salicylates and Arthritis--Rheumatoid

Topics: Acetylation; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Humans; Osteoarthritis; Patient Compliance; Salicylates; Stereoisomerism

An overview of the literature on the effects of salicylic acid and its derivatives with particular consideration being given to their antiinflammatory properties is presented. While acetylsalicylic acid, in common with most non-steroidal anti-inflammatory drugs, has a marked inhibitory effect on cyclooxygenase in vitro, salicylic acid only weakly inhibits this enzyme. Animal inflammation models, however, have shown that the two substances are comparable in terms of efficacy. It is therefore assumed that the antiinflammatory properties of salicylic acid and its derivatives are also based on prostaglandin-independent mechanisms. Both salicylates and salicylic acid are used for topical applications. Their penetration into deeper tissue layers, as also their efficacy after local application have been demonstrated in both animal studies and clinical trials.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Aspirin; Humans; Inflammation; Salicylates; Salicylic Acid

Topics: Adrenal Cortex Hormones; Arthritis, Rheumatoid; Autoimmune Diseases; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Myasthenia Gravis; Pemphigoid Gestationis; Polyarteritis Nodosa; Pregnancy; Pregnancy Complications; Salicylates; Scleroderma, Systemic; Thrombocytopenia; Thyroid Diseases

Aspirin, nonacetylated salicylates, and numerous other nonsteroidal antiinflammatory drugs (NSAIDs) are used in rheumatoid arthritis (RA) patients to decrease joint inflammation and improve function. The choice of medication and its optimum dosage must be individualized because of marked intersubject variations in drug metabolism, excretion, antiinflammatory and analgesic efficacy, and susceptibility to adverse effects. Equivalent doses of aspirin and of nonacetylated salicylates are equally antiinflammatory in RA, although the nonacetylated salicylate is a poor inhibitor of prostaglandin synthesis. Chronopharmacology studies suggest that many patients may have better efficacy and fewer side effects with evening doses than with morning doses of certain NSAIDs; however, the optimum time must be individualized by trial and error because some patients do better with other regimens. The gastric, renal, and platelet adverse effects of NSAIDs are related to their inhibition of prostaglandin synthesis, and tend to be related to dose and intensity of therapy. Various strategies can minimize the impact of these side effects, such as coadministration of gastric protectants or the use of short half-life NSAIDs to decrease the duration of preoperative NSAID withdrawal needed to ensure adequate platelet coagulation during surgery. An intramuscular analgesic NSAID is now available and is reported to be equivalent to morphine sulfate in some painful postsurgical conditions. Although associated with many problems, chronic corticosteroid therapy is, or has been, a major therapeutic component for many RA patients who consequently are unable to respond adequately to the stresses of general anesthesia and surgery because of complete or partial adrenal insufficiency. These patients must be given appropriate supplemental corticosteroid therapy perioperatively.

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Humans; Salicylates

Topics: Anti-Inflammatory Agents; Arthritis, Juvenile; Arthritis, Rheumatoid; Azathioprine; Chloroquine; Cyclophosphamide; Drug Therapy, Combination; Felty Syndrome; Gold; Humans; Hydroxychloroquine; Immunosuppressive Agents; Leukapheresis; Lung Diseases; Lymphoid Tissue; Methotrexate; Penicillamine; Plasmapheresis; Radiotherapy; Rheumatic Diseases; Salicylates; Sjogren's Syndrome; Spinal Diseases; Vasculitis

The treatment of RA is complex and often frustrating. The pathologic process of RA is composed of acute inflammation, chronic immunologic phenomenon, and chronic connective tissue degradation. It is important to understand not only the pathophysiology of RA but also the mechanism of action of our therapeutic drugs so that treatment can be tailored to affect the important aspects of the process leading to end-organ damage. Despite the many drugs available, therapy is still unsatisfactory. Many drugs work in only certain patients. This could be secondary to variability in the disease state or to difference in drug metabolism. A better understanding of both disease and therapeutic agents may lead to better use of our present agents and development of new, more effective treatment modalities.

Topics: Adrenal Cortex Hormones; Animals; Anti-Inflammatory Agents; Antimalarials; Arthritis, Rheumatoid; Aspirin; Drug Interactions; Gold; Humans; Immunosuppressive Agents; Penicillamine; Salicylates

Successful treatment of patients with rheumatoid arthritis demands an understanding of the rationale, clinical use, and side effects of the various antirheumatic modalities. Most patients can be treated effectively with salicylates or other nonsteroidal anti-inflammatory drugs, although some with more serious disease require the addition of a slow-acting agent such as gold, d-penicillamine, or methotrexate.

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Antimalarials; Arthritis, Rheumatoid; Azathioprine; Blood Component Removal; Cyclophosphamide; Exercise Therapy; Gold; Humans; Injections; Methotrexate; Patient Education as Topic; Penicillamine; Rest; Salicylates; Self-Help Devices

Nonsteroidal anti-inflammatory drugs (NSAIDs) provide potent analgesic, anti-inflammatory activity as a result of their inhibition of prostaglandin synthesis. They are highly bound to plasma proteins and have half-lives that vary from two hours to more than 24 hours. While gastrointestinal reactions are well known, the renal and hepatic toxicities of NSAIDs have only recently been characterized. Elderly patients in general may be at risk of toxicity and should be evaluated frequently.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Dysmenorrhea; Female; Humans; Joint Diseases; Kinetics; Pain; Salicylates

General mechanisms of drug interactions are reviewed, as well as the effects of various drugs on the absorption, distribution, protein binding, eliminations and cellular transport of methotrexate. Published studies demonstrate that prior or concomitant administration of other drugs can alter the efficacy and toxicity of methotrexate. Nonabsorbable antibiotics can decrease methotrexate absorption. Nephrotoxic drugs can decrease methotrexate renal clearance. Salicylates and probenecid may decrease the plasma protein binding and renal tubular secretion of methotrexate. However, the clinical significance of many of these drug interactions is not known or has not been substantiated by extensive clinical observations.

Topics: Absorption; Anti-Bacterial Agents; Arthritis, Rheumatoid; Aspirin; Biological Transport; Cell Membrane; Cisplatin; Dose-Response Relationship, Drug; Drug Interactions; Folic Acid; Humans; Kidney Tubules; Methotrexate; Probenecid; Protein Binding; Salicylates; Serum Albumin; Sulfamethoxazole; Sulfonamides; Tissue Distribution

Rheumatoid Arthritis (RA) is a progressive disease of unknown aetiology which may be caused by faulty immune mechanisms. Early diagnosis and correct treatment can be extremely effective. Fast and lasting results can only be obtained by an appropriate combination of NSAID and DMARD drugs which both reduce subjective symptoms and halt the progression of the disease.

Topics: Adjuvants, Immunologic; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antimalarials; Arthritis, Rheumatoid; Azathioprine; Gold; Humans; Indomethacin; Levamisole; Penicillamine; Phenylbutazone; Propionates; Salicylates; Sulindac; Tolmetin

The pharmacologic properties, clinical efficacy and tolerability of the newer non-steroidal anti-rheumatic drugs are compared. Guidelines for a prescribing policy are given in which a safety-first approach is adopted. Propionic acid derivatives or newer drugs with similar properties are proposed as initial therapy to control symptoms of rheumatoid arthritis or osteoarthrosis. Special problems such as compliance in chronic disease, treatment of ulcer patients with anti-rheumatic drugs, therapy in the elderly, treatment for juvenile rheumatoid arthritis and treatment during pregnancy are considered.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Carbazoles; Chronic Disease; Diclofenac; Diflunisal; Humans; Indomethacin; ortho-Aminobenzoates; Osteoarthritis; Phenylbutazone; Piroxicam; Rheumatic Diseases; Salicylates; Thiazines; Tolmetin

Topics: Anti-Inflammatory Agents; Arthritis, Juvenile; Arthritis, Rheumatoid; Chemical and Drug Induced Liver Injury; Cryoglobulinemia; Felty Syndrome; Giant Cell Arteritis; Humans; Liver Diseases; Lupus Erythematosus, Systemic; Polymyalgia Rheumatica; Rheumatic Diseases; Rheumatic Fever; Salicylates; Scleroderma, Systemic; Sjogren's Syndrome; Vasculitis

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Humans; Indoles; ortho-Aminobenzoates; Propionates; Pyrazoles; Rheumatic Diseases; Salicylates

Evidence is presented that rheumatoid arthritis is a disease resulting from abnormal protein binding and that anti-rheumatic drugs act by correcting the abnormal binding.

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Binding, Competitive; Blood Proteins; Humans; Kinetics; Protein Binding; Salicylates; Serum Albumin; Tryptophan

Topics: Allopurinol; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Gold; Gout; Humans; Lupus Erythematosus, Systemic; Osteoarthritis; Penicillamine; Rheumatic Diseases; Salicylates; Spondylitis, Ankylosing; Vasculitis

It is given a short, oriented to practice survey on the at present internationally most usual non-steroidal antirheumatic drugs. Picture of effect and efficiency, side-effects, indications and contraindications of these remedies are described and compared. The description comprises salicylates, phenylbutazone, indomethacin, flufenamine acid and mefenamine acid, ibuprofene as well as new substances (benorylate, clofezone, nuflumine acid, azapropazone, bumadizone calcium, naproxene and others). In their qualitities of effect the new drugs do not essentially differ from the classical antirheumatic drugs. However, they partly reveal a more favourable relation between desirable and undesirable effects.

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Fenoprofen; Flufenamic Acid; Humans; Indomethacin; Ketoprofen; Mefenamic Acid; Naproxen; Phenylbutazone; Propionates; Salicylates

Topics: Adult; Arthritis, Rheumatoid; Blood Sedimentation; Coitus; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Indomethacin; Male; Middle Aged; Phenylbutazone; Physical Therapy Modalities; Rest; Rheumatoid Factor; Salicylates; Sexual Dysfunction, Physiological

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Arthritis, Rheumatoid; Atrophy; Betamethasone; Drug Interactions; Glucocorticoids; History, 20th Century; Humans; Hydrocortisone; Infections; Injections, Intra-Articular; Joint Diseases; Methylprednisolone; Necrosis; Osteoporosis; Peptic Ulcer; Prednisolone; Prednisone; Rheumatic Diseases; Salicylates; Skin Diseases; Substance Withdrawal Syndrome; Synovitis; Triamcinolone; Vascular Diseases

Topics: Acute Disease; Adolescent; Age Factors; Arthritis, Rheumatoid; Child; Chronic Disease; Diagnosis, Differential; Glucocorticoids; Humans; Indomethacin; Salicylates; Sex Factors; Somatotypes; Spondylitis, Ankylosing

Topics: Adrenocorticotropic Hormone; Analgesics; Antimalarials; Arthritis, Rheumatoid; Arthrodesis; Cortisone; Diazepam; Gold; Humans; Immunosuppressive Agents; Indomethacin; Phenylbutazone; Physical Therapy Modalities; Rest; Salicylates

Topics: Adrenocorticotropic Hormone; Aged; Aminopyrine; Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Dogs; Drug Hypersensitivity; Duodenal Ulcer; Esophageal Diseases; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Glucocorticoids; Humans; Hydrocortisone; Indomethacin; Intestinal Mucosa; Osteoarthritis; Penicillins; Phenylbutazone; Prednisolone; Rats; Rheumatic Diseases; Salicylates; Sodium Salicylate; Stomach Diseases; Stomach Ulcer; Streptomycin

Topics: Activities of Daily Living; Arthritis, Rheumatoid; Bursitis; Chloroquine; Diagnosis, Differential; Finger Joint; Gold; Gout; Hot Temperature; Humans; Hydroxychloroquine; Methylprednisolone; Neuralgia; Osteoarthritis; Pain; Physical Examination; Physical Exertion; Physical Therapy Modalities; Prednisolone; Rest; Salicylates; Synovectomy; Triamcinolone; Wrist Joint

Topics: Anti-Inflammatory Agents; Antineoplastic Agents; Arthritis, Rheumatoid; Chronic Disease; Glucocorticoids; Gold; Humans; Immunosuppressive Agents; Indomethacin; Injections, Intra-Arterial; Penicillamine; Pyrazoles; Salicylates

Topics: Anemia; Anemia, Hypochromic; Anemia, Macrocytic; Anemia, Sideroblastic; Arthritis, Rheumatoid; Erythrocyte Count; Folic Acid Deficiency; Gastrointestinal Hemorrhage; Hemolysis; Humans; Iron; Plasma Volume; Salicylates; Vitamin B 12 Deficiency

Topics: Anemia; Anemia, Hypochromic; Anemia, Macrocytic; Anemia, Sideroblastic; Arthritis, Rheumatoid; Bone Marrow; Cobalt; Erythrocytes; Female; Folic Acid; Folic Acid Deficiency; Gastric Acidity Determination; Hemoglobinometry; Humans; Intestinal Absorption; Iron; Liver Extracts; Male; Mononuclear Phagocyte System; Plasma Volume; Potassium; Salicylates; Sex Factors; Steroids; Vitamin B 12

Topics: Analgesics; Arthritis, Rheumatoid; Aspirin; Headache; Humans; Ischemia; Kinetics; Neoplasms; Neuralgia; Phenacetin; Phenylbutazone; Salicylates; Time Factors; Wounds and Injuries

Topics: Arthritis, Rheumatoid; Glucocorticoids; Humans; Pituitary-Adrenal Function Tests; Rheumatic Fever; Salicylates; Time Factors

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Analgesics; Anti-Inflammatory Agents; Antimalarials; Arthritis, Rheumatoid; Child; Chronic Disease; Female; Flufenamic Acid; Gold; Humans; Immunosuppressive Agents; Indomethacin; Infant; Long-Term Care; Male; Mefenamic Acid; Middle Aged; Muscles; Oxyphenbutazone; Phenylbutazone; Physical Therapy Modalities; Prednisone; Rehabilitation; Salicylates

Topics: Adolescent; Adrenal Cortex Hormones; Anti-Bacterial Agents; Antistreptolysin; Arthritis, Rheumatoid; Blood Proteins; C-Reactive Protein; Child; Chorea; Dermatology; Humans; Mucoproteins; Rheumatic Fever; Rheumatic Heart Disease; Salicylates; Serologic Tests

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Arthritis; Arthritis, Rheumatoid; Azoles; Gold; Humans; Quinolines; Salicylates

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Antimalarials; Arthritis; Arthritis, Rheumatoid; Chlorpromazine; Clinical Laboratory Techniques; Diagnosis, Differential; Gold; Orthopedics; Pathology; Phenylbutazone; Physical Therapy Modalities; Physiology; Pyrazoles; Radiography; Rheumatoid Factor; Salicylates

Two clinical studies were carried out to investigate the efficacy and safety as well as the local and systemic availability of a hydroxyethylsalicyclate gel. A double blind, multicenter trial, involving 113 patients with nonarticular rheumatic back pain, revealed statistically significant relief of pain as compared with placebo. Local and systemic tolerance was excellent. An open study of bioavailability after local application in 16 patients showed a mean salicylate concentration of 0.93 +/- 0.5 microgram/ml in the synovial fluid and 0.40 +/- 0.23 microgram/ml in the synovial membrane, compared with 0.14 +/- 0.04 microgram/ml in the serum. Genetisinic acid was not detected, while OH-hippuric acid was detected only in the serum and synovial fluid.

Topics: Administration, Topical; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Biological Availability; Double-Blind Method; Female; Gels; Humans; Male; Middle Aged; Pain Measurement; Salicylates

To investigate the efficacy of salsalate, a nonacetylated salicylate, in the treatment of patients with rheumatoid arthritis (RA).. Three hundred and one patients meeting the ACR criteria for RA were drawn from 16 centers. After withdrawal of nonsteroidal antiinflammatory drugs (NSAID) and subsequent flare, patients were randomized to receive either salsalate or diclofenac for 8 weeks, according to a double blind, double dummy protocol. Initial doses of salsalate 3.0 g/day and diclofenac 75 mg/day were titrated for the first 5 weeks. The primary outcome measure was a multivariate analysis at 8 weeks of tender joint count, pain, visual analog scale score, and physician's global assessment.. One hundred and ninety patients completed the study. The mean stabilized dose of salsalate was 3.55 g/day, and that of diclofenac 112 mg/day. Discontinuations were due to lack of efficacy (17 salsalate vs 15 diclofenac); adverse events [19 salsalate (mainly tinnitus and hearing loss; p = 0.0001 and p = 0.04, respectively) vs 9 diclofenac]; laboratory abnormalities (3 salsalate vs 1 diclofenac); and other reasons, including protocol violations, intercurrent illness, and personal factors (24 salsalate vs 23 diclofenac). Both treatments produced significant improvement from flare (p < 0.0001). Post hoc power analysis showed that the study had sufficient power (0.60 to 0.90) to detect clinically important differences between the 2 drugs in the primary outcome measures; however, no statistically significant (p = 0.29) or clinically important treatment differences were recorded. Other than a difference in erythrocyte sedimentation rate that favored salsalate, there were no significant differences in secondary outcome measures between the 2 groups. All outcomes showed a tendency for more improvement with salsalate.. Salsalate is as efficacious as diclofenac. Salsalate may be considered an alternative to other NSAID in the first line treatment of patients with RA.

Topics: Aged; Arthritis, Rheumatoid; Diclofenac; Double-Blind Method; Female; Humans; Male; Middle Aged; Multivariate Analysis; Pain; Salicylates; Treatment Outcome

1. Five rheumatoid patients with a knee joint effusion participated in the study. An aqueous solution (0.1 to 0.2 ml) containing paracetamol, salicylate, diclofenac and [125I]-albumin was injected into a given joint to yield target concentrations of approximately 20 micrograms ml-1 for diclofenac, salicylate and paracetamol and 10(8) counts ml-1 for [125I]-albumin. 2. Paracetamol, salicylate and diclofenac were analysed in synovial fluid by h.p.l.c. [125I]-albumin was analysed using gamma counting. 3. The clearances (+/- s.d.) obtained for the solutes were [125I]-albumin (0.0053 +/- 0.0019 l h-1), diclofenac (0.0096 +/- 0.0061 l h-1), salicylate (0.024 +/- 0.022 l h-1) and paracetamol (0.055 +/- 0.041 l h-1). The corresponding fractions unbound of these solutes in synovial fluid were 0.0, < or = 0.01, 0.34 +/- 0.09 and 0.85 +/- 0.10, respectively. 4. Diffusion of unbound solute through the synovium is estimated to account for (+/- s.d.) 0.52 +/- 0.08, 0.87 +/- 0.06 and 0.99 +/- 0.01 of the total clearance of diclofenac, salicylate and paracetamol from the joint space, respectively. The remaining proportion of clearance is accounted for by efflux of solute bound to albumin. 5. An expression for the ratio of synovial fluid to total plasma concentrations after systemic administration was developed to include both diffusion of unbound solute and albumin flux. Most solutes appear to satisfy the conditions in which this expression reduces to the limiting case where the unbound concentration of the solute is identical in the synovial fluid and plasma under steady state conditions.

Topics: Acetaminophen; Adult; Albumins; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Chromatography, High Pressure Liquid; Diclofenac; Female; Half-Life; Humans; Hydrogen-Ion Concentration; Injections, Intra-Articular; Knee Joint; Male; Metabolic Clearance Rate; Middle Aged; Models, Theoretical; Protein Binding; Salicylates; Salicylic Acid; Serum Albumin; Synovial Fluid

To examine the influence of specially trained physical therapists (PT) on patterns and outcome of care, relating to inflammatory disease status as measured by disease outcomes.. Fifty-four patients were allocated at random to specially trained PT, and to traditional PT. Outcomes were measured at baseline and at 4 months by independent assessors.. There was no statistically significant or clinically important difference in outcome between the 2 groups. The advice of specially trained PT significantly improved compliance with salicylates.. The effectiveness of this therapy was not demonstrated, likely due to incomplete compliance along the therapeutic chain, beginning with the PT's report, through a variety of possible responses, and ending with patient outcome.

Topics: Adolescent; Adult; Aged; Arthritis, Rheumatoid; Attitude of Health Personnel; Female; Hospitalization; Humans; Male; Middle Aged; Physical Therapy Modalities; Physicians; Referral and Consultation; Rheumatology; Salicylates; Severity of Illness Index; Treatment Outcome

Lysine acetyl salicylate [1.8 g t.d.s. (Aspergesic 1,000 sachet)] has been compared to 400-mg ibuprofen tablets t.d.s. in a randomized double-blind trial in patients with rheumatoid arthritis using double-dummy technique. Both drugs proved effective in relieving symptoms. Three patients experienced drug-related side-effects with Aspergesic, and one patient with ibuprofen, that necessitated early discontinuation of treatment. Aspergesic was associated with a greater number of haemoglobin values falling below the normal range than ibuprofen. At the end of the study, eight out of 10 patients who expressed a preference selected Aspergesic for improving mobility whilst 15/24 selected Aspergesic for improving pain.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Aspirin; Double-Blind Method; Female; Humans; Ibuprofen; Lysine; Male; Randomized Controlled Trials as Topic; Salicylates

This randomized, investigator-blinded, parallel group endoscopic study evaluated the effects of salsalate and naproxen on the gastroduodenal mucosa over a 3-month period in patients with RA. Using therapeutic doses of the drugs, 8 of 21 patients (38%) in the naproxen group had endoscopically shown active ulcers (seven patients) or diffuse erosions (one patient), whereas none of the 18 patients treated with salsalate (0%) had such lesions (P = .003). Five of the eight naproxen-treated patients with evidence of GI damage were asymptomatic at the time of endoscopic verification of their lesions. The most significant disadvantage of salsalate was its higher incidence of otologic problems accounting for six of the nine discontinuations with salsalate. However, the findings of this study suggest that patients receiving salsalate are at lower risk for developing significant gastropathy than those treated with naproxen. The relative benefit-to-risk ratio of salsalate indicates that this drug should be considered as a significant alternative NSAID therapy.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Double-Blind Method; Duodenal Ulcer; Female; Gastric Mucosa; Gastroscopy; Humans; Intestinal Mucosa; Linear Models; Male; Middle Aged; Multicenter Studies as Topic; Naproxen; Prospective Studies; Randomized Controlled Trials as Topic; Salicylates; Stomach Ulcer

In a multicenter, double-blind, parallel-group study, 233 patients with classical or definite RA who demonstrated disease flare during a prestudy washout period were randomized to 12 weeks of treatment with either the nonacetylated salicylate, salsalate (salicylsalicylic acid), or aspirin. Of the 150 patients who completed the study, 83 received salsalate and 67 were treated with aspirin. Doses of the two drugs were calculated to provide equal amounts of bioavailable salicylic acid. The efficacy of salsalate and aspirin, as measured by all the usual variables, was equivalent but aspirin-treated patients had a higher incidence of severe gastrointestinal problems. Thus, this study demonstrated that the acetyl group of aspirin does not enhance the anti-inflammatory efficacy of salicylic acid in RA.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Aspirin; Double-Blind Method; Female; Humans; Male; Multicenter Studies as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Salicylates

Choline magnesium trisalicylate (3.0 g/day) and enteric-coated acetylsalicylic acid (3.0 g/day) have been compared in a double-blind, crossover study on 19 patients with rheumatoid arthritis using the double-dummy technique. Patients were allocated to receive 3-weeks' treatment with each trial drug in random sequence and were assessed at Weeks-1, 0, 3 and 6. Apart from an unexplained significant improvement in grip strength (p less than 0.01) that occurred in patients on choline magnesium trisalicylate when this followed aspirin but not when it preceded it, there was no significant clinical difference between treatments in any of the clinical parameters of improvement that were measured. There was also no clear difference in the side-effects profile produced by the two drugs, but the number of patients recruited to this study was small.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Aspirin; Choline; Disability Evaluation; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Pain Measurement; Randomized Controlled Trials as Topic; Salicylates

In a multicenter, double blind, parallel group study, 233 patients with classical or definite rheumatoid arthritis (RA) were randomized to 12 weeks of either salsalate (salicylsalicylic acid, nonacetylated salicylate) or aspirin following disease flare. One hundred-fifty patients completed, 83 taking salsalate and 67 taking aspirin. Patients received initial doses of 3 g/day of salsalate or 3.6 g/day of aspirin. Doses were adjusted during the first 5 weeks for efficacy and tolerance. Both treatments were equally effective as measured by all the usual variables, but there was a higher incidence of severe gastrointestinal problems among patients taking aspirin. Thus, this study demonstrated that the acetyl group of aspirin does not enhance the antiinflammatory efficacy of salicylic acid in RA.

Topics: Acetylation; Adult; Aged; Arthritis, Rheumatoid; Aspirin; Double-Blind Method; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Prospective Studies; Random Allocation; Salicylates; Therapeutic Equivalency

Tinnitus or subjective hearing loss, or both, were reported by 61 of 134 (45%) patients with rheumatoid arthritis (RA) taking regular salicylates and by 73 of 182 (40%) untreated healthy subjects. In the patients with RA mean salicylate levels were not higher in those with tinnitus than in those without tinnitus, but levels were significantly higher in those with subjective hearing loss than in those with no symptoms. Twenty five per cent of the patients with RA had tinnitus or subjective hearing loss with salicylate levels less than 1.42 mmol/l. Audiometric responses in 31 patients correlated poorly with symptoms. Tinnitus and subjective hearing loss may be too non-specific to be reliable as tools for adjusting the salicylate level into the therapeutic range.

Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Aspirin; Audiometry; Clinical Trials as Topic; Hearing Loss, Sensorineural; Humans; Middle Aged; Salicylates; Tinnitus

In a 24-week multicenter double-blind clinical trial, efficacy and safety of the novel nonsteroidal anti-inflammatory drug imidazole salicylate (750 mg t.i.d. per os) and ibuprofen (600 mg t.i.d. per os) were compared in 60 patients with classical or definite rheumatoid arthritis, randomly assigned to one of the two treatment groups. The patients improved significantly with both treatments in all the clinical parameters examined such as the duration of morning stiffness, grip strength of both hands, Ritchie's articular index and severity of joint pain. The systemic tolerability, assessed by hematological, liver and kidney function tests was excellent with both treatments. The incidence of side effects was overall fairly low with both drugs, and lower in the group treated with imidazole salicylate (23% vs. 33%).

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Ibuprofen; Imidazoles; Male; Middle Aged; Random Allocation; Salicylates

The efficacy and tolerability of diflunisal (500 mg orally, twice daily) and piroxicam (20 mg orally, once daily) were compared in a 12-week open-label study in 44 patients with active rheumatoid arthritis. Both medications were equally effective and generally well tolerated. No significant differences were found between drug groups. Both groups showed statistically significant improvement in the overall number of swollen and tender joints, painful joint count, and the patients' assessment of pain and disease severity. Two (9%) of 23 patients in the diflunisal group and one (5%) of 21 patients in the piroxicam group reported adverse effects. Only one patient withdrew from the study because of side effects (lightheadedness during use of diflunisal). It is concluded that both diflunisal and piroxicam are highly effective and generally well tolerated in the management of rheumatoid arthritis.

Topics: Adult; Aged; Arthritis, Rheumatoid; Clinical Trials as Topic; Diflunisal; Female; Humans; Male; Middle Aged; Pain; Piroxicam; Prospective Studies; Random Allocation; Salicylates

Previous studies of combinations of nonsteroidal drugs used in the treatment of rheumatoid arthritis (RA) have yielded conflicting results. We used standard methods to measure disease activity and high pressure liquid chromatography to measure plasma drug concentrations. We used doses of choline magnesium trisalicylate, adjusted to achieve therapeutic serum salicylate concentrations, and naproxen in a randomized, double-blind, placebo-controlled cross-over study of full dose trisalicylate (CMT), full dose naproxen (N), full dose of both (CMT-N), and half dose of both (cmt-n) to examine their relative efficacy and toxicity in treating RA. CMT-N was statistically superior to all other treatments in only 1 of 12 efficacy variables, but was equal to N and better than CMT or cmt-n for 7 variables. There were minimal differences among treatments for the other 4 efficacy variables. The mean percentage difference for the efficacy variables between CMT-N and N was 3%, between CMT-N and CMT was 10.6%, and between CMT-N and cmt-n was 10.5%. Thirteen percent of patients manifested toxic reactions during the initial open dose-adjustment salicylate run-in phase. During the double-blind phases of the study, CMT-N was more toxic than N, CMT, or cmt-n (7.5% versus 3.4%, 1.8%, and 3.7%, respectively). Tinnitus was more common when full-dose CMT was used; N (N or CMT-N) was associated with increased skin toxicity. Gastrointestinal complaints were equally common with all regimens. CMT-N, although sometimes statistically superior to CMT, N, or cmt-n, showed no clinically important additive or synergistic effect versus N or CMT alone.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Choline; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Naproxen; Random Allocation; Salicylates

The efficacy and safety of the nonsteroidal anti-inflammatory drugs imidazole.2-hydroxybenzoate and sulindac were compared in 30 patients with classical or definite rheumatoid arthritis. The trial was designed as a randomized parallel-group study comprising 15 patients given imidazole.2-hydroxybenzoate and 15 given sulindac orally for 28 days. Patients in both groups improved significantly in almost all of the variables evaluated. Imidazole.2-hydroxybenzoate was more effective than sulindac on Ritchie's articular index, left hand proximal interphalangeal joint circumference, erythrocyte sedimentation rate, and C-reactive protein. The incidence of side effects was significantly higher in patients treated with sulindac.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Blood Sedimentation; C-Reactive Protein; Clinical Trials as Topic; Female; Humans; Imidazoles; Indenes; Male; Middle Aged; Pain; Random Allocation; Salicylates; Sulindac

Diflunisal, a nonacetylated salicylate preparation with a prolonged duration of action, was compared with ibuprofen for the treatment of rheumatoid arthritis in a multicenter trial comprising 210 patients. Diflunisal was administered twice a day (500 to 750 mg/day) and ibuprofen was administered four times a day (1,600 to 2,400 mg/day). To maintain double-blind conditions, all patients ostensibly followed the same regimen, ingesting their assigned drug and a matching placebo of their nonassigned drug. Disease activity assessments and laboratory tests were done periodically throughout the 12 weeks of the study, and results were compared with pretreatment findings. Efficacy evaluations in 187 patients showed that both treatments were similarly efficacious. Safety and tolerability also were similar in the two groups. Diflunisal, however, offers a more acceptable BID treatment schedule.

Topics: Adult; Aged; Arthritis, Rheumatoid; Clinical Trials as Topic; Diflunisal; Double-Blind Method; Drug Administration Schedule; Drug Tolerance; Humans; Ibuprofen; Middle Aged; Random Allocation; Salicylates; Time Factors

A multicenter, open-label clinical trial evaluated the efficacy and tolerability of diflunisal given twice daily and aspirin given four times daily in the long-term treatment of patients with rheumatoid arthritis. Patients who successfully completed a 12-week, double-blind, parallel study comparing diflunisal (500 to 750 mg daily) with aspirin (2.6 to 3.9 gm daily) continued on the same medication in a 40-week, open-label segment of the study. The dosage of diflunisal could be increased to a maximum of 1 gm daily during the open-label phase. Both regimens were effective during the 40-week study. Diflunisal was better tolerated than aspirin as judged by the overall incidence of clinical adverse experiences. Patients treated with diflunisal had significantly fewer adverse experiences involving the digestive system and organs of special sense than did those treated with aspirin.

Topics: Adult; Aged; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Diflunisal; Double-Blind Method; Drug Tolerance; Female; Humans; Male; Middle Aged; Random Allocation; Salicylates; Time Factors

A 4-week, double-blind, controlled multi-centre study was carried out in 235 patients with active rheumatoid arthritis to compare the efficacy and tolerance of 500 mg or 1000 mg diflunisal per day administered once daily, in the evening, or in divided, twice daily dosage. The results showed that diflunisal given once daily was at least as effective as diflunisal given twice daily. Day pain, morning stiffness, average grip strength and erythrocyte sedimentation rate improved similarly in both groups. Significant differences favouring the once-daily regimen were observed for improvement in night pain, Ritchie index and overall assessments by patient and investigator. Adverse experiences were slightly more common in patients taking diflunisal once daily (24% vs 19%) but this difference was not significant. It is concluded, therefore, that diflunisal once-a-day is an alternative regimen for the treatment of rheumatoid arthritis. It is at least as effective as the twice-daily regimen and may provide additional convenience to the patient and potential enhancement of compliance.

Topics: Adolescent; Adult; Aged; Arthritis, Rheumatoid; Clinical Trials as Topic; Diflunisal; Double-Blind Method; Drug Administration Schedule; Drug Eruptions; Drug Tolerance; Female; Gastritis; Humans; Male; Melena; Middle Aged; Patient Compliance; Salicylates; Thrombocytopenia

In an open-label trial, 182 patients with common forms of arthritis were treated with 3 gm of salsalate daily (two 750-mg tablets twice daily) for 15 days. Before entering the study, these patients had received a wide variety of antiarthritic medications. Five indices of disease severity (pain, stiffness, joint swelling, limitation of motion, and disability) were evaluated before and after salsalate therapy, the incidence of side effects was tabulated before and after treatment, and patient compliance with the salsalate regimen was assessed. A reduction in disease symptoms was noted in 79% of the treated patients. Median improvement, measured on a summary index, was 47%. The incidence of side effects experienced with previous therapy was reduced by 65% during salsalate administration. Patient compliance with the regimen was greater than 95%. The findings show salsalate to be effective and safe in ameliorating the symptoms of arthritic disease. The convenient twice-daily dosage regimen makes this drug particularly suitable for chronic use.

Topics: Adult; Aged; Arthritis, Rheumatoid; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Osteoarthritis; Salicylates

Twenty-three patients with rheumatoid arthritis were given choline magnesium trisalicylate (CMT) (Trilisate; Adcock-Ingram) in a dose of 1.5 g (3 tablets) twice daily and were followed up for 6 weeks. Nineteen patients completed the study and the data obtianed were subjected to statistical analysis. There was a statistically significant improvement in the indices of inflammation. Seven patients developed tinnitus, which resolved on reduction of the dose to 1 g (2 tablets) twice daily. Four patients developed pruritus and minor gastro-intestinal side-effects were present in 3 patients, but all these side-effects were transient and no change in therapy was necessary.

Topics: Adult; Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Choline; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Salicylates

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Clinical Trials as Topic; Drug Evaluation; Gold; Humans; Research Design; Salicylates

The results of three double-blind, multicentre trials are reviewed to compare the efficacy of acetysalicylic acid (ASA) and a non-acetylated salicylate, choline magnesium trisalicylate (CMT), in the treatment of rheumatoid arthritis. In each trial, patients were randomly assigned to receive comparable doses of salicylate as either ASA or CMT. Mean values for clinical indicators of rheumatoid arthritis (number of painful joints, articular index, number of swollen joints, swelling index, duration of morning stiffness) showed similar or greater improvement among groups of patients receiving CMT, compared to those receiving ASA. In addition, the incidence of gastro-intestinal side-effects was lower among patients receiving CMT.

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Choline; Clinical Trials as Topic; Double-Blind Method; Humans; Random Allocation; Salicylates

Topics: Adult; Aged; Arthritis, Rheumatoid; Clinical Trials as Topic; Diflunisal; Double-Blind Method; Female; Humans; Male; Middle Aged; Salicylates

Diflunisal, a new nonsteroidal, Aspirin-like anti-inflammatory agent has been compared with Ibuprofen und Placebo in a six-week double-blind randomized crossover controlled study in 24 patients with rheumatoid arthritis. There was a statistically significant improvement for all variables while on Diflunisal and Ibuprofen. Adverse reactions were seen in each of the three treatment groups. Clinical determinations and physiological examinations gave no indication of any potential harm from therapy with Diflunisal.

Topics: Aged; Arthritis, Rheumatoid; Clinical Trials as Topic; Diflunisal; Double-Blind Method; Humans; Ibuprofen; Middle Aged; Salicylates

A randomized, double-blind trial was carried out in 47 hospital out-patients, with classical rheumatoid arthritis, to compare the efficacy and tolerance of diflunisal with that of naproxen. After an initial one week washout period the patients received diflunisal 1000 mg daily or naproxen 750 mg daily using a double placebo, crossover method. Each drug was administered for a three week period separated by a one week between treatment washout. With both drugs there was an improvement in objective and subjective assessments of response indicating that they each had an effective anti-inflammatory action. Diflunisal produced a significantly greater improvement in evening pain (p = 0.03), morning stiffness (p = 0.01) and the average total grip strength (p = 0.05). Nearly 60% of patients preferred diflunisal to naproxen but this was not of statistical significance. Frequency and severity of side-effects were similar. The similarity of diflunisal to aspirin in urate lowering is commented upon.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Clinical Trials as Topic; Diflunisal; Double-Blind Method; Female; Humans; Male; Middle Aged; Naproxen; Random Allocation; Salicylates

Topics: Adult; Arthritis, Rheumatoid; Clinical Trials as Topic; Diflunisal; Female; Humans; Male; Middle Aged; Osteoarthritis; Salicylates

Topics: Adult; Arthritis, Rheumatoid; Clinical Trials as Topic; Diflunisal; Double-Blind Method; Female; Humans; Male; Naproxen; Salicylates

Topics: Adult; Aged; Arthritis, Rheumatoid; Drug Combinations; Female; Humans; Humic Substances; Joint Diseases; Joints; Male; Middle Aged; Salicylates

Topics: Arthritis, Rheumatoid; Clinical Trials as Topic; Diflunisal; Double-Blind Method; Female; Humans; Male; Middle Aged; Salicylates

Both diflunisal (750 mg/day) and ibuprofen (1600 mg/day) were shown to be superior to placebo in the treatment of rheumatoid arthritis in a double-blind cross-over trial. Neither drug affected lymphocyte transformation to plant mitogens. Diflunisal scored better than ibuprofen at the dose levels chosen but the differences did not reach significance.

Topics: Arthritis, Rheumatoid; Clinical Trials as Topic; Diflunisal; Double-Blind Method; Female; Humans; Ibuprofen; Lymphocytes; Male; Random Allocation; Salicylates

In an eight-week double-blind study comparing the new long-acting aspirin derivative, diflunisal, in doses up to 1 g/day with aspirin in doses up to 4 g/day in 16 patients with classical or definite rheumatoid arthritis, diflunisal was more effective in reducing the total articular index (Ritchie) and erythrocyte sedimentation rate and in increasing grip strength. Diflunisal had an earlier effect on erythrocyte sedimentation rate than antiinflammatory doses of aspirin. Patients on diflunisal experienced fewer side effects than patients on aspirin. Ten patients with rheumatoid arthritis who previously participated in the eight-week study comparing diflunisal to aspirin (five patients from each group) were continued on 1 g diflunisal per day for six months. The efficacy of diflunisal therapy persisted during a six-month period, and there were no side effects. The switchover from 4g aspirin to 1g diflunisal a day was accompanied by further improvement in the Ritchie total score, erythrocyte sedimentation rate, and grip strength and by disappearance of side effects. Diflunisal 1 g/day proved to be an efficient and well-tolerated drug in patients with rheumatoid arthritis.

Topics: Aged; Arthritis, Rheumatoid; Aspirin; Blood Sedimentation; Clinical Trials as Topic; Diflunisal; Double-Blind Method; Female; Humans; Male; Middle Aged; Salicylates; Time Factors

Diflunisal (Dolobid; Frosst-MSD) is an acetylsalicylic acid (ASA) derivative and has potential advantages over ASA, e.g. a longer half-life, higher potency and better tolerance. It has been shown to be effective as an analgesic in a variety of conditions. In a 12-week double-blind controlled trial diflunisal was compared with naproxen (Naprosyn; Syntex) in patients with rheumatoid arthritis. Suitable efficacy data were only available at week 4 owing to a number of withdrawals from the naproxen group. Both drugs, however, produced improvement in all the indices measured. At week 12 the initial improvement in the diflunisal group was maintained. Side-effects from diflunisal were mainly related to the gastro-intestinal tract but were not of serious nature; tinnitus and deafness did not occur. Diflunisal is an effective analgesic and also has anit-inflammatory action. It is a useful addition to the range of aspirin derivatives available for the treatment of rheumatoid arthritis.

Topics: Adult; Aged; Arthritis, Rheumatoid; Clinical Trials as Topic; Diflunisal; Double-Blind Method; Female; Humans; Male; Middle Aged; Naproxen; Random Allocation; Salicylates

A double-blind comparison of the clinical efficacy and tolerance of varying doses of diflunisal (DFS) and acetylsalicylic acid (ASA) was carried out in 15 patients with rheumatoid arthritis who were given no other antirheumatic medication. An effort was made to select appropriate anamnestic, functional and sociofunctional tests and to optimize their validity by careful measurements performed by the same specialized physiotherapist and occupational therapist. In addition, the serum concentration of DFS and salicylic acid were monitored by high-pressure liquid chromatography. The therapeutic effects of DFS was at least as good as that of ASA. Moreover, DFS was better tolerated; all 7 patients on DFS could sustain the maximum dose (1g) of this drug, while that of ASA (4g) was tolerated by only one of 8 patients. All these experienced side effects, necessitating drug withdrawal in 3 cases, one being a serious hepatotoxic reaction. DFS treatment, on the other hand, was associated with only one minor side effect. The side effect difference was statistically significant (p less than 0.01). The analyses of drug concentrations in serum verified that all patients were exposed to DFS and ASA as planned, adding safety to the judgement of the therapeutic effects. The findings support the view that the novel salicylic acid derivative DFS may offer a therapeutic advantage in the treatment of rheumatoid arthritis; it seems to have at least the same therapeutic effect as ASA an may be better tolerated.

Topics: Adult; Aged; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Diflunisal; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Salicylates

Diflunisal, a new difluorophenyl derivative of salicylic acid was compared with acetylsalicylic acid in 16 patients with rheumatoid arthritis in a double-blind study during 8 weeks. All patients who had taken Diflunisal and showed a good therapeutic response were treated with Diflunisal over additional 24 weeks. Diflunisal showed a statistically significant better efficacy than acetylsalicylic acid in all subjective and objective parameters. Above all the grip strength improved greatly in the Diflunisal group. In the patients who were included in the following 24 week study with Diflunisal the successful treatment could be continued through the whole study period. Day-pain and morning stiffness showed statistically significant improvement. Side effects appeared during the double-blind study only in the acetylsalicylic acid group. The results of the study showed Diflunisal in an average dosage of 500 to 1000 mg per day to be a useful drug in the treatment of rheumatoid arthritis not least due to the negligible side effects.

Topics: Adult; Aged; Arthritis, Rheumatoid; Aspirin; Diflunisal; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Salicylates

Disalcid, a salicylic acid pro-drug, was administered for 3 months to eighteen rheumatoid arthritis patients, with monitoring of clinical response, side-effects and laboratory changes. The drug produced a satisfactory to excellent response in fourteen patients and was unsatisfactory in four. Gastric side-effects occurred in three patients and allergic reaction in one. Serum salicylic acid concentrations were adequately maintained between 15 to 25 mg/100 ml. Funduscopic monitoring revealed one retinal defect in a patient with hypertension. Laboratory examinations, blood chemistry and urine analyses remained within normal limits during the 12-week trial.

Topics: Adult; Arthritis, Rheumatoid; Clinical Trials as Topic; Female; Humans; Long-Term Care; Male; Middle Aged; Salicylates

Twenty-three patients with rheumatoid arthritis on orthodox first-line anti-inflammatory treatment plus homeopathy were compared wtih a similar group of twenty-three patients on orthodox first-line treatment plus an inert preparation. There was a significant improvement in subjective pain, articular index, stiffness and grip strength in those patients receiving homoeopathic remedies whereas there was no significant change in the patients who received placebo. Two physicians were involved in prescribing for the patients and there were no significant differences in the results which they obtained. No side effects were observed with the homoeopathic remedies.

Topics: Adult; Aged; Arthritis, Rheumatoid; Clinical Trials as Topic; Double-Blind Method; Female; Homeopathy; Humans; Male; Middle Aged; Placebos; Salicylates

Topics: Adult; Aged; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Diflunisal; Double-Blind Method; Humans; Middle Aged; Salicylates

The anti-inflammamtory effectiveness and side-effects of magnesium dithiosalicylate were compared to aspirin in a 3-month, parallel, double-blind trial in 40 patients suffering from active rheumatoid arthritis. The results showed that 3 g magnesium dithiosalicylate daily had anti-inflammatory properties similar to those of 3 g aspirin daily in rheumatoid arthritis. A statistically significant change in morning stiffness, number of tender joints, pain score and erythrocyte sedimentation rate was observed in the magnesium dithiosalicylate group. In the magnesium dithiosalicylate group, 8 patients had to be withdrawn from the trial because of serious side-effects compared to 5 in the aspirin group. Gastro-intestinal intolerance occurred as frequently in both treatment groups. Hypersensitivity to magnesium dithiosalicylate was a serious problem and the reason for withdrawal in 4 cases. The high frequency of side-effects to magnesium dithiosalicylate makes this drug unacceptable for treatment of rheumatoid arthritis at the present time. Further pharmacological studies might reveal new derivatives which are as effective but with less side-effects. The anti-inflammatory activity of magnesium dithiosalicylate resembled that observed with gold and penicillamine. The fact that all these drugs have a sulphhydril group in common is stressed.

Topics: Adult; Aged; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Salicylates

A double-blind study compared choline magnesium trisalicylate (Trilisate tablets, Purdue Frederick) (CMT) and ibuprofen (IPF) in the treatment of rheumatoid arthritis. The seven-week trial in 134 ambulatory patients, of whom 68 received CMT and 66 received IPF, was conducted as a multicentre study. Both CMT and IPF were highly effective in reducing significantly all symptoms that had worsened following the discontinuance of previous therapy. The anti-inflammatory effect of CMT produced a significantly (P less than 0.05) greater reduction in the number of swollen joints, compared to IPF, in patients completing all required visits. Further clinical study will be required before the full clinical significance of this observation emerges. Incidence of adverse effects for each drug did not differ significantly.

Topics: Adult; Aged; Arthritis, Rheumatoid; Choline; Female; Humans; Ibuprofen; Male; Middle Aged; Salicylates

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Antimalarials; Arthritis, Rheumatoid; Clinical Trials as Topic; Gold; Humans; Immunosuppressive Agents; Patient Education as Topic; Penicillamine; Physical Therapy Modalities; Pregnanes; Salicylates

A multicentre double-blind comparison of choline magnesium trisalicylate (CMT) and acetylsalicylic acid (ACSA) compared the two medications for seven weeks in rheumatoid arthritis patients. Investigators measured the number of painful and swollen joints and the duration of morning stiffness, and assessed the overall condition of each patient. Both medications were highly effective in significantly reducing the severity of symptoms flaring after interruption of prior therapy. CMT achieved a greater reduction in the number of swollen joints than did ACSA (P less than 0.05). The incidence of adverse side-effects per patient was significantly less with CMT (P less than 0.05) (ACSA 32.1%; CMT, 16.3%. A larger percentage of ACSA patients (50.8%) reported adverse side-effects than did CMT patients 28.4%) (P less than 0.02).

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Aspirin; Choline; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Salicylates

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Clinical Trials as Topic; Diethylamines; Drug Combinations; Drug Evaluation; Esters; Female; Gels; Heparin; Humans; Male; Middle Aged; Nicotinic Acids; Salicylates

1 This was a double-blind crossover trial of ibuprofen and soluble aspirin against each drug alone and against placebo in patients with rheumatoid arthritis. Two dosage regimes were tested. 2 A weak clinical additive effect was demonstrated between soluble aspirin and ibuprofen in patients with rheumatoid arthritis using moderate (1600 mg ibuprofen and 3.6 g aspirin daily) but not low (800 mg ibuprofen and 2.4 g aspirin daily) dosages of both drugs. 3 A significant correlation between clinical efficacy and serum ibuprofen but not salicylate level was found in the single drug periods of the trial. 4 No consistent effect of ibuprofen administration on serum salicylate levels was found. 5 Concurrent salicylate administration produced significant lowering of serum ibuprofen levels without affecting elimination half-lives of the drug.

Topics: Adult; Aged; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Double-Blind Method; Drug Combinations; Female; Humans; Ibuprofen; Male; Middle Aged; Salicylates; Time Factors

Topics: Acetanilides; Adult; Aged; Arthritis, Rheumatoid; Aspirin; Cervical Vertebrae; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Middle Aged; Salicylates

This paper reports the results of a pilot study in which 41 patients with rheumatoid arthritis were treated with high doses of salicylate, 3.9 g per day, and the results compared with a further 54 similar patients treated with homoeopathy. Both groups were compared with 100 patients who received placebo. 2 The patients who received homoeopathy did better than those who received salicylate. The design of the trial was such, however, that it was not possible to distinguish between the effects due to the physicians and the effects due to the drugs and a further trial is planned to elucidate this point. 3 Patients on homoeopathic treatment did not experience toxic effects.

Topics: Adult; Arthritis, Rheumatoid; Clinical Trials as Topic; Female; Homeopathy; Humans; Male; Middle Aged; Salicylates; Time Factors

Thirty patients with rheumatoid arthritis were randomly assigned to two groups: aspirin and placebo. Aspirin group subjects received five grain ASA capsules and placebo group subjects received lactose placebo for seven days. Blood salicylate level (BSL) and audiological evaluations were performed on Days 0, 3 and 7. BSLs never exceeded 21 mg/100 ml. BSLs during the seven days varied only slightly among aspirin group subjects but dropped consistently in the placebo group. Intra-subject comparison of scores on low versus high BSL days indicated significant differences between mean speech reception thresholds (SRT) scores and pure-tone air-conduction thresholds at all test frequencies for both groups, except at 2000 Hz for the aspirin group. Inter-group differences occurred on SRT and high-frequency pure-tone thresholds. The results indicate that moderate BSLs adversely affect hearing ability. These adverse effects appear to be temporary.

Topics: Adult; Aged; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Drug Evaluation; Female; Hearing; Hearing Tests; Humans; Male; Middle Aged; Placebos; Salicylates

A short-term, double-blind, placebo-controlled crossover study was completed in 15 patients with classical or definite rheumatoid arthritis to compare the antirheumatic activity of salsalate (3 g/day) with placebo and indomethacin (75 mg/day). Subjective and objective assessments showed that both salsalate and indomethacin were significantly superior to placebo. Grip strength was not improved by either of the drugs. Patient preference was in favour of indomethacin, but the difference between it and salsalate was insignificant.

Topics: Adult; Aged; Arthritis, Rheumatoid; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Indomethacin; Male; Middle Aged; Placebos; Salicylates

A single-blind non-crossover method for assessing the potential effectiveness of antirheumatic drugs has been described. The method employs entirely subjective indices and incorporates a daily pain chart for measuring the pain response over the duration of the trial. In addition, the mean number of days withdrawn and patients' satisfaction rating are measured. The statistical method can correct for initial imbalances between groups and allows for the valid comparison of drugs from separate trials. Ten antirheumatic medications were evaluated using this technique in 684 patients with rheumatoid arthritis, and the results are in agreement with those of previous studies using standard clinical methods. The new method is simple, rapid in performance, economical in terms of cost and time, and has been shown to be sensitive and reproducible. The results indicate that there are no significant differences in efficacy between the currently available non-steroidal, anti-inflammatory analgesic drugs, in the treatment of rheumatoid arthritis.

Topics: Acetaminophen; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Flurbiprofen; Humans; Ibuprofen; Indomethacin; Ketoprofen; Mefenamic Acid; Pain; Phenylacetates; Placebos; Prednisone; Salicylates

Topics: Adult; Aged; Arthritis, Rheumatoid; Chemical Phenomena; Chemistry; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Male; Middle Aged; Salicylates

Topics: Arthritis, Rheumatoid; Aspirin; Biological Availability; Buffers; Clinical Trials as Topic; Humans; Salicylates; Tablets, Enteric-Coated

Benorylate and ibuprofen appear to be useful drugs for pain relief in rheumatoid arthritis but benorylate would appear to have a slightly better effect on the pain score and it improved the grip strength more than the moderate doses of ibuprofen. It could be a most useful drug when gastric problems limit the dose of aspirin or of other analgesics.

Topics: Arthritis, Rheumatoid; Clinical Trials as Topic; Hand; Humans; Ibuprofen; Pain; Propionates; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Clinical Trials as Topic; Female; Humans; Indomethacin; Male; Middle Aged; Osteoarthritis; Salicylates

Topics: Adult; Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Clinical Trials as Topic; Diet, Reducing; Drug Interactions; Female; Humans; Imidazoles; Indoles; Indomethacin; Male; Middle Aged; Obesity; Osteoarthritis; Placebos; Salicylates; Time Factors

64 patients with rheumatoid arthritis (R.A.) entered the trial: 40 of them still remain on medication; 28 have so far completed 2 years; 23, 3 years; 12, 4 years using D-2-(6'-methoxy-2'-naphthyl)-propionic acid (naproxen) as the principal anti-inflammatory agent. Tolerance has been good: side effects or complaints, when reported, were mild and transient in nature. Close monitoring of a range of biochemical values by sequential laboratory studies has not revealed naproxen to have many adverse effects. After two years of daily continuous naproxen administration, 19 volunteer patients were subjected to a short-term double-blind cross-over placebo experiment. The results were in favor of a continued therapeutic efficacy of naproxen. The possible gastrointestinal bleeding found in the majority of anti-inflammatory drugs has been studied on 12 volunteers using 51-Cr. Naproxen exhibited a mean G.I. blood loss comparable to placebo or to physiological blood loss in normal volunteers. The conclusion drawn is that naproxen shows a good therapeutic index.

Topics: Adult; Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Chromium Radioisotopes; Clinical Trials as Topic; Drug Evaluation; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Long-Term Care; Male; Middle Aged; Naphthaleneacetic Acids; Naproxen; Placebos; Salicylates

The range of plateau serum salicylate concentrations was 4.4 to 33 mg/100 ml in patients with rheumatoid arthritis after they were treated with 50 mg/kg of aspirin daily for 5 days. Individual plateau serum levels correlated better with urinary excretion rates of the metabolite, salicylurate (whose maximum production is capacity-limited), than with total urinary excretion of salicylates. These observations suggest that large intersubject variations in plateau serum salicylate levels are determined, at least in part, by similar differences in the maximum rates of capacity-limited metabolic reactions. For optimal therapeutic responses, individualization of aspirin dosage by following serum salicylate levels is recommended.

Topics: Administration, Oral; Adult; Aged; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Female; Humans; Injections, Intravenous; Male; Middle Aged; Salicylates; Time Factors

Topics: Adolescent; Adult; Aged; Agglutination Tests; Alpha-Globulins; Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Blood Sedimentation; Calcium; Clinical Trials as Topic; Ergocalciferols; Female; Hemoglobins; Humans; Male; Middle Aged; Placebos; Salicylates; Sheep; Time Factors

Topics: Acetanilides; Acetates; Analgesics; Arthritis, Rheumatoid; Aspirin; Blood Sedimentation; Clinical Trials as Topic; Female; Humans; Inflammation; Male; Middle Aged; Pain; Salicylates

Topics: Acetanilides; Acetates; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Humans; Salicylates; Tinnitus

In a double-blind between-patient study of aspirin and benorylate carried out in 72 outpatients with rheumatoid arthritis, benorylate 4 g twice daily was shown to be an effective analgesic and anti-inflammatory drug, its effects being indistinguishable from those of aspirin 1.2 g four times daily. Compared with the pretreatment values both drugs produced a statistically significant improvement (P < 0.01) in functional grade, overall pain, articular index, and grip strength at the end of the first and second weeks. The overall incidence of side effects was less with benorylate, though this difference was not significant at the 5% level.

Topics: Adolescent; Adult; Aged; Analgesics; Aniline Compounds; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Movement; Pain; Phenols; Physical Examination; Salicylates; Tinnitus

Topics: Arthritis, Rheumatoid; Benzoates; Brachial Plexus Neuritis; Clinical Trials as Topic; Drug Combinations; Glycols; Humans; Nicotinic Acids; Ointments; Osteoarthritis; Rheumatic Diseases; Salicylates; Skin Temperature; Thermography

Topics: Action Potentials; Adult; Aged; Analgesics; Arthritis, Rheumatoid; Audiometry; Clinical Trials as Topic; Electromyography; Female; Humans; Irritants; Male; Methane; Middle Aged; Muscle Cramp; Osteoarthritis; Pain; Placebos; Salicylates; Sensation

Topics: Arthritis, Rheumatoid; Clinical Trials as Topic; Humans; Rest; Salicylates

Topics: Aminobenzoates; Arthritis, Rheumatoid; Aspirin; Blood Coagulation; Buffers; Dyspepsia; Gastritis; Gastrointestinal Hemorrhage; Humans; Intestinal Absorption; Kidney Diseases; Placebos; Salicylates; Sodium Salicylate; Tablets, Enteric-Coated

Topics: Aluminum; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Delayed-Action Preparations; Humans; Oxides; Polymers; Salicylates; Sodium; Tablets, Enteric-Coated

Topics: Adolescent; Adult; Aged; Ambulatory Care; Arthritis, Rheumatoid; Clinical Trials as Topic; Dimethyl Sulfoxide; Female; Follow-Up Studies; Humans; Male; Methods; Middle Aged; Ointments; Pharmaceutic Aids; Placebos; Salicylates; Urticaria

Topics: Acetaminophen; Analgesics; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspartate Aminotransferases; Aspirin; Clinical Trials as Topic; Female; Hand; Humans; Isocitrate Dehydrogenase; Male; Placebos; Salicylates; Thiazoles

Topics: Arthritis, Rheumatoid; Circadian Rhythm; Clinical Trials as Topic; Finger Joint; Fingers; Humans; Manometry; Methadone; Methylprednisolone; Movement; Pain; Placebos; Polymers; Salicylates

Topics: Acute Disease; Arthritis, Rheumatoid; Bone Diseases; Clinical Trials as Topic; Drug Synergism; Humans; Osteoarthritis; Osteochondritis; Osteoporosis; Pain; Penicillins; Placebos; Pleurisy; Prednisolone; Rheumatic Diseases; Rheumatic Fever; Salicylates; Spondylitis

Topics: Adult; Aged; Ambulatory Care; Arthritis, Rheumatoid; Comprehensive Health Care; Female; Humans; Long-Term Care; Male; Middle Aged; Physical Therapy Modalities; Salicylates; Socioeconomic Factors

Topics: Acetaminophen; Anthropometry; Arthritis, Rheumatoid; Clinical Trials as Topic; Humans; Placebos; Prednisone; Salicylates

Topics: Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Delayed-Action Preparations; Female; Humans; Male; Salicylates

Topics: Adult; Arthritis, Rheumatoid; Chronic Disease; Female; Gold; Humans; Indomethacin; Male; Middle Aged; Prednisolone; Salicylamides; Salicylates

Topics: Abdomen, Acute; Acetaminophen; Aluminum; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspartate Aminotransferases; Aspirin; Clinical Trials as Topic; Codeine; Diarrhea; Female; Flufenamic Acid; Fluorine; Humans; Mefenamic Acid; ortho-Aminobenzoates; Phenylbutazone; Phosphates; Placebos; Salicylates; Stomatitis

To investigate the relative risk of cancer development in rheumatoid arthritis (RA) patients in Greece after taking into consideration treatment modalities. The present analysis used data on the medical history of 26 331 participants in the Greek arm of the European Prospective Investigation into Cancer and Nutrition that were collected at enrollment and thereafter during active follow-up. A history of RA and of drug treatment for the disease, as reported at baseline examination, was linked to cases of cancer reported during follow-up. A total of 91 (9.9%) patients with RA developed a cancer compared with 1542 (6.1%) patients without RA. The overall hazard ratios of all cancers increased 25% [95% confidence interval (CI): 1-54] among participants with prevalent RA, and almost all the site-specific incident cancer sites considered had rate ratios above unity. In terms of the contribution of RA medication, the hazard ratios of patients treated with salicylates was close to unity (1.07, 95% CI: 0.69-1.65), whereas those who were not treated with salicylates had a 31% (95% CI: 3-67) increased risk for cancer incidence compared with those without RA at baseline. RA patients have excess cancer risk because of either underlying complex disease pathways or treatment agents targeting immune function. Administration of salicylates appears to reduce the risk of developing malignancies.

Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Carcinogenesis; Cyclooxygenase Inhibitors; Female; Follow-Up Studies; Greece; Humans; Incidence; Male; Middle Aged; Neoplasms; Prevalence; Proportional Hazards Models; Prospective Studies; Risk Factors; Salicylates; Young Adult

Methyl salicylate 2-O-β-D-lactoside (MSL) is a derivative of natural salicylate isolated from Gaultheria yunnanensis (Franch.) Rehder, which is widely used for treating rheumatoid arthritis (RA), swelling and pain. The aim of the present study was to investigate the effect of MSL on the progression of adjuvant-induced arthritis (AIA) in rat in vivo and explore the anti-inflammatory effects and mechanism of MSL in lipopolysaccharide (LPS)-treated murine macrophages RAW264.7 cells in vitro. Our results showed that MSL significantly inhibited the arthritis progression in AIA rats, decreasing the right hind paw swelling and ankle diameter, attenuating histopathological changes and suppressing the plasma levels of TNF-α and IL-1β in AIA rats. Besides, MSL had potent anti-inflammatory effects on the LPS-activated RAW264.7. MSL dose-dependently inhibited the activity of COX-1, and COX-2. Moreover, MSL prominently inhibited LPS-induced activation of MAPK in RAW264.7 cells by blocking phosphorylation of p38 and ERK. Our study suggests that MSL may be effective in the treatment of inflammatory diseases by inhibiting the pro-inflammatory cytokine production and regulating the MAPK signal pathway.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Cell Line; Cyclooxygenase 1; Cyclooxygenase 2; Disease Progression; Gaultheria; Humans; Interleukin-1beta; Lactose; Lipopolysaccharides; Macrophages; Male; MAP Kinase Signaling System; Mice; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Rats; Rats, Sprague-Dawley; Salicylates; Tumor Necrosis Factor-alpha

Rheumatoid arthritis (RA) is an autoimmune disease characterized by pronounced inflammation and leucocyte infiltration in affected joints. Despite significant therapeutic advances, a new targeted approach is needed. Our objective in this work was to investigate the anti-inflammatory effects of the Ras inhibitor farnesylthiosalicylic acid (FTS) on adjuvant-induced arthritis (AIA) in rats, an experimental model for RA. Following AIA induction in Lewis rats by intradermal injection of heat-killed Mycobacterium tuberculosis, rats were treated with either FTS or dexamethasone and assessed daily for paw swelling. Joints were imaged by magnetic resonance imaging and computerized tomography and analysed histologically. The anti-inflammatory effect of FTS was assessed by serum assay of multiple cytokines. After adjuvant injection rats demonstrated paw swelling, leucocyte infiltration, cytokine secretion and activation of Ras-effector pathways. Upon FTS treatment these changes reverted almost to normal. Histopathological analysis revealed that the synovial hyperplasia and leucocyte infiltration observed in the arthritic rats were alleviated by FTS. Periarticular bony erosions were averted. Efficacy of FTS treatment was also demonstrated by inhibition of CD4(+) and CD8(+) T cell proliferation and of interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-17 release. The Ras effectors PI3K, protein kinase B (AKT), p38, and extracellular-regulated kinase (ERK) were significantly attenuated and forkhead box protein 3 (FoxP3) transcription factor, a marker of regulatory T cells, was significantly increased. Thus, FTS possesses significant anti-inflammatory and anti-arthritic properties and accordingly shows promise as a potential therapeutic agent for RA. Its effects are apparently mediated, at least in part, by a decrease in proinflammatory cytokines.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Cytokines; Disease Models, Animal; Farnesol; Inflammation Mediators; Joints; Male; ras GTPase-Activating Proteins; Rats; Salicylates; Signal Transduction; T-Lymphocyte Subsets

Leukocyte recruitment of sites of inflammation and tissue injury involves leukocyte rolling along the endothelial wall, followed by firm adherence of the leukocyte, and finally transmigration of the leukocyte across cell junctions into the underlying tissue. The initial rolling step is mediated by the interaction of leukocyte glycoproteins containing active moieties such as sialyl Lewisx (sLex) with P-selectin expressed on endothelial cells. Consequently, inhibition of this interaction by means of a small molecule P-selectin antagonist is an attractive strategy for the treatment of inflammatory diseases such as arthritis. High-throughput screening of the Wyeth chemical library identified the quinoline salicylic acid class of compounds (1) as antagonists of P-selectin, with potency in in vitro and cell-based assays far superior to that of sLex. Through iterative medicinal chemistry, we identified analogues with improved P-selectin activity, decreased inhibition of dihydrooratate dehydrogenase, and acceptable CYP profiles. Lead compound 36 was efficacious in the rat AIA model of rheumatoid arthritis.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Arthritis, Rheumatoid; Biological Availability; Cytochrome P-450 Enzyme Inhibitors; Databases, Factual; Edema; Humans; Hydroxyquinolines; In Vitro Techniques; Leukocyte Rolling; Male; P-Selectin; Quinolines; Rats; Rats, Sprague-Dawley; Salicylates; Structure-Activity Relationship

Topics: Arthritis, Rheumatoid; Echocardiography, Transesophageal; Female; Humans; Middle Aged; Mitral Valve; Mitral Valve Prolapse; Platelet Aggregation Inhibitors; Recurrence; Salicylates; Stroke; Treatment Outcome

Dental health professionals are being asked to care for a growing number and range of medically compromised patients living with chronic health problems. Although tooth loss overall has declined in the United States, millions of persons, particularly those of more advanced age, still require treatment for the edentulous condition. Particular challenges are faced when this oral state is combined with a complex medical history. The primary learning objective for this case is to increase your general knowledge of and skills in the dental management of the complete denture patient with a dry mouth.

Topics: Adhesives; Aged; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Dental Care for Chronically Ill; Denture Retention; Denture, Complete; Drug Interactions; Humans; Male; Methotrexate; Mouth, Edentulous; Patient Education as Topic; Prednisone; Salicylates; Xerostomia

It is suggested that some drugs may be converted by inflammatory cells to yield active species. The transformation may be non-enzymatic, although being driven by the enzymatic production of highly reactive species which are normal products of activated leukocytes, such as singlet oxygen, hydrogen peroxide, hypochlorite, hydroxyl radical and nitric oxide. Drugs which may be transformed in this fashion are the anti-rheumatic gold complexes which may be converted either to aurocyanide or to Au(III) complexes by myeloperoxidase in polymorphonuclear leukocytes. Salicylate may also be activated by its oxidation to dihydroxybenzoates although evidence for its transformation is weaker than for the gold complexes.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Biotransformation; Cyanates; Cyanides; Gold; Gold Compounds; Humans; Hydroxylation; Monocytes; Neutrophils; Oxidation-Reduction; Peroxidase; Salicylates

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Humans; Male; Middle Aged; Salicylates

We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently treated with choline magnesium trisalicylate, ibuprofen, naproxen, or a non-NSAID analgesic (control treatment). The apparent systemic clearance of methotrexate was significantly reduced by all three treatments. Trisalicylate and ibuprofen both significantly reduced methotrexate renal clearance, but only the trisalicylate significantly displaced methotrexate from protein, increasing the fraction unbound by 28%. These data show that NSAIDs can affect the disposition of methotrexate, possibly increasing the potential for toxicity and necessitating dosage adjustments. However, large inter-subject variability precludes specific dosage recommendations.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Blood Proteins; Choline; Female; Humans; Ibuprofen; Kidney; Male; Metabolic Clearance Rate; Methotrexate; Middle Aged; Naproxen; Protein Binding; Salicylates

Topics: Alzheimer Disease; Arthritis, Rheumatoid; Disease Susceptibility; Humans; Middle Aged; Risk Factors; Salicylates

A three phase study was designed to define further the sensitivity and specificity of symptomatic salicylate ototoxicity (primarily tinnitus) for serum salicylate concentrations. In phase one 260 patients with osteoarthritis and 112 with rheumatoid arthritis, none taking salicylates, were interviewed about their ear symptoms. Their responses were not significantly different from those of 134 salicylate treated patients with rheumatoid arthritis previously reported. In the second phase 56 patients who were taking salicylates, and who volunteered the complaint of tinnitus, had serum salicylate concentrations measured while symptomatic, and 30 (54%) had concentrations less than 1.3 mmol/l. Few tolerated an upward salicylate dose adjustment. For phase three, 94 patients were found to have a salicylate concentration above 2.2 mmol/l on one or more occasion, and these subjects were interviewed. Fifty two patients (55%) had no tinnitus, and tinnitus correlated with the blood salicylate concentration in only 28 (30%). Audiological evaluation of most of the symptomatic patients was carried out, and results were abnormal in the majority, even in those patients not reporting tinnitus. Symptomatic salicylate ototoxicity is too nonspecific and too insensitive to be a useful indicator of serum salicylate concentration.

Topics: Adult; Aged; Arthritis, Rheumatoid; Hearing Disorders; Humans; Middle Aged; Osteoarthritis; Salicylates; Sensitivity and Specificity; Tinnitus

Diflunisal, a nonsteroidal antiinflammatory drug, is not metabolized to the free salicylate moiety, but yields serum salicylate levels. We describe 2 patients who unexpectedly had toxic range serum salicylate levels while taking diflunisal and aspirin for rheumatoid arthritis. Diflunisal is measured by standard salicylate assays, a fact not widely appreciated. Serum salicylate levels by these assays cannot be used to determine salicylate toxicity when a patient is taking both aspirin and diflunisal. High pressure liquid chromatography can be used to distinguish true salicylate toxicity from interference with diflunisal.

Topics: Arthritis, Rheumatoid; Aspirin; Diflunisal; Female; Humans; Male; Middle Aged; Salicylates

Protein binding of sodium salicylate in synovial fluid and in serum from 23 inpatients with rheumatic diseases were studied, ex vivo, by equilibrium dialysis. Scatchard model with two classes of sites was used as a mathematical tool. At therapeutic concentrations, protein binding of sodium salicylate was significantly higher in serum than in synovial fluid. The ratio of areas under the curves for bound concentrations for synovial fluid to that for serum was 0.867. This difference was attributed to the hypoalbuminemia observed in the synovial fluid; for a given molar ratio of drug to albumin, or in other words, for the same amount of available drug per mole of albumin. The number of sites occupied was the same in the two biological media.

Topics: Adolescent; Adult; Aged; Albumins; Arthritis, Rheumatoid; Binding Sites; Blood Proteins; Female; Humans; Knee Joint; Male; Middle Aged; Models, Biological; Protein Binding; Salicylates; Synovial Fluid

In preliminary investigation of the pharmacokinetics of aspirin in dogs it became apparent that the drug was well absorbed following oral ingestion with food. Multiple dosing appeared to lead to a substantial increase in half-life; a twice daily dosage regimen would, therefore, be adequate for maintenance of therapeutic levels in dogs. The marked variation in pharmacokinetic parameters observed suggested that therapeutic drug monitoring would be benefit in the control of canine inflammatory conditions using aspirin. Therapeutic monitoring of dogs (n = 20) showed that clinical improvement paralleled plasma salicylate concentrations and the therapeutic concentrations so determined were within the range considered therapeutic in humans. No overt gastric irritation was noted in this study over a period of a year which suggests that aspirin can be successfully used to treat canine inflammatory disorders, routine monitoring of plasma salicylate being recommended to ensure therapeutic success.

Topics: Animals; Arthritis, Rheumatoid; Aspirin; Dog Diseases; Dogs; Female; Male; Salicylates

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Azathioprine; Cyclophosphamide; Gold; Humans; Hydroxychloroquine; Methotrexate; Penicillamine; Salicylates; Sulfasalazine

1. The pharmacokinetics of salicylic acid (SA) and its major metabolite salicyluric acid (SU) were studied in nine patients with rheumatoid arthritis following a 900 mg oral dose of acetylsalicylic acid and during 6 weeks of chronic administration of enteric coated aspirin (3,900 mg day). Response to therapy was also monitored. 2. The various pharmacokinetic parameters determined in the study were similar to those observed in other single dose salicylate studies amongst healthy volunteers but were not predictive of salicylate concentration in the chronic dose study. 3. Plasma concentrations of SA (total and unbound) were found to decline significantly over the 6 weeks and plasma SU concentrations increased. 4. During the chronic dosing study, there was a significant increase in the Vmax (total and unbound) for the formation of SU, whilst the Km and SU clearance remained constant. Also, the elimination rate constant (k) for salicylate was not significantly affected. 5. Therapeutic response to salicylate therapy was not significantly affected by the decline in SA concentrations.

Topics: Aged; Arthritis, Rheumatoid; Aspirin; Humans; Hydrogen-Ion Concentration; Middle Aged; Salicylates

The single-dose plasma kinetics of diflunisal was studied in healthy young and old subjects, in patients with rheumatoid arthritis, and in patients with renal failure. The plasma and urine kinetics of the glucuronidated metabolites of diflunisal were studied in the healthy elderly subjects and in the patients with renal failure. In addition, the multiple-dose plasma kinetics of diflunisal was assessed in healthy volunteers and in patients with rheumatoid arthritis. After a single dose of diflunisal the terminal plasma half-life, mean residence time and apparent volume of distribution were higher in elderly subjects than in young adults. No difference was observed in any pharmacokinetic parameter between age-matched healthy subjects and patients with rheumatoid arthritis. The elimination half-life of unchanged diflunisal was correlated with the creatinine clearance (r = +0.89) and its apparent total body clearance exhibited linear dependence on creatinine clearance (r = +0.78). In patients with renal failure, the terminal plasma half-life and mean residence time of diflunisal were prolonged. The renal and apparent total body clearances were lower, the mean apparent volume of distribution was higher and the mean area under the concentration-time curve extrapolated to infinity (AUC) was greater in the renal failure patients than in controls. The plasma concentration of the glucuronidated metabolites rapidly rose to levels above those of unchanged drug in renal patients, whereas they were lower than those of unchanged diflunisal in controls. The AUC (0-96 h) of diflunisal glucuronides in the patients was four-times that in controls, and the terminal elimination half-life of the glucuronides was prolonged in them. The renal excretion and clearance of diflunisal glucuronides were reduced when renal function was impaired. After multiple dosing, the pre-dose steady-state plasma-concentration increased with decreasing creatinine clearance (r = -0.79). When the plasma concentration exceeded 200 mumols.l-1, the elimination half-life was doubled, due to partial saturation of diflunisal conjugation. This finding suggests that lower doses could be used in long-term treatment. Thus, old age and arthritic disease appear to have little influence on the kinetics of diflunisal in the absence of renal functional impairment. Ordinary doses can be given for short term treatment of elderly patients with or without RA. In patients with renal failure, however, reduced doses of di

Topics: Adolescent; Adult; Aged; Aging; Arthritis, Rheumatoid; Diflunisal; Female; Half-Life; Humans; Kidney Failure, Chronic; Male; Middle Aged; Salicylates

Topics: Arthritis, Rheumatoid; Aspirin; Humans; Salicylates

In this solid-phase competitive enzyme-linked immunosorbent assay for alpha 1-acid glycoprotein in serum or urine, antiserum to human alpha 1-acid glycoprotein is incubated with solid-phase-bound alpha 1-acid glycoprotein in the presence of standard or sample. Incubation with second antibody labeled with alkaline phosphatase then follows, before development with substrate. Results obtained correlate well with a fluorescent assay involving the dye Auramine O (r = 0.953) and with radial immunodiffusion (r = 0.921). The present assay covers the range 0.2 to 5 mg/L and 16 samples take 2.5 h to complete. This assay is useful for measuring concentrations of alpha 1-acid glycoprotein in serum and also in urine, for which other assay methods are not sufficiently sensitive.

Topics: Arthritis, Rheumatoid; Benzenesulfonates; Benzophenoneidum; Enzyme-Linked Immunosorbent Assay; Humans; Immunodiffusion; Methods; Orosomucoid; Salicylates

Recent studies indicate the adherence of many patients with rheumatoid arthritis (RA) to their treatment regimens is poor. Management of this problem depends on identification of noncompliant patients, followed by interventions to increase their level of adherence. In this study, 63 patients with RA receiving salicylate drugs completed a questionnaire during an outpatient visit. The questionnaire contained items believed to be predictive of future compliance, including patient self-predictions regarding future compliance, ratings of behavior in similar situations and barriers to compliance, such as ease of transportation to the clinic. Compliance was estimated via a salicylate assay that was taken during a subsequent outpatient appointment. Multivariate analyses of our data revealed that significant predictions could be made regarding future compliance, with 75% of the noncompliant patients correctly identified. Variables contributing significantly included behavioral self-predictions and a measure of current behavior in similar situations, as assessed by a salicylate assay that was collected during the 1st outpatient visit.

Topics: Arthritis, Rheumatoid; Forecasting; Humans; Middle Aged; Patient Compliance; Regression Analysis; Risk Factors; Salicylates; Salicylic Acid; Surveys and Questionnaires

Topics: Adult; Arthritis, Rheumatoid; Diflunisal; Humans; Male; Salicylates; Thrombocytopenia

Topics: Arthritis, Rheumatoid; Humans; Intestines; Lymphocyte Activation; Lymphocytes; Salicylates; Salicylic Acid; Sulfapyridine; Sulfasalazine

Our study of 13 hospitalized patients with rheumatoid arthritis examined the effect of intraarticular injection of steroid on serum salicylate levels. A mean decrease in serum salicylate levels of 42 +/- 14.5% was observed in 12 patients within 12-36 hours post-injection (P less than 0.005). This interaction, though transient, may be very significant clinically. It may lead to erroneous conclusions concerning patient compliance, unwarranted increases in salicylate dosage and resultant toxicity, and delay of appropriate therapeutic maneuvers.

Topics: Adult; Aged; Arthritis, Rheumatoid; Child; Drug Interactions; Female; Humans; Injections, Intra-Articular; Male; Methylprednisolone; Middle Aged; Salicylates; Salicylic Acid

Using the American Rheumatism Association Medical Information System, we studied the effect of age upon salicylate toxicity in elderly patients with rheumatoid arthritis. Data were gathered from 545 patients by self-reported questionnaires for the 6 months and also the 7 days before the visit of interest. With one week data and weight adjusted doses in 253 patients in whom data were available, age related differences in lower gastrointestinal symptoms (p = 0.05) and tinnitus (p = 0.01) were found, despite the fact that elderly patients (E) took less salicylate than younger ones (y)--E [39.1 +/- 2.4 (SD) mg/kg/day] vs Y [49.8 +/- 3.89 mg/kg/day] (p = 0.02). Our data indicate a difference in salicylate dynamics among the elderly (i.e., increased toxicity in the face of decreased salicylate doses).

Topics: Adult; Age Factors; Aged; Arthritis, Rheumatoid; Aspirin; Central Nervous System Diseases; Dose-Response Relationship, Drug; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Salicylates; Tinnitus

The pharmacokinetics of salicyl phenolic glucuronide (SPG) and other salicylic acid (SA) metabolites were studied at three aspirin dosage regimens in eight patients with rheumatoid arthritis. Each patient received 1, 2 and 4 g enteric coated aspirin (ASA) daily in ascending order. At the end of each 2-week dosage period, plasma and urine were collected over a dosage interval for the estimation of various pharmacokinetic parameters. With increasing ASA dosage, mean clearance of SA to SPG was approximately constant (1.8 +/- 0.3, 1.7 +/- 0.2, and 1.5 +/- 0.2 ml/min at 1, 2 and 4 g/day, respectively) when related to plasma concentrations of total SA. The percentage of the ASA dosage recovered in urine as SPG increased from 5.2 +/- 1.1 to 7.1 +/- 1.1 to 10.5 +/- 1.7 at 1, 2 and 4 g/day, respectively. It was concluded, however, that the conversion of SA to SPG is saturable, since the mean clearance of SA to SPG decreased when calculated with respect to the plasma concentration of unbound SA (13.4 +/- 1.6, 11.0 +/- 1.4, and 6.6 +/- 1.9 ml/min at 1, 2 and 4 g/day, respectively). The kinetics of the formation and excretion of salicylurate and the excretion of gentisate were similar to those found in previous studies.

Topics: Adult; Aged; Arthritis, Rheumatoid; Aspirin; Female; Glucuronates; Humans; Kinetics; Male; Middle Aged; Salicylates; Salicylic Acid

After one to 2 weeks of 45 mg/kg/day choline magnesium trisalicylate (CMT) in 2 divided doses, 51 of 71 patients with rheumatoid arthritis (72%) had observed steady state serum salicylate concentrations between 150 and 300 mg/l (mean salicylate: 213 +/- 10 mg/l), although 17 later required dose adjustment. CMT dosing was changed in 37 cases by using the formula: dosing rate = total clearance X concentration. The expected and observed concentrations were not different (p = 0.31); thus, this formula can help calculate salicylate dosing changes to bring the serum salicylate level to within the therapeutic range.

Topics: Arthritis, Rheumatoid; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Osmolar Concentration; Salicylates; Salicylic Acid

The kinetic interaction between salicylate and naproxen was investigated in 25 rheumatoid arthritis patients. Kinetic interactions were tested in serum after patients had been on each drug regimen for 1 month. Salicylate decreased serum naproxen concentration from 89.5 mg/liter to 65.9 mg/liter (P less than 0.001) and increased serum naproxen clearance by 56%. Naproxen had minimal effect on serum salicylate concentrations.

Topics: Arthritis, Rheumatoid; Choline; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Humans; Metabolic Clearance Rate; Naproxen; Random Allocation; Salicylates

Topics: Arthritis, Rheumatoid; Aspirin; Female; Humans; Male; Salicylates

Early rheumatoid arthritis is a diagnosis most often made by history and physical examination and is frequently a diagnosis of exclusion. Differential diagnosis can be difficult because of the wide variation in age, sex, constitutional symptoms, physical findings, and joint distribution. Early, aggressive therapy should include patient education, rest, graded exercise, counseling, and appropriate medication. Absence of subcutaneous nodules and joint erosion may indicate a better prognosis in rheumatoid arthritis. Presence of rheumatoid factor, eosinophilia, thrombocytosis, and/or vasculitis suggests a less favorable course.

Topics: Adult; Arthritis, Rheumatoid; Counseling; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Patient Education as Topic; Prognosis; Rheumatoid Factor; Salicylates; Sex Factors

A woman experienced exacerbations of bronchial asthma after taking aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) for rheumatoid arthritis. On oral challenges, she developed an urticarial reaction after tartrazine; urticarial and bronchospastic reactions after salicylsalicylic acid; and urticarial and bronchospastic reactions after choline magnesium trisalicylate. Non-acetylated salicylates have been recommended for use in aspirin- and/or tartrazine-sensitive patients. The results of sensitivity studies of our patient indicates that such patients may also be sensitive to non-acetylated salicylates.

Topics: Albuterol; Arthritis, Rheumatoid; Asthma; Bronchial Spasm; Choline; Drug Combinations; Drug Hypersensitivity; Female; Humans; Middle Aged; Nasal Polyps; Salicylates; Tartrazine; Urticaria

Topics: Anti-Inflammatory Agents; Antigen-Antibody Complex; Arthritis, Rheumatoid; Cartilage; Collagen; Humans; Immune Complex Diseases; Immunity; Inflammation; Osteoarthritis; Proteoglycans; Salicylates; Steroids; Water

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Drug Tolerance; Female; Humans; Imidazoles; Male; Middle Aged; Naproxen; Salicylates

Topics: Adrenal Cortex Hormones; Arthritis, Rheumatoid; Delivery, Obstetric; Female; Humans; Infant; Infant Care; Labor, Obstetric; Pregnancy; Pregnancy Complications; Recurrence; Salicylates

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Dose-Response Relationship, Drug; Humans; Indomethacin; Kinetics; Phenylbutazone; Salicylates; Synovial Fluid

Concentrations of gentisate found in plasma and synovial fluid were in excess of concentrations required to exert an antioxidant effect in vitro. Studies of diphenol/aminophenols suggested that an ortho or para configuration of functional groups was required for this in vitro antioxidant activity. Animal studies indicated some correlations between in vitro activity and pharmacology of these agents.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Arthritis, Rheumatoid; Aspirin; Biotransformation; Gentisates; Humans; Joint Diseases; Rats; Salicylates; Synovial Fluid

Our study was undertaken to assay gentisate, an oxidation metabolite of salicylate, in plasma and synovial fluid (SF) samples from patients taking antiinflammatory doses of aspirin. A close correlation between plasma and SF concentrations was found for (1) salicylate, (2) salicylurate, and (3) gentisate, in 20 patients studied. Our data suggest ready equilibration of these compounds between the plasma and synovial spaces. In vitro experiments confirmed that in the presence of an oxy radical flux, salicylate is oxidized to gentisate. However, no evidence was obtained to implicate peripheral conversion of salicylate to gentisate in inflamed joints where oxy radicals may be produced.

Topics: Arthritis, Rheumatoid; Chromatography, High Pressure Liquid; Gentisates; Humans; Joint Diseases; Salicylates; Synovial Fluid

A high unit dose (15 grain/975 mg) enteric coated aspirin preparation was studied in normal individuals and patients with arthritis to determine how readily well tolerated, therapeutic (150-300 micrograms/ml) salicylate (SA) levels could be achieved using a twice daily dosing regimen. Of 36 participants enrolled, 33 (92%) achieved this goal (mean SA = 224 micrograms/ml), while in the remaining 3 an initially toxic level fell below the therapeutic range after reducing the dose by one tablet/day. Although the relationship between dose (mg/kg) and steady state SA levels was roughly linear (r = 0.74), in some subjects there was a striking incremental change in the SA level when the dose was adjusted. Over 90% of subjects taking a starting dose between 45-60 mg/kg/day achieved a therapeutic level. Thus, antiinflammatory therapy using 15 grain/975 mg enteric coated aspirin given twice daily appears to be feasible.

Topics: Adult; Aged; Arthritis, Rheumatoid; Aspirin; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Osteoarthritis; Salicylates; Salicylic Acid; Tablets, Enteric-Coated; Tinnitus

A crossover double-blind controlled trial was performed on 36 patients with rheumatoid arthritis to assess the necessity for serum salicylate monitoring in determining optimal dosage. There was no clinically or statistically significant increase in the clinical improvement of patients associated with serum monitoring but potentially toxic serum levels occurred without tinnitus when serum monitoring was not used.

Topics: Arthritis, Rheumatoid; Aspirin; Deafness; Double-Blind Method; Drug Administration Schedule; Evaluation Studies as Topic; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Salicylates; Tinnitus

This article reviews the efficacy of NSAIDs and their pharmacokinetic and pharmacodynamic properties. The assumption that classic pharmacokinetic dose/plasma concentration response relationships can be applied to NSAIDs has tenuous support in the biomedical literature. Comparative efficacy studies, using ASA and indomethacin as the standards for comparison, ignore the fact that the major outcome variables are subjective responses among patients, not among drugs. Comparing inhibition of platelet malonyldialdehyde, synovial drug concentrations, urinary prostaglandin metabolites, and plasma free and total concentration with the clinical outcome provides no guidelines to serve as predictors of response. The individual agents, indomethacin, salicylates, sulindac, piroxicam, and naproxen, illustrate the complexities of NSAID pharmacotherapy. Recent proliferation of newer NSAIDs will not add significantly to the efficacy of these agents in the treatment of pain and inflammatory disease states. However, knowledge of pharmacokinetic population parameters for the individual NSAIDs will increase the likelihood of therapeutic success and diminish the possibilities for adverse reactions.

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Dose-Response Relationship, Drug; Humans; Indomethacin; Kinetics; Naproxen; Piroxicam; Prostaglandin Antagonists; Salicylates; Sulindac; Thiazines

This study was designed to investigate the relationship of free plasma salicylate to total plasma salicylate and to determine the clinical utility of monitoring the free plasma salicylate concentration. Analysis of 46 patient samples indicated a close correlation between the free and total plasma concentration and that there is no additional advantage to monitoring the free plasma salicylate concentration. Also this study re-emphasizes the unique pharmacokinetic characteristics of salicylate, whereby the amount of free plasma salicylate increases disproportionately with increased total plasma salicylate concentration.

Topics: Adult; Aged; Arthritis, Rheumatoid; Female; Humans; Male; Middle Aged; Protein Binding; Salicylates

A pilot study evaluated once-daily treatment of rheumatoid arthritis with choline magnesium trisalicylate (CMT) in patients diagnosed as having classical or definite rheumatoid arthritis, with morning stiffness as a major complaint. Twenty patients were selected who, in an earlier phase of the study, had found twice-daily treatment with CMT effective and tolerable. Efficacy was evaluated in 15 of these patients and safety was evaluated in all 20. Comparisons were made with the twice-daily regimen and with previous nonsteroidal anti-inflammatory drug (NSAID) therapy. Changes in clinical indicators (numbers of painful and swollen joints and the duration of morning stiffness) showed that once-daily treatment with CMT was as effective as twice-daily treatment with CMT or as treatment with other prior NSAIDs in controlling signs and symptoms of rheumatoid arthritis. Side effects in both the twice-daily and the once-daily treatment regimens were similar in incidence and nature.

Topics: Adult; Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Choline; Female; Hearing Loss; Humans; Male; Middle Aged; Pilot Projects; Salicylates; Tinnitus

Topics: Ankle Joint; Arthritis, Rheumatoid; Cartilage Diseases; Cartilage, Articular; Chronic Disease; Foot Deformities, Acquired; Hallux Valgus; Humans; Joint Dislocations; Metatarsophalangeal Joint; Orthotic Devices; Physical Exertion; Salicylates; Shoes; Toes

The disposition of salicylic acid (SA) and its metabolites and the clinical response to long-term aspirin treatment at varying doses were assessed in patients with rheumatoid disease. Steady-state kinetics of SA (total and unbound), salicyluric acid (SUA), gentisic acid (GA), and clinical status were estimated weekly in 10 patients with rheumatoid arthritis. Eight received a soluble aspirin form and two received an enteric-coated form. The starting dose of aspirin in each patient was 1.8 gm (soluble) or 1.95 gm (enteric-coated) daily. Weekly increments in dose were made until a satisfactory clinical outcome was achieved. The final aspirin dose range was 3.6 to 8.1 gm daily, which resulted in mean steady-state plasma SA concentrations (CpSA) from 56 to 375 mg/l. Since the mean total CpSA increased approximately proportionately over the dose range, there was little change in total SA clearance. By contrast, increasing aspirin dosage resulted in decreased clearance and disproportionate increases in unbound SA (CpuSA). The maximum velocity of conversion of SA to SUA (Vm) increased significantly, from 57.3 +/- 11.7 mg/hr at an aspirin dose of 1.8 gm/day to 71.4 +/- 19.4 mg/hr at the next highest dose (2.7 to 3.6 gm/day), with no further change with increasing dosage. Km ranged from 0.4 to 1.2 mg/l for CpuSA and from 5.5 to 17.2 for total CpSA. Renal clearance of SUA (ClSUA) ranged from 124 to 893 ml/min and correlated with creatinine clearance. ClGA ranged from 23 to 164 ml/min, and ClSA ranged from 0.1 to 17.1 ml/min; neither correlated with creatinine clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Arthritis, Rheumatoid; Creatinine; Dose-Response Relationship, Drug; Female; Humans; Hydrogen-Ion Concentration; Kinetics; Male; Middle Aged; Salicylates; Salicylic Acid; Solubility

Topics: Acetates; Adult; Aged; Analgesics; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Child; Drug Interactions; Female; Gout; Humans; Phenylbutazone; Pregnancy; Propionates; Salicylates

Salicylate availability from salsalate (SSA) and aspirin (ASA) was examined in six rheumatoid arthritis patients in a multiple-dose double-blind crossover study. Doses contained equimolar amounts of salicylic acid. After initial ASA treatment to achieve therapeutic salicylate levels (150 to 300 micrograms/ml) the patients received equimolar doses of SSA or ASA. When steady state was achieved patients were hospitalized, and blood and urine specimens were obtained during three dosing intervals and during the washout period that followed. Thereafter, patients were placed on the alternate medication for at least a week and the in-hospital pattern was repeated. Despite insignificant differences in absorption of the formulations, as measured by urinary salicylate recovery, the plasma salicylic acid AUC was lower after SSA. Evidence indicates that this apparent lower availability of salicylate from SSA is due to incomplete hydrolysis to salicylic acid, the unhydrolyzed SSA being excreted mainly as glucuronide conjugates.

Topics: Arthritis, Rheumatoid; Aspirin; Biological Availability; Chromatography, High Pressure Liquid; Double-Blind Method; Drug Evaluation; Female; Gentisates; Humans; Hydroxybenzoates; Male; Salicylates; Salicylic Acid

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Azathioprine; Gold; Humans; Penicillamine; Salicylates

The binding of ibuprofen to human serum albumin, normal plasma and plasma obtained from rheumatoid arthritic patients was studied using the method of ultracentrifugation. It was found that ibuprofen is more strongly bound to normal plasma than to human serum albumin although this result is probably explained by fatty acid contamination of the human serum albumin. The fraction of ibuprofen not bound to normal plasma rose significantly from a value of 0.0128 at an ibuprofen concentration of 2 mg X l-1 to 0.0155 at a concentration of 50 mg X l-1. Ibuprofen was less strongly bound to rheumatoid plasma than to normal plasma but this difference can be accounted for by the difference in albumin concentration between the two plasmas. It was found that salicylic acid can displace ibuprofen from protein binding sites, in vitro, and that this is the probable cause of the pharmacokinetic interaction between the two drugs.

Topics: Arthritis, Rheumatoid; Binding, Competitive; Humans; Ibuprofen; Protein Binding; Salicylates; Salicylic Acid; Serum Albumin

The authors reviewed the quality of information shared by referring doctors with hospital consultants, in regard to past drug treatment in the cases of 95 consecutive patients with rheumatoid arthritis. Information contained in referral letters was compared with information obtained from patient interviews. It was found that the referral letters often contained little information on drug use and included no information on adverse reactions to drug therapy.

Topics: Arthritis, Rheumatoid; Communication; Drug Therapy; Humans; Mental Recall; Patients; Referral and Consultation; Salicylates

To assess the effects of long-term aspirin ingestion on renal function, we studied all of the patients at the Massachusetts General Hospital Arthritis Clinic who had been taking aspirin continuously for ten or more years. Aspirin ingestion was documented by multiple, random, unannounced blood salicylate levels. Most of these 46 patients had seropositive rheumatoid arthritis. All creatinine and BUN levels were normal. Maximum recorded specific gravities were greater than 1.019 in 43 of 46 patients. These data suggest that long-term salicylate ingestion does not cause renal damage.

Topics: Adult; Aged; Arthritis, Rheumatoid; Aspirin; Creatinine; Female; History, 17th Century; Humans; Kidney; Kidney Diseases; Male; Nephritis, Interstitial; Proteinuria; Random Allocation; Salicylates; Time Factors

In vivo and in vitro binding of salicylate to plasma proteins was studied by ultrafiltration at room temperature. The nonlinearity of the Scatchard and Klotz plots were explained by the presence of lipid-soluble substances in plasma. Delipidation of plasma resulted in changes of the binding characteristics of plasma in that more moles of salicylate could be bound per mole of protein. This changed the appearances of the Scatchard and Klotz plots so that a much larger range of salicylate concentration could be accommodated by the linear portion of the graphs. The equilibrium constant for the in vitro salicylate binding was identical for the delipidated and untreated plasma. However, the in vivo binding constant for salicylate in plasma was higher than the in vitro binding constant.

Topics: Adult; Aged; Arthritis, Rheumatoid; Aspirin; Binding Sites; Blood Proteins; Female; Humans; In Vitro Techniques; Kinetics; Male; Middle Aged; Protein Binding; Salicylates; Salicylic Acid

Topics: Adult; Aged; Arthritis, Rheumatoid; Aspirin; Choline; Female; Humans; Male; Middle Aged; Salicylates

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Humans; Salicylates

Protein binding of salicylates was determined in 16 control subjects and 27 patients suffering from rheumatoid arthritis. Results obtained after separation of the free and bound fractions by dialysis to equilibrium and measured by spectrofluorometry were analyzed using a new mathematical model. In correlation with the decrease in plasma albumin concentrations, a decrease was found in the protein binding of salicylates in patients with rheumatoid arthritis. This phenomenon was less marked in therapeutic zones and was related to the degree of severity of the inflammatory syndrome. The binding capacity per albumin molecule at saturation was decreased in patients suffering from advanced forms, suggesting that the changes seen were not due solely to quantitative variations in serum albumin levels. This study confirms the value of the determination of free salicylate levels in patients suffering from inflammatory rheumatic disorders.

Topics: Adolescent; Adult; Aged; Arthritis, Rheumatoid; Humans; Middle Aged; Protein Binding; Salicylates; Serum Albumin

Ninety patients with active rheumatoid arthritis took part in a cross-over trial comparing diclofenac sodium, diflunisal and naproxen. The efficacy of the three drugs was similar though there were trends in favour of diclofenac sodium in some measurements. The incidence of side-effects was similar with the three drugs and each was chosen by a significant group of patients as continuation therapy at the end of the study.

Topics: Adult; Aged; Arthritis, Rheumatoid; Consumer Behavior; Diclofenac; Diflunisal; Female; Humans; Male; Middle Aged; Naproxen; Patient Participation; Phenylacetates; Salicylates

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Choline; Humans; Salicylates

Sixty patients with active rheumatoid arthritis (mean ESR = 51 mm/h) were treated for six months with D-penicillamine (15 patients), sodium aurothiomalate (15 patients), hydroxychloroquine (15 patients) or enteric-coated aspirin (15 patients). The three groups receiving specific anti-rheumatoid therapy were also allowed enteric-coated aspirin in the dose of their choice as the only 'back-up' drug; the group treated with aspirin alone was encouraged to take the maximum tolerated dose. The mean duration of treatment tolerated by patients receiving aspirin alone was 12.3 weeks. Only four patients completed a 24-week treatment period and n improvement was seen in acute-phase reactants. Those patients receiving an anti-rheumatoid drug showed serial improvements in ESR as the dose of aspirin required fell. Plasma salicylate concentrations correlated well with aspirin dosage. Even as an enteric-coated formulation, aspirin alone is not the treatment of choice for active rheumatoid disease.

Topics: Arthritis, Rheumatoid; Aspirin; Blood Sedimentation; Gold Sodium Thiomalate; Humans; Hydroxychloroquine; Penicillamine; Salicylates; Tablets, Enteric-Coated

Topics: Arthritis, Rheumatoid; Evaluation Studies as Topic; History, 20th Century; Humans; Salicylates; Surveys and Questionnaires

Topics: Anti-Inflammatory Agents; Arthritis; Arthritis, Rheumatoid; Aspirin; Bursitis; Humans; Osteoarthritis; Salicylates; Spondylitis; Tendinopathy

To evaluate the effect of anti-inflammatory drug therapy on ulcer healing, we studied retrospectively patient records listing the dual diagnoses of rheumatoid arthritis and peptic ulcer (1953-1975). Forty-three ulcers (23 gastric and 20 duodenal) occurred in 41 subjects. Evaluation of ulcer healing was possible in 35 patients, 27 of whom had continued on anti-inflammatory drug therapy while being treated for ulcer disease and eight who did not. In 21 of the 27 patients the ulcer healed; in six the ulcer failed to heal, including one who died from gastric carcinoma. Fourteen of the 21 patients whose ulcer healed were taking both aspirin and corticosteroids; in all eight patients who stopped taking anti-inflammatory drugs, the ulcers (eight gastric, one duodenal) healed. In six patients no evaluating was possible because the outcome of ulcer therapy was unknown. The numbers of patients not studied, unlisted or unretrieved are unknown, though probably small, and while no data are available on controls drawn from the same population or on the rates of spontaneous ulcer healing and recurrence in this population, our study nevertheless establishes that ulcer healing does occur in many patients with rheumatoid arthritis despite continued treatment with salicylate, corticosteroid, or other anti-inflammatory drugs.

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Humans; Peptic Ulcer; Salicylates; Stomach Ulcer; Wound Healing

Topics: Animals; Arthritis, Rheumatoid; Copper; Drug Therapy, Combination; Humans; Rheumatic Diseases; Salicylates

Topics: Arthritis, Rheumatoid; Choline; Drug Combinations; Female; Humans; Male; Middle Aged; Salicylates

1. The effects of chronic administration of aspirin in therapeutic doses (3.9 g/day) on plasma and salivary salicylate levels were studied in eight subjects. 2. The urinary excretion profile for free salicylic acid and metabolites of salicylate were examined. 3. Plasma and salivary salicylate levels declined significantly after peak levels were achieved between days 3 and 10. 4. The decline in plasma and salivary salicylate levels may be due to an induction of a metabolic pathway such as salicylurate formation (Furst, Gupta & Paulus, 1977). Only the mean fraction of salicylate excreted as salicylurate appears to increase with time during the present study, although the change was not significant statistically. 5. The decline in plasma and salivary salicylate levels during chronic therapy may lead to an apparent 'tolerance' of some rheumatoid patients to aspirin.

Topics: Arthritis, Rheumatoid; Aspirin; Female; Humans; Hydrogen-Ion Concentration; Male; Salicylates; Saliva; Time Factors

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Humans; Salicylates

Aspirin, salicylic acid and indomethacin reversibly inhibit prostaglandin binding to human serum proteins. This effect was demonstrated in the sera of normal subjects and of rheumatoid arthritis patients treated with aspirin as well as by addition of these drugs to serum in vitro. The displacement of serum prostaglandins by salicylate is likely to affect the kinetics of prostaglandin transport and may facilitate the delivery of prostaglandins from serum to tissue receptors.

Topics: Arthritis, Rheumatoid; Aspirin; Humans; Indomethacin; Prostaglandins; Prostaglandins A; Prostaglandins E; Prostaglandins F; Protein Binding; Salicylates; Serum Albumin

A method for the quantitative analysis of indomethacin and salicylic acid in blood serum and urine by high-performance liquid chromatography is described. A C18-bonded silica was used as the stationary phase and mixtures of ethanol, n-butanol and aqueous buffer as the mobile phase. Before injection the serum is deproteinized and extracted in one step. The recovery of the extraction was found to be 88% and 77% for indomethacin and salicylic acid, respectively. The relative standard deviations of the analysis for 0.5 micrograms indomethacin and 5 micrograms salicyclic acid per ml serum were 3.6% and 3.2%, respectively. The detection limits for indomethacin and salicylic acid were 2 ng. This corresponds for both substances to 0.1 micrograms/ml serum for an injection volume of 100 microliters. The method enables simultaneous determination of possibly formed metabolites. A number of concurrently administered drugs do not interfere with the analysis. The interactive effects of co-medication of indomethacin and salicylic acid on the serum concentration of indomethacin is demonstrated by measuring the pharmacokinetic curves.

Topics: Arthritis, Rheumatoid; Chromatography, Liquid; Drug Interactions; Humans; Hydrogen-Ion Concentration; Indomethacin; Kinetics; Salicylates

Topics: Arthritis, Rheumatoid; Chemical and Drug Induced Liver Injury; Female; Humans; Middle Aged; Salicylates

Protein binding of salicylate in synovial fluid and plasma from patients with rheumatoid arthritis was studied by equilibrium dialysis. Protein binding in the synovial fluid was considerably lower at all salicylate concentrations studied (0.07 - 2.2 mM). Scatchard plots of the data were analyzed assuming binding to two classes of binding sites, each plasma sample being diluted to an albumin concentration equal to that in synovial fluid from the same patient. Binding to the primary binding sites was considerably decreased in synovial fluid in comparison with plasma. The affinity of the secondary binding sites was slightly lower. Thus, at a low therapeutic drug concentration, the decreased binding of salicylate to synovial fluid protein in patients with rheumatoid arthritis could mainly be accounted for by decreasing affinity of binding to the primary binding sites.

Topics: Arthritis, Rheumatoid; Blood Proteins; Female; Humans; Kinetics; Male; Protein Binding; Salicylates; Synovial Fluid

The concentration of salicylic acid in human tears has been measured by using reverse-phase, high-pressure liquid chromatography. Pharmacokinetic profiles in tears and in plasma have been obtained following oral administration of 650, 1300, and 1950 mg of aspirin in normal subjects. Salicylate excretion in tears is dose-dependent and is proportional to the plasma concentration. Tear and plasma salicylate levels for rheumatology patients on salicylates are also included.

Topics: Administration, Oral; Adult; Arthritis, Rheumatoid; Aspirin; Chromatography, High Pressure Liquid; Humans; Salicylates; Tears

Thirty-one patients with rheumatoid arthritis in the Veterans General Hospital from July 1978 to June 1979 were treated with acetylsalicylic acid. The serum salicylate level was determined twice a week. The dose of acetylsalicylic acid was adjusted to keep the serum salicylate level around 15-30 mg%. All patients were started with an initial dose of 65 mg/kg/day. The serum salicylate levels at the 4th day varied greatly from 5.6 to 29.5 mg%. Tinnitus was noted in 24 patients. It occurred when the serum salicylate level reached 28.41 +/- 1.84 mg%. Abnormal liver function was noted in 19.35% (6/31) patients during treatment. It returned to normal after withdrawal of acetylsalicylic acid in 3 cases, after decrease of the dosage in 2 cases and on the same dosage in 1 case. Patients with positive FANA and RF were more prone to develop abnormal liver function during treatment. Monitoring of serum salicylate level may decrease the incidence of hepatic toxicity and maintain the dosage of acetylsalicylic acid in optimal range.

Topics: Adult; Arthritis, Rheumatoid; Aspirin; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Rheumatoid Factor; Salicylates; Tinnitus

Topics: Anti-Inflammatory Agents; Antimalarials; Arthritis, Rheumatoid; Aspirin; Drug Therapy, Combination; Glucocorticoids; Gold; Humans; Patient Education as Topic; Physical Therapy Modalities; Rest; Salicylates

Topics: Arthritis, Rheumatoid; Humans; Rheumatic Diseases; Salicylates

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Aspirin; Gold; Humans; Immunosuppressive Agents; Indomethacin; Levamisole; Penicillamine; Phenylbutazone; Propionates; Salicylates

Twenty-eight medical specialists (internists, rheumatologists) selected 102 primarily arthritic patients for a two-week efficacy and safety field study of salicylsalicylic acid. Data were gathered on pain, morning stiffness, range of motion, serum salicylate concentration, erythrocyte sedimentation rate (ESR) and gastro-intestinal bleeding before and after a 15-day drug trial. Results showed a 67% favourable clinical response in the physician's global evaluation and a 60% improvement in pain; the drug itself was well tolerated by 96% of patients. Response correlations with morning stiffness and range of motion were equivocal. Of fifty-four patients examined before and after treatment for intestinal bleeding, only two (3.7%) had detectable faecal blood loss. Good clinical response had a statistically significant association with serum drug concentrations of 13.6 to 13.8 mg%; unsatisfactory response was noted in those patients with mean serum salicylate levels of 8.6 mg%. ESR decreased or was unchanged in thirty-five patients with satisfactory clinical response and in fourteen patients with unsatisfactory response.

Topics: Adult; Aged; Analgesics; Arthritis; Arthritis, Rheumatoid; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Osteoarthritis; Salicylates

When the total daily drug dose was individualized to produce a steady-state serum salicylate concentration between 20 and 35 mg/dl, clinically acceptable fluctuations of serum concentrations occurred during both twice daily and three times daily administration. In 6 rheumatoid arthritis patients receiving choline magnesium trisalicylate, mean steady-state serum levels were the same, and the ranges of hourly mean concentrations during 8 and 12 hour dosage intervals were 19 to 27 mg/dl and 17 to 30 mg/dl, respectively. Changing the dosing interval from 8 to 12 hours required a 50% increase in the fractional doses, but resulted in an increase of only 3 mg/dl in mean peak concentration and a ddecrease of 1 mg/dl in mean minimum concentration.

Topics: Adult; Arthritis, Rheumatoid; Choline; Drug Evaluation; Female; Humans; Magnesium; Male; Middle Aged; Salicylates; Time Factors

Topics: Arthritis, Rheumatoid; Aspirin; Female; Humans; Male; Salicylates

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Humans; Indomethacin; Injections, Intra-Articular; Phenylbutazone; Salicylates

Ten patients with rheumatoid arthritis were given identical amounts of conventional aspirin (Magnecyl) tablets and micro-encapsulated aspirin (Reumyl) capsules. Steady-state salicylate levels were determined after 4 days' treatment at 8 a.m., 12 noon, 4 p.m., 10 p.m. and again at 8 a.m. No difference was noted between the levels at 12 noon or 4 p.m. The 10 p.m. levels were slightly though not significantly higher and the last set of 8 a.m. levels were significantly higher during the capsule administration. A criterion for inclusion was good tolerance of Magnecyl. The clinical effectiveness was not evaluated, but the observed good absorption features of Reumyl indicate that this preparation may prove to be of value in long-term treatment.

Topics: Arthritis, Rheumatoid; Aspirin; Capsules; Humans; Salicylates; Tablets

Topics: Arthritis, Rheumatoid; Homeopathy; Humans; Research Design; Salicylates

Topics: Adult; Aged; Alanine Transaminase; Arthritis, Rheumatoid; Aspartate Aminotransferases; Female; Humans; L-Lactate Dehydrogenase; Liver; Male; Middle Aged; Salicylates; Transaminases

Topics: Adolescent; Arthritis, Rheumatoid; Chemical and Drug Induced Liver Injury; Drug Synergism; Drug Therapy, Combination; Female; Humans; Penicillamine; Salicylates

The drug therapy prescribed for a group of 50 patients with rheumatoid arthritis in Otago prior to specialist referral was examined. Thirty-two patients were receiving some first-line anti-inflammatory drugs and six were receiving no therapy at the time of their first hospital clinic visit. Salicylates had been prescribed first in only 16 of the 50 patients while this drug had been withdrawn because of side effects in about one-third of the patients who had been treated with it prior to specialist referral. Seven patients had received phenylbutazone and six corticosteroids as the first treatment for their rheumatoid arthritis. About one-third of the patients were receiving more than one anti-inflammatory drug at the time of their initial clinic visit.

Topics: Adult; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Drug Prescriptions; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Male; Middle Aged; New Zealand; Salicylates

In the introduction the chemistry of some bivalent copper complexes of aspirin and salicylate is briefly reviewed and the biological importance of mixed-ligand complexes of bivalent copper is illustrated. The nature of hydroxy-bridged copper (II) complexes and their possible role in the physiological activity of histamine is also discussed. Several neutral, insoluble copper (II) complexes of the type (Chelate-Cu-salicylate) 0-lambda H2O where chelate = 1, 10-phenanthroline (phen), chi = 1; 2,2'-bipyridyl (bipy), chi = 2; histamine (Ha), chi = 1; and where salicylate (sal) = dianion of salicylic acid have been prepared for the first time. They have been characterised by physico-chemical methods and the role of binuclearhydroxy-bridged copper (II) complex ions in their formation is demonstrated. Such complexes may be relevant to the pharmacological action of histamine and of the salicylates, the copper complexes of which are potential anti-inflammatory drugs. Results of some in vivo experiments that have been carried out with mice are also presented.

Topics: Animals; Arthritis, Rheumatoid; Chelating Agents; Chemical Phenomena; Chemistry; Copper; Histamine; Humans; Ligands; Mice; Rheumatic Fever; Salicylates; Sciatica

Topics: Anti-Inflammatory Agents; Antimalarials; Arthritis, Rheumatoid; Humans; Indomethacin; Propionates; Pyrazoles; Salicylates

Total and free plasma salicylate as well as saliva salicylate was measured in 13 patients with rheumatoid arthritis treated with different doses of acetylsalicylic acid alone. Although the clinical response was judged moderately effective to effective in all cases, total and free plasma salicylate varied markedly. Saliva salicylate correlated well with both total plasma salicylate and fre plasma salicylate. Determination of saliva salicylate may be a simple and useful technique for the monitoring of salicylate therapy.

Topics: Adult; Arthritis, Rheumatoid; Blood Proteins; Humans; Middle Aged; Protein Binding; Salicylates; Saliva

Topics: Analgesics; Anti-Inflammatory Agents; Antimalarials; Arthritis, Rheumatoid; Glucocorticoids; Gold; Humans; Immunosuppressive Agents; Muscle Relaxants, Central; Pyrazoles; Salicylates

To conduct studies of therapy of rheumatoid patients at the primary care level two new assessment techniques were developed. The "independent assessor" (IA) was a nonmedical person trained to gather information using a questionnaire, a guided count of tender joints, grip strength, and blood tests. The "polled index" was a statistical device for summarizing all abailable information, constructed by transformation of various clinical measures of treatment effects to a common scale, based on standard deviation units. A validation study is reported, which involved 33 rheumatoid patients, each studied by four trained observers plus the IA, before and after 10 days of hospital therapy. Major gains in sensitivity and reliability were achieved by the pooled index. The IAs total assessment provided 84% of the information available in the pooled index, and was more sensitive and reliable than any other single clinical measure. The efficacy of a brief period of hospital therapy for rheumatoid patients was also strikingly demonstrated.

Topics: Analysis of Variance; Animals; Arthritis, Rheumatoid; Evaluation Studies as Topic; Female; Glucocorticoids; Length of Stay; Salicylates; Statistics as Topic; Surveys and Questionnaires

Intersubject differences in the volume of distribution, whole body clearance, and steady-state plasma concentrations of salicylic acid (SA) were studied in a series of patients with rheumatoid arthritis and healthy control subjects. The measurement of the plasma concentration of SA 12 hr after an oral dose of 1.2 gm aspirin appears predictive of the success of long-term dosage of aspirin. Concentrations below 5 microgram/ml in this single-dose test were associated with failure to achieve therapeutic plasma concentrations of SA (above 150 microgram/ml during long-term therapy with approximately 4.8 gm aspirin per day. Conversely, plasma concentrations above 10 microgram/ml in the single-dose test were associated with levels above 150 microgram/ml during long-term therapy. The volume of distribution of SA correlated poorly with body weight (r = 0.51, p less than 0.01) and did not correlate significantly with plasma albumin levels. Corticosteroids appear to induce the metabolism of SA and most subjects dosed with oral corticosteroids and aspirin 4.8 gm/day did not attain plasma levels of SA above 150 microgram/ml. The clearance of SA was greater in male than in female patients. The difference appears to be of clinical significance since fewer men than women achieved therapeutic plasma concentrations of SA.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Arthritis, Rheumatoid; Aspirin; Drug Interactions; Female; Humans; Kinetics; Male; Middle Aged; Salicylates; Sex Factors; Time Factors

The author discusses the part that certain anti-inflammatory drugs have played in increasing our understanding of the pathogenesis of rheumatoid arthritis and in adding to our knowledge of the mediators of the inflammatory response. Increasingly, the therapeutic agents under discussion have directed attention to the role of the macrophage in inflammation. Closer examination of existing anti-inflammatory or anti-rheumatic drugs and their mode of action has more recently directed attention towards immunomodulation.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Cell Migration Inhibition; Histamine; Kinins; Macrophages; Monocytes; Prostaglandins; Rats; Salicylates; Serotonin

Topics: Adrenal Cortex Hormones; Arthritis, Rheumatoid; Child; Chloroquine; Female; Gold; Humans; Hydroxychloroquine; Ibuprofen; Indomethacin; Injections, Intra-Articular; Male; Penicillamine; Phenylbutazone; Physical Therapy Modalities; Pregnancy; Pregnancy Complications; Prognosis; Salicylates

The effect of salicylate treatment on the kidney, particularly medullary function, was investigated. In a retrospective analysis patients with rheumatoid arthritis (RA) treated with high doses of salicylates were shown to have inferior urinary concentrating power and increased excretion of N-acetyl-beta-D-glucosaminidase (NAG) when compared with patients who had not received salicylate treatment. A prospective study of renal funcition in healthy people and patients with RA starting salicylate in therapeutic doses showed that while epithelial cell excretion was only transiently raised in both groups the excretion of NAG was increased in all cases at three days and this increase was sustained at 10 days, all values being much higher in the patients than in the healthy subjects. Thus salicylate treatment does cause renal tubular damage but this damage results in only minimal impairment of function and does not constitute a reason for withholding salicylate treatment.

Topics: Acetylglucosaminidase; Arthritis, Rheumatoid; Female; Humans; Hydrogen-Ion Concentration; Kidney Concentrating Ability; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Male; Middle Aged; Salicylates

Topics: Arthritis, Rheumatoid; Carrier Proteins; Humans; Hydrogen-Ion Concentration; Salicylates; Tryptophan

Topics: Arthritis, Rheumatoid; Copper; Free Radicals; Humans; Leukocytes; Salicylates; Synovial Fluid

Topics: Adult; Arthritis, Rheumatoid; Female; Humans; Male; Middle Aged; Salicylates

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Glucocorticoids; Gold; Humans; Hydroxychloroquine; Injections, Intra-Articular; Physical Therapy Modalities; Rest; Salicylates

Caffeine has been found to potentiate the acute anti-inflammatory activity of aspirin, indomethacin, and phenylbutazone, but not the activity of sodium salicylate or hydrocortisone, in the carrageenan pleurisy or hindlimb models of inflammation in the rat. The mobilization of inflammatory cells was not affected by aspirin in the presence or absence of caffeine. The mild analgesia produced by aspirin was confined to a hyperalgesic test in which this drug was able to reduce inflammation and concomitant hyperalgesia and thereby produce an "apparent" analgesic effect. This "apparent" analgesia produced by aspirin was potentiated by caffeine. The mechanism responsible for the potentiated anti-inflammatory and mild analgesic activity of aspirin remains unknown since caffeine did not alter the plasma salicylate levels or prostaglandin synthetase inhibition produced by aspirin.

Topics: Animals; Arthritis, Rheumatoid; Aspirin; Caffeine; Cyclooxygenase Inhibitors; Drug Therapy, Combination; Indomethacin; Inflammation; Male; Phenylbutazone; Rats; Salicylates

A volunteer study was undertaken in which the effect of the co-administration of therapeutic doses of aluminium hydroxide and magnesium trisilicate on the excretion of aspirin derived from enteric-coated preparations was studied. A significant alteration in the pattern of salicylate excretion was seen, but the mechanism of the interaction cannot be deduced from the present study. It was concluded that the interaction was of potential therapeutic importance, and further studies based on this pilot investigation have been initiated.

Topics: Adult; Antacids; Arthritis, Rheumatoid; Aspirin; Dyspepsia; Female; Humans; Male; Middle Aged; Salicylates; Tablets, Enteric-Coated; Time Factors

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Antidepressive Agents; Arthritis, Rheumatoid; Gold; Humans; Immunosuppressive Agents; Penicillamine; Salicylates

Decreased total complement serum level (C'H50) was established in 72 per cent of the 78 patients examined, associated most likely with the developing processes of antigen-antibody reaction and the severe course of the illness. The applied treatment with different antirheumatic remedies, according to their mechanism of action, determined the respective changes in the complement level. Indomethacinum and chinoline derivatives induce complement values elevation, whereas the corticosteroids, salicylate and pyrazolone preparations lead to the complement values normalization.

Topics: Adrenal Cortex Hormones; Antimetabolites; Arthritis, Rheumatoid; Complement System Proteins; Female; Humans; Indomethacin; Male; Middle Aged; Pyrazoles; Quinolines; Salicylates

Only some of the areas of drug interactions of relevance to those treating rheumatic diseases have been mentioned and there are still enormous gaps in our knowledge. It is likely that some potential areas of danger have been over-emphasised, being based on speculation rather than real data or purely animal experiments using non-clinical doses of drugs. We are learning how certain drugs can stimulate or inhibit the metabolism of other drugs through effects on liver enzymes systems. For example, the metabolism of corticosteroids is induced by phenylbutazone (and also by phenobarbital and phenytoin). The patient with active rheumatoid arthritis with a low serum albumin would be unusually susceptible to changes induced by combinations of highly protein-bound anti-inflammatory drugs. Finally, although drug interactions are responsible for adverse effects it has been suggested that a more frequent cause of therapeutic failure is not drug interactions but the increase in the number of drug defaulters when more than one drug is prescribed.

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Drug Interactions; Drug Therapy, Combination; Humans; Indomethacin; Phenylbutazone; Prednisolone; Protein Binding; Salicylates

Topics: Acetates; Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Chelating Agents; Copper; Disease Models, Animal; Edema; Granuloma; Hydrocortisone; Lethal Dose 50; Mice; ortho-Aminobenzoates; Rats; Salicylates; Tryptophan; Ulcer

The early course of newly diagnosed RA among young adult patients (16-44 yr) is described from results of an ongoing study with a mean follow-up of 3.4 yr. Study diagnosis was based on the judgement of experienced rheumatologists, and data on several hundred variables were obtained on entry and annually for the purpose of defining patterns of onset and course of disease. Race and sex factors, as well as certain entry manifestations, e.g., RF, were found to correlate with onset and course patterns. Females, and especially white females, had significantly greater numbers of swollen upper extremity joints than males at entry and at last observation, with increased likelihood of developing bone erosions. At entry, RF positive patients differed only on few articular manifestations from RF negative patients, but had a higher frequency of positive ANA at entry and more subcutaneous nodules and bone erosions during follow-up. Seropositive white females at entry had significantly more swollen upper joints than their seronegative counterparts, but with no difference found at last follow-up. White females of each serogroup had more joint involvement at last examination than patients of other race-sex groups. Males had more acute onset, especially under age 30, with significantly greater improvement in arthritis and in ESR than did females. The majority (55%) of patients entered as seropositive, converted to seronegative during follow-up, and no correlation of either joint swelling or erosions was noted with this phenomenon. At last visit, RF positively did not correlate with bone erosions, but patients developing bone erosions had higher frequency of ANA and higher mean serum complement levels at last examination. The following entry factors were found to correlate significantly with a better outcome: maleness, acute onset under age 30, less swollen upper joints, and negative RF. Type of drug therapy tended to reflect severity of arthritis, rather than vice versa, and functional capacity improved significantly from entry to last evaluation in both males and females, even though the latter had stable or progressive arthritis. Further study is necessary over long intervals and in wider age range to more adequately interpret the biologic implications of findings of this ongoing study. A better understanding of the pathogenesis of RA may be derived from critical studies of the contribution of host factors, e.g., sex, and other variables predisposing to the development o

Topics: Adolescent; Adult; Age Factors; Arthritis, Rheumatoid; Demography; Female; Follow-Up Studies; Gold; Humans; Male; Racial Groups; Rheumatoid Factor; Salicylates; Steroids

Six patients, not previously treated, with classical seropositive rheumatoid arthritis and highly active synovitis of one or both knee joints were treated with 4 g of 40% benorylate suspension twice daily for a period of 9--14 days prior to synovectomy. Blood samples were taken at scheduled times during administration of the drug. At operation, synovial fluid and tissue samples were taken and their salicylate, paracetamol and benorylate content measured. Plasma levels of salicylate and paracetamol were, in general, significantly higher than the concentration of these metabolites in the synovial fluid. Benorylate was found in the synovial tissues concentrated especially in the highly inflamed synovial villi. It is probable that benorylate and its metabolites penetrate the synovia but further studies are needed to determine if the metabolites are concentrated in the different synovial cell layers in the same way as benorylate itself. It is possible that part of the clinical effect of benorylate is due to its presence in the synovial tissue and that it has a direct effect in vivo on the synovial membrane. It is also possible that the pharmacokinetic properties of benorylate permit it to enter cell layers inaccessible to its metabolites.

Topics: Acetaminophen; Arthritis, Rheumatoid; Chronic Disease; Humans; Salicylates; Synovectomy; Synovial Fluid; Synovial Membrane

After a preliminary wash-out period of 3-7 days during which no anti-inflammatory drugs were given, 11 female patients with classical or definite rheumatoid arthritis were given 8 g of benorylate as the 40% suspension 3-7 days prior to synovectomy of the knee. Samples of synovial tissue and fluid from the affected knee were assayed for their content of benorylate, salicylate and paracetamol in an attempt to relat these concentrations to the length of medication and the severity of the disease process as measured clinically, by X-ray, by open inspection at operation and by histology of the synovial tissue. The esterase activity of the blood and synovial fluid was also measured by the capacity to hydrolyse benorylate used as substrate.

Topics: Arthritis, Rheumatoid; Female; Humans; Salicylates; Synovial Fluid; Synovial Membrane

The analgesic and anti-inflammatory efficacy and adverse effects of benorylate were studied over a period of 6 months in 33 patients suffering from definite or classical rheumatoid arthritis. The average dose used was 6 g daily and examinations were made before treatment and at regular intervals during treatment to assess the clinical status of the patient, tolerance to the drug and any effect on blood, liver or renal function. Benorylate had a satisfactory effect in 28 patients. Additional treatment was requried in 3 cases and treatment discontinued in 2 cases. Distinct improvement of grip strength, morning stiffness and E.S.R. in 25 cases indicates the anti-inflammatory efficacy of benorylate. There were no signs of toxicity to bone marrow, liver or kidney. Severe side effects such as stomch ulcers, gastrointestinal bleeding and severe allergic complications were not observed. Side effects such as constipation and tinnitus that occurred at the beginning of treatment were mainly of a a passing nature and disappeared without a need to change therapy. Benorylate is suitable for the treatment of recent rheumatoid arthritis of a low to moderate activity as well as for long-term treatment.

Topics: Arthritis, Rheumatoid; Drug Evaluation; Drug Hypersensitivity; Gastrointestinal Diseases; Humans; Salicylates; Time Factors

52 outpatients with rheumatoid arthritis or osteoarthritis were given benorylate (as the 40% suspension) in doses of up to 8 g daily. Peroids of medication were varied but some patients were given the drug for nearly 2 years. Assessments of clinical progress were made at regular intervals by recording both subjective and objective measurements including duration of morning stiffness, grip strength, joint size. Laboratory investigations include renal function tests, liver function tests, blood picture and occult blood. No serious side effect, attributable to benorylate was reported and it was concluded that the drug is satisfactory for the long term treatment of rheumatic diseases.

Topics: Arthritis, Rheumatoid; Blood Sedimentation; Drug Evaluation; Dyspepsia; Humans; Nausea; Osteoarthritis; Rheumatic Diseases; Salicylates; Urea; Vomiting

Benorylate is obtained by esterification of acetylsalicylic acid and N-acetyl p-aminophenol (4-acetamidophenyl 2-acetoxybenzoate). Experimentally, this new product has been shown to be a good analgesic and anti-inflammatory agent. A clinical trial was carried out in order to study the efficacy, side effects and tolerance of this new product. In a group of 49 hospitalised patients aged from 20 to 70 years who were treated with this new product, 15 had ankylosing spondylitis, 11 had chronic progressive rheumatoid arthritis, 4 had Reiter's syndrome, 4 had psoriatic arthropathy, 8 had osteoarthrosis of the hip and 7 had various forms of rheumatism. The drug was administered orally in suspension form, initially three times per day, then twice, the total daily doses being 15 ml (6 g) or 20 ml (8 g). Treatment was regarded as effective in 62% of the cases, and of these 62%, 46% good and very good results were obtained. In 88% of the patients, tolerance was satisfactory and of these, it was excellent in 80%. Only in 2 cases did treatment have to be discontinued on account of side effects. From the biological point of view, uricaemia was significantly reduced in 7 patients, and in 6 patients uricuria increased. With regard to the level of salicylate in the blood assays showed that it is the same for 6 g benorylate and for 4 g aspirin. Benorylate has been shown to be an effective treatment for both inflammatory and degenerative rheumatic disorders. The results of its use can be compared with those obtained by acetylsalicylic acid, but is better tolerated. In addition, in chronic disorders it is better to have to take the product only twice per day.

Topics: Administration, Oral; Adult; Aged; Arthritis; Arthritis, Rheumatoid; Drug Evaluation; Female; Humans; Male; Middle Aged; Osteoarthritis; Rheumatic Diseases; Salicylates

Twenty patients with definite or classical rheumatoid arthritis and chronic knee effusions were each given an oral dose of 4 g benorylate as the 40% suspension. Synovial fluid and plasma samples were obtained up to 9 hours after drug administration and assayed for their salicylate and benorylate content. A mean peak benorylate plasma level of 2.18 +/- 0.19 mug/ml occurred 30 min after drug administration but declined rapidly and benorylate was virtually undetectable in the plasma 90 min later. The mean peak benorylate synovial fluid level of 0.74 +/- 0.21 mug/ml occurred 3 hours after drug administration but the concentration remained steady for at least a further 9 hours. A mean peak plasma salicylate level of 119 +/- 14.2 mug/ml and mean peak synovial fluid salicylate level of 78 +/- 13.6 mug/ml occurred 3 hours after benorylate administration. Both levels declined slowly over some hours. This study shows that benorylate per se readily enters the synovial fluid in patients with rheumatoid arthritis and continues to accumulate there even when undetectable in the plasma. It is possible that the lipophilic nature of the benorylate molecule facilitates its uptake by the inflamed synovial tissue.

Topics: Arthritis, Rheumatoid; Chronic Disease; Humans; Salicylates; Synovial Fluid

Topics: Adult; Aged; Ambulatory Care; Aminopyrine; Arthritis, Rheumatoid; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prednisolone; Rural Health; Russia; Salicylates

1 Nine patients with rheumatoid arthritis or non-inflammatory backache were given soluble aspirin (65 mg/kg body weight) daily. There was no significant difference between the plasma salicylate of those with rheumatoid arthritis and those with backache. 2 Two patients had plasma salicylate values that differed significantly from the remainder but neither these results nor the marginal differences between plasma salicylate levels of the others could be explained by individual variations in the capacity for excreting salicyluric acid or salicyl phenolic glucuronide. 3 Increasing the dose of aspirin in four patients demonstrated the reduced proportions of salicyluric acid and salicyl phenolic glucuronide excreted at high doses and the increased importance of unchanged salicylic acid as an excretory pathway. These findings are consistent with a limiting capacity for salicyluric acid and salicyl phenolic glucuronide synthesis and excretion. 4 The findings in one patient suggested that inter-subject variations in the capacity for producing salicyl phenolic glucuronide and salicyluric acid may have an effect on plasma salicylate levels at high doses of aspirin.

Topics: Arthritis, Rheumatoid; Aspirin; Back Pain; Female; Humans; Male; Middle Aged; Salicylates

Topics: Adrenocorticotropic Hormone; Anti-Inflammatory Agents; Antimalarials; Arthritis, Rheumatoid; Cortisone; Gold Sodium Thiomalate; History, 20th Century; Humans; Immunosuppressive Agents; Joint Prosthesis; Methods; Salicylates

Topics: Adult; Arthritis, Rheumatoid; Female; Glomerulonephritis; Humans; Male; Middle Aged; Salicylates

Salicylates form the basis of drug treatment in rheumatoid arthritis. Despite their use for many decades, there is considerable confusion about what constitutes a regime which will ensure anti-inflammatory properties. We have found that blood vessels in the proposed therapeutic range can be maintained overnight on a four times daily dose regime, using either soluble aspirin (in the form of "Disprin") or aloxiprin ("Palaprin Forte"), and on a 12 hourly regine using an aspirin-sustained release aspirin combination ("BiPrin"). Because of variation in the levels reached using a fixed dosage schedule, treatment should be individualised. No correlation was found between dosage levels and either disease activity or serum albumin levels. No significant alteration in free or total salicylate levels was found following the addition of indomethacin to therapy.

Topics: Adult; Arthritis, Rheumatoid; Aspirin; Delayed-Action Preparations; Drug Therapy, Combination; Female; Humans; Indomethacin; Male; Middle Aged; Salicylates

Topics: Adrenal Glands; Adrenal Insufficiency; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antimalarials; Arthritis, Rheumatoid; Endocrine System Diseases; Glucocorticoids; Gold; Humans; Hypopituitarism; Immunosuppressive Agents; Infections; Metyrapone; Orthotic Devices; Physical Therapy Modalities; Pituitary Gland; Pituitary Hormones; Pyrazoles; Salicylates

Urine levels of the lysosomal enzyme beta-N-acetylglucosaminidase have been measured in patients with arthritic disorders; significantly higher levels were found in patients with rheumatoid arthritis (mean: 332.9 nmol/h/mg creat.) than in those with degenerative joint disease (mean: 86.31 nmol/h/mg creat.; P less than 0.001). Analysis of the results shows that salicylates were responsible for some of this difference, but suggests that rheumatoid disease itself may cause renal damage.

Topics: Acetylglucosaminidase; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Hexosaminidases; Humans; Kidney Diseases; Salicylates

Topics: Arthritis, Rheumatoid; Aspirin; Back Pain; Glucuronates; Humans; Kinetics; Salicylates; Time Factors; Uric Acid

Topics: Acetaminophen; Acetanilides; Administration, Oral; Arthritis, Rheumatoid; Aspirin; Foot; Gout; Hand; Humans; Indomethacin; Injections, Intra-Articular; Knee; Prednisolone; Salicylates; Thermography

While rheumatic fever is relatively uncommon except where there are poor and crowded living conditions, sporadic acute attacks continue to occur in a family or pediatric medical practice. The physician's role in management of the sore throat in the diagnosis of suspected cases of rheumatic fever and in follow-up for continued prophylaxis is discussed. The frequency of admissions and presenting features of 159 patients with acute rheumatic fever is reviewed. Continued surveillance is required if we are to achieve a further reduction in attack rate and complications.

Topics: Acute Disease; Adolescent; Antistreptolysin; Arthritis, Juvenile; Arthritis, Rheumatoid; Child; Child, Preschool; Diagnosis, Differential; Heart Murmurs; Heart Valve Diseases; Humans; Manitoba; Penicillins; Prednisone; Rheumatic Fever; Rheumatic Heart Disease; Salicylates; Streptococcal Infections; Streptococcus; Time Factors

Topics: Arthritis, Juvenile; Arthritis, Reactive; Arthritis, Rheumatoid; Chemotaxis; Exudates and Transudates; Humans; Joint Diseases; Leukocytes; Osteoarthritis; Phenylbutazone; Rheumatoid Factor; Salicylates; Synovial Fluid

Topics: Aged; Ankle Joint; Arthritis; Arthritis, Rheumatoid; Arthroplasty; Bursitis; Gout; Hip Joint; Humans; Indomethacin; Knee Joint; Laminectomy; Middle Aged; Osteoarthritis; Osteotomy; Phenylbutazone; Physical Therapy Modalities; Radiography; Salicylates; Shoulder Joint; Spinal Diseases; Tarsal Joints; Wrist Joint

Topics: Animals; Arthritis, Rheumatoid; Carbon Radioisotopes; Chloroquine; Collagen; Freund's Adjuvant; Hydroxyproline; Male; Phenylbutazone; Phosphates; Proline; Rats; Salicylates; Skin; Sodium; Solubility

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Drug Interactions; Freund's Adjuvant; Male; Phenylpropionates; Rats; Salicylates; Time Factors

Topics: Arthritis, Rheumatoid; Blood Proteins; Calcium; Chromatography, Gel; Humans; Protein Binding; Salicylates; Serum Albumin

A total of 125 patients with rheumatoid arthritis were investigated about their drug therapy before referral to a specialist centre. Most referrals were from general practitioners. Only 47 of the patients had received salicylates as the first drug and 18 had never had them at all. Soluble aspirin was the preparation of salicylates most frequently prescribed (for 63 patients). Only 60 patients had been given an adequate dose and only 62 an adequate course of treatment with salicylates. In 28 patients salicylates had been stopped on account of side effects. About one-third of the patients had been prescribed oral corticosteroids.The referral letters were poor in giving details of past and present drug therapy, and there were serious omissions in reporting of previous side effects.Seventy-five general practitioners were asked to rate several currently marketed antirheumatic drugs in terms of effectiveness. Though prednisolone 15 mg daily ranked higher than aspirin 4 g daily the difference was not significant. The study shows the inadequacies of drug prescribing for rheumatoid arthritis in the Glasgow area.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Arthritis, Rheumatoid; Aspirin; Drug Prescriptions; Dyspepsia; Family Practice; Female; Gastrointestinal Hemorrhage; Humans; Indomethacin; Male; Middle Aged; Phenylbutazone; Prednisone; Salicylates; Scotland

A survey of 763 patients with rheumatoid arthritis and 145 with osteoarthritis in six clinics in New Zealand showed no association between aspirin intake and a score designed to detect analgesic nephropathy. Analgesic nephropathy was diagnosed clinically in three patients taking APC (aspirin, phenacetin, and caffeine or codeine or both) and in one who took aspirin and phenylbutazone and was suspected in one who took aspirin and paracetamol. Isolated aspirin was not implicated. The study showed that most people can take large quantities of salicylates without renal injury.The findings are, however, consistent with the view that there is a risk from APC compounds taken in large quantity, but the numbers at risk in this study were small. Aspirin may have an additive effect with other analgesics in causing renal damage. An increased frequency of urinary tract symptoms in those taking analgesics requires further investigation.

Topics: Acetaminophen; Adult; Arthritis, Rheumatoid; Aspirin; Caffeine; Codeine; Drug Synergism; Female; Humans; Kidney Diseases; Male; Middle Aged; New Zealand; Osteoarthritis; Phenacetin; Phenylbutazone; Salicylates; Urinary Tract Infections

Topics: Adult; Arthritis, Rheumatoid; Cervical Vertebrae; Gold; Humans; Lumbar Vertebrae; Male; Middle Aged; Military Medicine; Phenylbutazone; Radiography; Salicylates; Spondylitis, Ankylosing; United Kingdom

Topics: Administration, Oral; Arthritis, Rheumatoid; Aspirin; Child; Choline; Female; Humans; Male; Rheumatic Fever; Salicylates

Topics: Acetanilides; Acetates; Arthritis, Rheumatoid; Deafness; Humans; Salicylates; Tinnitus

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Exercise Therapy; Humans; Osmium; Physical Therapy Modalities; Salicylates

Topics: Arthritis, Rheumatoid; Arthrodesis; Arthroplasty; Chloroquine; Fingers; Gold; Humans; Indomethacin; Joint Prosthesis; Knee; Penicillamine; Pyrazoles; Radiography; Salicylates; Synovectomy

Topics: Acetanilides; Analgesics; Arthritis, Rheumatoid; Blood Sedimentation; Chronic Disease; Edema; Female; Finger Joint; Fingers; Humans; Male; Middle Aged; Muscle Contraction; Nausea; Pain; Physical Exertion; Salicylates; Suspensions

Topics: Age Factors; Aged; Arthritis, Rheumatoid; Aspirin; Audiometry; Drug Tolerance; Humans; Indomethacin; Middle Aged; Salicylates; Spectrophotometry; Time Factors; Tinnitus

Topics: Administration, Oral; Adult; Arthritis; Arthritis, Rheumatoid; Aspirin; Bursitis; Humans; Middle Aged; Osteoarthritis; Psoriasis; Salicylates; Synovial Fluid; Synovitis; Time Factors

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Cortisone; Humans; Methods; Pain; Phenylbutazone; Salicylates

Topics: Aged; Arthritis, Rheumatoid; Aspirin; Drug Compounding; Female; Foreign Bodies; Humans; Hydrogen-Ion Concentration; Jejunum; Pyloric Stenosis; Salicylates; Stomach; Tablets, Enteric-Coated; Vagotomy

Topics: Adult; Agranulocytosis; Aminopyrine; Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Benzyl Compounds; Collagen; Dimethylamines; Erythrocytes; Female; Gold; Half-Life; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Indazoles; Indomethacin; Male; Mice; Middle Aged; Phenylbutazone; Prednisone; Salicylates; Synovial Fluid; Thiosulfates; Triaziquone

Topics: Adrenal Cortex Hormones; Arthritis, Rheumatoid; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Quinolines; Salicylates; Time Factors

Topics: Adrenal Cortex Hormones; Arthritis, Rheumatoid; Gold; Humans; Immunosuppressive Agents; Salicylates

Topics: Adrenal Cortex Hormones; Antimalarials; Arthritis, Rheumatoid; Gold; Humans; Immunosuppressive Agents; Indomethacin; Injections, Intra-Arterial; Phenylbutazone; Salicylates

Topics: Antibodies, Antinuclear; Arthritis, Rheumatoid; Biopsy; Connective Tissue; Dermatomyositis; Diphosphates; Gout; Humans; Hyperparathyroidism; Inflammation; Joint Diseases; Lupus Erythematosus, Systemic; Neutrophils; Polyarteritis Nodosa; Psoriasis; Rheumatoid Factor; Salicylates; Sarcoidosis; Spondylitis, Ankylosing; Synovial Fluid; Synovial Membrane; Uric Acid

Topics: Adenocarcinoma, Bronchiolo-Alveolar; Adult; Arthritis, Rheumatoid; Aspirin; Bronchial Neoplasms; Female; Humans; Lung; Radiography; Rheumatoid Nodule; Salicylates

Topics: Animals; Arthritis, Rheumatoid; Aspirin; Diatrizoate; Gastrointestinal Hemorrhage; Humans; Platelet Adhesiveness; Rats; Salicylates; Sorbitol

Topics: Adolescent; Antibodies, Antinuclear; Arthritis, Juvenile; Arthritis, Rheumatoid; Autopsy; Biopsy; Blood Pressure; Child; Child, Preschool; Creatinine; Cryoglobulins; Female; Gold; Humans; Infant; Kidney; Kidney Function Tests; Male; Phenylbutazone; Proteinuria; Rheumatoid Factor; Salicylates; Time Factors

Topics: Adult; Age Factors; Aged; Arthritis, Rheumatoid; Audiometry; Ear; Ear Diseases; Ear, Middle; Hearing Disorders; Hearing Loss, Noise-Induced; Hearing Tests; Humans; Indomethacin; Meniere Disease; Middle Aged; Neuritis; Pilot Projects; Salicylates

Topics: Adult; Age Factors; Aged; Arthritis, Rheumatoid; Bone Resorption; Creatinine; Female; Glomerular Filtration Rate; Gold; Humans; Kidney; Kidney Glomerulus; Male; Middle Aged; Prednisolone; Salicylates; Serologic Tests; Sex Factors

Topics: Alkylating Agents; Analgesics; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antimalarials; Antimetabolites; Arthritis, Rheumatoid; Chronic Disease; Enzymes; Glucocorticoids; Gold; Humans; Immunosuppressive Agents; Indoles; Mefenamic Acid; Physical Therapy Modalities; Pyrazoles; Salicylates

Topics: Adult; Aged; Arthritis, Rheumatoid; Autoantibodies; Autoradiography; Diagnosis, Differential; Hemagglutination Tests; Humans; Immunoglobulins; Iodine Isotopes; Lipoproteins; Male; Precipitin Tests; Salicylates

Topics: Acetaminophen; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Cells, Cultured; Histamine; Humans; In Vitro Techniques; Inflammation; Lysosomes; Membranes; Permeability; Salicylates; Skin Diseases; Synovial Membrane

Topics: Arthritis, Rheumatoid; Glucuronates; Half-Life; Humans; Kinetics; Salicylates

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Blood Proteins; Cattle; Chloroquine; Dipeptides; Gold; Humans; Indomethacin; Phenylalanine; Phenylbutazone; Prednisolone; Protein Binding; Salicylates; Serum Albumin, Bovine; Tryptophan

Topics: Arthritis, Rheumatoid; Chloroquine; Drug-Related Side Effects and Adverse Reactions; Glucocorticoids; Gold; Humans; Hydroxychloroquine; Iatrogenic Disease; Indomethacin; Phenylbutazone; Salicylates

Topics: Acid-Base Equilibrium; Adrenal Cortex Hormones; Aminopyrine; Antineoplastic Agents; Arthritis, Rheumatoid; Autoimmune Diseases; Gold; Health Education; Home Care Services; Humans; Indenes; Indomethacin; Inflammation; Phenylbutazone; Pyrazoles; Quinolines; Rest; Salicylates

Using a new in vitro method of measuring the chemotaxis of polymorphonuclear leukocytes from peripheral blood, a chemotactic index has been calculated. The mean chemotactic index of 320 in 24 patients with definite rheumatoid arthritis, was significantly less (P < 0.0005) than the mean of 555 in 24 normal controls matched for age and sex. The mean chemotactic index of 435 in eight patients with juvenile rheumatoid arthritis was also significantly less (P < 0.01) than that of 553 in similarly matched controls. The chemotactic index could not be correlated with age, sex, disease activity, drugs used in treatment, latex titer, immunoglobulin levels, or protein coating on the cells. However, there was a correlation between the chemotactic index and the serum complement B(1e)/B(1a) value (P < 0.01) in 17 patients with adult onset rheumatoid arthritis. Although the serum complement B(1e)/B(1a) values were within the normal range, the lowest chemotactic indices were associated with the lowest complement values. The chemotactic indices in three patients with severe connective tissue disease (seropositive rheumatoid arthritis, systemic lupus erythematosus, and polymyositis) returned to normal after 5 days' treatment with 60 mg of prednisolone per day. Incubation of the cells from patients with rheumatoid arthritis with hydrocortisone in vitro failed to alter the chemotactic indices. Prior incubation of normal cells with purified rheumatoid factor complexes, rheumatoid serum, or macromolecules of iron dextran impaired their chemotaxis. It is suggested that phagocytosis of complexes in vivo is a possible mechanism by which the chemotaxis of the polymorphonuclear leukocytes of patients with rheumatoid arthritis is impaired. This impairment in chemotaxis may explain the increased incidence of bacterial infection, both during life and as a cause of death in these patients.

Topics: Adolescent; Adult; Aged; Arthritis, Rheumatoid; Chemotaxis; Child; Complement System Proteins; Female; Humans; Hydrocortisone; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Latex Fixation Tests; Leukocytes; Lupus Erythematosus, Systemic; Male; Methods; Middle Aged; Myositis; Phagocytosis; Prednisolone; Rheumatoid Factor; Salicylates

Topics: Anti-Inflammatory Agents; Antigens; Antilymphocyte Serum; Arthritis, Rheumatoid; Chloroquine; Glucocorticoids; Gold; Humans; Indomethacin; Lymphocytes; Lysosomes; Rheumatic Diseases; Rheumatoid Factor; Salicylates

Topics: Acetaminophen; Adrenal Cortex Hormones; Arthritis; Arthritis, Rheumatoid; Aspirin; Chloroquine; Codeine; Cortisone; Cyclophosphamide; Dextropropoxyphene; Gold; Gout; Humans; Indomethacin; Mefenamic Acid; Pentazocine; Phenylbutazone; Salicylates; Spondylitis, Ankylosing

Topics: Adult; Aged; Arthritis, Rheumatoid; Female; Humans; Indomethacin; Male; Middle Aged; Peptic Ulcer Hemorrhage; Peptic Ulcer Perforation; Prednisone; Salicylates; Stomach Ulcer

Topics: Adrenal Cortex Hormones; Arthritis, Rheumatoid; Gold; Humans; Immunosuppressive Agents; Indomethacin; Physical Therapy Modalities; Rest; Salicylates

Topics: Adolescent; Adult; Anemia, Hypochromic; Arthritis, Rheumatoid; Child; Female; Humans; Iron; Male; Middle Aged; Rheumatic Diseases; Salicylates

Topics: Adrenal Cortex Hormones; Age Factors; Aged; Arthritis, Rheumatoid; Chronic Disease; Female; Gold; Hospitalization; Humans; Indomethacin; Male; Middle Aged; Rest; Salicylates

Topics: Adult; Arthritis; Arthritis, Rheumatoid; Chronic Disease; Exudates and Transudates; Female; Humans; Male; Salicylates; Synovial Fluid

Topics: Arthritis, Rheumatoid; Chronic Disease; Cortisone; Flufenamic Acid; Gold; Humans; Indoles; Mefenamic Acid; Physical Therapy Modalities; Salicylates

Topics: Arthritis, Rheumatoid; Humans; Salicylates

Topics: Arthritis, Rheumatoid; Salicylates

Topics: Adolescent; Adult; Aged; Arthritis, Rheumatoid; Female; Follow-Up Studies; gamma-Globulins; Hemoglobinometry; Humans; Male; Middle Aged; Nigeria; Radiography; Rheumatoid Factor; Salicylates; Synovial Fluid; Uric Acid

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Antimalarials; Antineoplastic Agents; Arthritis, Rheumatoid; Female; Gold; Humans; Male; Rest; Salicylates

Topics: Adrenal Cortex Hormones; Analgesics; Anti-Inflammatory Agents; Antidepressive Agents; Arthritis, Reactive; Arthritis, Rheumatoid; Drug Synergism; Humans; Osteoarthritis; Rheumatic Diseases; Salicylates; Spondylitis, Ankylosing

Topics: Adrenal Cortex Hormones; Antimalarials; Antineoplastic Agents; Arthritis, Rheumatoid; Aspirin; Chronic Disease; Gold Colloid, Radioactive; Humans; Immunosuppressive Agents; Indomethacin; Pyrazoles; Rheumatic Diseases; Salicylates; Ultrasonic Therapy

Topics: Analgesics; Anti-Inflammatory Agents; Antimalarials; Arthritis, Rheumatoid; Gold; Humans; Salicylates

Topics: Adult; Aged; Arthritis, Rheumatoid; Bone Resorption; Calcium; Calcium Isotopes; Female; Humans; Indomethacin; Intestinal Absorption; Male; Middle Aged; Prednisolone; Salicylates; Time Factors; Triamcinolone

Topics: Administration, Topical; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Blood Protein Electrophoresis; Blood Proteins; Humans; Hydrocortisone; Injections, Intra-Articular; Quinones; Salicylates

Topics: Angiography; Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Dogs; Injections, Intra-Articular; Knee Joint; Methylprednisolone; Microradiography; Microscopy, Electron; Prednisolone; Rabbits; Regeneration; Salicylates; Synovectomy; Synovial Membrane

Topics: Arthritis, Rheumatoid; Collagen Diseases; Humans; Lupus Erythematosus, Systemic; Prednisolone; Pyrazoles; Rheumatic Fever; Rheumatic Heart Disease; Salicylates; Scleroderma, Systemic; Triamcinolone

Topics: Analgesics; Arthritis, Rheumatoid; Comprehensive Health Care; Humans; Immobilization; Occupational Therapy; Salicylates; Splints

Topics: Adult; Aged; Arthritis, Rheumatoid; Female; Glaucoma; Humans; Indomethacin; Intraocular Pressure; Male; Middle Aged; Pilocarpine; Salicylates; Tonometry, Ocular

Topics: Adult; Arthritis; Arthritis, Rheumatoid; Emulsions; Female; Heparinoids; Humans; Male; Middle Aged; Nicotinic Acids; Osteoarthritis; Salicylates; Spinal Diseases

Topics: Adrenal Cortex Hormones; Arthritis, Rheumatoid; Balneology; Drug Synergism; Electric Stimulation Therapy; Flufenamic Acid; Gold; Humans; Immunosuppressive Agents; Indomethacin; Prednisolone; Pyrazoles; Salicylates; Time Factors

Topics: Analgesics; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Collagen Diseases; Humans; Indomethacin; Phenylbutazone; Physician-Patient Relations; Quinolines; Salicylates; Spondylitis, Ankylosing

Topics: Arthritis; Arthritis, Rheumatoid; Collagen Diseases; Gold; Humans; Otorhinolaryngologic Diseases; Phenylbutazone; Respiratory Insufficiency; Rheumatic Fever; Salicylates; Tonsillectomy

Topics: Arthritis, Rheumatoid; Humans; Nutritional Physiological Phenomena; Physical Therapy Modalities; Rest; Salicylates

Topics: Alkalosis; Antacids; Anti-Inflammatory Agents; Antibody Formation; Arthritis, Rheumatoid; Aspirin; Drug Hypersensitivity; Gastritis; Humans; Salicylates

Topics: Arthritis, Rheumatoid; Chloroquine; Gold; Humans; Phenylbutazone; Prednisone; Salicylates

Topics: Adrenal Cortex Hormones; Arthritis, Rheumatoid; Chronic Disease; Gold; Humans; Indomethacin; Salicylates

Topics: Adult; Aged; Arthritis, Rheumatoid; Aspirin; Body Weight; Circadian Rhythm; Female; Humans; Intestinal Absorption; Male; Middle Aged; Salicylates; Solubility; Tablets, Enteric-Coated

Topics: Adolescent; Adult; Arthritis; Arthritis, Rheumatoid; Butadienes; Child; Glucocorticoids; Health Resorts; Humans; Mud Therapy; Rheumatic Fever; Salicylates

Topics: Arthritis, Rheumatoid; Female; Humans; Male; Salicylates

Topics: Analgesics; Arthritis, Rheumatoid; Diabetes Complications; Female; Humans; Kidney Papillary Necrosis; Male; Middle Aged; Phenacetin; Salicylates; Scotland; Urologic Diseases

Topics: Arthritis, Rheumatoid; Glucocorticoids; Gold; Humans; Hydroxychloroquine; Salicylates

Topics: Arthritis, Rheumatoid; Cell Membrane Permeability; Humans; In Vitro Techniques; Latex Fixation Tests; Lymph Nodes; Salicylates; Synovial Fluid; Synovial Membrane

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Arthritis, Rheumatoid; Female; Humans; Male; Middle Aged; Physical Therapy Modalities; Prednisone; Salicylates; Substance Withdrawal Syndrome

Topics: Adrenal Cortex Hormones; Ambulatory Care; Arthritis, Rheumatoid; Chloroquine; Chronic Disease; Family Practice; Gold; Gout; Humans; Mineral Waters; Physical Therapy Modalities; Prednisone; Rheumatic Diseases; Salicylates; Spondylitis, Ankylosing

Topics: 17-Ketosteroids; Adult; Arthritis, Rheumatoid; Baths; Female; Humans; Humic Substances; Male; Middle Aged; Salicylates; Skin Absorption; Solutions

Topics: Adult; Arthritis, Rheumatoid; Child; Female; Humans; Infant; Joint Diseases; Male; Pyrazoles; Radiography; Salicylates

Topics: Analgesics; Arthritis, Rheumatoid; Atropa belladonna; Humans; Joint Diseases; Ointments; Phytotherapy; Plants, Medicinal; Plants, Toxic; Salicylates

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Chloroquine; Gold; Humans; Hyaluronic Acid; Hydrocortisone; Joints; Osteoarthritis; Salicylates; Synovial Fluid

Topics: Adrenal Cortex Hormones; Adult; Aged; Arthritis, Rheumatoid; Bradykinin; Enzyme Precursors; Enzymes; Erythrocytes; Gold; Humans; Hydroxychloroquine; Indomethacin; Male; Middle Aged; Phenylbutazone; Phosphotransferases; Salicylates

Topics: Adrenocorticotropic Hormone; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Chloroquine; Dimethyl Sulfoxide; England; Europe; Flufenamic Acid; Gold; Humans; Indomethacin; Injections, Intra-Articular; Japan; ortho-Aminobenzoates; Oxyphenbutazone; Phenylbutazone; Prednisolone; Salicylates; South America; United States

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Anti-Bacterial Agents; Arthritis, Rheumatoid; Endocarditis; Female; Gold; Humans; Penicillin G Benzathine; Phenylbutazone; Pregnancy; Pregnancy Complications; Rheumatic Fever; Salicylates

Topics: Adrenal Cortex Hormones; Arthritis, Rheumatoid; Exercise Therapy; Gold; Hot Temperature; Osteoarthritis; Salicylates; Temporomandibular Joint

Topics: Adolescent; Adult; Arthritis, Rheumatoid; Female; Heart; Humans; Male; Middle Aged; Salicylates

Topics: Adrenal Cortex Hormones; Adult; Aged; Amyloidosis; Arthritis, Rheumatoid; Female; Humans; Kidney Diseases; Kidney Papillary Necrosis; Male; Middle Aged; Nephritis, Interstitial; Phenacetin; Phenylbutazone; Pyelonephritis; Salicylates

Topics: Adrenal Cortex Hormones; Arthritis, Rheumatoid; Dyspepsia; Female; Humans; Male; Peptic Ulcer; Phenylbutazone; Salicylates

Topics: Adrenal Cortex Hormones; Adult; Anemia, Hypochromic; Arthritis, Rheumatoid; Dyspepsia; Female; Hemagglutination Tests; Hemoglobinometry; Hemoglobins; Humans; Iron; Male; Middle Aged; Phenylbutazone; Salicylates

Topics: Arthritis, Rheumatoid; Humans; Salicylates

Topics: Adult; Aged; Aging; Anthropometry; Arthritis, Rheumatoid; Bone and Bones; Bone Development; Bone Resorption; Humans; Middle Aged; Salicylates; Tetracycline

Topics: Adrenal Cortex Hormones; Arthritis; Arthritis, Rheumatoid; Blindness; Cataract; Conjunctivitis; Diplopia; Drug Therapy; Edema; Eye Diseases; Eye Manifestations; Glaucoma; Gold; Humans; Iatrogenic Disease; Intraocular Pressure; Iridocyclitis; Iritis; Keratitis; Lupus Erythematosus, Systemic; Myopia; Rheumatic Diseases; Salicylates; Spondylitis; Spondylitis, Ankylosing; Toxicology; Uveitis

Topics: Adrenal Cortex Hormones; Antigen-Antibody Reactions; Antineoplastic Agents; Arthritis; Arthritis, Rheumatoid; Autoantibodies; Autoimmune Diseases; Drug Therapy; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Phenylbutazone; Salicylates; Toxicology

Topics: Arthritis; Arthritis, Rheumatoid; Aspirin; Drug Therapy; Salicylates; Toxicology

Topics: Adolescent; Arthritis; Arthritis, Juvenile; Arthritis, Rheumatoid; Child; Child Care; Chloroquine; Diagnosis; Drug Therapy; Family Practice; General Practice; Gold; Humans; Penicillins; Prednisone; Rheumatic Fever; Salicylates

Topics: Adrenal Cortex Hormones; Arthritis; Arthritis, Rheumatoid; Body Fluids; Drug Therapy; Edema; Electrophoresis; Phenylbutazone; Proteins; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Aspirin; Dosage Forms; Drug Therapy; Geriatrics; Humans; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Chloroquine; Drug Therapy; Female; Gold; Humans; Hydrocortisone; Indomethacin; Phenylbutazone; Pregnancy; Pregnancy Complications; Salicylates; Toxicology

Topics: Arthritis; Arthritis, Rheumatoid; Circadian Rhythm; Drug Therapy; Humans; Inflammation; Joint Diseases; Pain; Rheumatic Diseases; Salicylates; Toxicology

Topics: Arthritis; Arthritis, Rheumatoid; Aspirin; Audiometry; Blood; Cochlea; Drug Therapy; Enzyme Inhibitors; Geriatrics; Hearing Disorders; Hearing Tests; Humans; Oxidoreductases; Salicylates; Tinnitus; Toxicology

Topics: Adult; Aged; Arthritis, Rheumatoid; Complement System Proteins; Female; Gold; Humans; Latex Fixation Tests; Male; Middle Aged; Prednisone; Rheumatoid Factor; Salicylates; Serologic Tests

Topics: Adult; Arteritis; Arthritis, Rheumatoid; Gangrene; Humans; Leg Ulcer; Male; Middle Aged; Physical Therapy Modalities; Salicylates; Skin Manifestations

Topics: Arthritis, Rheumatoid; Baths; Female; Humans; Humic Substances; Male; Salicylates

A number of acute and chronic inflammatory disorders are amenable to varying degrees of therapeutic control with the administration of nonspecific anti-inflammatory drugs. An evaluation of these suppressive agents in the field of rheumatic diseases and practical suggestions regarding their administration are presented. Eight synthetically modified corticosteroid compounds are available commercially. Each of them exhibits qualitative differences in one or several physiologic actions, each has certain advantages and disadvantages in therapy, and each shares the major deterrent features of corticosteroids. Prednisone, prednisolone, methylprednisolone, fluprednisolone and paramethasone have similar therapeutic indices, and there is little choice between them for the usual rheumatoid patient requiring steroid therapy. Conversely, the therapeutic indices of dexamethasone, betamethasone and triamcinolone are lower than that of prednisolone; they are less desirable for routine use and should be reserved for specially selected cases. Salicylates are preferred to adrenocortical steroids in the treatment of the ordinary patient with acute rheumatic fever. Steroid therapy should be reserved for resistant cases and for those with significant carditis. Salicylates are mainstays for pain relief in rheumatoid arthritis, but with the analgesic doses usually employed their anti-inflammatory action is slight.Phenylbutazone is a highly useful anti-inflammatory agent, especially in management of acute gouty arthritis and ankylosing (rheumatoid) spondylitis; its metabolite, oxyphenylbutazone, does not exhibit clear-cut advantages. Colchicine specifically suppresses acute gouty arthritis. Its analogues, desacetylcolchicine and desacetylthiocolchicine, produce fewer unpleasant gastrointestinal symptoms, but may promote agranulocytosis and alopecia.A number of indole preparations with anti-inflammatory activity have been tested clinically. One of them, indomethacin, has received extensive therapeutic trial; with dosages that can be tolerated the drug is fairly effective in the symptomatic control of ankylosing (rheumatoid) spondylitis but it is of questionable value in peripheral rheumatoid arthritis.

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Arthritis; Arthritis, Rheumatoid; Betamethasone; Colchicine; Dexamethasone; Humans; Indoles; Indomethacin; Methylprednisolone; Oxyphenbutazone; Paramethasone; Pharmacology; Phenylbutazone; Prednisolone; Prednisone; Rheumatic Fever; Salicylates; Toxicology; Triamcinolone

Topics: Adrenal Cortex Hormones; Arthritis; Arthritis, Rheumatoid; Gold; Methylprednisolone; Office Management; Phenylbutazone; Prednisone; Salicylates; Toxicology

Topics: Arthritis; Arthritis, Rheumatoid; Aspirin; Carbohydrate Metabolism; Delayed-Action Preparations; Humans; Polysaccharides; Salicylates; Uracil Nucleotides

Topics: Arthritis; Arthritis, Rheumatoid; Blood Transfusion; Collagen Diseases; Connective Tissue; Cortisone; Humans; Lung Diseases; Lupus Erythematosus, Systemic; Pathology; Physical Therapy Modalities; Polyarteritis Nodosa; Radiography, Thoracic; Salicylates; Scleroderma, Systemic

Topics: Aged; Allergy and Immunology; Arthritis; Arthritis, Rheumatoid; Diabetic Retinopathy; Geriatrics; Humans; Middle Aged; Salicylates; Statistics as Topic

Topics: Arthritis; Arthritis, Rheumatoid; Ascorbic Acid; Aspirin; Blood Chemical Analysis; Humans; Knee; Plasma; Proteins; Salicylates; Serum Albumin; Synovial Fluid

Topics: Anemia; Arthritis; Arthritis, Rheumatoid; Climate; Diet; Diet Therapy; Exercise Therapy; Gold; Hot Temperature; Humans; Hydrocortisone; Hyperthermia, Induced; Phenylbutazone; Physician-Patient Relations; Prednisone; Rest; Salicylates; Toxicology

Topics: Arthritis; Arthritis, Rheumatoid; Cervical Vertebrae; Cortisone; Deglutition Disorders; Hoarseness; Humans; Larynx; Pathology; Prednisone; Salicylates; Spinal Cord Compression; Synovitis; Voice; Wrist

Topics: Aluminum; Arthritis; Arthritis, Rheumatoid; Biomedical Research; Dyspepsia; Geriatrics; Hydroxides; Pharmacology; Placebos; Salicylates; Silicones; Toxicology

Topics: Adolescent; Adrenal Cortex Hormones; Antimalarials; Arthritis; Arthritis, Juvenile; Arthritis, Rheumatoid; Child; Diagnosis; Drug Therapy; Gold; Humans; Phenylbutazone; Physical Therapy Modalities; Salicylates

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Antimalarials; Arthritis; Arthritis, Rheumatoid; Child; Drug Therapy; Gold; Phenylbutazone; Salicylates; Toxicology

Topics: Arthritis; Arthritis, Rheumatoid; Diagnosis, Differential; Humans; Pathology; Phenylbutazone; Prednisolone; Prednisone; Prognosis; Salicylates

Topics: Adrenal Cortex Hormones; Arthritis; Arthritis, Rheumatoid; Humans; Phenylbutazone; Rheumatic Fever; Salicylates

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Analgesics; Analgesics, Non-Narcotic; Antimalarials; Antipyretics; Arthritis; Arthritis, Rheumatoid; Gout; Pyrazoles; Rheumatic Fever; Salicylates; Spondylitis; Spondylitis, Ankylosing

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Antimalarials; Arthritis; Arthritis, Rheumatoid; Gold; Gout; Humans; Pyrazoles; Rheumatic Diseases; Rheumatic Fever; Salicylates; Spondylitis; Spondylitis, Ankylosing; Uricosuric Agents

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Arthritis; Arthritis, Rheumatoid; Gold; Injections; Phenylbutazone; Salicylates; Therapeutics

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Arthritis; Arthritis, Rheumatoid; Asian People; Gold; Humans; Jews; Salicylates; Toxicology

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Arthritis, Rheumatoid; Fever; Humans; Rheumatic Fever; Rheumatic Heart Disease; Salicylates; Statistics as Topic; Streptococcal Infections; Tonsillectomy

Topics: Adrenal Cortex Hormones; Analgesics; Analgesics, Non-Narcotic; Antipyretics; Arthritis; Arthritis, Rheumatoid; Gold; Indoles; Indomethacin; Phenylbutazone; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Aspirin; Drug Therapy; Gastric Acidity Determination; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Drug Therapy; Israel; Prednisone; Salicylates; Toxicology

Topics: Adrenal Cortex Hormones; Aminopyrine; Antirheumatic Agents; Arthritis; Arthritis, Rheumatoid; Chloroquine; Drug Therapy; Gold; Humans; Prednisone; Pyrazoles; Rheumatic Diseases; Rheumatic Fever; Salicylates; Toxicology

Topics: Arthritis; Arthritis, Rheumatoid; Drug Therapy; Hearing Disorders; Hearing Tests; Humans; Research; Rheumatic Fever; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Humans; Hypoparathyroidism; Osteoarthritis; Pantothenic Acid; Phenylbutyrates; Salicylates

Topics: Adrenal Cortex Hormones; Antimalarials; Arthritis; Arthritis, Rheumatoid; Gold; Humans; Osteoarthritis; Phenylbutazone; Physical Therapy Modalities; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Gout; Humans; Salicylates

Topics: Adolescent; Arthritis; Arthritis, Juvenile; Arthritis, Rheumatoid; Exercise Therapy; Gold; Humans; Phenylbutazone; Salicylates

Topics: Adrenal Cortex Hormones; Antimalarials; Arthritis; Arthritis, Rheumatoid; Gold; Humans; Physical Therapy Modalities; Pyrazoles; Salicylates

Arthritis induced in rats by mycobacterial adjuvant has been used for the study of compounds of known value in the treatment of rheumatoid arthritis in man. The development of the arthritic syndrome in treated and control rats was followed by measuring the changes in foot thickness of both hind-feet with a micrometer. This method allowed the effect of anti-inflammatory compounds to be expressed quantitatively. Anti-inflammatory activity was readily observed in certain steroids, pyrazolidines, salicylates and sodium aurothiomalate. Chloroquine and hydroxychloroquine were inactive. The inhibition obtained by daily treatment with the steroid paramethasone disappeared when treatment was withdrawn.

Topics: Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Arthritis; Arthritis, Rheumatoid; Aspirin; Betamethasone; Chloroquine; Cortisone; Dexamethasone; Humans; Hydroxychloroquine; Male; Mycobacterium; Paramethasone; Phenylbutazone; Prednisolone; Rats; Research; Salicylates; Sodium Salicylate

Topics: Analgesics; Antipyretics; Arthritis; Arthritis, Rheumatoid; Aspirin; Fibromyalgia; Humans; Neuritis; Salicylates; Urea

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Antimalarials; Arthritis; Arthritis, Rheumatoid; Copper; Exercise Therapy; Gold; Humans; Phenylbutazone; Physical Therapy Modalities; Physiology; Rehabilitation; Rest; Salicylates

Topics: Adolescent; Adrenal Cortex Hormones; Arthritis; Arthritis, Juvenile; Arthritis, Rheumatoid; Blood Sedimentation; Child; Chloroquine; Diagnosis, Differential; England; Genetics, Medical; Gold; Hemoglobins; Humans; Infant; Iridocyclitis; Mortality; Pathology; Phenylbutazone; Physical Therapy Modalities; Radiography; Salicylates; Splints; Spondylitis; Spondylitis, Ankylosing

Topics: Adolescent; Adrenocorticotropic Hormone; Arthritis; Arthritis, Rheumatoid; Child; Chloroquine; Cortisone; Drug Therapy; Humans; Infant; Prednisone; Pyrazoles; Salicylates; Triamcinolone

Topics: Adrenal Cortex Hormones; Arthritis; Arthritis, Rheumatoid; Chloroquine; Glucocorticoids; Gold; Phenylbutazone; Salicylates

Topics: Achlorhydria; Arthritis; Arthritis, Rheumatoid; Aspirin; Gastric Juice; Salicylates; Stomach Diseases

Topics: Arthritis; Arthritis, Rheumatoid; Blood Sedimentation; Erythrocytes; Salicylates; Steroids

Topics: Arthritis; Arthritis, Rheumatoid; Humans; Hydroxychloroquine; Muscle Relaxants, Central; Phenylbutazone; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Carbohydrate Metabolism; Carbohydrates; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Chlorpromazine; Humans; Hyperuricemia; Salicylates; Uric Acid

Topics: Adrenal Cortex Hormones; Arthritis; Arthritis, Rheumatoid; Glucocorticoids; Humans; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Humans; Salicylates; Sulfanilamide; Sulfanilamides; Sulfonamides

Topics: Adrenal Cortex; Arthritis; Arthritis, Rheumatoid; Humans; Salicylanilides; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Aspirin; Humans; Phenylbutazone; Prednisone; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Glucocorticoids; Humans; Prednisolone; Prednisone; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Humans; Osteoarthritis; Rheumatic Diseases; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Humans; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Colitis; Colitis, Ulcerative; Erythema Nodosum; Humans; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Aspirin; Humans; Osteoarthritis; Salicylates; Succinates; Succinic Acid

Topics: Administration, Intravenous; Antirheumatic Agents; Arthritis; Arthritis, Rheumatoid; Glucose; Hypertonic Solutions; Salicylates; Sodium

Fifty-six patients with rheumatoid arthritis were treated continuously with cortisone for periods ranging between 4 and 38 months, in daily doses of 15 to 100 mg. Concomitant therapy included periods of rest, physical therapy, and salicylates. The incidence of subjective improvement exceeded that of objective improvement. The incidence of objective improvement was higher in females; also, in those patients whose disease was in an early stage and of short duration at the time therapy was begun, and who required relatively smaller maintenance doses of cortisone. Therapeutic results were not affected by the age of the patient or by the presence of spondylitis. Despite precautions, the long-term administration of cortisone was, in some patients, productive of serious undesirable side-effects. Although cortisone usually suppressed the symptoms and signs of rheumatoid arthritis, progression of the disease was frequently noted during its long-term administration.

Topics: Arthritis, Rheumatoid; Cortisone; Disease Progression; Female; Humans; Incidence; Long-Term Care; Physical Examination; Physical Therapy Modalities; Rest; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Salicylates

Topics: Anthelmintics; Arthritis; Arthritis, Rheumatoid; Ascorbic Acid; Mephenesin; Salicylates; Vitamins

Topics: Adrenal Cortex; Adrenal Cortex Hormones; Arthritis; Arthritis, Rheumatoid; Aspirin; Humans; Rheumatic Fever; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Disease; Humans; Neuritis; Peripheral Nerves; Salicylamides; Salicylates

Topics: Adrenocorticotropic Hormone; Arthritis; Arthritis, Rheumatoid; Camphor; Humans; Rheumatic Diseases; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Ascorbic Acid; Carbohydrate Metabolism; Electrolytes; Humans; Leukocyte Count; Minerals; Rheumatic Diseases; Salicylates; Sodium Salicylate; Uric Acid

Topics: Arthritis; Arthritis, Rheumatoid; Balneology; Humans; Salicylates

Topics: Adrenocorticotropic Hormone; Arthritis; Arthritis, Rheumatoid; Cortisone; Gold; Humans; Salicylates

Topics: Administration, Oral; Arthritis; Arthritis, Rheumatoid; Calcium; Calcium, Dietary; Humans; Pantothenic Acid; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Humans; Hypersensitivity; Salicylamides; Salicylates

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Benzocaine; Drug Combinations; Humans; Niacin; Salicylates

Topics: Aminopyrine; Analgesics; Arthritis; Arthritis, Rheumatoid; Humans; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Cortisone; Humans; Joints; Salicylates

Topics: Adrenocorticotropic Hormone; Arthritis; Arthritis, Rheumatoid; Coal Tar; Cortisone; Humans; Rheumatic Diseases; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Catechols; Humans; Rheumatic Fever; Salicylates; Sodium

Topics: 4-Aminobenzoic Acid; Arthritis; Arthritis, Rheumatoid; Salicylates; Sodium Salicylate

Topics: 4-Aminobenzoic Acid; Arthritis; Arthritis, Rheumatoid; Rheumatic Diseases; Salicylates

Topics: Aminosalicylic Acid; Arthritis; Arthritis, Rheumatoid; Female; Humans; Parity; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Humans; Salicylates

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Arthritis; Arthritis, Rheumatoid; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Salicylates