PubMed Health⌕ Search

Biomedical subjects

B Ferguson

Publications and source records attributed to B Ferguson.

At least 19 recordsLinked to original sources
PubMed2007

Evidence for the receipt of DNA damage stimuli by PML nuclear domains.

Promyelocytic leukaemia nuclear domains (PML-NDs) comprise a shell of PML protein and many labile cargo proteins. The nature of their cargo, their juxtaposition to foci of damaged DNA following ionizing radiation (IR), and the altered DNA damage responses in PML null cells all implicate PML-NDs in the DNA damage response. In this work, the propensity of PML-NDs to increase in number and decrease in size following IR has been studied. Serial quantitative studies of endogenous PML-NDs prove that the PML-ND response to IR is not the result of the asymmetry in cell cycle distribution that can follow IR, but reflects more directly the process of DNA damage. The response is swift, sensitive (evident after 1 Gy), and potentially reversible in untransformed fibroblasts. In these cells and in HCT116 colon cancer cells, failure to restore PML-ND number within 24 h correlates with later loss of growth potential--in fibroblasts, through prolonged cell cycle arrest and in HCT116 cells, through apoptosis. Failure to express an intact ATM/CHK2 DNA damage signalling pathway in either cell type leads to a delay in the PML-ND response to IR. Conversely, cell cycle progression following IR in cells that detect damaged DNA accelerates PML-ND reorganization. Collectively, these data show that the increase in PML-ND number seen after irradiation is, in part, triggered by the receipt of the DNA damage stimulus. The senescent cell state is also associated with chronic DNA damage and Hayflick-limited fibroblasts were found to express nuclei with elevated numbers of PML-NDs before IR that remained unresponsive to IR. Though the underlying reasons for damage-induced PML alteration remain obscure, it is noteworthy that significant numbers of PML-NDs juxtapose with ionizing radiation-induced foci after IR. The co-regulation of these structures may necessitate the stereotyped increases in PML-ND number following damage.

Apoptosis↗
PubMed2004

Endoscopic ultrasonography in the diagnosis and staging of neoplasms of the head and neck.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a minimally invasive and highly accurate method of detecting mediastinal lymph-node metastases in gastrointestinal and lung cancer. Little information is available regarding the use of EUS-FNA to stage tumors in the head and neck region. This study reports experience with EUS in the diagnosis and staging of these tumors and their mediastinal spread. PATIENTS AND METHODS: The records of patients who underwent EUS for diagnosis and/or staging of head and neck tumors were reviewed. Referral criteria were suspected invasion of the esophagus by a lower-neck mass on cervical computed tomography (CT) or magnetic resonance imaging (MRI), or mediastinal lymphadenopathy > 10 mm on a chest CT. RESULTS: Thirty-two patients (23 men, nine women; mean age 65 years, range 44 - 80) were referred and underwent 35 EUS examinations. In one patient, EUS was not possible due to a benign esophageal stricture. In 17 patients with suspected esophageal invasion on CT scans, EUS demonstrated invasion of the esophagus in four cases and of the pleura in one; 12 tumors showed no visible invasion of adjacent structures. The other 17 examinations were carried out for suspected mediastinal metastatic disease. In eight cases, EUS-FNA confirmed metastatic disease, whereas only benign changes were shown in the other nine cases. EUS-FNA also provided the first tissue diagnosis in two primary tumors and identified malignancy in one patient with no CT suspicion of positive mediastinal lymph nodes. EUS avoided the need for more invasive investigations in all patients with mediastinal lymphadenopathy, and it changed the management in 12 of the 17 patients (71 %) with suspected esophageal invasion and in eight of the 17 patients (47 %) with suspected mediastinal disease. CONCLUSIONS: EUS with FNA provides a viable approach to the diagnosis and staging of tumors in the head and neck region when there is a suggestion of esophageal invasion on CT or MRI, or enlarged mediastinal lymph nodes. EUS with FNA may avoid the need for mediastinoscopy or other more invasive techniques for staging of these neoplasms.

Adult↗
PubMed2003

New algorithms for multi-class cancer diagnosis using tumor gene expression signatures.

MOTIVATION: The increasing use of DNA microarray-based tumor gene expression profiles for cancer diagnosis requires mathematical methods with high accuracy for solving clustering, feature selection and classification problems of gene expression data. RESULTS: New algorithms are developed for solving clustering, feature selection and classification problems of gene expression data. The clustering algorithm is based on optimization techniques and allows the calculation of clusters step-by-step. This approach allows us to find as many clusters as a data set contains with respect to some tolerance. Feature selection is crucial for a gene expression database. Our feature selection algorithm is based on calculating overlaps of different genes. The database used, contains over 16 000 genes and this number is considerably reduced by feature selection. We propose a classification algorithm where each tissue sample is considered as the center of a cluster which is a ball. The results of numerical experiments confirm that the classification algorithm in combination with the feature selection algorithm perform slightly better than the published results for multi-class classifiers based on support vector machines for this data set. AVAILABILITY: Available on request from the authors.

Algorithms↗
PubMed2003

Randomized controlled trial of brief cognitive behaviour therapy versus treatment as usual in recurrent deliberate self-harm: the POPMACT study.

BACKGROUND: We carried out a large randomized trial of a brief form of cognitive therapy, manual-assisted cognitive behaviour therapy (MACT) versus treatment as usual (TAU) for deliberate self-harm. METHOD: Patients presenting with recurrent deliberate self-harm in five centres were randomized to either MACT or (TAU) and followed up over 1 year. MACT patients received a booklet based on cognitive behaviour therapy (CBT) principles and were offered up to five plus two booster sessions of CBT from a therapist in the first 3 months of the study. Ratings of parasuicide risk, anxiety, depression, social functioning and global function, positive and negative thinking, and quality of life were measured at baseline and after 6 and 12 months. RESULTS: Four hundred and eighty patients were randomized. Sixty per cent of the MACT group had both the booklet and CBT sessions. There were seven suicides, five in the TAU group. The main outcome measure, the proportion of those repeating deliberate self-harm in the 12 months of the study, showed no significant difference between those treated with MACT (39%) and treatment as usual (46%) (OR 0.78, 95% CI 0.53 to 1.14, P=0.20). CONCLUSION: Brief cognitive behaviour therapy is of limited efficacy in reducing self-harm repetition, but the findings taken in conjunctin with the economic evaluation (Byford et al. 2003) indicate superiority of MACT over TAU in terms of cost and effectiveness combined.

Adult↗
PubMed2003

"Cold calling" in psychiatric follow up studies: is it justified?

BACKGROUND: The ethics of cold calling-visiting subjects at home without prior appointment agreed-in follow up research studies has received little attention although it is perceived to be quite common. We examined the ethical implications of cold calling in a study of subjects with defined neurotic disorders followed up 12 years after initial assessment carried out to determine outcome in terms of symptoms, social functioning, and contact with health services. The patients concerned were asked at original assessment if they would agree to be followed up subsequently and although they agreed no time limit was put on this. OBJECTIVES: To decide if cold calling was ethically justifiable and, if so, to set guidelines for researchers. DESIGN: The study was a cohort study of patients with neurotic disorder treated initially for 10 weeks in a randomised controlled trial. FINDINGS: At follow up by a research medical practitioner 18 of the 210 patients had died and of the remaining 192 patients 186 (97%) were seen or had a telephone interview. Four patients refused and two others did not have interviews but agreed to some data being obtained. However, only 104 patients (54%) responded to letters inviting them to make an appointment or to refuse contact and the remainder were followed up by cold calling, with most patients agreeing readily to the research interview. The findings illustrate the dilemma of the need to get the maximum possible data from such studies to achieve scientific validity (and thereby justify the ethics of the study) and the protection of subjects' privacy and autonomy. CONCLUSIONS: More attention needs to be paid to consent procedures if cold calling is to be defended on ethical grounds but it is unreasonable to expect this to be obtained at the beginning of a research study in a way that satisfies the requirements for informed consent. A suggested way forward is to obtain written consent for the research at the time that cold calling takes place before beginning the research.

Adult↗
PubMed2001

Mutations within a furin consensus sequence block proteolytic release of ectodysplasin-A and cause X-linked hypohidrotic ectodermal dysplasia.

X-linked hypohidrotic ectodermal dysplasia (XLHED) is a heritable disorder of the ED-1 gene disrupting the morphogenesis of ectodermal structures. The ED-1 gene product, ectodysplasin-A (EDA), is a tumor necrosis factor (TNF) family member and is synthesized as a membrane-anchored precursor protein with the TNF core motif located in the C-terminal domain. The stalk region of EDA contains the sequence -Arg-Val-Arg-Arg156-Asn-Lys-Arg159-, representing overlapping consensus cleavage sites (Arg-X-Lys/Arg-Arg( downward arrow)) for the proprotein convertase furin. Missense mutations in four of the five basic residues within this sequence account for approximately 20% of all known XLHED cases, with mutations occurring most frequently at Arg156, which is shared by the two consensus furin sites. These analyses suggest that cleavage at the furin site(s) in the stalk region is required for the EDA-mediated cell-to-cell signaling that regulates the morphogenesis of ectodermal appendages. Here we show that the 50-kDa EDA parent molecule is cleaved at -Arg156Asn-Lys-Arg(159 downward arrow)- to release the soluble C-terminal fragment containing the TNF core domain. This cleavage appears to be catalyzed by furin, as release of the TNF domain was blocked either by expression of the furin inhibitor alpha1-PDX or by expression of EDA in furin-deficient LoVo cells. These results demonstrate that mutation of a functional furin cleavage site in a developmental signaling molecule is a basis for human disease (XLHED) and raise the possibility that furin cleavage may regulate the ability of EDA to act as a juxtacrine or paracrine factor.

Amino Acid Sequence↗
PubMed2001

Incentives and clinical governance: money following quality?

This paper attempts to define quality (particularly in terms of evidence-based health care) and considers the incentives available to bring about improvements in quality. It examines the contribution that economics, as a discipline, can make to the debate on clinical governance. It considers the nature and importance of clinical governance, measuring quality, objectives and behaviour in questions raised concerning objectives and individual and team behaviour.

Evidence-Based Medicine↗
PubMed2000

Population requirement for adult critical-care beds: a prospective quantitative and qualitative study.

BACKGROUND: The provision of adult critical-care facilities is not based on a rational or scientific assessment of need. We aimed to define the numbers of adult critical-care beds required for a population of 500000. METHODS: In five hospitals in Wales, UK, we classified patients who might be suitable for critical care in intensive-care or high-dependency units. On every 12th day for 1 calendar year, we counted the numbers of such patients admitted in a defined geographical population. A panel of ten intensivists made consensus decisions about whether individual patients were in the appropriate unit. The data were used to predict the numbers of beds and units required for the population. FINDINGS: 4058 patients were suitable for critical care, of whom 3028 lived in the study area. 56.4% were in general wards, 22.3% in high-dependency units, and 21.3% in intensive-care units. The mean risk of death was 22.0% and the in-hospital death rate 17.3%. According to the masked consensus, 41.3% of patients required high-dependency beds and 21.5% intensive-care beds. Mean risk of death increased from general wards (14.7%) to high-dependency units (19.2%) to intensive care (37.0%). Based on the consensus decisions, the average daily requirement of intensive-care beds was 21 and of high-dependency beds 43; to meet needs 95% of times required 30 and 55 beds, respectively, in a single critical-care unit. INTERPRETATION: We estimated, scientifically, numbers of adult critical-care beds required to meet population needs. Studies are necessary periodically to track changes in admissions requiring critical care.

APACHE↗
PubMed2000

Cognitive difficulty in physicians.

PURPOSE: Remediation of some incompetent physicians has proven difficult or impossible. The authors sought to determine whether physicians with impaired competency had neuropsychological impairment sufficient to explain their incompetence and their failure to improve with remedial continuing medical education (CME). METHOD: During a one-year period, 1996-97, all 27 participants in the Physician Review Program (PREP) conducted at McMaster University, a physician competency assessment program, undertook a detailed neuropsychological screening battery. RESULTS: Nearly all physicians assessed as competent also performed well on the neuropsychological testing. However, a significant number (about one third) of the physicians who performed poorly on the competency assessment had neuropsychological impairments sufficient to explain their poor performances. The difficulties were more marked in elderly physicians. CONCLUSION: A significant minority of incompetent physicians have cognitive impairments sufficient to explain both their incompetence and, probably, their failure to improve with remedial CME. Testing physicians for these impairments is important: to detect and treat reversible conditions, to manage irreversible conditions that preclude successful educational intervention, and to facilitate compensation in this instance. Serious consideration should be given to the incorporation of neuropsychological screening in all intensive physician review programs.

Adult↗
PubMed2000

Assessing payback from NHS reactive research programmes.

Aims to assess retrospectively the payback from NHS reactive research programmes in the Northern and Yorkshire region. A questionnaire was sent to all recipients of regional reactive research programme funding (biomedical, health services research (HSR), and primary and community care programmes) between 1 April 1991 and 31 March 1996. The sample available for analysis involved 174 respondents covering 119 projects, with a total financial value of 2.2 million Pounds. The main outcome measures used were peer-reviewed publications, changes in individual practice, changes in NHS service delivery and organisation, and impact on the careers of researchers. Overall, 119 projects produced 230 peer-reviewed publications: this was achieved at an average cost of 10,673 Pounds, 6,386 Pounds and 22,310 Pounds per publication for the biomedical, HSR, and primary and community care programmes respectively. From the qualitative data analysis, important changes in individual practice and NHS service delivery were identified by respondents. The researchers in our sample appeared to have attracted over 6 million Pounds in R&D funding related to the initial regional grant. Although based on self-report, there is evidence to suggest that the return on investment from NHS R&D can be substantial, taking a broad view of benefits to the NHS and to researchers. The findings also confirm the need for more effective dissemination and implementation of research findings.

Efficiency, Organizational↗
PubMed2000

Longitudinal study of the influence of life events and personality status on diagnostic change in three neurotic disorders.

It has been known for many years that diagnosis within the neurotic spectrum of disorders is temporally unstable and also that life events can be major precipitants of change in symptoms. Reasons for this instability could include inherent inadequacy of current diagnostic practice, the influence of life events as an agent of diagnostic shift, and an innate course of disorder with features dependent on the stage at which disorder presents (e.g., development of panic to agoraphobia). These possibilities were examined in a prospective study that was initially a randomised controlled trial. Two hundred ten patients recruited from primary care psychiatric clinics with DSM-III diagnosed dysthymic, generalised anxiety, and panic disorders were randomly allocated to either drug treatment (mainly antidepressants), cognitive-behaviour therapy, or self-help therapy over a 2 year period, irrespective of original diagnosis. Life events were recorded by using a standard procedure over the period 6 months before starting treatment and at five occasions over 2 years; 181 (86%) of the patients had follow-up data and 76% maintained compliance with the original treatment allocated over the 2 years; and 155 of the 181 patients (86%) had at least one diagnostic change in this period. There was no difference in the number of diagnostic changes between the three original diagnostic groups, but dysthymic disorder changed more frequently to major depressive episode than did GAD or panic disorder (20; 11; 12) (%) and panic disorder changed more frequently to agoraphobia (with or without panic) than did dysthymia or GAD (18; 8; 6) (%). There was no relationship between loss events and depressive diagnoses or between addition events and anxiety diagnoses, but greater numbers of conflict events were associated with diagnostic change. More life events were associated with the flamboyant and dependent personality disorders, reinforcing other evidence that many life events are internally generated by personality characteristics and cannot be regarded as truly independent.

Cognitive Behavioral Therapy↗
PubMed1999

Effect of discussion and deliberation on the public's views of priority setting in health care: focus group study.

OBJECTIVE: To investigate the extent to which people change their views about priority setting in health care as a result of discussion and deliberation. DESIGN: A random sample of patients from two urban general practices was invited to attend two focus group meetings, a fortnight apart. SETTING: North Yorkshire Health Authority. SUBJECTS: 60 randomly chosen patients meeting in 10 groups of five to seven people. MAIN OUTCOME MEASURES: Differences between people's views at the start of the first meeting and at the end of the second meeting, after they have had an opportunity for discussion and deliberation, measured by questionnaires at the start of the first meeting and the end of the second meeting. RESULTS: Respondents became more reticent about the role that their views should play in determining priorities and more sympathetic to the role that healthcare managers play. About a half of respondents initially wanted to give lower priority to smokers, heavy drinkers, and illegal drug users, but after discussion many no longer wished to discriminate against these people. CONCLUSION: The public's views about setting priorities in health care are systematically different when they have been given an opportunity to discuss the issues. If the considered opinions of the general public are required, surveys that do not allow respondents time or opportunity for reflection may be of doubtful value.

Adolescent↗
PubMed1999

Risk assessment and suicide prevention in primary care.

General practitioners (GPs) are assumed to occupy an important position in the prevention of suicide through the introduction of risk assessment techniques commonly used in psychiatric practice. Despite this theoretical role for primary care services, it remains unclear how frequently GPs implement risk assessment in patients who may be vulnerable to suicide. To address this, a retrospective survey of probable suicides was conducted within a primary care setting utilizing a questionnaire of GPs who had experienced a patient suicide and was augmented by hospital and coroners' records. 85% of questionnaires were returned and 61 deaths were adjudged as suicides during the year long census period. 75% of suicides were male and 54% were aged under 35.28% were in contact with psychiatric services prior to death, although 60% had some diagnosis of mental disorder. GPs had little knowledge of a patient's life circumstances in up to half of cases. Recording of risk assessment occurred in 38% of subjects, was positively associated with prior psychiatric contact (p = 0.001) but negatively associated with presence of physical illness (p = 0.004), older patient age (p = 0.04), and GPs length in practice (p = 0.05). One GP felt their suicide case was preventable. The low rate of risk assessment and limited knowledge of patient lifestyle point to the need for active engagement of GPs in future suicide prevention strategies and should influence the content of training programs in primary care.

Adult↗
PubMed1999

Contracting for quality: does length matter?

OBJECTIVES: To examine whether longer-term contracts for health services will shift attention away from concern for finance and activity levels and towards the achievement of better quality services. METHODS: Analysis of 288 contracts from the British National Health Service (NHS) and 12 semi-structured interviews with staff from provider (NHS hospital trusts) and purchaser (health authorities) organisations. RESULTS: No relationship was found between the duration of a contract and the duration of service specifications or quality frameworks. The annual contracting cycle is concerned largely with ensuring that all parties stay within activity targets and financial constraints, and this is unlikely to be affected by a shift to longer-term contracts. The setting of standards and initiatives to improve quality is largely independent of the contracting process and the duration of contracts, and relies on relationships rather than contracts. CONCLUSIONS: It is optimistic to expect longer-term contracts automatically to produce a greater focus on quality and the incentives needed to ensure that improvements in quality are delivered. However, this may not matter as issues of quality are being addressed more appropriately in the British NHS through a variety of other routes.

Contract Services↗