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Biomedical subjects

C D Rose

Publications and source records attributed to C D Rose.

At least 37 records · Page 2Linked to original sources

Serial measurements of soluble interleukin 2 receptor levels (sIL2-R) in children with juvenile rheumatoid arthritis treated with oral methotrexate.

OBJECTIVE: To investigate the potential clinical utility of serial levels of sIL2-R as a marker of disease activity among children with juvenile rheumatoid arthritis (JRA) treated with methotrexate (MTX). METHODS: sIL2-R levels, measured by ELISA, were evaluated in 16 JRA patients (10 polyarticular, six systemic-onset) treated with oral, weekly MTX. sIL2-R values were compared with those of 49 normal controls. Medical record review was used to obtain relevant clinical data. Joint counts (number of swollen joints) were used as indicators of clinical change. A reduction of 50% in joint counts between pre and post treatment measurements was considered a clinically significant response. RESULTS: The mean (SEM) sIL2-R value of pre treatment JRA of 1728(290) U/ml was significantly higher than the post treatment value of 921(229) U/ml (Wilcoxon Rank test, p < or = 0.001). Pre treatment values were also significantly different from the mean(SEM) of healthy controls of 519(19) U/ml (p < 0.001). Pre treatment sIL2-R levels of 2417(291) U/ml in systemic-onset JRA were significantly higher than sIL2-R values in polyarticular JRA patients of 1218(884) U/ml (Mann-Whitney rank test p < 0.001). Among the 13/16 children with good therapeutic responses (> or = 50% improved), the range of sIL2-R decreases was 154-2641 U/ml (mean 842 U/ml); sIL2-R levels increased in the three children with poor clinical responses to methotrexate. CONCLUSIONS: sIL2-R levels paralleled the course of disease in all patients. sIL2-R levels may be useful for monitoring therapeutic responses in children with JRA.

Administration, Oral↗

Physician beliefs, attitudes, and approaches toward Lyme disease in an endemic area.

To assess the beliefs and practice habits regarding Lyme disease among practitioners, questionnaires were sent to physicians in a seven-county Lyme-endemic region. One hundred twenty-four evaluable responses were returned from 53 family physicians, 39 pediatricians, 27 internists, and five subspecialists who diagnosed three to four cases of Lyme disease per year, on average. The majority presented with erythema migrans (EM) or other early symptoms, although arthritis was the presenting sign in 16%. The enzyme-linked immunosorbent assay (ELISA) was the most frequently ordered diagnostic test, but 45% of respondents did not specify which test when ordering Lyme serology. The majority would use amoxicillin or doxycycline to treat EM in children or adults, respectively. Nearly all would use ceftriaxone for meningitis, and half would use it to treat Lyme arthritis or Bell's palsy. Physicians differed markedly in the duration of therapy they would prescribe. Eighty-three percent would treat a patient for possible Lyme disease with antibiotics (many intravenously), even in the absence of EM or positive serology. Thirty-five percent of practitioners prescribed antibiotics for deer-tick bites. Our survey documents significant variation in approaches to Lyme disease among primary-care physicians and suggests the need for well-designed clinical trials, continuing basic research, and physician education.

Adult↗

The overdiagnosis of Lyme disease in children residing in an endemic area.

The medical records of 227 children ages 1 to 19 years referred to the Lyme disease pediatric clinic over a 32-month period since May 1990 were reviewed. Clinico-serologic criteria for a positive diagnosis were applied. One hundred thirty-eight of 227 referred children did not fulfill those criteria and became the study population. Four subsets of patients emerged: (1) 54 patients with predominantly subjective symptoms; (2) 52 patients with objective evidence for an alternative diagnosis; (3) eight patients who had documented infection in the past and continued with symptoms after antibiotic treatment; and (4) 24 patients with a history of tick attachment or prenatal/family history of Lyme disease. Serologic testing data from commercial laboratories were available for the 54 children from the "predominantly subjective" group; 50% were negative, and 50% were borderline or positive. Ninety-two percent of these patients were negative at retesting by our enzyme-linked immunosorbent assay (ELISA) and 100% were negative by Western blot. Fifty-seven percent of these patients had received treatment prior to our evaluation. Children residing in an endemic area who present with vague symptoms are being diagnosed with and treated for Lyme disease without clinical or serologic documentation. In addition, fear in the lay community may be inducing doctors to diagnose Lyme disease in patients with symptoms that may be suggestive of an alternative diagnosis.

Adolescent↗

Cognitive effects of Lyme disease in children.

OBJECTIVE: To measure possible cognitive sequelae of Lyme disease (LD) within a pediatric population. DESIGN: Prospective, blinded, controlled study of cognitive skills in children who had been treated for LD. SETTING: A children's hospital in an area endemic for LD. PATIENTS: Forty-one children with strictly defined LD were compared with 14 control children who had subacute rheumatological diseases, and with 23 healthy sibling controls. OUTCOME MEASURES: Neuropsychologic measures were administered to each child to assess the following cognitive areas: IQ information processing speed, fine-motor dexterity, novel-problem solving and executive functioning, short-term and intermediate memory, and the ability to acquire new learning. Predisease and postdisease academic achievement test scores were also gathered. Impressions from parents concerning the disease's subsequent impact were also obtained. RESULTS: No differences between LD and control groups were found for any of the numerous neuropsychologic measures. Analyses also failed to show differences between LD patients grouped with respect to the presence or absence of known neurologic involvement, disease stage, duration of symptoms before therapy, or type of antibiotic treatment. No predisease versus post-disease difference in academic performance was found. No perceived long-term deterioration in cognitive, social, or personality areas was reported by parents. CONCLUSION: Children appropriately treated for LD have an excellent prognosis for unimpaired cognitive functioning.

Achievement↗

Serial measurement of soluble interleukin 2 receptor levels: an early indicator of treatment response for Lyme disease.

Detection of antibodies produced in response to infection with Borrelia burgdorferi provides a valuable aid for diagnosing Lyme disease. However, anti-Borrelial antibody titers are of little value in determining treatment success or providing evidence of persistent infection as levels of specific antibodies can remain elevated even after successful treatment. Pretreatment and posttreatment measurement of soluble interleukin 2 receptor (sIL-2R) levels was evaluated for use in predicting treatment response in Lyme disease. Results indicate that serial measurement of serum sIL-2R levels can provide an early indicator of response to treatment and outcome.

Adolescent↗

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↗

Protrusio acetabuli in adult rheumatoid arthritis.

In a retrospective study of 100 patients with adult rheumatoid arthritis, 23/100 (23%) were found presenting protrusio acetabuli (PA). PA of the hips was present in 28/193 (14.5%). This complication was more frequent in females, with 19/23 cases (82%), and its presence and severity were associated with longer duration of disease. On analysing the probable relationship between PA and glucocorticoid intake, no statistically significant differences were found between patients who had received such drugs and those who had not. With the method employed and in a selected rheumatoid arthritis population, PA was found in high prevalence.

Acetabulum↗

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↗

Safety and efficacy of methotrexate therapy for juvenile rheumatoid arthritis.

Twenty-nine children with juvenile rheumatoid arthritis were studied to determine the safety and efficacy of methotrexate therapy. The initial dose of methotrexate averaged 7.1 mg/m2/wk and was given as a single, oral weekly dose or as three divided doses, each separated by 12 hours. Current antiinflammatory medications were continued; 25 of 29 children had had lack of efficacy, and 8 of 29 had toxic effects, with one or more prior drugs such as intramuscularly or orally administered gold, hydroxychloroquine, or D-penicillamine. Intolerable corticosteroid dependency or toxic effects were present in 18 of 29 cases. Methotrexate-treated patients were examined monthly; minimum treatment duration required to assess efficacy and toxicity was 6 months. The range of treatment duration was 8 to 39 months (mean 18.5 months). Efficacy was assessed by comparing pretreatment versus posttreatment fever and rash, swollen-joint counts, articular indexes, duration of morning stiffness, functional class, hemoglobin levels, and platelet counts. Treatment with methotrexate effectively controlled fever and rash in 83% of children with systemic juvenile rheumatoid arthritis, reduced morning stiffness by 63%, eliminated recalcitrant joint restriction in 48%, and reduced numbers of swollen joints and swelling indexes by 46% and 52%, respectively. No significant toxic effects were observed. Juvenile rheumatoid arthritis of long duration, or with major erosions, was more likely to be refractory to methotrexate therapy. We recommend earlier consideration of methotrexate in place of other slow-acting antirheumatic drugs for juvenile rheumatoid arthritis not responding well to usual therapy. Future studies should address potential methotrexate toxic effects in the lungs and reproductive system, as well as outcome after discontinuation of methotrexate treatment.

Adolescent↗

Early onset sarcoidosis with aortitis--"juvenile systemic granulomatosis?".

A syndrome of granulomatous arthritis-uveitis-rash has been described in children. Since the clinical features of arthritis in this syndrome closely resemble those seen in early onset sarcoidosis, and since large vessel vasculitis has been seen in children with sarcoidosis, it is possible that early onset sarcoidosis and granulomatous arthritis-uveitis-rash syndrome are part of the same clinical spectrum. Clinical features of a child with sarcoidosis and Takayasu arteritis described in this report support this hypothesis.

Aortic Arch Syndromes↗

Rapid effects of insulin on the cycling of the insulin receptor in a human monocyte cell line (U-937).

The insulin receptor and its regulation by insulin was studied in U-937 monocytes, a human cell line with properties similar to those of normal peripheral blood monocytes. Treatment of this cell with insulin for 8-16 h produced an overall loss in the insulin receptor, i.e., a loss of receptors from the cell surface and internal pools. In contrast, short-term insulin treatment (15-30 min) caused a reduction in cell surface receptors but an increase in the internal receptors, as judged by pronase treatment at 4 degrees C to distinguish receptor location. After the removal of insulin and pronase, the internalized receptors were rapidly reinserted back into the cell surface after warming to 37 degrees C. Further studies showed an insulin-mediated increase in fluid-phase pinocytosis as measured by horseradish peroxidase (HRP) uptake. The amount of HRP accumulation and the time course for this stimulation were similar to those for receptor internalization. These features plus other results suggest that the insulin-stimulated internalization of insulin receptors may require an acceleration in the rate of pinocytic vesicle formation.

Cell Line↗