PubMed Health⌕ Search

Biomedical subjects

M Neale

Publications and source records attributed to M Neale.

At least 19 recordsLinked to original sources
PubMed2004

The relation between c-myc expression and interferon sensitivity in uveal melanoma.

BACKGROUND/AIM: Interferons (IFN) are currently being used to treat melanoma, including some patients with uveal melanoma. IFN is thought to inhibit tumour growth through downregulation of the c-myc oncogene; the overexpression of which has been shown to be associated with resistance in cell lines. The aim of this study was to investigate the relation between c-myc gene expression and IFN sensitivity in a series of uveal melanomas in a short term chemosensitivity assay. METHODS: Tumours from 45 patients with uveal melanoma who had undergone enucleation were studied. The ATP chemosensitivity assay was used to study sensitivity to IFN-alpha-2b in freshly isolated cells from each tumour. Flow cytometry was used to assess c-myc expression in formalin fixed material from the primary specimens. RESULTS: There was a wide range of IFN sensitivity between the specimens whereas c-myc expression was universal and present in 80% of the tumour cells in 80% of the specimens. Higher c-myc expression was associated with IFN-alpha resistance as measured by the maximum percentage of inhibition (p = 0.05) and there was a trend with the IFN sensitivity index (p = 0.07). CONCLUSIONS: These results demonstrate that tumours with high c-myc expression are also associated with IFN resistance. Future research is required to explore the potential of c-myc gene manipulation combined with IFN therapy.

Adult↗
PubMed2003

Rupture of the aorta following road traffic accidents in the United Kingdom 1992-1999. The results of the co-operative crash injury study.

OBJECTIVE: The true incidence and survivability of blunt traumatic aortic rupture following road traffic accidents in the UK is unclear. The objective of this study was to determine the extent of blunt traumatic aortic rupture in the UK after road traffic accidents and the conditions under which it occurs. METHODS: Data for the study was obtained from the Co-operative Crash Injury Study database. Road traffic accidents that happened between 1992 and 1999 and included in the Co-operative Crash Injury Study database were retrospectively investigated. RESULTS: A total of 8285 vehicles carrying 14,435 occupants were involved in 7067 accidents. There were 132 cases of blunt traumatic aortic rupture, of which the scene survival was 9% and the overall mortality was 98%. Twenty-one percent of all fatalities had blunt traumatic aortic rupture (130/613). Twenty-nine percent were due to frontal impacts and 44% were due to side impacts. Twelve percent of the blunt traumatic aortic rupture cases in frontal vehicle impacts were wearing seat belts and had airbag protection and 19% had no restraint mechanism. The Equivalent Test Speed of the accident vehicles, (where equivalent test speed provides an estimate of the vehicle impact severity and not an estimate of the vehicle speed at the time of the accident), ranged from 30 to 110 km/h in frontal impacts and from 15 to 82 km/h in side impacts. CONCLUSION: Blunt traumatic aortic rupture carries a high mortality and occurred in 21% of car occupant deaths in this sample of road traffic accidents. Impact scenarios varied but were most common from the side. The use of an airbag or seat belt does not eliminate risk. The injury can occur at low severity impacts particularly in side impact.

Accidents, Traffic↗
PubMed2002

The mechanism of injury in blunt traumatic rupture of the aorta.

Rupture of the aorta accounts for a significant proportion of fatalities following blunt trauma. A great deal of consensus exists describing the circumstances under which acute traumatic aortic dissection occurs as well as its investigation and management. However, there remains some controversy surrounding the pathogenic aetiology underlying this injury. Univariate and multivariate models of blunt traumatic aortic rupture (BTAR) are discussed. To account for the consistency in the nature of BTAR, despite a range of trauma scenarios, the concepts of dynamic multivariate models and a final common pathway are introduced. Clinical management is described elsewhere. Greater understanding of the mechanism of BTAR could lead to a range of safety systems aimed at a reduction in its incidence and severity.

Aorta, Thoracic↗
PubMed2001

Poor durability of carotid angioplasty and stenting for treatment of recurrent artery stenosis after carotid endarterectomy: an institutional experience.

PURPOSE: Recurrent stenosis after carotid endarterectomy (CEA) is often regarded as an optimal application of carotid artery angioplasty and stenting (CAS). The extended durability of CAS for recurrent carotid artery stenosis after CEA is unknown. We present the intermediate-term surveillance results for all eight CAS procedures performed over a 28-month period at a single tertiary referral center. METHODS: Patients had recurrent carotid stenosis after CEA, whether symptomatic or asymptomatic, of 80% to 99% stenosis on preprocedural carotid duplex scan examination. Uncovered, self-expanding metal stents, in conjunction with angioplasty, were used in all patients. Baseline and scheduled interval follow-up duplex ultrasound scan was used to assess intrastent restenosis. Further angiography was reserved for those patients obtaining additional intervention. RESULTS: One transient ischemic attack was observed 1 day after the procedure, and no cerebral infarcts occurred. All patients had angiographic resolution of the stenosis and postprocedural duplex scan studies without residual stenosis. Subsequent interval surveillance duplex scan examinations revealed significant (60%-79%) to critical (80%-99%) recurrent stenosis in six (75%) of eight patients, two of whom went on to further interventions. Of those with intrastent restenosis, four (75%) progressed to critical (80%-99%) stenosis. Mean follow-up was 20.2 months (range, 12-37 months). The two lesions that have not yet shown restenosis are those with the shortest follow-up interval, each at 12 months. CONCLUSIONS: In contrast to the optimistic claims in other series, this limited series suggests that angioplasty with stenting for recurrent carotid artery occlusive disease after CEA, although relatively safe in the short term, has significant limitations in terms of durability of results.

Aged↗
PubMed2001

Genetic moderation of environmental risk for depression and anxiety in adolescent girls.

BACKGROUND: There is huge individual variation in people's response to negative life events. AIMS: To test the hypothesis that genetic factors moderate susceptibility to the environmentally mediated risks associated with negative life events. METHOD: The Virginia Twin Study of Adolescent Behavioral Development (VTSABD) was used to study the effects of independent life events (assessed from maternal interview) on depression/anxiety (assessed from child interview) in 184 same-gender female twin pairs, aged 14--7 years, measured on two occasions. RESULTS: There was no genetic effect on the independent negative life events studied. A significant gene-environment interaction was found using structural equation modelling. There was no effect of independent life events on adolescents' depression in the absence of parental emotional disorder, but a significant effect in its presence. CONCLUSIONS: There is an environmentally mediated effect of life events on depression/anxiety. Genetic factors play a significant role in individual differences in susceptibility to these environmentally mediated risks.

Adolescent↗
PubMed2000

Anorexia nervosa and major depression: shared genetic and environmental risk factors.

OBJECTIVE: The authors sought to derive heritability estimates for anorexia nervosa and to explore the etiology of the comorbid relationship between anorexia nervosa and major depression. METHOD: They applied bivariate structural equation modeling to a broad definition of anorexia nervosa and lifetime major depression as assessed in a population-based sample of 2,163 female twins. RESULTS: Anorexia nervosa was estimated to have a heritability of 58% (95% confidence interval=33%-84%). The authors were unable to completely rule out a contribution of shared environment. The comorbidity between anorexia nervosa and major depression is likely due to genetic factors that influence the risk for both disorders. CONCLUSIONS: Although the study was limited by the small number of affected twins, the results suggest that genetic factors significantly influence the risk for anorexia nervosa and substantially contribute to the observed comorbidity between anorexia nervosa and major depression.

Adult↗
PubMed1999

c-myc, p53, and Bcl-2 expression and clinical outcome in uveal melanoma.

AIMS: Overexpression of c-myc protein has independent prognostic significance in a variety of primary and metastatic cutaneous melanomas which suggests a possible role for this gene in melanomagenesis. We have therefore examined the importance of this oncogene in uveal melanoma and studied the coexpression of two other gene products, Bcl-2 and p53, which might contribute to its effect. METHODS: The percentage of cells positive for nuclear c-myc expression was estimated by flow cytometric analysis of nuclei extracted from paraffin blocks. The expression of Bcl-2 and p53 protein was assessed by immunohistochemistry. A total of 71 tumours were studied and the results compared with survival with a mean follow up period of 6 years. RESULTS: c-myc was expressed in > 50% of the cells by 70% of the tumours, and was independently associated with improved survival in a Cox multiple regression-model. Although Bcl-2 was expressed by the majority of the cells in 67% tumours, it was without effect on prognosis. None of the cases studied showed convincing positivity for p53. Analysis of coexpression showed that the best survival was seen in c-myc+/Bcl-2+ tumours and the worst in c-myc-/Bcl-2-tumours. CONCLUSION: The finding of improved rather than reduced survival in c-myc positive tumours is at variance with skin melanoma. There was no evidence to suggest that c-myc was modulated by upregulation of Bcl-2 or p53 inactivation/mutation. Although Bcl-2 is unlikely to have any effect on tumour growth or metastasis, it could contribute to the general lack of susceptibility to apoptosis in these tumours.

Adolescent↗
PubMed1999

Comparing the biological and cultural inheritance of personality and social attitudes in the Virginia 30,000 study of twins and their relatives.

Measures of four dimensions of personality (Psychoticism, Extraversion, Neuroticism, and Lie scores) and six aspects of social attitudes (to sex, taxation, militarism, politics, religion and a general conservatism scale) were obtained by mailed questionnaire from 29,691 US subjects including adult twins (n = 14,761) their parents (n = 2360), their spouses (n = 4391), siblings (n = 3184) and adult children (n = 4800). After correction for the average effects of age, sex and source of sample, familial correlations were computed for 80 distinct biological and social relationships. The data allow for the estimation of the additive and non-additive effects of genes, assortative mating, vertical cultural inheritance and other non-parental effects of the shared environment on differences in personality and social attitudes. The interaction of genetic and environmental effects with sex may also be analyzed. Model-fitting analyses show that personality and social attitude measures differ markedly in major features of family resemblance. Additive and dominant genetic effects contribute to differences in both personality and attitudes, but the effects of the family environment, including vertical cultural transmission from parent to child, are much more marked for social attitudes than for personality. There is substantial assortative mating for social attitudes and almost none for personality. The causes of family resemblance depend significantly on sex for almost every variable studied. These findings clarify and extend the more tentative findings derived from previous twin, family and adoption studies.

Adult↗
PubMed1998

Intersite variation in the impact of intensive psychiatric community care on hospital use.

Differences among treatment facilities in effectiveness of intensive psychiatric community care (IPCC) for reducing hospital dependence are examined. Experimental data from nine VA hospitals showed IPCC to be most effective where former orientation to inpatient care was changing to improved accessibility of outpatient services. These hospitals appeared to have the greatest need for community care programs and to be most committed to shifting their system of service delivery.

Adult↗
PubMed1998

Models for the longitudinal genetic analysis of same-age twins: application to HDL cholesterol.

Models are presented for the analysis of longitudinal data from same-age twins which permit the exploration of a remarkably diverse array of alternative explanations for continuity and change during development. Data of this type permit the detection of new sources of genetic or environmental covariation during development that are not expressed at earlier ages and, because they include the effects of age-specific genes, the resulting heritability estimates are more reliable than those obtained from relatives who differ in age. The proposed models were applied to measurements of HDL cholesterol obtained on 81 pairs of monozygotic (MZ) twins and 69 dizygotic (DZ) pairs at 11, 12.5 and 14 years of age. All three MZ co-twin correlations were substantially higher than the self correlations across occasions, suggesting that new sources of genetic or environmental covariation must be expressed during early adolescence. This interpretation was confirmed by analysis of the full covariance matrices which showed that only models which assumed the expression of new or age-specific genes could explain the observed pattern of covariation. Because they include the effects of age-specific genes, the resulting heritabilities (0.80-0.83) were substantially higher than many previous estimates.

Adolescent↗
PubMed1997

The art of the deal. Interview by Joe Flower.

Health care today is a maelstrom of deals-massive contracts, joint ventures, mergers, strategic alliances. Margaret Neale, a professor of organizational behavior at Stanford University's Graduate School of Business, has studied deal-making for most of her professional life. As she tells freelance writer Joe Flower, the focus shouldn't be on power tactics or how to be tough, but on what we can do to make negotiations work better-for all sides.

Decision Making, Organizational↗
PubMed1997

Age changes in the causes of individual differences in conservatism.

Age-related changes are analyzed in the correlation of 3416 monozygotic and 3780 dizygotic U.S. twin pairs aged between 9 and 75+ years for conservatism scores derived from a 28-item social attitude inventory. The effects of the shared environment are overwhelming in twins aged 20 years or younger. In older twins, genetic effects appear to play a larger role. A more dynamic conception of the interaction between genes and environment in the development of complex human differences is needed.

Adolescent↗
PubMed1996

Ruptured abdominal aortic aneurysms: who should be offered surgery?

PURPOSE: Operation for ruptured abdominal aortic aneurysm is generally still associated with a high mortality rate. A review of our experience over a 9-year period was undertaken to identify factors present on admission associated with 30-day operative mortality. METHODS: A retrospective analysis of 154 patients with ruptured abdominal aortic aneurysm submitted for operation in a university teaching hospital between January 1985 and December 1993 was undertaken. RESULTS: The hospital mortality rate was 39%. Logistic regression identified a set of five independent preoperative factors associated with mortality: age (> 76 years), creatinine level (> 0.19 mmol/L), loss of consciousness after arrival, Hb (< 9 g%), and electrocardiographic ischemia. In the 52 patients with a single risk factor present, the mortality rate was 37%, with two factors (32 patients) it was 72%, with three or more factors (8 patients), it was 100%, and no patient had all five risk factors. A 16% mortality rate was found in the 62 patients with no risk factors. CONCLUSION: These risk factors can be easily determined on admission and may be used to help improve patient selection for surgical intervention. The current operative mortality rate for ruptured abdominal aortic aneurysm remains high, and in some cases health care resources are used in a nonproductive fashion. Restricted patient selection and allocation of scarce resources will bring advantages to both the patient and the community.

Aged↗
PubMed1995

Multiple raters of disruptive child behavior: using a genetic strategy to examine shared views and bias.

Most research on child behavior incorporates information from different individuals. While agreement between informants is generally only modest, there is little understanding of the processes underlying disagreement. In twin studies, differential agreement among raters for MZ and DZ twins is of particular concern. The processes underlying differences among mother, father, and child ratings of oppositional and conduct disorder symptoms are explored. Evidence in favor of a shared parental view of behavior is presented. Parental ratings give higher intrapair correlations, which could be due to either parents rating their twins more similarly or twins contrasting themselves. Rater bias and situational specificity are among the possible explanations of differential ratings. The effects of incorporating multiple raters of behavior on estimates of genetic and environmental effects are explored. These suggest that genetic influences are greater for the shared (multiple-rater) phenotype than for individual ratings; reduction in measurement error is only a partial explanation.

Adolescent↗
PubMed1995

Issues in estimating the cost of innovative mental health programs.

This paper reviews problems encountered in estimating the unit cost of services provided by innovative mental health programs and illustrates methods for addressing these problems. Generally, the cost of a health care service is determined by identifying all resources used in its production and the cost of those resources. These costs are divided by appropriate workload measures to determine the cost per unit of service or per client. Issues that must be addressed include: 1) direct program costs; 2) indirect costs (including administration and capital costs); 3) program resources used to support research and other non-program activities; and 4) identification of "typical" workloads as the program is implemented. Application of these methods is illustrated with data from a multi-site study of intensive psychiatric community care conducted at nine Department of Veterans Affairs Medical Centers in the Northeast. A sensitivity analysis revealed that estimates of program costs vary by 59% over the entire program, and from 17%-168% at individual sites, depending on which cost estimation methods were included. The average cost of case management in this program varied considerably across sites, primarily reflecting differences in caseload size and staffing levels. Adjusting for inflation, the cost of this program falls below the cost of other published intensive community programs.

Community Mental Health Services↗
PubMed1995

Multisite experimental cost study of intensive psychiatric community care.

A 2-year experimental cost study of 10 Intensive Psychiatric Community Care (IPCC) programs was conducted at Department of Veterans Affairs (VA) medical centers in the Northeast. High hospital users were randomly assigned to either IPCC (n = 454) or standard VA care (n = 419) at four neuropsychiatric (NP) and six general medical and surgical (GMS) hospitals. National computerized data were used to track all VA health care service usage and costs for 2 years following program entry. At 9 of the 10 sites, IPCC treatment resulted in reduced inpatient service usage. Overall, for IPCC patients compared with control patients, average inpatient usage was 89 days (33%) less while average cost per patient (for IPCC inpatient, and outpatient services) was $15,556 (20%) less. Additionally, costs for IPCC patients compared with control patients were $33,295 (29%) less at NP sites but were $6,273 (15%) greater at GMS sites. At both NP and GMS sites, costs were lower for IPCC patients in two subgroups: veterans over age 45 and veterans with high levels of inpatient service use before program entry. No interaction was noted between the impact of IPCC on costs and other clinical or sociodemographic characteristics. Similarly, no linear relationship was observed between the intensity of IPCC services and the impact of IPCC on VA costs, although the two sites that did not fully implement the IPCC program had the poorest results. With these sites excluded, the total cost of care for IPCC patients at GMS sites was $579 (3%) more per year than that for the control patients.

Activities of Daily Living↗
PubMed1994

A simple method for censored age-of-onset data subject to recall bias: mothers' reports of age of puberty in male twins.

Genetic analysis of variation in age of onset of development milestones or psychopathological behaviors has been little researched, owing largely to the computational difficulty of dealing with "censored" observations. Censored observations arise when the only information on individuals is that they have reached a particular age but without onset having occurred. This paper shows how models can be simply fitted to such data using programs that can perform genetic analysis of categorical data by maximum likelihood. The method is illustrated using the program Mx with data on maternal report of the onset of puberty in twin sons from the Virginia Twin Study of Adolescent Behavioral Development. Frequently, data on age of onset is collected by retrospective recall. This can pose a variety of measurement problems. Suggestions are made for models that account for some of these problems or are robust to their presence. Substantial evidence for "telescoping" of onset dates is found for the puberty data. If left unaccounted for, these effects can artifactually inflate estimates of common environment effects.

Adolescent↗