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M Murphy

Publications and source records attributed to M Murphy.

At least 109 records · Page 6Linked to original sources
PubMed2000

Evaluation of thresholds for benomyl- and carbendazim-induced aneuploidy in cultured human lymphocytes using fluorescence in situ hybridization.

Threshold mechanisms of activity for mutagenic agents have been debated for some time, especially for those substances which induce aneuploidy by inhibiting mitotic spindle function. No observed effect levels (NOELs) or "practical thresholds" have been demonstrated for several aneugens both in vitro and in vivo generally by either counting chromosomes in metaphase preparations or by observing micronuclei. Recently, fluorescence in situ hybridization (FISH) has proven to be a sensitive and useful technique for the assessment of aneuploidy at low concentrations. Using binucleate human lymphocytes coupled with FISH, we have been able to characterize a threshold mechanism of action for two spindle inhibitors, benomyl and its active metabolite, carbendazim. Test chemicals were added 24 h following culture initiation. After a further 20 h, cytochalasin B was added, and cells were harvested 28 h later (72 h post initiation). The distribution of chromosomes between the nuclei of binucleate cells was evaluated by fluorescence microscopy for the simultaneous detection of centromeres labeled with FITC (green) or Cy-3 (red). Six human chromosomes were investigated in pairs (1 and 8, 11 and 18, and X and 17). Abnormalities were classified as chromosome loss (including centromeric positive micronuclei), chromosome gain, non-disjunction, or polyploidy. Dose-response data were generated over a range of closely spaced concentrations at 100 ng/ml intervals. The threshold, defined as the lowest "effect" concentration using statistical methods, was determined for each chromosome. Non-disjunction proved to be the most sensitive endpoint for the detection of aneuploidy occurring at higher frequencies and lower concentrations. Results for the six chromosomes demonstrated similar dose-response data which included a series of concentrations with no statistically significant increase above background, followed by a second range of higher concentrations with a statistically significant, concentration-dependent increase. Nearly equimolar threshold concentrations were determined for benomyl- and carbendazim-induced non-disjunction.

Adult↗
PubMed2000

Psychosocial morbidity: the economic burden in a pediatric health maintenance organization sample.

OBJECTIVES: To evaluate psychosocial morbidity in pediatric primary care and to determine displaced health care utilization. DESIGN AND SETTING: A cross-sectional sample of parent-child dyads was screened using the Pediatric Symptom Checklist (PSC) at 6 pediatric sites of a health maintenance organization (HMO). Cost and utilization data were retrieved from regional databases for this sample. PARTICIPANTS: Parent-child dyads from an HMO in northern California (N = 1840). The children ranged in age from 2 to 18 years. RESULTS: In all, 13.0% of children exhibited psychosocial dysfunction. The rate of children's chronic illness was 18.4%. Multiple regression analyses measured utilization and cost of health and psychiatric care for the selected population for the previous year; the average log cost of health care per child was $393. The average health care cost for children with anxious, depressed symptoms was $805. Chronically ill children were the highest utilizers of health care, with an average log cost of $1138. When psychosocial dysfunction was present, regression models showed that health care spending was highest for young children. CONCLUSIONS: Health care utilization was higher for children with psychosocial morbidity, was higher among younger children, and decreased with age as psychiatric costs progressively increased.

Adolescent↗
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↗