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J Devlin

Publications and source records attributed to J Devlin.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effect of vitamin D receptor gene alleles on bone loss in early rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is a polygenic disease characterized by localized joint destruction and generalized osteoporosis resulting in increased fracture risk. The pathogenetic mechanisms that determine the severity of generalized bone loss in RA are poorly understood. Polymorphisms in the vitamin D receptor (VDR) gene have been described as a significant determinant of bone turnover and mass. In this prospective study we describe VDR gene allele effects on bone loss in patients with early RA. METHODS: We recruited 232 patients with early RA. Bone mineral density measurements were repeated in 167 patients. Serial clinical and laboratory measures were recorded during the period of followup. DNA extraction, polymerase chain reaction amplification, and restriction fragment length polymorphism analysis of VDR alleles were performed using standard techniques. Presence of the Taq restriction site for both alleles was denoted "tt", and absence "TT". RESULTS: In women with RA the tt genotype group lost bone more rapidly than subjects with TT genotype at both the lumbar spine (-0.1 vs -4.9% p.a, respectively; p < 0.05) and femoral neck (-3.9 vs -9.6%, respectively; p < 0.01). The effect was independent of other disease characteristics. CONCLUSION: The presence of the VDR gene "t" allele in female patients with RA was associated with accelerated bone loss.

Alleles↗
PubMed1998

Osteoclastic activation is the principal mechanism leading to secondary osteoporosis in rheumatoid arthritis.

OBJECTIVE: To use clinical measures and biochemical markers of bone turnover to investigate mechanisms of generalized bone loss in early rheumatoid arthritis (RA). METHODS: We studied 232 patients with RA of less than 2 years' duration and 72 healthy controls using serial dual x-ray absorptiometry scanning of lumbar spine and hips. Patients attended the clinic for clinical and laboratory assessment with storage of serum, urine, and plasma at each visit. Change in bone mineral density (BMD) was calculated for patients and controls and compared with baseline and mean serial values of bone markers over the same intervals. Serum was assayed for procollagen I carboxyterminal propeptide (PICP) and skeletal alkaline phosphatase (sALP); urine for pyridinoline and deoxypyridinoline corrected for creatinine; and plasma for interleukin 1 (IL-1) and IL-6. RESULTS: Patients lost bone significantly faster than controls at all sites (p < 0.01 for all). At first visit patients had significantly lower PICP levels than controls (p < 0.05) and sALP correlated with initial BMD in both patients (p < 0.01, r > 0.35, all sites) and controls (p < 0.0001, r > 0.50, all sites). We rescanned 167 patients at one year and 121 patients at 2 years. Mean urinary pyridinoline and deoxypyridinoline levels correlated strongly with BMD change at all sites, were increased in patients with active disease (p < 0.005), and correlated closely with mean C-reactive protein (CRP) (p < 0.005, r > 0.41 for both). CONCLUSION: This study suggests that osteoclastic activation, rather than suppression of bone formation, is the dominant process leading to bone loss in early RA. Although urinary pyridinoline and deoxypyridinoline were excellent markers of BMD change, CRP was found to be best overall. This provides a rational approach for selecting and treating patients with RA to reduce their established longterm risk of osteoporotic fracture.

Absorptiometry, Photon↗
PubMed1997

Clinical characteristics affecting the outcome of liver retransplantation.

BACKGROUND: The outcome of retransplantation remains unsatisfactory when compared with primary transplantation of the liver. The aim of the present study was to determine which preoperative clinical and laboratory risk variables are implicated in the poorer outcome. METHODS: The preoperative status of 70 retransplanted patients was compared with a group of 303 time-matched recipients receiving their first graft. RESULTS: Survival at 1 year was reduced in the retransplant versus the primary transplant group (50% vs. 80%, P<0.001). Preoperatively older age, high United Network of Organ Sharing score, inpatient status, elevated bilirubin, and creatinine levels were associated with increased mortality after a second transplant. Preoperatively, the retransplant group had higher encephalopathy grades, were more likely to be inpatients, and had higher serum creatinine, bilirubin, and white cell levels than the primary recipients (P<0.05 in all cases). The median length of inpatient stay was longer after the second transplant (25 vs. 19 days, P<0.001). CONCLUSIONS: These factors assist in the stratification of patients awaiting retransplantation; however, the outcome of this procedure is only likely to be improved with an earlier identification of the patients who require it, along with an increased priority in organ allocation.

Adolescent↗
PubMed1997

Graft and systemic disease in long-term survivors of liver transplantation.

In this clinicopathological study, we have examined the prevalence of biochemical and histological graft abnormalities in 116 patients who have lived for longer than five years since orthotopic liver transplantation (mean, 8.4 years [range, 5.2-19.5 years]). In each patient, the protocol biopsy was carried out in addition to full clinical, biochemical, and immunological evaluation. The renal function was preserved in most patients (mean creatinine, 86 micromol/L [0.95 mg%]) with only 35% showing any degree of impairment, and only one patient with pretransplant renal failure required dialysis. Forty one (35%) of the patients had normal biochemical liver function tests (LFTs); 19 of these patients had histologic abnormalities. Of the remaining 75 patients with abnormal LFTs, 65 were found to have histological abnormalities on liver biopsy. Some of the 84 patients with an abnormal histology had more than one finding but were placed into 6 categories according to the main change as follows: chronic hepatitis in 27; primary biliary cirrhosis-like changes in 8; cholangitis in 15; structural anomalies in 26; chronic rejection in 2; mild acute cellular rejection in 1; and miscellaneous in 5. The recurrence of B, C, or autoimmune hepatitis accounted for 14 cases of chronic hepatitis, whereas, in 13 cases, no cause could be detected. The latter cases included 8 patients who had liver transplants for primary biliary cirrhosis (PBC), leaving suboptimally treated rejection or disease recurrence as possible causes. Characteristic histological features of PBC were observed in 8 additional cases that had liver transplantations for this disease. Of the 26 cases with structural anomalies, various types of occlusive vasculopathy were detected during pre- or posttransplantation in 12 cases. All but one of these were maintained on azathioprine, the only possible etiological factor in the 14 other cases, 5 of whom showed stabilization or clinical and histological improvement following withdrawal of the drug. De-novo malignancy was seen in 3.4% of cases, causing mortality in only one patient to date. This study demonstrates an unexpectedly high prevalence of histological abnormalities that is found often in the presence of normal biochemical liver-function in liver grafts of long-term survivors. Although graft loss at this time is rare, protocol liver biopsies at 5 years, and thereafter at 2-year intervals, may allow for earlier beneficial therapeutic intervention.

Adolescent↗
PubMed1997

N-acetylcysteine improves indocyanine green extraction and oxygen transport during hepatic dysfunction.

OBJECTIVES: To investigate whether the beneficial systemic hemodynamic effects of N-acetylcysteine, an agent that increases cyclic guanosine monophosphate (cGMP) concentration in fulminant hepatic failure, are present in a range of liver disorders and what concurrent effect this agent has on the hepatic-splanchnic circulation. SETTING: Liver Failure Unit, King's College Hospital, London, UK. PATIENTS: Fifteen patients with hepatic dysfunction who were mechanically ventilated, either after liver transplantation or during an acute or decompensated chronic liver disorder. INTERVENTIONS: Prostacyclin was administered at a continuous infusion rate of 5 ng/kg/min for 60 mins. After a washout period, the hemodynamic effects of this infusion were compared with the effects present during infusion of N-acetylcysteine at 150 mg/kg in 250 mL of 5% dextrose in water over 15 mins and then 50 mg/kg in 250 mL of 5% dextrose for 45 mins at an infusion rate of 62.5 mL/hr. MEASUREMENTS AND MAIN RESULTS: Following N-acetylcysteine infusion, the baseline oxygen delivery (DO2) increased from 667 +/- 154 to 751 +/- 166 (SD) mL/min/m2, and oxygen consumption (VO2) improved in 13 of 15 patients (150 +/- 30 to 169 +/- 25 mL/min/m2) (p< .01). Indocyanine green clearance, as determined by a fiberoptic physiologic monitoring system, also improved in 13 of 15 patients (7.3 +/- 4.2% to 11.8 +/- 4.0% [mean change 100%, 95% confidence interval 9 to 256]) (p = .002). Patients who were defined as responders in relation to systemic hemodynamics (VO2 of >10% from baseline [n = 6; 40%]) had a significantly lower baseline consumption compared with that of nonresponders (133 vs. 162 mL/min/m2, p = .04). No clear relationship between the increments in VO2 and indocyanine green clearance was observed (r2 = .21; p = .08). Prostacyclin resulted in moderate improvements in systemic DO2 (but not VO2) and a nonsignificant increase in indocyanine green clearance. CONCLUSION: N-acetylcysteine increases systemic VO2 in a proportion of patients with a wide variety of hepatic disorders. In addition, N-acetylcysteine elicits an improvement in indocyanine green clearance. These properties may be clinically useful in a range of critical illnesses where systemic or hepatic-splanchnic circulations are compromised.

Acetylcysteine↗
PubMed1997

The acute phase and function in early rheumatoid arthritis. C-reactive protein levels correlate with functional outcome.

OBJECTIVE: To discover whether normalization of C-reactive protein (CRP) in patients with rheumatoid arthritis (RA) results in stabilization of their functional state, and whether a measure of disease activity can be used as a predictor of functional outcome. To examine the relationship between change of CRP and Health Assessment Questionnaire (HAQ) over a 24 mo period to define the sensitivity of HAQ to change. METHODS: A prospective study of 109 consecutive patients who fulfilled the American College of Rheumatology criteria for RA and had elevated CRP before steroid or 2nd line therapy. A full clinical assessment including HAQ was performed at presentation and at 3, 6, 12, and 24 mo. On the basis of the change in CRP at 6 mo, patients were divided into 3 groups: (1) CRP suppression to normal, (2) 50% reduction in CRP, and (3) less than 50% CRP change. RESULTS: The 3 groups were clinically and immunologically similar at onset. At 6 mo the median HAQ fell to 5 (lower to upper quartiles 7.5 to 19) in Group 1 (CRP normalized, n = 34), 6 (3.75 to 10) in Group 2 (CRP reduced by 50%, n = 30), and 12 (6 to 18) in Group 3 (less than 50% CRP change, n = 44), p < 0.005 for Groups 1 and 2 versus Group 3. At 12 and 24 mo HAQ remained significantly lower in Groups 1 and 2 compared with Group 3. In Group 1, patients either maintained a normal CRP (n = 28) or their CRP became elevated (n = 6). Only in those patients in whom a re-elevation of the CRP occurred was deterioration in HAQ subsequently seen. CONCLUSION: Suppression of elevated CRP in patients with active RA is associated with improvement in functional score, whereas persistent elevation of CRP is associated with functional deterioration. Once abnormal CRP is suppressed, no functional deterioration is likely to occur without re-elevation in CRP. Therefore, elevated CRP provides a convenient short term correlation with functional outcome and can be used as a guide for therapy. A HAQ score is a sensitive indicator of change in early disease.

Analysis of Variance↗
PubMed1996

Transplantation for fulminant hepatic failure: comparing tacrolimus versus cyclosporine for immunosuppression and the outcome in elective transplants. European FK506 Liver Study Group.

Within the multicenter European FK506 (tacrolimus) liver study, patients who received transplants for fulminant hepatic failure (FHF) were stratified separately from those having an elective transplant procedure. At 2-year follow-up, in addition to a comparison of the outcome between these two clinical groups, we report the efficacy and safety of tacrolimus primary immunosuppression (n=32) as compared with a cyclosporine-based regimen (n=23) in FHF. The FHF patients experienced more episodes of acute rejection and sepsis with reduced patient and graft survival rates compared with the elective group (e.g., retransplantation rate of 10/44 [22.7%] vs. 47/485 [9.7%], respectively). Among the FHF patients, tacrolimus reduced the actuarial incidence of acute rejection compared with patients treated with cyclosporine, and whereas refractory acute and chronic rejection occurred in four (17.4%) and two patients (8.7%), respectively, treated with cyclosporine, no rejection episodes were recorded in patients receiving tacrolimus. No difference in the actuarial patient or graft survival rates was observed between the two groups. Patients treated with tacrolimus tended to have a lower incidence of infection (pneumonia, 19.0% vs. 26.1%; cytomegalovirus infection, 9.5% vs. 26.1%; and sepsis, 23.8% vs. 39.1%). Corticosteroid dosage requirements were reduced in the tacrolimus-treated group with the cumulative dosage exposure from 20.8% to 37.2% lower on a monthly basis. No significant differences in adverse events attributable to the immunosuppressive drugs were found.

Cyclosporine↗
PubMed1996

Repeat HLA-B and -DR loci mismatching at second liver transplantation improves patient survival.

The role of HLA matching in liver transplantation remains uncertain, and the effect of HLA mismatches on the outcome of second transplants has not been studied. In renal transplantation, if HLA mismatches are repeated in the second graft there is a greatly increased risk of immunological graft failure. In the present study, 78 patients who had received second liver transplants were studied. HLA typing was performed using standard complement-dependent microcytotoxicity for class I (A and B) antigens, and a combination of restriction fragment length polymorphism and serology for HLA-DR. Patient survival at follow-up for those with a repeat B locus mismatch was improved (79% compared with 43%, P < 0.02), and a similar effect was noted for repeat DR mismatches (67% vs. 47%, P = 0.06). In the subgroup of patients who received a second transplant for graft rejection, 90% of patients with a repeat B mismatch were alive at follow-up compared with 46% without B mismatches (P = 0.02). This improvement in patient survival was evident during the first 2 months after the second transplant. In this study, repeat HLA-B and -DR mismatching improves survival after second transplantation.

Adolescent↗
PubMed1996

DXA scanning.

The steady improvement in densitometric technique is reviewed in this paper culminating in the newest generation of DXA scanners. The suitability of the lumbar spine, femur and hand as sites for the densitometric measurement of bone loss in rheumatoid disease is assessed. The recent improvement in hand scanning technique using DXA has led to improved clinical utility in the detection of juxta-articular bone loss. The enhanced resolution offered by the newest, solid state detector DXA scanners, and their ability to detect bone loss where no systemic features are evident, makes it possible that DXA scanning of the hand will be a useful modality for the monitoring of early rheumatoid disease.

Absorptiometry, Photon↗
PubMed1996

High frequency of chromosome 9 deletion in ovarian cancer: evidence for three tumour-suppressor loci.

We have screened 33 ovarian tumours of various grades and stages for the loss of heterozygosity (LOH) of markers on chromosome 9. LOH was detected in 26 cases (79%). Eleven tumours (33%) showed LOH of all informative markers. The remaining 15 cases had partial deletions. Of these, six (18%) had losses on 9p only, three (9%) had LOH confined to 9q and six (18%) had losses on both chromosome arms, four of which had a retention of hetereozygosity in between. There was no association between tumour grade stage or histopathology and any losses. High-density deletion mapping was carried out in 12 selected cases that had partial deletions of 9p and/or 9q. The deleted region on 9p included the cyclin-dependent kinase inhibitor 2 (CDKN2) locus and one tumour was found to have a homozygous deletion of CDKN2. LOH on 9q extended over a larger region. We found evidence for two regions of deletion on 9q, one at 9q34 and the other encompassing the nevoid basal cell carcinoma (Gorlin) syndrome locus on proximal 9q.

Adenocarcinoma↗
PubMed1996

Clinical associations of dual-energy X-ray absorptiometry measurement of hand bone mass in rheumatoid arthritis.

Hand bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry (DXA) has potential as a marker of progression in early rheumatoid arthritis (RA). We examined a DXA methodology and studied in a cross-sectional manner 202 patients with RA. Hand BMD correlated inversely with age and was higher in males. Hand BMD correlated with lumbar and femoral sites. In females, BMD of the hand correlated positively with grip strength and negatively with disability. Those with higher C-reactive protein (CRP) had significantly lower hand BMD than those with normal CRP. In patients with a normal CRP, the hand BMD:lumbar BMD ratios were significantly higher in patients with longer disease duration. Hand BMD correlates with measures of disease activity, functional capacity and also with lumbar and femoral BMD. Hand bone loss occurs in early disease, in the absence of detectable systemic disease, and before lumbar BMD loss. It has the potential to be an outcome measure in early disease.

Absorptiometry, Photon↗
PubMed1995

Detailed deletion mapping of chromosome 9q in bladder cancer: evidence for two tumour suppressor loci.

Loss of heterozygosity (LOH) at loci on chromosome 9p and/or 9q is the most frequent genetic alteration in transitional cell carcinoma (TCC) of the bladder. However, localisation of the tumour suppressor locus or loci on 9q has been hampered by the relative infrequency of tumours with subchromosomal deletions. We have used 24 microsatellite markers to examine LOH in 70 new cases of TCC of the bladder and upper urinary tract. Forty tumours (57%) showed LOH at one or more loci on 9q and partial deletions were detected in five tumours (7%). Combined data from the five cases with partial deletions place one tumour suppressor locus at 9q34 between D9S61 and D9S66 (an estimated distance of 13-14 cM). This region is frequently deleted in other sporadic tumours and encompasses one of the loci for tuberous sclerosis (TSC1). One tumour contained a distinct deletion between D9S153 and D9S109 (9q13-q31), which encompasses the locus for the familial nevoid basal cell carcinoma syndrome (Gorlin syndrome). This may indicate the presence of another tumour suppressor locus on 9q for TCC. Our findings significantly reduce the regions of 9q within which suppressor genes for TCC may reside. The possible involvement of two deletion targets on 9q in addition to the locus at 9p21 implicated in TCC may explain why LOH at all loci on chromosome 9 is frequent in TCC.

Chromosome Mapping↗
PubMed1995

Relationship between early liver graft viability and enzyme activities in effluent preservation solution.

Determination of cellular enzyme activities in washout preservation solution used in hypothermic liver graft storage may allow development of an index that could be clinically valuable in prediction of early post-transplant graft function. In the present study, we collected washed out preservation fluid at the time of graft rinsing from 53 liver recipients. Aspartate aminotransferase and, to a lesser extent, lactate dehydrogenase levels correlated with early postoperative graft viability as assessed by 1-month graft survival and standard biochemical indices of liver function. Those patients with the highest aspartate aminotransferase activity in the washout preservation solution experienced the highest levels of this enzyme postoperatively (area-under-the-curve day 1-3; 1340 vs. 788 IU/L), total bilirubin (area-under-the-curve day 1-5; 901 vs. 538 mumol/L), and rejection frequency (67% vs. 31%) (all P < 0.05), with a significantly lower 1-month graft survival rate compared with patients with low effluent levels (62% vs. 92%, P < 0.05). Two markers of endothelial cell damage, purine nucleoside phosphorylase and a creatine kinase isoenzyme, measured in the fluid did not correlate with early graft viability. It is suggested that assay of aspartate aminotransferase activities in preservation fluid washout samples is a clinically useful indicator of graft viability.

Adult↗
PubMed1995

Importance of concomitant viral infection during late acute liver allograft rejection.

We have determined accompanying events and reviewed the management and outcome of late acute cellular rejection episodes in 384 consecutive liver recipients. A significant proportion of patients experienced concomitant viral infection (group 1, n = 15 [41%]), with CMV infection comprising the largest group and smaller contributions from other viruses (CMV, 30%; HSV, 5%; EBV, 3%; varicella zoster virus, 3%). Thirteen (35%) patients (group 2) developed late rejection associated with low maintenance immunosuppression, and in a further 10 patients (group 3), no accompanying factor could be identified. Refractory rejection was higher in late compared with early rejection episodes in our series (29% vs. 9.2%, P < 0.05). Antiviral chemotherapy administered in rejection episodes with concomitant viral infection, either as sole treatment in cases with accompanying hepatitis or as adjunctive therapy to further supplemental immunosuppression in episodes of steroid-resistant rejection, controlled the rejection process in all treated patients.

Adolescent↗