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Biomedical subjects

A Ward

Publications and source records attributed to A Ward.

At least 19 recordsLinked to original sources
PubMed2006

Clinical outcome and service implications of screening women at increased breast cancer risk from a family history.

INTRODUCTION: The value of special screening for women at moderate breast cancer risk with a family history of breast cancer remains controversial. Little is known about recall rates, false negative outcomes and the impact on clinical service. Despite this, surveillance programmes within breast units have been established in the United Kingdom. PATIENTS AND METHODS: In our institution, screening of women at moderate (lifetime risk, 17-30%) and high risk (>30%) consisted of annual clinical examination and mammography from the age of 35 years. The active study period ran for four months and each patient was followed through a further screening cycle (whole study period), providing information on interval cancers and detection at the subsequent screen. RESULTS: One thousand one hundred and thirty-two women attended for their incident screen: 137 at high risk, 803 at moderate risk and 192 at standard risk. The median age at cancer diagnosis in the moderate risk group was 54 (range, 45-68) years and the high-risk group 51 (46-52) years, compared to 63 (45-69) years in the standard risk group. Seven cancers were diagnosed during the four-month active study period. Two patients were diagnosed with interval cancers and eight at the next screen, giving a cancer incidence in the whole study period of 17/1132 (1.5%). Thirteen patients had invasive cancer and four had ductal carcinoma in situ (DCIS) The median invasive tumour size was 15 had (range, 7-28)mm and the median DCIS size was 4 (2-30)mm. 10/13 (76.9%) invasive cancers were < or =20mm and 2/13 patients (15.4%) with invasive cancer were lymph node positive. The sensitivity and specificity of mammography were 85.7% and 98.8%, respectively. The mammogram recall rate was 27.6 per 1000. The benign to malignant surgery ratio was 8:17. CONCLUSION: Screening women at increased breast cancer risk is effective. Early detection and recall rates are comparable to that of older women attending the British National Breast Screening Programme.

Adult↗
PubMed2006

The influence of radiotherapy on capsule formation and aesthetic outcome after immediate breast reconstruction using biodimensional anatomical expander implants.

BACKGROUND: Capsular contracture occurs more frequently when immediate breast reconstruction (IBR) is associated with radiotherapy (RT) in a post-mastectomy field. The aim of this study was to investigate the impact of RT on surgical outcome after IBR using a single implant type. METHODS: One hundred and thirty-six breast reconstructions were studied in 114 patients: 62 reconstructions were performed using submuscular implants alone and 74 had an implant-assisted latissimus dorsi myocutaneous flap using a McGhan 150 biodimensional permanent expander implant. Data were prospectively collected on capsule contracture, geometric measurements, photographic assessments and pain scores. The median follow-up was 4 (range, 2-5) years. RESULTS: The mean age of the 114 patients studied was 45 (range, 20-77) years. Forty-four reconstructed breasts received RT. Capsule formation was detected in 13/92 (14.1%) reconstructed breasts with no RT and in 17/44 (38.6%) reconstructed breasts with RT. On univariate analysis, RT was the only variable related to capsule formation (p<0.001). Significant differences in geometric measurements of symmetry were identified in patients with capsules compared with those without capsules. Photographic assessments were worse in the capsule group: mean photo score 8 (95% CI 8, 8.5) compared with the no capsule group 6.5 (95% CI 5, 7.5), p<0.001. Persistent pain two years or more after surgery was present in 8/30 patients with capsules and 1/106 with no capsule group, p<0.01. Capsule formation is three times more likely to occur after IBR in association with an RT field. However, as more than 60% of patients do not get capsules despite RT at four years, implant-assisted tissue expansion techniques using a biodimensional device is a viable breast reconstructive option in selected cases.

Adult↗
PubMed2006

Different isoforms of the Wilms' tumour protein WT1 have distinct patterns of distribution and trafficking within the nucleus.

The Wilms' tumour suppressor gene WT1 encodes multiple isoforms of a transcription factor essential for correct mammalian urogenital development. Maintenance of the correct isoform ratio is critical. In humans, perturbation of this ratio causes Frasier syndrome, which is characterized by developmental defects of the kidney and urogenital tract. Different WT1 isoforms are thought to regulate transcription and participate in mRNA processing, functions reflected by a complex sub-nuclear distribution. However, the role of individual WT1 isoforms remains unclear and pathways leading to WT1 sub-nuclear localization are completely unknown. Here we use cells expressing green fluorescent protein-tagged WT1 to demonstrate that the two major WT1 isoforms occupy separate and dynamic intranuclear locations in which one isoform, WT1+KTS, preferentially associates with the nucleolus. The alternatively spliced zinc finger region is found to be critical for the initial sub-nuclear separation of WT1 isoforms, but interactions between different isoforms influence the sub-nuclear distribution of WT1. We illustrate how disruption of WT1 nuclear distribution might result in disease. This study contributes to the emerging picture of intranuclear protein trafficking.

Alternative Splicing↗
PubMed2006

Regulation of growth and metabolism by imprinted genes.

A small sub-set of mammalian genes are subject to regulation by genomic imprinting such that only one parental allele is active in at least some sites of expression. Imprinted genes have diverse functions, notably including the regulation of growth. Much attention has been devoted to the insulin-like growth factor signalling pathway that has a major influence on fetal size and contains two components encoded by the oppositely imprinted genes, Igf2 (a growth promoting factor expressed from the paternal allele) and Igf2r (a growth inhibitory factor expressed from the maternal allele). These genes fit the parent-offspring conflict hypothesis for the evolution of genomic imprinting. Accumulated evidence indicates that at least one other fetal growth pathway exists that has also fallen under the influence of imprinting. It is clear that not all components of growth regulatory pathways are encoded by imprinted genes and instead it may be that within a pathway the influence of a single gene by each of the parental genomes may be sufficient for parent-offspring conflict to be enacted. A number of imprinted genes have been found to influence energy homeostasis and some, including Igf2 and Grb10, may coordinate growth with glucose-regulated metabolism. Since perturbation of fetal growth can be correlated with metabolic disorders in adulthood these imprinted genes are considered as candidates for involvement in this phenomenon of fetal programming.

Animals↗
PubMed2005

Evaluation of Streptomyces sp. strain g10 for suppression of Fusarium wilt and rhizosphere colonization in pot-grown banana plantlets.

Streptomyces sp. strain g10 exhibited strong antagonism towards Fusarium oxysporum f.sp. cubense (Foc) races 1, 2 and 4 in plate assays by producing extracellular antifungal metabolites. Treating the planting hole and roots of 4-week-old tissue-culture-derived 'Novaria' banana plantlets with strain g10 suspension (10(8) cfu/ml), significantly (P < 0.05) reduced wilt severity when the plantlets were inoculated with 10(4) spores/ml Foc race 4. The final disease severity index for leaf symptom (LSI) and rhizome discoloration (RDI) was reduced about 47 and 53%, respectively, in strain g10-treated plantlets compared to untreated plantlets. Reduction in disease incidence was not significant (P < 0.05) when plantlets were inoculated with a higher concentration (10(6) spores/ml) of Foc race 4. Rhizosphere population of strain g10 showed significant (P = 0.05) increase of more than 2-fold at the end of the 3rd week compared to the 2nd week after soil amendment with the antagonist. Although the level dropped, the rhizosphere population at the end of the 6th week was still nearly 2-fold higher than the level detected after 2 weeks. In contrast, the root-free population declined significantly (P = 0.05), nearly 4-fold after 6 weeks when compared to the level detected after 2 weeks. Neither growth-inhibiting nor growth-stimulating effects were observed in plantlets grown in strain g10-amended soil.

Fusarium↗
PubMed2005

Continued axillary sampling is unnecessary and provides no further information to sentinel node biopsy in staging breast cancer.

INTRODUCTION: Sentinel lymph node biopsy (SLNB) has become increasingly accepted as a diagnostic method to stage the axilla in breast cancer, selecting women with a positive sentinel node for completion axillary clearance. As SLNB became established, many surgeons supplemented SLNB to sample a minimum of four lymph nodes, on the assumption that the four-node technique is supported by randomised trial data. We hypothesised that the practice of undirected sampling to supplement SLNB adds little information to the status of the residual axilla. METHODS: One hundred and sixty-five patients with early breast cancer were studied. Following successful identification of the sentinel node, 84 women had completion axillary dissection and 81 women had an axillary sample with at least four nodes available for pathological assessment. RESULTS: Following successful identification of the sentinel node in 165 patients, the false negative rate (FNR) was 2/44=4.5% (95% CI 0.6-15.5), sensitivity 42/44=95.5% (84.5-99.4) and negative predictive value (NPV) 121/123=98.4% (94.2-99.8). In the axillary dissection cohort, the FNR was 2/26=7.7% (0.9-25.1), sensitivity 24/26=92.3% (74.9-99.1) and NPV 58/60=96.7% (88.5-100). In the axillary sample group, the FNR was 0/18=0% (0-18.5), sensitivity 18/18=100% (81.5-100) and NPV 63/63=100% (94.3-100). The SLNB was the only positive node in 12/26 (46.2%) in the axillary dissection group and 10/18 (55.6%) in the axillary sampling group. There was no patient in the axillary sampling group where the sample node was positive and the sentinel node negative. CONCLUSION: Once SLNB is validated within the multidisciplinary unit, undirected sampling of the axilla following identification of the sentinel node(s) is unnecessary. The additional sampling of non-sentinel nodes has no role to play either in the assessment of a potential false negative SLNB nor as predictive information on the status of the residual axillary nodes.

Adult↗
PubMed2005

Care needs and economic consequences after acute ischemic stroke: the Erlangen Stroke Project.

The objective was to determine the functional outcome, location of care and economic consequences in the first 3 months after ischemic stroke. As part of the Erlangen Stroke Project, (ESPro) information was collected on patients suffering a first-ever ischemic stroke. Three months after the stroke, location of care, dependence on caregivers and function based on Barthel Index: poor (0-55), moderate (60-90) or good function (95-100) were recorded. Data about health services used were combined with cost estimates for Germany (2000 Euros, undiscounted). Of 491 patients hospitalized, 383 were alive 3 months afterwards, 79% residing in the community. The majority of patients with poor function (60%) were still in institutional care. Patients with good function typically accrued the lowest costs, whether in an institution (17 965) or not (11 032) compared with poorer function who were living in an institution (poor: 26 370; moderate: 28,121), or community (poor: 27,207; moderate: 19,350). Hospitalization and rehabilitation services were the major costs accrued at each level of function. Many patients were left requiring a substantial amount of care and the costs associated with providing institutional care has a major impact on the economic consequences of a stroke.

Adult↗
PubMed2003

Assessment of health economics in Alzheimer's disease (AHEAD): treatment with galantamine in the UK.

OBJECTIVE: To assess the long-term health and economic impact of treating mild to moderate Alzheimer's disease (AD) with galantamine (16 mg or 24 mg per day) compared to no cholinesterase therapy in the UK. METHODS: The long-term costs and outcomes were assessed using a model developed from longitudinal data on a cohort of AD patients. The model predicts the time until patients require full-time care, defined as the consistent requirement for a significant amount of care and supervision each day. Efficacy data were obtained from three clinical trials comparing galantamine with placebo, forecasts were made for ten years. Costs were determined in 2001 British pounds and discounted at 6% per annum, while outcomes such as time to full-time care were discounted at 1.5%. RESULTS: Without pharmacological treatment, patients are expected to incur costs of 28,134 British pounds over ten years, 70% of costs accrue from providing full-time care. Galantamine (16 mg per day) is predicted to reduce the duration of the full-time care state by 12%; approximately five patients need to be treated to avoid one year of full-time care. The ten-year incremental costs per month of full-time care avoided average pound 192 British pounds per patient and 8,693 British pounds per QALY. Savings (1380 British pounds) are predicted for patients who continue treatment beyond six months and whose cognitive function is maintained or improved. Comparable results were estimated for the 24 mg dose. CONCLUSION: In addition to the clinical benefits associated with galantamine treatment, the savings predicted from delaying when full-time care is needed may offset the treatment costs.

Aged↗
PubMed2003

The London nail bombings: the St. Thomas' Hospital experience.

At 18:00 h on 17 April 1999 a nail bomb exploded outside a supermarket in Brixton, London. This was the first of a series of three identical nail bombs. The injuries were due to penetrating nails, most were relatively minor, with only three patients requiring general anaesthesia for removal of nails and debridement. One 6-year-old child subsequently underwent onward referral for neurosurgical treatment. At 18:40 h on 30 April 1999, the third bomb exploded (there were no casualties at our hospital from the second bomb, that in Brick Lane on 24 April 1999) in the confined environment of the Admiral Duncan public house in Soho. The injuries were much more severe than those seen from the Brixton bomb. Two persons died on the scene and 81 were injured; 27 were transferred to our hospital. Three primary lower limb amputations were performed. Within the first 24h, four patients required ITU care and two onward referral to the regional burns unit. Injuries such as those seen in these two bombings are common in war situations. In peacetime it is rare to see this spectrum of injury and hence surgeons can be unaware of optimal management protocols. Our approach in these patients, based on thorough initial debridement and delayed closure/split skin grafting is similar to that advocated by the International Committee of the Red Cross based on their war surgery experience. We emphasise debridement without any initial reconstructive procedures. We also discuss some logistic problems of major incidents.

Adolescent↗
PubMed2003

Current practice in the management of Attention Deficit Disorder with Hyperactivity (ADHD).

BACKGROUND: The management of Attention Deficit Disorder with Hyperactivity (ADHD) is controversial and guidance published by the National Institute for Clinical Excellence (NICE) suggests a multidisciplinary approach. METHODS: We evaluated the patterns of referral and techniques used in the diagnosis and management of ADHD in Wirral Health Authority by studying the case notes of 391 children diagnosed between 1994 and August 2000. RESULTS: The majority of cases were referred from Primary Care and the detected prevalence was 8/1000. Boys were diagnosed more frequently than girls (12 : 1) and the mean age at diagnosis was 8.7 years; girls were more likely to have been diagnosed prior to age 8. The use of behaviour rating questionnaires and school visits as an aid to diagnosis increased during the study period. Management by Child Psychiatry and Community Paediatric services was similar with stimulant medication prescribed in 91% of cases; Child Psychiatry services were more likely to give advice on behaviour management than Paediatric services. Twelve per cent of cases were managed by both services, or in joint Outpatient clinics. Outpatient follow-up was most likely to occur at six monthly intervals and required 1312 appointments per year. CONCLUSIONS: This study shows that the management of children with ADHD in Wirral Health Authority is compatible with NICE guidance. Attention Deficit Disorder with Hyperactivity is a significant burden on clinical services and long-term planning is required.

Attention Deficit Disorder with Hyperactivity↗
PubMed2003

Factor Xa is highly protected from antithrombin-fondaparinux and antithrombin-enoxaparin when incorporated into the prothrombinase complex.

Antithrombin and its cofactor, heparin, target both the product of prothrombin activation by prothrombinase, thrombin, as well as the enzyme responsible for the reaction, factor (F)Xa. These studies were carried out to quantify the effects of each of the prothrombinase components on the half-life of FXa in the presence of antithrombin and the low-molecular-weight heparins (enoxaparin, Aventis, Laval, Quebec, Canada) or the heparin pentasaccharide (fondaparinux, Organon Sanofi-Synthelabo, Cypress, TX, USA). Experiments were carried out using a recombinant form of prothrombin in which the active site serine has been mutated to cysteine and subsequently labeled with fluorescein. This mutant allowed calculation of the second order rate constant for inhibition of FXa by antithrombin in such a way that competition for antithrombin by thrombin is eliminated and competition for FXa by prothrombin is accounted for. Intrinsic rate constants for the inhibition of FXa by antithrombin-enoxaparin and antithrombin-fondaparinux, in the presence of the various prothrombinase components, were calculated. Addition of phospholipid had no significant effect on the second order rate constant for inhibition of FXa by antithrombin, while addition of FVa appeared to be mildly protective. Further addition of prothrombin however, caused profound protection of FXa, increasing its half-life from 1.1 to 353 s in the case of fondaparinux, and from 0.4 to 42 s in the case of enoxaparin. Similar results were reported for unfractionated heparin previously [1]. Therefore, in the presence of unfractionated heparin, fondaparinux, or enoxaparin, prothrombinase is profoundly protected from antithrombin.

Antithrombin III↗
PubMed2003

Congenital brachial palsy: incidence, causes, and outcome in the United Kingdom and Republic of Ireland.

OBJECTIVES: To determine the incidence and study the causes and outcome of congenital brachial palsy (CBP). DESIGN: Active surveillance of newborn infants using the British Paediatric Surveillance Unit notification system and follow up study of outcome at 6 months of age. SETTING: The United Kingdom and Republic of Ireland. PARTICIPANTS: Newborn infants presenting with a flaccid paresis of the arm (usually one, rarely both) born between April 1998 and March 1999. MAIN OUTCOME MEASURES: Extent of the lesion at birth and degree of recovery at 6 months of age. FINDINGS: There were 323 confirmed cases giving an incidence of 0.42 per 1000 live births (1 in 2300). Significant associated risk factors in comparison with the normal population were shoulder dystocia (60% v 0.3%), high birth weight with 53% infants weighing more than the 90th centile, and assisted delivery (relative risk (RR) 3.4, 95% confidence interval (CI) 2.9 to 3.9, p = 0.0001). There was a considerably lower risk of CBP in infants delivered by caesarean section (RR 7, 95% CI 2 to 56, p = 0.002). At about 6 months of age, about half of the infants had recovered fully, but the remainder showed incomplete recovery including 2% with no recovery. The relative risk of partial or no recovery in infants with extensive lesions soon after birth compared with those with less extensive lesions was 11.28 (95% CI 2.38 to 63.66, p = 0.000005). CONCLUSIONS: The incidence of CBP in the United Kingdom and Republic of Ireland is strikingly similar to that previously reported nearly 40 years ago. Most cases are due to trauma at delivery, which is not necessarily excessive or inappropriate. Given the uncertainty about the appropriate management of these infants, serious consideration should be given to a formal clinical trial of microsurgical nerve repair.

Arm↗
PubMed2002

Glucocorticoid epidural for sciatica: metabolic and endocrine sequelae.

OBJECTIVE: The study was designed to investigate the effect of epidural administration of glucocorticoid on insulin sensitivity. METHODS: Ten healthy individuals with sciatica underwent a short insulin tolerance test before and twice following (at 24 h and 1 week) a caudal epidural containing 80 mg triamcinolone. Fasting glucose, insulin and cortisol concentrations were also measured. RESULTS: The rate of glucose disappearance after insulin administration (k(ITT)) fell from 3.6%/min before the epidural to 1.9%/min 24 h afterwards (P=0.001) and returned to pretreatment values by 1 week. Significantly raised fasting insulin and glucose levels also reflected impaired insulin sensitivity immediately after the epidural. Morning cortisol levels were suppressed after the epidural (49 nmol/l at 24 h and 95 nmol/l at 1 week vs 352 nmol/l at baseline; P<0.01). CONCLUSIONS: Epidural administration of glucocorticoid results in potent suppression of insulin action and this should be taken into account when patients with diabetes require treatment for sciatica.

Adult↗
PubMed2002

Detection of serum M2 anti-mitochondrial antibodies by enzyme-linked immunosorbent assay is potentially less specific than by immunofluorescence.

AIM: To compare the predictive values of enzyme-linked immunosorbent assays (ELISAs) and indirect immunofluorescence (IIF) techniques for the detection of M2 anti-mitochondrial antibodies. METHODS: Commercial ELISAs are widely available for the detection of anti-mitochondrial antibody subtypes in primary biliary cirrhosis (PBC). We compared the results from two ELISAs (one recombinant, one purified antigen) with those from two IIF methods in a well-defined cohort of PBC patients and in patients with systemic lupus erythematosus, Sjögren's syndrome, sicca syndrome, systemic sclerosis, rheumatoid arthritis and blood donor controls. RESULTS: There was good correlation between a rodent substrate IIF and ELISA A (r=0.9134), but poor correlation with ELISA B (r=0.5999), which produced many false-positive results in the control population. We show that rodent IIF alone or human epithelial cell (HEp-2000) screening with confirmation by ELISA produce similar predictive values for PBC and require lesser degrees of skilled interpretation of IIF patterns. CONCLUSIONS: We conclude that the specificities of IIF are greater than the ELISA methods (99% versus 85-97%), although the ELISAs are slightly more sensitive in biopsy-proven PBC. Careful in-house validation of all new ELISA technologies is mandatory for good laboratory practice, but IIF in experienced hands remains an effective and specific assay.

Animals↗
PubMed2002

Information for community hospitals.

OBJECTIVE: To design and test a revised data collection system for routine patient based data in the Community Hospital setting in Scotland. DESIGN: A two part qualitative study was designed to identify the requirements for Community Hospital information, develop a data set to meet these requirements and pilot a proposed Community Hospital Information System. SETTING: Identification of the information deficit (Stage 1) involved administering face to face questionnaires in all relevant Health Board areas in Scotland; piloting of the proposed information system (Stage 2) was carried out in four Community Hospitals in Scotland. RESULTS: Stage 1 of the study highlighted the information requirements as including: who is being treated; why they are there; how complex their needs are; what is being done and by whom; and what is happening next. The additionally required data included: admission reason--medical/social; type of care--intended and provided; all relevant diagnoses and social factors; medication--on admission and discharge; interventions--nursing/GP/consultant; dependency throughout stay; delayed discharge information; and discharge plan. The summary of recommendations that flowed from this part of the study includes: incremental electronic record; link with GP and acute systems; interface with other community systems; duplication of recording; accessibility at local level with variable levels of access (to protect patient confidentiality). Stage 2 of the study piloted the collection of the proposed dataset and permitted development of suitable feedback information, in particular the patient summary screens. Economic evaluation of the proposed dataset compared to the existing data was carried out in parallel with the study and is reported elsewhere. CONCLUSION: It is feasible and highly desirable to collect clinically useful information at little additional cost and to provide relevant feedback, including useful patient summary screens, representing the patient stay in hospital.

Data Collection↗
PubMed2001

Assessment of health economics in Alzheimer's disease (AHEAD) based on need for full-time care.

OBJECTIVE: To develop a framework for estimating the long-term health and economic consequences of AD based on patient characteristics at a given point in time. METHODS: A pharmacoeconomic model (Assessment of Health Economics in Alzheimer's Disease, AHEAD) was developed based on equations that relate the probability of needing full-time care (FTC) over time to patient characteristics summarized in index scores. These equations were developed from published data on interquartile times until FTC is needed and until death, using nonlinear regressions of the resulting index-specific hazards. These equations were then incorporated into a hidden Markov framework that allows for calculation of expected time to FTC and to death, as well as of the economic consequences of disease progression. There are three major states in the model: not requiring FTC ("pre-FTC"), requiring FTC, and death. RESULTS: Outcomes for five sample patients are derived to illustrate application of the AHEAD model. The impact of altering disease markers in these patients is also considered. CONCLUSION: The need for a generally applicable tool to forecast long-term outcomes based on relatively short-term data is becoming increasingly acute with the advent of new therapies for AD. The AHEAD model provides a relatively simple framework for the prediction of time to FTC requirement based on short-term observed data such as those from clinical trials. Although subject to the uncertainties inherent in modeling, the model nevertheless provides a standard estimation technique that may facilitate comparisons between existing and emerging therapies.

Aged↗
PubMed2001

CpG methylation regulates the Igf2/H19 insulator.

The differentially methylated 5'-flank of the mouse H19 gene unidirectionally regulates the communication between enhancer elements and gene promoters and presumably represses maternal Igf2 expression in vivo [1-6]. The specific activation of the paternally inherited Igf2 allele has been proposed to involve methylation-mediated inactivation of the H19 insulator function during male germline development [1-4, 6]. Here, we addressed the role of methylation by inserting a methylated fragment of the H19-imprinting control region (ICR) into a nonmethylated episomal H19 minigene construct, followed by the transfection of ligation mixture into Hep3B cells. Individual clones were expanded and analyzed for genotype, methylation status, chromatin conformation, and insulator function. The results show that the methylated status of the H19 ICR could be propagated for several passages without spreading into the episomal vector. Moreover, the nuclease hypersensitive sites, which are typical for the maternally inherited H19 ICR allele [1], were absent on the methylated ICR, underscoring the suggestion that the methylation mark dictates parent of origin-specific chromatin conformations [1] that involve CTCF [2]. Finally, the insulator function was strongly attenuated in stably maintained episomes. Collectively, these results provide the first experimental support that the H19 insulator function is regulated by CpG methylation.

Alleles↗