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Biomedical subjects

R A Doughty

Publications and source records attributed to R A Doughty.

At least 19 recordsLinked to original sources

Pharmacological management of juvenile rheumatoid arthritis.

The goals of pharmacotherapy in juvenile rheumatoid arthritis (JRA) are to suppress chronic synovitis which causes potential cartilage destruction and deformities, to control the systemic effects of inflammation (including growth retardation and nutritional deficits), relieve pain and limit psychological impact of disease. Currently available methods include nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, salicylates, naproxen, tolmetin, ibuprofen and indomethacin; disease modifying antirheumatic drugs (DMARDs) such as oral and injectable gold salts, hydroxychloroquine, penicillamine, oral and injectable methotrexate, and sulfasalazine; oral (daily or on alternate days), intravenous pulse or intra-articular corticosteroids; immunosuppresants, including cyclophosphamide, chlorambucil, cyclosporin, and azathioprine; and gammaglobulin and other experimental therapies. Over the past 10 years, rheumatologists have adopted more aggressive pharmacological treatment of JRA. As time progresses and the safety of certain drugs such as methotrexate and sulfasalazine becomes clearer, wider and earlier use of these agents can be expected. Still the approach to treatment is a 'step by step' one, starting with the classical NSAIDs and ending with the DMARDs as needed.

Adrenal Cortex Hormones

Frequency and specificity of antibodies that crossreact with Borrelia burgdorferi antigens.

The frequency and specificity of antibodies that bind antigens of Borrelia burgdorferi in sera from 200 individuals with no evidence of past or current Lyme disease was determined. Sera were tested for both IgG and IgM antibodies to B. burgdorferi by Western blotting. The non-Lyme serum group included specimens from healthy adults and children in addition to specimens from patients with viral infection and rheumatic diseases. Crossreactive IgG antibodies occurred more frequently than IgM antibodies. The most frequently bound antigens corresponded to 41 kDa and 60 kDa Borrelial components. Of 200 specimens tested, 100 had antibodies that bound at least 1 antigen. Binding to multiple antigens occurred at much lower frequency. Our results indicate that determination of maximum crossreactivity of non-Lyme sera can be used to establish minimum criteria for determining a positive Western blot result for Lyme disease.

Adult

The pediatric program director. An analysis of the role and its problems.

A questionnaire designed to elicit information about the work environment, knowledge, and stresses of pediatric residency program directors was mailed to the 235 member programs of the Association of Pediatric Program Directors (APPD). At the time that the 187 respondents (80% return rate) assumed responsibility for their training programs, many rated their knowledge of various aspects of residency program administration as "poor." The respondents indicated that a lack of time, the pressures of too many other academic responsibilities, and a fear of not "filling" all positions in the National Intern Matching Program created much personal stress. Most program directors felt that educational conferences designed to teach educational methods, and administrative skills, and provide technical information knowledge necessary for residency program supervision would be beneficial.

Adult

Chief resident training. Developing leadership skills for future medical leaders.

Most future medical leaders receive little or no formal exposure to management and leadership training activities. Industry invests considerable resources in such training for middle and senior level managers. With the increasing complexity of health care delivery systems and the increased involvement of diverse teams of individuals in the care of patients, it was believed that a training activity designed to enhance participant human interaction skills and teach about group behavior and team management might be valuable to pediatric chief residents. This article describes a 3-day workshop designed to develop such leadership skills. It has been conducted for 3 years with 117 participants. Results of end-of-course and 6-month follow-up evaluations show that participants enjoyed the training experience and believed it was valuable in helping them fulfill their leadership role as chief resident.

Curriculum

Adsorption with a soluble E. coli antigen fraction improves the specificity of ELISA tests for Lyme disease.

We reported that preadsorption of patient serum with heat killed E. coli increased the specificity of ELISA for antibodies to Borrelia burgdorferi. That procedure required extra specimen handling and a preincubation. We report the use of a soluble E. coli antigen fraction that is included in serum diluent, eliminating additional steps. Sera from 220 individuals were tested for antibodies to B. burgdorferi. Twenty sera were obtained from patients with Lyme disease and 200 sera were from a population that included healthy controls and patients with different inflammatory conditions (viral infections and various rheumatic disorders). Testing was performed using either a standard serum diluent or one containing soluble E. coli antigen fraction. Results demonstrate that inclusion of soluble E. coli antigen fraction in serum diluent increased assay specificity from 88% for the standard protocol to 98%, with no change in test sensitivity.

Antigens, Viral

Use of western blot and enzyme-linked immunosorbent assays to assist in the diagnosis of Lyme disease.

Without evidence of erythema chronicum migrans, diagnostic confirmation of Lyme disease may be difficult, particularly if there are conflicting laboratory results. Often, for families and physicians, the clinical dilemma is whether fatigue, arthritis/arthralgias, a positive enzyme-linked immunosorbent assay (ELISA), and tick exposure, but no evidence of erythema chronicum migrans, are sufficient to diagnose and treat Lyme disease. Patients with discordant ELISA and Western blot (WB) assay results for Borrelia burgdorferi were studied to determine whether there was sufficient clinical evidence to support a diagnosis of Lyme disease. Of 650 consecutive sera analyzed by ELISA in a laboratory within a 1-year period, 77 were subsequently tested by WB. The clinical data from these patients were then analyzed. The study population was divided into three groups: group 1 (positive ELISA, positive WB), group 2 (positive ELISA, negative WB), and group 3 (negative ELISA, negative WB). Findings included the following: (1) Patients with a strong clinical history of Lyme disease were usually positive by both WB and ELISA (group 1). (2) All patients with erythema chronicum migrans had both positive WB and ELISA tests. (3) Ninety-one percent of group 2 had a rheumatic or inflammatory condition other than Lyme disease. (4) A definite response to antibiotics occurred in 75% of patients wherein both ELISA and WB were positive but in only 11% of cases with a positive ELISA but a negative WB. (5) History of tick exposure and degree of fever were not significantly different among the three serologic groups, and thus they were not diagnostically helpful.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Induction of humoral manifestations of autoimmunity following intraperitoneal injection of complete Freund's adjuvant in mice.

Several animal models of arthritis are produced using complete Freund's adjuvant (CFA) alone or with collagen as an arthritogen. Successful induction of arthritis is reported to require that the adjuvant mixture be administered by intradermal or subcutaneous routes. The resulting arthritis is caused by primarily cellular immune responses. Data presented in this paper show that giving CFA by intraperitoneal (I.P.) inoculation results in a humoral autoimmune response, with no obvious signs of arthritis. This humoral autoimmune response is characterized by production of autoantibodies to nuclear and cytoplasmic antigens, elevated levels of circulating immune complexes, and in approximately 25% of mice, rheumatoid factor.

Animals

An adsorption procedure to increase the specificity of enzyme-linked immunosorbent assays for Lyme disease without decreasing sensitivity.

Previous efforts to use adsorption techniques to enhance the specificity of enzyme-linked immunosorbent assays for antibodies to the spirochete that causes Lyme disease resulted in unacceptable reductions in assay sensitivity. We present here evidence that preadsorption of serum with Escherichia coli can enhance test specificity without significantly reducing test sensitivity.

Adsorption

Suppression of malaria-induced autoimmunity by immunization with cryoglobulins.

Cryoglobulins obtained from malaria-infected (Plasmodium berghei berghei) Balb/c mice were administered intraperitoneally to naive Balb/c mice. Ten days or 9 months following cryoglobulin administration, the naive mice were infected with malaria. Comparison of sera from cryoglobulin-treated malaria-infected mice with sera from control infected mice revealed that pretreatment with cryoglobulins resulted in (1) reduced levels of circulating immune complexes; (2) reduced levels of autoantibodies reactive with nuclear and cytoplasmic antigens; and (3) suppressed development of cryoglobulinemia. Furthermore, the effect of cryoglobulins was long lasting, suggesting that recipient mice may have been actively immunized against autoantibody production.

Animals

Synovial fluid eosinophilia in Lyme disease.

We describe three 14-year-old boys who developed synovial fluid eosinophilia associated with Lyme disease. One patient, with arthritis that began in 1975, had the first documented case of Lyme disease in New Jersey. Lyme disease should be considered when eosinophilia is noted on analysis of synovial fluid from patients with undiagnosed arthritis.

Adolescent

Growing pains.

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Child

Esophageal motor abnormalities in children and adolescents with scleroderma and mixed connective tissue disease.

To determine the frequency and nature of esophageal motor abnormalities in children and adolescents with scleroderma syndromes and mixed connective tissue disease, esophageal manometry was performed on seven patients with progressive systemic sclerosis, four patients with mixed connective tissue disease, and two patients with linear scleroderma. A total of 73% of patients with progressive systemic sclerosis and mixed connective tissue disease had symptoms of esophageal dysfunction. A significant association between the presence of Raynaud phenomenon and esophageal symptoms was noted. Esophageal motor abnormalities were detected in 73% of patients with progressive systemic sclerosis and mixed connective tissue disease; these abnormalities were characterized by decreased lower esophageal sphincter pressure and abnormal peristalsis in the distal two thirds of the esophageal body. They resemble those described among adults with progressive systemic sclerosis and mixed connective tissue disease but were not related to disease duration or to the presence of Raynaud phenomenon. Patients with linear scleroderma did not have esophageal symptoms and demonstrated only nonspecific motor abnormalities that did not worsen during several years of follow-up.

Adolescent

Childhood Lyme arthritis: experience in an endemic area.

We report 25 children with oligoarticular arthritis associated with Lyme disease. There were 16 boys (male/female ratio 1.8:1); ages ranged from 2 to 15 years. Thirteen (52%) children had no history of erythema chronicum migrans or other rash. Thirteen had temperatures as high as 41 degrees C for up to 2 months before the onset of arthritis. Twelve recalled definite tick bites. Ten (40%) children, of whom seven had no history of rash, were hospitalized for presumed septic arthritis. Another four had diagnoses of pauciarticular juvenile rheumatoid arthritis for as long as 3 years. Seven patients had less acute, recurrent episodes of synovitis. Two children had seventh nerve palsies 2 months before onset of arthritis. All patients had antibodies to the Lyme spirochete. In 14 patients, synovial fluid white blood cell counts ranged from 180 to 97,700/mm3 (greater than or equal to 76% polymorphonuclear leukocytes). Antibiotic therapy was effective in all patients; in 13, orally administered therapy alone resulted in elimination of synovitis and recurrent attacks. Lyme arthritis may be confused with acute bacterial septic arthritis or recurrent "pauciarticular juvenile rheumatoid arthritis," particularly when there is no history of erythema chronicum migrans.

Adolescent

Utility of rheumatoid factor in the diagnosis of juvenile rheumatoid arthritis.

Rheumatoid factor is commonly used by clinicians to assess children with possible juvenile rheumatoid arthritis. To assess its usefulness, we reviewed the case histories of patients in whom latex agglutinating rheumatoid factor was determined during 1981 to 1982 at our institution. A total of 437 charts were available for review. There were 11 patients with positive tests for rheumatoid factor, of whom five had juvenile rheumatoid arthritis, all polyarticular. A total of 426 children had negative results, of whom 100 had juvenile rheumatoid arthritis. This yields a sensitivity of 4.8% and a specificity of 98%. We then estimated the prevalence of juvenile rheumatoid arthritis in three clinical settings: a primary practitioner's office, a tertiary children's hospital walk-in clinic, and a pediatric rheumatology center. The predictive values and marginal benefits for rheumatoid factor were then calculated in those settings using Bayes' theorem. In the two general outpatient settings, the primary practitioner's office and tertiary walk-in clinic, the positive predictive values were 0.7% and 0.5%, respectively; marginal benefits were 0.4% and 0.3%, respectively. Rheumatoid factor testing appeared to be of some benefit in the pediatric rheumatology center with a positive predictive value of 72.5% and marginal benefit of 22.5%. In no case was rheumatoid factor testing helpful in establishing a diagnosis of juvenile rheumatoid arthritis or in ruling it out. Testing for rheumatoid factor is a poor screening procedure for juvenile rheumatoid arthritis in the general situations in which it is more likely to be requested and of supportive diagnostic value only in the highly restricted population of older children with polyarticular arthritis.

Arthritis, Juvenile