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Biomedical subjects

R Treves

Publications and source records attributed to R Treves.

At least 19 recordsLinked to original sources
PubMed2002

Opioid rotation in the treatment of joint pain. A review of 67 cases.

OBJECTIVE: To determine that opioid rotation can be useful for establishing a more advantageous analgesia/toxicity relationship in rheumatologic pain. METHODS: Among patients treated with opioids for rheumatologic non-malignant pain, 67 patients with opioid rotation were enrolled retrospectively. In all cases, the other analgesics had failed. The opioids used were: oral morphine, oral hydromorphone, oral buprenorphine and transdermal fentanyl. The reasons for rotation were noted and the improvement of pain was assessed by comparing baseline and post-treatment visual analog scales (VAS in mm). RESULTS: The 67 patients suffered from low back pain with sciatica in 27 cases, inflammatory arthritis in 14 cases, brachial neuralgia in six cases, osteoarthritis in eight cases and miscellaneous in 12 cases. The opioid rotations were the substitution of morphine by transdermal fentanyl, by oral hydromorphone in most of the cases. The principal reason for opioid rotation was failure of the first treatment. The mean of VAS improvement was 30 mm (P < 0.001). CONCLUSION: In rheumatologic non-malignant pain, the opioid rotation might allow the physician to bypass side effects or failure to alleviate pain in most cases.

Administration, Cutaneous↗
PubMed1998

Methotrexate and cyclooxygenase metabolism in cultured human rheumatoid synoviocytes.

OBJECTIVE: Our objective was to characterize the effect of methotrexate (MTX) on prostaglandin E2 (PGE2) synthesis in cultured human rheumatoid synovial cells. Prostaglandins (PG) are important mediators of inflammation and joint destruction in rheumatoid arthritis (RA). Two isoforms of cyclooxygenase (COX), the key enzyme in PG synthesis, have been characterized: a constitutively expressed form, COX-1, and an inducible form, COX-2. The mechanisms of action of low dose MTX in RA treatment are still poorly understood. As the clinical effects are often first noticed within a month of starting MTX therapy, an antiinflammatory action has been proposed. METHODS: Adherent synovial cells were obtained by collagenase digestion of rheumatoid synovium, isolated from patients with RA undergoing synovectomy. Between passages 3 and 6, cultured synovial cells were incubated with or without MTX for 54 h, at various concentrations. Interleukin (IL)-1beta (1 ng/ml) was added or not for the last 6 h of incubation. Supernatants were harvested and assayed for PGE2 by enzyme immunoassay (EIA). Exogenous [1-14C]arachidonic acid metabolism of synoviocytes was analyzed by reverse phase high performance liquid chromatography (RP-HPLC). COX-1 and COX-2 mRNA expression was determined by total RNA extraction and reverse transcription polymerase chain reaction. RESULTS: Cellular viability was not affected by MTX. EIA showed that MTX decreased IL-1beta induced PGE2 production by synoviocytes in a dose dependent manner. RP-HPLC analysis confirmed the inhibition of PGE2 and (12S)-12-hydroxy-5,8,10-heptadecatrienoic acid production. COX-1 and IL-1beta induced COX-2 mRNA expression were not inhibited by MTX. CONCLUSION: MTX has an inhibitory effect on IL-1beta stimulated production of PGE2 by cultured human rheumatoid synoviocytes, without affecting either COX mRNA expression. Among various biochemical and immunologic events, MTX could have an antiinflammatory action by decreasing PGE2 release.

Antirheumatic Agents↗
PubMed1998

Influence of biological variables upon pharmacokinetic parameters of intramuscular methotrexate in rheumatoid arthritis.

The pharmacokinetics of methotrexate were studied in 22 patients receiving 5-15 mg per week in a single i.m. administration for rheumatoid arthritis. The data consisted of 3 plasma levels per patient, taken at 2, 6, and 12 hours after the administration. The concentration of methotrexate was determined by fluorescence polarization immunoassay. The pharmacokinetic parameters of a 2-compartment model were determined by Bayesian estimation using the population values of Bressolle et al. [1996]. The fitted parameters were: total plasma clearance of methotrexate (CL), first-order absorption constant (ka), volume of central compartment (V1), and transfer constants between the 2 compartments (k12 and k21). Additional parameters were derived from the fitted ones: maximal concentration (Cmax), time to maximum (tmax), volume of distribution at steady-state (Vss), and terminal half-life (t1/2). Twenty-one biological covariates were considered to explain the interpatient variability. The relationships between these covariates and the pharmacokinetic parameters were investigated by principal component analysis and multiple regression analysis. About 90% of the variability of CL were explained by 4 variables (sex, age, height and serum creatinine). About 50%-70% of the variability of the other pharmacokinetic parameters were explained by a set of covariates including age, height, creatinine, creatinine clearance, and dose. The effect of dose was noticed mainly on k12, Vss, and t1/2, thus suggesting that the transfer of the drug from plasma to tissues may be nonlinear. The possibility of predicting CL with a good precision would facilitate the computation of dosage regimens in these patients.

Adult↗
PubMed1997

Effects of cyclical etidronate therapy on bone loss in early postmenopausal women who are not undergoing hormonal replacement therapy.

This study was carried out to investigate the effectiveness and tolerability of cyclical etidronate therapy in the prevention of bone loss occurring in early postmenopausal women who are not undergoing hormone replacement therapy (HRT). A total of 109 Caucasian women aged 45-60 years were treated with etidronate 400 mg/day or placebo for 14 days followed by calcium supplementation 500 mg/day for 77 days. Ninety-one women completed the 2 years of the study. After 2 years, the estimated difference between the two groups as regards lumbar spine bone mineral density (BMD) was 2.53% (SEM 1.07%; p = 0.01); BMD of the hip and wrist were not significantly different between treatment groups. A clear reduction in bone turnover was obtained as evidenced by a significant decrease in serum alkaline phosphatase level and in urinary N-telopeptide/ creatinine ratio in the etidronate group; the difference between the two groups was -12% +/- 3.2% for serum alkaline phosphatase level (p = 0.019) and -22.9% +/- 13.7% for the urinary N-telopeptide/creatinine ratio (p = 0.047). There was no statistically significant difference between the two groups in terms of the serum osteocalcin levels and urinary hydroxyproline/ creatinine and calcium/creatinine ratios. Etidronate was generally well tolerated and its adverse event profile was similar to that of placebo. The results of this study indicate that cyclic etidronate therapy can prevent trabecular bone loss, with no deleterious effect on cortical bone, in the first 5 years of menopause and that it has a very high safety margin.

Alkaline Phosphatase↗
PubMed1997

Airway obstruction and rheumatoid arthritis.

The aim of this study was to assess the percentage of respiratory disorders and airway obstruction in patients with rheumatoid arthritis by comparing lung function test results between patients with rheumatoid arthritis and control subjects with other rheumatological conditions. A prospective case-control study of respiratory symptoms and lung function abnormalities was performed in a series of 100 patients with rheumatoid arthritis. Eighty eight patients with other rheumatological diseases served as controls. Diagnosis of respiratory disorders was based on clinical, radiological and spirometric findings. Airway obstruction was determined from predicted values. The results were compared using Student's t-test and Chi-squared tests. An explanatory analysis was carried out by linear regression. The number of symptoms, respiratory disorders (including bronchiectasis) and lung function abnormalities was higher in patients with rheumatoid arthritis than in controls. After exclusion of smokers, the proportion of airway obstruction in patients with rheumatoid arthritis was 16% (versus 0% in controls), although the patients with rheumatoid arthritis still had more symptoms and respiratory disorders. The Chi-squared test did not identify any relationship between airway obstruction, duration of rheumatoid arthritis and type of treatment and occurrence of Sjögren's syndrome. In the nonsmokers, different explanatory models for the patients with and without a history of cardiac and respiratory disease emerged from multivariate analysis of indices of obstruction. These models included variables characterizing the severity and course of the rheumatoid arthritis. Respiratory disorders (including bronchiectasis) and airway obstruction are more frequent among patients with rheumatoid arthritis than in rheumatological controls. Although the exact pathophysiology of the link between bronchial obstruction and rheumatoid arthritis is still a matter of debate, explanatory factors for obstruction included variables characterizing the rheumatoid arthritis.

Adult↗
PubMed1996

[Medical treatment of osteoarthritis].

Immediate symptom relief, long-term symptom relief and chondroprotection comprise the basis of medical treatment of degenerative joint disease. Nonsteroid anti-inflammatory agents, antalgics and intra-articular infiltrations with corticosteroids provide rapid relief. A more delayed long-term effect can be obtained with a large number of drugs. Chondroprotectors are currently the focus of therapeutic research. Advances in our knowledge of the pathophysiological processes involved in the development of the degenerative process, a critical analysis of current medical therapies and rigorous methodology in clinical trials will soon provide a better range of treatments for patients suffering from degenerative joint disease.

Humans↗
PubMed1996

Fluoroquinolone induced tendinopathy: report of 6 cases.

We describe 6 cases of fluoroquinolone induced Achilles tendinitis in 4 women and 2 men, mean age 68.6 years. Patients presented with pain and swelling of sudden onset, which was most often bilateral. Tendon rupture was frequent, accompanied by nodules and ecchymoses. The diagnosis was clinical, occasionally ultrasonography was helpful; the role of magnetic resonance imaging has yet to be defined. Certain risk factors were found, particularly association with longterm steroid therapy, and close surveillance of high risk subjects is mandatory. Although proper dosage and duration of treatment were respected, the principal fluoroquinolones were clearly incriminated. We found no correlation between treatment duration and the degree of involvement. Nevertheless, immediate discontinuation of the antibiotic and placement of both Achilles tendons at rest is essential. Early and appropriate management did not prevent prolonged recovery times and there was always a risk of functional sequelae. This side effect is class related and rare. Its physiopathologic mechanism is poorly understood.

Adult↗
PubMed1996

Bovine collagen induced systemic symptoms: antibody formation against bovine and human collagen.

We describe the first case of systemic symptoms after injection of bovine collagen and silicone polymers associated with antibodies to both native type I and II bovine and human collagen that varied with clinical features. Joint inflammation, edema at the injection site of bovine collagen implant and fever appeared 6 months after injection. Our patients history raises the question of whether the injection of animal derived collagen, particularly combined with silicone, induces or exacerbates autoimmune disease.

Adult↗
PubMed1996

Synovial cyst at the C1-C2 junction and spondyloarthropathy.

A spinal synovial cyst is a rare extradural benign tumor generally located at the lumbar spine, arising at the facet joint capsule, and usually associated with degenerative changes. We describe a 64-year-old woman with a synovial cyst involving the quadrate ligament of the odontoid process, which caused neurologic signs. Her family history was positive for spondyloarthropathy. The radiologic investigations, preoperative differential diagnosis, and association of spondyloarthropathy with this rare benign foramen magnum tumor are of particular interest.

Cervical Vertebrae↗
PubMed1995

Lipoxygenase products and expression of 5-lipoxygenase and 5-lipoxygenase-activating protein in human cultured synovial cells.

5-Lipoxygenase products are pro-inflammatory mediators. Their roles and cellular origin in chronic inflammatory rheumatisms such as rheumatoid arthritis (RA) are poorly understood. The expression of arachidonate 5-lipoxygenase (5-LOX, arachidonate: oxygen 5-oxydoreductase; EC 1.13.11.34) and the 5-lipoxygenase activating protein (FLAP) genes in osteoarthritis and RA synoviocytes was studied at the transcriptional level by reverse transcription-polymerase chain reaction (RT-PCR) methodology. Arachidonic acid metabolism was analyzed by reverse-phase high pressure liquid chromatography. 5-LOX and FLAP mRNA were detectable using RT-PCR in all sources of synoviocytes tested. The expression of 5-LOX and FLAP mRNA led to the synthesis of 5-LOX metabolites. 12- and 15-LOX activities were also present. These LOX products can participate in inflammatory processes leading to joint destruction in RA.

5-Lipoxygenase-Activating Proteins↗
PubMed1994

Efficacy and tolerability of a new formulation of oral tiludronate (tablet) in the treatment of Paget's disease of bone.

We sought to assess efficacy and safety of a new oral formulation (tablet) of tiludronate in Paget's disease of bone. We studied 128 patients with Paget's disease in an open-label uncontrolled trial. Patients received a daily dose of 400 mg oral tiludronate (two tablets). Treatment was for 6 months. Serum alkaline phosphatase activity (SAP) and fasting urinary excretion of hydroxyproline/creatine (OH/Cr) were measured every 3 months, as were biochemical parameters reflecting renal, hepatic, and hematologic functions. Analgesic efficacy was self-evaluated from a visual analog scale (VAS). Statistical analysis revealed a significant reduction from baseline in SAP and OH/Cr levels, as well as VAS scores. In the whole population with evaluation under treatment, there was a reduction in initial SAP activity after 3 months (47.2 +/- 2.2%, mean +/- SEM) and 6 months (58.3 +/- 2.3%). In the population with SAP levels above twice the upper limit at inclusion and with evaluation at month 3 and month 6 (n = 96), the reduction in SAP levels was 49.3 +/- 2.4% after 3 months and of 59.5 +/- 2.6% after 6 months (ANOVA time effect, p = 0.0001). Aside from mild gastrointestinal disturbances, as experienced with other oral bisphosphonates, clinical tolerance was good. Exhaustive biochemical investigation failed to reveal significant toxicity of tiludronate tablets at the dose of 400 mg/day. The dose of 400 mg daily of this new formulation appears to be a satisfactory tiludronate regimen for the treatment of Paget's disease of bone.

Aged↗
PubMed1994

Sodium naproxen: concentration and effect on inflammatory response mediators in human rheumatoid synovial fluid.

Twelve patients suffering from rheumatoid arthritis and having swollen knees were treated with 1.1 g/day of sodium naproxen administered in one dose, daily for 5 days. The 72-h wash-out period was verified by the absence of any nonsteroidal anti-inflammatory drug using a HPLC screening. Blood and synovial fluid samples were drawn just before treatment and 24 h after the last dose. Eicosanoids (PGE2, 6-keto-PGF1 alpha, TXB2, LTB4, LTC4) in synovial fluid were determined by immunoenzymatic assays. In plasma and synovial fluid, hyaluronic acid was assayed by radiometric assay and sodium naproxen by HPLC. Free drug was determined by equilibrium dialysis. Statistical analysis used nonparametric tests. Pain relief (evaluated on a visual scale), morning stiffness, and scores on the Lee and Ritchie indices all decreased significantly, as did PGE2 and LTB4 concentrations. The decrease in 6-keto-PGF1 alpha and TXB2 was not significant. No significant change was found for LTC4 and hyaluronic acid. Total concentrations of sodium naproxen were equivalent in plasma (16.1 micrograms.ml-1) and synovial fluid (18.9 micrograms.ml-1). Free fractions were significantly higher in synovial fluid (0.14%) than in plasma (0.11%), as shown by binding of the drug to human serum albumin, at various protein concentrations. Interestingly, the clinical efficacy, as shown by decreases in morning stiffness and in the Lee index score, correlated with the free concentration of naproxen in synovial fluid.

6-Ketoprostaglandin F1 alpha↗