Heating and humidifying carbon dioxide is indicated.
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Carbon Dioxide↗
Biomedical subjects
E Wilson
Publications and source records attributed to E Wilson.
Definition of novel GP6 polymorphisms and major difference in haplotype frequencies between populations by a combination of in-depth exon resequencing and genotyping with tag single nucleotide polymorphisms.
BACKGROUND: Common genetic variants of cell surface receptors contribute to differences in functional responses and disease susceptibility. We have previously shown that single nucleotide polymorphisms (SNPs) in platelet glycoprotein VI (GP6) determine the extent of response to agonist. In addition, SNPs in the GP6 gene have been proposed as risk factors for coronary artery disease. METHODS: To completely characterize genetic variation in the GP6 gene we generated a high-resolution SNP map by sequencing the promoter, exons and consensus splice sequences in 94 non-related Caucasoids. In addition, we sequenced DNA encoding the ligand-binding domains of GP6 from non-human primates to determine the level of evolutionary conservation. RESULTS: Eighteen SNPs were identified, six of which encoded amino acid substitutions in the mature form of the protein. The single non-synonymous SNP identified in the exons encoding the ligand-binding domains, encoding for a 103Leu > Val substitution, resulted in reduced ligand binding. Two common protein isoforms were confirmed in Caucasoid with frequencies of 0.82 and 0.15. Variation at the GP6 locus was characterized further by determining SNP frequency in over 2000 individuals from different ethnic backgrounds. CONCLUSIONS: The SNPs were polymorphic in all populations studied although significant differences in allele frequencies were observed. Twelve additional GP6 protein isoforms were identified from the genotyping results and, despite extensive variation in GP6, the sequence of the ligand-binding domains is conserved. Sequences from non-human primates confirmed this observation. These data provide valuable information for the optimal selection of genetic variants for use in future association studies.
Amino Acid Sequence↗
Two cases of retroperitoneal haematoma caused by interaction between antibiotics and warfarin.
Several commonly prescribed antibiotics are known to interact with warfarin, increasing its anticoagulant effect by different mechanisms. Retroperitoneal bleeding with consequent haematoma is recognised as a complication of over-anticoagulation. Consequences, which are potentially fatal, include hypovolaemic shock and compression of retroperitoneal structures such as the ureter and inferior vena cava.
Aged↗
[Penetrating wound of the abdomen. Profile of the suffering patient at Dakar teaching hospital].
INTRODUCTION: In Senegal, the rate of penetrating wound of the abdomen seems to be in great progression. The purpose of this study was to make a descriptive analysis of the epidemiological data on the patient suffering from a penetrating wound of the abdomen. MATERIAL AND METHOD: It is about a retrospective study performed on a 5 years period from January 1997 to January 2002. This study covered 90 cases of penetrating wounds of the abdomen listed at the emergency department of Dakar teaching hospital. The rate, age, sex, responsible agent, circumstances of the wound, place of the injury, evacuation mode, time of admission and check-up injury were studied. RESULTS: The average absolute rate of the penetrating wounds of the abdomen was 18 cases per year. The average age was about 27 +/- 10 years with 88 men for 2 women. The responsible agent was a knife (87%), a firearm (6%), a broken glass (4%), a bullock horn (2%) and a piece of iron (1%). Circumstances of the injury was aggression (91%), accident (6%), self-mutilation (2%), suicide attempt (1%). Evacuation was done by firemen (60%), by the ambulances of the medical structures (22%), and by private individuals (18%). The average time of admission was 5 hours. Nearly 61% of the wounds were located in the umbilical, epigastric, left hypochondre and left side areas. Wound was single in 93,4% of cases and linear in 71,8% of cases. We noted an exit of epiploon (38 cases), peritoneal signs (13 cases) and a small bowel evisceration (9 cases). The treatment was a systematic laparotomy (68%) and a simple closure of the wound with a good follow-up for any further aggravation (32%). CONCLUSION: The patient admitted at the surgical emergency unit of Dakar teaching hospital for penetrating wound of the abdomen is generally a young man, victim of aggression by knife, evacuated by firemen within 5 hours, which present a single and linearwound in perish-umbilical area with exit of epiploon and/or small bowel evisceration, which would undertaken a surgical operation in 68% of cases.
Abdominal Injuries↗
A randomised controlled trial of nurse-managed trial conclusion following early phase cancer trial participation.
The effect of a nurse-managed intervention, for early phase cancer trial participants at trial conclusion, on psychosocial outcomes was evaluated at two cancer centres in the Midlands, England using a randomised controlled trial. It involved 117 patients who were participating in an early phase cancer clinical trial. It was a nurse-managed trial exit, which included a trial exit interview, trial feedback information leaflet and telephone follow-up compared with standard care at trial conclusion. Psychological distress at 1 week and 4-6 weeks post-trial conclusion, patient's knowledge and understanding and patient's satisfaction were assessed. The results showed there was no significant difference between the two groups regarding scores for anxiety and depression at time one and time two. There is some suggestion that the intervention reduced anxiety from trial conclusion to follow-up (P=0.27). Patients in both groups felt they had contributed to cancer research through trial participation. However, intervention patients were more likely to feel that they knew how the trial was going (P<0.001), knew how other people in the trial were doing (P=0.001), had all the feedback they needed about the trial they took part in (P<0.01) and knew how they would be followed up (P=0.02). Patient satisfaction with the intervention was high (median score=4.5 where 5 is greatest satisfaction). In conclusion, nurse-managed trial conclusion led to positive outcomes for patients who had recently completed a clinical trial.
Antineoplastic Agents↗
Novel genomic targets in oxidant-induced vascular injury.
To study the complex interaction between oxidative injury and the pathogenesis of vascular disease, vascular gene expression was examined in male Sprague-Dawley rats given 35 or 70 mg/kg allylamine, a synthetic amine converted to acrolein and hydrogen peroxide within the vascular wall. Vascular lesions and extensive vascular remodeling, coupled to increased production of 8-epi-PGF2alpha, nuclear localization of NFkappaB, and alterations in glutathione homeostasis, were observed in animals treated with allylamine for up to 20 days. Transcriptional profiling, immunohistochemistry, and in situ hybridization showed that genes involved in adhesion and extracellular matrix (ECM) (alpha(1) integrin, collagen), cytoskeletal rearrangements (alpha-smooth muscle actin, alpha-tropomyosin), and signal transduction (NFkappaB, osteopontin, and LINE) were altered by oxidant treatment. To evaluate mechanisms of gene dysregulation, cultured aortic smooth muscle cells were challenged with allylamine or its metabolites and processed for molecular analysis. These agents increased formation of reactive oxygen species and elicited changes in gene expression similar to those observed in vivo. Oxidative stress and changes in gene expression were inhibited by N-acetyl cysteine, a precursor of glutathione. These results indicate that genes along the ECM-integrin-cytoskeletal axis, in addition to LINE, are molecular targets in oxidant-induced vascular injury.
Acetylcysteine↗
An evaluation of the introduction of Clinical Trial Officer roles into the cancer clinical trial setting in the UK.
The National Cancer Research Network (NCRN) was created in 2001 to improve the infrastructure for cancer research within the National Health Service (NHS) in the UK and ensure that research is better integrated with cancer care. The NCRN consists of 34 regional networks which map onto the 34 cancer networks that were established following the publication of the NHS Cancer Plan with its aim of improving the coordination and delivery of cancer care and treatment nationally. An objective of the NCRN is to increase recruitment into cancer trials through improved support. One cancer research network responded by introducing Clinical Trial Officers (CTOs) into the cancer clinical trial setting in order to combine the range of tasks required to support clinical trials into a single role with the ultimate aim of increasing recruitment into cancer clinical trials. Evaluation during the first 14 months of their introduction assessed the impact of the new CTO role on cancer trial recruitment, its acceptability to those involved in trials and its effectiveness in achieving increased recruitment. Evaluation identified appropriate induction and training programmes required to support these new roles and the identification of a model for the introduction of CTO posts in other networks across the country. The findings presented in this paper identify that CTO roles can effectively be introduced into a cancer network and have an impact on recruitment to clinical trials within that network. The data collected provided an in-depth insight into how these roles were perceived, have developed and what supporting structures need to be in place to enable them to flourish. Recruitment in the network has increased and there has been a raising of awareness of clinical trials and cancer research across the whole of the cancer network where the CTOs were based. We conclude that CTO roles can offer a creative alternative to staffing cancer clinical trial units and that such a model could be introduced across other networks. Similar models could also be introduced into other disease settings where clinical research is taking place.
Administrative Personnel↗
Discordant PKU phenotype in one family due to disparate genotypes and a novel mutation.
Classical phenylketonuria (PKU) and mild hyperphenylalaninaemia (MHP) are two ends of the broad diagnostic spectrum in phenylalanine hydroxylase (PAH) deficiency. We have analysed a family in which classical PKU, MHP and a normal phenotype occurred in family members with different mutations. Sequence analysis revealed three mutations segregating in the family. The individual with classical PKU had two previously reported deleterious mutations. A third novel mutation was identified in the other two individuals. This report demonstrates that when discordant phenotypes occur in a family, without protein loading or phenylalanine tolerance test, complete analysis of the PAH gene may be performed in order to support the diagnosis and assist in accurate genetic counselling and patient management.
Alleles↗
Ultrasound guided 'low approach' femoral vein cannulation.
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Catheterization, Central Venous↗
A multiaxial computer-controlled organ culture and biomechanical device for mouse carotid arteries.
Much of our understanding of vascular mechanotransduction has come from studies using either cell culture or in vivo animal models, but the recent success of organ culture systems offers an exciting alternative. In studying cell-mediated vascular adaptations to altered loading, organ culture allows one to impose well-controlled mechanical loads and to perform multiaxial mechanical tests on the same vessel throughout the culture period, and thereby to observe cell-mediated vascular adaptations independent of neural and hormonal effects. Here, we present a computer-controlled perfused organ culture and biomechanical testing device designed for small caliber (50-5000 micron) blood vessels. This device can control precisely the pulsatile pressure, luminal flow, and axial load (or stretch) and perform intermittent biaxial (pressure-diameter and axial load-length) and functional tests to quantify adaptations in mechanical behavior and cellular function, respectively. Device capabilities are demonstrated by culturing mouse carotid arteries for 4 days.
Animals↗
Outcome of three consecutive inadequate cervical smears.
A retrospective audit of women with three consecutive inadequate cervical smears during 1998-99 was conducted at Birmingham Heartlands Hospital. The commonest reasons were obscured by polymorphs (34.5%) and sparse cellularity (28.9%). Seventy-three per cent (73%) were followed up at colposcopy and 22.1% had histological assessment; 15.9% of women had an abnormality detected, 10.6% with abnormal histology and 5.3% with a cytological abnormality only. Cytological abnormalities were seen in 11.1% of the screening population. This study did not identify a cytological criterion to differentiate those that would or would not have an abnormality on follow-up. It is suggested that all women with three consecutive inadequate smears should have adequate follow-up, although this may place increased demands on colposcopy services.
Cervix Uteri↗
An assessment of care of paediatric and adolescent patients with diabetes in a large district general hospital.
AIMS: To assess the process of clinical care and outcomes of young patients with diabetes attending clinics at a large district general hospital. METHODS: Retrospective analysis of data obtained from 106 case notes of patients aged 12-22 years attending the paediatric, combined adolescent or adult diabetes clinics between 1998 and 2000. The frequency of follow-up, rate of admission, glycaemic control, systolic blood pressure, weight change and screening for complications were assessed. RESULTS: The mean attendance rate was 78%. The admission rate was 91 admissions per 1000 patient years. Overall, the mean HbA1c was 9.1% with only 15% of paediatric and adolescent patients having mean HbA1c<or= 8.0%. Mean systolic blood pressure was 124 mmHg. There was a significant increase in obesity with mean weight for height at diagnosis increasing from 89% to 111% after 7 years of diabetes. Mean daily insulin dose was 1.51 U per kg body weight and decreased with increasing age. Screening for complications and associated conditions was variable: 91% for retinopathy, 86% for foot problems, 64% for thyroid dysfunction, 22% for coeliac disease and 10% for microalbuminuria. The overall rate of retinopathy was low at 4% of those screened. CONCLUSIONS: Providing satisfactory care for young people with diabetes remains a difficult challenge. Although the complication rate observed was low in this group, the most important issues are the need for improvement in glycaemic control, weight gain and high drop-out rate.
Adolescent↗
Development and characterization of endothelial cells from rat microlymphatics.
BACKGROUND: The lymphatic endothelium is important to the functioning of the lymphatic system, including lymphatic remodeling, control of vessel tone, and lymphatic movement of fluids, macromolecules, and cells. Many of these events occur principally at the level of the microlymphatics. To evaluate the role of the microlymphatic endothelium, a suitable cultured cell line would be useful. We have developed a technique to isolate and culture endothelial cells from microscopic lymphatics, approximately 100 microm in diameter. METHODS AND RESULTS: To isolate the rat mesenteric lymphatic endothelial cells (RMLEC), the rat was anesthetized and the mesentery carefully exteriorized. A suitable microlymphatic was located and carefully microdissected from the surrounding mesentery. The vessel was carefully cleaned, cannulated, everted, and then incubated on a gelatin-coated plastic culture dish until small patches of cells migrated off of the vessel (3-4 days later.) The explanted vessel was then removed. The remaining cells were cultured and screened for endothelial phenotype. Nonendothelial cells were destroyed. The endothelial nature of the remaining cells was verified by: 1) morphology, 2) uptake of fluorescent acetylated-LDL, 3) staining for von Wille-brand factor, PECAM-1, ecNOS, LYVE-1, VEGFR-3, and 4) essentially negative alpha-vascular smooth muscle actin staining. The defined RMLEC were passed and the profile of adhesion molecules present on the RMLEC was then determined using PCR and immunofluorescence. CONCLUSIONS: We developed and partially characterized a line of cultured microlymphatic endothelium. RMLEC express known endothelial- and lymphatic-specific markers as well as the following adhesion molecules: N-cadherin, E-cadherin, PECAM-1, alpha-catenin, beta-catenin, gamma-catenin, p120, and a variety of integrins.
Actins↗
A comparison of travel related ID admissions in Glasgow: (1985; 1998/99).
A comparative study was made of patients admitted over 12 months to the principal infectious diseases unit for Glasgow in 1985 and in 1998/99. During this interval UK travel statistics show a 135% growth in visits abroad and a 5% rise to 17% in destinations with a risk of malaria. Travel associated admissions rose by 96% to a total of 108. Patients of Asian/Oriental ethnicity declined from 55% to 18%, whilst Caucasians increased from 38% to 81%. Travellers aged 20-39 years formed the modal age groups (51% and 50%). Gastro-intestinal problems accounted for the largest single diagnostic category in both study periods, 38% and 40% respectively. In-patients diagnosed with malaria fell by 20%; these figures are cause for encouragement to those involved in the teaching and dissemination of advice on malaria prophylaxis. The findings re-enforce the need for the continuation and expansion of travel health education for both healthcare professionals and the public.
Adolescent↗
Poly-L-glutamate, an anionic polymer, enhances transgene expression for plasmids delivered by intramuscular injection with in vivo electroporation.
Intramuscular (i.m.) injection of plasmids followed by electropermeabilization is an efficient process to deliver genes into skeletal myofibers that permits proteins to be produced and secreted at therapeutically relevant levels. To further improve skeletal muscle as a bioreactor, we identified a formulation that elevates transgene expression in myofibers after i.m. injection and electroporation. With secreted placental alkaline phosphate (SEAP) as reporter gene, plasmid formulated with poly-L-glutamate produced two- to eight-fold higher levels of SEAP in mouse serum than plasmid in saline. Various concentrations and molecular weights of poly-L-glutamate were similarly effective, but 6 mg/ml of 15-50 kDa poly-L-glutamate consistently yielded the highest expression levels. The poly-L-glutamate formulation was effective in two different muscle groups in mice at various plasmid doses for several transgenes, including an erythropoietin (EPO) gene, for which expression was elevated four- to 12-fold in comparison to animals that received EPO plasmid in saline. Transgene expression was localized to myofibers. Poly-L-glutamate may improve transgene expression in part by increasing plasmid retention in skeletal muscle. Poly-L-glutamate did not enhance gene transfer in the absence of electroporation. Therefore, the polymer is a novel formulation that specifically enhances the transfer and expression of genes delivered with electroporation.
Alkaline Phosphatase↗
Radiological stenting provides effective palliation in malignant central venous obstruction.
Malignant superior vena caval obstruction (SVCO) due to lung cancer carries a poor prognosis and response to palliative radiotherapy is variable. Eighteen patients presenting with the appearance of malignant SVCO (thirteen due to primary bronchial tumours) in a four year period from June 1995 to July 1999 underwent venography with a view to placement of an expanding metal stent under radiological control. Fourteen patients were male and four female with a mean age at presentation of 65 years (range 44-84 years). At venography only three patients had isolated SVC stenosis, fivealso had brachiocephalic, internal jugular or subclavian vein stenoses and one had an isolated right brachiocephalic stenosis. Venography demonstrated thrombus in eight of the remaining patients, seven in association with stenosis. In one patient stenosis of the SVC was thought to be due to radiation fibrosis as no mass was visible. All underwent Seldinger catheterization of the great veins via a right femoral puncture with deployment of the stent over a guide wire. Balloon angioplasty was performed prior to stent placement in eight patients. The eight patients with thrombus underwent thrombolysis using rt-PA (recombinant tissue-type plasminogen activator) with subsequent stent placement in seven. Radiological relief of obstruction with abolition of collateral flow was observed in all cases. One patient required further stenting for recurrent obstruction after 160 days of palliation. The median duration of palliation after stenting was 87 days. No procedure-related morbidity was observed. Thrombolysis was of value in patients with occlusive thrombus, either in isolation or complicating a malignant stricture, where radiotherapy may not have been effective. Radiological stenting is a safe technique which offers rapid palliation of SVCO.
Adult↗
Dose-escalation with CHARTWEL (continuous hyperfractionated accelerated radiotherapy week-end less) combined with neo-adjuvant chemotherapy in the treatment of locally advanced non-small cell lung cancer.
PURPOSE: a radiation-dose-escalation study was undertaken to assess the therapeutic benefit of combining accelerated hyperfractionated radiotherapy (RT) with neo-adjuvant chemotherapy (CT) in non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: One hundred and thirteen patients with locally advanced NSCLC were entered into a phase II trial of CHARTWEL (CHART Week-End-Less) 54 Gy or 60 Gy with or without three cycles of CT. Acute oesophageal reactions and analgesia were scored for up to 8 weeks after the start of RT. Pneumonitis, lung fibrosis, spinal cord and oesophageal strictures, were assessed using clinical and radiological criteria from 3 months onwards and throughout the study. Haematological and gastrointestinal toxicity was monitored in those patients undergoing CT. Endpoints for treatment outcome were overall survival, disease-free survival and loco-regional control. RESULTS: Chemotherapy enhanced the incidence and duration of acute dysphagia,but the increase was transient. Healing occurred in all cases and there has been no evidence of long-term oesophageal complications. Clinically, almost 25% of those receiving CT+RT had Grade 2 pneumonitis, higher than seen with RT alone. However, the 1 patient with severe Grade 3 pneumonitis was in the RT 60 Gy alone group. An incidence of 17% Grade 2 pulmonary fibrosis at 2 years was seen with CT, slightly lower than with RT alone. To date, there is no evidence of Grade 3 lung fibrosis. There was a higher scoring of lung damage with the radiological endpoint, which gave no indication that CT increased pulmonary toxicity over that of RT alone. Loco-regional control at 2 years was 37% and 55% for CHARTWEL 54 Gy and 60 Gy alone compared with 72% in those treated with 60 Gy and neo-adjuvant CT However, this did not translate into a survival advantage. CONCLUSIONS: This study of CHARTWEL combined with induction chemotherapy, has shown that the strategy is feasible and that a possible therapeutic benefit may be obtained by the addition of CT. Although neo-adjuvant treatment increased acute mucosal reactions and slight-to-moderate pneumonitis seen with CHARTWEL 60 Gy, the clinical management and quality of life of these patients is similar to those treated with radiotherapy alone.
Adult↗
The use of a standard proforma in breast cancer reporting.
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Breast Neoplasms↗