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C O'Neill

Publications and source records attributed to C O'Neill.

At least 37 records · Page 2Linked to original sources
PubMed2002

Inpatient costs and paramilitary punishment beatings in northern Ireland.

BACKGROUND: Paramilitary punishment beatings are a common occurrence in Northern Ireland. Little is known about the costs such attacks impose on the health service. METHODS: Data was collected retrospectively on victims treated by Northern Ireland's regional specialist orthopaedics unit. Data related to all victims treated in the unit between January 1999 and May 2000. RESULTS: Average inpatient care costs were 2010 Pounds ($2914). There was no significant difference in these between patients who were shot and those who were beaten. CONCLUSION: Punishment beatings present a small but significant cost burden to the health service. A fuller understanding of them from a health care perspective is warranted.

Adolescent↗
PubMed2001

FKBP12 associates tightly with the skeletal muscle type 1 ryanodine receptor, but not with other intracellular calcium release channels.

This study compared the relative levels of ryanodine receptor (RyR) isoforms, inositol 1,4,5-trisphosphate receptor (IP(3)R) isoforms, and calcineurin, plus their association with FKBP12 in brain, skeletal and cardiac tissue. FKBP12 demonstrated a very tight, high affinity association with skeletal muscle microsomes, which was displaced by FK506. In contrast, FKBP12 was not tightly associated with brain or cardiac microsomes and did not require FK506 for removal from these organelles. Furthermore, of the proteins solubilised from skeletal muscle, cardiac muscle and brain microsomes, only skeletal muscle RyR1 bound to an FKBP12-glutathione-S-transferase fusion protein, in a high affinity FK506 displaceable manner. These results suggest that RyR1 has distinctive FKBP12 binding properties when compared to RyR2, RyR3, all IP(3)R isoforms and calcineurin.

Animals↗
PubMed2001

Chlamydia pneumoniae exposure and inflammatory markers in acute coronary syndrome (CIMACS).

Previous studies have shown higher levels of Chlamydia pneumoniae (C. pneumoniae, CP) antibody titers (CPIgG), C-reactive protein (CRP), and fibrinogen in patients with coronary artery disease. The role of these infectious and inflammatory markers in precipitating acute coronary syndrome (ACS) is unclear. We conducted a cross-sectional study on patients (n = 830, mean age 63 +/- 15 years, 57% male) admitted to the chest pain center of our institution. The differences in the CPIgG, CRP, and fibrinogen levels in patients who were diagnosed with ACS versus those who were not (non-ACS) were evaluated. CPIgG titers tended to be higher in the ACS group than in the non-ACS group. However, when different titers were used to define seropositivity, the difference achieved statistical significance only at the titer of > or =1:1,024 (35% vs 26%, p = 0.004). CRP (median 0.48 vs 0.33 mg/dl, p <0.0001), fibrinogen (median 317 vs 293 mg/dl, p <0.0001), and leukocyte count (median 7.7 vs 6.9 10(9)/L, p <0.0001) were higher in the ACS group. On multivariate analysis, CPIgG > or =1:1,024 (odds ratio [OR] 1.62), diabetes (OR 1.91), hypertension (OR 1.46), prior myocardial infarction (OR 1.78), smoking (OR 1.70), Caucasian race (OR 1.7), high-density lipoprotein (OR 0.98), and elevated troponin-T (OR 12.44) were the only factors independently associated with ACS. Thus, we found a strong association between high level seropositivity to CP and ACS. This may indicate recent re-infection or an exaggerated immune response to CP as an etiologic factor for ACS. This study also suggests that therapeutic interventions may need to be specifically targeted to these patients.

Acute Disease↗
PubMed2001

Evidence for the autocrine induction of capacitation of mammalian spermatozoa.

Mammalian spermatozoa require a maturational event after ejaculation that allows them to acquire the capacity for fertilization. This process, known as capacitation, occurs spontaneously in simple defined medium implicating a potential role of autocrine induction. This study shows that the ether phospholipid 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphocholine (PAF) meets the criteria for an autocrine mediator of capacitation. Sperm released PAF after their dilution into capacitation medium and expressed a receptor for PAF on their membranes. PAF stimulated changes in the motility of sperm and enhanced fertilization in vitro. These actions were inhibited by a PAF receptor antagonist (UR-12519) and by extracellular recombinant PAF:acetylhydrolase (an enzyme that degrades PAF to a biologically inert form). Seminal plasma contained an acid-labile PAF:acetylhydrolase, whereas capacitation was inhibited by an acid-labile factor within seminal plasma, implicating this factor as a potential decapacitation factor within seminal plasma. Sperm from a PAF receptor knock-out mouse strain failed to express the receptor and displayed a significantly (p < 0.01) reduced rate of capacitation, as assessed by the spontaneous onset of the acrosome reaction in vitro. When used for in vitro fertilization, sperm from PAF receptor knock-out mice gave a significantly lower rate of fertilization (21.5%) than did wild-type sperm (66.7%). The study shows for the first time the operation of an autocrine loop that induces capacitation in sperm in vitro and shows that this loop acts in concert with other mediators of capacitation to promote efficient fertilization.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2001

Indirect costs, cost-utility variations and the funding of paediatric cochlear implantation.

OBJECTIVE: To demonstrate the existence of variations in cost-utility associated with indirect costs in paediatric cochlear implantation; to illustrate the implications of this for purchasing decisions and; to posit a potential solution to anomalies in purchasing that may otherwise result when services are publicly funded. METHODS: Data was taken from published sources on the cost of implantation, outcomes measured in terms of quality adjusted life years (QALY) and in savings in education costs associated with paediatric cochlear implantation. Cost-utility ratios across education authorities were calculated using a single centre's implantation costs. RESULTS: Variations in savings across education authorities show that the cost per QALY gain associated with paediatric cochlear implantation can vary between approximately $12,000 and $18,000 assuming an exchange rate of $1.45 = 1 pound sterling for the same implant centre. These variations have the potential to produce situations in which less efficient implant centres are preferred by purchasers over more efficient ones or in which candidates with poorer outcomes are selected for funding over candidates with superior outcomes. It is important that savings associated with education be taken into consideration in evaluations intended to inform purchasing decisions regarding implantation. Equally it is important that potentially anomalous decisions be avoided if evaluations are to remain credible. It is argued that this may be achievable if public funding for implantation is determined at a national level and ring-fenced i.e. devoted exclusively to use in cochlear implantation.

Child↗
PubMed2001

Rapid detection of the R408W and I65T mutations in phenylketonuria by glycosylase mediated polymorphism detection.

Mutation detection methods based upon chemical or enzymatic cleavage of DNA offer excellent detection efficiencies coupled with high throughput and low unit cost. We describe the application of the novel technique of Glycosylase Mediated Polymorphism Detection (GMPD) to the detection of two of the most common mutations of the PAH gene in the Irish population that cause phenylketonuria (PKU), R408W and I65T, which occur at relative frequencies of 41.0% and 10.4% respectively. GMPD assays for R408W and I65T were developed permitting fluorescent detection of cleavage products on the ALFexpresstrade mark automated DNA sequencer. The method was validated by screening a panel of PKU patients whose mutant genotypes had previously been characterised by standard methods. It also proved possible to perform multiplex detection of the two mutations by co-electrophoresis of GMPD products. GMPD is a rapid and robust method for the detection of the R408W and I65T mutations, whose key advantage lies in its use of a pair of enzymes with high cleavage efficiency to detect a number of mutations as compared to the use of individual digestions with a range of specific restriction endonuclease enzymes. Hum Mutat 17:432, 2001.

Alleles↗
PubMed2001

Purification of woodchuck hepatitis surface antigen using a monoclonal antibody raised against the antigen.

Woodchuck hepatitis virus (WHV) is closely related to the human hepatitis B virus (HBV) and infection of woodchucks with WHV creates a useful model for studies of immunity, pathogenesis and therapy of HBV infection. To increase the usefulness of this model, monoclonal antibodies were raised to woodchuck hepatitis surface antigen (WHsAg) and one of these antibodies was used to purify the antigen by affinity chromatography from serum, a simpler and quicker method of purification than the current ultracentrifugation methods. The bands found by SDS-polyacrylamide gel electophoresis of WHsAg were the major 25 and 29 kilodalton (kDa) bands and a triplet of 45, 51 and 55 kDa which are thought to be the glycosylated and unglycosylated middle and large WHsAg. Both the antibody and the antigen are valuable reagents for the study of WHV infection.

Animals↗
PubMed2001

Receptor-G-protein signalling in Alzheimer's disease.

Based on radioligand binding studies, it has long been assumed that the neurochemical pathology of Alzheimer's disease (AD) does not involve widespread changes in post-synaptic neurotransmitter function. However, more recent studies suggest that receptor function in AD may be compromised due to disrupted post-receptor signal transduction, in particular that mediated by the G-protein regulated phosphoinositide hydrolysis and adenylate cyclase (AC) pathways. The phosphoinositide hydrolysis pathway has been shown to be altered at a number of levels in AD post-mortem brains, including impaired agonist and G-protein regulation of phospholipase C, decreased protein kinase C (PKC) levels and activity, and a reduced number of receptor sites for the second messenger, Ins(1,4,5)P3. Of these, loss of Ins(1,4,5)P3 receptors and PKC in the entorhinal cortex and hippocampus correlates with AD-related neurofibrillary changes, as staged according to Braak's protocol. Disregulation of the phosphoinositide hydrolysis pathway may therefore have consequences for the progression of AD pathology. In contrast to the extensive pattern of disruption seen with the phosphoinositide hydrolysis pathway, changes to AC signalling in AD appear more circumscribed. Disruptions include a lesion at the level of Gs-protein stimulation of AC and, at least in the hippocampus, reduced enzyme activities in response to forskolin stimulation. Of these, the latter change has been shown to precede neurofibrillary changes. Apart from a loss of calcium/calmodulin sensitive AC isoforms, other components of this signalling pathway, including G-protein levels, Gi-protein mediated inhibition and protein kinase A levels and activity, remain relatively preserved in the disorder.

Adenylyl Cyclases↗
PubMed2001

Dysfunctional intracellular calcium homoeostasis: a central cause of neurodegeneration in Alzheimer's disease.

The clinical symptoms of all forms of Alzheimer's disease (AD) result from a slowly progressive neurodegeneration that is associated with the excessive deposition of beta-amyloid (A beta) in plaques and in the cerebrovasculature, and the formation of intraneuronal neurofibrillary tangles, which are composed primarily of abnormally hyperphosphorylated tau protein. The sequence of cellular events that cause this pathology and neurodegeneration is unknown. It is, however, most probably linked to neuronal signal transduction systems that become misregulated in the brains of certain individuals, causing excessive A beta to be formed and/or deposited, tau to become aggregated and hyperphosphorylated and neurons to degenerate. We hypothesize that a progressive alteration in the ability of neurons to regulate intracellular calcium, particularly at the level of the endoplasmic reticulum, is a crucial signal transduction event that is linked strongly to the initiation and development of AD pathology. In this chapter we will discuss the key findings that lend support to this hypothesis.

Alzheimer Disease↗
PubMed2001

Identification and regulation of the platelet-activating factor acetylhydrolase activity in the mouse uterus in early pregnancy.

Platelet-activating factor (PAF) is a product of the embryo and the endometrium in early pregnancy. The actions of PAF may be regulated by its degradation and this is largely achieved by the enzyme PAF acetylhydrolase (PAF:ah; EC 3.1.1.47). The present study characterized the PAF:ah in the endometrium and uterine fluid of mice during early pregnancy. The enzyme activity from uterine endometrium and luminal fluids had the same biochemical characteristics as the plasma form of the enzyme. The three sources of enzyme activity (i) had an apparent native molecular mass greater than 10(6) Da, but this was reduced after detergent treatment and purification to 60-65 kDa; (ii) bound to cholesterol hemisuccinate agarose matrix; and (iii) were found in the high density lipoprotein-enriched fraction after density gradient ultracentrifugation. In castrate females, oestradiol-17beta (E2) caused a dose-dependent increase in the activity of the enzyme in endometrium and luminal fluid. Progesterone (P4) inhibited the E2-induced increase in PAF:ah in uterine tissue. Treatment with E2 alone caused an increase in endometrial PAF:ah activity within 24 h, which declined within 48 h. In luminal fluid, the same treatment caused increased activity within 24 h, peaking after 48 h of treatment and then declining. In E2-treated castrate females, mRNA for an intracellular (but not plasma) form of PAF:ah was detected, yet the intracellular form was not detected biochemically. The results suggest that most of the enzyme activity was not produced locally, but probably resulted from the influx of the plasma form of the enzyme.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2001

In vitro fertilization causes epigenetic modifications to the onset of gene expression from the zygotic genome in mice.

The effect of in vitro fertilization (IVF) and culture of mouse preimplantation embryos in vitro on the onset of expression of insulin-like growth factor 1 (IGF-1) ligand and receptor, insulin ligand and receptor, alpha-transforming growth factor (alpha-TGF) ligand, PAF:acetylhydrolase 1b (Pafah1b; alpha(1), alpha(2), and beta subunits of the enzyme), and the transcription requiring complex proteins (TRC) was examined. The IGF-1 ligand was detected in preimplantation embryos by immunofluorescence at all developmental stages tested. However, IVF and culture significantly reduced the amount of protein detected in the 8-cell embryo and blastocyst (P: < 0.001), and this was due to a delayed onset of expression of the mRNA for IGF-1 ligand from the zygotic genome. The expression of the alpha(1) subunit of Pafah1b was first detected at the 2-cell stage in fresh embryos, but expression was significantly retarded (P: < 0.001) when IVF and ISF (in situ-fertilized) zygotes were cultured in vitro. In vitro fertilization or ISF did not delay the onset of expression of TRC nor mRNA for the IGF-1 receptor, insulin receptor, alpha(2) or beta subunit of Pafah1b, nor did they effect alpha-TGF protein synthesis. Thus, IVF causes epigenetic modification in the normal pattern of expression of some but not all genes involved in normal embryo growth and survival.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2000

Characterization and functional significance of calcium transients in the 2-cell mouse embryo induced by an autocrine growth factor.

Growth of preimplantation embryos is influenced by autocrine trophic factors that need to act by the 2-cell stage, but their mode of action is not yet described. This report shows that late zygote and 2-cell stage mouse embryos responded to embryo-derived platelet-activating factor (PAF) with transient increases in intracellular calcium concentration ([Ca(2+)](i)). [Ca(2+)](i) transients were single global events and were specifically induced by embryo-derived PAF. They were blocked by inhibition of phospholipase C (U 73122) and an inositol trisphosphate (IP(3)) receptor antagonist (xestospongin C), indicating the release of calcium from IP(3)-sensitive intracellular stores. Transients were also inhibited by the absence of calcium from extracellular medium and partially inhibited by treatment with dihydropyridine (nifedipine, 10 micrometer), but not pimozide (an inhibitor of an embryonic T-type calcium channel). (+/-)BAY K8644 (an L-type channel agonist) induced [Ca(2+)](i) transients, yet these were completely inhibited by nifedipine (10 micrometer). The complete inhibition of BAY K8644, but only partial inhibition of PAF by nifedipine shows that L-type channels were only partly responsible for the calcium influx. Depolarization of 2-cell embryos by 50 mm K(+) did not inhibit PAF-induced calcium transients, showing that the influx channels were not voltage-dependent. Depletion of intracellular calcium stores by thapsigargin revealed the presence of store-operated channels. The interdependent requirement for IP(3)-sensitive internal calcium stores and extracellular calcium in the generation of PAF-induced transients may be explained by a requirement for capacitative calcium entry via store-operated channels. A functionally important role for the PAF-induced transients is supported by the observation that inhibition of [Ca(2+)](i) transients by a PAF-antagonist (WEB 2086) or an intracellular calcium chelator (1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetrakis-acetoxymethyl ester; BAPTA-AM) caused marked inhibition of early embryo development. Growth inhibition by BAPTA-AM was relieved by addition of exogenous PAF.

Animals↗
PubMed2000

Age and proximity to death as predictors of GP care costs: results from a study of nursing home patients.

This paper reports the results of a study of GP costs associated with a group of nursing home patients who died at various stages during a 12-month period. The relationship between costs per month of care, patient age and proximity to death, where sex and diagnosis are controlled for are reported. A comparison of care costs for patients in their last year of life and those who survived the course of the study is also made. The study found that those in their last year of life were significantly more expensive to care for than those who survived the duration of the study, but that there was no statistically significant difference in age. In multivariate regression analyses, it was also found that among those who died during the study care costs were unrelated to age, but significantly related to proximity to death. The study supports the contention of others (Zweifel P, Felder S, Meiers M. Ageing of population and health care expenditure: a red herring? Health Econ 1999; 8: 485-496) that health care costs are more directly related to proximity to death than age.

Age Factors↗
PubMed2000

Azo-dye degradation in an anaerobic-aerobic treatment system operating on simulated textile effluent.

Decolorisation of azo dyes during biological effluent treatment can involve both adsorption to cell biomass and degradation by azo-bond reduction during anaerobic digestion. Degradation is expected to form aromatic amines, which may be toxic and recalcitrant to anaerobic treatment but degradable aerobically. Methods for the quantitative detection of substituted aromatic amines arising from azo-dye cleavage are complex. A simple qualitative method is suggested as a way in which to investigate whether decolorisation is actually due to degradation, and whether the amines generated are successfully removed by aerobic treatment. Samples from a combined anaerobic-aerobic system used for treating a simulated textile wastewater containing the reactive azo dye Procion Red H-E7B were analysed by high-performance liquid chromatography/ultraviolet (HPLC-UV) methods. Anaerobic treatment gave significant decolorisation, and respiration-inhibition tests showed that the anaerobic effluent had an increased toxicity, suggesting azo-dye degradation. The HPLC method showed that more polar, UV-absorbing compounds had been generated. Aerobically, these compounds were removed or converted to highly polar compounds, as shown by HPLC analysis. Since the total organic nitrogen (TON) decreased aerobically as organic N-containing compounds were mineralised, aromatic amine degradation is suggested. Although only a simple qualitative HPLC method was used, colour removal, toxicity and TON removal all support its usefulness in analysing biotreatment of azo dyes.

Aerobiosis↗
PubMed2000

Adoption, permanent care and foster care: home-based care in and beyond the 1990s.

Home-based care in Australia has changed considerably in the past two decades. The majority of children in adoptive, permanent care and foster families are likely to have experienced abuse, neglect and multiple placements. The disruptive behaviours displayed by these children undermine the potential for attachment offered by their new families. While the needs of the child will be obvious, the challenge for paediatricians is to recognize the relative instability of these newly established families and the high levels of stress they experience.

Adoption↗
PubMed2000

A cost analysis of neonatal care in the UK: results from a multicentre study. ECSURF Study Group.

BACKGROUND: A number of papers have recently been published examining the magnitude of scale economies in neonatal care and the level of activity at which these become attainable. Although these agree there is scope for economies in the production of neonatal care, they debate the extent to which such economies are attainable and how they might best be detected. A major multicentre study of neonatal units in the United Kingdom has produced costing and activity data allowing these issues to be explored afresh. METHODS: A postal questionnaire was used to determine neonatal cost and activity levels in 57 UK neonatal units. Costs for the financial year 1990-1991 related to clinical staffing, support (such as pathology) and overheads (such as heat, light, power and administrative overheads). Activity related to the total number of care days provided and the number of these that were intensive in nature. All data were scrutinized to ensure consistent definitions. A multivariate regression analysis was used to investigate the relationship between costs and activity. RESULTS: A double-log function relating variations in total costs to total days, case-mix and an interaction term provided the best fit to the data. The analysis suggests that significant economies of scale are possible within the observed range of provision of intensive care. CONCLUSIONS: Significant economies of scale may be attainable. Nevertheless, these results should be carefully interpreted. In particular, the costs of neonatal care should not be examined in isolation but in relation to outcomes. In certain instances, units of inefficient scale but acceptable outcome may be defensible on grounds of ease of access.

Health Care Costs↗
PubMed2000

A cost-utility analysis of pediatric cochlear implantation.

OBJECTIVE/HYPOTHESIS: The aim of this study was to explore the cost-utility of pediatric cochlear implantation, incorporating savings associated with education into the analysis. METHODS: The costs of pediatric cochlear implantation were based on the full costs levied to purchasers, inclusive of complications and maintenance, by a large pediatric cochlear implant program in the United Kingdom. After implantation, profoundly hearing-impaired children have been found to develop hearing threshold levels equivalent to severely hearing-impaired children who wear hearing aids. An independent study calculated the educational costs for severely hearing-impaired and profoundly hearing-impaired children. From this study, savings in educational costs that would result from enabling the profoundly hearing-impaired to function as severely hearing-impaired were determined. Cost-utility was established conservatively by applying to children the known gains in utility reported by adults with cochlear implants. RESULTS: The discounted costs of creating a pediatric cochlear implant user and of maintaining the child over the first 12 years were 48,757 pound silver($78,011). The discounted difference in education costs associated with a profoundly hearing-impaired child (HL >95 dB) as compared with a severely hearing-impaired child (HL 70-95 dB) over the same period was 26,781 pound silver($42,850). These represent the potential savings in educational costs associated with pediatric cochlear implantation. Assuming implantation at age 4 years, the discounted net average cost of pediatric cochlear implantation over compulsory school years (ages 4-16) was 21,976 pound silver ($35,162). Cochlear implants have been shown to improve the quality of life in adults by 0.23 points per annum (where quality of life is rated on a scale from 0 to 1). Applying this weight to children receiving implantation at age 4 years, and assuming a life expectancy of 74 years, the quality-adjusted life-year (QALY) gain is calculated to be 16.33. The cost per undiscounted QALY gain was estimated to be 1,345.70 pound silver ($2153.12) and per discounted QALY gain to be 10,341 pound silver ($16,545.60). CONCLUSION: This study provides evidence, based on conservative assumptions, to support the view that pediatric cochlear implantation is a cost-effective health care intervention in profoundly hearing-impaired young children.

Child↗