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Biomedical subjects

E Wilkinson

Publications and source records attributed to E Wilkinson.

At least 19 recordsLinked to original sources

The hottest sentinel lymph node is not always the positive node.

The technique of identifying the sentinel lymph node (SLN) varies from each individual institution. Generally, the highest isotope count in a lymph node is considered the SLN, whereas other radioactive nodes might also be removed. The purpose of our study was to determine if the hottest node was always the tumor-containing node. Two hundred forty-seven breast cancer patients underwent SLN biopsy from April 1998 to April 2002. Lymphatic mapping involved a radiocolloid injection and lymphoscintigraphy followed by intraoperative assessment with a hand-held gamma probe. All SLN(s) with radioactive counts 10 per cent or more of the ex vivo counts of the most radioactive SLN were removed. The SLN were sliced at 2-mm intervals with 4-microm step-sections (92-microm spacing) and evaluated by microscopy and immunohistochemistry. One hundred twenty (49%) of the 247 patients had 2 or more nodes resected. Of these 120 patients, 33 (28%) had a tumor-bearing node. In 25 (74%) cases, the tumor-bearing node was the most radioactive; however, in 8 (26%) cases, the positive node was a lesser reactive node. Although the most radioactive node in a draining basin is considered the SLN, this is often not the metastatic node. Therefore, all nodes with significant radioactive counts must be removed to ensure accurate staging.

Breast Neoplasms↗

A laboratory based intervention to improve appropriateness of lipid tests and audit cholesterol lowering in primary care.

PROBLEM: A need exists to reduce inequalities in lipid testing, to provide relevant, individual, patient based interpretation for users, and to audit lipid lowering in primary care. DESIGN: Model to compare laboratory activity between different general practices; construction of computer based strategies to define the lipid tests to be done and to interpret results for primary and secondary coronary prevention patients; introduction of the strategies into routine use; monitoring of any change after the intervention; and investigation of the potential of the strategies to produce audit data for primary care groups. BACKGROUND AND SETTING: Hospital clinical laboratory serving 22 general practices covering 150 000 patients in Bishop Auckland area County Durham. Key measurements for improvement: Reduction in differences in testing for the different serum lipids in coronary prevention. Production of usable audit data for the primary care groups involved. STRATEGIES FOR CHANGE: Four different categories of coronary prevention patient, with, for each category, the defined lipid tests to be done and advice to be given (based on the results), using the computer based strategies. EFFECTS OF CHANGE: Standardised test activity and the qualitative profile of the tests performed changed significantly. The strategies were readily adopted (median use 78%) within six months of introduction. LESSONS LEARNT: Computer based strategies can correct qualitative and quantitative differences in test requesting, provide interpretative guidance in accordance with national guidelines, and offer a cost effective model to monitor results of cholesterol lowering in general practice.

Cholesterol, HDL↗

Technique for narrow-band imaging in the far ultraviolet based on aberration-corrected holographic gratings.

We have developed a new family of imaging spectrometer designs that combine the imaging power of two-element telescopes with the aberration control of first-generation holographic gratings. The resulting optical designs provide high spatial resolution over modest fields of view at selectable wavelengths. These all-reflective designs are particularly suited for narrow-band imaging below 1050 A, the wavelength below which there are no transmitting materials in the UV. We have developed designs to efficiently map the spatial distribution of UV-emitting material. This mapping capability is absent in current and future astronomical instruments but is crucial to the understanding of the nature of a variety of astrophysical phenomena. Although our examples focus on UV wavelengths, the design concept is applicable to any wavelength.

Journal Article↗

A comparison of mammography spectral measurements with spectra produced using several different mathematical models.

Due to the relatively complex nature of spectral measurements from x-ray machines, many researchers use mathematical models to simulate the spectra they need. However, there is concern over their accuracy, and hence the impact that their accuracy may have, on subsequent calculations that rely upon the spectra modelled. With this in mind spectral measurements have been performed on a mammography machine and a comparison with spectra calculated using several different models is presented. Several different techniques have been investigated in the spectral measurements to allow for pulse pileup and other effects of high count rate. Comparison with half value layer (HVL) measurements shows that the use of a gating signal in conjunction with the air-free path provides accurate results without the need for a pinhole collimator. Comparison of the measured spectra with those calculated using different models proposed in the literature suggests that accurate results can be produced by all models, but only if the user attempts to match the calculated HVL of the modelled spectrum with the physically measured HVL. If this is not done the modelled spectra may be in error. The impact of such an error is demonstrated in calculations of mean glandular dose, which indicate a possible underestimate of the dose by up to 20%.

Female↗

Recurrent atypical myxoid fibroepithelial polyp associated with vulvar Crohn's disease.

Fibroepithelial polyps of the lower female genital tract are common lesions that can rarely exhibit atypical features including increased and atypical mitoses, bizarre nuclei, and hypercellularity, a combination of findings that may suggest malignancy. Five recurrent cases have been published to date, two of which were in pregnant females; the other three followed incomplete excisions. Our case is that of a 25-year-old female with Crohn's disease who developed multiple recurrences of polypoid and domed lesions of the labium minus following surgical excision. Histologic findings in the initial and recurrent lesions were consistent with atypical myxoid fibroepithelial polyps with underlying vulvar Crohn's disease. The lesions subsequently improved with standard Crohn's treatment including 5-amino-salicylic acid (Pentasa) and prednisone. The present case represents the only example of this entity associated with Crohn's disease, and it is the only reported recurrent case not associated with pregnancy, tamoxifen administration, or positive excision margins. The clinical, microscopic, and immunohistochemical findings of this case suggest that atypical fibroepithelial polyps of the lower female genital tract, cutaneous pleomorphic fibroma, and lesions such as fibroepithelial polyps of the anus may represent variants of the same atypical reparative process.

Adult↗

Screening for the IDDM high-risk genotype. A rapid microtitre plate method using serum as source of DNA.

Norwegian babies born with the HLA-DRB1*0401-DQA1*03-DQB1*0302/DRB1*03-DQA1+ ++*05-DQB1*0201 genotype have an estimated 17% lifetime risk of developing insulin-dependent diabetes mellitus (IDDM). Identifying these children is important for future prevention, and for studies of the non-genetic factors involved in IDDM. The aim of the study was to develop a rapid screening method for this high-risk genotype. DNA was extracted from serum collected during routine newborn screening for phenylketonuria and hypothyreosis. The second exons of HLA-DQA1 and DQB1 were co-amplified using biotinylated primers, amplicons were hybridized to a set of seven probes immobilized on a microtitre plate using a single hybridisation temperature, and detected colorimetrically by streptavidin-HRP conjugate and tetramethylbenzidine substrate. The DRB1*04 subtyping was performed using six different probes at identical conditions. The prevalence of the DRB1*0401-DQA1*03-DQB1*0302/DRB1*03-DQA1*0 5-DQB1*0201 genotype among 1,026 Norwegian babies was 2.7% (CI 95%: 1.7-3.7%). The new high-throughput genetic screening method for IDDM risk can easily be automated and included in newborn screening programs.

Alleles↗

Clinical governance in primary care groups: the feasibility of deriving evidence-based performance indicators.

OBJECTIVES: To test the feasibility of deriving comparative indicators in all the practices within a primary care group. DESIGN: A retrospective audit using practice computer systems and random note review. SETTING: A primary care group in southern England. SUBJECTS: All 18 general practices in a primary care group. MAIN OUTCOME MEASURES: Twenty six evidence-based process indicators including aspirin therapy in high risk patients, detection and control of hypertension, smoking cessation advice, treatment of heart failure, raised cholesterol levels in those with established cardiovascular disease, and the treatment of atrial fibrillation. Feasibility was tested by examining whether it was possible to derive these indicators in all the practices; the problems and constraints incurred when collecting data; the variations in indicator values between practices in both their identification of diseases and in the uptake of various interventions; the possible reasons for these variations; and the cost of generating such indicators. RESULTS: It was possible to derive eight indicators in all practices and in three practices all 26 indicators. The median number of indicators derived was 12 with two practices able to generate eight. There was considerable variation in the use of computers between practices and in the ability and ease of various practice computer systems to generate indicators. Practices varied greatly in the identification of diseases and in the uptake of effective interventions. Variation in identification of ischaemic heart disease could not be explained by a higher prevalence in practices with a more deprived population. The cost of generating these indicators was 5300 Pounds. CONCLUSION: Comparative evidence-based indicators, used as part of clinical governance in primary care groups, could have the potential to turn evidence into everyday practice, to improve the quality of patient care, and to have an impact on the population's health. However, to derive such indicators and to be able to make meaningful comparisons primary care groups need greater conformity and compatibility of computer systems, improved computer skills for practice staff, and appropriate funding.

Benchmarking↗

Do out-of-hours co-operatives improve general practitioners' health?

General practitioners (GPs) have been found to have a higher level of anxiety and depression then hospital managers and consultants. In 1995 and 1998, we surveyed GPs in Buckinghamshire. We found that the development of out-of-hours co-operatives was an important factor in the improvement in GPs' health status.

Female↗

Serum thyroxine binding capacity-dependent bias in an automated free thyroxine assay.

The magnitude of serum thyroxine (T4) binding capacity (sBC) dependent bias in the AXSYM free thyroxine (FT4) assay was assessed using two recently described tests. One of the tests uses a direct equilibrium dialysis (ED) FT4 assay as the reference method. The results obtained with the AXSYM method were compared with those obtained by the ED FT4 method in patient sera having a wide range of sBC. The other test involves comparison of the FT4 results obtained following dilution of sera by an inert buffer, to theoretically derived FT4 results. As serum dilution causes a predictable decrease in sBC, the demonstration of a negative bias whose magnitude increases in parallel to the dilution, is indicative of an sBC-dependent bias. The AXSYM FT4 assay exhibited a significant sBC-dependent bias. This sBC-dependent bias is likely to have been caused by the presence of significant amounts of T4 binding proteins in the assay reagents.

Dialysis↗

Assessment of serum thyroxine binding capacity-dependent biases in free thyroxine assays.

BACKGROUND: Free thyroxine (FT4) assays may exhibit biases that are related to serum T4 binding capacity (sBC). We describe two tests that can be used to assess the presence and magnitude of sBC-dependent biases in FT4 assays. METHODS: We used a direct equilibrium dialysis FT4 assay as the reference method and compared the results obtained with those of the FT4 assays under investigation, in patient sera having a wide range of sBC. We then compared the expected and observed FT4 results for sera diluted with an inert buffer. Because serum dilution causes a predictable decrease in sBC, an increasingly negative bias on progressive dilution is indicative of a sBC-dependent bias. RESULTS: The automated FT4 assay investigated (Vitros FT4) showed no demonstrable sBC-dependent bias by either test. CONCLUSION: These two tests can be used to screen for sBC-dependent biases in FT4 assays.

Bias↗

The epidemiology of burns in secondary care, in a population of 2.6 million people.

The numbers of residents of the four counties in the west of Anglia and Oxford Region (UK) who were treated for burns (including scalds) in accident and emergency (A&E) departments or admitted to hospital in 1994-95 were obtained from A&E departments and district health authority records. Burns comprised about 1 per cent of the workload in the A&E departments. Using the data from district health authorities, the rate of admission with a main diagnosis of burns to any hospital was 0.14 per thousand population per year. Children under five had the highest rate of admission. Approximately half the patients admitted to hospital with burns were admitted to burns units, a quarter to plastic surgery wards and the rest to different specialties including trauma and orthopaedics, paediatrics, and ophthalmology. The median length of stay was 6 days for burns units and 3 days for plastic surgery units.

Adolescent↗

The implementation of evidence-based medicine in general practice prescribing.

BACKGROUND: Research on the implementation of evidence-based medicine has focused on how best to influence doctors through information and education strategies. In order to understand the barriers and facilitators to implementation, it may also be important to study the characteristics of those doctors and practices that successfully implement evidence-based changes. AIM: To determine the relationship between practice and doctor characteristics and the implementation of recommended evidence-based changes in the area of prescribing. METHOD: Visits were made to 39 practices in southern England. Audits of three key prescribing changes were carried out and amalgamated to produce an 'implementation score' for each practice. These scores were related to a wide range of practice and doctor variables obtained from a questionnaire survey of doctors and practice managers. RESULTS: There was wide variation between the practices' implementation scores (mean 67%, range 45% to 88%). The only factors that had a significant relationship with implementation of these important prescribing changes were an innovative approach among the doctors (most practitioners were cautious of change), and fundholding status. Use of clinical protocols, disease registers, or computers was not associated with overall implementation score, nor was the doctor's age. Doctors complained of information overload. CONCLUSIONS: The emphasis on the need for evidence in medicine, and better transmission of information, needs to be balanced by a recognition that most general practitioners are pragmatic, averse to innovation, and already feel overwhelmed with information. Important advances in therapy may be crowded out. More attention should be given to the facilitation of priority changes in practices.

England↗

Inherited somatic mosaicism caused by an intracisternal A particle insertion in the mouse tyrosinase gene.

A recessive, fully penetrant mutation (c(m1OR)) at the mouse albino locus that results in coat-color mottling has been characterized at the molecular level. Restriction mapping and DNA sequencing analyses provide evidence that mutants carry a 5.4-kb intracisternal A particle (IAP) element insertion upstream of the tyrosinase (Tyr) promoter. Northern blot analysis and reverse transcription-PCR results show that the tyrosinase gene is expressed at much lower levels in mutant than in wild-type mice. The mutant Tyr gene still retains the tissue-specific expression pattern, and the Tyr transcript is not initiated from the IAP long terminal repeat promoter. We propose that the IAP insertion isolates the promoter of the tyrosinase gene from upstream cis-acting regulatory elements, leading to a substantially decreased level of Tyr gene expression in mutants.

Animals↗