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Biomedical subjects

S Murray

Publications and source records attributed to S Murray.

At least 19 recordsLinked to original sources
PubMed2006

Mutations of the epidermal growth factor receptor tyrosine kinase domain and associations with clinicopathological features in non-small cell lung cancer patients.

Somatic tyrosine kinase (TK) domain mutations of the epidermal growth factor receptor (EGFR) gene are associated with sensitivity of non-small cell lung cancer (NSCLC) to tyrosine kinase inhibitors (TKI's), however their incidence in distinct populations is not clarified. We sequenced exons 18-21 of the EGFR TK domain from 60 Greek and Czech patients, enrolled in an adjuvant chemotherapy trial following total resection for stages I-IIIa disease. Somatic mutations were found in 9/60 patients (15.0%), several being novel. EGFR mutations were more common in Stage I tumors (p = 0.023), they were also more common in women and never smokers; however, no other significant association of clinicopathological features with mutations was found. Median TTP and OS of patients with and without mutations were 13.2 and 40 months compared to 22.9 and 43.2 months, respectively. These differences were not statistically significant. K-ras (5/60, 8%) and EGFR mutations were found to be mutually exclusive. We identified a wide spectrum of somatic EGFR TK mutations reporting a relatively high incidence (15%) in NSCLC patients of Greek and Czech origin. As ethnicity seems to be a factor for the origin of these mutations, further studies in distinct populations are warranted.

Adult↗
PubMed2006

Element levels in snakes in South Carolina: differences between a control site and exposed site on the Savannah River site.

Levels of 18 elements, including lead, mercury, selenium, and uranium, were examined in three species of snakes from an exposed and reference site on the Department of Energy's Savannah River Site in South Carolina. We tested the hypotheses that there were no differences as a function of species, and there were no difference between the exposed and control site for blood and muscle (tail) samples for banded water snake (Nerodia fasciata), brown water snake (N. taxispilota) and cotton mouth (Akistrodon piscivorous). The banded water snakes collected were significantly smaller than the other two species. For blood, there were significant species differences only for barium, copper, selenium, uranium and zinc, while for muscle tissue there were significant interspecific differences in aluminum, arsenic, barium, cobalt, cesium, copper, iron, lead, mercury, manganese, strontium, vanadium and zinc, suggesting that muscle tissue in the tail is a better indicator of potential interspecific differences. It is also easier logistically to collect tail tissue than blood. Where one species had significantly higher levels than the other species in muscle tissue levels, cottonmouth had higher levels of five elements (aluminum, cobalt, lead, mercury, vanadium), brown water snake had two (lead, strontium), and banded water snake had only barium. There were few significant differences between the control and reference site for levels of blood, but several for muscle tissue. All three species had significantly higher levels of arsenic and manganese at Tim's Branch than the reference site, and nickel and uranium were significantly higher for banded water snake and cotton mouth, the larger species. Individuals with high exposure of one element were exposed to high levels of other elements.

Animals↗
PubMed2006

Development of the new lung allocation system in the United States.

This article reviews the development of the new U.S. lung allocation system that took effect in spring 2005. In 1998, the Health Resources and Services Administration of the U.S. Department of Health and Human Services published the Organ Procurement and Transplantation Network (OPTN) Final Rule. Under the rule, which became effective in 2000, the OPTN had to demonstrate that existing allocation policies met certain conditions or change the policies to meet a range of criteria, including broader geographic sharing of organs, reducing the use of waiting time as an allocation criterion and creating equitable organ allocation systems using objective medical criteria and medical urgency to allocate donor organs for transplant. This mandate resulted in reviews of all organ allocation policies, and led to the creation of the Lung Allocation Subcommittee of the OPTN Thoracic Organ Transplantation Committee. This paper reviews the deliberations of the Subcommittee in identifying priorities for a new lung allocation system, the analyses undertaken by the OPTN and the Scientific Registry for Transplant Recipients and the evolution of a new lung allocation system that ranks candidates for lungs based on a Lung Allocation Score, incorporating waiting list and posttransplant survival probabilities.

Adolescent↗
PubMed2005

A two-compound product containing calcipotriol and betamethasone dipropionate provides rapid, effective treatment of psoriasis vulgaris regardless of baseline disease severity.

BACKGROUND: A two-compound product containing calcipotriol and betamethasone dipropionate (Daivobet/Dovobet) has been evaluated in a large clinical trial programme, providing a wealth of data on the treatment of psoriasis vulgaris. OBJECTIVE: To determine the effectiveness of the two-compound product in patients with mild, moderate and severe psoriasis vulgaris. METHODS: Data from over 1,534 patients with psoriasis vulgaris who received the two-compound product once daily for at least 4 weeks in four randomised, double-blind studies were pooled. A meta-analysis of the pooled data is presented. Severity of psoriasis at baseline was determined by investigator assessment and Psoriasis Area and Severity Index (PASI) score. RESULTS: For patients with severe disease defined by PASI score (PASI baseline > or = 17), the mean reduction in PASI after up to 4 weeks of treatment was 71.6% compared with 68.9 and 67.2% for those with moderate (PASI baseline 5.1-16.0) and mild disease (PASI baseline < or = 5). Corresponding reductions for investigator-assessed severity were 72.6, 69.1 and 68.7%, respectively. CONCLUSION: Although the meta-analysis of the data from these four studies was performed post hoc, we may conclude that the two-compound product provided highly effective treatment of psoriasis, regardless of the category of baseline disease severity.

Administration, Topical↗
PubMed2005

Co-culture of Trypanosoma musculi with spleen-derived adherent fibroblasts: possible transfer of small molecules via connexons.

Trypanosoma musculi, a protozoan parasite specific to mouse, was cultured in vitro in the presence of spleen-derived adherent cells. T. musculi co-cultured with adherent cells survived and proliferated indefinitely as long as cellular contact was retained. Scanning and transmission electron microscopy confirmed intimate membrane-to-membrane contact between the adherent cells and parasites. Cellular contact, therefore, seemed to be essential for trypanosomal survival and growth. Immunocytochemical studies demonstrated intense fibroblast growth factor (FGF) activity in adherent cells, and FGFR-2 in associated trypanosomes. BioPorter Lucifer yellow protein delivery reagent studies demonstrated that Lucifer yellow transfected into fibroblast was incorporated into associated trypanosomes. The results suggest the existence of viable channels reminiscent of gap junctions between associated cells. Such transfer of low molecular weight molecules might represent antiapoptotic metabolic factors that support survival of adherent trypanosomes in vitro. Immunocytochemical studies also detected connexin-32 and connexin-43 in the cytoplasm of fibroblasts and associated trypanosomes, however, restriction of connexons to trypanosome/fibroblast adherent sites was not observed. Western blots confirmed the presence of connexin protein molecules in trypanosomes.

Animals↗
PubMed2004

A randomized comparison of alternative methods of information provision on the acceptability of elective single embryo transfer.

BACKGROUND: The purpose of this study was to assess the effect of alternative ways of providing information about the risks of twins on couples' perceptions about elective single embryo transfer (eSET). METHODS: Couples undergoing IVF were randomized into three groups. Group 1 received a standard information pack, group 2 an extra information leaflet about twin pregnancy, and group 3 an additional discussion session. The primary outcome measure was acceptability of a hypothetical policy of eSET. Data were collected by means of a questionnaire. RESULTS: eSET was acceptable to 17 (27%), 20 (30%) and 24 (32%) couples in groups 1, 2 and 3, if it meant a slight reduction in pregnancy rates, and to 51 (82%), 55 (83%) and 53 (87%) couples, respectively, if pregnancy rates were unchanged. A fixed charge for all fresh and frozen embryo transfers following a single oocyte retrieval led to acceptability rates of 35 (57%), 36 (55%) and 38 (65%). CONCLUSIONS: Additional information, involving an extra information leaflet and face to face discussion, did not changes couples' attitudes towards eSET. Maintaining existing rates of pregnancy and offering a fixed charge for all embryo transfers resulting from an oocyte recovery may encourage more couples to consider eSET.

Embryo Transfer↗
PubMed2004

An investigation into the 'carry over' effect of neurostimulation in the treatment of angina pectoris.

Neurostimulation, by way of transcutaneous electrical nerve stimulation (TENS) and spinal cord stimulation, improves signs and symptoms of myocardial ischaemia, with evidence (from non-randomised studies) that this effect extends beyond the period of stimulation itself ('carry-over' effect). In this randomised controlled trial, 10 patients underwent baseline treadmill-exercise-testing (TET), followed by two further tests at fortnightly intervals. TENS was compared to placebo in a randomised fashion. TENS produced a significant increase in total exercise time (399.3 vs. 364.5 s, p < 0.05) and time to maximum ST depression (374 vs. 324 s, p = 0.01) without a significant difference in the maximum degree of ST depression (2.0 vs. 2.1 mm, p = NS). Rate-pressure product at peak exercise was not significantly different (197 vs. 193, p = NS). TENS produced a nonsignificant change in time to onset of angina (352 vs. 325 s, p = 0.07). Pre-treatment with TENS produces a significant improvement in exercise tolerance and measures of ischaemia but not significant improvement in symptoms.

Aged↗
PubMed2004

Epidemiology of multiple sclerosis in Glasgow.

STUDY OBJECTIVE: The objectives of the study were to establish the prevalence and incidence of multiple sclerosis in Glasgow and to assess the epidemiological importance of deprivation and ethnicity. DESIGN: The study was a descriptive cross-sectional study. Multiple sources of ascertainment were used to identify cases. SETTING AND PATIENTS: The study was carried out in the population of three Local Health Care Cooperatives (LHCCs) in the area of Greater Glasgow NHS Board. The total population was approximately 169,000. MAIN RESULTS: In total, 245 patients with multiple sclerosis were identified. The mean age of patients was 49.8 years, the female to male ratio was 3.2:1, and the mean duration of disease was 16 years. The overall prevalence was 14.5 per 10,000, and the overall incidence 5.7 per 100,000 per year. Both the prevalence and incidence of multiple sclerosis were higher in the more affluent population. The crude prevalence in the Asian population was 6.3 per 20,000. CONCLUSIONS: The epidemiology of multiple sclerosis in Glasgow was similar, in most respects, to the epidemiology described in other parts of the U.K. There was evidence for the importance of deprivation as a determinant of both incidence and prevalence of disease. The reasons for the higher incidence and prevalence of multiple sclerosis in less deprived populations are not clear.

Adolescent↗
PubMed2003

Novel antisense oligonucleotides targeting TGF-beta inhibit in vivo scarring and improve surgical outcome.

The scarring response is an important factor in many diseases throughout the body. In addition, it is a major problem in influencing results of surgery. In the eye, for example, post-operative scarring can determine the outcome of surgery. This is particularly the case in the blinding disease glaucoma, where several anti-scarring regimens are currently used to improve glaucoma surgery results, but are of limited use clinically because of severe complications. We have recently identified transforming growth factor-beta (TGF-beta) as a target for post-operative anti-scarring therapy in glaucoma, and now report the first study of novel second-generation antisense phosphorothioate oligonucleotides against TGF-beta in vivo. Single applications of a TGF-beta OGN at the time of surgery in two different animal models closely related to the surgical procedure performed in glaucoma patients, significantly reduced post-operative scarring (P<0.05) and improved surgical outcome. Our findings suggest that TGF-beta antisense oligonucleotides have potential as a new therapy for reducing post-surgical scarring. Its long-lasting effects after only a single administration at the time of surgery make it particularly attractive clinically. Furthermore, although we have shown this agent to be useful in the eye, it could have widespread applications anywhere in the body where the wound-healing response requires modulation.

Amino Acid Sequence↗
PubMed2003

A comparison of headnet electrode arrays for electrical impedance tomography of the human head.

Three types of commercially available headnet electrode arrays, designed for use in EEG, and conventional EEG Ag/AgCl cup electrodes were tested on human subjects, and a realistic, saline-filled head-shaped tank was prepared with vegetable skin to simulate human skin in order to determine the optimum electrode system for electrical impedance tomography (EIT) of the human head. Impedance changes during EIT acquisition were produced in healthy volunteers during a finger-thumb apposition task and in tanks by the insertion of a Perspex rod. Signal-to-baseline noise, measured from raw EIT data, was 2.3 +/- 0.3 and 2.3 +/- 0.2 for the human and tank data, respectively. In both the human and tank experiments, a commercial hydrogel elasticated electrode headnet produced the least amount of baseline noise, and was the only headnet in the human data with noise levels acceptable for EIT imaging. Image quality measured in the tank was similar for most of the headnets tested, except that the EEG electrodes produced a higher positional error and electrodes in a geodesic elasticated net produced images with worse subjective image quality. Overall, the hydrogel elasticated headnet was judged to be the most suitable for human neuroimaging with EIT.

Adult↗
PubMed2003

Radiological versus histological diagnosis in UIP and NSIP: survival implications.

BACKGROUND: High resolution computed tomography (HRCT) has an important diagnostic role in idiopathic interstitial pneumonia (IIP). We hypothesised that the HRCT appearance would have an impact on survival in patients with IIP. METHODS: HRCT scans from patients with histological usual interstitial pneumonia (UIP; n=73) or histological non-specific interstitial pneumonia (NSIP; n=23) were characterised as definite UIP, probable UIP, indeterminate, probable NSIP, or definite NSIP. Cox regression analysis examined the relationships between histopathological and radiological diagnoses and mortality, controlling for patient age, sex, and smoking status. RESULTS: All 27 patients with definite or probable UIP on HRCT had histological UIP; 18 of 44 patients with probable or definite NSIP on HRCT had histological NSIP. Patients with HRCT diagnosed definite or probable UIP had a shorter survival than those with indeterminate CT (hazards ratio (HR) 2.43, 95% CI 1.06 to 5.58; median survival 2.08 v 5.76 years) or HRCT diagnosed definite or probable NSIP (HR 3.47, 95% CI 1.58 to 7.63; median survival 2.08 v 5.81 years). Patients with histological UIP with no HRCT diagnosis of probable or definite UIP fared better than patients with histological UIP and an HRCT diagnosis of definite or probable UIP (HR 0.49, 95% CI 0.25 to 0.98; median survival 5.76 v 2.08 years) and worse than those with a histological diagnosis of NSIP (HR 5.42, 95% CI 1.25 to 23.5; median survival 5.76 v >9 years). CONCLUSIONS: Patients with a typical HRCT appearance of UIP experience the highest mortality. A surgical lung biopsy is indicated for patients without an HRCT appearance of UIP to differentiate between histological UIP and NSIP.

Algorithms↗
PubMed2002

Suspected pulmonary embolism in pregnancy: clinical presentation, results of lung scanning, and subsequent maternal and pediatric outcomes.

BACKGROUND: Ventilation-perfusion (VQ) scanning is used when pulmonary embolism (PE) is suspected during pregnancy; however, the distribution of lung scan results and safety of VQ scanning have never been studied. OBJECTIVE: To study the distribution of lung scan results and safety of VQ scanning as well as the safety of withholding anticoagulation therapy following a normal or nondiagnostic scan in pregnant women. METHODS: The study group comprised 120 consecutive pregnant women who presented with suspected PE. Clinical data were collected, and the lung scans were reinterpreted by 2 independent experts. Subsequent pregnancy and pediatric outcomes were determined by direct patient follow-up. RESULTS: During the study period, 120 pregnant women (mean age, 32 years) underwent 121 VQ scans. Eight cases (6.6%) were already receiving treatment for venous thromboembolism prior to VQ scanning. In the remaining 113 scans, 83 (73.5%) were interpreted as normal, 28 (24.8%) as nondiagnostic, and 2 (1.8%) as high probability. In the 104 women who did not receive anticoagulation therapy following lung scanning (80 normal and 24 nondiagnostic), no venous thromboembolic events were reported (mean [range] length of follow-up, 20.6 [0.5-108] months). Examination of pediatric data from 110 live births (90.2%) (mean [range] age, 20.5 [0.5-100] months) revealed no increase in the rates of congenital and developmental anomalies. CONCLUSIONS: The prevalence of high-probability VQ scans in pregnant women with suspected PE and probable PE is very low. Withholding anticoagulation in pregnant women with normal or nondiagnostic VQ scans is probably safe. In addition, pediatric risks from VQ scans are low. Large prospective studies are needed to evaluate diagnostic strategies for pregnant women with suspected PE.

Anticoagulants↗
PubMed2002

Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis.

The normal plasma protein serum amyloid P component (SAP) binds to fibrils in all types of amyloid deposits, and contributes to the pathogenesis of amyloidosis. In order to intervene in this process we have developed a drug, R-1-[6-[R-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid, that is a competitive inhibitor of SAP binding to amyloid fibrils. This palindromic compound also crosslinks and dimerizes SAP molecules, leading to their very rapid clearance by the liver, and thus produces a marked depletion of circulating human SAP. This mechanism of drug action potently removes SAP from human amyloid deposits in the tissues and may provide a new therapeutic approach to both systemic amyloidosis and diseases associated with local amyloid, including Alzheimer's disease and type 2 diabetes.

Amyloidosis↗
PubMed2002

Effect of in vivo administration of anti-CTLA-4 monoclonal antibody and IL-12 on the induction of low-dose oral tolerance.

Oral tolerance has been characterized as an immunological hyporesponsiveness to fed antigen. Previous studies have suggested that high-dose oral tolerance involves the preferential interaction of B7 with CTLA-4 on the T cell. To determine whether similar mechanisms are involved in the induction of low-dose oral tolerance, mice were treated with anti-CTLA-4 monoclonal antibody (MoAb), with or without IL-12, at the time of feeding. Results showed that anti-CTLA-4 MoAb alone failed to restore cellular proliferation, antibody titres and IFN-gamma levels; however, IL-4 cytokine levels in OVA-fed mice were partially restored. In contrast, administration of IL-12 along with anti-CTLA-4 MoAb to mice during feeding completely prevented the suppression of Th1 immune responses, as shown by increased serum IgG2a titres, IFN-gamma production and cell proliferation. These results suggest that blocking B7-CTLA-4 interactions in the presence of IL-12 prevents the induction of low-dose oral tolerance at the Th1 cell level.

Abatacept↗
PubMed2002

Changes in prevalence and treatment need for traumatic dental injuries among 14-year-old children in Newham, London: a deprived area.

OBJECTIVE: The study was carried out to assess the prevalence of traumatic injuries to the permanent incisors of 14-year-old schoolchildren in Newham in 1998-99, the treatment needed and to compare the results with data from 1995-96. Also, to test whether different levels of deprivation within an area would increase the risk of dental injury. BASIC RESEARCH DESIGN: A cross-sectional study was carried out. One dentist (SM) carried out all dental examinations. Upper and lower permanent incisors were examined for dental injuries. The examiner recorded the type of damage sustained, any treatment carried out and the treatment need. PARTICIPANTS: 411 14-year-old schoolchildren in Newham in 1998-99. Results The prevalence of traumatic injuries was 43.8% (95% CI 39.0, 48.7) in 1998-99, compared to 23.7% (95% CI 22.0, 25.5) in 1995-96. Boys sustained statistically significantly more dental injuries than girls, 50.2% and 37.1% respectively (P<0.01). In 1998-99 92.7 per thousand incisors were damaged, 6.7 per thousand incisors were treated and 28.9 per thousand incisors needed treatment. Two components of the Jarman Index were associated with dental injuries. Overcrowded household was statistically significantly related to dental injuries in both studies. Ethnicity was associated with dental injury in 1998-99, but not tested in 1995-96. CONCLUSIONS The prevalence of traumatic dental injury in Newham increased from 23.7% to 43.8% between 1995-96 and 1998-99, it was higher than the overall prevalence in the United Kingdom (17%) and its treatment had been neglected. Area-based measures of deprivation such as an overcrowded household and ethnicity were predictors of traumatic dental injuries.

Adolescent↗
PubMed2001

Development and application of a sensitive high performance ion-exchange chromatography method for the simultaneous measurement of dopamine, 5-hydroxytryptamine and norepinephrine in microdialysates from the rat brain.

A high performance liquid chromatography (HPLC) method based on cation exchange separation has been developed for the measurement of dopamine (DA), 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in microdialysates. The separation conditions have been optimised for using electrochemical detection. All three bioamines were resolved in less than 22 min using isocratic conditions. The optimum oxidation potential for the three bioamines was found to be +0.4 V vs. in situ Ag/AgCl reference electrode. Linear regression analysis of HPLC-peak area as a function of concentrations in the range 1-50 ng x ml(-1) gave coefficients of correlation between 0.998 and 0.999. The limit of detection for DA, 5-HT and NE was found to be between 50 and 100 pg x ml(-1) with a signal to noise ratio of 3:1. The method has been applied to the simultaneous measurement of the three monoamines in microdialysates from the medial prefrontal cortex under basal conditions and following the administration of the antipsychotic drug clozapine (10 mg x kg(-1) s.c.).

Animals↗