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Biomedical subjects

P Wilson

Publications and source records attributed to P Wilson.

At least 19 recordsLinked to original sources

Computer technology and the childhood immunization programme: an investigation of low uptake rates in Coventry Primary Care Trust.

BACKGROUND: The childhood vaccination programme in Coventry Primary Care Trust (PCT) has resulted in consistently low uptake rates for a number of years. After an evaluation of operational processes, an examination of the data systems was performed. METHODS: The under-reporting of vaccinations performed and methodology issues were investigated using data collected by the Child Health Information Department (CHID) and the Finance Department. RESULTS: Data held by the Finance Department result in an uptake rate of between 0.79 and 1.92% higher than those held by the CHID. Locally, the Southwest Child Health (SWIFT) system, the programme used to calculate uptake rates by many of the PCTs across the country, excludes those children residing outside the boundary but registered within it. Coventry PCT's Cover of Vaccination Evaluated Rapidly (COVER) statistics are based on a subgroup of the responsible population. CONCLUSIONS: The computer technology currently utilized by the NHS provides inaccurate statistics for the COVER programme. Systematic under-reporting to the CHID results in moderately lowered uptake rates. A programming anomaly in the SWIFT system has resulted in the collection of data based on a subgroup of the responsible population. This undermines the validity of the statistics collected and renders comparability of data between different PCTs, particularly those using different systems, difficult.

Ambulatory Care Information Systems↗

Building an anonymized catalogued radiology museum in PACS: a feasibility study.

The aim of this study was to test the feasibility of a software application that would allow the anonymization and cataloguing of whole DICOM datasets in order to build searchable radiology museums within PACS. The application was developed on a dedicated networked PC, using C# and HL7 coding. Whole DICOM datasets were pushed from PACS to a networked PC on which the application, Museum Builder, was developed. Museum Builder works by replacing the patient specific data (the forename, surname and hospital number) within each header of each DICOM file with terms from anatomical and surgical sieve menus. The date of birth is anonymized to 1 January of the same year. Whole DICOM datasets comprising hundreds of images can be anonymized and catalogued in a single episode. Museum Builder primes PACS with an HL7 script to receive a "new" patient. DICOM datasets are then pushed back to PACS where they are added to the database as "new" cases. The museum cases can then be searched for, on PACS, by any combination of terms that correspond to appropriate anatomical units, surgical sieve headings or radiological specialty. New radiology reports containing clinical histories, radiological descriptions, differential diagnoses and discussion can be added through the report window. Our institution has developed and used this tool to generate a PACS based radiology museum containing not only full DICOM datasets, but also relevant histological and clinical photographs. In conclusion, this technique offers a mechanism for generating anonymized catalogued radiology museums in PACS. Museum Builder represents a working prototype that demonstrates some of the archiving functions that are expected by teaching institutions from PACS.

Cataloging↗

Unusual middle-ear mischief: trans-tympanic trauma from a hair grip resulting in ossicular, facial nerve and oval window disruption.

A case of piercing of the tympanic membrane, resulting in unusual consequences, is described. This is the first reported case of the long process of a dislocated incus resulting in trauma to the horizontal portion of a dehiscent facial nerve. Simultaneous depression of the stapes footplate resulted in a perilymph leak, but with delayed presentation.

Accidents, Home↗

Endotoxin immunity and the development of the systemic inflammatory response syndrome in critically ill children.

BACKGROUND: The systemic inflammatory response syndrome (SIRS) may be triggered by endotoxin. Humans have antibodies directed against the core of endotoxin (endotoxin core antibodies, EndoCAb) that appear to be protective following surgery and in sepsis. We hypothesised that children with elevated antibodies to endotoxin core would be less likely to develop SIRS in their initial period on intensive care. Because of the existing literature we defined two sub-groups according to the primary reason for ICU admission: infection and non-infection. METHODS: We recruited 139 consecutive patients admitted to a paediatric intensive care unit (PICU) with more than one organ failure for longer than 12 h as part of another study. Patients were classified on admission to PICU as having an infectious or a non-infections diagnosis. The occurrence of SIRS within 48 h of admission was recorded along with detailed clinical and demographic data, EndoCAb concentration and the potential confounding variables C-reactive protein and mannose-binding lectin. RESULTS: In the 71 patients admitted without infection (primarily post-operative and head injured) IgG EndoCAb was significantly lower in patients who developed SIRS than those who did not (72 vs. 131 MU/ml), independent of potential confounding variables. In patients with infection there was no significant difference in IgG EndoCAb between children developing SIRS and those who did not (111 vs. 80 MU/ml). CONCLUSION: Head injured and post-operative patients admitted to PICU who develop early SIRS have significantly lower serum IgG EndoCAb levels than those who do not.

Adolescent↗

Door-opening motion can potentially lead to a transient breakdown in negative-pressure isolation conditions: the importance of vorticity and buoyancy airflows.

A patient with severe chickenpox was admitted to a negative-pressure isolation room. He remained sedated, intubated and mechanically ventilated throughout his admission. He was managed only by nurses immune to chickenpox. A non-immune male nurse occasionally handed equipment through the doorway, without entering the room. Ten days later, he also developed chickenpox. Sequencing of viruses from the patient and nurse showed the same rare genotype, indicating nosocomial transmission. An experimental model demonstrated that, despite negative pressure, opening the door could have resulted in transport of infectious air out of the isolation room, leading to a breakdown in isolation conditions.

Air Pressure↗

Detection of TP53 mutation using a portable surface plasmon resonance DNA-based biosensor.

A DNA-based surface plasmon resonance (SPR) biosensor has been developed for the detection of TP53 mutation using the inexpensive and commercially available instrument, SPREETA SPR-EVM-BT, from Texas Instruments. A direct immobilisation procedure, based on the coupling of thiol-derivatised oligonucleotide probes (Probe-C6-SH) to bare gold sensor surfaces, was optimized using synthetic oligonucleotides. Hybridisation reactions between the immobilised probe and a short sequence (26 mer) complementary, non-complementary and one-point mutation DNA were then investigated. The main analytical parameters of the sensor system were studied in detail including selectivity, sensitivity, reproducibility and analysis time. Finally, the sensor system was successfully applied to polymerase chain reaction (PCR)-amplified real samples, DNA extracted from both normal, wild-type, (Jurkat) and mutated (Molt 4), carrying the mutation at codon 248 of the TP53 cell lines. The results obtained demonstrate that the DNA-based SPR biosensor was able to distinguish sequences present in the various samples that differ only by one base; and hence, it appears to be a strong candidate technique for the detection of gene mutation.

Biosensing Techniques↗

Chlorambucil and lomustine (CL56) in absolute hormone refractory prostate cancer: re-induction of endocrine sensitivity an unexpected finding.

The management of androgen independent prostate cancer is increasingly disputed. Diethylstilbestrol and steroids have useful second-line activity in its management. The value of chemotherapy still remains contentious. This paper reports a phase 2 study of two orally active chemotherapy drugs in patients who are absolutely hormone refractory having failed primary androgen blockade and combined oestrogens and corticosteroids. In total, 37 patients who were biochemically castrate with absolute hormone refractory prostate cancer and performance status of 0-3 were enrolled. Therapy consisted of chlorambucil 1 mg kg(-1) given as 6 mg a day until the total dose was reached and lomustine 2 mg kg(-1) given every 56 days (CL56). During this time all hormone therapy was stopped. One patient normalised his PSA with a further two having a greater than 50% decline leading to an objective response rate of 10%. The median time to progression was 3.6 months with an overall survival of 7.1 months. The median survival of this group of patients from first becoming androgen independent was 23.5 months. Eight of 17 (47%) patients who were subsequently re-challenged with hormonal therapy following failure of chemotherapy had a further PSA reduction, three (17%) of which were >50%. The median progression-free interval for the eight patients was 4 months. In conclusion, CL56 has a low objective response rate in the management of absolute hormone refractory prostate cancer. Toxicity was mild. Re-induction of hormone sensitivity following failure of chemotherapy was an unexpected finding that requires further study.

Aged↗

Down syndrome with pure partial trisomy 21q22 due to a paternal insertion (4;21) uncovered by uncultured amniotic fluid interphase FISH.

OBJECTIVE: To emphasize the usefulness and reliability of fluorescence in situ hybridization (FISH) on uncultured amniotic fluid cells in the prenatal diagnosis of common chromosomal aneuploidies. METHODS: FISH analyses utilizing centromeric, locus-specific or whole chromosome paint DNA probes specific for chromosomes X, Y, 13, 18, 21, and 4 were performed on uncultured amniotic fluid cells or the peripheral blood specimen from the father. Routine chromosome analysis was carried out as well. RESULTS: A prenatal case with partial trisomy 21 due to a paternal cryptic insertion (4;21) was ascertained by a rapid overnight FISH on uncultured amniotic fluid cells. The fetus was delivered at term and had classical features of Down syndrome. CONCLUSION: Our results stress the importance of FISH on uncultured amniotic fluid cells to supplement routine cytogenetics, especially in cases with abnormal ultrasound findings.

Adult↗

Benefits and harms of direct to consumer advertising: a systematic review.

BACKGROUND: Direct to consumer advertising is increasingly used by the pharmaceutical industry, but its benefits and harms have yet to be summarised in a comprehensive and rigorous manner. METHODS: A systematic review was conducted of robust evaluations of the impact (positive and negative) of direct to consumer advertising. A broad range of databases and data sources (including Cinahl, Embase, HMIC, HSRProj, Medline, PsycInfo, and the internet) were searched from inception to 2004. RESULTS: From 2853 citations only four reports were found that met the strict inclusion criteria and provided usable results. Direct to consumer advertising is associated with increased prescription of advertised products and there is substantial impact on patients' request for specific drugs and physicians' confidence in prescribing. No additional benefits in terms of health outcomes were demonstrated. DISCUSSION: Direct to consumer advertising is banned in most countries, and the research evidence tends to support the negative impact that is feared by those who support a legislative ban. Further research is needed into the clinical and economic impact of direct to consumer advertising in healthcare systems.

Advertising↗

Defining poor ovarian response during IVF cycles, in women aged <40 years, and its relationship with treatment outcome.

BACKGROUND: Poor ovarian response limits IVF success but assessing interventions is difficult because of the wide variation in definition. This study attempts to derive objective definitions of poor response. METHODS: A retrospective study of a consecutive series of 1190 patients aged <40 years undergoing their first IVF/ICSI cycle was undertaken. Factors adversely affecting implantation, including advanced female age, were excluded. Clinical outcome in cycles reaching oocyte retrieval (n = 1036) were evaluated with respect to gonadotrophin dose used and oocyte number. Cancelled cycles (n = 154) were analysed in relation to the stimulation dose at cancellation and outcome of their subsequent cycle. RESULTS: Cycle cancellation for patients on >/=300 IU FSH/day compared to those on a lower dose was associated with a significantly worse outcome in the subsequent cycle. If <3000 IU FSH/cycle were administered, clinical pregnancy rates remained favourable if <4 eggs were recovered (29 versus 33% for >/=5 eggs). By contrast, if >/=3000 IU FSH was required, the pregnancy rate was 25% if >/=5 eggs were recovered but declined to 7% if <4 were obtained. CONCLUSIONS: Definitions of poor response should include the degree of ovarian stimulation used. A low oocyte number is only detrimental if the cumulative dose is >3000 IU FSH. Cancellation at >/=300 IU FSH/day is associated with a significantly worse prognosis and could define poor response.

Adult↗

Solitary infantile myofibroma compromising the airway.

Infantile myofibromatosis is an uncommon and benign condition presenting in the neonatal period. It is self-limiting disease that may present as a localised or generalised process. Various examples of this entity have been reported in the literature. This report describes a neonate with a rapidly growing oropharyngeal lesion obstructing the airway that had the typical histological features of an infantile myofibroma. This case report highlights that a solitary myofibroma may be incredibly extensive making complete excision impossible and can be particularly challenging to manage in terms of airway stabilisation.

Airway Obstruction↗

Antibacterial activity of a new, stable, aqueous extract of allicin against methicillin-resistant Staphylococcus aureus.

The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals and the community has led to a demand for new agents that could be used to decrease the spread of these bacteria. Topical agents such as mupirocin have been used to reduce nasal carriage and spread and to treat skin infections; however, resistance to mupirocin in MRSAs is increasing. Allicin is the main antibacterial agent isolated from garlic, but natural extracts can be unstable. In this study, a new, stable, aqueous extract of allicin (extracted from garlic) is tested on 30 clinical isolates of MRSA that show a range of susceptibilities to mupirocin. Strains were tested using agar diffusion tests, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Diffusion tests showed that allicin liquids produced zone diameters >33 mm when the proposed therapeutic concentration of 500 microg/mL (0.0005% w/v) was used. The selection of this concentration was based on evidence from the MIC, MBC and agar diffusion tests in this study. Of the strains tested, 88% had MICs for allicin liquids of 16 microg/mL, and all strains were inhibited at 32 microg/mL. Furthermore, 88% of clinical isolates had MBCs of 128 microg/mL, and all were killed at 256 microg/mL. Of these strains, 82% showed intermediate or full resistance to mupirocin; however, this study showed that a concentration of 500 microg/mL in an aqueous cream base was required to produce an activity equivalent to 256 microg/mL allicin liquid.

Anti-Bacterial Agents↗

Analysis of full-length HIV type 1 env genes indicates differences between the virus infecting T cells and dendritic cells in peripheral blood of infected patients.

Dendritic cells (DC) are targets for HIV-1 infection and may harbor distinct populations of virus variants. To test this hypothesis full length env genes have been amplified and sequenced from DC and T cells purified from the blood of five symptomatic HIV-1-infected patients. For three of the patients, showing slow and slow/standard disease progression, distinct subsets of HIV variants infected DC and T cells, and the diversity of the DC-derived env genes was less than that observed in T cells. Amino acid substitutions differentiating DC and T cell variants were dispersed throughout the length of the glycoproteins and were patient/HIV-1 strain specific. However, the V1 and V2 domains of T cell-derived clones were generally shorter than those from DC. These findings suggest that there may be distinct populations of HIV-1 variants infecting blood DC and T cells in patients showing slow and slow/standard disease progression.

Adult↗

'Anti-bee' and 'pro-bird' changes during the evolution of hummingbird pollination in Penstemon flowers.

Floral phenotypes may be as much the result of selection for avoidance of some animal visitors as selection for improving the interaction with better pollinators. When specializing on hummingbird-pollination, Penstemon flowers may have evolved to improve the morphological fit between bird and flower, or to exclude less-efficient bees, or both. We hypothesized how such selection might work on four floral characters that affect the mechanics of pollen transfer: anther/stigma exsertion, presence of a lower corolla lip, width of the corolla tube, and angle of flower inclination. We surgically modified bee-pollinated P. strictus flowers changing one trait at a time to make them resemble hummingbird-pollinated P. barbatus flowers, and measured pollen transfer by bumblebees and hummingbirds. Results suggest that, apart from 'pro-bird' adaptations, specific 'anti-bee' adaptations have been important in shaping hummingbird-flowers. Moreover, some trait changes may have been selected for only if changing in concert with other traits.

Adaptation, Biological↗

Long-term outcomes in patients with prostate cancer managed with intermittent androgen suppression.

OBJECTIVES: To assess the long-term outcomes of patients with prostate cancer managed with intermittent androgen suppression (IAS) following their enrollment in an open, non-randomised feasibility study initiated 10 years ago. PATIENTS AND METHODS: Patients with prostate cancer who developed marked side effects following androgen deprivation were considered for entry into the study. All patients were required to have been managed with androgen deprivation for a minimum of 9 months and to have achieved PSA remissions to levels <4 ng/ml or falls to greater than 90% of pre-treatment levels. Patients remained off treatment until PSA values rose to >20 ng/ml or individuals became symptomatic--at which stage a 9-month cycle of androgen suppression was repeated. Such on-off cycling continued until hormone-resistant disease developed and patients proceeded (off trial) to second-line therapies. RESULTS: 75 patients were recruited to the study following an initial referral with treatment-related side effects specifically associated with androgen deprivation. 86% of these remain alive at a median of 134 months (11 years) since initial histological diagnosis. Survival times and times to hormone resistance (from first cycle hormone deprivation) have also been calculated. Overall there is a median survival time of 95 months (8 years) from initial (first-cycle) androgen deprivation in those presenting with localised or locally advanced disease and a median survival time of 87 months (7 years) for those presenting with metastatic disease. There exists a median of 83 months to hormone resistance in the localised and locally advanced group and a median of 50 months in those presenting with metastatic disease. We have calculated a 100% 5-year actuarial survival rate for those presenting with localised or locally advanced disease (from time of first cycle hormone ablation) and a 70% 5-year actuarial survival rate for those presenting with metastatic. CONCLUSIONS: Long-term outcome figures and actuarial survival rates presented here provide further support for a pulsed or intermittent approach to androgen ablation in patients with prostate cancer. In addition, they serve as valuable extended outcome data for patients managed in this way. Likewise, data presented here suggests that apparent survival advantages appear related, at least in part, to a delay in the onset of androgen resistance and that such a management approach is both safe and effective in those presenting with both metastatic disease as well as those with more localised pathology.

Androgen Antagonists↗