Showing papers by "Trinity College, Dublin published in 1996"

Eradication of Helicobacter pylori Using One‐week Triple Therapies Combining Omeprazole with Two Antimicrobials: The MACH I Study

Abstract: The discovery of Helicobacter pylori (H. pylori) opened the doors to new insight and therapy for peptic ulcer disease. Earlier eradication treatment modalities based on bismuth compounds, with or without additional antimicrobials, were not well accepted mainly because of the, at least hypothetical, risks for neurological and/or renal side effects. The first proton pump inhibitor, omeprazole, had been proven as a very effective short-term anti-ulcer therapy, but after withdrawal of the drug, the recurrence rate was high. theoretically, acid suppression was believed to increase the H. pylori infestation as the environment became more neutral. On the other hand, acid suppression could increase the effect of acid labile antimicrobials. This was not investigated before the studies presented in this thesis were performed.A small pilot study (Paper I) in 24 patients showed that 7 out of 8 patients treated for fourteen days with omeprazole 40 mg o.m. + amoxicillin 750 mg b.i.d. were cleared of H. pylori, while it remained in 7/8 patients on omeprazole as monotherapy and in 2/7 patients on amoxicillin as monotherapy. However, the eradication rates 4 weeks after treatment were 5/8, 0/8 and 1/7 in the three groups, respectively. These results were confirmed in a large study (Paper II) comprising 248 consecutive patients with active duodenal ulcer disease. All had an initial treatment period for two weeks with omeprazole 40 mg o.m., followed by continued omeprazole in combination with amoxicillin 750 mg b.i.d. or amoxicillin placebo for a further two weeks. In the dual therapy group, 54% of patients were H. pylori eradicated compared to 4% in the omeprazole mono therapy group. Furthermore, the duodenal ulcer relapse rate was significantly lower in the combination group compared to the monotherapy group (p<0,001). Paper III represents a study that was preformed to assess whether improved results could be obtained by adding two antimicrobials to omeprazole. In total 787 patients were randomized to six treatment arms, where omeprazole was combined with two of the three antimicrobials amoxicillin, metronidazole and c!arithromycin in various doses and combinations. The results showed that one week's treatment was sufficient for a very high eradication rate. A combination of omeprazole 20 mg b.i.d. + amoxicillin 1000 mg b.i.d. + clarithromycin 500 mg b.i.d. was superior to a combination with a lower clarithromycin dose of 250 mg b.i.d. or amoxicillin in combination with metronidazole, but not significantly better than the other two arms containing metronidazole+ clarithromycin in a dose of 250 mg b.i.d. 500 mg b.i.d. Paper IV was designed to establish whether or not acid suppression is necessary during antimicrobial treatment. In total 539 patients were randomized. Eradication rates with omeprazole added to antimicrobials were much higher than in treatment groups not receiving omeprazole. In metronidazole resistant strains, only 76% were eradicated in comparison to 95% in susceptible strains. Amoxicillin resistance did not occur and clarithromycin resistance was found in only 3% of patients. Thus, papers I-IV proved the efficacy ofthe new treatment modality, which, however, represented high costs in the short-term perspective.The cost-effectiveness of various treatment strategies in regular use at that time was evaluated in paper V. The economic model showed that in comparison to continuous therapy with gastric acid suppressive drugs, the extra initial cost for eradication therapy was paid within one year and, in comparison to intermittent therapy, within three years.Conclusion: These studied have shown convincingly that eradication of H. pylori with a combination of gastric acid suppression and two antimicrobials (amoxicillin and clarithromycin) is the most effective treatment in PUD, giving a high eradication rate and consequently lower peptic ulcer recurrence. Thus, this treatment strategy is also very cost-effective for society.

Mitochondrial diversity and the origins of African and European cattle

Abstract: The nature of domestic cattle origins in Africa are unclear as archaeological data are relatively sparse. The earliest domesticates were humpless, or Bos taurus, in morphology and may have shared a common origin with the ancestors of European cattle in the Near East. Alternatively, local strains of the wild ox, the aurochs, may have been adopted by peoples in either continent either before or after cultural influence from the Levant. This study examines mitochondrial DNA displacement loop sequence variation in 90 extant bovines drawn from Africa, Europe, and India. Phylogeny estimation and analysis of molecular variance verify that sequences cluster significantly into continental groups. The Indian Bos indicus samples are most markedly distinct from the others, which is indicative of a B. taurus nature for both European and African ancestors. When a calibration of sequence divergence is performed using comparisons with bison sequences and an estimate of 1 Myr since the Bison/Bos Leptobos common ancestor, estimates of 117-275,000 B.P. and 22-26,000 B.P. are obtained for the separation between Indians and others and between African and European ancestors, respectively. As cattle domestication is thought to have occurred approximately 10,000 B.P., these estimates suggest the domestication of genetically discrete aurochsen strains as the origins of each continental population. Additionally, patterns of variation that are indicative of population expansions (probably associated with the domestication process) are discernible in Africa and Europe. Notably, the genetic signatures of these expansions are clearly younger than the corresponding signature of African/European divergence.

Watermarking digital images for copyright protection

Abstract: A watermark is an invisible mark placed on an image that is designed to identify both the source of an image as well as its intended recipient. The authors present an overview of watermarking techniques and demonstrate a solution to one of the key problems in image watermarking, namely how to hide robust invisible labels inside grey scale or colour digital images.

Pulsed laser deposition of thin films of (

Abstract: Manganites of the series , with x = 0, 0.1, 0.3, 0.5, 0.7 and 1.0, have been characterized in ceramic form and thin films have been prepared by pulsed laser deposition. Characterization techniques included x-ray diffraction, conductivity and magnetoresistance, magnetization and susceptibility, optical spectroscopy and the Faraday effect. Both the films and ceramics exhibit a maximum low-temperature conductivity at which is coexistent with ferromagnetic order. The negative magnetoresistance effect is qualitatively different for the x = 0.3 and x = 0.5 compositions. For x = 0.3 the magnetoresistance peak occurs around the Curie point, whereas for x = 0.5 the onset of magnetoresistance is somewhat below and increases monotonically as . The applied field appears to modify the magnetic order (on the scale of the spin diffusion length) down to the lowest temperatures for x = 0.5, but for x = 0.3 the ferromagnetic order is essentially complete and collinear below the Curie point.

Rare-earth iron permanent magnets

Abstract: Introduction 1. Intrinsic magnetic properties 2. Phase diagrams 3. Gas-solid reactions 4. Coercivity 5. Microstructure and magnetic domains 6. Processing 7. Static applications 8. Magneto-mechanical devices 9. Permanent magnet motors 10. Actuators Index

The common 'thermolabile' variant of methylene tetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia

Abstract: Mild hyperhomocysteinaemia is a major risk factor for vascular disease and neural tube defects (NTDs), conferring an approximately three-fold relative risk for each condition. It has several possible causes: heterozygosity for rare loss of function mutations in the genes for 5,10-methylene tetrahydrofolate reductase (MTHFR) or cystathionine-beta-synthase (CBS); dietary insufficiency of vitamin co-factors B6, B12 or folates; or homozygosity for a common 'thermolabile' mutation in the MTHFR gene which has also been associated with vascular disease and NTDs. We quantified the contribution of the thermolabile mutation to the hyperhomocysteinaemic phenotype in a working male population (625 individuals). Serum folate and vitamin B12 concentrations were also measured and their relationship with homocysteine status and MTHFR genotype assessed. The homozygous thermolabile genotype occurred in 48.4, 35.5, and 23.4% of the top 5, 10, and 20% of individuals (respectively) ranked by plasma homocysteine levels, compared with a frequency of 11.5% in the study population as a whole, establishing that the mutation is a major determinant of homocysteine levels at the upper end of the range. Serum folate concentrations also varied with genotype, being lowest in thermolabile homozygotes. The MTHFR thermolabile genotype should be considered when population studies are designed to determine the effective homocysteine-lowering dose of dietary folate supplements, and when prophylactic doses of folate are recommended for individuals.

Ebb and flow of the chloroplast inverted repeat

Abstract: The endpoints of the large inverted repeat (IR) of chloroplast DNA in flowering plants differ by small amounts between species. To quantify the extent of this movement and define a possible mechanism for IR expansion, DNA sequences across the IR-large single-copy (IR-LSC) junctions were compared among 13 Nicotiana species and other dicots. In most Nicotiana species the IR terminates just upstream of, or somewhere within, the 5' portion of the rps19 gene. The truncated copy of this gene, rps19', varies in length even between closely related species but is of constant size within a single species. In Nicotiana, six different rps19' structures were found. A phylogenetic tree of Nicotiana species based on restriction site data shows that the IR has both expanded and contracted during the evolution of this genus. Gene conversion is proposed to account for these small and apparently random IR expansions. A large IR expansion of over 12 kb has occurred in Nicotiana acuminata. The new IR-LSC junction in this species lies within intron 1 of the clpP gene. This rearrangement occurred via a double-strand DNA break and recombination between poly (A) tracts in clpP intron 1 and upstream of rps19. Nicotiana acuminata chloroplast DNA contains a "molecular fossil' of the IR-LSC junction that existed prior to this dramatic rearrangement.

The foam drainage equation

Abstract: The drainage of liquid in a foam may be described in terms of a nonlinear partial differential equation for the foam density as a function of time and vertical position. We review the history and recent development of this theory, analysing various exact and approximate solutions and relating them to each other.

Treatment of menorrhagia during menstruation: randomised controlled trial of ethamsylate, mefenamic acid, and tranexamic acid

Abstract: Objective: To compare the efficacy and acceptability of ethamsylate, mefenamic acid, and tranexamic acid for treating menorrhagia. Design: Randomised controlled trial. Setting: A university department of obstetrics and gynaecology. Subjects: 76 women with dysfunctional uterine bleeding. Interventions: Treatment for five days from day 1 of menses during three consecutive menstrual periods. 27 patients were randomised to take ethamsylate 500 mg six hourly, 23 patients to take mefenamic acid 500 mg eight hourly, and 26 patients to take tranexamic acid 1 g six hourly. Main outcome measures: Menstrual loss measured by the alkaline haematin method in three control menstrual periods and three menstrual periods during treatment; duration of bleeding; patient9s estimation of blood loss; sanitary towel usage; the occurrence of dysmenorrhoea; and unwanted events. Results: Ethamsylate did not reduce mean menstrual blood loss whereas mefenamic acid reduced blood loss by 20% (mean blood loss 186 ml before treatment, 148 ml during treatment) and tranexamic acid reduced blood loss by 54% (mean blood loss 164 ml before treatment, 75 ml during treatment). Sanitary towel usage was significantly reduced in patients treated with mefenamic acid and tranexamic acid. Conclusions: Tranexamic acid given during menstruation is a safe and highly effective treatment for excessive bleeding. Patients with dysfunctional uterine bleeding should be offered medical treatment with tranexamic acid before a decision is made about surgery. Key messages In any year around 5% of women aged 30-49 years visit their general practitioners with menor-rhagia Every year in the United Kingdom around 45 000 hysterectomies and a further 10 000 endometrial ablations are performed for menorrhagia The commonest drug prescribed in the British Isles for menorrhagia (norethisterone) has little or no effect in reducing menstrual bleeding Tranexamic acid (an antifibrinolytic) 1 g six to eight hourly reduces menstrual blood loss by over half and should be offered to women with dysfunctional bleeding before a decision is made about surgery

Homocysteine and Risk of Premature Coronary Heart Disease Evidence for a Common Gene Mutation

Abstract: Background Plasma homocysteine levels are modulated by nutritional and genetic factors, among which is the enzyme methylenetetrahydrofolate reductase (MTHFR) A common defective (thermolabile) variant of this enzyme is causally associated with elevated plasma homocysteine, itself an independent risk factor for coronary heart disease Methods and Results To examine the hypothesis that the allele (T) that codes for the thermolabile defect increases the risk of coronary heart disease, we studied 111 patients with clinical and objective investigational evidence of coronary heart disease and 105 control subjects The frequencies of the thermolabile defect (T) in patients and control subjects were measured, and the prevalence of elevated plasma total homocysteine according to genotype was assessed The frequency of the defective allele was higher in patients than in control subjects with an OR of 16 (95% CI, 11 to 24; P=02) The OR in the coronary heart disease group for the homozygous TT genotype was 29 (

Giant Magnetoresistive Effects in a Single Element Magnetic Thin Film.

Abstract: By exploiting the simplicity of a novel transport measurement on a ferromagnetic striped domain structure in a thin film of cobalt, we report the first direct observation of ferromagnetic domain wall scattering and what we believe to be the first clear indication of giant magnetoresistive effects in a homogeneous magnetic system. $($The colossal MR effect, while seen in homogeneous materials, is believed to originate from a charge ordering phenomenon [see, for example, Y. Tokura et al., J. Appl. Phys. 79, 5288 (1996), and references therein], and is therefore distinct from GMR, which is an effect arising from spin dependent scattering. $)$ A new model is proposed to describe these observations which highlights the crucial role played by electron spin precession in determining the electrical transport properties of magnetic interfaces.

Average Entropy of a Quantum Subsystem.

Abstract: It was recently conjectured by D. Page that if a quantum system of Hilbert space dimension $\mathrm{nm}$ is in a random pure state then the average entropy of a subsystem of dimension $m$ where $m\ensuremath{\le}n$ is ${S}_{m,n}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}\left(\ensuremath{\Sigma}{k\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}n+1}^{\mathrm{mn}}1/k\right)\ensuremath{-}(m\ensuremath{-}1)/2n$. In this Letter a simple proof of this conjecture is given.

Role of the lactate transporter (MCT1) in skeletal muscles

Abstract: We used an antibody, constructed against the monocarboxylate transporter 1 (MCT1) protein (L. Carpenter, R. C. Poole, and A. P. Halestrap. Biochim. Biophys. Acta 1279: 157-165, 1996), to study the expression and role of MCT1 in rat skeletal muscles. MCT1 was higher in red than in white muscles (P 0.05). MCT1 was highly correlated with citrate synthase activity, a marker of the oxidative capacity of muscle (r = 0.82). Therefore, MCT1 may have kinetics that favor the uptake of L-lactate into the muscle cell for oxidative metabolism, and MCT1 may be coordinately expressed with the heart forms of LDH and enzymes of oxidative metabolism.

Additional support for schizophrenia linkage on chromosomes 6 and 8: A multicenter study

Abstract: In response to reported schizophrenia linkage findings on chromosomes 3, 6 and 8, fourteen research groups genotyped 14 microsatellite markers in an unbiased, collaborative (New) sample of 403-567 informative pedigrees per marker, and in the Original sample which produced each finding (the Johns Hopkins University sample of 46-52 informative pedigrees for chromosomes 3 and 8, and the Medical College of Virginia sample of 156-191 informative pedigrees for chromosome 6). Primary planned analyses (New sample) were two-point heterogeneity lod score (lod2) tests (dominant and recessive affected-only models), and multipoint affected sibling pair (ASP) analysis, with a narrow diagnostic model (DSM-IIIR schizophrenia and schizoaffective disorders). Regions with positive results were also analyzed in the Original and Combined samples. There was no evidence for linkage on chromosome 3. For chromosome 6, ASP maximum lod scores (MLS) were 2.19 (New sample, nominal p = 0.001) and 2.68 (Combined sample, p = .0004). For chromosome 8, maximum lod2 scores (tests of linkage with heterogeneity) were 2.22 (New sample, p = .0014) and 3.06 (Combined sample, p = .00018). Results are interpreted as inconclusive but suggestive of linkage in the latter two regions. We discuss possible reasons for failing to achieve a conclusive result in this large sample. Design issues and limitations of this type of collaborative study are discussed, and it is concluded that multicenter follow-up linkage studies of complex disorders can help to direct research efforts toward promising regions.

Pressure fluctuations, phase separation, and gold precipitation during seismic fracture propagation

Abstract: Gold mineralization at Croagh Patrick, western Ireland, occurs in quartz veins associated with three synchronous oblique tensile shear systems. The veins evolved by progressive thickening of isolated, en echelon, lensoid tensile fractures that show a power-law relation between their length and thickness. A change in power-law exponent marks the linking of the en echelon arrays by large, oblique-tensile veins. Fluid-inclusion data show that gold was deposited due to unmixing of an H 2 O-CO 2 -NaCl fluid at 320–240 °C and 160–30 MPa primarily due to decreases in fluid pressure. Evidence for phase separation is only observed in the large linking veins and is abundant close to intersections of the vein arrays. These sites are where high gold grades occur. The distribution of gold is believed to reflect both spatial and temporal variations in fluid pressure fluctuation during seismic fracture propagation, controlled by the vein growth mechanism and zones of maximum dilation.

Spin scattering in ferromagnetic thin films

Abstract: By combining parallel and transverse magnetoresistance measurements on thin films of Co and Ni, the contribution of spin scattering at the domain walls is separated from the anisotropic magnetoresistance (AMR). A model, based on the Larmor-precession-induced deviation of the conduction electron spin direction during domain-wall traversal is developed. By using a scattering probability which varies with the cosine of the angle between the carrier spin and the local exchange field (as used for giant magnetoresistance systems) it is possible to account for the amplitude of the measured magnetoresistive effect. \textcopyright{} 1996 The American Physical Society.

Allelic association between a Ser-9-Gly polymorphism in the dopamine D3 receptor gene and schizophrenia

Abstract: We examined a Ser-9-Gly polymorphism in the dopamine D3 receptor gene for allelic association with schizophrenia in 133 patients currently treated with clozapine and 109 controls. Allele 1 (Ser-9) was significantly more frequent in the patients (69%) than in the controls (56%) (P = 0.004). The 1-1 genotype was more common (43% vs 30%) and the 2-2 genotype less common (5% vs 18%) in patients than in controls. When the patient group was subdivided on the basis of clinical response to clozapine, using a 20-point improvement in the global assessment scale as cut-off, genotype 1-1 was found to be more frequent among the non-responders (53% vs 36%, P = 0.04). To place our results in the context of previous studies of this polymorphism and schizophrenia, we performed a meta-analysis of all published data including the present sample. The combined analysis shows evidence for a modest association between genotype 1-1 and schizophrenia (odds ratio 1.25, 95% confidence interval 1.05-1.49, P = 0.01). These results suggest that the Ser-9 allele, or a nearby polymorphism in linkage disequilibrium, results in a small increase in susceptibility to schizophrenia.

The effects of caring for a spouse with Parkinson's disease on social, psychological and physical well-being

Abstract: BACKGROUND: Several previous studies have examined the health of carers, but they have usually focused on elderly subjects and have often not had representative control samples. AIM: To determine whether caring for a partner with Parkinson's disease is associated with a worsening social, psychological and physical well-being than people with partners who do not suffer with Parkinson's disease. METHOD: One hundred and fifty-four carer spouses of subjects with Parkinson's disease, and 124 non-carer spouses of randomly selected population controls recruited from a national case-control study of early-onset Parkinson's disease in the Republic of Ireland, between 1992-1994, were studied. Outcome was measured along three dimensions: social functioning, assessed by the frequency of social contacts, outings and holidays; psychological well-being, measured by the General Health Questionnaire; and physical health, measured by the career's use of medical services, medications and episodes of chronic illness. RESULTS: Carer spouses were less likely to get out of the house once a week at least (odds ratio 1.79, 95% confidence intervals 1.00-3.20) or to have had a holiday in the last year (odds ratio 1.71, 95% confidence intervals 1.01-2.90). Contact with friends and neighbours decreased with increasing care provision. For spouses providing a lot of care, there was an almost fivefold increase in psychiatric morbidity (odds ratio 4.86, 95% confidence intervals 1.5-15.9) after adjusting for other variables. Most of the medical outcomes were less favourable among carers, but only the use of tranquilizers (odds ratio 3.73, 95% confidence intervals 1.18-11.8) and episodes of chronic illness (odds ratio 2.96, 95% confidence intervals 1.27-6.94) were significant. CONCLUSIONS: Overall, career spouses have slightly worse social, psychological and physical profiles. For social outcomes, increasing care provision is associated with fewer contacts, outings and holidays. For psychological and physical measures, carers providing a lot of care experience worse health. These results have implications for targeting appropriate interventions.

2-mercaptoethanol restores the ability of nuclear factor kappa B (NF kappa B) to bind DNA in nuclear extracts from interleukin 1-treated cells incubated with pyrollidine dithiocarbamate (PDTC). Evidence for oxidation of glutathione in the mechanism of inhibition of NF kappa B by PDTC.

Abstract: The metal chelator and anti-oxidant pyrollidine dithiocarbamate (PDTC) has been used extensively in studies implicating reactive oxygen intermediates in the activation of nuclear factor kappa B (NF kappa B). In agreement with other studies, we have shown that PDTC inhibits NF kappa B activation in response to the pro-inflammatory cytokines interleukin 1 (IL1) and tumour necrosis factor (TNF). However, we have found that the inhibition was reversed by treatment of inhibited nuclear extracts with the reducing agent 2-mercaptoethanol. This was observed in extracts prepared from IL1-treated EL4.NOB-1 thymoma cells and TNF-treated Jurkat E6.1 lymphoma cells. These results suggested that the inhibition was caused by oxidation of NF kappa B on a sensitive thiol, possibly on the p50 subunit (which was detected in NF kappa B complexes in both cell types), and not by inhibition of the activation pathway. The possibility that PDTC was acting as a pro-oxidant was therefore investigated. PDTC caused an increase in oxidized glutathione, suggesting that it acts as an oxidizing agent in the cells tested rather than as an anti-oxidant. Similar results were obtained with diamide, a compound designed to oxidize glutathione. Finally, an increase in the ratio of oxidized to reduced glutathione was shown to inhibit NF kappa B-DNA binding in vitro. On the basis of these results we suggest that, while NF kappa B activation is unaffected by PDTC, DNA binding is inhibited through a mechanism involving a shift towards oxidizing conditions, and that this is the mechanism of action of both PDTC and diamide in the cells tested here.

Learning Adaptation Rules from a Case-Base

Abstract: A major challenge for case-based reasoning (CBR) is to overcome the knowledge-engineering problems incurred by developing adaptation knowledge. This paper describes an approach to automating the acquisition of adaptation knowledge overcoming many of the associated knowledge-engineering costs. This approach makes use of inductive techniques, which learn adaptation knowledge from case comparison. We also show how this adaptation knowledge can be usefully applied. The method has been tested in a property-evaluation CBR system and the technique is illustrated by examples taken from this domain. In addition, we examine how any available domain knowledge might be exploited in such an adaptation-rule learning-system.