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Biomedical subjects

J Devlin

Publications and source records attributed to J Devlin.

At least 55 records · Page 3Linked to original sources
PubMed1995

Illness in a community associated with an episode of water contamination with sewage.

Following an episode of water contamination with sewage in a rural Irish town, a community-wide survey of gastrointestinal-associated illness and health service utilization was conducted. Random sampling of households yielded residents who were surveyed using a self-administered questionnaire. Of 560 respondents from 167 (84%) households, equal proportions lived in areas known to have been exposed and unexposed to the contaminated water, although 65% of subjects reported using contaminated water. Sixty-one percent of subjects met the case definition. The most common symptoms among cases were abdominal cramps (80%), diarrhoea (75%), appetite loss (69%), nausea (68%) and tiredness (66%). Mean duration of illness was 7.4 days. Only 22% of cases attended their general practitioner. Drinking unboiled water from the exposed area was strongly associated with being a case. A substantial degree of community illness associated with exposure to contaminated water was observed. The episode ranks as one of the largest reported water-borne outbreaks causing gastrointestinal illness in recent times.

Disease Outbreaks↗
PubMed1995

p16 (CDKN2) is a major deletion target at 9p21 in bladder cancer.

The p16 gene has been identified as a candidate tumour suppressor gene at 9p21, a region commonly deleted in bladder cancer. We screened 140 bladder tumours and 16 cell lines for deletions and sequence variants of p16. Eight cell lines showed homozygous deletion of p16 and two had small sequence variations. All 13 tumours with small defined deletions of 9p21, 18/31 (58%) of tumours with monosomy 9 and 9/91 (10%) of tumours with no chromosome 9 loss of heterozygosity had homozygous deletion of p16. No tumour-specific sequence variants were identified. Deletion mapping revealed a nested set of deletions focused on p16. Six deletions involved p16 but not the related and adjacent gene p15 and one tumour had an intragenic deletion of p16. All other deletions involved both p16 and p15. We conclude that p16 represents the major target for deletion at 9p21 in bladder cancer.

Base Sequence↗
PubMed1995

Pretransplantation clinical status and outcome of emergency transplantation for acute liver failure.

Emergency transplantation for acute liver failure has a significantly inferior outcome than transplantations performed for elective indications. The severity of the pretransplantation clinical illness in this group will contribute to the reduced patient survival. We have reviewed the outcome of our first 100 consecutive adult patients who received transplants for acute liver failure and have evaluated and determined which recipient clinical parameters present on admission and at transplantation act as risk factors in early posttransplantation outcome. In patients who received transplants for nonacetaminophen-induced liver failure (n = 79), no static variable determinable on admission (including age, sex, year of transplantation, hospital admission to transplantation period, and fulminant or late-onset presentation) other than cause was predictive of 2-month patient survival. Fulminant Wilson's disease and idiosyncratic drug reactions with 2-month survival rates of 100% and 12.5%, respectively, had significantly different outcomes from other causes. By the time of transplantation, of four dynamic variables significant in a univariate analysis (serum creatinine, encephalopathy grade, Apache 111 and organ system failure scores, and P values < .05), only the creatinine level was an independent variable in a stepwise logistic regression for 2-month survival (r = .33). In patients who received transplants for acetaminophen hepatotoxicity (n = 21), overdose to hepatectomy period was the only significant static variable, with no parameter predictive of outcome present on admission.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1994

Nitric oxide generation. A predictive parameter of acute allograft rejection.

The L-arginine:nitric oxide (NO) biosynthetic pathway has been proposed as an important mediator in host defense mechanisms and may therefore play a role in the acute allograft response. We have studied NO generation in liver allograft rejection and determined its value in immunological monitoring. Stable end products of this pathway have been determined serially in 50 primary liver recipients and compared with 2 known mediators and markers of acute allograft rejection (IL-2R positive lymphocytes and circulating TNF alpha). Plasma concentrations of acid-labile nitrosocompounds (NOx), which increased during acute allograft rejection (P < 0.0001), correlated with rejection severity and were reduced after administration of supplemental high dose glucocorticoids. Concentrations were significantly lower in nonrejection graft complications but were elevated during episodes of sepsis. Correlations between plasma NOx levels and circulating TNF-alpha (r = 0.451, P < 0.001) and IL-2R-positive lymphocytes in peripheral blood (r = 0.781, P < 0.001) were demonstrated. In a logistic analysis of these variables, plasma NOx was the most predictive parameter of an episode of acute cellular rejection. Nitric oxide generation in FK506-treated patients was lower compared with patients receiving a CsA-based immunosuppression regimen and was associated with a reduced frequency of acute rejection in the FK506 group. These data are consistent with a role for NO in the cellular alloantigen immune response and indicate that monitoring of plasma levels of NOx may be useful in the detection of acute allograft rejection.

Biomarkers↗
PubMed1994

Selective incorporation of fibronectin isoforms into the extracellular matrix of hybrids between human fibrosarcoma cells and normal human fibroblasts.

A matched pair of tumorigenic and nontumorigenic human hybrids between GM0097 diploid fibroblasts and HT1080 fibrosarcoma cells was used to investigate further the relationship between the amount of surface fibronectin and the malignant potential of the cell. We can confirm that the malignant phenotype in these hybrids cosegregates with a decrease in cell-surface fibronectin. Moreover, the nontumorigenic hybrid incorporates into its extracellular matrix a significantly higher proportion of fibronectin isoforms that do not contain the alternatively spliced regions ED-A and ED-B. When, after chromosome segregation, malignant potential reappears in the hybrid cells, they incorporate more ED-A+ and ED-B+ isoforms than do the nontumorigenic hybrids from which they were derived.

Alternative Splicing↗
PubMed1994

Impact of immunoprophylaxis and patient selection on outcome of transplantation for HBsAg-positive liver recipients.

We have studied the roles of immunoprophylaxis, patient selection policy and coexistent hepatitis D virus infection in the outcome of 56 HBsAg-positive elective liver transplant recipients. Twenty-nine unselected patients not treated with immunoprophylaxis formed group 1 and were compared to a recent consecutive series of 27 patients (group 2) in whom pre-transplant serological status was determined and who received immunoprophylaxis. One-year actuarial HBsAg serological recurrence rates were 48% in group 2 and 90% in group 1 with particular improvement in recipients who were either HBV DNA-negative or who had co-existent hepatitis delta virus infection. One-year patient survival has improved from 62% in group 1 to 86% in group 2 with improvements in hepatitis delta virus-negative and replicating recipients. Patients who have either co-existent hepatitis delta virus infection or are in group 2 have 1-year survival rates comparable to elective HBsAg-negative recipients (19/21 (90%), 22/27 (86%) vs 87%, respectively). In the event of recurrence, severe graft injury is diminished in recent patients and in those with coexistent delta infection who also have lower levels of circulating HBV DNA. Retransplantation for associated graft injury has a poor prognosis irrespective of administration of immunoprophylaxis. In elective liver recipients, immunoprophylaxis and/or hepatitis delta virus infection modulate hepatitis B virus recurrence and associated graft injury with consequent improvement in patient survival.

Adult↗
PubMed1994

Renal complications and development of hypertension in the European study of FK 506 and cyclosporin in primary liver transplant recipients.

We examined the occurrence of renal complications and hypertension in 540 primary liver recipients entered into the European liver trial comparing primary FK 506 to a cyclosporin A based immunosuppression regimen (CBIR). No difference in serious renal impairment or mean creatinine levels was observed with similar rates of "kidney failure" (FK 506 9.4% vs. CBIR 7.3%) and dialysis requirements (FK 506 12% vs. CBIR 11%). "Abnormal kidney function", a less serious parameter of renal impairment, was reported in 89 recipients (33%) in the FK 506 group versus 58 (21%) in the CBIR group (P < 0.01). Development of this complication was associated with elevated intravenous FK 506 dosing schedules, with the mean cumulative dose 43% higher than treated patients with unaffected kidney function. In a later cohort of patients where intravenous dosing was lower, no significant difference in renal complications was detectable. The 6-month prevalence rate of systemic arterial hypertension was noted to be lower in the FK 506-treated patients compared to the CBIR group [33 (17.2%) vs. 47 (25.7%)].

Adolescent↗
PubMed1994

FK 506 primary immunosuppression following emergency liver transplantation for fulminant hepatic failure. European FK 506 Study Liver Group.

The efficacy and safety of an FK 506-compared to a cyclosporin A based immunosuppression regimen was examined in liver recipients who underwent transplantation for fulminant hepatic failure in the European FK 506 liver study. A consistent trend towards improved patient and graft survival noted in the FK 506-treated patients was apparent from the first postoperative week (e. g. patient survival: day 7, 95.5% vs. 82.1% and month 6, 72.7% vs. 60.7%). Acute (in particular intractable) rejection was less frequent in the FK 506 group (e. g. cumulative intractable rejection rate at 6 months, 6.2% vs. 22.6%). In a single centre (Kings College Hospital), 17 patients were studied in more detail. The FK 506 treatment group had improved graft function, lower steroid requirements and episodes of infection. Accompanying these benefits, apache 111 and TISS scores were lower in this group in the early posttransplant period. Intensive care discharge was earlier and both treatment groups experienced similar toxicity.

Adolescent↗
PubMed1994

FK 506 rescue therapy for intractable liver allograft rejection.

Intractable liver allograft rejection remains an important cause of graft loss. In this present study, we evaluated the role of oral FK 506 in 30 rejection episodes resistant to conventional cyclosporin-based triple immunosuppression in a series of 28 patients. Rejection was reversed in 11 (91.7%) of 12 patients for intractable acute rejection and in 10 (58.8%) of 17 patients for chronic rejection. A progressive decline in serum bilirubin was observed within 14 days in those successfully salvaged and a serum bilirubin of less than 200 micromol/l at the time of FK 506 conversion in the chronic rejection subgroup was found to be good predictor of response (specificity 100%, sensitivity 60%). New onset diabetes mellitus (29%) and reversible renal impairment (32%) were the commonest adverse events observed. Eleven (52%) of the responding patients successfully discontinued corticosteroid medication and are currently on FK 506 monotherapy. FK 506 therapy has a significant impact in the control of both intractable acute and chronic allograft rejection with an acceptable toxicity profile.

Acute Disease↗
PubMed1994

Importance of cytochrome P-450IIIA activity in determining dosage and blood levels of FK 506 and cyclosporine in liver transplant recipients.

We have investigated the importance of cytochrome P-450IIIA enzyme activity in influencing dosage of the immunosuppressive drugs FK 506 and cyclosporine after liver transplantation. Cytochrome P-450IIIA enzyme activity in vivo was measured 1 yr postoperatively in 37 stable orthotopic liver graft recipients (21 receiving FK 506 and 16 given cyclosporine) by the erythromycin breath test and the production of monoethylglycinexylidide from lignocaine. A strong correlation existed between FK 506 dose and erythromycin breath test results (r = 0.583, p < 0.007), but no corresponding relationship with monoethylglycinexylidide production was observed. The FK 506 dose (14 to 196 micrograms/kg/day) also correlated closely with circulating predose levels of the drug in both plasma and blood (r = 0.538 and 0.731, p = 0.015 and < 0.001, respectively). Although no correlation existed between cyclosporine dose (0.254 to 0.494 mg/kg/day) and trough blood levels, a relationship was demonstrated when erythromycin breath test results were included in the derived equation: Drug dose/cytochrome P-450IIIA activity alpha drug level (p = 0.011 vs. 0.175 without erythromycin breath test). A corresponding enhancement was demonstrated with erythromycin breath test results to relate FK 506 dose and plasma levels (p = 0.006 versus 0.015 without erythromycin breath test results), although breath test results and FK 506 levels were highly discordant (p > 0.8). The use of monoethylglycinexylidide test results as an alternative measure of cytochrome P-450IIIA activity provided no comparable increase in correlation for FK 506 or cyclosporine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aryl Hydrocarbon Hydroxylases↗
PubMed1994

Homozygous deletion mapping at 9p21 in bladder carcinoma defines a critical region within 2cM of IFNA.

We have screened 165 cases of primary transitional cell carcinoma of the bladder for loss of heterozygosity of markers on chromosome 9. High density deletion mapping was then carried out on a panel of 16 tumours with partial deletions of 9p using 15 microsatellite markers. Seven tumours had hemizygous deletions which included small interstitial losses and large terminal deletions. Homozygous deletions of one or more markers were identified in the remaining 9 tumours. By comparing the limits of hemi- and homozygous deletions in these tumours we have defined a single common region of 2cM flanked by IFNA and D9S171.

Chromosome Deletion↗
PubMed1993

Angiographically determined arteriopathy in liver graft dysfunction and survival.

We evaluated the contribution of flush and selective hepatic angiography in defining the extent and pattern of major vessel and microvascular arterial lesions and their significance in graft survival. The 50 consecutive patients investigated comprised three clinical groups: Group A (n = 18) were patients with severe graft dysfunction within the first seven days post-transplantation. In this group six of 18 angiograms demonstrated intrahepatic attenuation of the arterial tree suggestive of acute cellular rejection and four of these grafts were lost, compared to a 78% graft survival in the non-arteriopathic group. Group B (n = 16) comprised patients with clinically suspected hepatic arterial thrombosis or stenosis, these diagnoses were confirmed in all patients compared to only 10 positive findings with doppler ultrasonography. Graft survival was only 10% in those patients with artery thrombosis as compared to 100% in those with arterial anastomotic stenoses. Group C patients (n = 16) had histologically confirmed chronic allograft rejection and in ten of them (65%) evidence of arteriopathy was demonstrated despite histological evidence of arteriopathy being present in only 19% of patients. All patients in this group with arteriopathic changes lost their grafts with the exception of one successfully treated with FK506. In two other patients reversibility of chronic rejection was observed, neither of whom had evidence of an arteriopathy.

Arterial Occlusive Diseases↗
PubMed1993

Growth in atopic eczema.

Growth was studied in 68 children aged 2-12 years with atopic eczema. Height SD scores were significantly correlated with the surface area of skin affected by eczema. The mean height of 41 patients with less than 50% of their skin surface affected (group I) was normal (mean SD score -0.11). The 27 children with more than 50% of their skin affected (group II) were significantly shorter (SD score -0.83) and were also short allowing for their parental target height. The predicted heights were also normal in group I but were lower than expected in group II. Regression analysis suggested that height was most dependent on parental height. The extent of the disease had a significant additional effect, whereas dietary treatment and treatment with topical steroids had only marginal additional effects. The growth of children with eczema affecting less than 50% of the skin surface area appears to be normal, and impaired growth is confined to those with more extensive disease.

Age Determination by Skeleton↗