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Biomedical subjects

R A Stewart

Publications and source records attributed to R A Stewart.

At least 19 recordsLinked to original sources
PubMed2006

Detection of Coccidioides species in clinical specimens by real-time PCR.

Coccidioides spp. are dimorphic fungal pathogens endemic to the semiarid regions of North, Central, and South America. Currently, direct smear and culture are the most common means of identifying Coccidioides spp. While these methods offer relatively sensitive and specific means of detecting Coccidioides spp., growth in culture may take up to 3 weeks, potentially delaying the diagnosis and initiation of appropriate antifungal therapy. In addition, growth of the organism represents a significant safety risk to laboratory personnel. The need for a rapid and safe means of diagnosing coccidioidomycosis prompted us to develop a real-time PCR assay to detect Coccidioides spp. directly from clinical specimens. Primers and fluorescent resonance energy transfer (FRET) probes were designed to target the internal transcribed spacer 2 region of Coccidioides. The assay's limit of detection is below 50 targets per reaction. An analysis of 40 Coccidioides sp. clinical isolates grown in culture demonstrated 100% sensitivity of the assay. A cross-reactivity panel containing fungi, bacteria, mycobacteria, and viruses was tested and demonstrated 100% specificity for Coccidioides spp. An analysis of 266 respiratory specimens by LightCycler PCR demonstrated 100% sensitivity and 98.4% specificity for Coccidioides spp. compared with culture. Analysis of 66 fresh tissue specimens yielded 92.9% sensitivity and 98.1% specificity versus those of the culture method. The sensitivity of the assay testing 148 paraffin-embedded tissue samples is 73.4%. A rapid method for the detection of Coccidioides spp. directly from clinical material will greatly assist in the timely diagnosis and treatment of patients, while at the same time decreasing the risk of accidental exposure to laboratory personnel.

Coccidioides↗
PubMed2001

Effects of variety, the 1B/1R translocation and xylanase supplementation on nutritive value of wheat for broilers.

1. Three consecutive studies were done with 12 wheat samples (4 per study), each of different variety (6 containing the 1B/1R rye translocation) to examine the effects of wheat variety, presence of 1B/1R and interactions with xylanase addition (Avizyme 1310). The wheat varieties covered a wide range of in vitro viscosity (6.3 to 19.8 cps). In each study 64 male, Ross broilers were individually caged and given the diets ad libitum from d 7 to 28. Bird performance, viscosity of ileal contents and diet metabolisability (AME) were measured. 2. The diets contained (g/kg): wheat 790, casein 134, dicalcium phosphate 21.4, potassium bicarbonate 10.8, sodium bicarbonate 7.5, soya oil 10, arginine 5, minerals etc. 21.3. 3. Within each study there were large differences in dry matter (DM) intake between varieties but the variety effect was significant (P<0.01) only in study 2. Liveweight gain (LWG) differences mirrored DM intake, being significant (P<0.01) in study 2. Mean gain:food was unaffected by variety in any study. 4. Calculated wheat AME (MJ/kg DM) ranged from 13.4 to 14.4 in study 2 (P<0.05), the values for studies 1 and 3 lying within this range. 5. Across all 3 studies, in vivo viscosity (proximal ileum) ranged from 5.0 to 37.6 in the absence of enzyme and from 3.9 to 12.1 with enzyme addition; in studies 1 and 2 variety differences were significant (P<0.05). 6. Enzyme addition had no effect on DM intake or LWG but gain:food tended to be improved (NS), metabolisability of energy (ME:GE) was increased (P<0.01) by 2.2% and calculated wheat AME by 4% while in vivo viscosity was reduced (P<0.001). 7. There were no significant differences in DM intake, LWG, gain:food, ME:GE or calculated wheat AME concentration associated with the presence of the 1B/1R translocation and no interactions between enzyme and 1B/1R. 8. There were poor relationships between either gain:food or wheat AME concentration and in vitro or in vivo viscosity. There was no significant relationship between AME concentration and either specific weight or thousand grain weight. 9. It was concluded that (a) variety differences tended to be small (b) there was no negative impact of the 1B/1R rye translocation with the diet formulation used (c) in vitro viscosity failed to predict satisfactorily any aspect of performance with the high wheat/low fat diet formulation used.

Animal Feed↗
PubMed2001

Importance of amino-acid and electrolyte balance in experimental diets used to determine the apparent metabolisable energy (AME) value of wheat.

1. An experiment was done with male, Ross broiler chicks to study the effect of diet composition and electrolyte balance on the measurement of diet AME and performance parameters in diets containing high levels of wheat inclusion. 2. The control diet (G) was based on wheat (667 g/kg) with full-fat soya, soyabean meal, Extrupro and herring meal providing the protein supplements. The experimental treatments were based on 2 diets, one based on wheat (790 g/kg) with casein as the protein supplement and the other containing 667 g/kg wheat plus casein, cellulose and starch. Each of these was formulated to contain one of three concentrations of sodium and potassium bicarbonate giving final values for dietary electrolyte balance of approximately 90, 180 and 280 meq/kg diet. 3. DM intake was numerically lower with the lower level of wheat inclusion and LWG (P < 0.05) and gain:food (P < 0.001) were reduced. ME:GE was similar for the two levels of wheat/casein but higher (P < 0.001) than for the control diet. 4. The two higher electrolyte balances improved DM intake (P < 0.01), LWG and gain:food (P < 0.01) compared with the diets containing no added bicarbonate. ME:GE was unaffected by electrolyte inclusion. 5. Viscosity of ileal digesta supernatant fell (P < 0.01) with increasing bicarbonate inclusion but the value for the highest electrolyte level was still higher than for the control diet. 6. It is concluded that addition of both arginine and electrolyte is needed with a wheat/casein diet to improve performance to levels seen with a more commercial diet but that the determination of diet AME, with the type of fat addition used in this study, is unaffected by electrolyte balance. The interaction between electrolyte balance and in vivo viscosity requires further study.

Amino Acids↗
PubMed2000

Long-term assessment of psychological well-being in a randomized placebo-controlled trial of cholesterol reduction with pravastatin. The LIPID Study Investigators.

BACKGROUND: There is controversial evidence that a low serum cholesterol level is associated with an increased risk of depression, suicide, and violence. The aim of this study was to identify or exclude any small or infrequent adverse effect of long-term reduction of serum cholesterol with pravastatin sodium on psychological well-being. METHODS: The study population consisted of 1130 respondents from a representative sample of 1222 patients with stable coronary artery disease participating in the Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) study. Subjects were randomized in a double-blind manner to treatment with pravastatin sodium, 40 mg/d (n = 559), or placebo (n = 571) for at least 4 years. Psychological well-being was assessed with a standard self-administered questionnaire at baseline and after 6 months, 1 year, 2 years, and 4 years. The questionnaire assessed anxiety and depression, anger, impulsiveness, alcohol consumption, and adverse life events. RESULTS: Serum cholesterol levels decreased by an average of 1.3 mmol/L (50 mg/dL) with pravastatin therapy and did not change with placebo. During follow-up there was no significant difference by treatment group in measures of anxiety and depression, anger expression, or impulsiveness (95% confidence interval excluded differences of >0.2 SD) and no difference in the proportion of subjects with excessive alcohol consumption or adverse life events (odds ratio, 1.0; 95% confidence interval, 0.8-1.2). There was no evidence of a treatment effect for persons whose baseline serum cholesterol level was in the lowest 10% (<4.6 mmol/L [178 mg/dL]) or whose scores for anxiety and depression, anger, or impulsiveness were in the highest 10% at baseline. There was no association between change in the serum cholesterol level and measures of anxiety and depression, anger, or impulsiveness during follow-up. CONCLUSION: Long-term reduction of serum cholesterol with pravastatin has no adverse effect on psychological well-being.

Adult↗
PubMed2000

Statistical methods to improve the precision of the treadmill exercise test.

OBJECTIVES: The study systematically compared different measures of ST segment depression from the treadmill exercise test. BACKGROUND: The value of the treadmill exercise test for objectively measuring treatment effects is limited by random error in the measurement of ST depression and may be biased by regression to the mean or by the decision to terminate the test. METHODS: Treadmill exercise was performed in 21 subjects with ischemic heart disease 1 h after isosorbide dinitrate 10 mg or placebo in a double-blind randomized crossover study. A 12-lead electrocardiogram (ECG) was recorded every 30 s during and at peak exercise. The relative sample size needed to detect the nitrate effect was compared for different summary measures of ST depression. RESULTS: The ST depression measured from a single unmatched lead at longest equivalent sub-maximal exercise needed the lowest sample size to detect the nitrate effect in paired comparisons (p = 0.000006). Averaging over multiple leads or times did not improve detection of the nitrate effect. The rate of increase in ST depression (in mm/min) calculated by linear regression needed a similar sample size (x1.32, 95% CI 0.62 to 2.58). A larger sample size was needed for ST depression at peak exercise (x2.9, CI 1.3, 11.1) and exercise duration (x4.5, CI 1.5, 38). Time to 1-mm ST depression was the least efficient measurement (relative sample size x15.5, CI 1.6, >1,000). Comparison of matched leads resulted in >2-fold differences in estimates of the nitrate effect because of bias from regression to the mean. CONCLUSIONS: Maximal ST depression at longest equivalent sub-maximal exercise and the maximal rate of increase in ST depression had less bias and random variation than did other commonly used measures. The rate of increase in ST depression is preferred because it can be calculated in either paired or unpaired studies.

Administration, Oral↗
PubMed2000

Collateral recruitment and "warm-up" after first exercise in ischemic heart disease.

BACKGROUND: Proposed mechanisms for "warm-up" after angina on first exercise include ischemic preconditioning and collateral recruitment. The aim of this study was to determine whether patients with ischemic heart disease and well-developed coronary collateral vessels have a greater warm-up response than those with no visible collateral vessels. METHODS AND RESULTS: Fifteen patients with a total coronary occlusion and collateral vessels and 18 patients with a single coronary artery stenosis and no angiographically visible collateral vessels were studied. Warm-up was measured as the difference in ST depression on the second compared with the first of 2 sequential treadmill exercise tests separated by 10 minutes of rest. There was a trend for the duration of second exercise to increase more in patients with occlusion than in those with stenosis (+1.3 vs +0.54 minutes, respectively, P =.087). In both groups, ST depression was less on second exercise than on first exercise. The size of this decrease was greater in the occlusion group than in the stenosis group. ST depression at equivalent submaximal exercise decreased by 0.52 vs 0.19 mm, respectively (P =.049). The rate of increase in ST depression during exercise decreased by 1.08 versus 0. 55 mm/min, respectively (P =.034). These differences were less after adjustment for ST depression on first exercise (P =.11 and P =.063, respectively). CONCLUSIONS: The trend for a greater decrease in ST depression on second compared with first exercise in the patients with total coronary occlusion suggests that an increase in collateral flow is a mechanism for warm-up after first exercise in ischemic heart disease.

Aged↗
PubMed2000

B7.1 costimulation increases T-cell proliferation and cytotoxicity via selective expansion of specific variable alpha and beta genes of the T-cell receptor.

BACKGROUND: Optimal T-cell activation requires not only ligation of the T-cell receptor (TcR) but also delivery of costimulatory signals by various accessory molecules. The interaction of the costimulatory molecule B7.1 (CD80) with its receptor CD28 provides a strong positive signal to T cells. METHODS: The B7.1 gene was transduced into cultured human ovarian, breast, and pancreatic tumor cells by using a retroviral vector. Autologous as well as allogeneic naive T-cells were stimulated with either wild-type or B7.1-transduced tumor cells in a mixed lymphocyte tumor cell culture (MLTC). In addition to cytolytic activity, T-cell proliferation, T-cell subset composition, and the frequencies of TcR variable (V) alpha and beta genes were compared in T cells from both types of MLTC. RESULTS: Introduction of the B7.1 gene into tumor cells was successful in all tumors to a varying degree. Those tumors expressing high levels of B7.1 induced significantly higher levels of T-cell proliferation than wild-type tumor cells. T-cell subset composition did not markedly differ between T cells stimulated with wild-type tumor cells or B7.1-expressing tumor cells. However, T cells stimulated with B7.1-expressing tumor cells showed a significantly increased cytolytic potential. The increased cytotoxic T lymphocyte activity was associated with a higher frequency of specific TcR V alpha and V beta genes. In addition, B7.1 costimulation promoted oligoclonality among the responding T cells. CONCLUSIONS: These data suggest that costimulation through B7.1 promotes T-cell proliferation and cytotoxic activity through clonal expansions of T cells bearing antigen-specific TcR V alpha and V beta genes and through promotion of oligoclonality. The data also suggest that promoting B7.1-mediated costimulation is an important aspect of immune therapies.

B7-1 Antigen↗
PubMed2000

Relation between duration and intensity of first exercise and "warm up" in ischaemic heart disease.

OBJECTIVE: To determine the importance of the duration and intensity of "warm up" exercise for reducing ischaemia during second exercise in patients with exertional angina. DESIGN: Randomised crossover comparison of three warm up exercise protocols. PATIENTS: 18 subjects with stable ischaemic heart disease and > 0.1 mV ST segment depression on treadmill exercise testing. INTERVENTIONS: The warm up protocols were 20 minutes of slow exercise at 2.7 km/h, symptom limited graded exercise for a mean of 7.4 (range 5.0 to 10.5) minutes, and three minutes of symptom limited fast exercise of similar maximum intensity. MAIN OUTCOME MEASURES: ST segment depression during graded treadmill exercise undertaken 10 minutes after each warm up protocol or no warm up exercise. RESULTS: Compared with exercise with no warm up, the duration of graded exercise after earlier slow warm up increased by 4.9% (95% confidence interval (CI), -3.3% to 13.7%), after graded warm up by 10.3% (95% CI, 5.6% to 15.2%), and after fast warm up by 16% (95% CI, 6.2% to 26.7%). ST segment depression at equivalent submaximal exercise decreased after slow warm up by 27% (95% CI, 5% to 44%), after graded warm up by 31% (95% CI, 17% to 44%), and after fast warm up by 47% (95% CI, 27% to 61%). Compared with slow warm up exercise, the more intense graded and fast warm up protocols significantly increased the duration of second exercise (p = 0.0072) and reduced both peak ST depression (p = 0.0026) and the rate of increase of ST depression (p = 0.0069). CONCLUSIONS: In patients with exertional angina the size of the warm up response is related to the maximum intensity rather than the duration of first exercise.

Aged↗
PubMed2000

Randomised comparison of the effects of nicardipine and esmolol on coronary artery wall stress: implications for the risk of plaque rupture.

OBJECTIVE: To determine whether the beta blocker esmolol reduces coronary artery wall stress more than the short acting dihydropyridine calcium antagonist nicardipine. DESIGN: Randomised double blind placebo controlled trial. SETTING: Tertiary cardiology centre. PATIENTS: Patients with coronary artery disease. INTERVENTIONS: 20 patients were randomised double blind to an infusion of nicardipine (n = 10) or esmolol (n = 10) titrated to reduce systolic blood pressure by 20 mm Hg. MAIN OUTCOME MEASURES: Peak systolic wall circumferential stress. RESULTS: Esmolol reduced peak coronary stress by a mean of 0.17 x 10(6) dyn/cm(2) (95% confidence interval (CI) 0.14 to 0.21 x 10(6) dyn/cm(2)) compared with a reduction of 0.07 x 10(6) dyn/cm(2) (95% CI 0.05 to 0.10 x 10(6) dyn/cm(2)) after nicardipine. Peak systolic radius was reduced by 0.04 mm (95% CI 0.03 to 0.06 mm) after esmolol compared with an increase of 0.08 mm (95% CI 0.05 to 0.10 mm) after nicardipine. Heart rate increased by 11.5 beats/min (95% CI 6.9 to 16.2 beats/min) after nicardipine and decreased by 5.3 beats/min (95% CI 1.9 to 8.6 beats/min) after esmolol. CONCLUSIONS: Intravenous esmolol is more effective than nicardipine at reducing circumferential coronary artery wall stress.

Adrenergic beta-Antagonists↗
PubMed1999

Coronary artery flow ten weeks after myocardial infarction or unstable angina: effects of combined warfarin and aspirin therapy.

Forty-three patients presenting with unstable angina or myocardial infarction were randomised double blind to warfarin [target international normalised ratio (INR), 2.0 to 2.5] and aspirin (150 mg) daily or placebo plus aspirin (150 mg) daily. Coronary flow was assessed with the thrombolysis in myocardial infarction (TIMI) flow grade and corrected TIMI frame count (CTFC). Coronary artery flow was reduced (higher CTFC) at baseline in culprit arteries (mean +/-SD, 37.1+/-15.4 frames) compared to nonculprit arteries (22.5+/-6.7 frames, P<0.0001). In patients with a patent artery at follow-up, coronary flow was unchanged after ten weeks of warfarin and aspirin (-2.0+/-19.9 frames) or aspirin alone (3.8+/-10.4 frames, P = 0.20). Patients randomised to aspirin alone were more likely to progress to total occlusion [aspirin, 7 of 19 (37%) vs. warfarin and aspirin, 1 of 24 (4%); P = 0.01). Higher baseline culprit artery CTFC was also associated with an increased risk of late occlusion [+10 frames; odds ratio (OR), 1.65; 95% CI, 1.01 to 2.33]. Coronary flow remained impaired ten weeks after presentation with myocardial infarction or unstable angina. Combination warfarin and aspirin therapy did not improve flow in vessels that remained patent but did reduce the risk of progression to occlusion.

Angina, Unstable↗
PubMed1999

Assessment of the mechanical properties of coronary arteries using intravascular ultrasound: an in vivo study.

The pressure-area relation of coronary arteries provides important information about the mechanical properties of these vessels. In human subjects methodological limitations have precluded measurement of instantaneous compliance and coronary stress in vivo. The purpose of this study was to assess a new method for measuring instantaneous values of coronary artery compliance and wall stress utilizing simultaneously acquired pressure and intravascular ultrasound measurements of vessel area. Ten subjects with coronary artery disease had intravascular ultrasound studies of the proximal left anterior descending or circumflex coronary arteries. Coronary luminal area was measured with a 30-MHz (3F or 3.5F) intravascular ultrasound catheter and simultaneous coronary pressure measured with a 2F micromanometer-tipped catheter. Using this technique the nonlinear pressure-area relation and mean circumferential wall stress were determined over the physiological pressure range. Coronary artery compliance at 100 mmHg ranged from 0.010 to 0.052 mm2/mmHg (mean +/- SD, 0.020+/-0.012 mm2/mmHg). Peak systolic circumferential stress ranged from 0.52 to 2.03 x 10(6) dyn/cm2 (1.09+/-0.42 x 10(6) dyn/cm2). This study describes a new method of determining coronary artery mechanical properties over the physiological pressure range. This technique may be useful in further studies of coronary artery mechanics.

Compliance↗
PubMed1999

Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity.

We have previously used mosaic flies to screen for tumour suppressors or negative regulators of cell proliferation. The cellular composition of these flies resembles that of cancer patients who are chimaeric individuals carrying a small number of mutated somatic cells. One of the genes we identified is the large tumour suppressor gene, lats (also known as wts), which encodes a putative serine/threonine kinase. Somatic cells mutant for lats undergo extensive proliferation and form large tumours in many tissues in mosaic adults. Homozygous mutants for various lats alleles display a range of developmental defects including embryonic lethality. Although many tumour suppressors have been identified in Drosophila melanogaster, it is not clear whether these fly genes are directly relevant to tumorigenesis in mammals. Here, we have isolated mammalian homologues of Drosophila lats. Human LATS1 suppresses tumour growth and rescues all developmental defects, including embryonic lethality in flies. In mammalian cells, LATS1 is phosphorylated in a cell-cycle-dependent manner and complexes with CDC2 in early mitosis. LATS1-associated CDC2 has no mitotic cyclin partner and no kinase activity for histone H1. Furthermore, lats mutant cells in Drosophila abnormally accumulate cyclin A. These biochemical observations indicate that LATS is a novel negative regulator of CDC2/cyclin A, a finding supported by genetic data in Drosophila demonstrating that lats specifically interacts with cdc2 and cyclin A.

Amino Acid Sequence↗
PubMed1998

Influence of heart rate on stroke volume variability in atrial fibrillation in patients with normal and impaired left ventricular function.

Both resting tachycardia and irregular ventricular rhythm may contribute to impaired cardiac performance in atrial fibrillation (AF). This study assesses the relation between resting heart rate and beat-to-beat changes in left ventricular (LV) ejection and filling in patients with normal and impaired LV systolic function. Beat-to-beat variation in LV outflow and inflow velocity-time integral was measured using pulsed Doppler ultrasound in 39 patients with chronic AF and normal (n=22) or impaired (n=17) LV systolic function. Aortic velocity-time integral variability increased with mean heart rate (p=0.003) even though RR interval variability decreased (p <0.001). Aortic velocity-time integral was more sensitive to the duration of both the preceding (p <0.001) and prepreceding (p <0.001) RR intervals at higher heart rates. These relations were similar for patients with normal and impaired LV systolic function. The sensitivity of the filling velocity-time integral to RR interval variability also increased with heart rate (p <0.001). However, at higher heart rates the filling velocity-time integral (p=0.009) and filling time (p=0.005) were less sensitive to change in RR intervals in patients with impaired LV function. We conclude that beat-to-beat stroke volume variability in AF increases with heart rate. Stroke volume variability was not influenced by LV systolic function.

Adult↗
PubMed1998

Long stenting in native coronary arteries: relation between vessel size and outcome.

Procedural and 6-mo clinical outcomes were evaluated in 34 consecutive patients who had stenting (<40 mm) of a long segment of coronary artery. Procedural success was achieved in 32 (96%) patients. Before stenting, 32 (96%) patients had Canadian Cardiovascular Society Class 3 or 4 angina compared to 7 (21%) at 6-mo follow-up (P<0.001). Eleven patients (32%) suffered either acute/subacute stent thrombosis (n=4) or restenosis (n=7). On logistic regression distal reference diameter <2.5 mm (odds ratio 26, P<0.01) and previous cardiac intervention (odds ratio 9.0, P<0.01) were independent predictors of a major adverse event during follow-up. There was no significant association between outcome and indication for stenting, type of stent, or use of ticlopidine and aspirin. These results indicate that distal vessel diameter <2.5 mm is a powerful predictor of subacute thrombosis or restenosis after long coronary artery stenting.

Adult↗