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Biomedical subjects

L Wilson

Publications and source records attributed to L Wilson.

At least 19 recordsLinked to original sources
PubMed2006

Do circulating leucocytes and lymphocyte subtypes increase in response to brief exercise in children with and without asthma?

BACKGROUND: Exercise can alter health in children in both beneficial (eg reduced long-term risk of atherosclerosis) and adverse (eg exercise-induced asthma) ways. The mechanisms linking exercise and health are not known, but may rest, partly, on the ability of exercise to increase circulating immune cells. Little is known about the effect of brief exercise, more reflective of naturally occurring patterns of physical activity in children, on immune cell responses. OBJECTIVES: To determine whether (1) a 6-min bout of exercise can increase circulating inflammatory cells in healthy children and (2) the effect of brief exercise is greater in children with a history of asthma. METHODS: Children with mild-moderate persistent asthma and age-matched controls (n = 14 in each group, mean age 13.6 years) performed a 6-min bout of cycle-ergometer exercise. Spirometry was performed at baseline and after exercise. Blood was drawn before and after exercise, leucocytes were quantified and key lymphocyte cell surface markers were assessed by flow cytometry. RESULTS: Exercise decreased spirometry only in children with asthma, but increased (p<0.001) most types of leucocytes (eg lymphocytes (controls, mean (SD) 1210 (208) cells/microl; children with asthma, 1119 (147) cells/microl) and eosinophils (controls, 104 (22) cells/microl; children with asthma, 88 (20) cells/microl)) to the same degree in both groups. Similarly, exercise increased T helper cells (controls, 248 (60) cells/microl; children with asthma, 232 (53) cells/microl) and most other lymphocyte subtypes tested. By contrast, although basophils (16 (5) cells/microl) and CD4+ CD45RO+ RA+ lymphocytes (19 (4) cells/microl) increased in controls, no increase in these cell types was found in children with asthma. CONCLUSIONS: Exercise increased many circulating inflammatory cells in both children with asthma and controls. Circulating inflammatory cells did increase in children with asthma, but not to a greater degree than in controls. In fact, basophils and T helper lymphocyte memory transition cells did not increase in children with asthma, whereas they did increase in controls. Even brief exercise in children and adolescents robustly mobilizes circulating immune cells.

Adolescent↗
PubMed2006

Renal colic during sexual intercourse: a unique presentation.

The average lifetime risk of renal stones has been reported to be in the range of 5-21%, and the majority of patients have recurrent stones (Tiselius et al. in Eur Urol 40:362-371, 2001). The peak incidence is between the fourth and fifth decades, and therefore generally active and working adults are most affected. Stones are usually formed in a calyx, and become symptomatic if they move to obstruct the upper urinary tract. In the majority of cases, there is no specific action which causes stone movement from a non-obstructing to an obstructing position. We present the first ever case report in the literature of an episode of renal colic during sexual intercourse. The role of percussion therapy and postural drainage are well established following shockwave lithotripsy (SWL) to enhance passage of lower pole stone fragments (Brownlee et al. in J Urol 143:1096, 1990), and it may well be the result of similar principles of motion and body positioning which caused the patient to present in this manner.

Adult↗
PubMed2006

Rapid development of polyclonal antisera against infectious salmon anaemia virus and its optimization and application as a diagnostic tool.

Infectious salmon anaemia is an important disease of Atlantic salmon. One of the current methods of diagnosis is the indirect fluorescent antibody test (IFAT), using a monoclonal antibody specific to the haemagglutinin of the virus. The conformationally dependent nature of this antibody could be a drawback in its usefulness in other tests. This study describes the development and optimization of a polyclonal antiserum against infectious salmon anaemia virus, including a method of separating virus from cell culture components within culture supernatant. The antiserum was subsequently optimized for use in a variety of immunological diagnostic tests, including IFAT and an alkaline phosphatase-based immunoassay, and Western blot.

Alkaline Phosphatase↗
PubMed2005

Assisted reproductive therapies and imprinting disorders--a preliminary British survey.

BACKGROUND: Recent reports have suggested a higher risk of Beckwith-Wiedemann syndrome (BWS) and Angelman syndrome (AS) after assisted reproductive technologies (ARTs), but it is unclear whether this might also apply to other disorders of genomic imprinting. METHODS: We contacted families of children with BWS, AS, Prader-Willi syndrome (PWS) and transient neonatal diabetes mellitus (TNDM) to determine use of ART. RESULTS: A statistically significant increased frequency of ART in children with BWS was confirmed [2.9%, 95% confidence interval (CI) 1.4-6.3% vs 0.8% expected] but there was no significant association with PWS or TNDM. Consideration of the molecular subgroup of BWS and AS suggested the feasibility of association with ART. CONCLUSIONS: These differences may relate to variations in (i) the molecular mechanisms for disordered imprinting in the different disorders and (ii) the susceptibility of specific imprinting control regions to ART-associated methylation alterations (epimutations).

Angelman Syndrome↗
PubMed2005

Analysis of clinical decision-making in multi-disciplinary cancer teams.

Management decisions for patients with cancer are frequently taken within the context of a multi-disciplinary team (MDT). There is little known, however, about decision-making at team meetings and whether MDT decisions are all implemented. This study evaluated team decision-making in upper gastrointestinal cancer. Consecutive MDT treatment decisions were recorded for patients with oesophageal, gastric, pancreatic and peri-ampullary tumours. Implementation of MDT decisions was investigated by examining hospital records. Where decisions were implemented it was recorded as concordant and discordant if the decision changed. Reasons for changes in MDT decisions were identified. 273 decisions were studied and 41 (15.1%) were discordant (not implemented), (95% confidence interval 11.1-20.0%). Looking at the reasons for discordance, 18 (43.9%) were due to co-morbid health issues, 14 (34.2%) related to patient choice and 8 (19.5%) decisions changed when more clinical information was available. For one discordant decision, the reason was not apparent. Discordant decisions were more frequent for patients with pancreatic or gastric carcinoma as compared to oesophageal cancer (P = 0.001). Results show that monitoring concordance between MDT decisions and final treatment implementation is useful to inform team decision-making. For upper gastrointestinal cancer, MDTs require more information about co morbid disease and patient choice to truly optimize the implementation of multi-disciplinary expertise.

Adult↗
PubMed2005

CYP2E1 inhibition enhances mallory body formation.

Mallory body (MB) formation is a complex phenomenon seen in chronic liver disease. CYP2E1 may play a role in preventing MB formation since it is involved in the elimination of toxic drugs and chemicals. When mice were fed with diethyl-1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate (DDC) for 10 weeks, Mallory bodies (MBs) developed in the liver at the end of this period. When DDC feeding was combined with CMZ (an efficient in vivo CYP2E1 inhibitor), more MBs formed compared to DDC feeding alone. DDC was shown to be a suicide inhibitor of CYP2E1. The level of CYP2E1 protein in the liver was further reduced by the DDC and CMZ treatment when measured by Western blot. To test whether CYP2E1 reduced MB formation, CYP2E1 knockout mice and CYP2E1 overexpressed mice were fed with DDC or DDC and CMZ for 10 weeks. MB formation increased markedly in the liver of CYP2E1 knockout mice when fed with DDC only. CYP2E1 overexpressed mice showed an increase in MB formation when the mice were fed with the combination of DDC and CMZ where the amount of CYP2E1 was reduced to levels seen in wild type mice. It was concluded that CYP2E1 inhibits MB formation by increasing the rate of elimination of DDC and/or its toxic intermediates.

Animals↗
PubMed2005

Is antibiotic prophylaxis required for flexible cystoscopy? A truncated randomized double-blind controlled trial.

PURPOSE: To examine the incidence of urinary tract infection (UTI) after flexible cystoscopy (FC) and determine whether prophylactic norfloxacin reduces this incidence compared with placebo. PATIENTS AND METHODS: A double-blind trial was performed, randomizing 234 patients to either 400 mg of norfloxacin or placebo prior to FC. All patients provided a midstream urine specimen (MSU) before the procedure, as well as at day 3 and day 7 after FC. In addition, a telephone questionnaire was performed to correlate the nature and severity of any symptoms associated with UTI. RESULTS: Interim analysis was performed because of the low recruitment rate, and a significantly lower infection rate than expected meant that the trial was discontinued. There was one symptomatic UTI in the placebo group (0.82%) and one in the norfloxacin group (0.89%). The UTI in the placebo group was de novo, while the infection in the norfloxacin group was secondary to pre-FC bacteriuria. There was no difference in the infection rates in the two groups. The overall infection rate (de novo and secondary to existing bacteruria) after FC was 0.85%. CONCLUSION: Infection after flexible cystoscopy is rare and not associated with significant morbidity. A much larger study would be required to determine whether antibiotic prophylaxis significantly reduces the rate of postprocedure UTI.

Anti-Infective Agents↗
PubMed2005

Health-related quality of life after retroperitoneoscopic and hand-assisted laparoscopic nephrectomy.

BACKGROUND AND PURPOSE: The assessment of postoperative recovery typically involves the use of measures that are open to bias. Whilst there has been some work done on the short-term postoperative recovery comparison for hand-assisted laparoscopic nephrectomy (HALN) and retroperitoneoscopic nephrectomy (RPN), to our knowledge, this is the first study to look at long-term health outcomes for these two procedures. This study sought objectively to compare long-term postoperative health-related quality of life (HRQoL) after retroperitoneoscopic and hand-assisted transperitoneal laparoscopic nephrectomy undertaken for renal pathology. This was achieved by both reviewing perioperative data from medical records and by using the SF-36 questionnaire postoperatively. PATIENTS AND METHODS: Patients who had undergone elective retroperitoneoscopic (N = 19) or transperitoneal HALN (N = 32) between 2001 and 2004 at our institution underwent objective HRQoL assessment via a validated telephone questionnaire (SF-36) and by review of postoperative data from the medical records. This survey was administered between 3 and 6 months after surgery. The data then underwent statistical analysis using the paired Student's t-test. RESULTS: Perioperative data showed no significant difference in the postoperative complication rate in the two groups. The HRQoL scores gathered from the SF-36 questionnaire gave mean scores of 67.4 and 68.5 for the HALN and RPN groups, respectively (100 represents maximum quality of life). This difference was not statistically significant. CONCLUSIONS: This is the first study to look at long-term (mean follow-up 6 months) health outcomes for patients undergoing RPN and HALN. The results show no greater long-term health benefit for one procedure over the other. This finding supports the data in the literature on the benefits of HALN over RPN in terms of a less protracted learning curve, greater technical ease, fewer intraoperative complications, and consequently reduced operating times with no loss of the long-term health benefit that is traditionally associated with the standard laparoscopic technique.

Female↗
PubMed2005

Transpiration-assisted perfusion fixation provides in situ preservation of developing ray parenchyma cells in Eucalyptus nitens.

The technique of animal vascular perfusion fixation was adapted for in situ fixation of the fragile and difficult to access cells of the ray parenchyma system in stems of 10-year-old Eucalyptus nitens trees. In situ fixation enabled tissue to be safely dissected for histological processing without risk of damage to microstructure or initiation of wound response. Fixative was perfused through the active vascular system under hydrostatic and transpiration pressure directly to vessel-associated ray cells. Diffusion from vessels allowed fixative to access nonvessel-associated ray cells. Acrolein was included to aid diffusion fixation and safranin dye was included to define fixed regions within the xylem. Sections prepared for light and electron microscopy from samples cut from regions showing intense safranin staining showed good microstructural preservation and were free of artefacts caused by mechanical injury or wound response.

Eucalyptus↗
PubMed2005

Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome.

BACKGROUND: Sotos syndrome is characterised by learning difficulties, overgrowth, and a typical facial appearance. Microdeletions at 5q35.3, encompassing NSD1, are responsible for approximately 10% of non-Japanese cases of Sotos. In contrast, a recurrent approximately 2 Mb microdeletion has been reported as responsible for approximately 50% of Japanese cases of Sotos. METHODS: We screened 471 cases for NSD1 mutations and deletions and identified 23 with 5q35 microdeletions. We investigated the deletion size, parent of origin, and mechanism of generation in these and a further 10 cases identified from published reports. We used "in silico" analyses to investigate whether repetitive elements that could generate microdeletions flank NSD1. RESULTS: Three repetitive elements flanking NSD1, designated REPcen, REPmid, and REPtel, were identified. Up to 18 cases may have the same sized deletion, but at least eight unique deletion sizes were identified, ranging from 0.4 to 5 Mb. In most instances, the microdeletion arose through interchromosomal rearrangements of the paternally inherited chromosome. CONCLUSIONS: Frequency, size, and mechanism of generation of 5q35 microdeletions differ between Japanese and non-Japanese cases of Sotos. Our microdeletions were identified from a large case series with a broad range of phenotypes, suggesting that sample selection variability is unlikely as a sole explanation for these differences and that variation in genomic architecture might be a contributory factor. Non-allelic homologous recombination between REPcen and REPtel may have generated up to 18 microdeletion cases in our series. However, at least 15 cannot be mediated by these repeats, including at least seven deletions of different sizes, implicating multiple mechanisms in the generation of 5q35 microdeletions.

Abnormalities, Multiple↗
PubMed2005

Assessment in vitro of a novel therapeutic strategy for glioma, combining herpes simplex virus HSV1716-mediated oncolysis with gene transfer and targeted radiotherapy.

Genetically engineered herpes simplex virus ICP34.5 null mutants replicate only in dividing cells and have shown potential for the treatment of malignant disease, including glioma. Phase I trials have demonstrated the safety of these viruses in various clinical settings but it is envisaged that for full efficacy they will be used in combination with other therapeutic modalities. To enhance virus-induced tumour cytotoxicity, we have engineered an ICP34.5 null mutant (HSV1716) of HSV1 which expresses the noradrenaline transporter gene (NAT). This virus is designated HSV1716/NAT. We have shown previously that introduction of the NAT gene into a range of tumour cells, via plasmid-mediated transfection, conferred the capacity for active uptake of the radiopharmaceutical [131I]MIBG and resulted in dose-dependent toxicity. In this study, combination therapy utilising HSV1716/NAT and [131I]MIBG was assessed in vitro by the MTT assay. We demonstrate that the NAT gene, introduced by HSV1716/NAT into cultured glioma cells, was expressed 1 h after viral infection, enabling active uptake of [131I]MIBG. The combination of viral oncolysis and induced radiopharmaceutical uptake resulted in significantly enhanced cytotoxicity compared to either agent alone and the response was dose- and time-dependent. These studies show that the combination of oncolytic HSV therapy with targeted radiotherapy has the potential for effective tumour cell kill and warrants further investigation as a treatment for malignant glioma.

3-Iodobenzylguanidine↗
PubMed2004

Cation-selective ion channels formed by p7 of hepatitis C virus are blocked by hexamethylene amiloride.

A 63 residue peptide, p7, encoded by hepatitis C virus was synthesised and tested for ion channel activity in lipid bilayer membranes. Ion channels formed by p7 had a variable conductance: some channels had conductances as low as 14 pS. The reversal potential of currents flowing through the channels formed by p7 showed that they were permeable to potassium and sodium ions and less permeable to calcium ions. Addition of Ca(2+) to solutions made channels formed by p7 less potassium- or sodium-selective. Hexamethylene amiloride, a drug previously shown to block ion channels formed by Vpu encoded by HIV-1, blocked channels formed by p7. In view of the increasing number of peptides encoded by viruses that have been shown to form ion channels, it is suggested that ion channels may play an important role in the life cycle of many viruses and that drugs that block these channels may prove to be useful antiviral agents.

Amiloride↗
PubMed2004

Should cryopreserved epididymal or testicular sperm be recovered from obstructive azoospermic men for ICSI?

OBJECTIVE: To determine the effect of the anatomical site of sperm recovery on intracytoplasmic sperm injection (ICSI) embryo implantation, pregnancy and live birth rates in couples with isolated obstructive azoospermia as the sole cause of infertility. DESIGN: Controlled, single centre, retrospective clinical study. SETTING: University Hospital, Centre for Reproductive Medicine. SAMPLE: One hundred and fifty-one cycles of ICSI were performed, using surgically recovered sperm, between August 1996 and March 2002. METHODS: The outcome of ICSI, with surgically recovered sperm, was compared between epididymal (Group E) and testicular (Group T) derived sperm. Inclusion was limited to couples undergoing their first treatment cycle, where female age was < or =39 years and a minimum of five oocytes were available for injection. Women with a history of ovarian surgery, ultrasonic evidence of polycystic ovaries, uterine anomalies or hydrosalpinx were excluded. MAIN OUTCOME MEASURES: Clinical pregnancy, implantation and live birth rate. RESULTS: Forty-two of 151 cycles met the strict inclusion criteria. Groups E and T were comparable with respect to age, basal serum FSH, ovarian response; number of oocytes injected and number of embryos available and transferred. No difference existed between Groups E and T in implantation, clinical pregnancy or live birth rate (28.8% vs 25.8%, 42.9% vs 42.9% and 39.3% vs 42.9%, respectively). CONCLUSIONS: Cryopreserved epididymal and testicular sperm, from men with obstructive azoospermia, appear equally effective in ICSI. Epididymal recovery should remain the method of first choice for obstructive azoospermic men but further study of sperm DNA damage rates in different testicular sites is required.

Adult↗
PubMed2004

New microtubule/tubulin-targeted anticancer drugs and novel chemotherapeutic strategies.

The clinical success of the taxanes and the vinca alkaloids has sparked a major search for new drugs that perturb mitotic spindle microtubule dynamics and function, yielding a large number of promising compounds. A potential valuable strategy would be to use core microtubule-targeted drugs along with novel targeted drug therapies as they are developed, where the antitumor activity of a targeted drug can be combined with the power of low dose microtubule-targeted therapy. The goal of such combination therapy is to achieve high efficacy, reduced toxicity, and reduced emergence of drug resistance.

Antineoplastic Agents, Phytogenic↗
PubMed2003

Head injuries: a prospective observational study evaluating the potential impact of the Galasko report on Accident and Emergency departments.

In June 1999, the Galasko report of the Royal College of Surgeons of England recommended that in the next 5 years, the Accident and Emergency (A&E) departments should admit and supervise head-injured patients for up to 48 h. A prospective observational study was carried out for a 6 weeks period at the A&E department of Birmingham Heartland's Hospital to identify the potential impact of implementation of the Galasko report. The cost implications of this perceived additional workload were considered.Of the 786 head-injured patients seen during study period, 665 (85%) were discharged home directly from the A&E department. Of the remaining 121 patients, who were hospitalized, 76 (63%) were admitted to the A&E observation ward (AEOW) and 19 (16%) patients were admitted to a paediatric ward. All of these patients were discharged home within 24 h. The remaining 21% patients were admitted to other specialities and had prolonged stays in hospital. All of the 9% of the patients admitted under orthopaedics would have been admitted to the AEOW if the Galasko recommendations were implemented leading to an extra 22 bed days over the 6 weeks study period. The estimated annual cost of admission alone for these patients would be pound 38,200. Our study has demonstrated an expected additional workload and cost implications on a single A&E department.

Craniocerebral Trauma↗