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Biomedical subjects

R Peacock

Publications and source records attributed to R Peacock.

At least 19 recordsLinked to original sources

Changing patterns of Helicobacter pylori gastritis in long-standing acid suppression.

BACKGROUND: Helicobacter pylori colonization and associated inflammation are influenced by local acid output. Infected subjects with acid-related diseases, such as gastroesophageal reflux disease (GERD) are likely to have an antral-predominant gastritis. We hypothesized that long-term acid suppression would result in relatively greater bacterial colonization in the corpus leading to diffuse or corpus-predominant gastritis and that this would be prevented by prior H. pylori eradication. MATERIALS AND METHODS: To investigate this, we conducted a prospective, double-blind trial of the effect on gastric histology of 12-month maintenance treatment with omeprazole in H. pylori-positive GERD patients randomly assigned to either an eradication or omeprazole-alone regime. A control group of 20 H. pylori-negative GERD patients also received omeprazole throughout the study period. Biopsies taken at baseline and at 12 months were graded "blind" by a single observer according to the updated Sydney System. The 41 H. pylori-positive subjects with grade B or C esophagitis were randomly assigned (20 to omeprazole alone, 21 to eradication) and 33 subjects completed the 12-month study. RESULTS: There was a significant decline in antral chronic inflammation in initially positive patients between baseline and end in both the eradication group (p =.035) and the omeprazole-alone group (p =.008). However, corpus chronic inflammation increased in the omeprazole-alone group (p =.0156) but decreased in the eradication group. The change toward corpus predominance between baseline and end for the omeprazole-alone group is highly significant (p =.0078). Furthermore, 5 of 11 in the omeprazole-alone group developed mild corpus atrophy, compared to 0 of 8 who had undergone H. pylori eradication. The change in frequency of corpus atrophy between the two groups is significant (p =.02). CONCLUSION: In H. pylori-positive subjects with GERD, long-term acid suppression leads to a shift from antral- to corpus-predominant gastritis that can be prevented by prior eradication. The shift is accompanied by an increase in corpus atrophy. H. pylori infection should be eradicated prior to long-term acid suppression with proton pump inhibitors.

Adolescent↗

Cost effectiveness of omeprazole and ranitidine in intermittent treatment of symptomatic gastro-oesophageal reflux disease.

OBJECTIVE: This 1-year study compared the cost effectiveness of omeprazole and ranitidine when used as initial therapy in an intermittent treatment strategy for the management of patients with symptomatic gastro-oesophageal reflux disease with or without erosive oesophagitis. DESIGN AND SETTING: A prospective health economic analysis was conducted alongside an international multicentre randomised, double-blind clinical study. The economic analysis was performed from a societal perspective. PATIENTS: A total of 704 patients in the UK, the Republic of Ireland, Germany, France, Italy and Spain were randomised to 1 of the 3 treatment groups. INTERVENTIONS: Patients were randomised to receive either omeprazole 20 mg once daily, omeprazole 10 mg once daily or ranitidine 150 mg twice daily. Initial treatment failure resulted in dose titration and drug switching from ranitidine to omeprazole, and subsequently open maintenance treatment. MAIN OUTCOME MEASURES AND RESULTS: The estimated mean direct medical costs (medication and number of visits and endoscopies) were found to be lower for both dosages of omeprazole than for ranitidine in all countries except Germany. However, none of the differences were statistically significant. The differences between omeprazole 10 mg and omeprazole 20 mg were small and nonsignificant. With regard to numbers of symptom-free days, both omeprazole 20 mg and omeprazole 10 mg were found to be more effective than ranitidine. However, none of the differences were statistically significant. CONCLUSIONS: Following a pragmatic interpretation, incorporating intermediate short term results, the results in this study give no support to the notion that a step-up approach, either as dose titration from omeprazole 10 mg to omeprazole 20 mg or as drug switching from ranitidine to omeprazole, will result in cost savings and thereby be cost effective.

Algorithms↗

Quality of life during acute and intermittent treatment of gastro-oesophageal reflux disease with omeprazole compared with ranitidine. Results from a multicentre clinical trial. The European Study Group.

AIMS: To investigate quality of life in patients with gastro-oesophageal reflux disease. PATIENTS: A series of 704 patients were randomised to treatment with ranitidine 150 mg bd, omeprazole 10 mg om or omeprazole 20 mg om for 2 weeks. Asymptomatic/mildly symptomatic patients were followed for 12 months. METHODS: The Psychological General Well-Being index and the Gastrointestinal Symptom Rating Scale were completed before and during short-term and intermittent treatment. RESULTS: The quality of life response rate was > 80%. The majority of the patients receiving omeprazole 20 mg om (55%) had symptom relief after 2 weeks despite the fact that more patients on ranitidine required 4 weeks' treatment and an increased dose. There was no difference in the reflux dimension of Gastrointestinal Symptom Rating Scale between treatments in the initial treatment phase, but the total Gastrointestinal Symptom Rating Scale score improved significantly more on omeprazole 10 mg om than on ranitidine 150 mg bd (p = 0.006). Both doses of omeprazole improved the total Psychological General Well-Being score more than ranitidine (omeprazole 10 mg om versus ranitidine 150 mg bd, p = 0.005, omeprazole 20 mg om versus ranitidine 150 mg bd, p = 0.031). During follow-up, relapsing patients returned to pre-treatment symptom and well-being scores, but these dimensions were restored after treatment. CONCLUSION: The quality of life is impaired in patients presenting with reflux symptoms. Irrespective of whether the patients presented with endoscopy positive or endoscopy negative reflux disease, treatment on demand improved the quality of life.

Adolescent↗

An update on ethylene oxide sterilization issues.

The regulations governing ethylene oxide sterilization are becoming clearer with the appearance of European standards for validation and routine control of the process. In addition, the process has undergone technological changes in recent years. In this article, the author outlines the developments that have taken place in the areas of residue reduction, biological indicators, and emission control and suggests further improvements that would ensure its place as the principle method of sterilization for the twenty first century.

Drug Residues↗

Apolipoprotein B gene polymorphisms, lipoproteins and coronary atherosclerosis: a study of young myocardial infarction survivors and healthy population-based individuals.

Association studies were carried out in a sample of 87 patients from Sweden who had survived a myocardial infarction (MI) before the age of 45, and 91 age-matched healthy individuals, to compare the impact of polymorphisms at the apolipoprotein (apo) E and B gene loci on among-individual differences in plasma lipid traits and progression of atherosclerosis. In the group of healthy individuals, polymorphisms creating the common apo E isoforms were, as expected, associated with significant differences in total and low density lipoprotein (LDL) cholesterol (11.7% and 11.6% of sample variance). For apo B, the polymorphism with the largest effect on apo B levels (16% of sample variance) was the C to T transition 265 bp 5' of the cap site, in the promoter (detectable by MspI). Both this polymorphism and the threonine2488 neutral substitution (detectable by XbaI) were associated with significant effects on LDL-cholesterol (8.3% and 9.3% of sample variance, respectively). The asparagine/serine4311 polymorphism was associated with a significant effect on high density lipoprotein (HDL) cholesterol alone, and there was no significant association with the glutamate/lysine4154 polymorphism (detectable by EcoRI) or the leucine-alanine-leucine (LAL) insertion/deletion polymorphism in the signal peptide. In the patients, polymorphisms creating the three common apo E isoforms were associated with large effects on cholesterol, apo B and triglyceride levels (19.9%, 20.3% and 23.9% of sample variance) of similar magnitude as in the healthy individuals. Apo B polymorphisms were found to be associated with much smaller effects on lipid traits than in the healthy individuals. The only significant association was between the asparagine/serine4311 polymorphism and HDL-triglyceride levels. However, global severity of coronary atherosclerosis at the first angiography was found to be significantly associated with the LAL insertion/deletion polymorphism (P = 0.008). Thus variation at the apo B gene locus is associated with the development of atherosclerosis, but the data suggests that this may act through mechanisms not directly related to effects on measured lipid traits.

Adult↗

Genetic relationship between the 3'-VNTR and diallelic apolipoprotein B gene polymorphisms: haplotype analysis in individuals of European and south Asian origin.

The genetic relationship amongst apolipoprotein B (apo B) gene polymorphisms (signal peptide insertion/deletion (Leu-Ala-Leu-16/-14), XbaI (Thr2488), EcoRI (Glu4154----Lys), Asn4311----Ser, 3'-VNTR) has been investigated in samples of South Asian (Indian) and Swedish individuals. The frequency distribution of alleles at all these sites was found to be significantly different between the South Asian and the Swedish samples (deletion allele: 0.20 v. 0.31, X+ (presence of XbaI cutting site): 0.29 v. 0.55, R- (absence of EcoRI cutting site): 0.11 v. 0.19, Ser4311: 0.45 v. 0.19). The distribution of allele frequencies at the VNTR site was bimodal in both populations. However, in South Asians, the most common allele was a 35 repeat unit allele, whilst in the Swedish sample, and in all other reports from Caucasian samples the 37 repeat unit allele was the most frequent (South Asian v. Swedish: 35 allele: 0.36 v. 0.19, 37 allele: 0.25 v. 0.48). Furthermore, four new alleles at the apo B gene 3'-VNTR site (15, 17, 32, 38 repeat unit alleles) were observed in South Asians, of which two (15 and 17 repeat unit alleles) were well outside the bimodal distribution. In both samples, strong linkage disequilibrium and allelic association were detected between alleles at the 3'-VNTR and each of the other sites, and also between the ins/del and XbaI sites and between the XbaI and Asn4311----Ser sites. The same five common haplotypes as defined by ins/del, XbaI, EcoRI and Asn4311----Ser were found to be present in both samples comprising 97 and 99% of the haplotypes observed in the South Asian and Swedish samples respectively. Detailed analysis revealed the predominant occurrence of certain 3'-VNTR alleles on specific haplotypes and demonstrates the usefulness of the VNTR site for haplotyping and representative association studies. A model for the evolutionary relationship of the major haplotypes including the 3'-VNTR site is presented. These findings support a mechanism of replication slippage as a major factor for the generation of new alleles at the apo B 3'-VNTR locus rather than unequal crossing over.

Adult↗

DNA polymorphism studies. Approaches to elucidating multifactorial ischaemic heart disease: the apo B gene as an example.

It is well established that elevated plasma levels of low-density lipoprotein (LDL) particles are a risk factor for ischaemic heart disease with the distribution in LDL levels seen in the general population being the result of interaction between environmental factors, such as dietary fat intake, and genetic variation that is present in different individuals. One of the candidate genes where such variation is likely to occur, is the gene coding for apolipoprotein B (apo B). Many studies have reported an association between a common polymorphism of the apo B gene, detected using the restriction enzyme XbaI, and differences in plasma lipid levels, explaining 3-5% of the variance in LDL-cholesterol levels in samples representative of the healthy population. It has been proposed that the mechanism of this association is due to functional amino acid changes within the apo B protein, that affect LDL catabolism by altering binding affinity to the LDL-receptor. Several amino acid substitutions in the apo B gene have now been characterized, and these form the basis of the different epitopes that create the Ag marker system. Previous studies have reported that the Ag(x) epitope is associated with lower plasma lipid levels, and until recently the molecular basis for this association has been unclear. We have determined that the Ag(x) epitope is associated with both a Pro-Leu2712, and Asn-Ser4311 substitution, with the Leu-Ser allele being associated with significantly lower levels of plasma lipids in a sample of healthy individuals from Sweden.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗

Two amino acid substitutions in apolipoprotein B are in complete allelic association with the antigen group (x/y) polymorphism: evidence for little recombination in the 3' end of the human gene.

We report the identification of an A-to-G base change, in exon 29 of the apolipoprotein B (apo B) gene, that results in the substitution of serine for asparagine at residue 4311 of mature apo B100. In a recent publication, Huang et al. have reported a C-to-T base change in exon 26 that causes the substitution of leucine for proline at residue 2712 of apo B. We have found complete linkage disequilibrium between the alleles at both these sites and an immunochemical polymorphism of LDL designated antigen group (x/y) (Ag(x/y)) in a sample of 118 Finnish individuals. This implies that either one of these substitutions--or both of them combined--could be the molecular basis of the Ag(x/y) antigenic determinants, with the allele encoding serine4311 plus leucine2712 representing the Ag(x) epitope, and that encoding asparagine4311 plus proline2712 the Ag(y) epitope. In a sample of 90 healthy Swedish individuals the Leu2712/Ser4311 allele is associated both with reduced serum levels of LDL-cholesterol and apo B and with raised levels of HDL. However, these differences are of smaller effect than those associated with the XbaI RFLP of the apo B gene in this sample. We have also genotyped 523 individuals from European, Asian, Chinese, and Afro-Caribbean populations and have found complete association between the sites encoding residues 2712 and 4311 in all of these samples, although there are large allele frequency differences between these populations. In addition, there is strong linkage disequilibrium with allelic association between the alleles of these sites and those of the XbaI RFLP in all the populations examined. Taken together, these data suggest that, since the divergence of the major ethnic groups, there has been little or no recombination in the 3' end of the human apo B gene.

Adult↗

Studies on the cryopreservation of Dictyocaulus viviparus (Nematoda) third-stage larvae.

Various cooling (0.1-5,100 degrees C min-1) and warming (20-6,800 degrees C min-1) rates, stepped cooling schedules and four cryoprotective additives (dimethyl sulphoxide, methanol, ethanediol and glycerol) were investigated in cryopreservation studies with Dictyocaulus viviparus third-stage larvae. Exsheathment with sodium hypochlorite was essential to achieve significant survival. With uninterrupted cooling, highest survival (30% normally motile) was achieved with rates of 10-70 degrees C min-1. Survival was higher (50-75%) using 1 degree C min-1 to -10 degrees C followed by plunging into liquid nitrogen. The optimum warming rate was 6,800 degrees C min-1. The use of cryoprotectants led to marginally lower survival while varying the suspending media had no significant effect on survival. X-irradiated, exsheathed third-stage larvae cryopreserved by the optimum protocol yielded 38.3 +/- 4.2% survival. Two calves each infected with 45,000 (15,000 viable) exsheathed, unirradiated, cryopreserved third-stage larvae harboured 494 worms (1.1% infectivity) and 355 worms (0.8%) at necropsy. Numbers of first-stage larvae in the faeces reached 420/g and 105/g respectively 27 days after infection.

Animals↗

Evidence for the uniqueness of eidetic imagery.

This research examined the performance of eidetic subjects, classified by the standard self-report criteria, on a set of objective and subjective measures. Eidetic subjects were statistically superior to controls on an 'accuracy of report' test and a superimposition task, but these differences were not so large as to provide compelling evidence for the uniqueness of eidetic imagery. Further experiments investigated the effects of stimulus manipulations--type of interference and level of illumination--on, respectively, visual retention and duration of phenomenal image. The pattern of effects differed markedly between eidetic subjects and a control group matched on a measure of capacity for visual memory. These findings provide converging evidence for a qualitative distinction between eidetic imagery and visual memory that does not rely on differences in storage capacity. Eidetic imagery appears to be a long-lasting, percept-like experience which varies considerably in clarity and definition; its duration is critically dependent on level of illumination and its contents are easily disrupted by after-coming visual stimuli.

Adolescent↗

Treatment of public masturbation by behavioral management.

This case history presents a treatment procedure for a nine-year-old girl who masturbated in the classroom. A fading procedure within a behavioral management contract was implemented which proved to be effective. One-, three-, six-, and nine-month follow-ups did not show any evidence of relapse or symptoms substitution.

Behavior Therapy↗

The incidence of bacteremia in pediatric patients following tooth extraction.

Procedures which produce bacteremias may lead to bacterial endocarditis in the susceptible patient. Recent work has suggested that bacteremia does not occur in children following extraction of teeth as it does in adults. One hundred and seven children were divided into four groups. Group I, which consisted of children who had nondiseased primary teeth extracted, had 35% positive blood cultures. Group II consisted of children who had diseased primary and permanent teeth removed. The incidence of positive blood cultures was 53%. Group III, which consisted of patients who had extractions of nondiseased permanent teeth, had a 61% incidence of positive blood cultures. Group IV served as a negative control. Bacteremias do occur in children following the extraction of normal and diseased primary and permanent teeth. Therefore, the susceptible pediatric patient who is to undergo a dental extraction procedure must be given prophylactic antibiotics.

Adolescent↗