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Biomedical subjects

J D Clough

Publications and source records attributed to J D Clough.

At least 37 records · Page 2Linked to original sources
PubMed1992

Serological detection of disease activity in SLE.

Laboratory tests are commonly used to aid in monitoring disease activity in patients with systemic lupus erythematosus. Typically, tests for antinative DNA, complement, acute phase reactants, and sometimes circulating immune complexes are used for this purpose. More recently, tests for complement activation products and immunocyte activation have been suggested. We measured antinative DNA, C4, Westergren sedimentation rate, iC3b, Bb, and sIL-2R levels in a group of 100 patients with SLE evaluated clinically for activity by a modified version of the Systemic Lupus Activity Measure (SLAM); iC3b and Bb were studied in 71 of the patients and sIL-2R in 52. We found that sIL-2R and sedimentation rate correlated best with SLAM, anti-DNA was intermediate, and C4, iC3b, and Bb correlated the least. None of the tests predicted severity of disease, but sIL-2R was highest in patients with active renal disease.

Adolescent↗
PubMed1992

A consumer guide for marketing medical services: one institution's experience.

This paper describes the Cleveland Clinic Foundation's experience with the development and implementation of a 20-page quality indicator consumer guide for patients with or at risk of developing coronary artery disease. The guide, which provides six "quality indicators," was designed to enable patients to evaluate and compare quality-related information when choosing a provider. Design elements for the guide included a user-friendly format to offset the amount of information consumers are asked to absorb. Data on inquiries showed that the majority were women (53%) and adults under the age of 65 years (57%). Although the media criticized the guide as a marketing tool, it represents an effort to educate consumers about the importance of research when choosing a provider.

Choice Behavior↗
PubMed1991

Local infectious complications following large joint replacement in rheumatoid arthritis patients treated with methotrexate versus those not treated with methotrexate.

We performed a 10-year retrospective analysis of the frequency of local postoperative infectious complications in methotrexate (MTX)-treated rheumatoid arthritis patients who underwent total joint arthroplasty. Sixty patients, who had a total of 92 joint arthroplasties, were receiving MTX. A comparison group of 61 patients with a combined total of 110 total joint arthroplasties were not receiving MTX. The 2 groups were compared for the occurrence of local postoperative infectious complications and poor wound healing. Eight patients in the MTX group experienced a total of 8 complications (8.7% of procedures). In comparison, 5 patients in the non-MTX group experienced a total of 6 complications (5.5% of procedures), a difference that was not statistically significant (chi 2 = 0.816, P = 0.366). Statistical analysis of many other variables revealed none that could be identified as risk factors for postoperative complications. These results suggest that treatment in the perioperative period with weekly low-dose pulse MTX does not increase the risk of local postoperative infectious complications or poor wound healing in rheumatoid arthritis patients who undergo total joint arthroplasty.

Adrenal Cortex Hormones↗
PubMed1991

Folate supplementation in methotrexate-treated rheumatoid arthritis patients.

Two hundred rheumatoid arthritis (RA) patients taking low dose methotrexate (MTX) were evaluated for adverse effects. During a mean follow up of 41.5 months, the mean cell volume (MCV) was elevated at some time during the course of treatment in 42 patients. The MCV was normal in the remaining 158 patients. One hundred ninety-eight patients were treated simultaneously with oral folic acid. With the exception of heartburn, which was seen more often in the high MCV group, there was no difference in the frequency of adverse effects attributable to MTX between groups. Severity of side effects and the frequency of MTX dose reduction and MTX discontinuation due to toxicity were also similar between groups. This analysis suggests that elevation of MCV in RA patients treated simultaneously with MTX and folate does not predict MTX toxicity. The authors also discuss the mechanism of action of MTX with regard to folate metabolism.

Arthritis, Rheumatoid↗
PubMed1991

Therapy for rheumatoid arthritis: combinations of disease-modifying drugs and new paradigms of treatment.

The last 10 years have witnessed a change in the way rheumatologists view rheumatoid arthritis (RA). It is no longer considered a slowly progressive disease limited to the joints, but rather an aggressive systemic disease that results in clinically significant morbidity early in its course and can contribute to excess mortality. Heightened awareness of the health impact of RA has spurred a search for effective therapy to be applied early in the course of disease for patients with moderate to severe RA. Combinations of disease-modifying antirheumatic drugs (DMARD) have become an increasingly popular alternative to sequential monotherapy. In this report, we review published series of patients with RA who have been treated with combinations of DMARDs, sometimes including chemotherapeutic agents, with some critical comment. Published paradigms of treatment are also reviewed and a new strategy is presented. The "step-down bridge" strategy allows early treatment with at least four DMARDs, but may place some patients with mild disease at an inappropriately high risk of adverse effects. The "sawtooth" strategy gives little guidance as to which DMARD(s) should be chosen for initial treatment. We describe a "graduated-step" strategy that provides numerical grading to match disease severity and disease activity with appropriate initial therapy and that facilitates therapeutic decisions throughout the course of treatment.

Anti-Inflammatory Agents↗
PubMed1991

Serum C3 levels are diagnostically more sensitive and specific for systemic lupus erythematosus activity than are serum C4 levels. The Lupus Nephritis Collaborative Study Group.

To determine whether serum C3 or C4 is more likely to be normal during systemic lupus erythematosus (SLE) remission and abnormal during SLE relapse we studied twelve SLE patients who presented with severe nephritis. The patients were followed long term (12 to 77 months) through multiple relapses (N = 41) and remissions (N = 13) defined by protocol. A total of 471 serum samples were obtained at defined intervals during these relapses and remissions and were analyzed for C3 and C4 levels by two different methods: nephelometry (N) and radial immunodiffusion (R). During SLE remission (defined by protocol and without reference to serum complement levels), C3 measured by N-assay (C3N) and by R-assay (C3R) tended to be normal (specificity of 93% and 71%, respectively). By contrast, C4 measured by N-assay (C4N) and by R-assay (C4R) showed no such tendency (specificity of 50% for both C4N and C4R). During SLE relapse (defined by protocol and without reference to serum complement levels), C3N and C3R were more likely to be abnormal (sensitivity 95% and 85%, respectively) compared with C4N and C4R (sensitivity 56% and 54%, respectively, P less than 0.001 compared with corresponding values for the C3 assay). Analysis by receiver-operator characteristic (ROC) curves demonstrated that the reduced diagnostic sensitivity of C4 versus C3 is not explained by use of an inappropriate lower limits of normal (LLN) for C4.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effectiveness of testing for anti-DNA and the complement components iC3b, Bb, and C4 in the assessment of activity of systemic lupus erythematosus.

Seventy-one patients with systemic lupus erythematosus (SLE), seen in an outpatient setting for follow-up evaluation during a 3-mo period, were tested (in addition to routine lupus monitoring studies) with enzyme immunoassays (EIAs) for anti-DNA, iC3b, and factor Bb to determine the relationship of these test results to disease activity. SLE activity was scored by four previously reported scoring systems, and six patients were identified as active by all four systems. We found that the EIA for anti-DNA was the best indicator of disease activity and that iC3b and Bb were not informative for this purpose in this group of patients. Mean iC3b levels were higher in a subset of seven patients with past biopsy evidence of severe (WHO class IV) glomerulonephritis than in the rest of the study population, even though none of these patients had active disease at the time of this study.

Adolescent↗
PubMed1990

Outcome of first-trimester exposure to low-dose methotrexate in eight patients with rheumatic disease.

PURPOSE: Methotrexate (MTX), when used to treat malignancy or psoriasis, has been implicated in anecdotal reports as a teratogen or abortifacient in the first trimester of pregnancy. We are unaware of any previous reports that describe the course of gestation and the effect on subsequent offspring in patients treated with low-dose oral MTX for rheumatoid arthritis, and therefore present our experience. PATIENTS AND METHODS: We report on eight women experiencing 10 pregnancies. Mean number of weeks of gestation while taking MTX was 7.5 (range 2 to 20 weeks). Outcome of pregnancies included five full-term babies (FTB), three spontaneous abortions (SAB), and two elective abortions. RESULTS: There were no significant differences in either the FTB or SAB group when considering risk factors including smoking, alcohol, concomitant medications, and age. One of three in the SAB group had recurrent abortions prior to MTX therapy. All five of the FTB group had uncomplicated pregnancies and deliveries. All offspring were of normal height and weight at birth with no physical abnormalities. All children reached growth, development, and intellectual stages normally, and their present mean age is 11.5 years. No observed learning disabilities or medical abnormalities have occurred in any of these children. CONCLUSION: In this uncontrolled study we failed to demonstrate tertogenicity of MTX. However, the possibility of abortion due to MTX use remains.

Abortifacient Agents↗
PubMed1990

Response of immunoregulatory lymphocyte subsets to methotrexate in rheumatoid arthritis.

In an attempt to define the immunoregulatory mechanisms operating in rheumatoid arthritis, the authors examined peripheral blood functional lymphocyte subsets in 15 patients with active rheumatoid arthritis who were not receiving remittive therapy, as well as 33 healthy controls. The percentage and absolute numbers of total T cells (CD3), T-helper/inducer cells (CD4), and T-suppressor/cytotoxic cells (CD8) did not differ among the groups, nor did the CD4:CD8 ratio or the numbers of T cells coexpressing CD4 and the activation markers Ia or IL-2R. However, rheumatoid arthritis patients did have reduced percentages and numbers of CD4+ cells coexpressing the 2H4 antigen (CD45R-naive T cells) (P less than .0003) and CD8+ cells coexpressing the Leu-15 (CD11b) marker (suppressor/effectors) (P less than .0005). Twelve patients then received oral methotrexate, 7.5 mg weekly. Most showed clinical improvement by 4 weeks and all did by 8 weeks. Although changes in the T-cell subsets were not statistically significant, several tended toward normalization. These findings may help explain the immunoregulatory defect in rheumatoid arthritis and the effectiveness of methotrexate in modifying disease activity.

Arthritis, Rheumatoid↗
PubMed1989

Predictive value of antinative DNA for systemic lupus erythematosus: comparison of radioimmunoassay and enzyme immunoassay.

Positive predictive values for the diagnosis of systemic lupus erythematosus (SLE) were determined for two antinative DNA assays: a Farr-type radioimmunoassay (RIA) and a solid-phase enzyme immunoassay (EIA). The study population consisted of all patients whose EIA anti-DNA results were positive (greater than 250 IU) during a 150 day period; in addition all patients whose EIA anti-DNA results were 100-250 IU during the first 25 days of this period were also included. Simultaneous Farr RIA were performed on all sera, and the Crithidia luciliae immunofluorescent assay was also carried out on those with positive RIA and/or EIA results. Diagnoses were established by chart review, and disease activity was scored for SLE patients. Positive predictive values for SLE were dependent on the level of test positivity, and "normal" limits of 10% binding for the Farr RIA and 800 IU for the EIA gave comparable results. Combination with Crithidia luciliae immunofluorescence increased the sensitivity of both assays, especially the EIA. Results of both assays correlated significantly with activity scores in SLE patients.

Antibodies, Antinuclear↗
PubMed1989

The ANA profile: quality and cost-effective laboratory utilization.

The ANA Profile was introduced in 1981 and computerized in 1984 as a means of facilitating follow-up testing for specific antibodies (anti-nDNA, anti-Sm, anti-RNP, anti-La/SS-B) in sera found to contain antinuclear antibodies (ANA). A second purpose was to avoid unnecessary specific antibody testing on negative or low-titer sera. This study was done to evaluate the effectiveness of the computerized ANA Profile reporting system in accomplishing these purposes. The authors compared ordering practices during two two-week periods, one in 1984 and a second in 1988, and found that follow-up testing on positive sera had improved from 27% to 70% with a reduction in unnecessary specific-antibody testing of ANA-negative or low-titer sera from 11% to 1.6%. In 1988 dollars, the annual savings from eliminating unnecessary testing was calculated to be $12,000. The ANA Profile has been partially successful in accomplishing the purposes for which it was introduced.

Antibodies, Antinuclear↗
PubMed1988

Two distinct subsets of patients with systemic lupus erythematosus.

This study was undertaken to examine the levels and function of peripheral blood immunoregulatory T cell subpopulations in systemic lupus erythematosus (SLE). T cell subpopulations can be distinguished by the T cell differentiation antigens CD4 (recognized by the monoclonal antibodies OKT4 or Leu3) and CD8 (recognized by the monoclonal antibodies OKT8 or Leu2). All SLE patients tested had normal percentages of CD8 cells in their peripheral blood. The SLE patients, however, fell into two groups based on their CD4 cell numbers. Fifty-five percent of the SLE patients had normal levels of CD4 cells (Group A) and therefore normal CD4/CD8 cell ratios, whereas 45% of the SLE patient population had markedly depressed CD4 cell levels (Group B) and significantly low CD4/CD8 cell ratios. T cells from normal donors and SLE patients were further examined for their ability to stimulate allogeneic normal B/M phi cells to secrete IgM in the presence of pokeweed mitogen (PWM). Utilizing this assay system two forms of immunosuppression were observed: (1) that mediated by high concentrations of purified CD4 cells and (2) that mediated by CD8 cells. High concentrations of purified CD4 cells, added to a constant number of allogeneic normal B/M phi cells, suppressed PWM-stimulated IgM synthesis. Group B SLE patients, with significantly low CD4 cell numbers, had defective CD4 cell-mediated suppression which was concentration dependent. This result was confirmed in a study using identical twins discordant for SLE. In this case CD4 cells from the SLE twin did not induce immunosuppression at a high concentration of CD4 cells whereas similar concentrations of CD4 cells from the normal twin resulted in suppression. SLE patients (Group A) with normal levels of CD4 cells had normally immunosuppressive CD4 cells. Suppression mediated by CD8 cells was demonstrated by the fact that removal of CD8 cells resulted in enhanced IgM synthesis induced by the remaining CD4 cells. Although all the SLE patients in this study had normal peripheral blood levels of CD8 cells, SLE Group A patients had defective CD8 cell suppression whereas CD8 function appeared to be normal in Group B patients. These results suggest that in SLE patients with depressed CD4 cell numbers (Group B) there is a corresponding defect in CD4 cell function. We demonstrate that in SLE Group B patients, defective suppression is due to a subset of T cells that bear the CD4 antigen. The SLE patient population (Group A) with normal CD4/CD8 ratios and normally functioning CD4 cells, however, appear to have normal CD4 cell-mediated suppression but defective CD8 suppressor cell function.

Antibody Formation↗
PubMed1988

Modulation of T-cell-mediated regulation of antibody production by interaction with specific immune complexes.

The importance of the phlogogenic effects of immune complexes in disease pathogenesis has been emphasized, but they also have a role in immunoregulation. We examined the effects of DNA: anti-DNA immune complexes, formed at different antigen:antibody ratios, on the ability of T cells to modulate DNA antibody production in vitro. We found that antigen-excess complexes promote IgM anti-DNA synthesis, whereas antibody-excess complexes favor a switch to IgG anti-DNA production. We suggest that interaction of T cells with immune complexes is an important feedback mechanism in control of the immune response.

Antibody Formation↗