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Biomedical subjects

E J Brewer

Publications and source records attributed to E J Brewer.

At least 19 recordsLinked to original sources

Methotrexate in resistant juvenile rheumatoid arthritis. Results of the U.S.A.-U.S.S.R. double-blind, placebo-controlled trial. The Pediatric Rheumatology Collaborative Study Group and The Cooperative Children's Study Group.

BACKGROUND: The antimetabolite methotrexate has been shown in placebo-controlled trials to be effective in adults with rheumatoid arthritis. Methotrexate may also be effective in children with resistant juvenile rheumatoid arthritis, but the supporting data are from uncontrolled trials. METHODS: Centers in the United States and the Soviet Union participated in this randomized, controlled, double-blind trial designed to evaluate the effectiveness and safety of orally administered methotrexate. Patients received one of the following treatments each week for six months: 10 mg of methotrexate per square meter of body-surface area (low dose), 5 mg of methotrexate per square meter (very low dose), or placebo. The use of prednisone (less than or equal to 10 mg per day) and two nonsteroidal antiinflammatory drugs was also allowed. RESULTS: The 127 children (mean age, 10.1 years) had a mean duration of disease of 5.1 years; 114 qualified for the analysis of efficacy. According to a composite index of several response variables, 63 percent of the children who received low-dose methotrexate improved, as compared with 32 percent of those in the very-low-dose group and 36 percent of those in the placebo group (P = 0.013). As compared with the placebo group, the low-dose group also had significantly larger mean reductions from base line in the number of joints with pain on motion (-11.0 vs. -7.1), the pain-severity score (-19 vs. -11.5), the number of joints with limited motion (-5.4 vs. -0.7), and the erythrocyte sedimentation rate (-19.0 vs. -6 mm per hour). In the methotrexate groups only three children had the drug discontinued because of mild-to-moderate side effects; none had severe toxicity. CONCLUSIONS: Methotrexate given weekly in low doses is an effective treatment for children with resistant juvenile rheumatoid arthritis, and at least in the short term this regimen is safe.

Administration, Oral

Auranofin in the treatment of juvenile rheumatoid arthritis. Results of the USA-USSR double-blind, placebo-controlled trial. The USA Pediatric Rheumatology Collaborative Study Group. The USSR Cooperative Children's Study Group.

A 6-month double-blind, parallel, randomized, placebo-controlled multicenter trial of auranofin (0.15-0.20 mg/kg/day) was conducted in 231 children with juvenile rheumatoid arthritis (JRA) in the United States and in the Union of Soviet Socialist Republics. Approximately 80% of the children had polyarticular disease. The auranofin-treated patients showed greater mean decreases from baseline in 11 of the 12 articular disease indices measured than did the placebo-treated subjects after 3 months of therapy, and in 9 of the 12 indices after 6 months. However, the actual intergroup mean differences were relatively small and were not statistically significant. According to the physician's global assessment, 69% of the auranofin-treated patients and 61% of the placebo-treated patients demonstrated clinically significant improvement from baseline after 6 months (P = 0.24). Children whose disease onset occurred less than 2 years prior to entry improved more than did those who had arthritis for a longer period. In addition, those with polyarticular involvement at baseline improved more than did patients with mild disease. However, these relationships were observed in both the auranofin- and placebo-treated groups, and again, there were no significant intergroup differences. Diarrhea was the most common adverse effect of auranofin. We conclude that the clinical efficacy of auranofin is modestly higher than that of placebo in the treatment of JRA, as evidenced by the consistent trends observed in the data. However, the magnitude of the individual intergroup differences is not statistically significant. Auranofin appears to be very safe in children with JRA.

Anti-Inflammatory Agents, Non-Steroidal

Ibuprofen suspension in the treatment of juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group.

Ninety-two children with juvenile rheumatoid arthritis were randomly assigned to treatment in a multicenter, double-blind, 12-week trial designed to compare the efficacy and safety of a liquid formulation of ibuprofen at a dosage of 30 to 40 mg/kg/day versus those of aspirin at a dosage of 60 to 80 mg/kg/day. No significant intergroup differences in response rates or in the amount of improvement in articular indexes of disease activity were observed. More children treated with aspirin discontinued treatment early because of adverse reactions. After this trial, 84 additional patients with juvenile rheumatoid arthritis entered a 24-week, multidose (30, 40, and 50 mg/kg/day), open trial of ibuprofen suspension. Favorable response rates for the three groups were similar, and continued improvement was observed throughout the 24-week period. A dose-response relationship was observed with respect to adverse reactions of the upper gastrointestinal tract. We conclude that ibuprofen suspension is an effective nonsteroidal antiinflammatory drug and that its tolerability in children is acceptable.

Adolescent

Characteristics of responders and nonresponders to slow-acting antirheumatic drugs in juvenile rheumatoid arthritis.

A 12-month double-blind, parallel, randomized, placebo-controlled multicenter trial of D-penicillamine and hydroxychloroquine was conducted in 162 children with juvenile rheumatoid arthritis in the United States and in the Union of Soviet Socialist Republics. No statistically significant intergroup differences were detected in primary outcome variables. We investigated the possible existence of select subgroups of patients who have a higher likelihood of response to active drugs than to placebo. Using previously published criteria, each patient was classified as a responder or nonresponder, and their demographic and disease characteristics at baseline were compared. We were unable to identify a subgroup of individuals who were more likely to respond to D-penicillamine or hydroxychloroquine than to placebo.

Antibodies, Antinuclear

Spinal cord compression by epidural lipomatosis in juvenile rheumatoid arthritis.

Two cases of spinal cord compression secondary to steroid-induced epidural lipomatosis in systemic juvenile rheumatoid arthritis (JRA) patients are reported. This complication of prolonged corticosteroid therapy has not been described previously in children with JRA. Epidural lipomatosis should be considered in the differential diagnosis of JRA patients receiving high-dose and/or prolonged corticosteroid therapy who present with neurologic signs and symptoms referable to the spinal cord.

Adrenal Cortex Hormones

HLA-B27-associated arthropathy in childhood: long-term clinical and diagnostic outcome.

We conducted HLA-B27 tissue typing assessments on 430 consecutive children whose main symptom at presentation to our clinic was arthritis/arthralgia. Eighty-five of them (20%) had the B27 antigen. Thirty-six of these children were reexamined after a mean followup period of 8.9 years. Although most had definable rheumatic diseases, only 2 met the New York criteria for ankylosing spondylitis (AS). Children with HLA-B27 and arthritis/arthralgia, although at increased risk of developing AS, have diverse diagnostic and clinical outcomes. The AS criteria used to diagnose the disease in adults may not be appropriate for use in children.

Arthritis, Juvenile

Radionuclide bone/joint imaging in children with rheumatic complaints.

We reviewed the medical records and technetium bone/joint scans of 160 children presenting to the inpatient Pediatric Rheumatology service over a 3-year period. When the scan result (normal versus abnormal) was considered for each patient as a whole, scan sensitivity and specificity were both approximately 75%. However, when each joint was considered individually, sensitivity decreased to 37%, while specificity rose to more than 95% when compared to clinical examination. Reasons for these variations and their clinical correlation are discussed. Overall, radionuclide bone/joint scanning was found to be very useful in the evaluation of monoarticular and nonrheumatic disorders, but it did not alter therapy in children with known connective tissue disorders or other polyarticular diseases.

Adolescent

Prognosis of children with poststreptococcal reactive arthritis.

Patients with Group A beta-hemolytic streptococcal infection and articular disease who do not fulfill the modified Jones criteria for a diagnosis of acute rheumatic fever (ARF) have been classified as poststreptococcal reactive arthritis/arthralgia. We reviewed the initial clinical characteristics and outcome of 12 poststreptococcal reactive arthritis/arthralgia patients. During the initial episode all had arthritis or arthralgia and a documented streptococcal infection. None had carditis and none received prophylactic antibiotic therapy during an average follow-up of 17 months (range, 6 to 42 months). One patient developed classic ARF with valvulitis 18 months after the initial episode. Two children had later episodes of arthritis and two had at least one additional episode of arthralgia. Poststreptococcal reactive arthritis/arthralgias seems to be part of the disease spectrum of ARF and therefore the use of prophylactic antibiotic therapy to prevent subsequent development of ARF and carditis in these patients should, perhaps, be reconsidered.

Adolescent

Arthritis/arthralgia and hypermobility of the joints in schoolchildren.

Studies of pediatric clinic populations have shown that a high proportion of children with rheumatic complaints demonstrate hypermobility of the joints. In order to compare the frequency and nature of articular complaints in children with hypermobility to that seen in nonhypermobile controls, we examined 192 normal students aged 5-19 years. Overall, 34% (41/109 girls and 25/83 boys) were found to be hypermobile. Consenting parents of hypermobile children were given a questionnaire and interview designed to detect a history of arthritis/arthralgia, as were parents of age and sex matched nonhypermobile controls. Fifty percent of the hypermobile group had a history of arthralgia, compared to 20% of controls. Ten percent in each group had had arthritis. Data from our comparative study supports the possible association between joint hypermobility and the development of articular complaints in children.

Adolescent

Poor correlation between the erythrocyte sedimentation rate and clinical activity in juvenile rheumatoid arthritis.

Despite questions regarding its validity as an estimator of inflammatory disease activity, monitoring of the erythrocyte sedimentation rate (ESR) continues to be routine practice among pediatric rheumatologists caring for children with juvenile rheumatoid arthritis (JRA). We studied a large group of patients with JRA in order to determine the degree of correlation between clinically apparent inflammation and the ESR. regression and correlation analyses and descriptive statistical techniques were used to establish the relationship between 1) the ESR and the amount of clinically apparent inflammation at a point in time, and 2) changes in the ESR and the corresponding changes in apparent inflammation. One hundred fifty-nine children with JRA who were participants in a double-blind, controlled trial of two antirheumatic drugs were assessed for clinical and laboratory evidence of inflammatory disease activity at an initial visit, and then periodically for the duration of the one year study. Results showed that, at the initial assessment, neither the total number of joints with active arthritis nor the severity score correlated well with the ESR (r = .196 and .245 respectively). These findings were independent of the course type of JRA and age of the child. Changes from baseline in inflammation showed little correlation (r less than .25) with changes in the ESR. These findings suggest that the ESR is a relatively poor indicator of the amount of articular inflammation present, and that changes of disease activity are not reflected closely by changes in the ESR among children with JRA.

Adolescent

Penicillamine and hydroxychloroquine in the treatment of severe juvenile rheumatoid arthritis. Results of the U.S.A.-U.S.S.R. double-blind placebo-controlled trial.

One hundred sixty-two children with severe juvenile rheumatoid arthritis were entered in a randomized, double-blind, placebo-controlled 12-month clinical trial designed to establish the efficacy and safety of two slower-acting antirheumatic drugs, penicillamine and hydroxychloroquine. The study was a cooperative effort of the United States and the Soviet Union. One group of subjects received 10 mg of penicillamine per kilogram of body weight per day, another group received 6 mg of hydroxychloroquine per kilogram daily, and a third group received placebo. All three groups were allowed a single concurrent nonsteroidal antiinflammatory drug, but no other antirheumatic medications, including corticosteroids. All three groups had dramatic improvement in many of the clinical and laboratory outcome variables after one year of study. There were no significant differences in efficacy between the penicillamine and placebo groups. Pain on movement was the only index of articular disease that was alleviated more by hydroxychloroquine than by placebo. Serious adverse drug reactions attributable to the active agents were rare. We were unable to demonstrate that, in the presence of a nonsteroidal antiinflammatory drug, either penicillamine or hydroxychloroquine is superior to placebo in the treatment of children with juvenile rheumatoid arthritis.

Administration, Oral

A study of classification criteria for a diagnosis of juvenile rheumatoid arthritis.

Criteria for the classification of juvenile rheumatoid arthritis were analyzed in a detailed database of 250 children in order to assess the accuracy of diagnosis and validity of onset types and course subtypes. A number of conclusions have been derived from this study: All definitions of the 1973 criteria for classification of juvenile rheumatoid arthritis should be retained. The addition of onset types to the 1976 revision of the criteria has been validated. The course of the disease after the onset period of 6 months is as important to the outcome of a group of children as is the onset type. The current classification should be broadened to include the course subtypes.

Age Factors

Congenital cytomegalovirus infection and maternal systemic lupus erythematosus: a case report.

We describe an infant with symptomatic congenital cytomegalovirus infection, who was born to a mother with active systemic lupus erythematosus. Infection in the child resulted from reactivation of maternal cytomegalovirus infection. The mother's use of prednisone may have contributed to the reactivation. The role of maternal immunosuppression in the acquisition of congenital viral infection by the neonate is discussed.

Adult

Pitfalls in diagnosis of arthritis in children.

Arthritis occurs quite frequently in childhood. By clinically recognizing arthritis, using the proper studies for evaluation, and then carefully weighing the diagnostic evidence, the primary care physician will avoid the common pitfalls in diagnosis of chronic arthritis in children.

Arthritis