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Biomedical subjects

C Neville

Publications and source records attributed to C Neville.

At least 19 recordsLinked to original sources
PubMed2006

The persistence of anticardiolipin antibodies is associated with an increased risk of the presence of lupus anticoagulant and anti-beta2-glycoprotein I antibodies.

OBJECTIVE: We studied antiphospholipid antibodies (aPL) in blood samples from a cohort of individuals followed for thrombosis to determine whether the persistent presence of anticardiolipin antibodies (aCL) is associated with a greater likelihood of having lupus anticoagulant and/or anti-beta2-glycoprotein I antibodies (LA/abeta2GPI). METHODS: Blood samples from 353 individuals who had been tested for aCL on at least two occasions were tested for abeta2GPI and LA. Two groups were defined: aCL-persistent, who tested aCL-positive on at least two occasions, and aCL non-persistent, who tested aCL-positive on fewer than two occasions. Multivariate logistic regressions were performed using LA/abeta2GPI, LA and abeta2GPI as outcome variables and the percentage of aCL-positive tests as the predictor variable, adjusted for age, gender, family history of cardiovascular disease (CVD), systemic lupus erythematosus (SLE), smoking and number of venous (VT) and arterial thromboses (AT). RESULTS: Sixty-eight (19%) individuals were aCL persistent and 285 (81%) were aCL non-persistent. LA/abeta2GPI was found in 36 (53%) of the aCL persistent group and 38 (13%) of the aCL non-persistent group. The two groups were similar for age, gender and smoking. Family history of CVD, SLE, VT and AT were more frequent in the aCL persistent group. Multivariate analyses revealed that odds ratios for LA/abeta2GPI, LA and abeta2GPI were 1.34 [95% confidence interval (CI) = 1.22-1.47], 1.36 (95% CI = 1.24-1.50) and 1.47 (95% CI = 1.31-1.65) respectively for each 10% increase in aCL-positive tests vs 0% positive tests. CONCLUSION: Persistence of aCL positivity is associated with an increased risk of LA/abeta2GPI.

Adult↗
PubMed2006

A comparison of damage accrual across different calendar periods in systemic lupus erythematosus patients.

Therapeutic approaches in systemic lupus erythematosus (SLE) have evolved over the last few decades, but their impact on prevention of organ damage is unknown. The objective of this study was to compare new cumulative damage in SLE patients across different calendar periods. Patients from a large SLE cohort were divided into two subcohorts; the first diagnosed and followed between 1978 and 1988 (cohort #1, n=100) and the second between 1989 and 1999 (cohort #2, n=51). Initial Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) scores, and changes in scores over the observation intervals, were compared for the two groups. Logistic regression estimated adjusted odds ratios (OR) comparing damage accrual between the two cohorts. Medication exposures were noted. Baseline characteristics were similar between the two groups. At first assessment, the adjusted OR for a SLICC/ACR DI score > or =1 was 1.79 (95% CI 0.82, 3.88) for cohort #1 versus cohort #2. At the end of the observation interval, the adjusted OR for a SLICC/ACR DI score > or =1 was 1.22 (0.58, 2.55) for cohort #1 versus cohort #2. The adjusted OR for accruing damage over the observation interval in cohort #1 versus cohort #2 was 0.94 (0.39, 2.44). Increased medication exposure was evident for cohort #2 compared to cohort #1. Despite increased therapeutic measures used for patients in more recent periods, our data do not establish a clear difference in damage accrual. This emphasizes the need for strategies to effectively treat lupus-specific manifestations, while minimizing side effects and comorbidities.

Adrenal Cortex Hormones↗
PubMed2002

Associations between physical fitness and activity patterns during adolescence and cardiovascular risk factors in young adulthood: the Northern Ireland Young Hearts Project.

The aim of the present study was to examine relationships between cardiovascular disease (CVD) risk factor status in young adulthood (mean age = 22.5 yrs) and antecedent physical fitness and physical activity at ages 12 and 15 years. The data were obtained from the Young Hearts Project, a longitudinal observational study of CVD risk factors in a representative sample of young people from Northern Ireland. Physical fitness was measured by the 20-metre endurance shuttle run, and physical activity and sports participation by a self-report recall questionnaire. CVD risk factors examined included serum total cholesterol (TC) and HDL cholesterol concentrations, the TC:HDL ratio, systolic and diastolic blood pressure and body fatness (sum of four skinfolds). Linear regression analyses showed modest relationships between physical fitness in adolescence and both TC:HDL ratio and body fatness in young adulthood. No such relationships were apparent for adolescent physical activity. The promotion of physical fitness during adolescence may reduce exposure to other risk factors lasting into early adulthood.

Adolescent↗
PubMed2001

Adaptation and validation of the rheumatoid arthritis quality of life scale for use in Canada.

OBJECTIVE: The Rheumatoid Arthritis Quality of Life questionnaire (RAQoL) was developed simultaneously in the UK and the Netherlands to measure quality of life in patients with RA. We adapted and validated the RAQoL for the English-Canadian and French-Canadian languages and culture. METHODS: The UK RAQoL was translated into French-Canadian by a bilingual translation panel. Separate lay panels were then used to ensure that this and the English-Canadian instruments were appropriate for use with Canadian patients. Interviews were conducted with 15 French-Canadian and 15 English-Canadian patients with RA to determine the content validity. Reliability and construct validity were established by means of test-retest mail surveys conducted with 92 French-Canadian and 87 English-Canadian RA patients. The survey consisted of the adapted RAQoL, the Health Assessment Questionnaire (HAQ), and a demographic questionnaire. RESULTS: The RAQoL was successfully adapted for both the French and English-Canadian cultures. Field testing showed both versions to be well received by respondents. Of the French-Canadian patients included in the postal survey, 52 responded at Time 1 and 50 at Time 2. For the English-Canadian sample, 54 responded at both time points. Missing data rates for the RAQoL were low and floor and ceiling effects were minimal. Test-retest reliability was good for both versions: 0.87 for the French-Canadian and 0.95 for the English-Canadian. Alpha coefficients (0.92 for the French-Canadian, 0.93 for the English-Canadian) showed the items to be adequately interrelated and scores on the measure showed moderate to high correlations with the HAQ, confirming construct validity. Both versions of the RAQoL were also able to distinguish patient groups that differed according to perceived health status and perceived severity of RA. In addition, the French-Canadian version was able to distinguish patients who rated today as bad or very bad from those who rated today as good or very good. CONCLUSION: The new versions of the RAQoL were well received by both French and English speaking Canadians. The psychometric quality of the adapted questionnaires means they are suitable for inclusion in clinical trials involving patients with RA.

Adult↗
PubMed2000

Association between IgM response to IgG damaged by glyoxidation and disease activity in rheumatoid arthritis.

OBJECTIVE: To determine the association of serum IgG advanced glycation endproducts (AGE) and IgM anti-IgG-AGE antibodies with clinical measurements of rheumatoid arthritis (RA) disease activity. METHODS: The study group consisted of 62 patients with RA and 16 control patients with osteoarthritis. Patient derived variables included perceived disease activity (10 cm visual analog scale, VAS) and Health Assessment Questionnaire (HAQ) results. Clinical measures of RA activity consisted of tender and swollen joint counts and a physician evaluation of disease activity (by VAS) as well as history of nodules, bone erosions, Sjogren's syndrome, and vasculitis documented by chart review. Patient sera were evaluated for glucose, glycosylated hemoglobin, and presence of RF, IgG-AGE and IgM anti-IgG-AGE. The nitroblue tetrazolium colorimetric and aminophenyl boronic acid methods were used for measurement of IgG-AGE, along with an ELISA for measurement of IgM anti-IgG-AGE. RESULTS: Significant correlations were found between the presence of IgM anti-IgG-AGE and clinical measurements of swollen joint count and physician VAS. CONCLUSION: IgM anti-IgG-AGE appears to be associated with clinical measurements of RA activity and represents a new marker of more active disease in RA.

Adult↗
PubMed2000

Learning from discordance in patient and physician global assessments of systemic lupus erythematosus disease activity.

OBJECTIVE: Differences have been described between patient and physician assessments of well being in several chronic illnesses, and these differences may affect outcome. Disagreement may lead to dissatisfaction and to behaviors with dangerous consequences. We describe and identify predictors of patient-physician differences on ratings of disease activity in systemic lupus erythematosus (SLE). METHODS: Data collected on 154 patients included age, education, disease duration, and patient and physician global assessments of lupus activity on a 10 cm visual analog scale (VAS), the Health Assessment Questionnaire (HAQ), the Medical Outcome Study Short-Form 36 (SF-36), the Systemic Lupus Disease Activity Index (SLEDAI), the Systemic Lupus Activity Measure (SLAM-R), and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Multiple linear regression models were performed using patient VAS scores, physician VAS scores, and patient minus physician VAS scores as the dependent variables, and age, disease duration, selected SF-36 and SLAM-R subscales, and SDI as independent variables. RESULTS: Patients were 90% female and 80% Caucasian, with a mean education of 13 +/- 2.8 years and a mean age of 43.1 +/- 13.6 years. The overall mean disease duration was 10.5 +/- 7.8 years. Physicians overscored patients by 2.5 cm in 6% of the cases and patients overscored physicians in 16% of the cases. The best multivariate model to predict overall differences included SF-36 mental health and SLAM-R kidney scores. CONCLUSION: Patient-physician differences may result from a divergence in focus. Patients score lupus activity based on their psychological status, while physicians rely more heavily on the physical effect of the disease.

Adult↗
PubMed2000

Do lupus disease activity measures detect clinically important change?

OBJECTIVE: New scales for the clinical assessment of patients with systemic lupus erythematosus (SLE) are valid and reliable, and quantitate disease activity. We assessed the responsiveness to change of 2 widely used standardized multi-item lupus activity measures, the revised Systemic Lupus Activity Measure (SLAM-R) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and their ability to detect clinically relevant changes. METHODS: Ninety-six (96) patients with definite SLE participated in this study. The group mean age was 45.0 (13.7) years, 91% were female, and the mean disease duration was 14.9 (7.5) years. Sociodemographic information, lupus activity (SLAM-R, SLEDAI), and damage were recorded at baseline. At each of the 5 monthly followup visits, the activity measures were repeated and a transition scale asked the physician if their patient's lupus activity had changed. Five different methods were used to compare the responsiveness of the activity measures studied: 1. the effect size; 2. the standardized response mean; 3. the control standardized response mean; 4. the area under the curve of a receiver operating characteristic (ROC) curve; and 5. a new multiple response modeling approach. RESULTS: Both SLAM-R and SLEDAI are responsive. SLAM-R is consistently, although moderately, more responsive than SLEDAI. All 5 methods of evaluating responsiveness yielded a consistent ranking of disease activity measures. CONCLUSION: SLAM-R and SLEDAI are responsive measures of lupus activity. SLAM-R appears to be more responsive than SLEDAI.

Activities of Daily Living↗
PubMed1999

The needs of patients with arthritis: the patient's perspective.

OBJECTIVE: To identify concerns and learning interests of patients with arthritis. METHODS: A questionnaire was developed, pilot tested, and then used to evaluate 197 patients with arthritis, including osteoarthritis (OA) (n = 41), rheumatoid arthritis (RA) (n = 57), back disease (n = 55), systemic lupus erythematosus (n = 27), and systemic sclerosis (SSc) (n = 17). Twenty concerns and 12 learning interests were rated. Questionnaires were also administered to assess physical disability (Health Assessment Questionnaire), psychological disability (Arthritis Impact Measurement Scales 2), and pain (visual analog scale). Participants addressed accessibility of health services, satisfaction with their physician, psychosocial needs, use of self-help groups, and behavioral strategies used to assist coping. Patients with RA, OA, and back disease, at both a community and a hospital center, were tested to assess whether concerns and learning interests differed based on site of treatment. Analytic methods included analysis of variance, factor analysis, and multiple linear regression. RESULTS: There were no differences in concerns or learning interests based on treatment site. Between diagnostic groups, patients with SSc were more interested in learning about self-help groups. The most frequently reported concern was worsening of the illness. The majority of respondents were interested in learning more about topics that were illness specific. The physician was chosen as the preferred source of information, and the preferred format was in writing. On factor analysis, the 20 concerns were reduced to 5 factors: psychological, coping, medication, social, and financial. Three factors were identified for learning interests: the illness, traditional health management topics, and nontraditional health management topics. Stepwise multiple linear regression revealed predictors for the 5 concern and 3 learning interest factors. The concerns were best predicted by self-reported disease severity, physical disability, and psychological distress, while learning interests were best predicted by self-reported disease severity, pain, and self-help group membership. CONCLUSION: Concerns and learning interests of persons with arthritis did not differ based on the center of treatment or the diagnosis, but can be predicted by the level of pain and simple measures of disability. Better understanding of the relationship between health status and patient-perceived needs will result in improved patient-centered care.

Activities of Daily Living↗
PubMed1999

Discordance between patients and their physicians in the assessment of lupus disease activity: relevance for clinical trials.

Discordance between patient and physician assessment of lupus activity occurs frequently and its determinants are not known. Examples of discordance between patients and physicians in other disease models can be found in the literature. A better understanding of the discordance between patients and physicians can help us achieve a shared decision-making model of health care, improve patient satisfaction, improve patient compliance, and improve physician understanding of how lupus impacts on their patients. Understanding discordance also impacts on the design and interpretation of clinical trials.

Clinical Trials as Topic↗
PubMed1999

Systemic lupus erythematosus, a disease associated with low levels of clusterin/apoJ, an antiinflammatory protein.

OBJECTIVE: To measure the serum levels of clusterin, an antiinflammatory protein, which binds and inactivates complement, in patients with systemic lupus erythematosus (SLE) to determine whether the levels correlate with disease. METHODS: The levels of serum clusterin were measured by ELISA in 80 patients with SLE (76 female, 4 male). Clinical and serological information was gathered on 115 visits. Overall disease activity scores were determined using the Systemic Lupus Activity Measure-Revised. RESULTS: Serum clusterin levels were significantly decreased in patients with SLE and correlated inversely with disease activity (p < 0.00001). Low clusterin levels were significantly associated with skin ulcers (p < 0.0001), loss of hair (p = 0.002), proteinuria (p = 0.018), low platelet count (p = 0.03), and arthritis (p < 0.0001). The clusterin levels did not correlate with either systemic complement consumption, as measured by C3 or C4, or with prednisone use. CONCLUSION: A highly significant correlation was observed between low levels of serum clusterin and a number of SLE disease features. This deficiency of clusterin could directly or indirectly affect the disease process. Individuals lacking sufficient amounts of clusterin systemically likely have poor control of antibody mediated inflammation at sites of apoptosis where autoantigens are exposed.

Autoantibodies↗
PubMed1999

Can health utility measures be used in lupus research? A comparative validation and reliability study of 4 utility indices.

OBJECTIVE: To assess validity and reliability of 4 utility indices in patients with systemic lupus erythematosus (SLE). METHODS: Twenty-five patients with stable SLE underwent assessment of disease activity [Systemic Lupus Disease Activity Measure (SLAM-R) and SLE Disease Activity Index (SLEDAI)] and damage [Systemic Lupus Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI)] and completed a health survey [Medical Outcome Survey Short Form-36 (SF-36)] and 4 utility measures: the visual analog scale (VAS), the time trade-off (TTO), the standard gamble (SG), and the McMaster Health Utilities Index Mark 2 (HUI2). To assess validity, Pearson's correlations were calculated between the SF-36 subscales and the utility measures. To assess reliability, intraclass correlations or kappa coefficients were calculated between first and second assessments, performed from 2 to 4 weeks apart, in patients without important clinical change in disease activity. RESULTS: Disease activity from a SLAM-R varied from 0 to 14 (median = 4) and SLEDAI from 0 to 18 (median = 0). All subscales of the SF-36 correlated well with the VAS [lowest r = 0.56, 95% confidence interval (CI) (0.17, 0.80)] and poorly with the SG [maximum r = 0.41, CI (-0.01, 0.70); minimum r = 0.10, CI (-0.32, 0.50)]. The subscales of bodily pain (r = 0.56), mental health (r = 0.45), physical functioning (r = 0.62), role-emotional (r = 0.47), social functioning (r = 0.49) and vitality (r = 0.44) correlated significantly with TTO. All subscales correlated significantly [lowest r = 0.48, CI (0.09, 0.75)] with the HUI2 index of pain. Intraclass correlations for the VAS (ICC = 0.67) and TTO (ICC = 0.60) were good. They were fair for the SG (ICC = 0.45). The kappa coefficient was poor (0.32) for the HUI attribute of pain, but varied from fair (0.46) to excellent (0.88) for the remaining attributes. Regression analysis showed that a model incorporating the SLAM-R value and SF-36 subset of mental health was a good predictor of VAS and TTO utility measures. CONCLUSION: The VAS, TTO, and to some extent, the HUI2, when compared with the SF-36 health survey, are valid and reliable measures to assess health related quality of life in a group of patients with SLE and may be useful for future research in this population. On the basis of these results the usefulness of the SG is questionable in these patients.

Adult↗
PubMed1998

Prostanoid signaling, localization, and expression of IP receptors in rat thick ascending limb cells.

It is widely held that only one prostacyclin (IP) receptor exists that can couple to guanine stimulatory nucleotide binding proteins (Gs) leading to activation of adenyl cyclase. Although IP receptor mRNA is expressed in vascular arterial smooth muscle cells and platelets, with lower level expression in mature thymocytes, splenic lymphocytes, and megakaryocytes, there is no molecular evidence for IP receptor expression in renal epithelial cells. The purpose of the present study was to obtain molecular evidence for the expression and localization of the IP receptor and to study the signaling pathways of IP receptor in rat medullary thick ascending limb (MTAL). Biochemical studies showed that IP prostanoids do not increase cAMP in rat MTAL. However, in the presence of vasopressin, inhibition of cAMP formation by prostacyclin (PGI2) analogs is pertussis toxin sensitive and does not activate protein kinase C. In situ hybridization studies localized IP receptor mRNA expression to MTAL in the rat kidney outer medulla. The results of RT-PCR of freshly isolated RNA from MTAL, with primers specific for the mouse IP receptor cDNA, produced an amplification product of the correct predicted size that contained an expected Nco I endonuclease restriction site. We conclude that rat renal epithelial cells express the IP receptor, coupled to inhibition of cAMP production.

Adenylate Cyclase Toxin↗
PubMed1998

Impact of disease activity and cumulative damage on the health of lupus patients.

To test if lupus activity and damage predict physical function and general health in lupus was the objective of this study. Ninety-six patients with lupus were seen at baseline and monthly for 4 months. Sociodemographic characteristics and lupus damage (SLICC/ACR DI), were collected at baseline while lupus activity (SLAM-R, SLEDAI), health status measures (HAQ, SF-36) and immunological tests were collected at each visit. Associations of lupus activity and damage with general health and physical function were evaluated. Baseline health status measures were greatly impaired and comparable to those of severe medical illnesses. In cross-sectional analyses, baseline activity score measured by SLAM-R, but not by SLEDAI, correlated with most subscales of SF-36. Baseline damage score SLICC/ACR DI correlated only with the HAQ and the physical function subscale of SF-36. Differences in both activity measures (SLAM-R and SLEDAI) over time correlated with change in health status measures while baseline cumulative damage (SLICC/ACR DI) correlated with the average level of physical function only. Lupus activity measures, SLAM-R and SLEDAI, although differing cross-sectionally, both reflected patients' health status performance over time and lupus damage measure, SLICC/ACR DI, performed well in assessing physical function. Lupus patients scores for health are poor and comparable to those found in severe medical illnesses.

Activities of Daily Living↗
PubMed1998

The relationship between disease activity and expert physician's decision to start major treatment in active systemic lupus erythematosus: a decision aid for development of entry criteria for clinical trials.

OBJECTIVE: To explore the relationship between patients' systemic lupus erythematosus (SLE) activity and physicians' decision to treat with steroids or alternative medication. METHODS: Baseline information and clinical status was extracted from case histories of 30 patients with lupus and represented in clinical vignettes. These vignettes were then mailed to 60 physicians (rheumatologists and immunologists with experience in the treatment of lupus), asking them in each case whether they would initiate treatment or not. The relationship between the 38 complete responses and the SLE Activity Measure (SLAM-R) and SLE Disease Activity Index (SLEDAI) lupus activity scores was analyzed using a general additive model. RESULTS: SLE disease activity measured by SLAM-R or SLEDAI is a significant predictor (p < 0.0001) of physicians' decision to initiate treatment for patients with lupus. Variation between physicians was observed but was mostly due to a few outliers. Some other variations remained unexplained by patients' SLE disease activity, damage, or by specific organ involvement. CONCLUSION: We present reference tables and curves for research that may be used as a basis to derive standardized quantitative criteria for entry in clinical trials. More research is needed on how these tools can be used by clinicians to guide them in their decision to treat or not.

Allergy and Immunology↗
PubMed1998

Inhibition of lupus anticoagulant activity by hexagonal phase phosphatidylethanolamine in the presence of prothrombin.

We have previously demonstrated that lupus anticoagulant antibodies from patients with systemic lupus erythematosus (SLE) specifically recognize hexagonal (II) phase phosphatidylethanolamine (PE), but not bilayer PE (Thromb Haemost 1989; 62: 892). In those studies, the involvement of proteins in this recognition was not evaluated. To address this issue, we have isolated IgG lupus anticoagulant antibodies from the plasma of SLE patients and evaluated the inhibition of lupus anticoagulant activity by hexagonal (II) phase PE in the presence and absence of purified plasma proteins. All six of the IgG lupus anticoagulant antibodies tested were inhibited by hexagonal (II) phase PE in the presence, but not the absence, of human prothrombin. In contrast, little or no inhibition was observed with prothrombin alone or with PE in combination with either beta2-glycoprotein I or annexin V. These data indicate that, for certain lupus anticoagulant antibodies, inhibition by hexagonal (II) phase PE is dependent on prothrombin, suggesting that these antibodies recognize a complex of PE and prothrombin.

Adult↗
PubMed1997

Developmental regulation of Zbu1, a DNA-binding member of the SWI2/SNF2 family.

The SWI2/SNF2 gene family has been implicated in a wide variety of processes, involving regulation of DNA structure and chromatin configuration, mitotic chromosome segregation, and DNA repair. Here we report the characterization of the Zbu1 gene, also known as HIP116, located on human chromosome band 3q25, which encodes a DNA-binding member of this superfamily. Zbu1 was isolated in this study by its affinity for a site in the myosin light chain 1/3 enhancer. The protein has single-stranded DNA-dependent ATPase activity, includes seven helicase motifs, and a RING finger motif that is shared exclusively by the RAD5, spRAD8, and RAD16 family members. During mouse embryogenesis, Zbu1 transcripts are detected relatively late in fetal development and increase in neonatal stages, whereas the protein accumulates asynchronously in heart, skeletal muscle, and brain. In adult human tissues, alternatively spliced Zbu1 transcripts are ubiquitous with highest expression in these tissues. Gene expression is also dramatically induced in human tumor lines and in Li-Fraumeni fibroblast cultures, suggesting that it is aberrantly regulated in malignant cells. The developmental profile of Zbu1 gene expression and the association of the protein with a tissue-specific transcriptional regulatory element distinguish it from other members of the SWI2/SNF2 family and suggest novel roles for the Zbu1 gene product.

Adenosine Triphosphatases↗