Search PubMed⌕ Search

Biomedical subjects

M Murphy

Publications and source records attributed to M Murphy.

At least 73 records · Page 4Linked to original sources
PubMed2000

Effects of a monetary incentive on primary care prescribing in Ireland: changes in prescribing patterns in one health board 1990-1995.

BACKGROUND: In an attempt to curb the rapidly rising costs of primary care prescribing in Ireland, the government introduced a financial incentive scheme in 1993, to encourage general practitioners to restrain their prescribing. PURPOSE: To investigate the effects of a financial incentive scheme on GP prescribing in Ireland on prescribing costs and volume, and on some specific therapeutic areas. METHODS: Prescribing for 3 years before (1990-1992) and 3 years (1993-1995) after the introduction of incentives, based on a defined cohort of 233 general practitioners in the area of one health board. GPs were divided into tertiles based on their performance against their prescribing budgets into 'savers' (generally underspent and received incentive payments), modest overspenders and large overspenders. RESULTS: Savers were always lower cost prescribers than the other groups. They contained their rate and costs of prescribing in contrast to the other groups, e.g. percentage rise in prescribing costs in the year after the introduction of the scheme -7.9%, +1.2% and +7.3% respectively, (P < 0.05) for savers, modest overspenders and large overspenders respectively. This effect was short lived however and was gone by the third year of the study. CONCLUSIONS: The financial incentives had a marked effect on prescribing volume and cost on some practices who could achieve targets and hence incentive payments. The incentives had little effect on high spending practices. Such incentive schemes need careful evaluation if they are not to become perverse to the good health of patients.

Drug Utilization↗
PubMed2000

A comparison of melanoma mortality among WWII veterans of the Pacific and European theaters.

PURPOSE: To determine whether cutaneous melanoma is associated with past military service in tropical locations, as a test of the 'critical period' sunlight exposure hypothesis. METHODS: Mortality data from a longitudinal follow-up study of 5524 former prisoners of war (POW) and 3713 non-POW veteran controls, all white male veterans of World War II (WWII), were examined to determine whether death attributed to melanoma was associated with history of military service in Pacific or European theaters during WWII or with POW status. Deaths from colon cancer were used as a comparison outcome. RESULTS: During 50 years of follow-up, there were 18 deaths from melanoma and 83 deaths from colon cancer among the cohort. Melanoma mortality varied with theater of war and POW status, whereas colon cancer mortality was similar for all subgroups. Pacific War POWs were at the highest risk overall (odds ratio (OR), 3.35; 95% confidence interval (CI), 0.39-28.76), whereas veterans of the Pacific War had nearly the same risk of melanoma (OR, 1.04; 95% CI, 0.09-11.94) compared with veterans of the European War. European theater POWs had a higher risk than non-POW veterans (OR, 2.76; 95% CI, 0.31-24.81). None of these differences, however, were statistically significant. CONCLUSIONS: To the extent that POW status is associated with higher sun exposure, these data are consistent with the hypothesis that exposure to high levels of solar radiation in young adulthood is associated with a higher risk of melanoma mortality.

Cohort Studies↗
PubMed2000

Personality traits of the relatives of autistic probands.

BACKGROUND: There is substantial evidence that the genetic liability to autism confers a risk for a range of more subtle social and communication impairments, as well as stereotyped and repetitive behaviours. Recent research suggests that increased expression of particular personality traits may be a manifestation of the liability to autism. METHODS: To investigate this we examined the personality traits of the adult relatives of 99 autistic and 36 Down's syndrome probands, using the informant version of the Modified Personality Assessment Schedule. RESULTS: There was significantly increased expression of the traits anxious, impulsive, aloof, shy, over-sensitive, irritable and eccentric among the autism relatives with evidence of different profiles for male and female relatives and for parents and adult children. Factor analysis revealed three broad groups of traits, two of which ('withdrawn' and 'difficult') appeared to reflect impairments in social functioning and a third group of anxiety related traits ('tense'). Each of these factors differed in their pattern of associations with the factor we termed 'withdrawn' showing a similar pattern of association to that found for other autism related conditions. The 'tense' factor appeared in part to be related to the burden of caring for an autistic child. CONCLUSIONS: This study confirms the finding that particular personality traits may aggregate in the family members of autistic individuals and furthermore that some of these traits may be a manifestation of the liability to autism.

Adult↗
PubMed2000

Detection of TCR-gamma gene rearrangements in early mycosis fungoides by non-radioactive PCR-SSCP.

Early mycosis fungoides (MF) can mimic numerous benign inflammatory dermatoses on routine histological examination. In this study, a recently developed non-radioactive polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) technique was used to assess T-cell clonality in paraffin-embedded skin biopsies clinically and pathologically suspicious for early MF. Non-radioactive PCR-SSCP is a simple, sensitive, reproducible and rapid procedure requiring minimal instrumentation. DNA was extracted from 22 skin biopsies of 20 patients with suspected patch stage MF and 15 skin biopsies of inflammatory dermatoses. V gamma1-8, V gamma9, V gamma10, V gamma11 and J gamma1/J gamma2 consensus primers were used for T-cell receptor (TCR)-gamma gene rearrangement amplification. PCR products were analyzed by non-radioactive SSCP. Clonal TCR-gamma gene rearrangements were detected in 17 of 22 (77%) suspected MF specimens. Clonal SSCP banding patterns were different among individual patients. In addition, identical banded patterns were demonstrated in serial skin biopsies from the same patient. No dominant T-cell clones were found in the inflammatory dermatoses studied. Therefore, non-radioactive PCR-SSCP is a useful molecular diagnostic tool for assessment of T-cell clonality in paraffin-embedded specimens suspicious for early MF. The SSCP imprint of PCR products is specific for each TCR-gamma gene rearrangement, and may be used to evaluate concurrent/recurrent disease in individual patients.

Biopsy↗
PubMed2000

Renal itch.

Renal itch is localized or generalized itch, affecting patients with chronic renal failure, where there is no primary skin disease and no systemic or psychological dysfunction that might cause pruritus. It does not result from raised serum urea levels. The prevalence of renal itch has increased with the growing population in chronic renal failure and is a considerable cause of morbidity. The prevalence of itch increases with deteriorating renal function but does not improve significantly with dialysis. The pruritus is independent of duration of dialysis or cause of renal failure. The aetiology of renal itch is unclear. There is little evidence of a major role for histamine and antihistamines are rarely beneficial. Hyperparathyroidism, abnormal cutaneous innervation and endogenous opioids have been postulated as contributory factors. Treatment of renal itch is difficult. Naltrexone, oral activated charcoal, UVB phototherapy and ondansetron have been shown to be effective. Topical capsaicin may be of benefit in patients with localized pruritus. The definitive treatment for renal itch remains renal transplantation.

Humans↗
PubMed2000

Enlarged cholinergic forebrain neurons and improved spatial learning in p75 knockout mice.

The p75 low affinity neurotrophin receptor (p75) can induce apoptosis in various neuronal and glial cell types. Because p75 is expressed in the cholinergic neurons of the basal forebrain, p75 knockout mice may be expected to show an increased number of neurons in this region. Previous studies, however, have produced conflicting results, suggesting that genetic background and choice of control mice are critical. To try to clarify the conflicting results from previous reports, we undertook a further study of the basal forebrain in p75 knockout mice, paying particular attention to the use of genetically valid controls. The genetic backgrounds of p75 knockout and control mice used in this study were identical at 95% of loci. There was a small decrease in the number of cholinergic basal forebrain neurons in p75 knockout mice at four months of age compared with controls. This difference was no longer apparent at 15 months due to a reduction in numbers in control mice between the ages of 4 and 15 months. Cholinergic cell size in the basal forebrain was markedly increased in p75 knockout mice compared with controls. Spatial learning performance was consistently better in p75 knockout mice than in controls, and did not show any deterioration with age. The results indicate that p75 exerts a negative influence on the size of cholinergic forebrain neurons, but little effect on neuronal numbers. The markedly better spatial learning suggests that the function, as well as the size, of cholinergic neurons is negatively modulated by p75.

Aging↗
PubMed2000

Atlantic salmon HNF-3/forkhead: cDNA sequence, evolution, expression, and functional analysis.

We report the isolation and characterization of a cDNA encoding an HNF-3 family member (as HNF-3) from Atlantic salmon (Salmo salar L). The important functional domains of HNF-3 proteins that have been characterized previously are revealed by segments of high identity along the alignment of the asHNF-3 with winged helix/forkhead amino acid sequences isolated from other species. A comparison of asHNF-3 cDNA and genomic DNA indicated that there were no introns present in the asHNF-3 gene. Expression of asHNF-3 protein in adult salmon tissues was not exclusive to liver but was also present in the pancreas and intestine. An RT-PCR analysis performed on salmon development showed that asHNF3 expression is detectable before gastrulation at the mid blastula transition stage. Functional analysis of the asHNF-3 protein using a characterized HNF-3 consensus binding site demonstrated that the protein can recognize and bind to specific HNF-3 consensus sequences. We also report the identification of a novel HNF3 binding site in the promoter of the Atlantic salmon transferrin gene.

Amino Acid Sequence↗
PubMed2000

The accuracy of general practitioner records of smoking and alcohol use: comparison with patient questionnaires.

BACKGROUND: General practitioner (GP) records are increasingly being used as sources of information on potential confounders such as smoking use and alcohol intake in epidemiological studies. The aim of this study was to assess the accuracy of GP records on smoking use and alcohol intake compared with data from patient questionnaires. METHODS: Patients registered with 42 practices in Oxfordshire that agreed to take part in a post-marketing surveillance study of omeprazole were sent a postal questionnaire that included questions about alcohol and tobacco use. Two years later, data on these aspects of lifestyle were abstracted from the GP records. RESULTS: A total of 892 patients agreed to take part in the study; 804 (90 per cent) completed the postal questionnaire, and the records of 856 (96 per cent) were reviewed. Information on smoking and alcohol use was present in 74 per cent and 63 per cent of GP records, respectively. Agreement between the two data sources was moderate for both smoking (kappa = 0.50) and alcohol use (kappa = 0.52). With regard to smoking, the main discrepancy between the two data sources was that 46 per cent (94/206) of patients who reported themselves as exsmokers were recorded as being never smokers in the GP record. With regard to alcohol, there were no systematic differences between the two data sources. CONCLUSION: Data from GP records on smoking status and alcohol use are incomplete and subject to some misclassification. This is a source of potential failed adjustment for confounding, which should be considered in epidemiological studies that make use of these records.

Alcohol Drinking↗
PubMed2000

Mesenchymal stem cells as vehicles for gene delivery.

Mesenchymal stem cells contribute to the regeneration of mesenchymal tissues such as bone, cartilage, muscle, ligament, tendon, adipose, and marrow stroma. Transduction of mesenchymal stem cells from species other than humans is required for the development of disease models in which mesenchymal stem cells-based gene delivery is evaluated. Attempts to transduce mesenchymal stem cells from some species with amphotropic retroviral vectors were unsuccessful, leading to comparative mesenchymal stem cells transductions with xenotropic and gibbon-ape leukemia virus envelope-pseudotyped retroviral vectors. Human, baboon, canine, and rat mesenchymal stem cells were transduced optimally with amphotropic vector supernatants. In contrast, sheep, goat, and pig mesenchymal stem cells showed highest transduction levels with xenotropic retroviral vector supernatant, and rabbit mesenchymal stem cells were transduced optimally with gibbon-ape-enveloped vectors. Using a myeloablative canine transplantation model and gene-marked canine mesenchymal stem cells, the biodistribution of infused and ex vivo expanded mesenchymal stem cells were examined. The majority of transduced canine mesenchymal stem cells were found in the bone marrow samples. The current study shows the use of mesenchymal stem cells as a delivery vehicle for gene transfer studies, and validates the feasibility of delivering mesenchymal stem cells to the marrow compartment for stromal regeneration after cancer-associated cytotoxic therapies.

Animals↗
PubMed2000

Your patient may be at risk for isolated systolic hypertension!

Isolated systolic hypertension is a risk factor for the development of stroke, heart attack, and left ventricular hypertrophy, which can result in eventual congestive heart failure. Recent studies have validated the benefits of treatment of isolated systolic hypertension in the elderly and have shown that treatment can reduce the risk for cardiovascular complications. An update on isolated systolic hypertension and the importance of detecting and treating are presented.

Aged↗
PubMed2000

Association between polymorphisms in dopamine metabolic enzymes and tobacco consumption in smokers.

Central dopaminergic reward pathways give rise to dependence and are activated by nicotine. Allelic variants in genes involved in dopamine metabolism may therefore influence the amount of tobacco consumed by smokers. We developed assays for polymorphisms in dopamine beta-hydroxylase (DBH), monoamine oxidase (MAO) and catechol O-methyl transferase (COMT) using the polymerase chain reaction with sequence specific primers (PCR-SSP). We then typed 225 cigarette smokers to assess whether genotype was related to the number of cigarettes smoked a day. Smokers with DBH 1368 GG genotype smoked fewer cigarettes than those with GA/AA [mean difference -2.9 cigarettes, 95% confidence interval (CI) -5.5, -0.4; P = 0.022]. The effect reached statistical significance in women (-3.8, 95% CI -6.4, -1.0, P = 0.007) but not in men (-1.5, 95% CI -6.0, 3.0, P = 0.498). Overall, the effect was greater when analysis was confined to Caucasians (-3.8, 95% CI -6.6, -1.1, P = 0.007). Smokers with MAO-A 1460 TT/TO smoked more cigarettes than those with CC/CT/CO (2.9, 95% CI 0.6, 5.1, P = 0.013). Within each sex group, the trend was similar but not statistically significant (difference for men 2.9, 95% CI -1.0, 6.7; for women 2.0, 95% CI -0.7, 4.8). The effect of the allele was greater in smokers with a high body mass index (> 26) (difference 5.1, 95% CI 1.4, 8.8, P = 0.008). More heavy smokers (> 20 a day) had the DBH 1368A allele when compared to light smokers (< 10 a day). (Relative risk 2.3, 95% CI 1.1, 5.0, P = 0.024.) The trend for increasing prevalence of the DBH A allele in heavy smokers was greater when analysis was restricted to Caucasians (relative risk 3.2, 95% CI 1.3, 8.2, P = 0.004). Conversely, heavy smokers were less likely to have the MAO-A 1460C allele (relative risk 0.3, 95% CI 0.1, 0.7, P = 0.012). Variations in DBH and MAO predict whether a person is a heavy smoker and how many cigarettes they consume. Our results support the view that these enzymes help to determine a smoker's requirement for nicotine and may explain why some people are predisposed to tobacco addiction and why some find it very difficult to stop smoking. This finding has important implications for smoking prevention and offers potential for developing patient-specific therapy for smoking cessation.

Adult↗
PubMed2000

The mechanism of actinomycin D-mediated increase of Borna disease virus (BDV) RNA in cells persistently infected by BDV.

The transcriptional mechanism of Borna disease virus (BDV) has been poorly understood. We have analyzed transcription of the virus upon various stimuli in Madin-Darby canine kidney cells which were persistently infected by BDV (MDCK/BDV). Treatment with actinomycin D (ActD) increased the level of BDV RNA, shifting the size of RNA from 1.9 kb to 2.3 kb beginning 5 hr after the treatment. To understand the mechanism of this unique modulation of BDV RNA, we conducted several experiments. The RNA increase occurred at the stage in which synthesis of cellular intrinsic mRNA was intact, suggesting BDV does not compete with cellular transcriptional machinery for intrinsic RNA polymerase II. The BDV transcription was also enhanced by cycloheximide treatment, indicating that newly synthesized viral or cellular proteins are not necessary for viral transcription. However, a shift in the RNA size was not observed for cycloheximide-induced BDV RNA. The increase in viral transcription persisted during the cellular apoptotic process consequent to p53 gene accumulation beginning 1 hr after ActD treatment. Caspase inhibitors Z-VAD and DEVD-CHO repressed the apoptotic process but failed to block the increase in BDV transcription. In addition, adenovirus-mediated transduction of wild-type p53 did not alter the BDV transcription, indicating that the increase in BDV transcription was independent of the p53-mediated apoptotic process. Other various stimuli that evoke cellular signal transductions failed to alter BDV transcription. Agents inhibitory to topoisomerase except adriamycin failed to enhance BDV transcription, indicating that the increase in BDV transcription is not mediated by an inhibitory action to the topoisomerase II of ActD. Adriamycin showed an increase and size-shift of BDV RNA similar to ActD. These results suggest that intercalation of the viral genome itself with ActD is related to the stabilization of viral RNA and alteration of RNA size rather than secondary host cell changes.

Animals↗
PubMed2000

Dietary folate and the prevalence of neural tube defects in the British Isles: the past two decades.

OBJECTIVES: To measure the changes in folate consumption and the prevalence of neural tube defects in the British and Irish populations during the past two decades. DESIGN: Ecological study. MAIN OUTCOME MEASURES: Average daily dietary folate consumption for Britain for the period 1980-1996 was estimated from the National Food Survey. Annual neural tube defect prevalences for the same period were obtained from the Oxford Record Linkage Study Neural Tube Defect register, the Glasgow EUROCAT register, and the three Irish EUROCAT registers (Belfast, Dublin and Galway). RESULTS: Dietary folate consumption increased on average by 1.6% per annum in Scotland and 1.4% in England during the study period. The annual rate of decline of neural tube defect prevalence averaged 10.4% in the Irish population, 8.2% in Glasgow, and 5.2% in Oxfordshire and West Berkshire. CONCLUSIONS: The decline in neural tube defect prevalence observed in all British and Irish populations since the early 1970s continued with the introduction of folate fortification of cereals, which produced measurable increases in average daily folate consumption. Further declines in neural tube defect prevalence may be achieved by targeted folate supplementation during the periconceptual period.

Diet↗