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Biomedical subjects

J P Raynauld

Publications and source records attributed to J P Raynauld.

17 recordsLinked to original sources
PubMed1995

The in vivo effects of intraarticular corticosteroid injections on cartilage lesions, stromelysin, interleukin-1, and oncogene protein synthesis in experimental osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is characterized by a progressive erosion of the articular cartilage. Studies suggest that cytokines and metalloproteases play an important role in this process. Previously, we found that corticosteroids given prophylactically reduce the severity of cartilage lesions. In this study, we examined and compared the in vivo efficacy of a corticosteroid, triamcinolone hexacetonide (TH), administered either prophylactically or therapeutically, on OA lesions and on cartilage metalloproteases, interleukin-1 beta (IL-1 beta), and oncogene synthesis in experimental OA. EXPERIMENTAL DESIGN: This study examines the effect of intraarticular injections of TH on the progression of lesions in the experimental dog model of OA. The animals had the anterior cruciate ligament of the right knee sectioned and were killed 12 weeks after surgery. A total of 30 dogs were used in four groups: group 1 (n = 8) had no treatment; group 2 (n = 8; TH-3) received TH at time of surgery and at 4 and 8 weeks later; group 3 (n = 7; TH-2) received TH at 4 and 8 weeks after surgery; and group 4 (n = 7; TH-1) received TH at 8 weeks after surgery. Knee cartilage was submitted to macroscopic and microscopic examinations, as well as immunohistochemical studies for stromelysin, IL-1 beta, and oncoproteins, c-Fos and c-Myc. RESULTS: Injections with TH significantly reduced the size of osteophytes in dogs from groups TH-3 (p < 0.0001) and TH-2 (p < 0.0002). The histologic severity of cartilage lesions was significantly reduced on condyles in all TH groups and on plateaus of dogs from groups TH-3 and TH-2. Immunohistochemistry revealed that TH significantly reduced the percentage of immunoreactive chondrocytes for stromelysin, and the effect was proportional to the number of injections received. For c-fos and c-myc, the reduction was particularly significant in the TH-3 and TH-2 groups. For IL-1 beta, the reduction was significant only in the TH-3 group. CONCLUSIONS: This study provides novel data showing the protective effect of corticosteroid injections on OA cartilage lesions not only under prophylactic but also under therapeutic conditions. The effect of TH may be mediated through a direct reduction in the expression and synthesis of proteolytic enzymes, such as stromelysin. Alternatively, the steroid could act by inhibiting the stimulation of protease synthesis by cytokines/oncogenes (IL-1 beta, c-Fos, and c-Myc).

Adrenal Cortex Hormones↗
PubMed1994

Intraarticular injections with methylprednisolone acetate reduce osteoarthritic lesions in parallel with chondrocyte stromelysin synthesis in experimental osteoarthritis.

OBJECTIVE: To examine the effect of intraarticular injections of methylprednisolone acetate (MA) on osteoarthritic lesions and chondrocyte stromelysin synthesis in experimental osteoarthritis (OA). METHODS: In 15 mongrel dogs, the anterior cruciate ligament of the right knee was sectioned by a stab wound. Eight dogs received intraarticular injections of MA (20 mg) at the time of surgery and 4 weeks later; 7 had no treatment. The dogs were killed 8 weeks after surgery. Five normal dogs were used as controls. Macroscopic evaluation of the lesions, including measurements of osteophytes and areas of surface lesions on the condyles and plateaus, was conducted, along with histologic evaluation of the severity of lesions. Immunohistochemical analysis was carried out using a rabbit polyclonal antibody against stromelysin, followed by evaluation of matrix and chondrocyte staining using morphometric analysis. RESULTS: Treatment with MA significantly reduced the incidence (P < 0.0004) and size (P < 0.0001) of osteophytes. The histologic grading of cartilage lesions was also significantly reduced both on condyles (P < 0.01) and on plateaus (P < 0.002). Immunohistochemical studies revealed, for OA cartilage, a marked increase (P < 0.002) in the percentage of chondrocytes positive for stromelysin and in the intensity of staining throughout all the layers of the cartilage, as well as specific matrix staining (P < 0.005). Treatment with MA reduced staining at both the chondrocyte (P < 0.002) and the matrix (P < 0.01) levels toward normal. CONCLUSION: These findings provide additional evidence for the protective effect of corticosteroid injections on OA lesions, and indicate that the effect of this drug may be mediated through the suppression of stromelysin synthesis.

Animals↗
PubMed1994

Serum keratan sulfate levels in rheumatoid arthritis: inverse correlation with radiographic staging.

OBJECTIVE: To correlate the serum levels of keratan sulfate (KS) in patients with rheumatoid arthritis (RA) with different clinical and radiographic variables. METHODS: Serum KS levels were measured in 85 patients with RA and 41 age matched controls. Patients with RA were classified according to their disease activity, the presence of rheumatoid factor, the medication prescribed, and to the severity of the joint radiographic changes. RESULTS: Patients with RA had significantly (p < 0.02) higher levels of serum KS compared to the healthy controls. More significantly, there was an inverse correlation of the serum KS levels with the disease activity (p = 0.02) and the severity of the radiographic changes (p = 0.012). CONCLUSIONS: Serum KS levels appear to correlate with the severity of articular cartilage damage in RA.

Aged↗
PubMed1993

A reevaluation of aspirin therapy in rheumatoid arthritis.

BACKGROUND: Aspirin therapy has been largely superseded by prescription nonsteroidal anti-inflammatory drug (NSAID) therapy in rheumatoid arthritis, in part because of premarketing studies suggesting lesser toxic effects for NSAIDs than for aspirin. This study evaluates these toxic effects in a postmarketing population of patients with rheumatoid arthritis. METHODS: We studied 1521 consecutive courses of aspirin and 4860 courses of NSAIDs in patients with rheumatoid arthritis from eight Arthritis, Rheumatism, and Aging Medical Information System Post-marketing Surveillance Centers. Toxicity index scores were generated from symptoms, laboratory abnormalities, and hospitalizations, weighted for variable severity and severity of side effect. RESULTS: The toxicity index was only 1.37 (SE = 0.10) for aspirin and 1.87 to 2.90 for selected nonsalicylate NSAIDs. These differences were consistent across centers and remained after statistical adjustment for differing patient characteristics. There was a different toxicity with different aspirin preparations, with a score for plain aspirin of 1.36 (SE = 0.23), for buffered aspirin of 1.10 (0.20), and for enteric-coated aspirin preparations of 0.92 (0.14). Most important, there were strong dose effects, with a score of 0.73 (0.09) for 651 to 2600 mg daily, 1.08 (0.17) for 2601 to 3900 mg, and 1.91 (0.38) for more than 3900 mg. The average aspirin dose taken was only 2665 mg/d, approximately eight "tablets," compared with 3600 to 4800 mg/d used in the 16 pivotal premarketing studies reviewed. Average NSAID doses were, on the other hand, lower in premarketing trials (eg, naproxen 500 mg/d vs 773 mg/d in the Arthritis, Rheumatism, and Aging Medical System clinical practices). CONCLUSIONS: Aspirin therapy, in doses commonly employed in practice, has an excellent safety profile in rheumatoid arthritis, and it is the least costly NSAID. The safety advantage is explained primarily by a dose effect and secondarily by possible differences between formulations. Newer management strategies for rheumatoid arthritis emphasize NSAID use as symptomatic therapy and use of disease-modifying anti-rheumatic drug therapy for anti-inflammatory objectives. Thus, the original recommendation for "anti-inflammatory" doses of aspirin now is less easily justified. Aspirin therapy merits reconsideration as adjunctive therapy for the management of rheumatoid arthritis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1993

Seasonal variation in the onset of Wegener's granulomatosis, polyarteritis nodosa and giant cell arteritis.

OBJECTIVE: The hypothesis of a seasonal pattern in the onset of symptoms for some vasculitides has been raised in previous small studies. METHODS: Using the data collected by the American College of Rheumatology (ACR) Subcommittee on Classification of Vasculitis, we specifically tested for a higher proportion of onset of symptoms in winter, lower in summer, and intermediate for the other seasons for polyarteritis nodosa (PAN) and Wegener's granulomatosis. We also tested for a higher proportion of onset of symptoms in the spring-summer months for giant cell arteritis (GCA). RESULTS AND CONCLUSIONS: The results of our study support the hypothesis of a seasonal trend for the onset of symptoms of Wegener's granulomatosis (p = 0.04) as described previously. No seasonal pattern was found for the other vasculitides studied (PAN and GCA).

Giant Cell Arteritis↗
PubMed1993

Unilateral ptosis as an initial manifestation of D-penicillamine induced myasthenia gravis.

We describe 2 patients presenting with isolated unilateral ptosis without other signs of cranial or peripheral nerve involvement or sympathetic denervation. Both patients (one case of progressive systemic sclerosis and one of rheumatoid arthritis) were currently taking D-penicillamine. In these cases, the ptosis was reversed a few minutes after a Tensilon test, hallmark of myasthenia gravis. Antibodies to acetylcholine receptors were present. Myasthenia gravis should be suspected with ptosis without other cranial nerve involvement or miosis, even if the ptosis is unilateral. Thus, unilateral ptosis can be the first manifestation of a toxic side reaction to D-penicillamine.

Adult↗
PubMed1992

The health assessment questionnaire 1992: status and review.

Over 100 papers describing and utilizing the Stanford Health Assessment Questionnaire (HAQ) have been published since 1980. A brief overview of the HAQ is presented along with a guide to the accumulated literature. The topics covered include: studies using the disability, pain, economic, and drug side effect dimensions of the HAQ; reliability and validity studies; applications to various rheumatic diseases; language adaptations; modifications and derivative scales; studies correlating the HAQ with sociodemographic, health status, laboratory, and physical measures; and randomized controlled trials and observational studies using the HAQ. A few comments regarding future directions for research are also presented.

Arthritis↗
PubMed1992

[A simplified terminology for abnormalities of the lumbar disks].

The terminology for abnormalities of the lumbar disk has always been a source of confusion. Recent advances in pathological studies have inspired the authors to propose a simple classification of common disk anomalies suitable not only for diagnostic radiologists but also for referring clinicians. Although the diagnosis of a few pathological entities will only be possible with specific imaging techniques, the proposed classification is appropriate for reporting observations from plain films, conventional tomograms, myelograms, discograms, computed tomography scans and magnetic resonance images. All lumbar disks can thus be classified into one or more of the following categories: normal, aging, scarred, ruptured and herniated. A disk herniation is defined as a localized exit of disk material beyond the limits of the original intervertebral space.

Adult↗
PubMed1991

A simplified terminology for abnormalities of the lumbar disk.

The terminology for abnormalities of the lumbar disk has always been a source of confusion. Recent advances in pathological studies have inspired the authors to propose a simple classification of common disk anomalies suitable not only for diagnostic radiologists but also for referring clinicians. Although the diagnosis of a few pathological entities will only be possible with specific imaging techniques, the proposed classification is appropriate for reporting observations from plain films, conventional tomograms, myelograms, diskograms, computed tomography scans and magnetic resonance images. All lumbar disks can thus be classified into one or more of the following categories: normal, aging, scarred, ruptured and herniated. A disk herniation is defined as a localized exit of disk material beyond the limits of the original intervertebral space.

Aging↗
PubMed1987

Micropipette holders: vented types are preferable to closed types.

Due to the large coefficient of volume expansion of water with temperature, the use of closed micropipette holders results in significant pipette motion and pressure ejection of electrolytes or marker dyes as the temperature of the pipette goes up upon insertion in the CNS or spinal cord of warm blooded preparations.

Iontophoresis↗
PubMed1987

The silver-silver chloride electrode: a possible generator of offset voltages and currents.

Large input currents can be generated by an asymmetry in the chloride activity seen by Ag-AgCl electrodes used at the input of intracellular amplifiers because offset compensation no longer takes place at the input of the amplifier but rather later in the circuit in many modern amplifiers. This situation occurs when chloride-free solution, such as potassium acetate, potassium citrate or various intracellular dyes are used as pipette and electrode holder filling solutions. Omitting the agar bridge at the reference electrode, or using a platinum electrode will have similar results. Values of cellular membrane potentials can be significantly contaminated under such conditions, particularly where the amplifier input resistance did not exceed 10(10) omega and where small cells were studied. Unexpected iontophoresis of Cl- can occur when the asymmetry is such as to make the recording pipette negative. These offsets can be avoided in all situations by the use of salt bridges which insure that the two Ag/AgCl junctions are in contact with Cl- of the same activity.

Electrophysiology↗
PubMed1986

Thermal stability of hydrolic drives.

The thermal stability of hydrolic drives is investigated theoretically and experimentally. A commonly used model is found to have a positive positional temperature coefficient of 7 microns per degrees C at 22 degrees C. A simple temperature compensator is described. This should lead to improved intracellular recording stability when recording from small cells.

Microelectrodes↗
PubMed1972

Goldfish retina: sign of the rod input in opponent color ganglion cells.

After light adaptation, all "on-center" ganglion cells in the dark became "red on-center," and all "off-center" cells turned into "red off-center" cells. On a chance basis, this similitude of effect between the rods and the red cones in opponent color cells was not expected. These findings indicate that in the goldfish there is some similarity between the connections of the rods and of the long-wavelength cones.

Adaptation, Physiological↗
PubMedDate not supplied

Comparing the bivariate effects of toxicity and efficacy of treatments.

Medical studies often involve comparing the toxicity and efficacy of drugs. Separately evaluating toxicity and efficacy, the usual practice, does not correspond to how doctors manage patients and does not use the information provided in their bivariate relationship. This paper presents methods for analysing the bivariate data. One method is based on assessing the benefit for patient values to lie in different regions of the toxicity-efficacy plane. A second method includes patient thresholds for tolerating drugs. We propose dividing the toxicity-efficacy plane into regions where patients are likely to tolerate the drug. Several statistics are defined on these regions for measuring the toxic-therapeutic relationship, and the bootstrap is proposed for estimating their variances. We illustrate with treatment information available on rheumatoid arthritis patients.

Arthritis, Rheumatoid↗