Reactive nitrogen species and proteins: biological significance and clinical relevance.
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Animals↗
Biomedical subjects
R Lightfoot
Publications and source records attributed to R Lightfoot.
Practice nurses in the Waikato, 1991-1992, I: Occupational profile.
AIMS: To describe the personal characteristics, working conditions, clinical activities and professional development of a representative sample of practice nurses in the Waikato during the period 1991-1992. METHODS: The data are from a survey of practice nurses drawn from a larger study of general practice carried out in the Waikato (the WaiMedCa Study). Eighty-nine percent of the 107 practices in the region participated in the study. The practice nurse survey was carried out on the 189 nurses working in these practices. Of these 149 replied, representing a response rate of 79%. RESULTS: On average, there was one nurse for each solo practice and two in most other practices. Only two practices--both solo--did not employ a nurse. Practice nurses were female and aged between 30 and 50. While only one-third had received a postgraduate qualification, two-thirds had been to recent professional development courses. The majority had worked as a practice nurse for between one and ten years. Nurses averaged just under 15 telephone contacts a day and 28 face-to-face contacts a week. Nurses' workload comprised general measurements and assessments, monitoring and surveillance procedures (such as diabetes, asthma and child development), and counselling and women's health activities. CONCLUSION: Practice nurses are an accepted and essential part of primary health care in New Zealand. However, their potential is probably underdeveloped and they could be more fully utilised for a wider range of nursing functions.
Adult↗
Test-treatment strategies for patients suspected of having Lyme disease: a cost-effectiveness analysis.
PURPOSE: To examine the cost-effectiveness of test-treatment strategies for patients suspected of having Lyme disease. DATA SOURCES: The medical literature was searched for information on outcomes and costs. Expert opinion was sought for information on utilities. STUDY SELECTION: Articles that described patient population, diagnostic criteria, dose and duration of therapy, and criteria for assessment of outcomes. DATA EXTRACTION: The decision analysis evaluated the following strategies: 1) no testing-no treatment; 2) testing with enzyme-linked immunosorbent assay (ELISA) followed by antibiotic treatment of patients with positive results; 3) two-step testing with ELISA followed by Western blot and antibiotic treatment for patients with positive results on either test; and 4) empirical antibiotic therapy. Three patient scenarios were considered: myalgic symptoms, rash resembling erythema migrans, and recurrent oligoarticular inflammatory arthritis. Results were calculated as costs per quality-adjusted life-year and were subjected to sensitivity analysis. Adjustment was made for the diagnostic value of common clinical features of Lyme disease. DATA SYNTHESIS: For myalgic symptoms without other features suggestive of Lyme disease, the no testing-no treatment strategy was most economically attractive (that is, had the most favorable cost-effectiveness ratio). For rash, empirical antibiotic therapy was less costly and more effective than other strategies. For oligoarticular arthritis with a history of rash and tick bite, two-step testing was associated with the lowest cost-effectiveness ratio. Testing with ELISA and empirical antibiotic therapy cost an additional $880,000 and $34,000 per quality-adjusted life-year, respectively. For oligoarticular arthritis with one or no other features suggestive of Lyme disease, two-step testing was most economically attractive. CONCLUSIONS: Neither testing nor antibiotic treatment is cost-effective if the pretest probability of Lyme disease is low. Empirical antibiotic therapy is recommended if the pretest probability is high, and two-step testing is recommended if the pretest probability is intermediate.
Anti-Bacterial Agents↗
Laboratory evaluation in the diagnosis of Lyme disease.
PURPOSE: To provide a qualitative evaluation of the predictive value of the laboratory diagnosis of Lyme disease and to use the resultant data to formulate guidelines for clinical diagnosis. DATA SOURCES: A MEDLINE search of English-language articles or articles with English-language abstracts published from 1982 to 1996. DATA EXTRACTION: Sensitivity, specificity, and likelihood ratios were calculated, and a random-effects model was used to combine the proportions from the eligible studies. Prespecified criteria were used to determine which studies were eligible for analysis. DATA SYNTHESIS: Laboratory testing in general is not clinically useful if the pretest probability of Lyme disease is less than 0.20 or greater than 0.80. When the pretest probability is 0.20 to 0.80, sequential testing with enzyme-linked immunosorbent assay and Western blot is the most accurate method for ruling in or ruling out the possibility of Lyme disease. CONCLUSIONS: Laboratory testing is recommended only in patients whose pretest probability of Lyme disease is 0.20 to 0.80. If the pretest probability is less than 0.20, testing will result in more false-positive results than true-positive results; a negative test result in this situation effectively rules out the disease.
Bacteriological Techniques↗
Comparison of the efficacy and safety of etodolac and piroxicam in patients with rheumatoid arthritis. Etodolac Study 326 Rheumatoid Arthritis Investigators Group.
The efficacy and safety of etodolac and piroxicam in patients with active rheumatoid arthritis were compared. A 12 week, double blind, parallel group study was conducted at 28 centers in patients 18 to 75 yrs old, randomized to receive etodolac or piroxicam. Primary efficacy criteria were investigators' and patients' global assessments and numbers of painful and swollen joints. Secondary criteria were duration of morning stiffness, grip strength, time to walk 50 feet. Westergren erythrocyte sedimentation rate (ESR), pain intensity, painful and swollen joint scores, and articular index. Of 426 patients enrolled, 140 received etodolac 200 mg bid (E200), 147 received etodolac 300 mg bid (E300), and 139 received piroxicam 20 mg qd (P20). Efficacy analyses included data from 361 patients. No significant differences occurred between the E300 and piroxicam groups in change from baseline for the primary efficacy variables. All treatments produced significant (p < 0.01) improvement from baseline in all efficacy variables, except that only E300 produced a significant decrease from baseline in ESR. No significant differences occurred in the incidence of any specific adverse event. Six patients given E200, 7 given E300, and 10 given piroxicam withdrew because of adverse reactions. The incidence of patients with hemoglobin and hematocrit results below the normal range was significantly higher for piroxicam than for either etodolac regimen. Three patients receiving piroxicam had gastrointestinal ulcers. Thus, E300 and P20 provided comparable efficacy. E200 was less effective for some variables early in the study.
Adolescent↗
Activation of heat shock factor by alkylating agents is triggered by glutathione depletion and oxidation of protein thiols.
Transcriptional activation of heat shock protein genes is a common response to proteotoxic stress. Many drugs and chemicals that form reactive electrophiles modify protein structure by binding covalently to nucleophilic functional groups. Although many of these agents also activate transcription of the inducible member of the hsp70 gene family, it is not clear if covalent modification of cellular proteins per se is sufficient. Iodoacetamide (IDAM) is a prototypical alkylating toxicant that induces hsp70 transcription. However, IDAM-induced cell death is indirectly linked to protein alkylation through depletion of glutathione, induction of oxidative stress, and increased lipid peroxidation. Therefore, we determined if any of these secondary cytotoxic events might lead to activation of hsp70 transcription. IDAM treatment increased hsp70 transcription by activating heat shock transcription factor-1 (HSF1). The addition of antioxidants and iron or calcium chelators prevented cell death but did not prevent hsp70 transcription or HSF1 activation. However, the protein synthesis inhibitor cycloheximide blocked activation of hsp70 by low concentrations of IDAM. Furthermore, the addition of dithiothreitol (DTT) after IDAM removal blocked hsp70 transcription and HSF1 activation without altering IDAM binding. DTT had no effect on activation of HSF1 by hyperthermia. After IDAM treatment, cellular nonprotein and protein thiols had decreased to less than 20 and 70%, respectively, of the value in control cells. DTT treatment in situ prevented the loss of cellular protein thiols and blocked the formation of high molecular weight protein aggregates. Thus, alkylation of proteins is insufficient to activate hsp70 transcription and DNA binding of HSF1. However, cellular thiol-disulfide redox status and formation of disulfide linked aggregates of cellular proteins are linked to HSF1 activation and hsp70 transcriptional activation.
Alkylating Agents↗
American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis.
OBJECTIVE: Trials of rheumatoid arthritis (RA) treatments report the average response in multiple outcome measures for treated patients. It is more clinically relevant to test whether individual patients improve with treatment, and this identifies a single primary efficacy measure. Multiple definitions of improvement are currently in use in different trials. The goal of this study was to promulgate a single definition for use in RA trials. METHODS: Using the American College of Rheumatology (ACR) core set of outcome measures for RA trials, we tested 40 different definitions of improvement, using a 3-step process. First, we performed a survey of rheumatologists, using actual patient cases from trials, to evaluate which definitions corresponded best to rheumatologists' impressions of improvement, eliminating most candidate definitions of improvement. Second, we tested 20 remaining definitions to determine which maximally discriminated effective treatment from placebo treatment and also minimized placebo response rates. With 8 candidate definitions of improvement remaining, we tested to see which were easiest to use and were best in accord with rheumatologists' impressions of improvement. RESULTS: The following definition of improvement was selected: 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: patient and physician global assessments, pain, disability, and an acute-phase reactant. Additional validation of this definition was carried out in a comparative trial, and the results suggest that the definition is statistically powerful and does not identify a large percentage of placebo-treated patients as being improved. CONCLUSION: We present a definition of improvement which we hope will be used widely in RA trials.
Adult↗
Double-blind, placebo-controlled multicenter trial using chimeric monoclonal anti-CD4 antibody, cM-T412, in rheumatoid arthritis patients receiving concomitant methotrexate.
OBJECTIVE: To evaluate the clinical response to and safety of single and repeat doses of a chimeric anti-CD4 monoclonal antibody, cM-T412, in patients with rheumatoid arthritis (RA) concomitantly treated with a stable regimen of low-dose methotrexate. METHODS: Sixty-four patients with refractory RA, who were already receiving stable doses of methotrexate, were randomized into a multicenter, double-blind, placebo-controlled trial to receive 3 monthly treatments with either a placebo, or 5, 10, or 50 mg cM-T412, given intravenously. RESULTS: Using > or = 50% improvement in swollen joint counts as a criterion for clinical response, 13%, 13%, 18%, and 13% of patients receiving 50, 10, or 5 mg cM-T412, or the placebo, respectively, exhibited a clinical response at 3 months of therapy. Using > or = 50% improvement in tender joint counts as a measure of clinical efficacy at 3 months, 19%, 13%, 12%, and 6% of patients receiving 50, 10, or 5 mg cM-T412, or the placebo, respectively, exhibited a clinical response. "Flu-like" symptoms (fever, chills, rigor) within 24 hours of the infusion occurred more frequently in the groups receiving 50-mg (29%) and 10-mg (31%) doses of cM-T412 than those receiving 5 mg cM-T412 (12%) or the placebo (13%). Significant CD4+ T cell depletion occurred in the 50-mg group (mean of 353 CD4+ T cells/mm3 at 6 months versus 856 CD4+ T cells/mm3 at baseline). All patients were followed up for 12 months after the final treatment; no opportunistic infectious complications occurred. CONCLUSION: Treatment with cM-T412 in this cohort of RA patients who were also taking methotrexate was not associated with clinical efficacy or enhanced toxicity from infectious complications, despite significant peripheral CD4+ T cell depletion.
Adult↗
Genes required for cellulose synthesis in Agrobacterium tumefaciens.
A region of the chromosome of Agrobacterium tumefaciens 11 kb long containing two operons required for cellulose synthesis and a part of a gene homologous to the fixR gene of Bradyrhizobium japonicum has been sequenced. One of the cellulose synthesis operons contained a gene (celA) homologous to the cellulose synthase (bscA) gene of Acetobacter xylinum. The same operon also contained a gene (celC) homologous to endoglucanase genes from A. xylinum, Cellulomonas uda, and Erwinia chrysanthemi. The middle gene of this operon (celB) and both the genes of the other operon required for cellulose synthesis (celDE) showed no significant homology to genes contained in the databases. Transposon insertions showed that at least the last gene of each of these operons (celC and celE) was required for cellulose synthesis in A. tumefaciens.
Agrobacterium tumefaciens↗
The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. The Committee on Outcome Measures in Rheumatoid Arthritis Clinical Trials.
OBJECTIVE: To develop a set of disease activity measures for use in rheumatoid arthritis (RA) clinical trials, as well as to recommend specific methods for assessing each outcome measure. This is not intended to be a restrictive list, but rather, a core set of measures that should be included in all trials. METHODS: We evaluated disease activity measures commonly used in RA trials, to determine which measures best met each of 5 types of validity: construct, face, content, criterion, and discriminant. The evaluation consisted of an initial structured review of the literature on the validity of measures, with an analysis of data obtained from clinical trials to fill in gaps in this literature. A committee of experts in clinical trials, health services research, and biostatistics reviewed the validity data. A nominal group process method was used to reach consensus on a core set of disease activity measures. This set was then reviewed and finalized at an international conference on outcome measures for RA clinical trials. The committee also selected specific ways to assess each outcome. RESULTS: The core set of disease activity measures consists of a tender joint count, swollen joint count, patient's assessment of pain, patient's and physician's global assessments of disease activity, patient's assessment of physical function, and laboratory evaluation of 1 acute-phase reactant. Together, these measures sample the broad range of improvement in RA (have content validity), and all are at least moderately sensitive to change (have discriminant validity). Many of them predict other important long-term outcomes in RA, including physical disability, radiographic damage, and death. Other disease activity measures frequently used in clinical trials were not chosen for any one of several reasons, including insensitivity to change or duplication of information provided by one of the core measures (e.g., tender joint score and tender joint count). The committee also proposes specific ways of measuring each outcome. CONCLUSION: We propose a core set of outcome measures for RA clinical trials. We hope this will decrease the number of outcomes assessed and standardize outcomes assessments. Further, we hope that these measures will be found useful in long-term studies.
Arthritis, Rheumatoid↗
A semiquantitative bioassay for relative virulence of Agrobacterium tumefaciens strains on Bryophyllum daigremontiana.
An assay to determine the relative virulence of wild-type and mutant strains of Agrobacterium tumefaciens on leaves of Bryophyllum daigremontiana has been developed. This assay is reproducible, is easy to learn, is not time consuming, and requires little space. The relative virulence of cellulose-minus mutants of A. tumefaciens was investigated with this assay. Some of these mutants were unaltered in virulence, while others showed a marked reduction in virulence.
Agrobacterium tumefaciens↗
Regional distribution of lysosomal enzymes in the canine retinal pigment epithelium.
We have investigated the activities of four lysosomal enzymes in RPE cells isolated from three regions of the canine fundus: the tapetal area, the central pigmented area and the peripheral area. The results obtained with freshly isolated cells showed that the activities of acid phosphatase, B-glucuronidase and N-acetyl-B-glucosaminidase were significantly higher in RPE cells derived from the peripheral region when compared to those from the two central regions. In contrast, the activity of cathepsin D was significantly higher in the tapetal region than in the periphery. The regional distribution of both acid phosphatase and B-glucuronidase observed in fresh RPE cells was progressively lost when these cells were grown in culture. Estimations of photoreceptor density per RPE cell from each of the regions indicated that the number of photoreceptors per RPE cell did not vary significantly with retinal location and suggested that variations in enzyme content were not related to differences in photoreceptor cell distribution.
Animals↗