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Biomedical subjects

M J Carter

Publications and source records attributed to M J Carter.

At least 19 recordsLinked to original sources
PubMed2004

Functional correlates of the interleukin-1 receptor antagonist gene polymorphism in the colonic mucosa in ulcerative colitis.

Association studies have identified the interleukin-1 receptor antagonist gene allele 2(IL-1RN*2) as a marker of susceptibility in ulcerative colitis (UC). This study investigated the significance of the IL-1RN genotype with respect to protein and mRNA expression in the colonic mucosa. Homogenates of rectal biopsies from 99 UC and 54 controls were assayed for cytokines IL-1ra, IL-1a and IL-1b using ELISA. IL1RN, IL1A and IL1B genotypes were determined using restriction-enzyme analysis. The ability of the two IL1RN alleles to generate steady-state mRNA accumulation was assessed in the colonic mucosa of seven heterozygous patients. Stepwise linear regression demonstrated that IL-1RN genotype (P=0.001), diagnosis (P<0.0001) and treatment (P<0.03) were independent factors associated with the IL-1ra protein level whilst IL1RN genotype (P=0.005) and macroscopic inflammatory grade (P<0.0001) were associated with the IL-1ra/ total IL-1 ratio. The IL1RN*2 correlated with reduced IL-1ra and IL-1ra/IL-1 ratio with a gene dosage effect. In heterozygous UC patients the ratio of allele 1 mRNA / allele 2 steady state mRNA was always greater than 1 (range: 1.2-3.1) (P=0.018). The IL-1RN*2 is associated with reduced levels of IL-1ra protein and IL-1RN mRNA in the colonic mucosa, providing a biologically plausible explanation for the observed association of the allele with the disease.

3' Untranslated Regions↗
PubMed2004

Heritability of progeny size in a terrestrial isopod: transgenerational environmental effects on a life history trait.

Maternal effects, the environment that mothers provide to their offspring, their provision of nutrients and the environment that offspring of the same clutch share, have come to be recognized as an important influence on offspring fitness. In addition, in invertebrates, maternal effects and common environment may change according to a mother's diet. We tested for the changes in quantitative genetic parameters in a half-sib design where mothers were fed diets varying in nutrient content. Surprisingly, we found that not only maternal and common environmental variance changed with experimental diets but also there were significant changes in narrow-sense heritabilities, with corresponding h(2) values of 0.61 (high protein), 0.08 (high carbohydrate) and 0.001 (equal carbohydrate:protein). Our results show how an environmentally driven evolutionary process could occur in nature, since the response to selection could change dramatically according to the composition of the diet that females are ingesting.

Animal Feed↗
PubMed2004

Quantitative RT-PCR for the enumeration of noroviruses (Norwalk-like viruses) in water and sewage.

AIMS: Aims of investigation: (i) develop a quantitative RT-PCR for noroviruses and (ii) evaluate it on environmental samples. METHODS AND RESULTS: Noroviruses in environmental water samples were concentrated by adsorption/elution/flocculation. Sewage was processed by clarification and protein flocculation. Norovirus-specific cDNA produced by primer-directed reverse transcription of extracted RNA was amplified by LightCycler and accumulation of product monitored by observation of fluorescence induced by the incorporation of SYBR Green. Absolute quantitation of product was achieved by construction of standard curves using quantitative standards produced by cloning a modified sequence of the 3'-region of the forward norovirus primer. Reaction specificity was confirmed by analysis of product melting curves. CONCLUSIONS: Sewage was found to contain up to 1.8 x 10(6) norovirus cDNA copies per 100 ml and effluent contained up to 1.7 x 10(6) copies per 10 l. Marine bathing water and recreational river waters also contained noroviruses. Sample inhibition was detected to varying degrees in most sample types. SIGNIFICANCE AND IMPACT OF THE STUDY: The study will enable quantitative comparisons be made of samples from different locations and treatment processes, and inform the debate on the revision of the EU Bathing Water Directive; it will have important implications for the analysis of samples derived from different aquatic matrices, and from foods.

Benzothiazoles↗
PubMed2003

Metastasis-free survival following treatment for uveal melanoma with either stereotactic radiosurgery or enucleation.

PURPOSE: To determine whether metastasis-free survival following stereotactic radiosurgery is comparable with that following enucleation in a cohort of patients with choroidal and ciliary body melanoma. METHODS: This was a non-randomized, retrospective study of 196 patients with uveal melanoma treated between 1990 and 2000. A total of 118 eyes were enucleated and 78 eyes were treated with stereotactic radiosurgery. The following variables were recorded: age and sex of patient; tumour location, volume and height; the presence of retinal detachment, and extrascleral extension. Tumour location was divided into three categories: within the posterior pole; beyond the limits of the posterior pole but not including the ciliary body, and ciliary body location. Analysis of survival time was performed using Kaplan-Meier estimation of survival curves and Cox's proportional hazards regression modelling. RESULTS: The 5-year cumulative metastasis-free survival rate was 51% in the enucleation treatment group compared to 74% in the stereotactic treatment group. However, in the multivariate analysis there was no statistical difference in survival rates between the two treatment groups. The only variables that influenced survival rates were tumour location (p = 0.002), ciliary body tumours with the worst prognosis, and tumour volume (p = 0.001). CONCLUSIONS: Tumour size and location at presentation determined metastasis-free survival. Large ciliary body tumours had the highest risk of metastasis. Metastasis-free survival after stereotactic radiosurgery was comparable to that after enucleation.

Adult↗
PubMed2002

Prospective validation of the Rockall risk scoring system for upper GI hemorrhage in subgroups of patients with varices and peptic ulcers.

OBJECTIVES: The Rockall risk assessment score was devised to allow prediction of the risk of rebleeding and death in patients with upper GI hemorrhage. The score was derived by multivariate analysis in a cohort of patients with upper GI hemorrhage and subsequently validated in a second cohort. Only 4.4% of patients included in the initial study had esophageal varices, and analysis was not performed according to the etiology of the bleeding. Our aim was to assess the validity of the Rockall risk scoring system in predicting rebleeding and mortality in patients with esophageal varices or peptic ulcers. METHODS: Admissions (n = 358) over 32 months to a single specialist GI bleeding unit were scored prospectively. The distribution of episodes of rebleeding and mortality by Rockall score were statistically analyzed using Fisher's exact test with 99% CIs calculated using a Monte Carlo method. The Child-Pugh score was determined in patients with esophageal varices. RESULTS: The Rockall score was predictive of both rebleeding and mortality in patients with variceal hemorrhage (both ps < 0.0005), as was the Child-Pugh score (p = 0.001 and p < 0.0005, respectively). The initial Rockall score was predictive of mortality in patients with peptic ulcers (p = 0.01), although the complete score was not (p > 0.05). The complete score did, however, predict rebleeding in these patients (p = 0.001). CONCLUSION: This is the first study to validate the Rockall score in specific subgroups of patients with esophageal varices or peptic ulcers and suggests that it is particularly applicable to variceal hemorrhage.

Adult↗
PubMed2002

Percutaneous endoscopic gastrostomy: a prospective audit of the impact of guidelines in two district general hospitals in the United Kingdom.

OBJECTIVE: Percutaneous endoscopic gastrostomy (PEG) is the accepted method for long-term enteral nutrition. Recent studies have suggested a higher mortality than was initially reported. The demands for gastrostomy insertion have risen, encompassing indications where the long-term outcomes are uncertain. We, therefore, constructed guidelines to try and improve the appropriateness of patient selection. Our aim was to prospectively assess the impact of guidelines for PEG insertion over a 1-yr period in a single center, Rotherham District General Hospital (hospital A) and compare against an adjacent center serving a similar population, Doncaster Royal Infirmary (hospital B) where guidelines had not been instituted. METHODS: Data were collected from June, 1998 to May, 1999. Indication for PEG was documented and survival analysis performed using the Kaplan-Meier survival method. RESULTS: The number of PEG insertions had been rising each year in both centers. After guidelines were introduced in hospital A, the number of procedures fell by 20, whereas in hospital B, the PEG insertion rate continued to rise (p = 0.02). There was a lower mortality observed in hospital A (at 1 month, 16%; at 3 months, 26%; at 6 months, 39%; and at 1 yr, 46%) than in hospital B (at 1 month, 26%; at 3 months, 44%; at 6 months, 58%; and at I yr, 68%), although this did not achieve statistical significance (log rank test, p = 0.1). CONCLUSIONS: This is the first study to prospectively assess the impact of guidelines and a proactive role in the decision for PEG insertion. Fewer procedures were performed, and there was a trend toward a reduction in mortality.

Adult↗
PubMed2001

Association of adult coeliac disease with irritable bowel syndrome: a case-control study in patients fulfilling ROME II criteria referred to secondary care.

BACKGROUND: Irritable bowel syndrome has a high prevalence. Consensus diagnostic criteria (ROME II) based on symptoms have been established to aid diagnosis. Although coeliac disease can be misdiagnosed as irritable bowel syndrome, no prospective study has been published in which patients with this disorder are investigated for coeliac disease. We aimed to assess the association of coeliac disease with irritable bowel syndrome in patients fulfilling ROME II criteria. METHODS: We undertook a case-control study at a university hospital. 300 consecutive new patients who fulfilled Rome II criteria for irritable bowel syndrome, and 300 healthy controls (age and sex matched) were investigated for coeliac disease by analysis of serum IgA antigliadin, IgG antigliadin, and endomysial antibodies (EMA). Patients and controls with positive antibody results were offered duodenal biopsy to confirm the possibility of coeliac disease. FINDINGS: 66 patients with irritable bowel syndrome had positive antibody results, of whom 14 had coeliac disease (11 EMA positive, three EMA negative). Nine patients with positive antibody results were lost to follow-up or refused biopsy (only one EMA-positive patient refused biopsy), and 43 had normal duodenal mucosa. Two controls, both of whom were EMA positive, had coeliac disease. Compared with matched controls, irritable bowel syndrome was significantly associated with coeliac disease (p=0.004, odds ratio=7.0 [95% CI 1.7-28.0]). INTERPRETATION: Patients with irritable bowel syndrome referred to secondary care should be investigated routinely for coeliac disease. With only EMA, three of 14 cases would have been missed.

Adult↗
PubMed2001

Percutaneous endoscopic gastrostomy: a prospective analysis of hospital support required and complications following discharge to the community.

INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) is the commonest method of long-term enteral nutrition. In the UK there is no nationally funded framework to provide community support for patients with gastrostomies. OBJECTIVES: To assess the hospital support required and the complications occurring in a cohort of patients discharged into the community with a gastrostomy in-situ. DESIGN AND SETTING: We prospectively collected data between June and November 1998 regarding patients (n=87) with PEG complications in the community following discharge from two adjacent hospitals in South Yorkshire (Rotherham District General Hospital and the Royal Hallamshire Hospital). RESULTS: The mortality within this cohort during the study period was 17.2%. Of these 15 patients 10.3% (n=9) were thought to have died as a result of the progression of their disease, whilst in the other 6.9% (n=6) pneumonia was documented as the cause of death. Problems with gastrostomies requiring telephone advice occurred in 24.1% of patients and 65.5% necessitated a home visit. However during this period of 6 months, 23% of patients were admitted as an emergency, accounting for 61 in-patient days. All were from nursing or residential homes and the emergency occurred after normal surgery hours. General practitioners dealt with aspiration pneumonia in 25.2% of the cohort but other tube problems were referred to the endoscopy unit. DISCUSSION: This is the first study to specifically highlight the specialist intervention and support required by patients discharged into the community with PEGs, a group for whom there is often no formal aftercare. A specialist nurse or dietician could establish a liaison service focusing on primary care and using hospital resources when appropriate. This study provides further evidence to support the recommendations for tube feeding made by the British Association for Parenteral and Enteral Nutrition.

Adult↗
PubMed2001

Helicobacter pylori antimicrobial resistance in the United Kingdom: the effect of age, sex and socio-economic status.

BACKGROUND: Helicobacter pylori antimicrobial resistance is the most common reason for eradication failure. Small studies have shown metronidazole resistance to be more prevalent in certain population groups. AIM: To determine the resistance rates in a large cohort of patients from a single centre in the UK, and to evaluate resistance patterns over time, according to age, sex and socio-economic status. METHODS: Consecutive patients with H. pylori-positive antral gastric biopsy samples were studied from 1994 to 1999. Susceptibility testing was performed to metronidazole, tetracycline, macrolide and amoxicillin by the modified disk diffusion METHOD: The Jarman under-privileged area score was used as a measure of socio-economic status. RESULTS: A total of 1064 patients were studied. Overall metronidazole resistance was 40.3%, decreasing with age (P < 0.0001, odds ratio for patients over 60 years 0.63, 95% CI: 0.48-0.80). Women were more likely to have metronidazole resistant strains (P=0.003, odds ratio 1.5, 95% CI: 1.15-1.91), but there was no association with Jarman score. Macrolide resistance was associated with metronidazole resistance (P=0.03, odds ratio 2.14, 95% CI: 1.07-4.28). CONCLUSIONS: Metronidazole resistance in H. pylori is highly prevalent and more common in women and the young, but does not appear to be related to socio-economic status.

Age Distribution↗
PubMed2001

The interleukin 1 receptor antagonist gene allele 2 as a predictor of pouchitis following colectomy and IPAA in ulcerative colitis.

BACKGROUND & AIMS: The interleukin 1 receptor antagonist gene allele 2 has been suggested as a determinant of both disease susceptibility and extent in ulcerative colitis. The aim of this study was to assess the allele as a predictor of both the indication for colectomy and the occurrence of pouchitis after ileal pouch-anal anastomosis formation. METHODS: Genotyping for the +2018 single nucleotide polymorphism in the interleukin 1 receptor antagonist gene was performed in 109 patients who had undergone colectomy, including 82 patients who had been followed prospectively after ileal pouch-anal anastomosis formation. RESULTS: Patients with pouchitis had a higher allele 2 carriage rate compared with those without pouchitis (72% vs. 45%) and Kaplan-Meier survival analysis showed that allele 2 carriers had a significantly increased incidence of pouchitis compared with noncarriers (log-rank test, 6.5). After adjustment for confounding covariates in a Cox proportional hazards model, the relative hazard was 3.1 (95% confidence interval [CI], 1.2-7.8; P = 0.02). Although there was a higher allele 2 carriage rate in patients with chronic refractory compared with acute severe ulcerative colitis (63% vs. 48%), this difference was not significant (odds ratio, 1.9; 95% CI, 0.9-4.1; P = 0.1). CONCLUSIONS: The interleukin 1 receptor antagonist gene allele 2 predicts pouchitis after ileal pouch-anal anastomosis in ulcerative colitis.

Adolescent↗
PubMed2001

Sacbrood virus of the honeybee (Apis mellifera): rapid identification and phylogenetic analysis using reverse transcription-PCR.

Sacbrood virus (SBV) infects larvae of the honeybee (Apis mellifera), resulting in failure to pupate and death. Until now, identification of viruses in honeybee infections has been based on traditional methods such as electron microscopy, immunodiffusion, and enzyme-linked immunosorbent assay. Culture cannot be used because no honeybee cell lines are available. These techniques are low in sensitivity and specificity. However, the complete nucleotide sequence of SBV has recently been determined, and with these data, we now report a reverse transcription-PCR (RT-PCR) test for the direct, rapid, and sensitive detection of these viruses. RT-PCR was used to target five different areas of the SBV genome using infected honeybees and larvae originating from geographically distinct regions. The RT-PCR assay proved to be a rapid, specific, and sensitive diagnostic tool for the direct detection of SBV nucleic acid in samples of infected honeybees and brood regardless of geographic origin. The amplification products were sequenced, and phylogenetic analysis suggested the existence of at least three distinct genotypes of SBV.

Amino Acid Sequence↗
PubMed2001

The 5' untranslated region of Rhopalosiphum padi virus contains an internal ribosome entry site which functions efficiently in mammalian, plant, and insect translation systems.

Rhopalosiphum padi virus (RhPV) is one of several picorna-like viruses that infect insects; sequence analysis has revealed distinct differences between these agents and mammalian picornaviruses. RhPV has a single-stranded positive-sense RNA genome of about 10 kb; unlike the genomes of Picornaviridae, however, this genome contains two long open reading frames (ORFs). ORF1 encodes the virus nonstructural proteins, while the downstream ORF, ORF2, specifies the structural proteins. Both ORFs are preceded by long untranslated regions (UTRs). The intergenic UTR is known to contain an internal ribosome entry site (IRES) which directs non-AUG-initiated translation of ORF2. We have examined the 5' UTR of RhPV for IRES activity by translating synthetic dicistronic mRNAs containing this sequence in a variety of systems. We now report that the 5' UTR contains an element which directs internal initiation of protein synthesis from an AUG codon in mammalian, plant, and Drosophila in vitro translation systems. In contrast, the encephalomyocarditis virus IRES functions only in the mammalian system. The RhPV 5' IRES element has features in common with picornavirus IRES elements, in that no coding sequence is required for IRES function, but also with cellular IRES elements, as deletion analysis indicates that this IRES element does not have sharply defined boundaries.

5' Untranslated Regions↗
PubMed2001

Association of the interleukin 1 receptor antagonist gene with ulcerative colitis in Northern European Caucasians.

BACKGROUND AND AIMS: An association between the allele 2 of the interleukin 1 receptor antagonist gene variable number tandem repeats polymorphism in intron 2 and ulcerative colitis was first reported in 1994. Subsequent studies in Caucasian Northern European patients have not confirmed this, although trends towards an association were observed. The lack of statistical significance could reflect inadequate power. In this study the association was reassessed in a large independent set of well characterised Caucasian patients and a meta-analysis of reported patient series was performed. PATIENTS AND METHODS: A total of 320 patients with endoscopically and histologically confirmed ulcerative colitis (124 pancolitis, 196 left sided and distal disease) and 827 ethnically matched controls were genotyped at polymorphic sites in the interleukin 1 receptor antagonist gene. Carriage rates were compared using chi(2) statistics. A meta-analysis of this and seven previous studies in North European Caucasian patients was performed using the Mantel-Haenszel chi(2) test. RESULTS: Patients had a significantly increased carriage rate of allele 2 compared with controls (52% v 45%; odds ratio 1.3 (95% confidence interval (CI) 1.01-1.7); p=0.04). The allele 2 carriage rate was highest in extensive colitis (carriage rate 56%; odds ratio 1.5 (95% CI 1.1-2.3) p=0.02) and in individuals who had undergone colectomy (carriage rate 55%; odds ratio 1.5 (95% CI 0.95-2.4); p=0.08). Meta-analysis of all eight studies showed a significant association between carriage of allele 2 and ulcerative colitis (odds ratio 1.23 (95% CI 1.04-1.45); p=0.01). CONCLUSIONS: The association of the interleukin 1 receptor antagonist gene polymorphism with ulcerative colitis is confirmed. The association is minor and confers only a small risk to an individual but will contribute a high attributable risk in a population due to the high allelic frequency. Accurate phenotypic characterisation defines more homogeneous subsets of patients, such as those with extensive disease, in whom the association is greater.

Adolescent↗