Search PubMed⌕ Search

Biomedical subjects

R M Laxer

Publications and source records attributed to R M Laxer.

At least 55 records · Page 3Linked to original sources
PubMed1996

Intravenous immunoglobulin in rheumatic disease.

With the advent of numerous commercial preparations of intravenous immunoglobulin preparations since 1981, it is now possible to administer these preparations in significant quantities to cause elevation of serum immunoglobulin levels both in patients with antibody-deficient states and in those with normal circulating immunoglobulin levels. This led to a report of dramatic improvement of thrombocytopenia in a child with agammaglobulinemia following the use of intravenous immunoglobulin preparations for recurrent infections, and further studies in both children and adults with associated symptoms suggested therapeutic efficacy of intravenous immunoglobulin preparations in controlling autoimmune symptoms.

Costs and Cost Analysis↗
PubMed1996

CT appearance of pulmonary vasculitis in children.

OBJECTIVE: The aim of this study was to determine whether a CT pattern that may represent early or subtle changes of pulmonary vasculitis in children exists. MATERIALS AND METHODS: High-resolution CT scans of the chest for 107 children were retrospectively reviewed by two radiologists who were unaware of the original study findings. Chest CT scans (conventional) for another 54 children who had symptoms or a diagnosis of vasculitis also were reviewed. RESULTS: We identified hazy or fluffy centrilobular, perivascular densities in 10 children, two of whom had small airways disease and eight of whom had vasculitis (Wegener's granulomatosis [n = 5], systemic lupus erythematosus [n = 1], scleroderma-polymyositis overlap syndrome [n = 1], and Churg-Strauss syndrome [n = 1]). The latter eight children underwent 35 scans, 17 of which were positive for these perivascular densities. All positive scans were associated with active disease of new onset (5/17) or with clinical exacerbation of preexisting systemic disease (12/17). The positive scans also were associated with an elevated erythrocyte sedimentation rate (13/17) and biopsy evidence of vasculitis from a variety of sites, including the lungs (n = 1), kidneys (n = 7), oropharynx (n = 5), skin (n = 9), lymph nodes (n = 1), and myocardium (n = 2). The single lung biopsy showed an angiocentric inflammatory-hemorrhagic process. Of the five patients who had positive scans, underwent therapy, and then had repeat studies, four patients had scans revert to normal in association with inactive disease. The remaining patient whose scan did not normalize failed to respond to treatment. CONCLUSION: The fluffy centrilobular pattern likely represents subtle changes of pulmonary vasculitis. In the appropriate clinical setting, such a finding may obviate the need for a lung biopsy.

Adolescent↗
PubMed1996

Intravenous immunoglobulin therapy in systemic onset juvenile rheumatoid arthritis: a followup study.

OBJECTIVE: To report the short and longterm effect of intravenous immunoglobulin (IVIG) in patients with systemic onset juvenile rheumatoid arthritis (SOJRA). METHODS: A retrospective chart review of 27 patients with SOJRA treated with IVIG and followed for 37.1 +/- 18.2 months was undertaken. Indications for treatment were fever, arthritis, or steroid dependency. RESULTS: We treated 27 patients with SOJRA with IVIG monthly for 3-54 months. Six months after IVIG therapy, 20 patients had a least a 50% decrease in at least one of the following: the number of days of fever; prednisone dose; or the number of active joints. Five patients failed to respond to IVIG, and 2 dropped out after 3 and 4 months. At last followup visit (mean 37.6 +/- 18 months), 11 of the initial 20 responder group patients were in remission, while 3 had significantly improved but still had active arthritis, and 6 were now unresponsive. Of the initial 5 patients in the nonresponder group, 4 had nonresponsive arthritis and 1 had improved at last followup. Three patients in the responder group subsequently developed other diseases. CONCLUSION: The main benefit of IVIG therapy to most of our patients was a significant improvement in the systemic features, with resolution of fever and a significant reduction in the steroid dose. The efficacy of IVIG in altering the course of arthritis was less predictable. We suggest that IVIG has a role in the management of SOJRA, but it should be limited to patients with severe SOJRA in whom prolonged unresponsiveness to standard therapy is present.

Adolescent↗
PubMed1996

Analysis of T cell receptor gamma transcripts in right and left knee synovial fluids of patients with rheumatoid arthritis.

OBJECTIVE: To establish the extent of clonal expansion of T cell receptor (TCR) gamma delta + T cells in synovial fluid (SF), and the sharing of the clones between affected knee joints from patients with rheumatoid arthritis (RA). METHODS: We quantified, using the polymerase chain reaction (PCR), the level of expression from each of the 4 V gamma gene families. We resolved PCR products on denaturing polyacrylamide gels to measure the proportion of mRNA transcripts contributed by clonally expanded gamma delta T cells. We subcloned and sequenced 509 cDNA clones derived from 8 SF and one peripheral blood sample from 2 patients with RA and one patient with juvenile onset RA to fully characterize the populations of T cell receptor gamma mRNA sequences. RESULTS: We found in each patient disproportionate expression of a subpopulation of T cell receptor gamma mRNA transcripts. Some of these transcripts are expressed by T cells found in both joints. CONCLUSION: Synovial TCR gamma delta + T cells are oligoclonal and some of these T cell clones are common to SF of both joints. The finding of identical T cell sequences from SF of both affected joints from each patient points to a role for gamma delta + T cells in disease progression.

Amino Acid Sequence↗
PubMed1996

Clinical significance of specific autoantibodies in juvenile dermatomyositis.

OBJECTIVE: To determine the prevalence and clinical association of myositis specific antibodies in an unselected group of patients with juvenile dermatomyositis (DM). METHODS: The sera of 42 subjects, representing an unselected group of patients from a single center, with juvenile DM and 7 others with idiopathic inflammatory myopathy (IIM) were examined for the presence of myositis specific antibodies by immunodiffusion against calf thymus extract and immunoprecipitation with HeLa extract. RESULTS: Of the subjects with juvenile DM, only 2 had evidence of antibodies specific to myositis (anti-Mi2). Three other patients with juvenile DM had defined autoantibodies not usually considered to be specific to myositis. Two of the 3 subjects had anti-PM-Scl; both developed features of scleroderma after the juvenile DM remitted. The 5 subjects with defined autoantibodies did not differ clinically from the remainder of the subjects with the exception of the late development of scleroderma features in 2. Fourteen other subjects with juvenile DM had unidentified bands on immunoprecipitation, which may represent as yet undiscovered myositis specific antibodies. No myositis specific antibodies were detected in any of the 7 subjects with other IIM syndromes. CONCLUSION: Based on our findings, we do not recommend routine clinical testing for these antibodies in children with typical juvenile DM. Further study of the unidentified bands seen in our subjects may lead to better understanding of the clinical groupings and etiopathogenesis of childhood myositis.

Adolescent↗
PubMed1995

Neurologic manifestations of pediatric systemic lupus erythematosus.

Central nervous system involvement is a common but rarely reviewed feature of pediatric systemic lupus erythematosus (SLE). We retrospectively reviewed the charts of 91 patients with pediatric SLE and using a standardized data abstraction form documented 40 patients with central nervous system (CNS-SLE) involvement. The mean age of onset of SLE was 13.3 years. In 19 patients the CNS manifestation was a presenting symptom, in 12 patients CNS involvement was present within the first year of diagnosis, and in 9 patients it took up to 7 years for CNS disease to become evident. Nineteen children (48%) manifested neuropsychiatric SLE, which included depression, concentration or memory problems, and frank psychosis. Seizures were present in 8 patients (20%), 6 had cerebral ischemic events (15%), 1 had chorea (3%), 2 had papilledema (5%), and 2 patients had a peripheral neuropathy (5%). Nine patients (22%) had severe headache consistent with lupus headache. Seven children had more than one CNS manifestation. In the investigation of CNS-SLE, computed tomography and/or magnetic resonance imaging scans were helpful in patients with focal ischemic lesions and venous sinus thrombosis. Electroencephalography was abnormal only in 33% of patients with seizure disorders and rarely helpful in patients with diffuse neuropsychiatric symptoms. Single-photon emission computed tomography scans were abnormal in most patients with neuropsychiatric SLE, especially in those with frank psychosis. The lupus anticoagulant was present in the patient with chorea and was frequently present in patients with cerebral vascular events. Long-term outcome was good: only 1 child died of cerebral hemorrhagic infarction and 3 others had significant persistent CNS deficits. The majority of patients (90%) had excellent recovery from CNS-SLE.

Adolescent↗
PubMed1995

Cerebral vein thrombosis in childhood systemic lupus erythematosus.

We describe three cases of cerebral vein thrombosis (CVT) in girls with systemic lupus erythematosus. Severe, persistent, unremitting headache was a common manifestation. In the first patient, although the clinical features were suggestive of CVT, the diagnosis was delayed and she had a significant cerebral infarct. In the other two patients the diagnosis was made earlier and led to more rapid treatment; the institution of early therapy may have prevented further sequelae. The CVT was diagnosed in all patients with a combination of computed tomography and magnetic resonance imaging studies without the need for angiography. All patients were treated for their underlying systemic lupus erythematosus and with anticoagulation. All are receiving long-term low doses of warfarin and have not had any recurrences.

Adolescent↗
PubMed1995

Scleroderma in children.

Childhood scleroderma may present in a variety of clinical forms that differ in clinical presentation, extracutaneous features, clinical course, and outcome. All include hardening of the skin as a major feature. This article reviews these various entities, focusing on primarily the clinical features. In addition, current concepts regarding pathogenesis and treatment are discussed.

Adolescent↗
PubMed1995

Evaluation of the cytokine response in Kawasaki disease.

Intracellular cytokines interleukin 6, tumor necrosis factor (TNF) alpha and TNF-beta were studied in peripheral blood mononuclear cells of patients with Kawasaki disease during the acute, subacute and convalescent stages of the disease utilizing cytokine-specific monoclonal antibodies and indirect immunofluorescence. Intracellular cytokines TNF-alpha and -beta were present only during the acute stage before initiation of therapy and not in the subacute or convalescent phase. Intracellular interleukin 6 was seen in both the acute phase and, in small numbers of patients, in the subacute stage of the illness. Overall 15 of 25 (60%) patients produced at least one intracellular cytokine. In the acute stage both monocyte and lymphocyte cytokines were detected intracellularly, TNF-alpha and TNF-beta in 58% of patients whereas interleukin 6 was seen in only 16%. This study provides evidence to support the involvement of activated mononuclear cells, both T cells and monocytes and their secreted soluble products, cytokines, in the pathogenesis of Kawasaki disease.

Acute Disease↗
PubMed1995

Autoantibody response to the Ro/La particle may predict outcome in neonatal lupus erythematosus.

This study was undertaken to determine the role of antibodies against both recombinant Ro (r-Ro) and La (r-La) proteins and polypeptides derived from the recombinant La protein in predicting fetal and neonatal outcome in children at risk to develop neonatal lupus erythematosus (NLE). All sera were obtained in the perinatal period and quantitative ELISA assays were used. We collected 41 maternal sera within 2 months of delivery of a child with NLE (21 with congenital heart disease block (CHB) and 20 with dermatologic NLE) and 19 sera from anti-Ro and/or anti-La antibody-positive mothers with systemic lupus erythematosus (SLE) who delivered a child without NLE. All sera were tested for anti-r-La and anti-r-Ro antibodies by ELISA, and most sera were tested for antibodies directed against La polypeptides by immunoblot. We found significantly higher anti-r-La antibody levels in the sera from mothers of children with NLE compared with sera from mothers of unaffected children (0.67 +/- 0.43 versus 0.14 +/- 0.30; P < 0.0001). There was a statistically significant difference in the mean anti-r-La levels between the sera of mothers of children with CHB compared with dermatologic NLE (0.51 +/- 0.45 versus 0.83 +/- 0.37 respectively; P = 0.0091). When we examined antibodies directed against the recombinant 52-kD Ro protein, there was a statistically significant elevation of titres in the sera of mothers of NLE children (0.77 +/- 0.35) compared with non-NLE mothers (0.29 +/- 0.39; P < 0.0001). There was no difference in the r-Ro levels between mothers of children with dermatologic NLE compared with CHB (0.82 +/- 0.37 versus 0.71 +/- 0.74; P = 0.32). When we examined polypeptides derived from the recombinant La protein, the mean number of polypeptides recognized by sera from mothers of children with NLE was significantly higher than the mean number of polypeptides recognized by sera from mothers of unaffected children (5.1 +/- 0.54 versus 2.3 +/- 0.54 respectively; P < 0.001). More importantly, when we examined the individual polypeptides, we found that only sera from mothers of children with NLE and not from mothers of unaffected children recognized a polypeptide designated DD (30% versus 0%, respectively). These studies indicate that the autoantibody response to the Ro/La particle can differentiate sera from mothers of children with NLE and sera from mothers of unaffected children. Furthermore, there was a difference in the anti-La autoantibody response between mothers of children with CHB and dermatologic NLE.(ABSTRACT TRUNCATED AT 400 WORDS)

Autoantibodies↗
PubMed1995

Experience with misoprostol therapy for NSAID gastropathy in children.

OBJECTIVE: To determine the effect of misoprostol, a synthetic prostaglandin E1 analogue, on the gastrointestinal tract (GIT) symptoms associated with non-steroidal anti-inflammatory drug (NSAID) administration and on the haemoglobin value, in children. METHODS: Retrospective chart review of children attending the paediatric rheumatology clinic at a tertiary referral hospital over a three year period, who were receiving NSAIDs and were prescribed misoprostol for treatment of GIT symptoms or anaemia. RESULTS: Twenty five children (mean age 12.0 (SD 2.8) (range 7-17) years were prescribed misoprostol (mean dose 308.4 (76.5) micrograms/m2/day; 9.8 (2.5) micrograms/kg/day) while NSAID therapy was continued. Of the 22 (88%) patients with GIT complaints, 18 (82%) had complete resolution of symptoms and two (9%) had some improvement. Four patients (18%) had a recurrence of symptoms after initial resolution while still receiving misoprostol. Misoprostol therapy was associated with a statistically significant increase in haemoglobin concentration (mean value before misoprostol 115 (18) g/l; after misoprostol 126 (15) g/l (p = 0.02)). The only adverse effect reported was self limited diarrhoea in one child. CONCLUSION: Misoprostol appeared to be effective in the treatment of GIT symptoms in children receiving NSAIDs and to result in significant increase in the haemoglobin concentration. Further prospective studies are needed to evaluate the role of misoprostol therapy for NSAID associated GIT complaints in the paediatric population.

Abdominal Pain↗
PubMed1995

Influence of food on the bioavailability of oral methotrexate in children.

OBJECTIVE: To determine the bioavailability of oral methotrexate (MTX) in patients with juvenile rheumatoid arthritis in the fasting and fed states. METHODS: Each patient randomly received their usual weekly MTX dose either orally (po) after an overnight fast, po immediately after a breakfast of their choice, or intravenously (iv) on 3 consecutive weeks. Blood samples were taken at 0, 0.5, 1, 1.5, 2, 3, 4, and 6 h after po and 0, 0.08, 0.25, 0.5, 1, 1.5, 2, 3, 4, and 6 h after iv administration. RESULTS: Fourteen patients (10 female) aged 2.8 to 15.1 yrs completed the study; the results of 13 patients were evaluable. The mean elimination rate constant was 0.27 +/- 0.065, 0.26 +/- 0.067, and 0.25 +/- 0.11 h-1 after po fasting, po fed, and iv administration, respectively. The total area under the serum concentration vs time curve was 1.87 +/- 0.83, 1.50 +/- 0.51, and 1.85 +/- 0.80 mumol/l.h after po fasting, po fed, and iv administration, respectively. The maximum serum MTX concentration (Cmax) was 0.65 +/- 0.33 and 0.39 +/- 0.18 mumol/l after po fasting and po fed administration, respectively (p = 0.0022). The time to Cmax was 0.94 +/- 0.40 and 1.32 +/- 0.68 h after po fasting and po fed administration, respectively (p = 0.1464). The bioavailability of oral MTX while fasting was 1.1 +/- 0.51, while that after a meal was 0.88 +/- 0.35 (p = 0.0211). CONCLUSION: These data indicate greater oral bioavailability of MTX in the fasting state. We recommend that children receive MTX on an empty stomach.

Administration, Oral↗
PubMed1995

Radiologic features of systemic onset juvenile rheumatoid arthritis.

OBJECTIVE: To document the radiologic abnormalities in patients with systemic onset juvenile rheumatoid arthritis (SOJRA) including abnormalities occurring early in the course of disease. METHODS: A retrospective review of the charts and radiographs of 42 consecutive children with SOJRA was carried out. Radiographs were reviewed by a single experienced radiologist with no knowledge of the clinical course of the patients. RESULTS: Soft tissue swelling and osteoporosis were the most common radiologic abnormalities (34/42; 81%). Cartilage loss and/or bone erosions were also common, occurring in 50% of patients. Erosions occurred within 2 years of disease onset in 11/36 (31%). Subchondral irregularity and sclerosis within 2 years of disease onset preceded erosions in 11 patients with serial radiographs. Severe radiologic abnormalities included joint ankylosis (8/42; 19%), subluxation (9/42; 21%), and protrusio acetabuli (4/42; 10%). Joint ankylosis occurred most commonly between 3 and 5 years after disease onset and subluxation between 2 and 6 years. CONCLUSION: A subgroup of children with SOJRA develops early destructive radiologic changes whose severity is comparable to those of children with rheumatoid factor positive polyarticular JRA. Early subchondral changes may be predictive of subsequent erosive disease in SOJRA and require prospective study using newer imaging techniques.

Adolescent↗
PubMed1995

Measuring disability in juvenile dermatomyositis: validity of the childhood health assessment questionnaire.

OBJECTIVE: Physical disability is perhaps the most important outcome of juvenile dermatomyositis (JDM). No functional assessment tool has been validated for inflammatory myopathies either in children or adults. We studied the measurement properties of the Childhood Health Assessment Questionnaire (CHAQ) in children with JDM. METHODS: We studied 37 patients followed at the JDM clinic and compared the results obtained by the CHAQ to a global disease severity score and quantitative muscle strength testing measured by sphygmomanometry (construct validity). We also measured the reliability of the CHAQ and its responsiveness to clinical change. RESULTS: For the initial measurement of each subject, the correlation between disease severity and CHAQ was high [Spearman's correlation, (rs = 0.71, p < 0.002)]. Disability as measured by the CHAQ was inversely correlated with proximal muscle strength (hip abduction rs = -0.57, p < 0.002; shoulder abduction rs = -0.51, p < 0.01) but, as expected, less so with more distal muscle strength (knee extension rs = -0.40, p = 0.05; grip strength rs = -0.079, p > 0.20). The CHAQ was reliable in subjects who showed no clinical change in muscle strength (intraclass correlation coefficient = 0.87) and responsive to treatment induced clinical change (responsiveness coefficient = 0.90). CONCLUSION: The CHAQ can serve as a valid and sensitive tool in the evaluation of functional outcomes in JDM.

Adolescent↗
PubMed1995

Autoantibodies to the nucleolar organizer antigen NOR-90 in children with systemic rheumatic diseases.

OBJECTIVE: To determine the frequency of autoantibodies directed against the nucleolar organizer antigen NOR-90 [human upstream binding factor (hUBF)] in pediatric patients with systemic rheumatic diseases. Two children with antibodies to NOR-90 are reported. METHODS: Two hundred thirty-eight sera from children with systemic rheumatic diseases were screened for autoantibodies directed against hUBF by indirect immunofluorescence and immunoblotting using MOLT-4 cell extracts. Reactivity with hUBF was confirmed by immunoprecipitation of the recombinant hUBF protein. RESULTS: Two sera out of 238 (< 1.0%) with reactivity against hUBF were identified. One patient had recurrent abdominal pain, headache, and Raynaud's phenomenon. There has been no evidence of an active systemic rheumatic disease in more than 8 years of followup. The 2nd patient had Raynaud's phenomenon and systemic lupus erythematosus. CONCLUSION: Antibodies to hUBF are rare in children with systemic rheumatic diseases. Raynaud's phenomenon was a clinical feature common to both patients.

Adolescent↗
PubMed1995

Hypoparathyroidism associated with systemic lupus erythematosus.

We describe a 15-year-old girl with systemic lupus erythematosus (SLE) who presented with hypocalcemia and a generalized seizure in the setting of an intercurrent illness and active central nervous system lupus. She was subsequently found to have idiopathic hypoparathyroidism. The association of SLE with hypoparathyroidism is extremely rare and this case represents the first pediatric report of this rare association. We suggest there may be a common underlying pathophysiological process linking these diseases.

Adult↗
PubMed1995

Antinuclear antibodies in children with localized scleroderma.

OBJECTIVE: To determine the prevalence and antigenic specificities of antinuclear antibodies (ANA) in children with localized scleroderma. METHODS: The ANA profiles of 27 children with localized scleroderma were determined. The study group comprised 21 children with linear scleroderma, 5 with morphea, and 1 with combined linear scleroderma and morphea. Sera were evaluated for the presence of ANA by indirect immunofluorescence and for reactivity with specific nuclear antigens by ELISA and immunoblotting. RESULTS: Seventeen patients (63%) had positive tests for ANA. Of these sera 10 displayed a finely speckled pattern, 5 a combined nucleolar and finely speckled nuclear pattern, and 2 a nucleolar pattern only. Fourteen of 21 (67%) with linear scleroderma were ANA positive. Three of 5 patients with morphea (60%) had ANA. The 1 patient with both linear scleroderma and morphea was ANA negative. Fifteen sera (56%) contained antibodies to denatured DNA (dDNA). Eleven sera (41%) had antibodies to one or more high mobility group (HMG) proteins, 4 (15%) reacted with one or more histones and 1 serum (4%) reacted with topoisomerase I (Sc1-70). CONCLUSION: ANA are present in most children with localized scleroderma and frequently have specificity for dDNA and HMG proteins. Children with localized scleroderma, like patients with systemic sclerosis (SSc), commonly have ANA and antibodies to dDNA. Unlike patients with SSc, however, childhood localized scleroderma is uncommonly associated with antibodies to certain specific nuclear and nucleolar constituents that typically occur in association with SSc.

Adolescent↗