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Biomedical subjects

W Kuis

Publications and source records attributed to W Kuis.

At least 73 records · Page 4Linked to original sources

Antineutrophil cytoplasmic antibodies in juvenile chronic arthritis.

OBJECTIVE: To evaluate the diagnostic significance of antineutrophil cytoplasmic antibodies (ANCA) by assessing the prevalence of ANCA in juvenile chronic arthritis (JCA) (n = 93) of either oligoarticular, polyarticular, or systemic onset. To investigate the prevalence of ANCA in other diseases of childhood characterized by chronic inflammation (n = 44), such as cystic fibrosis, juvenile diabetes mellitus, and connective tissue diseases. METHODS: Indirect immunofluorescence on both ethanol and paraformaldehyde fixed neutrophils, ELISA for specific antigens, Western blotting using sonicated neutrophils. RESULTS: ANCA were detected in the sera from 35% of patients with JCA, and in only 7% of patients with other inflammatory diseases. Regarding the onset type of JCA, ANCA were present in 44% of patients with oligoarticular onset, in 36% with polyarticular onset, and in 16% with systemic onset. All but one ANCA positive serum sample produced a perinuclear fluorescence pattern on ethanol fixed granulocytes. However, on neutrophils fixed with paraformaldehyde either a cytoplasmic (14%) or a nuclear (23%) staining pattern was observed, suggesting that both cytoplasmic and nuclear autoantibodies occur in JCA. Further characterization studies showed that ANCA in JCA are not directed against proteinase 3, elastase, or myeloperoxidase. On Western blots ANCA in JCA incidentally showed reactivity with either lactoferrin (5%) or 2 polypeptides of 66/67 kDa (9%). CONCLUSION: Prevalence and antigenic specificity of ANCA in JCA are clearly different from adult onset rheumatoid arthritis or other juvenile chronic inflammatory disorders.

Adolescent↗

Autoreactivity to human heat-shock protein 60 predicts disease remission in oligoarticular juvenile rheumatoid arthritis.

OBJECTIVE: To determine whether T lymphocyte reactivity to endogenous human hsp60 plays a regulatory role in the course of oligoarticular juvenile rheumatoid arthritis (JRA). METHODS: A prospective, longitudinal study of T cell reactivity to HSP in 15 patients with newly diagnosed HLA-B27 negative oligoarticular JRA was performed. Results were compared with those in a group of 20 patients with newly diagnosed polyarticular or systemic JRA or with acute arthritis caused by other systemic diseases or viral infections, as well as with those in a group of 9 healthy control subjects. RESULTS: In 86% of the patients with oligoarticular JRA (13 of 15), significant T lymphocyte proliferative responses to hsp60 were found in peripheral blood mononuclear cells and/or synovial fluid mononuclear cells within 3 months after the onset of arthritis. Only 5% of the patients in the rheumatologic disease control group (1 of 20) showed such positivity. All patients with oligoarticular JRA and positive responses to human hsp60 developed a remission of their disease within 12 weeks. During this period of remission, blood samples were taken from 8 patients and showed significantly lower and even negative responses to hsp60, compared with active disease, when all 8 patients had good responses. CONCLUSION: The results show that significant proliferative responses to human hsp60 can be found early in the course of oligoarticular JRA. Furthermore, these responses correlate with disease activity in such a manner that T cell reactivity to human hsp60 seems to be associated with disease remission.

Adolescent↗

The autonomic nervous system and the immune system in juvenile rheumatoid arthritis.

This study demonstrates that juvenile rheumatoid arthritis is associated with a dysregulation of the autonomic nervous system as well as with disturbances in the capacity of the immune system to respond to mediators of the autonomic nervous system. In patients with active disease heart rate at rest is higher than in healthy controls. In addition, 3-hydroxy-4-phenoxyphenylglycol levels in urine are higher in all patients than in the control group. Cardiovascular responses to an orthostatic stress test (tilt up) are reduced in patients with active and nonactive disease. Plasma norepinephrine responses to tilt up are reduced in subjects with active juvenile rheumatoid arthritis. In summary, our data show that patients with juvenile rheumatoid arthritis have an altered function of the autonomic nervous system associated with increased central noradrenergic outflow, presumably leading to increased vasoconstriction, resulting in a decreased response to an orthostatic stressor. The altered function of the autonomic nervous system is associated with changes in the response of leukocytes to mediators of the autonomic nervous system via beta2-adrenergic receptors. Leukocytes of patients with active juvenile rheumatoid arthritis have a lower cAMP response to a beta2-adrenergic agonist, presumably due to increased cAMP-phosphodiesterase activity in these cells.

Adolescent↗

Functional alpha 1-adrenergic receptors on leukocytes of patients with polyarticular juvenile rheumatoid arthritis.

During the last decade it has been shown that the central nervous system can influence the immune system. In healthy individuals, catecholamines can inhibit the production of pro-inflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) via interaction with beta 2-adrenergic receptors. In contrast, we show here that catecholamines can stimulate the production of the interleukin-6 (IL-6) in children with the chronic inflammatory disease polyarticular juvenile rheumatoid arthritis (JRA). The induction of IL-6 is mediated by triggering of alpha 1-adrenergic receptors on peripheral blood leucocytes of the patients with polyarticular JRA. Functional alpha 1-adrenergic receptors are absent on leukocytes of normal donors and on leukocytes of patients with the oligoarticular form of the disease.

Adolescent↗

The influence of site of stimulation, age, and gender on pain threshold in healthy children.

BACKGROUND AND PURPOSE: Factors influencing mechanical pain thresholds (MPThs) in children are not understood. Reports conflict on whether MPThs increase with age. The purposes of this study were to determine whether MPTh values change with age in children and to investigate the influence of the site of stimulation and gender. SUBJECTS: Sixty-nine children of both genders, aged 6 to 17 years, were divided into two age groups: 6 to 11 years and 12 to 17 years. METHODS: Mechanical pain thresholds were determined by applying pressure three times on both sides of the body at the elbow, wrist, knee, and ankle and paraspinally at C-6, T-1, T-3, T-6, T-10, L-1, L-3, and L-5. The influence of body site, gender, and age on MPThs was analyzed by multivariate analysis of variance. The relationship between MPThs at different sites was analyzed by correlations and factor analysis. RESULTS: There was a trend for the paraspinal MPThs to be greater the more caudally they were located. The MPThs increased with age in the paraspinal region, but they did not increase with age at the extremities. The MPThs of the male subjects did not differ from those of the female subjects. CONCLUSION AND DISCUSSION: Measurements of MPTh can be reproducibly performed in children. The level of MPThs is reliant on age and body site. In MPTh studies in children, age- and site-matched controls seem to be more relevant than gender-matched controls.

Adolescent↗

Correlates of disablement in polyarticular juvenile chronic arthritis--a cross-sectional study.

To assess the impact of disease on the functional outcome of patients with polyarticular juvenile chronic arthritis (JCA), the relationship between impairments and functional limitations was studied. Therefore, variables from the impairment domain were correlated with variables of the functional limitation domain and outcome variables were analysed for differences as a result of inflammatory disease, rheumatoid factor (RF), disease duration and age at onset. Twenty-three patients with polyarticular JCA were subjected to auxologic evaluation, a laboratory check, radiographic evaluation, joint count on tenderness and swelling, joint mobility/deformity examination, functional assessment of skills, health assessment and psychosocial evaluation. Inflammatory disease parameters, like CRP, ESR, thrombocytosis and leucocytosis, were increased in 6/23 patients. The parameters of the impairment domain, like joint tenderness and swelling, showed mild outcome, while parameters of the functional limitation domain showed more severe outcome. Generally, perceived competence was found to be normal. A clinically relevant number of patients (10/13) showed low scores on the activity factor of the Child Behaviour Check List (CBCL). A significant relationship was found between inflammatory disease variables and functional limitation outcome. RF seropositivity was not a good outcome predictor. Disease duration and age of onset showed no significant difference in the outcome of the domains. Significant correlation was found between the parental report of the Childhood Health Assessment Questionnaire (CHAQ) and all impairment parameters. Joint swelling showed a significant relationship with CHAQ and Juvenile Arthritis Functional Assessment Report (JAFAR). Disability outcome did not correlate with functional limitation. In general, children with polyarticular JCA function rather well when using a multidomain evaluation approach. Compensatory and adaptational mechanisms might contribute to the poor correlation between impairment and functional limitation parameters. Laboratory evaluation of inflammatory disease, a joint count of swollen joints and parent's report of the child's health status related best in our study.

Adolescent↗

Incidence and hemodynamic characteristics of near-fainting in healthy 6- to 16-year old subjects.

OBJECTIVES: We studied the incidence and hemodynamic characteristics of near-fainting under orthostatic stress in healthy children and teenagers. BACKGROUND: Orthostatic stress testing is increasingly used to identify young subjects with unexplained syncope. However, the associated incidence of syncope and hemodynamic responses in normal young subjects are not well known. METHODS: Eighty-four healthy subjects 6 to 16 years old performed forced breathing, stand-up and 70 degrees tilt-up tests. An intravenous line to sample blood for biochemical assessment of sympathetic function was introduced between the stand-up and tilt-up tests. Finger arterial pressure was measured continuously. Left ventricular stroke volume was computed from the pressure pulsations. RESULTS: Sixteen of the 84 subjects were excluded because of technical problems. The incidence of a near-fainting response in the remaining 68 subjects was 10% (7 of 68) for the stand-up test and 40% (29 of 68) for the tilt-up test. Baseline parasympathetic and sympathetic activity of nonfainting and near-fainting subjects was not different. Near-fainting was characterized by attenuated systemic vasoconstriction and exaggerated tachycardia that occurred as early as 1 min after return to the upright position. On tilt-up, plasma adrenaline levels increased by a factor of 2, with slightly higher increments in the near-fainting subjects. CONCLUSIONS: Inadequate vasoconstriction is the common underlying mechanism of near-fainting in young subjects. The remarkably high incidence of near-fainting during the tilt-up test after intravascular instrumentation raises serious doubts about the utility of this procedure in evaluating syncope of unknown origin in young subjects.

Adolescent↗

The pain threshold in juvenile chronic arthritis.

An algometer was used to study the pain threshold (PT) on pressure at the joint capsules of the wrists, elbows, knees, ankles and at paravertebral soft tissues in 57 patients with juvenile chronic arthritis (JCA) and 69 healthy controls, aged 6-17 yr. The PTs were correlated to visual analogue scales (VAS) and values of articular disease activity, to define their relation with pain perception and joint inflammation. The PTs in JCA patients were significantly lower than in their healthy peers, both in children with active inflammation as well as in children without detectable inflammation. The JCA group with active inflammation showed significant lower PTs than without detectable inflammation. Disease activity and VAS correlated significantly with PT (r = -0.5). There is an enhanced sensitivity to noxious stimuli in all measured body areas, suggesting a change in the pain processing system in JCA. The sensitivity endures in JCA patients without clinically active disease, probably due to prolonged central sensitization after periods of active disease.

Adolescent↗

Juvenile chronic arthritis: T cell reactivity to human HSP60 in patients with a favorable course of arthritis.

Synovial fluid and peripheral blood mononuclear cell proliferative responses to the 60-kD human heat shock protein (HSP60) were studied in 23 patients with juvenile chronic arthritis (JCA) and 7 non-JCA control patients. All patients showed active arthritis at the time of study. The patients were divided into two groups according to the presence (group A) or absence (group B) of T lymphocyte reactivity to human HSP60. We show that reactivity to human HSP60 is primarily, though not exclusively, occurring in patients with a remitting course of disease, i.e., the subgroup of HLA-B27 negative JCA patients with an oligoarticular onset. Immunohistochemical analysis of HSP expression in synovial membranes showed a significantly higher intensity of staining in JCA patients than in non-JCA controls. The results suggest that, in accordance with the earlier observation made in experimental models, T lymphocyte reactivity to human HSP60 in this subgroup of JCA patients may be part of T cell regulatory mechanisms that control the development of arthritis.

Adolescent↗

Musculoskeletal disorders in juvenile onset mixed connective tissue disease.

OBJECTIVE: We studied the occurrence of musculoskeletal involvement in patients with juvenile onset mixed connective tissue disease (MCTD) and their functional ability. METHODS: Thirteen patients who fulfilled the Kasukawa criteria of MCTD, were subjected to a general orthopedic assessment, as well as to a specific examination of tenderness and swelling of joints, muscle strength, joint motion and alignment, radiographical evaluation, and on disability and discomfort. RESULTS: Low indices were found on the modified Ritchie Articular Index (RI) (0.07) and the Fuchs Swelling Index (0.13). Mild to moderate indices were measured on the Joint Alignment and Motion Scale (JAM) (0.52) and on the Larsen Radiographic Evaluation Scales for the wrist, metacarpal, proximal and distal interphalangeal joints (L-RES) (1.40, 0.62, 0.31, 0.31). The mean pulp-thickness ratio was 22%, which is an indication for sclerodermic changes in the hands. Proximal muscle weakness was found in 10/13 patients (mainly in the upper extremity), distal muscle weakness was found in 12/13 patients. On the pediatric version of the Stanford Health Assessment Questionnaire (C-HAQ), pain and discomfort scored 0.04, disability scored 0.46; those scores were considered to below. Between L-RES and JAM a significant correlation was found (0.74, 0.74 and 0.73; p < 0.01). Another significant correlation was found between the RI and the disability score of the HAQ (0.58; p < 0.05). CONCLUSION: Sclerodermic changes as well as arthritic changes are of a benign character in our population of patients with juvenile onset MCTD.

Adolescent↗

Deficiency of the beta subunit of the eighth component of complement presenting as arthritis and exanthem.

A 13-year-old boy presented with juvenile chronic arthritis of 6 months' duration. Antinuclear antibodies, anti-double-stranded DNA antibodies, and rheumatoid factor were not detected. Western blotting showed a deficiency of the beta subunit of the eighth component of complement. The same deficiency was present in the patient's sister. C8 beta deficiency is usually detected in individuals who survive meningococcal disease. There was no such history in this family. Juvenile chronic arthritis has not previously been described in patients with C8 beta deficiency.

Adolescent↗

Prevalence of circulating immune complexes in patients with cystic fibrosis and arthritis.

We report the clinical and laboratory characteristics of eight patients with cystic fibrosis (CF) and arthropathy. Five patients had frequently relapsing, episodic arthritis; one had chronic arthritis with high titers of rheumatoid factors that could not be distinguished from juvenile chronic arthritis. In two patients the arthropathy did not relapse. Forty-six patients with CF but without arthropathy, seen during the same 1-year period, served as control subjects. Results of lung function tests and sputum cultures were similar in both groups. The sera of six of the eight patients with CF-arthropathy had high levels of circulating immune complexes, measured both by C1q-binding and the indirect granulocyte phagocytosis test, whereas only 1 of 12 control patients tested had positive C1q binding (p < 0.023). Serum complement levels were normal in both groups. Synovial biopsies, performed in three patients, showed only scanty lymphocytic infiltrates; immunofluorescent staining showed deposits of IgM, IgG, and components of complement C1q, C3, and C4. These findings suggest that the arthropathy found in CF is an immune-mediated phenomenon.

Adolescent↗