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Background: The AP Advance (APA) is a videolaryngoscope with interchangeable blades: intubators can choose standard Macintosh blades or a difficult-airway blade with increased curvature and a channel to guide the tube to the larynx. The APA may therefore be comparably effective in both normal and difficult airways. We tested the hypotheses that intubation with the APA is no slower than Macintosh laryngoscopy for normal mannequin airways, and that it is no slower than videolaryngoscopy using a GlideScope Ranger in difficult mannequin airways., Methods: Medical professionals whose roles potentially include tracheal intubation were trained with each device. Participants intubated simulated (Laerdal SimMan) normal and difficult airways with the APA, GlideScope, and a conventional Macintosh blade. Speed of intubation was compared using Cox proportional hazards regression, with a hazard ratio >0.8 considered noninferior. We also compared laryngeal visualization, failures, and participant preferences., Results: Unadjusted intubation times in the normal airway with the APA and Macintosh were virtually identical (median, 22 vs 23 seconds); after adjustment for effects of experience, order, and period, the hazard ratio (95% confidence interval) comparing APA with Macintosh laryngoscopy was 0.87 (0.65, 1.17), which was not significantly more than our predefined noninferiority boundary of 0.8 (P = 0.26). Intubation with the APA was faster than with the GlideScope in difficult airways (hazard ratio = 7.6 [5.0, 11.3], P < 0.001; median, 20 vs 59 seconds). All participants intubated the difficult airway mannequin with the APA, whereas 33% and 37% failed with the GlideScope and Macintosh, respectively. In the difficult airway, 99% of participants achieved a Cormack and Lehane grade I to II view with the APA, versus 85% and 33% with the GlideScope and Macintosh, respectively. When asked to choose 1 device overall, 82% chose the APA., Conclusions: Intubation times were similar with the APA and Macintosh laryngoscopes in mannequins with normal airways. However, intubation with the APA was significantly faster than with the GlideScope in the difficult mannequin simulation.

Earl Brewer discusses his journey into pediatric rheumatology from 1958 to retirement in 1990 in three parts.

Earl Brewer discusses his journey into pediatric rheumatology from 1958 to retirement in 1990 in three parts.

Results from three randomized placebo-controlled trials were combined in a meta-analysis to compare the clinical utility of four advanced drug therapy agents used to treat juvenile rheumatoid arthritis (JRA): D-penicillamine (10 mg/kg/d), hydroxychloroquine (6 mg/kg/d), auranofin (oral gold, 0.15 to 0.20 mg/kg/d), and two low dose levels of methotrexate [5MTX, 5 mg/M2/wk; 10MTX, 10 mg/M2/wk]. A total of 520 children with JRA were enrolled into these trials. Only 10MTX resulted in significantly greater improvement than placebo in variables that assess effectiveness: physician's global assessment, a composite index, and erythrocyte sedimentation rate. Treatment effect sizes were the largest in the 10MTX group for all articular disease indices. The short-term safety profiles were similar across all treatment groups. It is concluded that the current trend among pediatric rheumatologists to use oral methotrexate as the first advanced drug therapy in JRA is appropriate and that the minimum effective dose is 10 mg/M2/wk.

It has been well established that joint hypermobility may predispose children to the development of joint pain. Joint hypermobility represents an extreme variation of normal joint mobility with no underlying connective tissue diseases. Its prevalence among children varies from series to series. Evidence that there are differences between races and sexes exist. Joint hypermobility diminishes markedly throughout childhood and then more slowly during adult life. Although quantitative measurements in the assessment of joint hypermobility have been described, the criteria defined by Carter and Bird are preferred. Any subject who is able to perform 3 or more of the 5 maneuvers devised by these criteria was considered to have joint hypermobility. The mechanism in which joint symptoms develop is not well understood. Excessive motion or inappropriate physical activities that hyperextend the joint capsule, the ligaments and soft tissue constituent causing injury. These injuries are manifested by pain. The clinical features, prognosis and relevance to pediatric practice are discussed.

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.

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.

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.

Auranofin (triethylphosphine gold) was administered to 21 patients with juvenile rheumatoid arthritis during an open-ended, open-label, noncontrolled trial designed to establish safety and preliminary efficacy. Initial dosage was 0.1 mg/kg/day; incremental increases to 0.2 mg/kg/day were allowed. Aspirin (80 mg/kg/day), tolmetin (20 to 40 mg/kg/day), and naproxen (400 to 600 mg/m2/day) were allowed as rapidly acting anti-inflammatory agents. All patients attained measurable plasma concentrations of gold during the study. Clinically significant improvement (greater than 25%) occurred in more than half the patients with regard to the number and severity of joints with swelling, pain on motion, and tenderness. The number of joints with active arthritis decreased by at least 25% in nine of the 19 patients. Group mean changes between the initial and final visit indicated improvement in all articular disease indices measured. Eleven of 16 patients with an elevated erythrocyte sedimentation rate showed decreases of at least 25%. The group given the higher dosage had a greater proportion of responders with decreases in erythrocyte sedimentation rate. Four of six patients whose sera contained rheumatoid factor showed decreases in its titer. Discontinuation of auranofin was necessary in two patients because of headaches and because of hematuria and anemia associated with a severe flare of polyarticular disease, respectively. The results from this trial are sufficiently encouraging to merit a double-blind trial of auranofin in children with juvenile rheumatoid arthritis.

Increased rates of spontaneous or induced chromosome breakage are seen in many types of diseases, including the 'collagen-type' autoimmune diseases. Using a 60Co gamma cell, we irradiated lymphocyte cultures from three related rheumatoid arthritis patients, their immediate family members, and two unrelated rheumatoid arthritis patients. Although these individuals had not shown abnormally high levels of spontaneous chromosome breakage, they did show an abnormal sensitivity to irradiation, which was manifested in several ways. Two of the probands showed induced breakage rates that were twice as high as those seen in controls. In addition, the reduction of mitotic index, due either to increased cell death or to induction of a G2 lag period, was higher in the arthritis group (including non-symptomatic family members) than in the control group. Finally, we observed a high frequency of an unusual type of cell in the arthritis group. These unusual cells resembled c-anaphases seen with extended colcemid treatment, and may indicate that the mitotic apparatus in cells from this group is particularly sensitive to ionizing radiation.

Segregation of chromosome #6 markers has been studied in a large family, identified by a proband with seronegative, juvenile-onset rheumatoid arthritis, which contains four other individuals with adult-onset rheumatoid arthritis (RA). Two of the adult-onset patients have classical seropositive RA. Sera from two healthy members of this family also contain rheumatoid factors (RF). Six family members had crossovers in the short arm of chromosome #6. Three individuals with recombinants between HLA-B and HLA-D were identified; three others had identifiable crossovers between HLA-D and GLO (Glyoxylase 1). Linkage analysis suggested that susceptibility to RA in this family was influenced by a dominant gene located centromeric to HLA-B. The highest lod score (1.64) was obtained for linkage to GLO at a recombination rate of zero. Inheritance of specific chromosome #6 or Gm immunoglobulin allotype markers did not appear to influence serum RF. These results agree with previous family studies which suggest that acquisition of childhood- and adult-onset RA is influenced by a common disease susceptibility gene, linked to the major histocompatibility gene complex.

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.

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.

Pharmacologic management of juvenile rheumatoid arthritis is only one of several modalities necessary for effective control. The stepping stones to proper management include a planned long-range program, physical therapy with swimming, good health habits, and consultation with other health professionals who are part of the management team. Pharmacologic therapy includes nonsteroidal anti-inflammatory drugs initially, occasionally corticosteroids, and slow-acting antirheumatic drugs, including injectable gold when therapeutic response is inadequate. Early experiences with oral gold are reported here. Auranofin (triethylphosphine gold) was administered to 21 patients with juvenile rheumatoid arthritis during a segment I, open ended, open-label, noncontrolled trial designed to establish safety and preliminary efficacy. Initial dosage was 0.1 mg/kg per day; incremental increases to 0.2 mg/kg per day were allowed (with usual increase to 0.15 mg/kg per day). Aspirin (80 mg/kg per day) or tolmetin (20 to 40 mg/kg per day), or naproxen (400 to 600 mg/m2 per day) were allowed as rapidly acting antiinflammatory agents. Stable measurable plasma concentrations of gold were attained in all patients during the study. More than half the patients sustained clinically significant improvement (greater than 25 percent) with regard to the number and severity of joints with swelling, pain on motion, and tenderness. In nine of the 19 patients, the total number of joints with active arthritis decreased by at least 25 percent. All articular disease indices measured indicated improvement of group mean changes between the initial and final visit. Eleven of 16 patients with an elevated erythrocyte sedimentation rate showed decreases of at least 25 percent. The group given higher dosages had a greater proportion of responders in regard to decreases in erythrocyte sedimentation rate (nine of 11 patients). Four of six patients whose serums contained rheumatoid factor showed decreases in the titers. Discontinuation of auranofin was necessary in two patients: one because of headache and one because of hematuria and anemia associated with a severe flare-up of polyarticular disease. The results from this trial reveal sufficient patient improvement to plan a double-blind trial of auranofin in children with juvenile rheumatoid arthritis.

Thirty-three patients with JRA were treated with proquazone during a 4-wk open-labeled, non-controlled trial. Increasing doses started at 400 mg/m2/d up to 800 mg/m2/d, not to exceed 960 mg/d. Oral administration was 4 times/d. One patient did not complete the study because an erythematous rash developed. Efficacy analysis showed significant decreases in the total number of active joints, the number and severity of joints with tenderness and LOM, DMS, and travel time (in all cases p less than .05). The drug appears to be similar in efficacy and safety to other NSAID that have been studied in children.

The nonsteroidal antiinflammatory agents do offer encouraging alternatives to presently used medications. The ultimate role of the agents will have to be established by usage and systematic study by such groups as the Pediatric Rheumatology Collaborative Study Group.

Juvenile rheumatoid arthritis (JRA) in the Union of Soviet Socialist Republics (USSR) and the United States (USA) shows a remarkable similarity in age of disease onset, subtype onset, frequency, and most laboratory measurements. There is variation in the therapeutic approach with heavier reliance on aspirin in the USA. The evolution of JRA from onset subtype to final subtype over 5 years was the same in both groups and was independent of the type of therapy.

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.

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.

Materials with the Clq binding properties of soluble immune complexes (IC) were found in sera from 11 of 51 consecutive (22%) children with juvenile rheumatoid arthritis (JRA) and in 17 of 20 adults with active seropositive rheumatoid arthritis (RA). IC appeared more frequently in children with systemic onset disease whereas antinuclear antibody (ANA) was found more frequently in sera from those with pauciarticular disease. Only 3 JRA sera contained anti-immunoglobulin (rheumatoid factor); those 3 also had high Clq binding activities. Seven of 50 patients (14%) carried HLA-B27 but B27 was not associated with high Clq binding activity or presence of ANA. The presence of free ANA more frequently in children with mild disease and IC more frequently in children with relatively severe disease suggests that children with systemic JRA may have a relative defect in antibody-forming capacity or reticuloendothelial function which results in decreased clearance of circulating IC. Alternatively, systemic, polyarticular, and pauciarticular JRA may represent a spectrum of clinically similar diseases resulting from different etiologic agents.

Thirty-two patients with JRA were enrolled in a 4-wk open-labeled, non-controlled multicentre trial of pirprofen. An initial dose of about 300 mg/m2/d (range 250-330) was gradually increased to a maximum of 600 mg/m2/d (range 413-761). The medication was provided as an aqueous suspension (10 mg/ml), and was given 4 times/d. Efficacy analysis showed significant decreases occurred in the DMS, travel time, grip strength, and the severity of swelling score (in all cases p less than 0.05 based on the paired Student t test, 2-tailed). Nineteen patients reported a total of 27 adverse experiences; 6 of which were attributable to pirprofen. At the study dosages used pirprofen seems to be very similar in efficacy and safety to other nonsteroidal antiinflammatory drugs investigated in children with JRA.

It has been suggested that hypermobility of the joints may predispose children to the development of arthritis or arthralgia. To determine the normal frequency of hypermobility, 260 normal schoolchildren (5 to 17 years of age) were examined. In addition, 34 patients with juvenile rheumatoid arthritis (JRA) and 32 children with juvenile episodic arthritis/arthralgia (JEA) were tested. Any child who met at least three of the following criteria was considered to have joint hypermobility: (1) passive apposition of the thumbs to the flexor aspect of the forearms; (2) passive hyperextension of the fingers so that they lie parallel with the extensor aspect of the forearms; (3) hyperextension of the elbows greater than 10 degrees; (4) hyperextension of the knees greater than 10 degrees; (5) flexion of the trunk with knees extended so the palms rest on the floor. Thirty-two (12%) of 260 normal schoolchildren and 21 (66%) of 32 with JEA had hypermobility. Further, a significantly higher proportion (23 of 126) of normal girls than normal boys (nine of 134) had hypermobility (chi 2 = 8.0, P less than 0.005). Hypermobility was not common in children with JRA. These findings support the hypothesis that hypermobility may be an important factor in the cause of JEA.

The study objective was to establish a safe and efficacious dose of ketoprofen in children with JRA during a 4-week, open-labeled, non-controlled trial. Initial dosage was 100 mg/m2/d, gradually increased up to 200 mg/m2/d, not to exceed 320 mg/d. One patient was removed from the study due to hematuria. Clinical improvement was observed in 50% or more of the patients in 8 of the 15 indices assessed. Statistical improvement was detected in the number and severity of joints with pain on motion, the duration of morning stiffness, and the time required to travel 50 feet (p less than .035). Significant laboratory changes included decreases in the mean hemoglobin and hematocrit, and increases in ESR and BUN (p less than .03). Twenty patients experienced a total of 39 adverse effects and of these, 6 were judged to be attributable to ketoprofen. These preliminary data suggest ketoprofen's efficacy and safety is comparable to that of other nonsteroidal antiinflammatory drugs.

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.

Auranofin (AF, Ridaura) was administered to 23 children with juvenile rheumatoid arthritis during a prospective, open labelled, noncontrolled trial designed to establish longterm safety and preliminary efficacy. Dosages of AF were up to 0.2 mg/kg/day, with either aspirin (60-80 mg/kg/day), naproxen (400-600 mg/m2/day), or tolmetin sodium (20-40 mg/kg/day) serving as the concurrent nonsteroidal antiinflammatory drug. Nearly all patients showed an initial favorable response, however tachyphylaxis occurred in one-third (mean duration of therapy prior to the development of inefficacy = 22.6 mo). Clinical remission was observed in 6 patients an average of 15 months after enrollment. The drug appears to be safe for extended periods; 7 children are continuing AF at the present time with a mean duration of therapy of 4.25 years (maximum followup = 4.6 years).

The prognosis of patients with diffuse proliferative lupus nephritis is generally poor, and the majority of patients with this lesion develop progressive deterioration in renal function. Intravenous "pulses" of methylprednisolone have been advocated for the treatment of severe nephritis. In this study, 15 patients with biopsy-proven diffuse proliferative lupus nephritis were treated with oral high-dose prednisone therapy, initially 2 mg/kg/day. They were compared with seven patients with similar renal pathology treated with six daily pulses of methylprednisolone (30 mg/kg/day, not to exceed 1 gm/day), followed by prednisone orally, initially 2 mg/kg/day. There were no deaths in either group and the side effects of therapy were similar in the two groups. Pretreatment GFRs for the pulse and high-dose groups were similar. There was a more rapid improvement in GFR following pulse therapy, but the long-term effects on renal function for the two modes of therapy were the same.

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.

The object of this investigation was to determine the prevalence of anti-T cell antibodies in 66 children with various connective tissue diseases. Anti-T cell antibodies were found in 43/44 juvenile rheumatoid arthritis (JRA) patients (mean cytotoxicity 15.0%) and in 10/10 children with systemic lupus erythematosus (mean cytotoxicity 20.0%), but in only 1/15 normal controls and in none of 12 children with other arthritides. There was no significant difference in mean percent cytotoxicity among the JRA subclasses. In the JRA patients, the percent cytotoxicity was positively correlated with the erythrocyte sedimentation rate (P = 0.01), but not with the presence or absence of rheumatoid factor, antinuclear antibodies, or immune complexes. The sera of 3 JRA patients repeatedly inhibited the stimulation of normal lymphocytes by mitogens and antigens by 47-99% (measured by the incorporation of 3H-thymidine into DNA) when added to the culture system in the first 24 hours; normal sera did not. Sera from patients with JRA have increased reactivity with mitogen-activated lymphocytes and T cells compared with unstimulated cells as determined by flow cytometry. The expression of the "JRA antigen" requires protein synthesis but not DNA synthesis or cell division. We conclude that the majority of patients with active JRA have cytotoxic anti-T cell antibodies and that in selected patients, these antibodies may play a role in regulation of the immune response.

During an uncontrolled, open-labelled, open-ended clinical trial of auranofin in children with juvenile rheumatoid arthritis (JRA) we obtained serial blood samples for the purpose of assessing gold content. Our objectives were (1) to observe the pattern of blood gold concentrations over a period of time in children undergoing long-term oral gold therapy, and (2) to observe the effect of changing dosage levels on blood gold concentrations. The initial dosage of auranofin was 0.1 mg/kg/day with allowable increases to 0.2 mg/kg/day. A concurrent nonsteroidal anti-inflammatory drug was allowed. Twenty-one patients were enrolled in the study, and we obtained 2 or more serial samples on 13 of the children. At a constant dosage of 0.1 mg/kg/day, steady state blood gold concentrations were attained in 11 to 13 weeks of therapy and, in the absence of a dosage change, remained remarkably constant through extended periods. The blood gold concentration was related to total daily dosage rather than to the cumulative amount of gold received. Increasing or decreasing the dose resulted in a direct effect on concentration. The clinical value of blood gold levels resulting from auranofin therapy in JRA will have to be established through double-blind controlled trials.

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.

The number of receptors for complement component C3b per erythrocyte reportedly is decreased in over half of adults with systemic lupus erythematosus. We have devised an immunoradiometric assay for C3b receptor (CR1) on erythrocytes, with which one can assess CR1 saturation due to in vivo binding of immune complexes or activated complement fragments (C3b). Using this assay, we examined binding by CR1 in normal adults and newborns, in lupus and juvenile rheumatoid arthritis patients, and in a population of patients with various general medical problems, including other connective tissue diseases. Binding by CR1 was decreased in eight of 15 SLE patients, four of 25 juvenile rheumatoid arthritis patients, and one of 14 patients with other diseases. We found no significant correlation between CR1 binding and either C1q binding, antinuclear antibody titer, results for complement C3 and C4, or the presence of renal disease. Using this assay, we were also able to show that the observed reduction in CR1 binding was not ascribable to prior saturation of CR1 or to blocking antibody against CR1. The assay is precise and easy enough for routine application.

Plasma exchange with either fresh-frozen plasma or 5% albumin solution as replacement fluid was performed in four selected patients with juvenile rheumatoid arthritis unresponsive to standard therapy. One 13-year-old boy with life-threatening systemic disease experienced a partial remission of disease and tolerated a decrease in prednisone dose from 15 to 4 mg daily following 14 exchanges with FFP. A 14-year-old girl, dwarfed by systemic disease and long-term corticosteroid therapy, was able to discontinue prednisone and grew 6.3 cm in 11 months following 18 plasma exchanges with FFP. An 8-year-old girl with pauciarticular disease, antinuclear antibody, and uncontrollable iridocyclitis underwent 16 plasma exchanges with 5% albumin solution as replacement; despite removal of antinuclear antibody, her eye disease and arthritis were not helped. A 16-year-old girl with erosive, polyarticular JRA showed no detectable change in her articular disease following nine exchanges. Transient decreases in hematocrit, complement components, and immunoglobulin concentrations occurred. In three patients Westergren sedimentation rate decreased for up to five months after exchanges. One patient died suddenly during an exchange with FFP; the cause of death appeared related to microemboli of unknown nature found in the lungs at autopsy. Plasma exchange should be done only in an intensive care setting and as a research procedure for children with JRA.

We compared efficacy and safety of aspirin (ASA) and fenoprofen in the treatment of JRA. Ninety-nine children with JRA were given ASA or fenoprofen in a 12-wk, multicentered, double-blind, parallel study. Initial fenoprofen dosage was 900 mg/m2/d increased to 1800 mg/m2/d (3200 mg/d-max). Initial ASA dosage was 1500 mg/m2/d increased to 3000 mg/m2/d (5450 mg/d-max). Adverse reactions forced removal of 14% of ASA treated patients from the trial, whereas no fenoprofen patient was removed for this reason. Forty of 50 ASA patients, and 47 of 49 fenoprofen patients completed at least 10 wk of therapy and analysis showed that the 2 drugs were nearly identical in efficacy, but toxicity was considerably less among fenoprofen treated patients.