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Biomedical subjects

R M Laxer

Publications and source records attributed to R M Laxer.

At least 37 records · Page 2Linked to original sources
PubMed1999

Autoantibodies to the extracellular matrix microfibrillar protein, fibrillin 1, in patients with localized scleroderma.

OBJECTIVE: Serum autoantibodies to fibrillin 1, the major component of microfibrils in the extracellular matrix, recently have been reported to occur in the tight skin mouse and in patients with systemic sclerosis, but not in patients with other connective tissue diseases. This study was undertaken to determine whether antifibrillin 1 antibodies could be detected in patients with localized forms of scleroderma. METHODS: Sera from 50 patients with localized scleroderma (27 with linear scleroderma and 23 with morphea) and 51 normal controls were tested for IgG and IgM antifibrillin 1 autoantibodies, using a radioimmunoassay (RIA) and a human recombinant fibrillin 1 protein (rFbn-1). RESULTS: Both in patients with linear scleroderma and in those with morphea, mean levels of IgM and IgG binding to rFbn-1 were significantly higher than in controls. Eight patients with linear scleroderma (30%) and 6 patients with morphea (26%) had IgG autoantibodies to fibrillin 1 (rFbn-1) by RIA, compared with 3 controls (6%) (P = 0.006 and P = 0.022, respectively). No correlations between antifibrillin 1 antibodies and active skin disease or antinuclear antibody positivity were found. CONCLUSION: Autoantibodies to fibrillin 1 occur in patients with both forms of localized scleroderma (linear scleroderma and morphea). The clinical and pathogenetic significance of this autoimmune response remains to be determined.

Autoantibodies↗
PubMed1999

Tubulointerstitial nephritis and uveitis in children and adolescents. Four new cases and a review of the literature.

We identified 35 cases of tubulointerstitial nephritis and uveitis (TINU), 31 from a MEDLINE search (1966-1996) of the English literature and 4 from our hospital records (1988-1996). To meet the case definition, the patient had to be less than 18 years old and have TINU of unknown cause. Common presenting symptoms included fatigue, weight loss, fever, and abdominal pain. The uveitis was usually anterior and could occur at any time with respect to the onset of the renal disease. Common laboratory features included anemia, increased erythrocyte sedimentation rate, and decreased creatinine clearance. Most patients (33 of 35) had renal biopsies that commonly revealed an intense inflammatory interstitial infiltrate, glomerular sparing, and negative immunofluorescence studies. Of the 35 patients, 26 received systemic corticosteroid therapy (5 of 26 for eye disease); 22 had follow-up for at least 1 year; 13 of 35 patients had a recurrence of their uveitis. The outcome in all 35 cases was normal renal function with no documented visual loss. In conclusion, TINU is a unique syndrome with characteristic clinical features, laboratory changes, and renal biopsy results. Treatment is controversial, and the outcome in children, even if untreated, is excellent.

Adolescent↗
PubMed1999

CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome.

Altered growth and function of synoviocytes, the intimal cells which line joint cavities and tendon sheaths, occur in a number of skeletal diseases. Hyperplasia of synoviocytes is found in both rheumatoid arthritis and osteoarthritis, despite differences in the underlying aetiologies of the two disorders. We have studied the autosomal recessive disorder camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP; MIM 208250) to identify biological pathways that lead to synoviocyte hyperplasia, the principal pathological feature of this syndrome. Using a positional-candidate approach, we identified mutations in a gene (CACP) encoding a secreted proteoglycan as the cause of CACP. The CACP protein, which has previously been identified as both 'megakaryocyte stimulating factor precursor' and 'superficial zone protein', contains domains that have homology to somatomedin B, heparin-binding proteins, mucins and haemopexins. In addition to expression in joint synovium and cartilage, CACP is expressed in non-skeletal tissues including liver and pericardium. The similarity of CACP sequence to that of other protein families and the expression of CACP in non-skeletal tissues suggest it may have diverse biological activities.

Amino Acid Sequence↗
PubMed1999

Long-term toxicity of immune suppression in juvenile rheumatic diseases.

Although there are not many studies which have addressed long-term outcomes in children with rheumatic disease treated with immunosuppressive agents, the data that are available, as well as information from adult studies, suggest significant long-term concerns with all the agents that have demonstrable efficacy. This must lead us to investigate new methods of treatment which will not only be more effective, but also less toxic.

Adolescent↗
PubMed1998

The camptodactyly-arthropathy-coxa vara-pericarditis syndrome: clinical features and genetic mapping to human chromosome 1.

OBJECTIVE: To delineate the clinical features in patients with the autosomal recessive camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP) and to determine the location of the involved gene. METHODS: Eight affected individuals (ages 2-15 years) with CACP from 4 consanguineous kindreds were clinically evaluated. Four patients are newly described and 4 have been reported previously. Findings were compared with those in 21 other previously reported cases. DNA obtained from the 8 affected patients and their available siblings and parents was used in a genome-wide search for linkage. RESULTS: Congenital camptodactyly and childhood-onset noninflammatory arthropathy were present in all affected patients. Seven patients developed bilateral coxa vara deformity, and 1 developed coxa magna with cystic erosions. Two of the patients also had symptoms or signs of pericarditis. A genome-wide search for linkage identified homozygosity for a series of genetic markers on human chromosome 1q in all affected patients. The marker D1S191 yielded a maximum logarithm of the odds ratio (LOD score) of 3.3 at theta = 0. The CACP gene lies within a 1.9-cM candidate interval defined by the markers D1S2107 and D1S222. CONCLUSION: The principal features of the CACP syndrome are congenital or early-onset camptodactyly and childhood-onset noninflammatory arthropathy. Coxa vara deformity or other dysplasia associated with progressive hip disease may develop over time. Clinical pericarditis may also occur. A locus responsible for causing CACP syndrome is assigned to a 1.9-cM interval on human chromosome 1q25-31 by homozygosity mapping. This now facilitates the identification of the responsible gene and permits testing for locus homogeneity in other CACP kindreds.

Adolescent↗
PubMed1998

Assessment of myocardial perfusion and function in childhood systemic lupus erythematosus.

OBJECTIVES: To determine the prevalence of abnormalities in myocardial perfusion or function in children with systemic lupus erythematosus (SLE), and describe potential factors that may predict their development. STUDY DESIGN: Patients (n = 40; 30 female) were enrolled through the Lupus Clinic at The Hospital for Sick Children between 1990 and 1992. Resting and exercise thallium myocardial perfusion scans, radionuclide angiography with multiple gated acquisition (MUGA), and resting M-mode and two-dimensional echocardiography were performed. RESULTS: All patients were free of symptoms, and none had a history of ischemic heart disease. Their median age was 15.9 years (range 10.5 to 19.8 years) at enrollment. Abnormalities of coronary perfusion were found in 5 (16%) of 31 patients (95% confidence interval: 3%, 29%) and included a large fixed perfusion defect in 1; 5 of 27 MUGA scans showed marginally low left ventricular ejection fractions at rest, whereas all had normal exercise responses. In the group with abnormal thallium scans, three of five patients had antiphospholipid antibodies detected, and two of four had an abnormal plasma lipid profile. This group tended to have a shorter disease duration and had received a lower cumulative dose of corticosteroids; these differences were not statistically significant compared with the group with normal scans. CONCLUSION: Asymptomatic abnormalities of myocardial perfusion occur in children with SLE and are more common than previously suspected. Patients with these abnormalities of myocardial perfusion may be predisposed to the previously recognized early-onset ischemic heart disease seen in adults with SLE.

Adolescent↗
PubMed1998

Systemic onset juvenile rheumatoid arthritis.

Systemic onset juvenile rheumatoid arthritis (SoJRA) accounts for 10-20% of all JRA, affecting males and females equally and occurring most frequently under the age of 5 years. It is characterized by arthritis, daily spiking fever, an evanescent rash, serositis and a variety of other extra-articular features. Exclusion of systemic infections, malignancies and connective tissue diseases is most important in establishing the diagnosis. The disease has a wide range of severity from a short monocyclic course to a prolonged chronic course with severe destructive arthritis in approximately one third of patients. Destructive arthritis, secondary amyloidosis and treatment complications including infections, osteoporosis, growth retardation and the macrophage activation syndrome account for the significant morbidity and mortality associated with the disease. Pharmacological management includes non-steroidal anti-inflammatory drugs, corticosteroids, methotrexate and an emerging role for cyclosporine A and cytotoxic drug therapy. Elucidation of the immunopathogenetic mechanisms may lead to new targeted therapy.

Age of Onset↗
PubMed1998

Single photon emission computed tomography scanning in childhood systemic lupus erythematosus.

OBJECTIVE: To determine the role of central nervous system (CNS) perfusion scanning in detecting CNS disease in childhood onset systemic lupus erythematosus (SLE) and serial single photon emission computed tomography (SPECT) scans in monitoring CNS disease activity in childhood. METHODS: The charts of 108 patients with a confirmed or suspected diagnosis of SLE during the period February 1987 to June 1992 were reviewed. Twenty patients with a diagnosis of CNS SLE and 10 patients without CNS involvement had at least one SPECT scan. Patients were divided into (a) focal CNS SLE, when there were clinical manifestations that could be attributed to localized lesions of the CNS (6 patients); and (b) diffuse CNS SLE, when there was a global defect in CNS function including organic brain syndrome, psychosis, and depression (14 patients). If a patient had both diffuse and focal CNS disease that patient was designated as having diffuse disease. Forty-three patients with a diagnosis other than SLE comprised our non-SLE control group. RESULTS: SPECT scans were performed in 20 patients with acute CNS involvement. In patients with acute diffuse CNS disease, diffuse patchy areas of hypoperfusion were seen in 86% of patients at presentation of the CNS event. In the focal CNS disease subgroup, 33% of patients had an abnormal scan at CNS presentation. In these patients focal rather than diffuse abnormalities were seen. Eight patients with diffuse CNS SLE had at least one followup study at intervals ranging from 1 month to 3 years after initial scan. In 50% of these patients with diffuse CNS involvement, improvement in their abnormal scan correlated with clinical improvement, while in the other 50% clinical improvement was not associated with SPECT scan improvement. The most common abnormal SPECT scan pattern in patients with CNS SLE was one of widespread multiple small areas of decreased uptake at multiple sites, suggestive of generalized patchy hypoperfusion. Although SPECT scans were sensitive to the presence of CNS disease, the diffuse hypoperfusion was not specific for clinically detectable CNS involvement. In patients with SLE, a diffusely abnormal scan had a specificity of 69% and a likelihood ratio of 2.2 to correctly detect overt diffuse CNS disease. CONCLUSION: Although we found that SPECT scanning was a highly sensitive method, it was not a specific method in correctly diagnosing diffuse CNS SLE in children. However, the presence of an abnormal SPECT scan in SLE patients with no history of overt CNS SLE may suggest that subclinical CNS disease may be more common in children than previously suggested.

Adolescent↗
PubMed1998

Cyclosporine in the treatment of an unusual case of juvenile systemic sclerosis.

We describe a child who initially presented with juvenile dermatomyositis (JDM). Four years after the complete remission of JDM she developed systemic sclerosis without internal organ involvement. She was unresponsive to a combination of systemic corticosteroid therapy and pencillamine. The institution of cyclosporine induced a complete remission.

Adolescent↗
PubMed1997

Neonatal lupus erythematosus.

This article discusses neonatal lupus erythematosus, which is a disease of the newborn defined by the presence of maternal autoantibodies and characteristic clinical features in the neonatal period. Although the autoantibodies often are not associated with clinical disease in the mother, neonatal lupus erythematosus is likely the result of fetal or neonatal tissue damage caused by maternally transmitted IgG autoantibodies.

Animals↗
PubMed1997

General and local scleroderma in children and dermatomyositis and associated syndromes.

Scleroderma in children virtually always manifests in the form of localized disease, whereas adult scleroderma usually manifests as systemic disease. The recent literature on childhood scleroderma is limited almost exclusively to localized disease. The treatment of this disease remains a dilemma, especially with regard to which patients should be treated, how they should be treated, and how the treatment response should be monitored. Our current therapeutic approach is reviewed. The recent literature regarding juvenile dermatomyositis is discussed. New understanding of the pathobiology of this disease should lead to improved, less toxic treatments in the future.

Child↗
PubMed1997

Patellar enthesopathy in childhood: a new clinical and radiographic observation.

Enthesitis occurs commonly in patients with seronegative spondyloarthropathies. The patella is frequently affected by enthesopathy, but overgrowth has not been reported as a manifestation of enthesitis in pediatrics. We describe 3 patients with seronegative enthesopathy and arthropathy syndrome and patellar overgrowth.

Child↗
PubMed1997

Evolution of the T cell receptor beta repertoire from synovial fluid T cells of patients with juvenile onset rheumatoid arthritis.

OBJECTIVE: To determine the level of T cell clonal expansion and the proportion of T cells that persist over time in the synovial fluid (SF) of patients with juvenile onset rheumatoid arthritis (JRA). METHODS: We collected SF samples from each of 3 patients with JRA at 2 to 3 year intervals. To measure expression across the entire spectrum of Vbeta families in each of 7 fluids examined, we synthesized and amplified dscDNA from all 24 Vbeta families with a single reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: The proportion of clonally expanded T cells and persistent T cells is low and variable among patients. CONCLUSION: The data are supportive of disease models not centered on T cells but centered on the changing nature of the disease over time.

Age of Onset↗
PubMed1996

Antiribosomal P antibodies in pediatric patients with systemic lupus erythematosus and psychosis.

OBJECTIVE: To study antibodies directed against ribosomal P proteins, a sensitive and specific marker of depression and psychosis in systemic lupus erythematosus (SLE), in pediatric patients with SLE. METHODS: One hundred six serum samples were obtained from 79 patients with SLE. Sixty age- and sex-matched control sera were obtained, and 12 samples were obtained from children with primary psychosis. Antibodies to recombinant ribosomal P (rRP) protein were detected using a standard enzyme-linked immunosorbent assay. RESULTS: All 12 children with non-SLE-associated psychosis had normal levels of anti-rRP antibodies. Elevated levels of anti-rRP were found in 11 of 64 pediatric SLE patients without a history of psychosis (17%). In the group of 13 SLE patients with psychosis, 5 (38%) had increased anti-rRP antibody levels during the time of acute psychosis, and which significantly decreased during remission. In addition, most of the SLE patients without a history of psychosis had a good correlation between anti-rRP antibody levels and disease activity. The patients with psychosis had significantly less renal involvement than the patients without a history of psychosis. This apparent protection from renal disease was not related to the presence or absence of either antiribosomal P or anti-DNA antibodies. CONCLUSION: Elevated serum levels of antibodies to ribosomal P protein can distinguish SLE-associated psychosis from primary psychosis of childhood. In SLE, elevated antiribosomal P antibody levels were not specific for psychosis. Serial assays were useful for monitoring the disease activity.

Antibodies, Anti-Idiotypic↗
PubMed1996

Long-term outcome of mothers of children with complete congenital heart block.

OBJECTIVES: To determine the health of mothers of offspring with complete congenital heart block (CHB) both at the time of delivery of the affected child and in the long-term, and the percentage of mothers and children with CHB who had anti-SSA/Ro and/or SSB/La antibodies. PATIENTS AND METHODS: Sixty-four mothers of 64 children with CHB (seen between 1964 and 1993) were identified through the Cardiology database of The Hospital for Sick Children, Toronto, Canada. Medical information from these of children with CHB was evaluated. Data were obtained from the mothers by mailed questionnaire, telephone interview, and/or from the attending physicians. The presence of anti-Ro antibodies and anti-La antibodies were evaluated by ELISA assay. RESULTS: The mean age at the time of delivery of the first child with CHB was 28 +/- 6 years. At the time of delivery 42 (66%) mothers were healthy, 2 (3%) had systemic lupus erythematosus (SLE), 2 (3%) had linear scleroderma, 2 (3%) had rheumatoid arthritis; 3 (5%) had a history of rheumatic fever (but were otherwise well), 1 (2%) had Sjogren's syndrome (SS), and 12 (19%) had an undifferentiated autoimmune syndrome (UAS) (arthralgia, myalgia, photosensitivity, skin vasculitis, Raynaud's phenomenon). The mean time to follow-up from deliver to study was 121 +/- 88 months. The mean maternal age at study was 38 +/- 9 years. Three of 12 mothers who initially had a UAS progressed to SLE (average follow-up time of 80 months, median 96), and 2 developed SS (with average follow-up time 140 months, median 132) and 1 went into remission. The mean follow-up time for the other mothers who did not develop an autoimmune disease was 150 +/- 102 months. Thirty-six of the 42 initially healthy mothers remained well. One mother developed SLE; 1 developed hyperthyroidism; 1 developed anky-losing spondylitis; and 3 developed an UAS. The mean follow-up time of the 36 mothers who remained healthy was similar (123 +/- 97 months) to the 6 initial healthy mothers who developed an autoimmune disease (121 +/- 36 months). Anti-Ro and/or anti-La antibodies were positive in 32 of 53 (60%) mothers tested. Fourteen of the 53 mothers were symptomatic at the time of delivery and 39 were asymptomatic. Anti-Ro and/or anti-La antibodies were positive in 12 of 13 mothers tested at the time of delivery. CONCLUSIONS: The long-term maternal outcome in our cohort was very good as most of the initially healthy mothers remained well at follow-up. Twenty-five percent of the mothers with a UAS and only 2% of the initially healthy mothers developed SLE. The development of an autoimmune disease in an asymptomatic mother identified by the birth of a child with CHB was less common in our study than in previous studies. However, close follow-up of mothers with UAS is warranted.

Adult↗
PubMed1996

Seasonal onset of systemic-onset juvenile rheumatoid arthritis.

OBJECTIVE: This study was undertaken to investigate the recent finding of a seasonal difference in the onset of systemic-onset juvenile rheumatoid arthritis (SoJRA). We hypothesized that a seasonal onset pattern might implicate on infectious agent as a cause of SoJRA. METHODS: The date of onset was collected from the records of all patients with SoJRA from 1980 to 1992 at presentation to pediatric rheumatology clinics across Canada. The onset pattern of SoJRA was then compared with incidence data on viral infections obtained for the same period. RESULTS: Across Canada the onset of SoJRA was constant across the seasons. However, in the Prairie region there was a statistically significant seasonal pattern, with peaks in autumn and early spring. We could find no evidence that viral incidence correlated with disease incidence either throughout Canada or in the Prairie region. CONCLUSIONS: If a seasonal infectious agent causes SoJRA, then it is likely only one of several causes and may act only in certain regions. Future studies should be carried out in those areas where SoJRA does have a seasonal onset pattern.

Adolescent↗
PubMed1996

Accelerated nodulosis during methotrexate therapy for juvenile rheumatoid arthritis.

We describe two patients with rheumatoid factor-positive, polyarticular-onset juvenile rheumatoid arthritis in whom accelerated nodulosis developed during methotrexate therapy. Although they had only a few nodules at diagnosis, the nodules increased in number and size 3 to 4 months after the start of methotrexate therapy in both patients. The nodules regressed after withdrawal of methotrexate therapy in one patient and were arrested with the addition of hydroxychloroquine in the other. Physicians treating patients with methotrexate for juvenile rheumatoid arthritis must be aware of this extraarticular side effect.

Adolescent↗