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Biomedical subjects

C O'Neill

Publications and source records attributed to C O'Neill.

At least 55 records · Page 3Linked to original sources

Do GPs working in practice with high or low prescribing costs have different views on prescribing cost issues?

BACKGROUND: In a previous study we found that a minority of general practitioners (GPs) had different views to health authority advisers on a number of prescribing cost issues. However, there were few differences between subgroups of GPs. We hypothesised that subgroups that might show differences were GPs from practices with either high or low prescribing costs. AIM: To assess differences in views on prescribing cost issues between GPs working in practices with either high or low prescribing costs. METHOD: Using PACTLINE data, prescribing costs were obtained for general practices within the Trent Region for the financial year 1996 to 1997. A questionnaire was sent anonymously to 340 GPs working in those practices with high prescribing costs, and to 322 GPs working in practices with the lowest prescribing costs. RESULTS: A total of 216 (63.5%) GPs from high-cost practices and 194 (60.2%) from low-cost practices responded. There were statistically significant differences between the two groups on seven out of 22 statements. However, when the confounding effect of fundholding was taken into account, significant differences were found for just three statements and each of these related to substitution with comparable but cheaper drugs. CONCLUSIONS: GPs working in practices with either high or low prescribing costs had different views on a number of statements concerning substitution with comparable but cheaper drugs. When encouraging GPs to control their prescribing costs, a different approach may be required for doctors in some high-cost practices.

Attitude of Health Personnel↗

Plasma xanthophyll carotenoids correlate inversely with indices of oxidative DNA damage and lipid peroxidation.

Post hoc analysis of data obtained from a study designed to modulate oxidative damage by dietary intervention revealed consistently strong inverse correlations between plasma xanthophyll carotenoids and oxidative damage indices. Thirty-seven women participated in a 14-day dietary intervention that increased mean vegetable and fruit (VF) consumption to approximately 12 servings/day. An additional 10 subjects participated in an intervention that limited VF consumption to less than four servings per day. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) in DNA isolated from peripheral lymphocytes and 8-OHdG excreted in urine were measured as indices of oxidative DNA damage. Lipid peroxidation was assessed by measuring 8-epiprostaglandin F2alpha (8-EPG) in urine. Plasma levels of selected carotenoids were also determined, with the intention of using a-carotene as a biochemical index of VF consumption. Urinary 8-OHdG and 8-EPG were measured by ELISA, and plasma carotenoids were measured by high performance liquid chromatography. Lymphocyte 8-OHdG was measured by reverse phase high performance liquid chromatography with electrochemical detection. We observed that the structurally related xanthophyll carotenoids, lutein and beta-cryptoxanthin, which occur in dissimilar botanical families, were consistently inversely associated with these oxidative indices. Statistically significant inverse correlations were observed between plasma lutein and/or beta-cryptoxanthin levels and lymphocyte 8-OHdG and urinary 8-EPG. Moreover, an inverse correlation was observed between change in plasma xanthophylls and change in lymphocyte 8-OHdG concentration that occurred during the course of the study. These data lead us to hypothesize that lutein and beta-cryptoxanthin serve as markers for the antioxidant milieu provided by plants from which they are derived. Whether these carotenoids are directly responsible for the observed antioxidant phenomena merits further investigation.

8-Hydroxy-2'-Deoxyguanosine↗

The impact of nursing home patients on general practitioners' workload.

BACKGROUND: Although the number of people in nursing homes has risen substantially in recent years, the shift of responsibility into general practice has rarely been accompanied by extra resources. These patients may be associated with a higher general practitioner (GP) workload than others of similar age and sex. AIM: To assess the GP workload associated with nursing home residents and its associated costs. METHOD: All nursing home residents aged over 65 years and registered with nine Nottinghamshire practices during one year were matched with patients living in the community for general practice, age, and sex. Data were collected retrospectively for both groups on key workload measures. Costs for the workload measures were calculated using published estimates. RESULTS: Data were collected for 270 pairs of patients. Nursing home patients had more face-to-face contacts in normal surgery hours, telephone calls, and out-of-hours visits. The mean workload cost per month of a nursing home patient (assuming that one patient was seen per visit) was estimated to be 18.21 Pounds (10.49 Pounds higher than the cost of controls). A sensitivity analysis demonstrated that potential savings in visiting costs associated with increasing the numbers of patients seen per visit were 27% for one extra patient seen per visit and 44% for four extra patients. CONCLUSION: Nursing home residents were associated with higher workload for GPs than other patients of the same age and sex living in the community. Our costings provide a basis for negotiating suitable reimbursement of GPs for their additional work.

Aged↗

Variations in GP nursing home patient workload: results of a multivariate analysis.

The number of old people living in UK nursing homes has increased substantially over the past 15 y. There is evidence that such patients generate larger workloads for primary carers than do those of similar age and sex living in their own homes. Clearly, any extra workload involved in providing primary care services to nursing home patients, needs to be reflected in the resources afforded general practitioners (GPs) who are tasked with its provision. By the same token variations in workloads between patients need to be examined and explained for any insights these might provide on funding issues. To examine and explain variations in GP workload associated with nursing home patients and determine the implications of these for GP funding, a 12 month case control study of all nursing home residents over 65 y old registered with nine general practices was undertaken. A multivariate regression analysis was used to examine variations in GP workload associated with 270 nursing home patients. Multivariate regression models explaining the variation in workload cost per month in terms of the GP practice delivering care and patients age and sex had little explanatory power (R(2)=0.07). A fuller method including the patient's Barthel score and initial diagnosis as additional explanatory variables added little to the explanatory power of the model (R(2)=0.12). The ability of the multivariate models used here to explain the variation in GP workload was poor. GPs may require an allowance to compensate for differences in workload associated with nursing home patients but adjusting these payments for differences in age, sex, initial diagnosis or the other variables included in this analysis would not appear to be supported.

Aged↗

Alterations in the ryanodine receptor calcium release channel correlate with Alzheimer's disease neurofibrillary and beta-amyloid pathologies.

Investigation of the integrity of the ryanodine receptor in Alzheimer's disease is important because it plays a critical role in the regulation of calcium release from the endoplasmic reticulum in brain, impairment of which is believed to contribute to the pathogenesis of Alzheimer's disease. The present study compared ryanodine receptor levels and their functional modulation in particulate fractions from control and Alzheimer's disease temporal cortex, occipital cortex and putamen. Relationships between ryanodine receptor changes and the progression of Alzheimer's disease pathology were determined by examining autoradiographic [3H]ryanodine binding in entorhinal cortex/anterior hippocampus sections from 22 cases that had been staged for neurofibrillary changes and beta-amyloid deposition. A significant (P < 0.02) 40% decrease in the Bmax for [3H]ryanodine binding and significantly higher IC50 values for both magnesium and Ruthenium Red inhibition of [3H]ryanodine binding were detected in Alzheimer's disease temporal cortex particulate fractions compared to controls. Immunoblot analyses showed Type 2 ryanodine receptor holoprotein levels to be decreased by 20% (P < 0.05) in these Alzheimer's disease cases compared to controls. No significant differences were detected in [3H]ryanodine binding comparing control and Alzheimer's disease occipital cortex or putamen samples. The autoradiography study detected increased [3H]ryanodine binding in the subiculum, CA2 and CA1 regions in cases with early (stage I-II) neurofibrillary pathology when compared to Stage 0 cases. Analysis of variance of data with respect to the different stages of neurofibrillary pathology revealed significant stage-related declines of [3H]ryanodine binding in the subiculum (P < 0.02) with trends towards significant decreases in CA1, CA2 and CA4. Post-hoc testing with Fisher's PLSD showed significant reductions (74-94%) of [3H]ryanodine binding in the subiculum, and CA1-CA4 regions of the late isocortical stage (V-VI) cases compared to the early entorhinal stage I-II cases. [3H]Ryanodine binding also showed significant declines with staging for beta-amyloid deposition in the entorhinal cortex (P < 0.01) and CA4 (P < 0.05) with trends towards a significant decrease in the dentate gyrus. We conclude that alterations in ryanodine receptor binding and function are very early events in the pathogenesis of Alzheimer's disease, and may be fundamental to the progression of both neurofibrillary and beta-amyloid pathologies.

Adult↗

Core competencies for preventive medicine residents: Version 2.0.

During the early 1990s, the American College of Preventive Medicine (ACPM), with support from the Health Resources and Services Administration (HRSA), identified core competencies and performance indicators (measures to assess their achievement) for all preventive medicine residents. After the competencies were approved, distributed by the ACPM and HRSA, and published in the American Journal of Preventive Medicine, they were integrated in various ways into the operation of individual residency programs. Changes in the health care system during the decade, however, necessitated an update of the original competencies to better equip preventive medicine educators to prepare residents for new roles those in preventive medicine can play in a restructured health care system. HRSA funded an effort to produce Version 2.0 of the preventive medicine competencies based on review and refinement of the original competencies through a consensus process. This article includes these revised core competencies and performance indicators.

Clinical Competence↗

Epidemiology of Chlamydia pneumoniae infection in a randomly selected population in a developed country.

This cross-sectional study of 400 sera from a randomly selected adult population in Northern Ireland, using a microimmunofluorescence assay, demonstrated high overall seropositivity (70%) for IgG Chlamydia pneumoniae antibodies in developed populations. Seropositivity was shown to be unrelated to gender, age or smoking but there was an inverse trend between infection and educational level achieved as a measure of socio-economic status. IgG levels were also higher during the winter months suggesting seasonal variation of Chlamydia pneumoniae infection. The high prevalence of evidence of exposure to Chlamydia pneumoniae as described in this study may have implications for prevention of cardiovascular disease if further evidence conclusively determines that infection with this organism is a risk factor for cardiovascular disease.

Adult↗

Genetic basis of transferase-deficient galactosaemia in Ireland and the population history of the Irish Travellers.

Transferase-deficient galactosaemia, resulting from deficient activity of galactose-1-phosphate uridyltransferase (GALT), is relatively common among the Travellers, an endogamous group of commercial/industrial nomads within the Irish population. This study has estimated the incidence of classical transferase-deficient galactosaemia in Ireland and determined the underlying GALT mutation spectrum in the Irish population and in the Traveller group. Based upon a survey of newborn screening records, the incidence of classical transferase-deficient galactosaemia was estimated to be 1 in 480 and 1 in 30,000 among the Traveller and non-Traveller communities respectively. Fifty-six classical galactosaemic patients were screened for mutation in the GALT locus by standard molecular methods. Q188R was the sole mutant allele among the Travellers and the majority mutant allele among the non-Travellers (89.1%). Of the five non-Q188R mutant alleles in the non-Traveller group, one was R333G and one F194L with three remaining uncharacterized. Anonymous population screening has shown the Q188R carrier frequency to be 0.092 or 1 in 11 among the Travellers as compared with 0.009 or 1 in 107 among the non-Travellers. The Q188R mutation was shown to be in linkage disequilibrium with a Sac I RFLP flanking exon 6 of the GALT gene. This represents the first molecular genetic description of classical transferase-deficient galactosaemia in Ireland and raises intriguing questions concerning the genetic history of the Irish Travellers.

Cohort Studies↗

Explaining variations in prescribing costs: results from a comparison of nursing home patients with matched pairs living in the community.

OBJECTIVES: To examine and explain variations in prescribing costs associated with nursing home patients and patients matched by age and sex living in the community. DESIGN: A 12-month case control study. SUBJECTS: All nursing home residents over 65-years-old registered with nine general practices and patients matched with them for age and sex living in the community. METHOD: Multivariate regression analysis of variations in monthly GP prescribing costs. RESULTS: Multivariate regression models explaining cost variations in terms of the GP practice delivering care and patients' age and sex had little explanatory power (R(2)=0.07 for nursing home patients, R(2)=0.03 for matched pairs). A fuller model for nursing home patients only, incorporating the patient's Barthel score and initial diagnosis as additional explanatory variables, added little to the explanatory power of the model (R(2)=0.16). CONCLUSION: The ability of the multivariate models used here to explain variations in prescribing costs among a group of elderly patients is poor. Adjusting weighted capitation formulae with respect to older patients to take account of such information or referring to it in negotiations on prescribing budgets would not appear to be warranted.

Age Factors↗

Effect of increased vegetable and fruit consumption on markers of oxidative cellular damage.

The goal of this study was to test the hypothesis that increased consumption of vegetables and fruit would reduce markers of oxidative cellular damage that can be assessed in blood or urine. Twenty-eight women participated in a 14 day dietary intervention. The primary end-points assessed were: 8-hydroxydeoxyguanosine (8-OHdG) in DNA isolated from peripheral lymphocytes, determined by HPLC with electrochemical detection; 8-OHdG excreted in urine, measured by ELISA; malondialdehyde (MDA) in urine, measured by fluorimetric detection following derivatization with thiobarituric acid and separation via HPLC; urinary 8-isoprostane F-2alpha (8-EPG) detected by ELISA. Pre- and post-intervention plasma levels of selected carotenoids were determined by HPLC. Subjects were free living and consumed a completely defined recipe-based diet that increased their average daily consumption of vegetables and fruit from 5.8 servings at baseline to 12.0 servings throughout the intervention. Overall, the level of 8-OHdG in DNA isolated from lymphocytes and in urine and the level of 8-EPG in urine were reduced by the intervention, whereas urine concentrations of MDA were minimally affected. The reduction in lymphocyte 8-OHdG was greater in magnitude (32 versus 5%) in individuals with lower average pre-intervention levels of plasma alpha-carotene (56 ng/ml) than in individuals with higher average pre-intervention plasma levels of alpha-carotene (148 ng/ml). The results of this study indicate that consumption of a diet that significantly increased vegetable and fruit intake from a diverse number of botanical families resulted in significant reductions in markers of oxidative cellular damage to DNA and lipids.

8-Hydroxy-2'-Deoxyguanosine↗

In-vitro fertilization and culture of mouse embryos in vitro significantly retards the onset of insulin-like growth factor-II expression from the zygotic genome.

In this study, the effect of in-vitro fertilization (IVF) and culture of mouse embryos in vitro on the normal expression of insulin-like growth factor-II (IFG-II) ligand and receptor was examined. The expression of IGF-II increased in a linear fashion at least up to the 8-cell stage of development. IGF-II expression in embryos collected fresh from the reproductive tract was significantly (P < 0.001) greater than in embryos fertilized in the reproductive tract and cultured in vitro (in-situ fertilized: ISF), and its expression was further reduced (P < 0.001) in IVF embryos at all development stages tested. The expression of IGF-II was significantly (P < 0.001) lower when embryos were cultured individually in 100 microl drops compared with culture in groups of 10 in 10 microl drops of medium. The addition of platelet activating factor to culture medium partially overcame this density-dependent decline of expression. Culture of ISF and IVF zygotes also caused the onset of new IGF-II mRNA transcription from the zygotic genome to be significantly (P < 0.001) retarded, until at least the 8-cell stage of development. This effect was greater (P < 0.05) for IVF than for ISF embryos. Neither IVF nor culture had any obvious effect on IFG-II/mannose-6-phosphate receptor (IGF-IIr) mRNA expression.

Animals↗

Ontogeny of expression of a receptor for platelet-activating factor in mouse preimplantation embryos and the effects of fertilization and culture in vitro on its expression.

Platelet-activating factor (PAF; 1-o-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent ether phospholipid. It is one of the preimplantation embryo's autocrine growth/survival factors. It may act via a G protein-linked receptor on the embryo; however, the evidence for this is conflicting. The recent description of the intracellular form of the PAF:acetlyhydrolase enzyme as having structural homology with G proteins and Ras also suggests this as a potential intracellular receptor/transducer for PAF. This study used reverse transcription-polymerase chain reaction to examine the ontogeny of expression of the genes for these proteins in the oocyte and preimplantation-stage embryo. Transcripts for the G protein-linked PAF receptor were detected in the late 2-cell-stage embryo and in all stages from the 4-cell stage to blastocysts. They were also present in unfertilized oocytes and newly fertilized zygotes but only at relatively low levels. The incidence of expression was generally low and variable in late zygotes and early 2-cell embryos. Expression past the 2-cell stage was alpha-amanitin sensitive. The results indicated that mRNA for this receptor is a maternal transcript that was degraded during the zygote-2-cell stage. New expression of the receptor transcript required activation of the zygotic genome. Fertilization of embryos in vitro caused this transcript not to be expressed in the zygote. Culture of zygotes (irrespective of their method of fertilization) caused expression from the zygotic genome to be retarded by more than 24 h. This retardation did not occur if culture commenced at the 2-cell stage. The transcripts for the subunits of intracellular PAF:acetylhydrolase were not detected in oocytes or at any stage of embryo development examined, despite their being readily detected in control tissue. This study confirms the presence of the G protein-linked PAF receptor in the 2-cell embryo and describes for the first time its normal pattern of expression during early development. The adverse effects of in vitro fertilization (IVF) and embryo culture on the expression of this transcript may be a contributing factor for the poor viability of embryos produced in this manner. The reduced expression of PAF-receptor mRNA following IVF predicts that such embryos may have a deficiency in autocrine stimulation and also suggests that supplementation of growth media with exogenous PAF would be only partially beneficial. The effect of IVF and culture may also explain the conflicting literature.

Animals↗

Chlamydia pneumoniae antibodies are associated with an atherogenic lipid profile.

OBJECTIVE: To determine, within a representative population group of men and women, whether alteration of the lipid profile might underlie the reported association between Chlamydia pneumoniae and ischaemic heart disease. DESIGN AND SETTING: Cross sectional survey in an area with a high incidence of ischaemic heart disease. SUBJECTS: 400 randomly selected participants in the World Health Organisation MONICA project's third population survey in Northern Ireland. MAIN OUTCOME MEASURES: Stored sera were examined by microimmunofluorescence for IgG antibodies to C pneumoniae at a dilution of 1 in 64. Mean total and high density lipoprotein (HDL) cholesterol were compared between seropositive and seronegative individuals with adjustment for age, measures of socioeconomic status, smoking habit, alcohol consumption, body mass index, and the season during which blood had been taken. RESULTS: In seropositive men, adjusted mean serum total cholesterol and HDL cholesterol were 0.5 mmol/l (9.2%) higher and 0.11 mmol/l (9.3%) lower, respectively, than in seronegative men. Differences in women did not achieve statistical significance, but both total cholesterol and HDL cholesterol were higher (3.6% and 5.8%, respectively) in seropositive than in seronegative individuals. CONCLUSIONS: There is serological evidence that C pneumoniae infection is associated with an atherogenic lipid profile in men. Altered lipid levels may underlie the association between C pneumoniae and ischaemic heart disease.

Adult↗

Platelet-activating factor may act as an endogenous pulse generator for sheep of luteolytic PGF2alpha release.

Pulsatile release of uterine prostaglandin F2alpha (PGF2alpha) induces luteolysis in ruminants. However, the mechanism(s) that initiates and maintains luteolysis has not been defined. The present study tested the hypothesis that the endogenous PGF2alpha pulse generator is uterine-derived platelet-activating factor (PAF). Ovariectomized ewes were given exogenous progesterone (P), estradiol (E), or both (P+E, mimicking the normal luteal phase). Only ewes treated with steroids released PAF into the uterine lumen and had increased PAF:acetylhydrolase activity in the uterine lumen. Steroid treatment also influenced the capacity of the uterus to release PGF2alpha in response to exogenous PAF. PAF infusion did not affect plasma PGF2alpha metabolite (PGFM) levels in control (no steroid treatment) ewes but increased plasma PGFM levels in P+E ewes (P < 0.001) and ewes treated with P or E alone (P < 0.05). Infusion of PAF followed by or coincident with oxytocin (OT) acted in a synergistic manner to increase plasma PGFM levels. Repeated infusion of PAF into the uterus at 1-h intervals induced tachyphylaxis of the PGFM response to PAF; however, sensitivity of the uterus to PAF returned spontaneously by the 6th h. Interferon-tau (IFN-tau) inhibits pulsatile release of PGF2alpha during pregnancy to prevent luteolysis. Exogenous recombinant ovine IFN-tau (50 microgram) inhibited the uterine response to PAF alone or the combined effects of PAF and OT. These results indicate that uterine PAF fulfills many of the criteria for an endogenous PGF2alpha pulse-generator: steroid induction of PAF production and uterine responsiveness to PAF-induced release of PGF; synergistic stimulation of PAF-induced PGF release by OT; inhibition of PAF effects by IFN-tau; and PAF's ability to induce pulses of PGF with a periodicity during a period of chronic exposure of the uterus to PAF.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Factor V Leiden (Arg506Gln), a confounding genetic risk factor but not mandatory for the occurrence of venous thromboembolism in homozygotes and obligate heterozygotes for cystathionine beta-synthase deficiency.

Thrombosis is the major cause of morbidity and mortality in individuals with untreated classical homocystinuria (HCU) due to cystathionine beta-synthase deficiency and characterised by severe hyperhomocysteinaemia. In addition, mild and moderate hyperhomocysteinaemia and Factor V Leiden (FVL; Arg506Gln) have recently been identified as thrombotic risk factors. FVL. which renders resistance to activated Protein C, is the most common inherited genetic risk factor for thrombosis with a high allelic frequency amongst Caucasians. As thrombophilia is a multigenic disorder, 26 individuals with HCU (median age 17.6 years, range 3.5-32.8 years) and 36 obligate heterozygotes (median age 51.5 years, range 34-74 years) were screened for FVL. All the HCU individuals received treatment, except one, within 6 weeks of birth for those who were diagnosed at birth through the national newborn screening programme (n = 20) and at the time of diagnosis for those late detected (n = 5, mean age of starting treatment 4.9 years, range 1.4-11 years). All had been free from venous thrombosis, except one HCU individual and one HCU obligate heterozygote. Neither of the two individuals with venous thrombosis carried FVL. Two independent individuals with HCU (male 14.8 years; female 18.2 years) were heterozygous for FVL (allelic frequency 3.8%) and three independent HCU obligate heterozygotes (males 40 and 45.8 years; female 45.6 years) were also heterozygous for FVL (allelic frequency 4.16%). The findings in this small group suggest that FVL is not a mandatory but a significant confounding risk factor for the occurrence of thrombosis in HCU individuals and additional contributing factors may be required for thrombosis to occur in HCU obligate heterozygotes with FVL heterozygosity. Our data also suggest that treatment of HCU not only reduces the thrombotic risk in patients with isolated HCU but also in those with the additional FVL heterozygosity.

Adolescent↗

The role of quality standards--accreditation in redressing asymmetry of information in health care markets.

Asymmetry of information presents major difficulties for the efficient operation of markets in health care. The use of accreditation schemes may reduce these difficulties by enhancing the availability of reliable, accessible information on aspects of service quality considered important by service users and their agents. The UK's Patients' Charter with its associated Charter Marks has the potential to perform such a function in respect of inpatient services. In as much as it refers to aspects of service valued by service users which are specified in contracts by service procurers and appear not to be negatively correlated with other aspects of service quality, it can be seen to provide unambiguous signals of service quality. Given the Charter is currently under review, it seems appropriate that such attributes are borne in mind by policy makers in their deliberations as to its future.

Accreditation↗