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Biomedical subjects

A Calin

Publications and source records attributed to A Calin.

At least 37 records · Page 2Linked to original sources
PubMed1999

Clinical relevance of C-reactive protein in axial involvement of ankylosing spondylitis.

To evaluate C-reactive protein (CRP) as a potential useful criterion of symptomatic severity of ankylosing spondylitis (AS), we conducted both a cross sectional and a longitudinal (6 week) clinical study in 443 patients with axial involvement in AS. During the 6 weeks of the study, patients received either a placebo or an active nonsteroidal antiinflammatory drug (NSAID). At baseline, CRP was increased in 173 patients (39%). A multivariate analysis in which CRP was the dependent variable and all clinical assessment criteria (pain, range of motion, functional disability, hemoglobin, platelet count) the independent variables showed that range of motion and laboratory signs of inflammation were the most significant variables to explain the CRP values. A similar multivariate analysis conducted on the changes in the variables during the 6 weeks of the study concluded that night pain and laboratory signs of inflammation were the most significant variables explaining the changes in CRP values. The capacity of CRP to discriminate between an active NSAID and a placebo was moderate. This study suggests than an increase in CRP in patients with AS with axial involvement is not a rare phenomenon and might be correlated with the clinical severity of the disease. This outcome measure does not seem to be of great interest in the short term evaluation of fast acting drugs. However, the longterm clinical significance of such an increase in CRP remains to be investigated.

Adult↗
PubMed1999

Outcome variables in ankylosing spondylitis: evaluation of their relevance and discriminant capacity.

The clinical status of ankylosing spondylitis (AS) can be defined by several domains (e.g., pain, function, metrology, laboratory) and subcomponents within each domain (e.g., pain using visual analog scale, Schober's within metrology). Our aim was (1) To define groups of highly correlated variables in order to determine the most relevant; and (2) to evaluate the capacity of different clinical and biological variables that best discriminate between placebo and active nonsteroidal drugs in AS. Patients with active AS (n=423) were followed prospectively over 6 weeks while receiving placebo (n=121) or active nonsteroidal antiinflammatory drugs (n=352). Eighteen variables were studied, including global assessment, pain, stiffness, functional indices, metrology, disease activity index, and laboratory markers. Statistics included (1) Evaluation of the relevance of the different domains by multivariate analysis (CART tree-structure classification; variable clustering); and (2) evaluation of the discriminant capacity by univariate analysis [i.e., differences in the standardized response mean (SRM) (mean change/SD) between placebo and active drug. A value > or =0.60 was considered relevant]. Four clusters were identified (patient's subjective perception, inflammatory symptoms, metrology, laboratory data) with multiple correlation R2 revealing the most relevant variables to be the Bath Ankylosing Spondylitis Functional Index (BASFI; 0.75), night pain (0.62), Schober's test (0.58), and platelet count (0.55), respectively, within each cluster. In terms of discriminant power (SRM) the patient perceived global status (0.84), lumbar pain (0.73), night pain (0.71), physician global assessment (0.66), and BASFI (0.65) were most relevant in the univariate analysis. Among the 4 most relevant domains are subjective perception, inflammatory symptoms, metrology, and laboratory. Multivariate analysis of the data reveals that the spinal pain and the patient global assessment are the variables that best discriminate between placebo and active nonsteroidal drug in short term studies.

Adult↗
PubMed1999

A new dimension to outcome: application of the Bath Ankylosing Spondylitis Radiology Index.

Our aim was to develop a reproducible and simple radiological scoring system for ankylosing spondylitis (AS) to use in cross sectional and prospective studies. Regarding validation of the BASRI (Bath Ankylosing Spondylitis Radiology Index), radiographs of 470 patients with AS were scored using the New York criteria for the sacroiliac joints. The lumbar and cervical spine, and hips were similarly graded 0-4. These scores were added together to give BASRI-t (total) and if the hips are excluded to give BASRI-s (spine). Radiographs of 188 patients were used to test reproducibility. Blinded radiographs of 89 non-AS patients were included randomly to assess disease specificity. Sensitivity to change was assessed using 177 radiographs from 40 patients. Regarding the cross sectional study, 2200 radiographs of 550 (104 F:446 M) patients were randomly selected and scored using BASRI. The frequency distribution of BASRI-t and BASRI-s were plotted using a probit plot. Inter and intraobservation showed between 73 and 82% and 73 and 88% complete agreement, with specificity of 0.78-0.89, suggesting scores are disease-specific. Sensitivity to change became apparent at 2 years (p<0.05). Scoring required 30 seconds to complete. BASRI-t was found to be normally distributed using a probit plot. The mean BASRI scores (total, spinal, hip) increased with disease duration. The correlation, however, was poor (r=0.293, 0.347, 0.263, respectively). Those with hip involvement had more severe spinal disease (p<0.0001). Men had more severe spinal disease than women (p<0.0001). We conclude BASRI is a reliable and rapid method to grade radiographic changes in AS. Using this scoring system it can be seen that AS is a slowly progressive disease with much individual variation. Hip patients have more severe spinal disease than those without hip involvement and men have more severe spinal disease than women.

Adult↗
PubMed1998

The effect of HLA-DR genes on susceptibility to and severity of ankylosing spondylitis.

OBJECTIVE: To analyze the effect of HLA-DR genes on susceptibility to and severity of ankylosing spondylitis (AS). METHODS: Three hundred sixty-three white British AS patients were studied; 149 were carefully assessed for a range of clinical manifestations, and disease severity was assessed using a structured questionnaire. Limited HLA class I typing and complete HLA-DR typing were performed using DNA-based methods. HLA data from 13,634 healthy white British bone marrow donors were used for comparison. RESULTS: A significant association between DR1 and AS was found, independent of HLA-B27 (overall odds ratio [OR] 1.4, 95% confidence interval [95% CI] 1.1-1.8, P = 0.02; relative risk [RR] 2.7, 95% CI 1.5-4.8, P = 6 x 10(-4) among homozygotes; RR 2.1, 95% CI 1.5-2.8, P = 5 x 10(-6) among heterozygotes). A large but weakly significant association between DR8 and AS was noted, particularly among DR8 homozygotes (RR 6.8, 95% CI 1.6-29.2, P = 0.01 among homozygotes; RR 1.6, 95% CI 1.0-2.7, P = 0.07 among heterozygotes). A negative association with DR12 (OR 0.22, 95% CI 0.09-0.5, P = 0.001) was noted. HLA-DR7 was associated with younger age at onset of disease (mean age at onset 18 years for DR7-positive patients and 23 years for DR7-negative patients; Z score 3.21, P = 0.001). No other HLA class I or class II associations with disease severity or with different clinical manifestations of AS were found. CONCLUSION: The results of this study suggest that HLA-DR genes may have a weak effect on susceptibility to AS independent of HLA-B27, but do not support suggestions that they affect disease severity or different clinical manifestations.

Age of Onset↗
PubMed1998

A genome-wide screen for susceptibility loci in ankylosing spondylitis.

OBJECTIVE: To localize the regions containing genes that determine susceptibility to ankylosing spondylitis (AS). METHODS: One hundred five white British families with 121 affected sibling pairs with AS were recruited, largely from the Royal National Hospital for Rheumatic Diseases AS database. A genome-wide linkage screen was undertaken using 254 highly polymorphic microsatellite markers from the Medical Research Council (UK) (MRC) set. The major histocompatibility complex (MHC) region was studied more intensively using 5 microsatellites lying within the HLA class III region and HLA-DRB1 typing. The Analyze package was used for 2-point analysis, and GeneHunter for multipoint analysis. RESULTS: When only the MRC set was considered, 11 markers in 7 regions achieved a P value of < or =0.01. The maximum logarithm of odds score obtained was 3.8 (P = 1.4 x 10(-5)) using marker D6S273, which lies in the HLA class III region. A further marker used in mapping of the MHC class III region achieved a LOD score of 8.1 (P = 1 x 10(-9)). Nine of 118 affected sibling pairs (7.6%) did not share parental haplotypes identical by descent across the MHC, suggesting that only 31% of the susceptibility to AS is coded by genes linked to the MHC. The maximum non-MHC LOD score obtained was 2.6 (P = 0.0003) for marker D16S422. CONCLUSION: The results of this study confirm the strong linkage of the MHC with AS, and provide suggestive evidence regarding the presence and location of non-MHC genes influencing susceptibility to the disease.

Chromosome Mapping↗
PubMed1998

Reference centile charts for measures of disease activity, functional impairment, and metrology in ankylosing spondylitis.

OBJECTIVE: To construct reference centile charts for validated measures of disease activity, functional impairment, and metrology (the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Bath Ankylosing Spondylitis Functional Index [BASFI], and Bath Ankylosing Spondylitis Metrology Index [BASMI]) in a population of patients with AS, and to explore the potential application of these charts in patient care and clinical research. METHODS: We collected BASDAI and BASFI data on 2,979 patients with AS from the Royal National Hospital for Rheumatic Diseases (RNHRD) database and BASMI data on 393 patients at RNHRD. Data on age, sex, and duration of AS were also obtained. Centile charts were constructed for the BASDAI, BASFI, and BASMI in both males and females, with duration of AS as the time-dependant variable. Where necessary, BASDAI, BASFI, and BASMI raw scores were transformed to ensure that the indices were normally distributed over the range of disease duration, and allowance was made for change in variability of the indices. RESULTS: Linear models were fitted to the mean and standard deviations of BASDAI, BASFI, and BASMI scores in males and females as a function of disease duration. A standard deviation score plot confirmed goodness of fit of the models, and fitted centiles were derived. Charts showing the 5th, 10th, 25th, 50th, 75th, 90th, and 95th centiles were constructed. The charts confirmed that AS remains active after 40 years' duration (mean BASDAI score 2.22 and 2.99 in males and females, respectively). The charts also demonstrated that females have greater disease activity and more functional impairment than males, despite better metrology. CONCLUSION: The use of centile reference charts for disease activity, functional impairment, and metrology in AS will allow physicians and patients to interpret index scores relative to a reference population and will provide the opportunity to assess change over time and response to therapeutic interventions, to improve definition of disease status, and to enhance patients' involvement in their care.

Aging↗
PubMed1998

The Bath Ankylosing Spondylitis Radiology Index (BASRI): a new, validated approach to disease assessment.

OBJECTIVE: To develop a reproducible and simple radiologic scoring system for the spine in patients with ankylosing spondylitis (AS): the Bath Ankylosing Spondylitis Radiology Index for the spine (BASRI-s). METHODS: Radiographs of 470 patients with AS were scored using the New York criteria for the sacroiliac joints and, similarly, grading the lumbar and cervical spine on a scale of 0-4 (for normal, suspicious, mild, moderate, and severe). These 3 scores were added together to produce the BASRI-s score (scored 2-12). Radiographs of 188 patients were used to test reproducibility. Blinded radiographs of 89 non-AS patients were included, randomly, to assess disease specificity. Sensitivity to change was assessed using 177 radiographs from 58 AS patients. RESULTS: Intra- and interobserver variation showed 75-86% and 73-79% complete agreement at all sites, respectively. Specificities of 0.83-0.89 suggested that the lumbar and cervical spine BASRI scores were disease specific. Sensitivity to change became apparent at 2 years (P < 0.001). Using a lateral view and an anteroposterior view of the lumbar spine was more sensitive than using a lateral view alone. Grading a set of radiographs (sacroiliac joints, lumbar spine, and cervical spine) took 30 seconds. CONCLUSION: BASRI is a reliable method for grading radiographic changes in patients with AS. It is disease specific, sensitive to change, valid, simple, and rapid to perform.

Adult↗
PubMed1998

The role of germline polymorphisms in the T-cell receptor in susceptibility to ankylosing spondylitis.

The role of germline polymorphisms of the T-cell receptor A/D and B loci in susceptibility to ankylosing spondylitis was investigated by linkage studies using microsatellite markers in 215 affected sibling pairs. The presence of a significant susceptibility gene (lambda > or = 1.6) at the TCRA/D locus was excluded (LOD score < -2.0). At the TCRB locus, there was weak evidence of the presence of a susceptibility gene (P = 0.01, LOD score 1.1). Further family studies will be required to determine whether this is a true or false-positive finding. It is unlikely that either the TCRA/D or TCRB loci contain genes responsible for more than a moderate proportion of the non-MHC genetic susceptibility to ankylosing spondylitis.

Family Health↗
PubMed1998

Exercise in ankylosing spondylitis: how much is optimum?

OBJECTIVE: To evaluate how much exercise patients with ankylosing spondylitis perform on a regular basis, to analyze demographic and clinical variables that might influence adherence to exercise, and to determine the effect of exercise on disease activity and function. METHODS: We analyzed 4282 patients who completed a self-administered questionnaire regarding physical exercise. To determine the relationship between exercise, demographic data, and clinical variables, patients who exercise 2 to 4 hours and 10 or more hours per week were compared to nonexercising controls matched for age, sex, and disease duration. RESULTS: Most of the patients reported 2 to 4 hours of exercise or no exercise. The group who performed moderate exercise had improved function and lower disease activity (p < 0.001, p < 0.015, respectively). The group who performed intensive exercise had improved function, but no difference in disease activity was found (p=0.033, p=0.394, respectively). Adherence to a regular exercise regime is associated with rheumatologist followup, beliefs in the benefits of exercise, and a higher education level. CONCLUSION: This study suggests there is an optimum duration for exercise performed over a weekly period. Consistency, rather than quantity, is of most importance. Individuals most likely to follow this regime attend a rheumatologist, believe that exercise is of benefit, and are in the higher education category. Those who are less educated and followed by general practitioners should be targeted.

Adult↗
PubMed1997

Susceptibility to ankylosing spondylitis in twins: the role of genes, HLA, and the environment.

OBJECTIVE: To determine the relative effects of genetic and environmental factors in susceptibility to ankylosing spondylitis (AS). METHODS: Twins with AS were identified from the Royal National Hospital for Rheumatic Diseases database. Clinical and radiographic examinations were performed to establish diagnoses, and disease severity was assessed using a combination of validated scoring systems. HLA typing for HLA-B27, HLA-B60, and HLA-DR1 was performed by polymerase chain reaction with sequence-specific primers, and zygosity was assessed using microsatellite markers. Genetic and environmental variance components were assessed with the program Mx, using data from this and previous studies of twins with AS. RESULTS: Six of 8 monozygotic (MZ) twin pairs were disease concordant, compared with 4 of 15 B27-positive dizygotic (DZ) twin pairs (27%) and 4 of 32 DZ twin pairs overall (12.5%). Nonsignificant increases in similarity with regard to age at disease onset and all of the disease severity scores assessed were noted in disease-concordant MZ twins compared with concordant DZ twins. HLA-B27 and B60 were associated with the disease in probands, and the rate of disease concordance was significantly increased among DZ twin pairs in which the co-twin was positive for both B27 and DR1. Additive genetic effects were estimated to contribute 97% of the population variance. CONCLUSION: Susceptibility to AS is largely genetically determined, and the environmental trigger for the disease is probably ubiquitous. HLA-B27 accounts for a minority of the overall genetic susceptibility to AS.

Adult↗
PubMed1997

Cervical spine surgery in ankylosing spondylitis: is the outcome good?

OBJECTIVE: To assess retrospectively, the outcome of cervical spine surgery in patients with ankylosing spondylitis (AS). METHODS: A cross-sectional study of 3464 patients with identified AS, 19 patients of whom had cervical spine surgery. A self-administered questionnaire (including the use of 10 cm visual analogue scales, 0 = none, 10 = worst) assessing the complications of the surgery, patients' neck symptoms and post-surgery functional ability was sent to the 19 patients. Available casenotes and radiographs were reviewed. RESULTS: The mean duration of follow-up was 10 years. One patient had two separate cervical spine operations. The types of surgery performed included cervical fusion (n=7), osteotomy (n=7) and laminectomy (n=6). Six patients had minor complications as a result of surgery. The majority of patients (93%) felt that their surgery had been successful. Most patients (81%) had a reduction in neck pain (mean pain score=3.1, SD 2.8) but increased neck stiffness (mean stiffness score=8.0, SD 2.9). Postoperative radiographs of 7 patients showed complete ankylosis of the cervical spine. Generally, few patients reported difficulty with reading/watching television (6%), sleep (19%) or driving (36%). A third of the patients were still in full time employment. CONCLUSIONS: About 1 in 200 patients with AS undergo cervical spine surgery. The surgery is often successful and complications are usually minor. Neck pain is often better after surgery and any remaining neck symptoms do not significantly affect the patient's sleep or functional activities. In this retrospective study, the long term outcome of cervical spine surgery in patients with AS appears to be good.

Adult↗
PubMed1997

Juvenile onset ankylosing spondylitis--more girls than we thought?

OBJECTIVE: To define the sex ratio of juvenile onset ankylosing spondylitis (AS) among a large population. METHODS: Using a standard questionnaire, data were collected from 3362 subjects, members of the National Ankylosing Spondylitis Society and patients at a tertiary referral center. RESULTS: Of 3362 patients, 2461 (73%) were male; male:female sex ratio was 2.7:1. Of the total, 379 (11%) had disease onset between the ages of 5 and 16 years. Of these, 278 were boys and 101 girls, giving an overall male:female ratio, in juvenile AS, of 2.6:1. For those with onset ages 5-13 years there was a ratio of 2.1:1, while for those aged over 14 years at onset, the ratio was 3.2:1. CONCLUSION: Older published ratios, ranging from 4.5:1 to 6:1, used smaller samples, focusing only on subjects who were juveniles at the time of the study. Our data collection method, which recruits from 2 sources and includes adults with juvenile onset, attempts to avoid these methodological problems. The data suggest a higher incidence of juvenile AS among females than previously described.

Adolescent↗
PubMed1997

Socioeconomic status in ankylosing spondylitis: relationship between occupation and disease activity.

OBJECTIVE: To identify the socioeconomic status through occupation of a large cohort of patients with ankylosing spondylitis (AS) and to determine possible relationships between occupation and clinical variables. METHODS: We analyzed the employment status of 1,044 patients with AS. RESULTS: 85% of patients (890 of 1,044) were in full employment at the time of the assessment compared to 15% who were unemployed. When 50 employed patients were compared to 50 unemployed cases, the latter had increased disease activity and lower psychosocial well being. CONCLUSION: Employed patients from the higher occupational group (I), had less disease activity, and lower pain and depression than patients from the lowest occupational group (IV).

Adult↗
PubMed1997

Low dose amitriptyline in ankylosing spondylitis: a short term, double blind, placebo controlled study.

OBJECTIVE: To define the effect of low dose amitriptyline on fatigue, pain, and stiffness in patients with ankylosing spondylitis (AS). METHODS: One hundred consecutive patients with AS were randomized to receive low dose amitriptyline up to 30 mg nightly or placebo for 2 weeks. Patients were assessed by the Bath Ankylosing Spondylitis Disease Activity (BASDAI) and Functional (BASFI) Indices pre and post-treatment. RESULTS: Eighty-eight patients (44 amitriptyline, 44 placebo) completed the study. Eight (5 amitriptyline, 3 placebo) stopped treatment because of side effects (e.g., drowsiness, dryness of mouth) and 4 provided insufficient data. Compared to placebo, the patients taking amitriptyline showed significantly greater improvement in restful sleep (66 vs 20%; p < 0.001) and their disease activity scores [BASDAI amitriptyline 1.18 (23%) vs placebo 0.52 (10%); p = 0.024]. All other variables showed a trend to greater improvement by amitriptyline, although the differences were not statistically significant. CONCLUSION: (1) In a 2 week study, low dose amitriptyline significantly improved sleep in AS and was well tolerated; (2) as defined by BASDAI, there was a significant reduction in disease activity with amitriptyline; (3) compared to placebo, there was a nonsignificant trend toward improvement in function; and (4) in spite of improvement in pain, fatigue, and sleep with amitriptyline, stiffness was not increased.

Adult↗
PubMed1997

Preliminary core sets for endpoints in ankylosing spondylitis. Assessments in Ankylosing Spondylitis Working Group.

An international working group was formed to select core sets to be used as endpoints in clinical trials in ankylosing spondylitis (AS). The results of the first steps of the selection of these core sets are described. The definition of the settings for which the core set will be intended are defined. The methods used to select the core sets were a combination of literature search, nominal group discussions, and plenary discussions. The following settings were defined: disease controlling antirheumatic therapy (DC-ART), symptom modifying antirheumatic drugs (SMARD)/physical therapy, and clinical record keeping. Over 110 variables used as endpoints in AS were found in the literature. The preliminary core set for DC-ART consists of physical function, pain, spinal mobility, patient global assessment, peripheral joints/entheses, x-ray spine. The selected core set for SMARD/physical therapy includes physical function, pain, spinal mobility, spinal stiffness, and patient global assessment. The core set for clinical record keeping includes all measures of the SMARD/physical therapy core set completed by peripheral joints/entheses, and acute phase reactants. Three preliminary core sets for AS have been defined. Further research will be performed to select specific measures for all domains.

Antirheumatic Agents↗