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Biomedical subjects

J T Cassidy

Publications and source records attributed to J T Cassidy.

At least 19 recordsLinked to original sources

Methotrexate in resistant juvenile rheumatoid arthritis. Results of the U.S.A.-U.S.S.R. double-blind, placebo-controlled trial. The Pediatric Rheumatology Collaborative Study Group and The Cooperative Children's Study Group.

BACKGROUND: The antimetabolite methotrexate has been shown in placebo-controlled trials to be effective in adults with rheumatoid arthritis. Methotrexate may also be effective in children with resistant juvenile rheumatoid arthritis, but the supporting data are from uncontrolled trials. METHODS: Centers in the United States and the Soviet Union participated in this randomized, controlled, double-blind trial designed to evaluate the effectiveness and safety of orally administered methotrexate. Patients received one of the following treatments each week for six months: 10 mg of methotrexate per square meter of body-surface area (low dose), 5 mg of methotrexate per square meter (very low dose), or placebo. The use of prednisone (less than or equal to 10 mg per day) and two nonsteroidal antiinflammatory drugs was also allowed. RESULTS: The 127 children (mean age, 10.1 years) had a mean duration of disease of 5.1 years; 114 qualified for the analysis of efficacy. According to a composite index of several response variables, 63 percent of the children who received low-dose methotrexate improved, as compared with 32 percent of those in the very-low-dose group and 36 percent of those in the placebo group (P = 0.013). As compared with the placebo group, the low-dose group also had significantly larger mean reductions from base line in the number of joints with pain on motion (-11.0 vs. -7.1), the pain-severity score (-19 vs. -11.5), the number of joints with limited motion (-5.4 vs. -0.7), and the erythrocyte sedimentation rate (-19.0 vs. -6 mm per hour). In the methotrexate groups only three children had the drug discontinued because of mild-to-moderate side effects; none had severe toxicity. CONCLUSIONS: Methotrexate given weekly in low doses is an effective treatment for children with resistant juvenile rheumatoid arthritis, and at least in the short term this regimen is safe.

Administration, Oral

Current status of the medical treatment of children with juvenile rheumatoid arthritis.

Based on clinical experience and the aforementioned studies, a number of opinions can be entertained concerning the historically traditional conservative management of children with JRA. 1. Because the inflammatory changes of JRA on the bones and joints once established are irreversible in most children, there are ample theoretical reasons to start more effective therapy (if available) early. 2. Most of the currently available drugs control inflammation only partially or temporarily. 3. Most children stop taking the various SAARDS after approximately 2 years of disease because of lack of efficacy or the development of toxicity. 4. Whereas corticosteroids are the most potent and effective anti-inflammatory agents, long-term use in children, even in low dosage, is severely limited, especially by their effect on growth. 5. Methotrexate appears to be the most effective of the alternative agents and much safer than expected when used in the currently recommended protocol. 6. More effective therapy must await a better understanding of the pathogenesis of JRA, although currently available medications might be used more rationally by taking into consideration available pharmacologic studies.

Anti-Inflammatory Agents

Estimation of bone mineral density in children with juvenile rheumatoid arthritis.

Bone mineral content of different areas of the skeleton was measured by dual photon absorptiometry in 20 children with juvenile rheumatoid arthritis (JRA) and compared to 20 age and sex matched healthy children. Spinal density was similar in both groups in prepubertal children but decreased in the postpubertal girls with JRA. Total bone density was also decreased in the postpubertal girls. Six children with JRA had repeat scans 12 to 24 months later; in 3 children total bone mineral content increased significantly with an intensive management program. Our study suggests that bone mineral density does not show a pubertal increase in children with JRA, as it does in healthy children.

Absorptiometry, Photon

Comparing information-gathering strategies of medical students and physicians in diagnosing simulated medical cases.

Using a broad range of written patient management problems (PMPs), this study examined (1) how each of three medical information-gathering processes (history-taking, physical examination, and diagnostic studies) influenced 175 second-year medical students' formulations of the differential (i.e., plausible) and the principal (i.e., most probable) diagnoses for each of 14 PMPs, and (2) the extent to which these results paralleled the emphases that experienced clinicians placed on these same information-gathering processes regarding each of the same PMPs. The results suggest that in ten of the 14 PMPs the students appeared to rely on specific information-gathering strategies in formulating their diagnoses, and that both similarities and differences existed between the levels of emphasis placed by the students and physicians on each of the three processes. In general, the physicians placed greater emphasis on the importance of the history, whereas the students relied more on diagnostic studies. These variations have implications for selecting medical problems for purposes of instruction and evaluation of students.

Diagnostic Techniques and Procedures

Immunity in dilated cardiomyopathy.

Although several immunologic parameters have been found to be abnormal, their precise relationship to the cause of the disease remains unclear. It is believed that a virus initiating a bout of myocarditis may play a role in the perpetuation of the chronic phase, probably via immunologic mediation. A selection acquired defect or damage to a subpopulation of suppressor T lymphocytes is possible, providing the basis for the development of an autoimmune disorder. Studies in mice have shown a clear link between active viral myocarditis and the subsequent development of cardiomyopathy. However, the trigger mechanism that initiates the cardiomyopathy is still elusive. Specific antigens, possibly altered virus or damaged cardiac tissue, may be playing the role of the "hidden or cloistered" antigen in eliciting the immunologic reactions through a cytotoxic T-cell mechanism. Identification and isolation of the specific "antigen" in question could resolve the dilemmas about the immunopathogenesis of cardiomyopathy in humans.

Animals

Juvenile rheumatoid arthritis with rice bodies: light and electron microscopic studies.

Rice bodies obtained from a young man with juvenile rheumatoid arthritis were found by light and electron microscopy to contain cells that appeared viable. The majority of these cells closely resembled type B synovial lining cells. Type A-like cells were also seen. The cells contained few mitochondria but often much lipid and glycogen, observations which suggested a dependence on anaerobic metabolic pathways in the avascular synovial fluid environment. Cells within the rice bodies lay in a matrix of collagen fibres, fibrin, and amorphous material. The source of the collagen appeared to be the cells themselves. The relatively normal appearance of the cells suggested that they were protected from many of the inflammatory stimuli present in rheumatoid synovia. This 'reversion' towards a normal appearance suggested that the stimuli inducing chronic rheumatoid inflammation might not originate in the synovial lining.

Adolescent

The association of autoimmune diseases and anti-IgA antibodies in patients with selective IgA deficiency.

The prevalence of antibodies to immunoglobulin A (IgA) was studied in eighty-three subjects with selective IgA deficiency (SIgAD), thirty-three normal individuals, thirty-two children with juvenile rheumatoid arthritis (JRA) and normal or elevated IgA, seventeen children with systemic lupus erythematosus (SLE) and normal or elevated IgA, and thirteen patients with hypogammaglobulinaemia. Anti-IgA antibodies were detected by haemagglutination of human erythrocytes coated with one of two IgA myelomas by the chromic chloride technique. Antibodies to IgA were not found in significant titre in individuals with normal or elevated IgA or in those with hypogammaglobulinaemia. In IgA deficient patients, elevated titres were found in 25--30% of those who were healthy or who had non-rheumatic diseases, 50% of those with rheumatoid arthritis, 77% of those with JRA and 100% of those with SLE. Patients with rheumatic diseases and SIgAD may therefore be particularly at risk of developing anti-IgA-mediated reactions to blood products.

Agammaglobulinemia

Lymphocyte ecto-5'-nucleotidase deficiency in agammaglobulinemia.

Fresh peripheral blood lymphocytes from eight patients with congenital agammaglobulinemia demonstrate reduced ecto-5'-nucleotidase activity when compared to the mean activity of normal subjects and patients with other forms of immunoglobulin deficiency. A specific defect of ecto-5'-nucleotidase is further suggested by normal values for lymphocyte ecto-adenosinetriphosphatase and ecto-nonspecific phosphatase. The data provide evidence for an enzyme deficiency in this X-linked, B lymphocyte deficiency syndrome.

Agammaglobulinemia

Intravenous gamma globulin in the management of patients with hypogammaglobulinemia.

The safety and efficacy of plasmin-treated gamma globulin (PG-GG), an intravenous preparation with low anticomplementary activity, was assessed as an antibody replacement therapy in 14 patients with hypogammaglobulinemia. Seven were studied in 2 treatment periods of 6 and 15 mo on PT-GG with an intervening control period of intramuscular gamma globulin (IM-ISG). Frequency of infusions ranged from 2 to 4 wk to maintain a serum IgG concentration of less than 2.5 mg/ml. Three patients with severe chronic pulmonary disease were removed from the study because of lack of clinical improvement and were placed on single-donor plasma. The remaining 11 patients had a decrease in the number of hospitalizations or severe infections. Five patients had one or more systemic reactions (21/240 infusions). Symptoms abated rapidly with temporary interruption of the infusion. From these results, we conclude that PT-GG represents a relatively safe, efficacious mode of replacement therapy which has had uniformly high acceptance in patients with hypogammaglobulinemia.

Adolescent

Diagnostic significance of antibody to native deoxyribonucleic acid in children with juvenile rheumatoid arthritis and other connective tissue diseases.

Sera of children with juvenile rheumatoid arthritis and other connective tissue diseases were tested for antibodies to native DNA by a radiolabeled-binding assay. Normal values were obtained in 130 children with JRA, including 28 with uveitis and 14 with selective IgA deficiency. Normal values were also found in sera from children with dermatomyositis, scleroderma, polyarteritis, ankylosing spondylitis, and a variety of other nonconnective tissue diseases. The only sera with elevated DNA-binding assays were from children with systemic lupus erythematosus. On the basis of these data, increased levels of antibodies to native DNA distinguished patients with active SLE from children with JRA.

Adolescent

Serum IgE levels in patients with selective IgA deficiency.

In this study serum IgE levels were measured by a double-antibody radioimmunoassay in 31 patients with serum IgA concentration less than 0.01 mg/ml who were followed in the arthritis and allergy clinics. On a group basis there was no significant difference in mean serum IgE levels between the IgA deficient patients and normal subjects of the same age. However, in the absence of atopic disease, IgA deficient patients had significantly lower serum IgE levels. When atopy was associated with IgA deficiency IgE levels were the same as in the normal subjects but significantly lower than those of atopic non-IgA deficient patients. IgE levels in those with recurrent respiratory tract infection were not different. Adults with anti-IgA antibodies had significantly lower IgE values. IgE levels in patients with RA, JRA or SLE were not significantly different. Selective IgA deficient patients may have a relative deficiency of serum IgE depending on the comparison group.

Adolescent

A syndrome of childhood polyarteritis.

In this report the clinical, laboratory, and histopathologic findings of nine children with polyarteritis are reviewed. All have had evidence of systemic involvement. Eight presented with fever, calf pain, erythematous painful nodules, and elevation of the acute-phase reactants. All were treated with prednisone at a dosage of 2 mg/kg/day. All of the children are alive but have had relapses at least once during the course of tapering the dosage of corticosteroids. Serious complications of disease have included myocardial infarction, hypertension, and impaired renal function.

Adolescent