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J Devlin

Publications and source records attributed to J Devlin.

At least 19 recordsLinked to original sources
PubMed2005

Anti-CCP antibodies measured at disease onset help identify seronegative rheumatoid arthritis and predict radiological and functional outcome.

OBJECTIVE: Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been identified as highly specific for rheumatoid arthritis (RA). Studies suggest an association with radiographic outcome. The aims of this study were to assess the diagnostic and prognostic utility of the second-generation anti-CCP(2) test in a large cohort of early RA patients compared with connective tissue disease (CTD) controls. METHODS: One hundred and eighty-two patients with RA and 121 patients with CTD were recruited. All RA patients had less than 24 months of symptoms and had CRP, rheumatoid factor (RF), HLA typing (SE) and anti-CCP(2) antibodies measured at baseline. Function was assessed using the Health Assessment Questionnaire (HAQ) and X-rays performed at 0, 12 and 24 months. RESULTS: The anti-CCP(2) antibody test demonstrated a specificity of 91% and sensitivity of 81% for RA when compared with controls. In RF-negative patients, specificity was 92% and sensitivity 60%. Baseline demographics of the RA cohort showed mean age 57 yr, mean symptom duration 7 months, 63% RF-positive patients, 72% SE-positive, 81% CCP-positive and 21% erosive. The only predictor of change in Larsen score from 0 to 24 months in the cohort was the presence of the shared epitope (P<0.05) and in the RF-negative subgroup it was CCP(2) antibody titre >100 (P<0.05). Baseline HAQ was the only significant predictor of HAQ at 24 months, but in the RF-negative subgroup CCP(2) antibody titre >100 predicted a poor functional response at 24 months (P<0.05). CONCLUSIONS: This study confirms the diagnostic utility of anti-CCP(2) antibodies in early RA, particularly in seronegative patients, in whom anti-CCP(2) positivity also conferred prognostic utility for radiographic and functional outcomes.

Arthritis, Rheumatoid↗
PubMed2004

Transmission of donor melanoma to multiple organ transplant recipients.

Malignant melanoma represents the most common tumour responsible for donor-derived post transplantation malignancies. We report the varied presentation and outcome of three graft recipients (two kidney and hepatic) who developed metastatic melanoma following cadaveric organ transplantation from a single multiorgan donor. Two of the recipients presented with symptomatic metastatic lesions and the third patient, despite being carefully monitored, developed evidence of metastatic cutaneous melanoma. Two of the patients died as a direct result of their melanomas. The recipients of corneal and cardiac grafts remain disease-free. We conclude that despite careful screening, donor-derived tumours remain a not uncommon clinical entity. The identification of a lesion in one recipient should prompt immediate examination and investigation of the remaining recipients of multiorgan donations.

Adult↗
PubMed2003

Serum MMP-3 and MMP-1 and progression of joint damage in early rheumatoid arthritis.

OBJECTIVE: Expression and activation of matrix metalloproteinases such as MMP-3 (stromelysin-1) and MMP-1 (collagenase-1) are increased in patients with rheumatoid arthritis (RA). Previous negative reports of their value as predictors of joint damage may be due to the lack of a large longitudinal study of early RA patients. This study evaluated their use in assessing early untreated patients with RA and predicting subsequent joint damage. METHODS: Ninety-eight patients with early untreated RA of less than 12 months duration and 20 normal controls had baseline serum samples tested with a double-antibody enzyme-linked immunosorbent assay for each of MMP-1 and MMP-3. The subsequent changes in Larsen score (DeltaLarsen) and Health Assessment Questionnaire (DeltaHAQ) over the first 12 months were recorded. RESULTS: Baseline serum levels of MMP-3 and MMP-1 correlated significantly with baseline C-reactive protein (CRP) (r=0.42 and 0.49, P<0.001), DeltaHAQ (r=0.32 and 0.30, P<0.01) and DeltaLarsen (r=0.23 and 0.32, P<0.05) respectively. Analysis of the group of patients with a normal CRP at presentation (n=21) showed correlation of the baseline MMP-3 and MMP-1 with the presence of erosive disease during the first 12 months (r=0.52 and 0.65 respectively, P<0.05). Logistic regression analysis, in the patients who were non-erosive at presentation, showed that the strongest correlation with progression in Larsen score was the baseline MMP-3 level (r=0.30, P=0.01). CONCLUSIONS: Baseline serum MMP-1 and MMP-3 levels correlate with disease activity and predict functional and radiographic outcome in early untreated RA. They may have a particular value in predicting the progression of erosive disease in patients who are not erosive at presentation.

Arthritis, Rheumatoid↗
PubMed2002

Which patients stop working because of rheumatoid arthritis? Results of five years' follow up in 732 patients from the Early RA Study (ERAS).

OBJECTIVES: To assess the occurrence and prognostic factors for the ability to maintain paid work in patients with rheumatoid arthritis (RA). SETTING: Inception cohort of patients with RA recruited from rheumatology departments in nine NHS Hospital Trusts in England. PATIENTS: All consecutive patients with RA of less than two years' duration, before any second line (disease modifying) drug treatment, and followed up for five years. METHODS: Clinical, laboratory, and radiological assessments, and all treatments were recorded prospectively using a standardised format at presentation and yearly. OUTCOME MEASURES: Changes in, and loss of paid work by five years' follow up. RESULTS: 732 patients completed the five year follow up. 353/721 (49%) were gainfully employed at the onset of RA, 211 (60%) were still working at five years, 104 (29%) stopped because of the disease, and 31 (9%) retired for reasons other than RA. Work disability at five years was more likely in manual workers (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.4 to 3.8) and worse baseline Health Assessment Questionnaire (HAQ>1.5, OR 2.26, 95% CI 1.38 to 3.7). In combination with other baseline variables (erythrocyte sedimentation rate, sex, age of onset, and radiological erosions), employment outcome was predicted in 78% using multivariate analysis. CONCLUSIONS: Nearly half of the patients with RA were in paid employment at onset, work disability was an adverse outcome for a third of these patients by five years, and manual work and high baseline HAQ were important predictors for this. These details are likely to be useful to clinicians, health professionals, and patients in order to plan medical, orthopaedic, and remedial treatments in early RA. Future disease modifying treatments could be compared with this cohort of patients who were treated with conventional second line drugs.

Adult↗
PubMed2001

Differences in arterial and mixed venous IL-6 levels: the lungs as a source of cytokine storm in sepsis.

BACKGROUND: Several investigators have shown that blood levels of interleukin 6 (IL-6) correlate with the severity of illness in critically ill or injured patients. However, little is known about differential arterial and venous blood levels of the cytokine, especially across the lungs. METHODS: We measured differences in IL-6 levels in pulmonary and systemic arterial blood and then documented the production or elimination of IL-6 by the lungs in 19 patients with severe illness. Prospective data were obtained from multiple, simultaneous systemic arterial (ART) and mixed venous (MV) blood samples that were drawn for IL-6 analysis from systemic arterial and pulmonary artery catheters in 7 patients awaiting vascular operation and in 12 trauma patients being treated in the intensive care unit. RESULTS: A lung disorder was present in 5 patients (pneumonia [n = 1], lung trauma [n = 4]) and absent in the remaining 14 patients. The following data were obtained (mean +/- SD) from the highest MV IL-6 levels (pg/mL) in each patient. In patients with a lung disorder (n = 5) compared with those with no disorder (n = 14), ART IL-6 was 9309 +/- 12,521 versus 134 +/- 128 (P =.010), MV IL-6 was 5516 +/- 7420 versus 137 +/- 129 (P =.011), the absolute difference was 3793 +/- 5271 versus -3 +/- 15 (P =.011), and the percentage difference was 37.4% +/- 29.8% versus 1.5% +/- 12.3% (P =.001). The ART and MV IL-6 levels tended to be much higher in the 5 patients with pneumonia (n = 1) and lung injuries (n = 4) than in the patients without apparent pulmonary problems. In addition, the patients with a primary lung disorder demonstrated a net increase in IL-6 levels across the lungs, whereas there was no increase, but rather, a net reduction of IL-6 levels across the lungs in patients without a lung disorder. CONCLUSIONS: The lung appears to be a major producer of IL-6 in patients with an inflammatory lung process. There is a 39% increase in the level of IL-6 as it passes through inflamed lung, producing a marked difference in ART and MV IL-6 levels. Normal lung demonstrated little effect on either ART or MV IL-6 levels.

Arteries↗
PubMed2000

Premitotic chromosome individualization in mammalian cells depends on topoisomerase II activity.

When DNA topoisomerase II (topo II) activity is inhibited with a non-DNA-damaging topo II inhibitor (ICRF-193), mammalian cells become checkpoint arrested in G2-phase. In this study, we analyzed chromosome structure in cells that bypassed this checkpoint. We observed a novel type of chromosome aberration, which we call omega-figures. These are entangled chromosome regions that indicate the persistence of catenations between nonhomologous sequences. The number of omega-figures per cell increased sharply as cells evaded the transient block imposed by the topo II-dependent checkpoint, and the presence of caffeine (a checkpoint-evading agent) potentiated this increase. Thus, the removal of nonreplicative catenations, a process that promotes chromosome individualization in G2, may be monitored by the topo II-dependent checkpoint in mammals.

Animals↗
PubMed2000

The outcome of knee synovitis in early arthritis provides guidelines for management.

The aim of the study was to examine the clinical outcome of patients presenting to an early arthritis clinic with synovitis of the knee. The patients were assessed at presentation for evidence and pattern of joint inflammation. These patients were then reassessed at 3, 6 and 12 months and thereafter annually to determine clinical outcome. One thousand six hundred and thirty-three consecutive referrals were examined, 903 of whom had early synovitis. One hundred and thirty had knee synovitis at presentation, of whom 73 fulfilled ACR criteria for rheumatoid arthritis (RA) during the study. All 73 presented with a symmetrical polyarthritis that included the small joints and had persistent disease at 1 year. Of the remaining 57 patients, 61% of those presenting with an oligoarthritis and 33% with a polyarthritis (including knee synovitis) were in remission at 1 year. None of those presenting as a monoarthritis of the knee had inflammation at 1 year or fulfilled ACR criteria for RA at any time. It was concluded that patients presenting with knee synovitis in the absence of a small joint polyarthritis usually have a benign course following standard therapy. No patient who presented with monoarthritis developed RA. Knee synovitis as part of a polyarthritis (even when not fulfilling ACR criteria) probably justifies disease-modifying antirheumatic drug at presentation.

Antirheumatic Agents↗
PubMed2000

How does functional disability in early rheumatoid arthritis (RA) affect patients and their lives? Results of 5 years of follow-up in 732 patients from the Early RA Study (ERAS)

OBJECTIVES: To assess the impact of rheumatoid arthritis (RA) on function and how this affects major aspects of patients' lives. METHODS: The inception cohort of RA patients was recruited from rheumatology out-patient departments in nine National Health Service (NHS) hospital trusts in England. All consecutive patients with RA of less than 2 yr duration, prior to any second-line (disease-modifying) drug treatment were recruited and followed-up for 5 yr. Standard clinical, laboratory and radiological assessments, and all hospital-based interventions were recorded prospectively at presentation and yearly. The outcome measures were clinical remission and extra-articular features, functional ability [functional grades I-IV and Health Assessment Questionnaire (HAQ)], use of aids, appliances and home adaptations, orthopaedic interventions, and loss of paid work. RESULTS: A total of 732 patients completed 5 yr of follow-up, of whom 84% received second-line drugs. Sixty-nine (9.4%) had marked functional loss at presentation, compared with normal function in 243 (33%), and by 5 yr these numbers had increased in each group, respectively, to 113 (16%) and 296 (40%). Home adaptations and/or wheelchair use by 5 yr were seen in 74 (10%). Work disability was seen in 27% of those in paid employment at onset. One hundred and seventeen (17%) patients underwent orthopaedic surgery for RA, 55 (8%) for major joint replacements. Marked functional loss at 5 yr was more likely in women [odds ratio (OR) 1.63, 95% confidence interval (CI) 1.04-2.5], patients older than 60 yr (OR 1.94, 95% CI 1.3-2.9), and with HAQ > 1.0 at presentation (OR 4.4, 95% CI 2.8-7.0). CONCLUSIONS: Clinical profiles of RA patients treated with conventional drug therapy over 5 yr showed that a small proportion of patients (around 16%) do badly functionally and in terms of life events, whereas around 40% do relatively well. The details and exact figures of cumulative disability are likely to be useful to clinicians, health professionals and patients. The rate of progression and outcome in these patients can be compared against future therapies with any disease-modifying claims.

Adult↗
PubMed1999

Mutation of the 9q34 gene TSC1 in sporadic bladder cancer.

Deletions involving chromosome 9 occur in more than 50% of human bladder cancers of all grades and stages. Most involve loss of the whole chromosome or of an entire chromosome arm but some small deletions are found which can be used to define critical regions which may contain tumour suppressor genes. We have localized such a critical region of deletion at 9q34 between the markers D9S149 and D9S66, an interval which contains the Tuberous Sclerosis gene TSC1. Single strand conformation polymorphism (SSCP) and sequence analysis of TSC1 in bladder tumours and cell lines with 9q34 loss of heterozygosity (LOH) has identified five mutations in retained TSC1 alleles. Our results support the hypothesis that TSC1 can act as a bladder tumour suppressor gene.

Chromosomes, Human, Pair 9↗
PubMed1999

Evaluation of finger ultrasound in the assessment of bone status with application of rheumatoid arthritis.

Osteoporosis associated with active rheumatoid arthritis (RA) has been demonstrated in both the axial and peripheral skeleton, especially the periarticular regions more directly affected by the disease. Quantitative ultrasound (QUS) is a recently accepted tool for the assessment of bone status, and therefore could be used to monitor bone changes in RA patients. In a cross-sectional study we measured ultrasound velocity (Ad-SOS) through the proximal phalanges in three groups of female subjects. These included: 51 patients with rheumatoid arthritis (group 1), 44 general practitioner (GP)-referred patients for osteopenia (group 2) and 52 young healthy volunteers (group 3). For groups 1 and 2 bone mineral density (BMD) of the lumbar spine and proximal femur were also measured. For the RA patients BMD of the hand, measurement of hand function (HAQ and grip strength) and disease activity (ESR and CRP) were also assessed. The precision of long-term Ad-SOS measurements on volunteers gave a root mean square coefficient of variation (CV) of 0.7% and standardized CV of 3.6%. No statistically significant effect of dominance was observed in the measured Ad-SOS between the dominant and non-dominant hand (r = 0.96, p < 0.001). Ad-SOS was found to be significantly different in the three groups (p < 0.0001). Ad-SOS was highly dependent on age (r = -0.67), with a gradual reduction (-5.2 m/s per year) after the age of 30 years for female patients in both group 1 and group 2. Ad-SOS was significantly correlated with lumbar spine, femoral neck and hand BMD, with correlation coefficients of 0.49, 0.51 and 0.72 respectively for RA patients. Finger ultrasound was moderately correlated with measures of hand function, with coefficients of 0.37 and 0.39 for HAQ and grip strength respectively. Hand BMD also correlated to the same power with these parameters. Neither finger ultrasound nor BMD was significantly correlated with ESR and CRP (measures of disease activity). We have demonstrated that bone status can be assessed quickly and cheaply using a portable QUS device. Ad-SOS relates to the measure of hand function in RA patients. Longitudinal studies are required to determine the usefulness of finger ultrasound for monitoring disease progression or the effect of treatment in RA.

Adult↗
PubMed1999

Assessment of potential donors for living related liver transplantation.

BACKGROUND: Living related liver transplantation has been developed as an important potential source of organs for treatment of children with acute and chronic liver disease. A single UK centre performing living related liver transplantation was established in 1993. METHODS: Parents who were potential donors for their children for living related liver transplantation were assessed for suitability according to a protocol based on one developed and published by the University of Chicago Transplant Group. Records kept by the transplant coordinators were retrieved and data were extracted. RESULTS: Of 64 potential donors for 32 potential recipients ten were excluded at a preliminary stage. Fourteen ultimately became donors. Of 54 parents who began evaluation 23 were finally considered to be suitable. There were 19 non-disease-related reasons for unsuitability: blood group mismatch (eight cases), size discrepancy (six), pregnancy (two), oral contraceptive medication (one), vascular anatomy variant (one) and age (one). Sixteen were unsuitable because disease was found, namely fatty liver (four), thyroid disease (two), hepatitis B positivity (two), cardiac murmur (one), anaemia (one), glucose-6-phosphate dehydrogenase deficiency (one), diabetes mellitus (one) and psychological problems (one), and three parents were affected by the same disorder as the child (Alagille syndrome, one; mitochondrial disorder, one; recurrent cholestasis, one). Three parents were rejected for more than one reason. Both parents were unsuitable for donation in 21 per cent of cases. CONCLUSION: Parents approach living related liver transplantation with enthusiasm. They should be advised of the high chance of unsuitability, including the finding of significant pathology. The limitation of living related liver transplantation as the major source of organs for children is recognized.

Adolescent↗
PubMed1999

Does the age of onset of rheumatoid arthritis influence phenotype?: a prospective study of outcome and prognostic factors.

OBJECTIVE: To identify factors affecting prognosis in patients with late-onset rheumatoid arthritis (RA). METHODS: A total of 400 patients with RA fulfilling the American College of Rheumatology criteria for diagnosis were prospectively recruited from two hospital rheumatology centres. Of these patients, 214 had disease onset above age 65 yr (LORA) and 186 below age 65 yr (YORA). Follow-up clinical, functional, laboratory and radiological assessments were compared. The Ritchie articular index (RAI) and joint erosions were used as markers of disease activity and damage, respectively. Disability was assessed using the Stanford Health Assessment Questionnaire (HAQ). RESULTS: At median follow-up of 3.6 yr, the frequency of joint erosions was similar (YORA, 51.6%; LORA, 54.2%). The remission rate was greater in the LORA group (YORA, 20.4%; LORA, 45.8%, P < 0.01). Factors associated with the development of erosions were: IgM rheumatoid factor (RF) seropositivity [odds ratio (OR) = 4.24, 95% confidence interval (CI) 2.56, 6.94], HLA DR4 (OR = 2.07, 95% CI 1.28, 3.35) and elevated inflammatory markers (OR = 1.81, 95% CI 1.04, 3.14). Continuous steroid use >3 months for the LORA group was associated with increased erosions (OR = 4.09, 95% CI 1.81, 9.27). LORA patients (OR = 2.99, 95% CI 1.77, 5.02) were more likely to go into remission and IgM RF-seropositive patients less likely to go into clinical remission (OR = 0.47, 95% CI 0.28, 0.77). Female patients with a high HAQ score at presentation experienced a poor functional outcome (female OR = 3.01, 95% CI 1.59, 5.68; high HAQ OR = 3.02, 95% CI 1.98, 4.62). CONCLUSION: LORA can be as damaging as classical RA and joint erosions are often observed at presentation. Being RF seropositive, DR4 positive, and having elevated inflammatory markers at onset, were associated with poor radiological outcome irrespective of age of onset. Being female and having marked disability at presentation were associated with poor functional outcome in both groups. These findings suggest that treatment approaches used in classical YORA should be instituted with equal vigour in patients with LORA.

Adult↗
PubMed1999

Granisetron (Kytril) suppresses methotrexate-induced nausea and vomiting among patients with inflammatory arthritis and is superior to prochlorperazine (Stemetil).

OBJECTIVE: Methotrexate (MTX) is an increasingly popular anti-rheumatic drug with its usefulness limited by toxicity, most commonly gastrointestinal (GI). The aim of the study was to study the effectiveness of the 5-HT3 receptor antagonist granisetron (GR) in the therapy of MTX-induced nausea. METHODS: A single-blind 8 week pilot study with random allocation to either GR 1 mg or prochlorperazine (Stemetil; PCh) 10 mg was undertaken in 13 patients who were taking or had taken MTX for either rheumatoid arthritis (10) or psoriatic arthritis (3). RESULTS: One in six patients treated with PCh completed the 8 week study compared to 7/7 treated with GR. After switching of symptomatic patients, 11 completed the study on GR and median improvement was by two grades (P < 0.001) with a significantly better visual analogue scale score for patient satisfaction compared to PCh. CONCLUSION: Treatment with GR may be useful in establishing and maintaining some patients on MTX where GI toxicity would have precluded such therapy.

Antiemetics↗
PubMed1998

Defining the outcome of immunosuppression withdrawal after liver transplantation.

Successful immunosuppression withdrawal should benefit the natural history of organ transplantation patients. To identify the clinical hazards of removing drug treatment and possible characteristics that predict a favorable outcome in long-term liver recipients, immunosuppression was withdrawn completely and the clinicopathological outcome documented in 18 liver recipients. Indication for transplantation, HLA matching, early rejection history, and presence of microchimerism were examined as predictors of outcome. Chimerism was determined by polymerase chain reaction-based examination for donor-specific HLA-DRB1 alleles and Y-gene-specific nucleotide sequences. At 3 years, 5 patients (28%) remained completely off immunosuppression; 12 patients (67%) experienced histological graft changes: acute rejection in 4, portal tract inflammation/hepatitis in 7, and necrosis in 1. Hepatitis B or C viral infections did not account for the nonrejection patterns. Unmasking of systemic disorders occurred. Chimerism, demonstrated in 7 patients (39%), with skin the optimal tissue, was not associated with tolerance. Parameters associated with successful drug withdrawal were transplantation for non-immune-mediated liver disorders, fewer donor-recipient HLA A, B, and DR mismatches, and a low incidence of early rejection. Immunosuppression withdrawal is a feasible option in a proportion of selected liver recipients, but identification of tolerant patients remains imprecise.

Adult↗
PubMed1998

Tolerance and latent cellular rejection in long-term liver transplant recipients.

Tolerance develops in a proportion of long-term liver transplant recipients but currently cannot be identified before an attempt at withdrawal from immunosuppression therapy. In the present study, we have examined the immunophenotypic characteristics of the cellular infiltrate in portal tracts and lobules as observed in liver biopsy specimens in relation to the outcome of subsequent withdrawal from immunosuppression therapy. Cryostat biopsy specimens from 27 long-term recipients before drug withdrawal, and from 10 patients with recent transplants who were having acute rejection, were analyzed. Immunohistochemical staining was performed for CD3+ (pan T cell), CD8+ (cytotoxic), CD4+ (helper), CD45RO+ (memory), CD45RA+ (naive), CD56+ (natural killer), CD68+ (macrophage), and CD8+ perforin+ cells. Fewer CD8+ and CD3+ cells were present in the lobular areas of biopsy specimens from patients who were successfully withdrawn from immunosuppression therapy (n = 6) compared with biopsy specimens from patients with nontolerant grafts (n = 9; 15 vs. 23 cells/high-power field [hpf] [P < .01] and 16 vs. 26 cells/hpf [P < .03], respectively) or biopsy specimens obtained during acute rejection (15 vs. 31 cells/hpf [P < .01] and 16 vs. 32 cells/hpf [P < .01]). Cell frequencies in the biopsy specimens of nontolerant long-term patients were similar to those found with acute rejection. Immunophenotyping the lobular inflammation within long-term liver allografts assists in identifying those patients in whom drug withdrawal is likely to be unsuccessful and in whom it is postulated a form of inactive, latent cellular rejection exists.

Adolescent↗