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G Coates

Publications and source records attributed to G Coates.

At least 19 recordsLinked to original sources
PubMed2006

Ensembl 2007.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of chordate genome sequences. Over the past year the number of genomes available from Ensembl has increased from 15 to 33, with the addition of sites for the mammalian genomes of elephant, rabbit, armadillo, tenrec, platypus, pig, cat, bush baby, common shrew, microbat and european hedgehog; the fish genomes of stickleback and medaka and the second example of the genomes of the sea squirt (Ciona savignyi) and the mosquito (Aedes aegypti). Some of the major features added during the year include the first complete gene sets for genomes with low-sequence coverage, the introduction of new strain variation data and the introduction of new orthology/paralog annotations based on gene trees.

Animals↗
PubMed2006

Ensembl 2006.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of large genome sequences. Over the last year the number of genomes available from the Ensembl site has increased from 4 to 19, with the addition of the mammalian genomes of Rhesus macaque and Opossum, the chordate genome of Ciona intestinalis and the import and integration of the yeast genome. The year has also seen extensive improvements to both data analysis and presentation, with the introduction of a redesigned website, the addition of RNA gene and regulatory annotation and substantial improvements to the integration of human genome variation data.

Animals↗
PubMed2005

Ensembl 2005.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of large genome sequences. Over the last year the number of genomes available from the Ensembl site has increased by 7 to 16, with the addition of the six vertebrate genomes of chimpanzee, dog, cow, chicken, tetraodon and frog and the insect genome of honeybee. The majority have been annotated automatically using the Ensembl gene build system, showing its flexibility to reliably annotate a wide variety of genomes. With the increased number of vertebrate genomes, the comparative analysis provided to users has been greatly improved, with new website interfaces allowing annotation of different genomes to be directly compared. The Ensembl software system is being increasingly widely reused in different projects showing the benefits of a completely open approach to software development and distribution.

Animals↗
PubMed2004

Ensembl 2004.

The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organize biology around the sequences of large genomes. It is a comprehensive and integrated source of annotation of large genome sequences, available via interactive website, web services or flat files. As well as being one of the leading sources of genome annotation, Ensembl is an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements. The facilities of the system range from sequence analysis to data storage and visualization and installations exist around the world both in companies and at academic sites. With a total of nine genome sequences available from Ensembl and more genomes to follow, recent developments have focused mainly on closer integration between genomes and external data.

Animals↗
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↗
PubMed2001

Selection of patients for resection of hepatic metastases: improved detection of extrahepatic disease with FDG pet.

A rapidly emerging clinical application of positron emission tomography (PET) is the detection of tumor tissue at whole-body studies performed with the glucose analogue 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG). High rates of recurrence after partial hepatic resection in patients with colorectal cancer liver metastases indicate that current presurgical imaging strategies are failing to show extrahepatic tumor deposits. Although FDG PET cannot match the anatomic resolution of conventional imaging techniques in the liver and the lungs, it is particularly useful for identification and characterization of extrahepatic disease. FDG PET can show foci of metastatic disease that may not be apparent at conventional anatomic imaging and can aid in the characterization of indeterminate soft-tissue masses. Several sources of benign and physiologic increased activity at FDG PET emphasize the need for careful correlation with findings of other imaging studies and clinical findings. FDG PET can improve the selection of patients for partial hepatic resection and thereby reduce the morbidity and mortality associated with inappropriate surgery.

Colorectal Neoplasms↗
PubMed2001

Visual and semiquantitative analysis of 18F-fluorodeoxyglucose positron emission tomography using a partial-ring tomograph without attenuation correction to differentiate benign and malignant pulmonary nodules.

OBJECTIVE: Many studies have reported the use of attenuation-corrected positron emission tomography with 18F-fluorodeoxyglucose (FDG PET) with full-ring tomographs to differentiate between benign and malignant pulmonary nodules. We sought to evaluate FDG PET using a partial-ring tomograph without attenuation correction. METHODS: A retrospective review of PET images from 77 patients (range 38-84 years of age) with proven benign or malignant pulmonary nodules was undertaken. All images were obtained using a Siemens/CTI ECAT ART tomograph, without attenuation correction, after 185 MBq 18F-FDG was injected. Images were visually graded on a 5-point scale from "definitely malignant" to "definitely benign," and lesion-to-background (LB) ratios were calculated using region of interest analysis. Visual and semiquantitative analyses were compared using receiver operating characteristic analysis. RESULTS: Twenty lesions were benign and 57 were malignant. The mean LB ratio for benign lesions was 1.5 (range 1.0-5.7) and for malignant lesions 5.7 (range 1.2-14.1) (p < 0.001). The area under the ROC curve for LB ratio analysis was 0.95, and for visual analysis 0.91 (p = 0.39). The optimal cut-off ratio with LB ratio analysis was 1.8, giving a sensitivity of 95% and a specificity of 85%. For lesions thought to be "definitely malignant" on visual analysis, the sensitivity was 93% and the specificity 85%. Three proven infective lesions were rated as malignant by both techniques (LB ratio 2.6-5.7). CONCLUSIONS: FDG PET without attenuation correction is accurate for differentiating between benign and malignant lung nodules. Results using simple LB ratios without attenuation correction compare favourably with the published sensitivity and specificity for standard uptake ratios. Visual analysis is equally accurate.

Adult↗
PubMed2000

The effects of beta(1)-blockade on oxidative metabolism and the metabolic cost of ventricular work in patients with left ventricular dysfunction: A double-blind, placebo-controlled, positron-emission tomography study.

BACKGROUND: The mechanism for the beneficial effect of beta-blocker therapy in patients with left ventricular (LV) dysfunction is unclear, but it may relate to an energy-sparing effect that results in improved cardiac efficiency. C-11 acetate kinetics, measured using positron-emission tomography (PET), are a proven noninvasive marker of oxidative metabolism and myocardial oxygen consumption (MVO(2)). This approach can be used to measure the work-metabolic index, which is a noninvasive estimate of cardiac efficiency. METHODS AND RESULTS: The aim of this study was to determine the effect of metoprolol on oxidative metabolism and the work-metabolic index in patients with LV dysfunction. Forty patients (29 with ischemic and 11 with nonischemic heart disease; LV ejection fraction <40%) were randomized to receive metoprolol or placebo in a treatment protocol of titration plus 3 months of stable therapy. Seven patients were not included in analysis because of withdrawal from the study, incomplete follow-up, or nonanalyzable PET data. The rate of oxidative metabolism (k) was measured using C-11-acetate PET, and stoke volume index (SVI) was measured using echocardiography. The work-metabolic index was calculated as follows: (systolic blood pressure x SVI x heart rate)/k. No significant change in oxidative metabolism occurred with placebo (k=0.061+/-0.022 to 0.054+/-0.012 per minute). Metoprolol reduced oxidative metabolism (k=0.062+/-0. 024 to 0.045+/-0.015 per minute; P:=0.002). The work-metabolic index did not change with placebo (from 5.29+/-2.46 x 10(6) to 5.14+/-2. 06 x 10(6) mm Hg. mL/m(2)), but it increased with metoprolol (from 5. 31+/-2.15 x 10(6) to 7.08+/-2.36 x 10(6) mm Hg. mL/m(2); P:<0.001). CONCLUSIONS: Selective beta-blocker therapy with metoprolol leads to a reduction in oxidative metabolism and an improvement in cardiac efficiency in patients with LV dysfunction. It is likely that this energy-sparing effect contributes to the clinical benefits observed with beta-blocker therapy in this patient population.

Acetates↗
PubMed2000

Standardization of a simplified scintigraphic methodology for the assessment of gastric emptying in a multicenter setting.

OBJECTIVE: Scintigraphy remains the gold standard to study gastric emptying. The technique is onerous and normal values vary between centers. Standardized protocols, although desirable, are not presently available. We validated a simplified scintigraphic protocol in a multicenter setting. METHODS: In 69 healthy volunteers from seven Canadian institutions, gastric emptying of a standard meal (99mTc-labeled beef liver) was assessed by scintigraphy every 10 min for 1 h, then every 20 min for the next 2 h. Gastric retention was fitted to a power exponential model, Prop(t) = (-(kappat)beta) with Prop(t) = proportion of retention at time t, either using all 13 time intervals (conventional technique) or using measurements at 0, 1, 2, and 3 h (simplified technique). RESULTS: The power exponential model yielded identical emptying curves and T 1/2 values with both techniques. Gastric emptying was more rapid in men than in women < 35 yr (p<0.01) and in younger than in older men (p<0.005). Gastric emptying was slower in women from Québec than in women from Ontario (p<0.04). Gastric retention was similar at 1, 2, and 3 h among the seven centers. Gastric emptying of a beef liver meal was slower than that of a low fat egg substitute (p<0.03). CONCLUSIONS: A simpler scintigraphic approach, using four rather than 13 samples, provides results comparable to those of the conventional technique. This simpler approach provides an economical, yet accurate, alternative to the techniques presently used and is applicable to a multicenter setting.

Adult↗
PubMed2000

FDG PET of recurrent or metastatic 131I-negative papillary thyroid carcinoma.

UNLABELLED: This study reports on the use of FDG PET in the follow-up of papillary thyroid cancer patients with negative findings on 131I total body scans and elevated levels of thyroglobulin after total thyroidectomy. METHODS: Eleven asymptomatic patients with previous papillary thyroid cancer, total thyroidectomy, 131I ablation, and treatment of all known metastases had negative findings on 131I total body scans after therapy but persisting elevations of thyroglobulin when not receiving thyroid hormone. All imaging before PET failed to show persisting tumor. FDG PET was performed on all patients while receiving full thyroid hormone replacement, except for the repeated scan of 1 patient (patient 6). After the PET scan, all patients were referred for supplementary CT, sonography, or biopsy of lesions in the neck. RESULTS: All 11 patients showed FDG uptake in the neck or upper mediastinum-in the initial scan in 10 and in a repeated scan in 1. Sonographically guided biopsy confirmed malignancy in 6, was nondiagnostic in 2, and showed normal findings in 1. In 2 patients, the sonographic results were normal and no biopsy was attempted. FDG imaging redirected the treatment of 7 patients, resulting in surgery and external beam radiotherapy in 3, surgery in 1, and external beam radiotherapy in 2. One patient declined further recommended surgery. The other 4 patients remain under observation. Surgical histopathology confirmed thyroid tumor in all 4 surgically treated patients. Retrospective review of the original histopathology slides showed no preponderance of aggressive histology. CONCLUSION: FDG PET is able to guide further evaluation of thyroid cancer patients who have elevated thyroglobulin levels and normal findings on 131I whole-body scanning.

Adult↗
PubMed1999

Vascular volumes and hematology in male and female runners and cyclists.

To examine the hypothesis that foot-strike hemolysis alters vascular volumes and selected hematological properties is trained athletes, we have measured total blood volume (TBV), red cell volume (RCV) and plasma volume (PV) in cyclists (n = 21) and runners (n = 17) and compared them to those of untrained controls (n = 20). TBV (ml x kg(-1)) was calculated as the sum of RCV (ml x kg(-1)) and PV (ml x kg(-1)) obtained using 51Cr and 125I-labelled albumin, respectively. Hematological assessment was carried out using a Coulter counter. Peak aerobic power (VO2peak) was measured during progressive exercise to fatigue using both cycle and treadmill ergometry. RCV was 15% higher (P < 0.05) in male cyclists [35.4 (1.0), mean (SE); n = 12] and runners [35.3 (0.98); n = 9] compared to the controls [30.7 (0.92); n = 12]. Similar differences existed between the female cyclists [28.2 (2.1); n = 9] and runners [28.4 (1.0); n = 8] compared to the untrained controls [24.9 (1.4); n = 8]. For the male athletes, PV was between 19% (cyclists) and 28% (runners) higher (P < 0.05) in the trained athletes compared to the untrained controls. The differences in PV between the female groups were not significant. Although the males had a higher (P < 0.05) TBV, RCV and PV than the females, no differences between cyclists and runners were found for either gender. Mean cell volume was not different between the athletic groups. VO2peak (ml x kg(-1) x min(-1)) was higher (P < 0.05) in both male [68.4 (1.5)] and female [54.8 (2.1)] runners when compared to the untrained males [47.1 (1.0)] and females [40.5 (2.1)]. Although differences existed between the genders in VO2peak for both cyclists and runners, no differences were found between the athletic groups within a gender. Since the vascular volumes were not different between cyclists and runners for either the males or females, foot-strike hemolysis would not appear to have an effect on that parameter. The significant correlations (P < 0.05) found between VO2peak and RCV (r = 0.64 and 0.64) and TBV (r = 0.82 and 0.63) for the males and females, respectively, suggests a role for the vascular system in realizing a high aerobic power.

Adult↗
PubMed1999

Recovery rates of regional sympathetic reinnervation and myocardial blood flow after acute myocardial infarction.

BACKGROUND: The implication of an arrhythmogenic role for infarction-induced disruption of regional myocardial sympathetic nerve activity has led to a search for noninvasive methods to study regional sympathetic nerve activity in patients after infarction. METHODS AND RESULTS: By using positron emission tomography, we measured the time course of myocardial hypoperfusion with [13N]-ammonia retention and sympathetic innervation with [18F]-6-fluorodopamine within the infarct zone in 10 patients at 2 weeks, 3 months, and 6 months after a first-onset Q-wave myocardial infarction. The time course for reestablishment of global cardiac autonomic function was also determined by measuring the power spectrum of heart rate variability with an autoregressive technique. The average infarct defect size as determined by the fractional uptake of [13N]-ammonia was 17.22% +/- 5.95% of the left ventricular myocardium. The fractional uptake of [18F]-fluorodopamine in the infarct zone was similar, at 15.83% +/- 4.45% (not significant). There was a significant increase (14% to 15%; P <.05) in myocardial blood flow and [18F]-fluorodopamine uptake to the infarct zone between 2 weeks and 3 months, with no further change between 3 months and 6 months. However, the average rate of loss (t1/ 2 hour) of [18F]- fluorodopamine continued to decrease between 2 weeks and 6 months. This paralleled a continuing fall in the low-frequency to high-frequency autospectral power ratio throughout the 6 months after infarction. CONCLUSIONS: This study demonstrates a modest increase in myocardial blood flow and evidence for sympathetic reinnervation to the infarct zone between 2 weeks and 3 months after acute myocardial infarction. Despite a flow-dependent effect on the uptake of [18F]-fluorodopamine by 3 months, there is a suggestion that restoration of sympathetic activity within the infarct zone continues between 3 months and 6 months after acute myocardial infarction.

Adult↗
PubMed1999

Estimation of pulmonary deposition of aerosol using gamma scintigraphy.

Following delivery of technetium 99m-labeled aerosols through a ventilator circuit, the amount of radioactivity in the lungs of 58 ventilated rabbits was estimated first by gamma scintigraphy via gamma camera and later by direct counting of the excised lungs (n = 116 specimens) with a gamma counter. The in situ radioactivity measured via scintigraphy was closely correlated with the gamma counter ex vivo tissue counts of the radioactivity (R2 = 0.997, P < 0.001). Overall, gamma scintigraphy gave slightly lower values of activity than the tissue counts from the gamma counter, but the limits of agreement between the two measurements were narrow enough for us to consider that the tissue and scintigraphy methods were in agreement. We conclude that gamma scintigraphy provides a convenient and noninvasive means for the accurate estimation of aerosol deposition in the lungs of small animals and possibly in small infants.

Aerosols↗
PubMed1997

Can nitrogen-13 ammonia kinetic modeling define myocardial viability independent of fluorine-18 fluorodeoxyglucose?

OBJECTIVES: The hypothesis of this study was that evaluation of myocardial flow and metabolism using nitrogen-13 (N-13) ammonia kinetic modeling with dynamic positron emission tomographic (PET) imaging could identify regions of myocardial scar and viable myocardium as defined by fluorine-18 fluorodeoxyglucose (F-18 FDG) PET. BACKGROUND: Uptake of most perfusion tracers depends on both perfusion and metabolic retention in tissue. This characteristic has limited their ability to differentiate myocardial scar from viable tissue. The kinetic modeling of N-13 ammonia permits quantification of blood flow and separation of the metabolic component of its uptake, which may permit differentiation of scar from viable tissue. METHODS: Sixteen patients, > 3 months after myocardial infarction, underwent dynamic N-13 ammonia and F-18 FDG PET imaging. Regions of reduced and normal perfusion were defined on static N-13 ammonia images. Patients were classified into two groups (group I [ischemic viable], n = 6; group II [scar], n = 10) on the basis of percent of maximal F-18 FDG uptake in hypoperfused segments. Nitrogen-13 ammonia kinetic modeling was applied to dynamic PET data, and rate constants were determined. Flow was defined by K1; volume of distribution (VD = K1/k2) of N-13 ammonia was used as an indirect indication of metabolic retention. RESULTS: Fluorine-18 FDG uptake was reduced in patients with scar compared with normal patients with ischemic viable zones (ischemic viable 93 +/- 27% [mean +/- SD]; scar 37 +/- 16%, p < or = 0.01). Using N-13 ammonia kinetic modeling, flow and VD were reduced in the hypoperfused regions of patients with scar (ischemic viable flow: 0.65 +/- 0.20 ml/min per g, scar: 0.36 +/- 0.16 ml/min per g, p < or = 0.01; VD: 3.9 +/- 1.3 and 2.0 +/- 1.07 ml/g, respectively, p < or = 0.01). For detection of viable myocardium in these patients, the sensitivity and specificity were 100% and 80% for N-13 ammonia PET flow > 0.45 ml/min per g; 100% and 70% for VD > 2.0 ml/g; and 100% and 90% for both flow > 0.45 ml/min per g and VD > 2.0 ml/g, respectively. The positive and negative predictive values for the latter approach were 86% and 100%, respectively. CONCLUSIONS: In this cohort, patients having regions with flow < or = 0.45 ml/min per g or VD < or = 2.0 ml/g had scar. Viable myocardium had both flow > 0.45 ml/min per g and VD > 2.0 ml/g. Nitrogen-13 ammonia kinetic modeling permits determination of blood flow and metabolic integrity in patients with previous myocardial infarction and can help differentiate between scar and ischemic but viable myocardium.

Aged↗
PubMed1997

Delivery of metered dose inhaler aerosols to paralyzed and nonparalyzed rabbits.

OBJECTIVE: To assess whether paralysis alters pulmonary deposition of albuterol delivered by metered dose inhaler and spacer to small animals. DESIGN: A parallel group study of intubated and ventilated rabbits. INTERVENTIONS: Animals in group 1 (n = 7) were paralyzed with intravenous pancuronium, and ventilated at a rate of 30 breaths/ min. The animals in group 2 (n = 6) were ventilated at a rate of 10 breaths/min under light anesthesia without paralysis. In this latter group, spontaneous respiration continued at a rate of 40 to 50 breaths/min. Both groups were maintained at PaCO2 of 35 to 40 torr (4.7 to 5.3 kPa), and other ventilatory settings were identical. MEASUREMENTS AND MAIN RESULTS: Technetium-99m labeled albuterol aerosol was delivered by metered dose inhaler via a spacer device to both groups. Pulmonary deposition of the aerosol, determined by measuring the radioactivity in the lung tissues at autopsy, was expressed as percent of the total radioactivity dispensed by the metered dose inhaler. Group 2 showed significantly greater lung deposition than group 1 (0.510 +/- 0.076 [SEM]% vs. 0.226 +/- 0.054%, p = .0094). Deposition in the airway, the endotracheal tube, and the ventilator circuit did not differ significantly. CONCLUSION: Metered dose inhaler delivery of aerosolized medications to ventilated rabbits is significantly enhanced if respiration is not controlled. This observation might have implications for the delivery of therapeutic aerosols to newborns and young infants receiving slow, intermittent, mandatory ventilation.

Aerosols↗
PubMed1997

[18F]fluorodeoxyglucose uptake in neonatal acute lung injury measured by positron emission tomography.

The objective of this study was to evaluate positron emission tomography (PET) of [18F]fluorodexoyglucose (18FDG) uptake as a measure of neonatal acute lung injury. Inasmuch as intrapulmonary sequestration of neutrophils is a hallmark of acute lung injury, quantification of neutrophil activity using 18FDG may offer a novel, in vivo technique to examine the progression and resolution of this disease. Ten newborn piglets were studied: six received bronchoalveolar lavage followed by 4 h of high pressure ventilation of create acute lung injury. Four healthy piglets served as controls. 18FDG (0.8 mCi/kg; 29.6 MBq) was given i.v. and PET (ECAT 953/31, Siemens) was performed for 90 min. During PET, all animals were sedated, paralyzed, and ventilated to maintain normal blood gases. The time course of radioactivity in lung regions and in plasma was used to calculate the rate constant for the metabolic trapping of 18FDG in tissue according to the method of C. S. Patlak. Median 18FDG influx constants were significantly higher in injured piglets (0.0187 min-1) than in control piglets (0.0052 min-1) (p < 0.01). Moreover, consistent with the 18FDG uptake data, injured piglets had moderate to severe injury on lung histology whereas control piglets had only slight and focal histologic changes. We conclude that PET of 18FDG uptake is an accurate, readily repeatable in vivo measure of neonatal acute lung injury.

Animals↗
PubMed1997

Pulmonary deposition of salbutamol aerosol delivered by metered dose inhaler, jet nebulizer, and ultrasonic nebulizer in mechanically ventilated rabbits.

The deposition efficiency of three methods of aerosol delivery of salbutamol into lungs of ventilated rabbits was compared: 1) metered dose inhaler (MDI) with holding chamber (HC), 2) jet nebulizer (JN), and 3) ultrasonic (US) nebulizer. The latter system was tested using two different sized medication reservoirs, a large (20 mL) cup (US20) and a small (10 mL) cup (US10). After delivery of technetium-99m-labeled salbutamol aerosol, deposition in the lungs, trachea, and ventilator circuit were estimated by a gamma counter. Total pulmonary deposition [mean(SEM)] as a percentage of the prescribed drug was: MDI + HC 0.22(0.05)%; JN 0.48(0.05)%; US20 0.90(0.13)%; US10 3.05(0.49)%. Only the deposition from the US10 was statistically significantly higher than the other modes (p < 0.05). Dynamic scintigraphy showed that, among the nebulizers, the US10 continued to deliver medication for longer than either the JN or the US20. We conclude that the US10 appears to be more efficient in delivering aerosol to the lung in this rabbit model and merits further evaluation for clinical efficiency.

Administration, Inhalation↗