Quantitation of diphtheria and tetanus antibodies by reversed rocket immunoelectrophoresis.

A reversed rocket immunoelectrophoresis technique, applying serum samples to antigen-containing gel, is described for quantitation of human antibodies to diphtheria and tetanus. Lowering of the pH of the buffer from 8.6 to 5.2 increased the height of the rockets, but also resulted in more non-specific precipitation. This smudging could be removed by dextran sulphate precipitation of the sera, a necessity when quantitating sera with small concentrations of anti-bodies. The merits of this method are discussed in relation to other in vitro as well as in vivo methods. The method was found to be reproducible, rapid, cheap and sensitive, and to require small samples of serum.

Effect of immune complex-containing sera from patients with rheumatic diseases on thromboplastin activity of monocytes.

Monocytes isolated from peripheral blood of patients with various rheumatic diseases and circulating immune complexes (IC) developed a significantly higher thromboplastin (tissue factor) activity than normal cells when cultured in vitro without inducers, but normal cells responded more strongly with thromboplastin production upon stimulation with IC or phytohaemagglutinin (PHA). Sera from patients with rheumatic diseases and circulating IC induced a significant increase in the thromboplastin activity of normal monocytes. Lysozyme release from patient monocytes was significantly lower than the release from control cells when stimulated with IC. Patient sera contained higher amounts of lysozyme than normal sera, indicating lysozyme release in vivo. These data suggest that activation of monocytes in vivo by IC may take place. The increased expression of thromboplastin in monocytes/tissue macrophages may be important for the development of microvascular thrombosis and fibrin deposition seen in chronic inflammatory lesions.

Juvenile chronic arthritis: a biobehavioral disease. Some unsolved questions.

This review presents a multidimensional biopsychosocial model suitable for evaluating medical and psychosocial empirical findings in juvenile chronic arthritis (JCA). The possible predisposing, provoking and modifying variables that have been assessed in studies of JCA are presented, together with suggestions for further research. The model is appropriate for structuring and validating data in future longitudinal studies and may also serve as a frame of reference for a multi-professional team approach in the care of rheumatic children and their families.

Use of a sicca symptoms questionnaire for the identification of patients with Sjögren's syndrome in a heterogeneous hospital population with various rheumatic diseases.

OBJECTIVE: A six-item questionnaire regarding sicca symptoms recently validated for primary Sjögren's syndrome (SS) was tested on 154 in-patients with a wide range of inflammatory rheumatic diseases. Patients with one or more positive responses underwent objective ocular and oral diagnostic procedures. Of 27 patients thus investigated, 19 could be classified as having SS. RESULTS: The positive answers obtained were mainly in response to 4 of the 6 questions: dry eyes, sensation of sand or gravel in the eyes, dry mouth, and drinking of liquids to aid in swallowing dry foods. Among the 19 patients found with SS, most had had earlier diagnoses of various connective tissue diseases (rheumatoid arthritis included) and most were female. CONCLUSION: In conclusion, this study indicates that the sicca symptom questionnaire may be useful when deciding which patients with inflammatory rheumatic diseases should be subjected to special investigations with regard to SS.

Is onset type evaluated during the first 3 months of disease satisfactory for defining the sub-groups of juvenile chronic arthritis? A EULAR Cooperative Study (1983-1986).

This study represents an attempt to collect observations from co-operating countries to evaluate the previously suggested criteria for juvenile chronic arthritis during the onset periods 0-3 and 3-6 months, preferably studied prospectively. Only 267 of 378 forms returned were satisfactory for inclusion because of failure to observe exclusion criteria or insufficient information. Despite this it was possible to conclude that systemic disease represented 25% of the group and that these features tended to decline during the 6 month period. Gut inflammation was seen in 4.5% and the frequency of chronic iridocyclitis increased during the observation period to 4.5%. Variation in joint state during this period suggests that course classification may be important, as 23 of 118 who were pauciarticular at 3 months became polyarticular by six months, but only 46 of 76 who were polyarticular at 3 months remained in this state at six months.

Increased mortality in Dupuytren's disease.

A previous study showed a dip in the prevalence curve of Dupuytren's disease in men over 79 years of age. This may indicate increased mortality. The aim of the present investigation was to study this hypothesis. Four hundred and twenty-six men with Dupuytren's disease, born between 1900 and 1924 were followed for 26 years (1969-1996). Their mortality was compared with that of an age-matched control group of 426 men. In 1996, 361 with Dupuytren's disease and 336 in the control group had died. Overall, patients with Dupuytren's disease had a significantly increased mortality of 22%. The mortality was highest among those with onset of disease before the age of 60. In this age group men with Dupuytren's disease had 70% higher mortality than that of the control group. Disease duration did not seem to influence the mortality.

Evidence for complement activation by the alternate pathway in the arthritis of hypogammaglobulinemic patients.

The chronic, rheumatoid synovitis in four patients (two children and two adults) with immunodeficiency was studied by means of immunopathological examination of synovial tissues and fluids. Their immunodeficiencies were extensively studied, with various tests for humoral and cell-mediated immunity. The two children were boys with Bruton's disease. One adult, female, had common variable immunodeficiency. One adult male had severe hypogammaglobulinemia. All patients had isolated deposits of complement component C3 in their synovial membranes, usually without traces of immunoglobulins. Depressed levels of complement component C3 were found in the joint fluid, in contrast to high levels in the corresponding serum in one patient. Components of the alternate pathway, properdin and C3A, were found in the tissues, but not components of the classic pathway, C1q and C4. The findings suggest that chronic, rheumatoid arthritis in hypogammaglobulinemic patients may be related to activation of C3 by the alternate pathway.

Changing structure and resources in a rheumatology combined unit during 1977-1999.

OBJECTIVE: The aim was to study the changing structure and resources in a rheumatism hospital during the period 1977-1999 when rheumatology care was decentralized and new treatment strategies were introduced. METHODS: Data on hospital management and production were retrieved retrospectively. RESULTS: The number of beds was stepwise reduced from 133 to 44 and the average length of stay declined from 48 to 16 days. The combined unit and multidisciplinary team organization was kept, ensuring the combined effort of rheumatologists, rheumasurgeons, registered nurses, physiotherapists, occupational therapists, and social workers. One-third of the total staff was rheumateam members in 1977 compared to one-half in 1999. The proportions of physicians and registered nurses increased while the proportion of physiotherapists was stable. The number of discharges remained relatively unchanged and the number of outpatient consultations increased. Inflammatory rheumatic diseases remained the largest diagnostic group of in- and outpatients. Hospitalized care was received primarily by patients with arthritis and spondylitis. Patients with vasculitis and diffuse disorders of connective tissue accounted for an increasing proportion of the outpatient clinic production. Surgical procedures became more prevalent. Since 1995 approximately 50 large joint replacements have been performed annually. CONCLUSION: The length of stay declined and patient care was shifted towards the outpatient clinic. The multidisciplinary team was strengthened. More resources were dedicated to physician-led and nurse-dependent procedures, but physiotherapy and rehabilitation remained part of inpatient care throughout the period. The expertise concentrated on inflammatory rheumatic disorders. The modesty of the large joint replacement caseload may challenge decentralized care.

Methodological problems--juvenile chronic arthritis.

This group of diseases comprises a heterogeneous syndrome with several characteristics different from adult rheumatoid arthritis. They are characterized by joint swelling, pain/tenderness, heat and limitation of motion with or without several extra-articular manifestations. The natural course is fluctuating. There is no uniform disease course. The prognosis is better for children than adults with rheumatic disorders. The etiology is partly known and the pathogenesis unclear. There are no uniformly accepted diagnostic criteria. Patient materials studied need therefore be described in detail. The methods used for evaluation of disease and functional activities are crucial. The statistical methods, ethical problems including consent/assent are highly relevant. The management including drug therapy, drug handling and compliance need also to be considered. Due to relative rareness of the syndrome, preferably a few investigators that think alike need to collaborate for more efficient and ethically sound investigations of such patients.

Granulocyte reactive antinuclear factors in juvenile rheumatoid arthritis.

The prevalence of mouse liver reactive antinuclear factors (L-ANF) and human granulocyte reactive antinuclear factors (G-ANF) was determined in sera from 34 age- and sex-matched pairs of patients with juvenile rheumatoid arthritis (JRA) and controls. Neither type of antinuclear factor was found in any of the control sera, whereas of the patient sera, 35% were L-ANF positive and 59% were G-ANF positive. 90% of the G-ANF positive sera were of the IgG class and 50% were able to fix complement. L-ANF was most frequent in female patients. Several types of ANF were associated with the polyarticular form of the disease. Such varying prevalences of ANF with disease types might indicate that JRA is a syndrome rather than a disease. In particular, the complement fixing G-ANF titre was positively correlated with parameters related to disease activity. The great variation in prevalence figures of different ANF types previously reported and the possible clinical significance of these auto-antibodies are discussed.

Platelet count and disease activity in juvenile rheumatoid arthritis.

Blood samples from 41 children with juvenile rheumatoid arthritis (JRA) were studied. The platelet count was tested for possible relationship and correlation with a number of clinical and laboratory parameters. High platelet count was associated with active disease, presence of secondary amyloidosis, and poor functional capacity. The platelet count was positively correlated with the erythrocyte sedimentation rate, anemia, and granulocytosis. The platelet count thus seems to provide an additional parameter of disease activity in patients with JRA.

Prediction of short-term prognosis by biopsychosocial variables in patients with juvenile rheumatic diseases.

We describe physical symptoms and signs, laboratory data and psychosocial assessments for 84 children (age 1-17) hospitalized for the first time with suspected or definite rheumatic disease. At 16 months (range 7-28) followup change of disease severity was assessed based on hospital records. The patients were categorized as unchanged/worse (n = 36) or improved (n = 48). A linear discriminant model applying a combined set of 6 medical and 2 psychosocial variables characterized correctly 68 of 84 patients (81%). The variables were age at onset, disease severity, months of disease duration, presence of rheumatic disease in the family, erythrocyte sedimentation rate (ESR), thrombocytes, total behavior problem score on the Child Behavior Checklist and maternal distress. By discriminant function analysis of biopsychosocial variables more homogeneous groups may be obtained. Study of such groups may improve prediction of the prognosis.

Tolerance of cyclosporine A in children with refractory juvenile rheumatoid arthritis.

In an open trial, tolerance and safety of cyclosporine A was studied in 14 patients with refractory juvenile rheumatoid arthritis (JRA). The doses varied from 4-15 mg/kg/day. Treatment lasted for greater than 12 months in 11 and 6 to 9 months in 3 patients. Eleven patients were withdrawn due to lack of efficacy (4) or side effects (7). A drop of greater than 2 g/l in hemoglobin and a marked rise in serum creatinine were the cause of withdrawal in 5 patients. The effect of cyclosporine on disease activity seemed to be mainly symptomatic and temporary. Probably, the dose should be kept below 5 mg/kg/day. Future controlled studies should be aware of a risk of aggravation of anemia in children treated with cyclosporine.

Agreement between parents and physicians regarding clinical evaluation of patients with juvenile rheumatoid arthritis.

The reliability of disease severity assessed by parents of children with juvenile rheumatoid arthritis was studied by a self-report questionnaire. Parents of 50 patients with a minimum disease duration of 6 months and two physicians participated. Good agreement was achieved between parents and physicians regarding global assessment of disease severity, pain, morning stiffness and activities of daily life. For joint swelling and restriction of movement, the physicians scored higher than did the parents. The findings demonstrate that, with some reservations, a parent questionnaire may be used in follow-up studies on children with juvenile rheumatoid arthritis.

Azathioprine versus placebo in patients with juvenile rheumatoid arthritis: a single center double blind comparative study.

Thirty-two patients with juvenile rheumatoid arthritis (JRA) entered a comparative, double blind, parallel 16-week clinical trial of azathioprine versus placebo. After 8 weeks of therapy the changes in disease activity measurements indicated an improvement in the azathioprine group compared to the placebo group. At the end of the study, most of the disease activity measurements were changed in favour of the azathioprine group compared to the placebo group, but statistically significant differences between the groups were found for only 2 disease activity measurements. Therapy was stopped for 2 patients in the azathioprine group because of reversible leukopenia. Our results and the risk for severe adverse reactions indicate that azathioprine remains a third line drug for patients with JRA.

Chronic family difficulties and stressful life events in recent onset juvenile arthritis.

The prevalence of chronic family difficulties, recent stressful life events and socioeconomic status were assessed in 106 families of children with juvenile arthritis, divided in 5 groups according to disease course types. Chronic family difficulties were assessed by semi-structured parent interviews and life events by questionnaires and interviews. Both chronic family difficulties and recent stressful life events appeared in about 2/3 of the families, but a correlation between these were found only for the pauci and polyarticular groups. Chronic family difficulties and recent stressful life events did not differ between groups and were not associated to severity of disease. To what extent stress influences the course of various disease types of juvenile arthritis warrants longitudinal follow-up. For this a life event questionnaire may be valuable.

Diagnostic criteria of rheumatoid arthritis in children. Proposed criteria for controlled clinical studies.

Several different sets of diagnostic criteria of rheumatoid arthritis in children are in practical use. The criteria most widely applied are discussed here, especially with regard to clinical studies. Reasons are presented for the selection of criteria used in the present controlled clinical studies on rheumatic children in Oslo. Three modifications were made in the North-American criteria: 1) disease onset before 16 years of age; 2) persistent arthritis for more than 3 months; 3) biopsy is preferable in monarticular cases, except in patients with chronic iridocyclitis.

Naproxen and acetylsalicylic acid in the treatment of pauciarticular and polyarticular juvenile rheumatoid arthritis. Assessment of tolerance and efficacy in a single-centre 24-week double-blind parallel study.

Naproxen (NAP) (10 mg/kg/day) and acetylsalicylic acid (ASA) (75 mg/kg/day) were compared in a 24-week randomized block, controlled, parallel, double-blind study in 80 patients with pauciarticular or polyarticular juvenile rheumatoid arthritis. Five NAP-treated compared with 20 ASA-treated patients stopped therapy because of adverse reactions. Both drug regimens seemed to be therapeutically effective. The outcome of the study indicated that ASA may have a slight advantage over NAP with regard to efficacy. However, the changes in disease activity measurements were similar in the two treatment groups.

C-reactive protein and delayed hypersensitivity in juvenile rheumatoid arthritis.

In patients with juvenile rheumatoid arthritis (JRA), the delayed hypersensitivity found when skin-testing with a panel of memory antigens appeared to be reduced. Since C-reactive protein (CRP) has recently been shown to inhibit various parameters of cellular immunity in vitro, we tested the concentration of CRP in serum from 44 patients with JRA who had previously been tested for delayed hypersensitivity. The mean concentration of CRP in the patients was 32.2mg/l, while in age-and sex-matched controls it was less than 5 mg/l. By scatter diagrams and statistical analysis no association was found between the concentration of CRP and various expressions of delayed hypersensitivity in vivo.