexate. This main, circulating metabolite is over 90% bound to serum albumin. Both methotrexate and 7-hydroxy-methotrexate may be converted to polyglutamyl derivatives which are selectively retained in cells. Methotrexate is mainly excreted by the kidney as intact drug regardless of the route of administration. The drug is filtered by the glomeruli, and then undergoes both secretion and reabsorption processes within the tubule. These processes are differentially saturable, resulting in possible nonlinear elimination pharmacokinetics. The usually reported mean values for the elimination half-life and the total body clearance of methotrexate are 5 to 8 hours and 4.8 to 7.8 L/h, respectively. A positive correlation between methotrexate clearance and creatinine clearance has been found by some authors. Finally, the pharmacokinetics of low-dose methotrexate appears to be highly variable and largely unpredictable even in patients with normal renal and hepatic function. Furthermore, studies in patients with juvenile rheumatoid arthritis provide evidence of age-dependent pharmacokinetics of the drug. These features must be considered when judging the individual clinical response to methotrexate therapy. Various drugs currently used in RA may interact with methotrexate. Aspirin might affect methotrexate disposition to a greater extent than other nonsteroidal anti-inflammatory drugs without causing greater toxicity. Corticosteroids do not interfere with the pharmacokinetics of methotrexate, whereas chloroquine may reduce the gastrointestinal absorption of the drug. Folates, especially folic acid, have been shown to reduce the adverse effects of methotrexate without compromising its efficacy in RA. Finally, both trimethoprim-sulfamethoxazole (cotrimoxazole) and probenecid lead to increased toxicity of methotrexate, and hence should be avoided in patients receiving these drugs. A relationship between oral dosage and efficacy has been found in the range 5 to 20mg methotrexate weekly. The plateau of efficacy is attained at approximately 10 mg/m2/week in most patients. No clear relationship between pharmacokinetic parameters and clinical response has been demonstrated. Overall, the dosage must be individualised because of interindividual variability in the dose-response curve. This variability is probably related, at least in part, to the wide interindividual variability in the disposition of the drug.
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Since both (R)- and (S)-enantiomers of ibuprofen may act on the central nervous system, we investigated their plasma and cerebrospinal fluid (CSF) concentrations in 46 patients with nerve-root compression pain requiring a lumbar puncture. Each patient received an oral dose of 800 mg rac-ibuprofen. A single blood and CSF sample was drawn concomitantly from each patient at intervals between 30 min and 8 h after dosing. Both isomers peaked later in the CSF (3 h) than in the plasma (1.5 h). Their CSF concentrations became higher than their concurrent free plasma concentrations after 90 min. The estimated elimination half-lives of (R)- and (S)-ibuprofen were 1.7 h and 2.5 h in plasma and 3.9 h and 7.9 h in CSF, respectively. The AUCCSF/AUCplasma ratios (0, 8 h) were 0.009 and 0.015 for the (R)- and (S)-forms, respectively.
Aspirin-like drugs mainly include paracetamol, salicylates and other non-steroidal anti-inflammatory drugs, and metamizole. Their analgesic effect is classically ascribed to a peripheral site of action, within the pain-processing site. There is, however, convincing evidence that a central component contributes to the overall analgesia provided by these agents. Experimental and clinical studies referring to this challenging proposal are reviewed here. The exact site and mode of action of aspirin-like drugs within the central nervous system remains controversial. It is likely that supraspinal mechanisms play an important role. Some experiments lend support to the involvement of monoaminergic control systems. Other data indicate that these drugs act centrally through the inhibition of cyclo-oxygenase activity. The interactions between prostaglandins and various neurotransmitters suggest that both mechanisms may be linked.
OBJECTIVE: To evaluate the outcome of patients with remitting seronegative symmetrical synovitis with pitting oedema (RS3PE). METHODS: In a retrospective chart review study, we identified all the patients presenting with polyarthritis and pitting oedema in the past 20 years. We tried to recall the 24 patients with characteristics of RS3PE according to McCarty et al. Two patients had died and four could not be traced. Five could not be seen after the initial period of follow up; relevant data were obtained from their practitioner. For the remaining 13 patients, clinical, radiological, and biological evaluation was performed in our department, with the last assessment in 1993. RESULTS: The follow up period was from one to 18 years (mean 4.6 (SD 4.5) years). Eleven patients developed one or several recurrences of articular manifestations consisting of mild oligoarthritis (n = 8), definite spondyloarthropathy (n = 2), and rheumatoid arthritis (n = 1). The delay of the first recurrence was 18 months to 12 years after the first attack. Thirteen patients had no recurrence, but three of them developed remarkable features: rheumatoid factor, antinuclear antibodies (1/2000), Sjögren's syndrome. HLA B typing was performed in nine patients and revealed B7 (n = 2), B27 (n = 2) and B22 (n = 2). Isolated HLA B27 typing was performed in two other patients and was positive in one. CONCLUSION: The long term outcome of RS3PE can lead to different rheumatic diseases. RS3PE appears to be a syndrome related to the elderly onset of the rheumatic diseases, including spondyloarthropathy and rheumatoid arthritis, rather than a specific entity.
We report two cases of epicondylitis of the elbow occurring after treatment with fluoroquinolone antibiotics. Both patients had intense pain which appeared very shortly after the first dose of the drug and was not relieved by conservative treatment. Ultrasonography revealed extensive inflammatory lesions with pseudonecrotic areas. MRI confirmed the lesions and also showed a subclinical abnormality of the adjoining tendons. The persistent nature of the pain was the indication for surgical release of the extensor mechanism. After operation pain disappeared completely and the patients were able to return to their normal activities. Lesions of the tendo Achillis are a well-known side-effect of treatment with fluoroquinolone. Our two cases show that such lesions may occur elsewhere. They also indicate the need for caution when prescribing these antibiotics to patients at risk of tendon lesions, such as top-level sportsmen or patients on dialysis or steroid treatment.