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Biomedical subjects

E D Silverman

Publications and source records attributed to E D Silverman.

At least 73 records · Page 4Linked to original sources
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

Renal hemodynamic response to the creation of vascular access in patients with end-stage renal disease.

To evaluate the possibility that the placement of arteriovenous anastomosis (a/v a) may lead to the attenuation of glomerular hyperfiltration, we studied 5 nondiabetic patients before and after creation of vascular access for hemodialysis. Patients received no EPO and antihypertensive therapy was discontinued 24 h before each study. Cardiac output (CO) and a/v a flow rates were measured by Doppler echo, and GFR and ERPF by plasma decay curves of Tc99m DTPA and 131I-hippuran, respectively. Other parameters were calculated by standard formulas. Augmentation of CO and decrease in systemic vascular resistance occurred in all patients (p = 0.05), yet renal findings were less predictable since only three patients showed a decrease in renal vascular resistance and filtration fraction post a/v a. Thus, there is a discordant pattern of renal hemodynamic response to the creation of a/v a in end-stage renal disease and further studies are needed to better define the subset of patients who are prone to renal vasodilation after the placement of a/v a.

Adult↗
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

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↗
PubMed1994

Serum levels of soluble interleukin-2 receptor. A marker of disease activity in localized scleroderma.

OBJECTIVE: To determine whether circulating serum levels of soluble interleukin-2 receptor (sIL-2R) are elevated in patients with localized scleroderma, and if levels of sIL-2R can differentiate between active and inactive disease. METHODS: Seventeen patients with localized scleroderma were categorized by overall physician assessment into active, inactive, and indeterminate groups, according to disease activity. Serum sIL-2R levels were analyzed and correlated with disease activity. RESULTS: The mean sIL-2R level was significantly higher (P = 0.005) in those with active disease (1,675 +/- 823 units/ml) than in those with inactive disease (722 +/- 218 units/ml). CONCLUSION: Serum sIL-2R levels are elevated in patients with localized scleroderma. When present, elevated sIL-2R levels appear to be able to differentiate active from inactive disease. This fact also suggests cell-mediated immune activation in this condition. Further serial studies are required to assess the value and sensitivity of sIL-2R levels in measuring changes in disease activity.

Adolescent↗
PubMed1994

Localized scleroderma in childhood: a report of 30 cases.

Localized scleroderma (LS), a rare disease that occurs primarily in the pediatric age group, differs from systemic sclerosis (SSc) in that it is usually limited to the skin and subcutaneous tissue and is only rarely associated with systemic manifestations. The authors' experience with pediatric LS seen in 30 patients at a tertiary care center was reviewed: 26 had linear scleroderma, 19 on an extremity and 7 on the face; 3 had morphea; and 1 had generalized morphea. Antinuclear antibodies were present in 76% and rheumatoid factor in 39%. Five of 19 patients with linear scleroderma that involved an extremity had growth failure in that limb, and 1 required surgery. Sclerodermatous involvement over a joint resulted in limited range of movement in 6 patients, and 1 required surgery. One of the 30 patients developed SSc and polymyositis. There was difficulty in evaluating disease activity and hence in evaluating treatment. This experience with a large patient population suggests that LS, although usually a self-limiting disease, can result in significant morbidity.

Adolescent↗
PubMed1994

Provocative red blood cell scintiscan in occult chronic gastrointestinal hemorrhage.

A patient with a chronic occult gastrointestinal bleeding site is described. Because an extensive examination failed to locate the site of bleeding, a heparin infusion was used in conjunction with a conventional Tc-99m labeled red cell bleeding study. A mid-jejunal ulcer was safely localized before elective surgery. A protocol for a heparin provocative bleeding study is proposed.

Aged↗
PubMed1994

Local synthesis of both macrophage and T cell cytokines by synovial fluid cells from children with juvenile rheumatoid arthritis.

The production of tumour necrosis factor-alpha (TNF-alpha), TNF-beta and IL-6 in synovial fluid was studied in 50 samples of synovial fluid from 44 children with juvenile rheumatoid arthritis (JRA) by identifying cytokine production at a single-cell level. Post Ficoll-separated synovial fluid mononuclear cells were permeabilized and then intracellular TNF-alpha, TNF-beta and IL-6 protein production was examined using indirect immunofluorescence and murine anti-cytokine MoAbs. All three cytokines were measured in 37 of the 50 samples. In 25 of the 37 samples there was complete concordance; all three cytokines were present in six and absent in 19 samples. At least one cytokine was present in 27/50 (54%) of synovial fluid samples. Overall, TNF-alpha was detected in 22/49 (45%) samples, TNF-beta in 15/41 (37%) and IL-6 in 16/45 (36%) samples. Five patients had serial arthrocentesis, and in these samples there were two patients who had initially positive cytokine production, which on subsequent measurement was negative; in the other three patients there was no change from the previous cytokine production. We provide evidence that synovial fluid mononuclear cells produce monocyte and T cell cytokines in JRA. These findings suggest a role for both T cell and macrophage products in the pathogenesis of JRA, and the potential for modulation of cytokine production as a target for therapeutic intervention.

Adolescent↗
PubMed1994

Intravenous immunoglobulin in the treatment of systemic juvenile rheumatoid arthritis: a randomized placebo controlled trial. Pediatric Rheumatology Collaborative Study Group.

OBJECTIVE: To assess the efficacy and safety of intravenous immunoglobulin (IVIG) in juvenile rheumatoid arthritis (JRA). METHODS: Thirty-one children with active, refractory, systemic JRA were randomized into a multicentered, double blinded, placebo controlled trial. Patients received infusions of 1.5 g/kg of IVIG or placebo (0.1% albumin) every 2 weeks for 2 months, then monthly for 4 months (total: up to 9 infusions over 6 months). Twenty-nine of the 31 patients were included in the efficacy subset. RESULTS: Fourteen patients discontinued prematurely from study, 7 in each treatment group. A higher proportion of patients in the IVIG group improved (50 vs 27%) as assessed by the physician's global assessment. However, the sample size was small and this difference was not statistically significant. IVIG was not more effective than placebo in reducing the number of days with fever or other systemic manifestations. Changes from baseline in the joint count, hemoglobin, albumin, platelet count, and erythrocyte sedimentation rate did not differ between treatment groups. CONCLUSION: Our results suggest that high dose IVIG has limited clinical utility in systemic JRA. However, this trial failed to enroll adequate numbers of patients to permit valid statistical intergroup comparisons, and the results must be considered nondefinitive.

Adolescent↗
PubMed1994

Phospholipase A2 in juvenile rheumatoid arthritis: correlation to disease type and activity.

OBJECTIVE: Secretory nonpancreatic phospholipase A2 (snpPLA2) is a proinflammatory enzyme and its activity in serum correlates with disease activity in adults with rheumatoid arthritis. Juvenile rheumatoid arthritis (JRA) may be stratified into 3 clinical types with differing degrees of disease activity. Since in JRA there are no reliable indices of disease activity, our objective was to find whether the level of circulating snpPLA2 correlates with the severity of inflammation and with JRA activity. METHODS: PLA2 enzymatic activity was assayed using E. coli membranes labelled with (14C)-oleic acid. SnpPLA2 immunoreactivity was tested by ELISA technique using monoclonal antibodies against recombinant human (rh) snpPLA2. SnpPLA2 activity was determined in sera of 127 children including 25 with systemic (S-JRA), 50 with polyarticular (Po-JRA) and 52 with pauciarticular (Pa-JRA) types of JRA. Twenty-five patients with active disease, were subsequently restudied in an inactive phase. RESULTS: Markedly increased snpPLA2 (> mean + 2 SD of normal mean, i.e., > 575 U/ml) was found during the active disease in 100% S-JRA, 57% Po-JRA and 25% Pa-JRA patients. The differences in the mean and median PLA2 activity among these 3 subtypes of JRA were highly significant (p < 0.001) with the highest levels found in S-JRA and the lowest in Pa-JRA. Presence of rheumatoid factor and/or of antinuclear antibody had no relation to the level of snpPLA2. SnpPLA2 activity became markedly lower when active inflammation became quiescent. In the whole group, snpPLA2 activity correlated highly with the Lansbury index, number of involved joints and number of effusions. A significant positive correlation was also found between snpPLA2 and erythrocyte sedimentation rate (ESR) and neutrophil count, while a significant negative correlation was noted with the level of albumin and hemoglobin. With the exception of snpPLA2, other laboratory variables did not correlate with the number of effusions or the number of active joints. However a negative correlation was noted between both hemoglobin and albumin, and Lansbury index. CONCLUSION: Circulating snpPLA2 significantly correlates with JRA activity and may serve as an index of activity in JRA especially in patients with systemic type of disease.

Adolescent↗
PubMed1994

The effect of in vivo erythropoietin on cytokine mRNA in CAPD patients.

There is increasing evidence that erythropoietin (EPO) affects immune function in addition to its well-known effects on the erythrogenesis. However, many of the studies examining the immunomodulatory capacity of this hormone have been in vitro. We examined mRNA signal for three important cytokines, interleukin 1(IL-1), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha), in stable continuous ambulatory peritoneal dialysis (CAPD) patients at baseline, and again at 2, 4, and 6 months after treatment with EPO. Significant changes were noted in all three cytokine mRNA signals in the majority of patients treated with this hormone. We conclude that EPO has significant immunomodulatory effects in vivo as defined by changes in cytokine mRNA compared to control. The significance of these changes, and their relationship to well-being and altered immune function remain to be better defined.

Adult↗
PubMed1994

Scintigraphic detection of hemobilia complicating angiodysplasia.

A 78-yr-old man underwent 99mTc-labeled red cell examination for a gastrointestinal bleeding episode. Gallbladder visualization was noted during the examination. Hemobilia has been reported in a variety of pathologic conditions; scintigraphic gallbladder visualization has also been reported as a result of the unusual radiolabeling characteristics of 99mTc during red cell scintigraphy. Postmortem examination revealed angiodysplasia of the gallbladder and other sites in the gastrointestinal tract. Angiodysplasia must be considered in the pathologic spectrum of causes of hemobilia.

Aged↗
PubMed1993

Clinical, serologic, and immunogenetic studies in childhood-onset systemic lupus erythematosus.

OBJECTIVE: To determine the frequency of systemic lupus erythematosus (SLE)-associated clinical manifestations, autoantibodies, and HLA class II alleles in a large cohort of patients with childhood-onset SLE. METHODS: Eighty children with SLE onset before age 18 (27 before age 11) were studied for the frequency of renal, neuropsychiatric, and hematologic complications as well as for anti-native DNA, Ro, La, Sm, and U1 RNP autoantibodies. HLA-DR, DQ, and DP alleles were determined by oligotyping. The results were compared with findings in 213 adults with SLE onset at or after age 18 years. RESULTS: Renal involvement was more frequent in those with childhood-onset SLE, especially those with onset before age 11 (82%, compared with 53% in adults). Anti-U1 RNP was more common in American blacks with SLE onset before age 18. HLA-DRB1*0301, DQA1*0501, DQB1*0201 was more common in Caucasians and DRB1*1503, DRB5*0101, DQA1*0102, DQB1*0602 in American blacks, regardless of age at SLE onset. Anti-Sm autoantibodies were most highly associated with HLA-DQA1*0102 and DQB1*0602. CONCLUSION: While childhood-onset SLE shares many immunogenetic and serologic similarities to adult-onset disease, important clinical differences nevertheless exist in children with this disease.

Adolescent↗