Contact allergy to beclomethasone dipropionate.
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Administration, Inhalation↗
Biomedical subjects
S M Cooper
Publications and source records attributed to S M Cooper.
Biased T-cell antigen receptor repertoire in Lyme arthritis.
A common concern with many autoimmune diseases of unknown etiology is the extent to which tissue T-lymphocyte infiltrates, versus a nonspecific infiltrate, reflect a response to the causative agent. Lyme arthritis can histologically resemble rheumatoid synovitis, particularly the prominent infiltration by T lymphocytes. This has raised speculation about whether Lyme synovitis represents an ongoing response to the causative spirochete, Borrelia burgdorferi, or rather a self-perpetuating autoimmune reaction. In an effort to answer this question, the present study examined the repertoire of infiltrating T cells in synovial fluid from nine Lyme arthritis patients, before and after stimulation with B. burgdorferi. Using a highly sensitive and consistent quantitative PCR technique, a comparison of the T-cell antigen receptor (TCR) beta-chain variable (Vbeta) repertoires of the peripheral blood and synovial fluid showed a statistically significant increase in expression of Vbeta2 and Vbeta6 in the latter. This is remarkably similar to our previous findings in studies of rheumatoid arthritis and to other reports on psoriatic skin lesions. However, stimulation of synovial fluid T cells with B. burgdorferi provoked active proliferation but not a statistically significant increase in expression of any TCR Vbeta, including Vbeta2 and Vbeta6. Collectively, the findings suggest that the skewing of the TCR repertoire of fresh synovial fluid in Lyme arthritis may represent more a synovium-tropic or nonspecific inflammatory response, similar to that occurring in rheumatoid arthritis or psoriasis, rather than a specific Borrelia reaction.
Adolescent↗
Meaningful improvement criteria sets in a rheumatoid arthritis clinical trial. MIRA Trial Group. Minocycline in Rheumatoid Arthritis.
OBJECTIVE: To compare 3 sets of criteria for meaningful improvement in a rheumatoid arthritis (RA) clinical trial, and to evaluate the implications of these criteria sets for RA trial design. METHODS: Data were obtained from the Minocycline in Rheumatoid Arthritis (MIRA) trial (primary outcome measures: 50% improvement in joint tenderness and 50% improvement in joint swelling, based on joint scores). These MIRA data were evaluated against 1) the Paulus criteria (20% improvement in 4 of 6 measures: joint tenderness scores, joint swelling scores, physician's and patient's global assessments, erythrocyte sedimentation rate [ESR], and morning stiffness); and 2) the American College of Rheumatology (ACR) criteria (20% improvement in joint tenderness and joint swelling counts, and in 3 of 5 other measures: physician's and patient's global assessments, ESR, modified Health Assessment Questionnaire, and patient's pain assessment). The ACR criteria were modified using 3 of 4 remaining measures, since baseline pain assessment data were not available. RESULTS: Percentages of minocycline-treated patients versus placebo-treated patients showing meaningful improvement were as follows: by MIRA criteria, for joint tenderness, 56% versus 41% (P = 0.021), and for joint swelling, 54% versus 39% (P = 0.023); by Paulus criteria, 41% versus 28% (P = 0.040); and by ACR criteria, 44% versus 26% (P = 0.004). Both the modified ACR criteria and the Paulus criteria demonstrated a reduced placebo response rate. Compared with the MIRA criteria, the ACR criteria increased, and the Paulus criteria decreased, absolute between-group differences in improvement; however, both criteria sets increased relative percentages of patients showing improvement in the minocycline group versus the placebo group. Study design considerations indicated that application of the ACR criteria would reduce the required sample size. CONCLUSION: Different placebo response rates and treatment group differences were found using the 3 RA improvement criteria sets. These findings support the use of the ACR criteria for defining improvement in RA clinical trials.
Adult↗
An evaluation of the quality and physical properties of calf leather following topical application of eprinomectin.
The gross and histological appearance of skins obtained from twelve 6-10 month-old Friesian X Hereford calves 14-15 days after they were treated with a topical formulation of 0.5% eprinomectin administered at 1 ml per 10 kg bodyweight was compared to that of skins from twelve untreated controls. No significant differences were observed and there were also no significant differences in the quality and physical properties of leather produced from the skins of treated and untreated groups, indicating that topical eprinomectin has no deleterious effects on the leather quality of calf skins.
Journal Article↗
Radiographic results from the Minocycline in Rheumatoid Arthritis (MIRA) Trial.
OBJECTIVE: To assess radiographically determined disease progression in patients in the Minocycline in Rheumatoid Arthritis (MIRA) Trial. METHODS: A double blind, randomized, multicenter, 48 week trial of oral minocycline (200 mg/day) or placebo in 6 clinical centers in the United States. Patients include 219 adults with active RA previously receiving limited treatment with disease modifying drugs. Posteroanterior films of the hands from baseline and final visits, blinded for sequence, were read for erosions and joint space narrowing by trained observers. Outcomes included rate of disease progression (change/month) and percentage of patients with progression from baseline, newly involved joints, and newly erosive disease. RESULTS: Using intent-to-treat analyses, progression rates for erosions (0.11 +/- 0.42 minocycline, 0.17 +/- 0.41 placebo; p = 0.47) and joint space narrowing (0.16 +/- 0.55 minocycline and 0.23 +/- 0.71 placebo; p = 0.14) were similar. (Power 43% to detect a 50% difference.) Newly erosive joints occurred more frequently in the placebo group (44 vs 32%; p = 0.08), not a statistically significant difference. CONCLUSION: Radiographic measurement of disease progression using 4 measures failed to show a significant difference between minocycline and placebo treatment, although for all methods there was a trend toward treatment benefit, consistent with reported clinical results. A one year trial duration, high measurement variability, and slow rate of radiographic progression in this cohort may explain the low power to detect a treatment effect. The measurement that denoted "newly involved" joints was most sensitive in detecting change. In future trials longer term assessment (minimum 2 years) of radiographic changes and further comparison of measures of disease progression are warranted.
Adult↗
Effects of low dose methotrexate on the bone mineral density of patients with rheumatoid arthritis.
OBJECTIVE: To determine the effects of low dose methotrexate (MTX) on bone mineral density (BMD) of patients with rheumatoid arthritis (RA). METHODS: We examined the relationship between BMD and disease modifying antirheumatic drug (DMARD) use with data from a prospective, randomized, placebo controlled trial assessing the effects of calcium and vitamin D3 supplementation on BMD of patients with RA. Measurements of BMD of the lumbar spine and femoral neck were performed at baseline and at yearly followup visits over 3 years. RESULTS: Information about DMARD use and BMD was available for 133 patients at baseline, and for 95 patients at Year 3. Lumbar spine and femoral neck BMD of MTX and non-MTX treated patients were similar at the start of the study. At the end of 3 years of followup, there was no significant differences in the change in BMD of the femoral neck and lumbar spine in MTX and non-MTX treated patients, in general. However, patients treated with prednisone > or = 5 mg/day plus MTX had greater loss of BMD in the lumbar spine than patients treated with a similar dose of prednisone without MTX (difference -8.08% over 3 years; p = 0.004). CONCLUSION: At the end of 3 years, low dose MTX use was not associated with change in femoral neck or lumbar spine BMD in patients who were not treated with corticosteroids. However, among patients treated with prednisone > or = 5 mg/day, combined treatment with MTX and prednisone was associated with greater bone loss in the lumbar spine than treatment with prednisone without MTX.
Absorptiometry, Photon↗
Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis. A randomized, double-blind, placebo-controlled trial.
BACKGROUND: Therapy with low-dose corticosteroids is commonly used to treat allergic and autoimmune diseases. Long-term use of corticosteroids can lead to loss of bone mineral density and higher risk for vertebral fractures. Calcium and vitamin D3 supplementation is rational therapy for minimizing bone loss, but little evidence for its effectiveness exists. OBJECTIVE: To assess 1) the effects of supplemental calcium and vitamin D3 on bone mineral density of patients with rheumatoid arthritis and 2) the relation between the effects of this supplementation and corticosteroid use. DESIGN: 2-year randomized, double-blind, placebo-controlled trial. SETTING: University outpatient-care facility. PATIENTS: 96 patients with rheumatoid arthritis, 65 of whom were receiving treatment with corticosteroids (mean dosage, 5.6 mg/d). INTERVENTION: Calcium carbonate (1000 mg/d) and vitamin D3 (500 IU/d) or placebo. MEASUREMENTS: Bone mineral densities of the lumbar spine and femur were determined annually. RESULTS: Patients receiving prednisone therapy who were given placebo lost bone mineral density in the lumbar spine and trochanter at a rate of 2.0% and 0.9% per year, respectively. Patients receiving prednisone therapy who were given calcium and vitamin D3 gained bone mineral density in the lumbar spine and trochanter at a rate of 0.72% (P = 0.005) and 0.85% (P = 0.024) per year, respectively. In patients receiving prednisone therapy, bone mineral densities of the femoral neck and the Ward triangle did not increase significantly with calcium and vitamin D3. Calcium and vitamin D3 did not improve bone mineral density at any site in patients who were not receiving corticosteroids. CONCLUSION: Calcium and vitamin D3 prevented loss of bone mineral density in the lumbar spine and trochanter in patients with rheumatoid arthritis who were treated with low-dose corticosteroids.
Adult↗
Apoptosis of Fashigh CD4+ synovial T cells by borrelia-reactive Fas-ligand(high) gamma delta T cells in Lyme arthritis.
The function of the minor subset of T lymphocytes bearing the gamma delta T cell antigen receptor is uncertain. Although some gamma delta T cells react to microbial products, responsiveness has only rarely been demonstrated toward a bacterial antigen from a naturally occurring human infection. Synovial fluid lymphocytes from patients with Lyme arthritis contain a large proportion of gamma delta cells that proliferate in response to the causative spirochete, Borrelia burgdorferi. Furthermore, synovial gamma delta T cell clones express elevated and sustained levels of the ligand for Fas (APO-1, CD95) compared to alpha beta T cells, and induce apoptosis of Fashigh CD4+ synovial lymphocytes. The findings suggest that gamma delta T cells contribute to defense in human infections, as well as manifest an immunoregulatory function at inflammatory sites by a Fas-dependent process.
Apoptosis↗
HLA-DRB1 genes and disease severity in rheumatoid arthritis. The MIRA Trial Group. Minocycline in Rheumatoid Arthritis.
OBJECTIVE: To examine the effect of alleles encoding the "shared"/"rheumatoid" epitope on rheumatoid arthritis (RA) disease severity in patients who participated in the minocycline in RA (MIRA) trial. METHODS: Of 205 patients with a week-48 visit, blood was available for typing of HLA-DRB1 and HLA-DQB1 in 174 (85%) and successfully completed in 169 (82%). Baseline erosions were used to assess disease severity and new erosions at the last visit served as a proxy for progression. RESULTS: At baseline, there was no association between the presence of erosive disease or rheumatoid factor status and the dose of rheumatoid epitope (homozygous, heterozygous, none) or the specific alleles identified. At the final visit, a gradient was observed for the 3 allelic subgroups (and their gene doses) in the occurrence of new erosions among the Caucasian placebo-treated, but not the minocycline-treated, patients. A treatment group/HLA-DR4 epitope interaction was demonstrated in multivariate analyses. Approximately two-thirds of African-American patients did not have the rheumatoid epitope. CONCLUSION: HLA-DRB1 oligotyping may be useful in predicting the progression of disease in some Caucasian patients. Our study corroborates the infrequency of the epitope among African-American patients with RA.
Alleles↗
The comparative ability of some lousicides to reduce cockle in sheep pelts.
Sheep naturally infested with the biting louse, Bovicola ovis were treated with a range of organophosphorus and synthetic pyrethroid dip formulations. The sheep were killed 42 days after treatment and the pelts examined for evidence of cockle, a nodular condition that appears in some sheep as a response to the presence of lice. Sheep treated to saturation with dip formulations produced more high quality pelts than did sheep treated with low volume, pour-on or spray-on dips. These differences are suspected to arise because louse populations decline more slowly after treatment with pour-ons or spray-ons than with saturation dips. The removal of lice and regression of cockle resulted in a high percentage of first grade pickled pelts. However, processing through to the dyed crust leather stage highlighted lesions in the same pelts that were not apparent at the pickle stage and lead to a substantial increase in the number of downgraded pelts.
Journal Article↗
Prevalence of pulmonary hypertension in limited and diffuse scleroderma.
STUDY OBJECTIVES: To characterize the prevalence of undiagnosed pulmonary hypertension in patients with limited and diffuse scleroderma. DESIGN: Prospective cross-sectional study. SETTING: University-based outpatient clinic. PATIENTS: Thirty-four consecutive patients with limited (n = 29) or diffuse (n = 5) scleroderma but without the clinical diagnosis of pulmonary hypertension. MEASUREMENTS AND RESULTS: All patients had 12-lead ECGs and two-dimensional and Doppler echocardiograms. The pulmonary artery systolic pressure (PAs) was calculated as the sum of the Doppler transtricuspid pressure gradient and the right atrial pressure as estimated by the caval respiratory index. Thirty-three patients (97%) had adequate spectral signals of tricuspid regurgitation. The velocity of tricuspid regurgitation ranged from 1.6 to 4.5 m/s. The calculated PAs ranged from 15 to 95 (mean +/- SD = 30 +/- 14 mm Hg). Twelve patients (35% of the total cohort) had pulmonary hypertension defined as PAs of 30 mm Hg or greater. CONCLUSIONS: Undiagnosed elevation of PAs is common in patients with scleroderma. Noninvasive assessment of PAs can be performed accurately in most patients independent of clinical signs of pulmonary hypertension. If successful treatment strategies are identified, it may be possible to identify patients early in the development of pulmonary hypertension and intervene before significant end-organ damage occurs.
Adult↗
Unstimulated rheumatoid synovial T-cells have a consistent V beta gene bias when compared to peripheral blood T-cells.
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Arthritis, Rheumatoid↗
T-cell receptor use in rheumatoid arthritis.
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Arthritis, Rheumatoid↗
Abnormal regulation of the IL-2 promoter in lpr CD4-CD8- T lymphocytes results in constitutive expression of a novel nuclear factor of activated T cells-binding factor.
The inert quality of MRL-Ipr/Ipr (Ipr) peripheral CD4-CD8- (CD4-8-) T cells manifests primarily as an inability to proliferate or produce IL-2 in response to TCR or mitogenic stimulation. Yet these same cells do initiate early TCR-mediated signaling events, such as generation of inositol phosphates and increased intracellular calcium. They also display constitutively high levels of p59fyn and CD3 zeta tyrosine phosphorylation. The generation of second messengers in T cells normally leads to downstream signaling that results in transcriptional activation of the IL-2 gene. We, therefore, compared the activation state of the IL-2 gene promoter region in freshly isolated and stimulated Ipr CD4-8- T cells with that of normal T lymphocytes. Levels of the octamer, NF-kappa B (p50-p65 heterodimer), and AP-1 transcriptional factors are constitutively elevated in freshly isolated Ipr CD4-8- T cells, consistent with the activated phenotype of these cells. Upon stimulation with mitogens, formation of the transactivating complex, nuclear factor of activated T cells (NF-AT), occurs with normal kinetics in Ipr CD4-8- T cells. Yet, the levels of the activating NF-AT complex never reach those observed in similarly stimulated normal T cells. Furthermore, nuclear extracts from Ipr CD4-8- T cells display high levels of a novel specific binding activity at the NF-AT site, which is present at much lower levels in freshly isolated normal T lymphocytes. Upon mitogenic stimulation, the binding activity of the novel NF-AT-binding factor is rapidly down-regulated in normal T cells, but persists at high levels in Ipr CD4-8- T cells. These two abnormalities at the NF-AT site provide a potential mechanism to account for the defect in IL-2 production from Ipr CD4-8- T cells.
Animals↗
Minocycline in rheumatoid arthritis. A 48-week, double-blind, placebo-controlled trial. MIRA Trial Group.
OBJECTIVE: To assess the safety and efficacy of minocycline in the treatment of rheumatoid arthritis. DESIGN: A double-blind, randomized, multicenter, 48-week trial of oral minocycline (200 mg/d) or placebo. SETTING: 6 clinical centers in the United States. PATIENTS: 219 adults with active rheumatoid arthritis who had previous limited treatment with disease-modifying drugs. MEASUREMENTS: As the primary outcomes, 60 diarthrodial joints were examined for tenderness, and 58 joints were examined for swelling (hips excluded). Grip strength, evaluator's global assessment, morning stiffness, Modified Health Assessment Questionnaire, patient's global assessment, hematocrit, erythrocyte sedimentation rate, platelet count, and IgM rheumatoid factor levels were also assessed; radiographs of both hands and wrists were taken. RESULTS: 109 and 110 patients were randomly assigned to receive minocycline and placebo, respectively. At entry, demographic, clinical, and laboratory measurements were similar in both groups. Most patients had mild to moderate disease activity and some evidence of destructive disease. At the week 48 visit, 79% of the minocycline group and 78% of the placebo group continued to receive the study medication. At 48 weeks, more patients in the minocycline group than in the placebo group showed improvement in joint swelling (54% and 39%) and joint tenderness (56% and 41%) (P < 0.023 for both comparisons). The minocycline group also showed greater improvement in hematocrit, erythrocyte sedimentation rate, platelet count, and IgM rheumatoid factor levels (all P values < 0.001), and more patients receiving minocycline had laboratory values within normal ranges at 48 weeks. For the remaining outcomes, P values ranged from 0.04 to 0.76, all greater than the critical value of 0.005 (Bonferroni adjustment for multiple comparisons). The frequency of reported side effects was similar in both groups, and no serious toxicity occurred. CONCLUSIONS: Minocycline was safe and effective for patients with mild to moderate rheumatoid arthritis. Its mechanisms of action remain to be determined.
Administration, Oral↗
Preliminary investigations into the aetiology and treatment of cockle, a sheep pelt defect.
A defect of sheep pelts known as cockle, detectable after depilation, but usually first noted only in the pickled pelt or tanned stage of processing, was studied to establish causal factor(s) and effective treatments. In addition, data on the histology and seasonal prevalence of the disease were obtained. Samples collected soon after slaughter from pelts identified at the pickled pelt stage as having cockle, had a superficial dermatitis with infiltration of eosinophils. This may represent an immediate hypersensitivity reaction of the sheep to lice. Treatments of sheep with either insecticides, disinfectants or shearing showed that where biting lice (Bovicola ovis) were removed, cockle lesions had either disappeared or regressed on pickled pelts. In Trial 1 diazinon reduced cockle prevalence and severity substantially; cypermethrin had a less pronounced effect. In Trial 2 diazinon, cypermethrin, Hibitane and Savlon were equally effective in reducing biting louse numbers as shown by counts of lice at 35 and 63 days post-treatment. Reduction of cockle on pelts from sheep slaughtered at 39 days post-treatment was achieved best by both diazinon and shearing. Examination of other pelts at 67 days post-treatment showed diazinon and Hibitane to be equally effective in reducing cockle. Furthermore, shearing in the absence of insecticides reduced the severity and extent of lesions on cockled pelts. The diazinon excipient and zinc sulphate were consistently poor at removing lice and reducing cockle prevalence and severity. The results have important implications for the leather industry in that shearing and good dipping practice with appropriate chemicals at the right time can lead to improved pelt quality. However, an incentive scheme for farmers, and a means of identifying individual pelts to the farms or origin, are both necessary before a marked improvement is likely to occur.
Animals↗
Evidence for the role of the sheep biting-louse Bovicola ovis in producing cockle, a sheep pelt defect.
The prevalence and severity of cockle, a sheep pelt defect characterised by raised lumps, was assessed on lambs that were either louse-infested (Bovicola ovis) or louse-free at birth. Assessments were made on pickled pelts, 10 months after the lambs had entered the trial. Lambs kept free of lice did not develop cockle, whereas the defect was common in lambs (about 90%) that were infested with lice. There was a direct correlation between louse scores and cockle, high louse scores being associated with a more severe degree of cockle. The results give support to the strong causal relationship between B. ovis and cockle, but questions such as the minimum number of lice needed to cause cockle and the time required for cockle to develop still need to be answered.
Animals↗
Sedation for fibre optic bronchoscopy.
Most current sedative regimens for fibre optic bronchoscopy use an opioid, a benzodiazepine or a combination of both. This study compares midazolam (M) (a benzodiazepine), alfentanil (A) (an opioid) and a combination of both drugs (M+A). One hundred and three patients were randomized in double-blind manner into groups M(35), A(33) and M+A(35). The number of coughs, number of additional aliquots of lignocaine and duration of the procedures were recorded along with oxygen desaturation. The patient's level of discomfort was assessed by patient and bronchoscopist and expressed as a visual analogue score. There were significantly fewer coughs per minute in Group A compared with Group M (P = 0.0053), and significantly less lignocaine was required in Group A (P = 0.005) and in Groups M+A (P < 0.002) compared with Group M. There was no significant difference in the assessment of discomfort between the groups. There was a trend for Group M+A to desaturate more than the other two with a significant difference between desaturation in Group M+A and Group A (P = 0.033). Alfentanil is a more effective anti-tussive agent than midazolam for outpatient fibre optic bronchoscopy. The combination of alfentanil and midazolam does not provide any better anti-tussive effect and may have the risk of a greater degree of desaturation secondary to increased sedation.
Alfentanil↗