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Biomedical subjects

R J Gibbons

Publications and source records attributed to R J Gibbons.

At least 37 records · Page 2Linked to original sources
PubMed2001

Gender differences and temporal trends in clinical characteristics, stress test results and use of invasive procedures in patients undergoing evaluation for coronary artery disease.

OBJECTIVES: This study examined gender differences and temporal changes in the clinical characteristics of patients referred for nuclear stress imaging, their imaging results and subsequent utilization of coronary angiography and revascularization. BACKGROUND: Gender bias may influence resource utilization in patients with coronary artery disease (CAD). No study has analyzed gender differences and time trends in patients referred for noninvasive testing and subsequent use of invasive procedures. METHODS: Between January 1986 and December 1995, 14,499 patients (5,910 women and 8,589 men) without established CAD underwent stress myocardial perfusion imaging. The clinical characteristics, imaging results, coronary angiograms and revascularization outcomes were compared in women and men over time. RESULTS: The mean pretest probability of CAD was lower in women (45%) than in men (70%) (p < 0.001). More women (69%) than men (42%) had normal nuclear images (p < 0.001). Men (17%) were more likely than women (8%) to undergo coronary angiography (p < 0.001). Male gender was independently associated with referral for coronary angiography (multivariate model: chi-square = 16, p < 0.001) but was considerably weaker than the imaging variables (summed reversibility score: chi-square = 273, p < 0.001). Revascularization was performed in more men (46% of the population undergoing angiography) than women (39%) (p = 0.01), but gender was not independently associated with referral to revascularization. There were no significant differences in clinical, imaging or invasive variables between the genders over time. CONCLUSIONS: There was little evidence for a bias against women in this study. Women were somewhat less likely to undergo coronary angiography but were referred for stress perfusion imaging more liberally. Practice patterns remained constant over this 10-year period.

Angioplasty, Balloon, Coronary↗
PubMed2001

ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation: executive summary. A Report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation): developed in Collaboration With the North American Society of Pacing and Electrophysiology.

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Algorithms↗
PubMed2001

Monosomy for the most telomeric, gene-rich region of the short arm of human chromosome 16 causes minimal phenotypic effects.

We have examined the phenotypic effects of 21 independent deletions from the fully sequenced and annotated 356 kb telomeric region of the short arm of chromosome 16 (16p13.3). Fifteen genes contained within this region have been highly conserved throughout evolution and encode proteins involved in important housekeeping functions, synthesis of haemoglobin, signalling pathways and critical developmental pathways. Although a priori many of these genes would be considered candidates for critical haploinsufficient genes, none of the deletions within the 356 kb interval cause any discernible phenotype other than alpha thalassaemia whether inherited via the maternal or paternal line. These findings contrast with previous observations on patients with larger (> 1 Mb) deletions from the 16p telomere and therefore address the mechanisms by which monosomy gives rise to human genetic disease.

Adolescent↗
PubMed2001

Use of a new myocardial centroid for measurement of regional myocardial dysfunction by electron beam computed tomography: comparison with technetium-99m sestamibi infarct size quantification.

RATIONALE AND OBJECTIVES: The study compared the performance of conventional endocardial and epicardial centroid algorithms with the new "myocardial" centroid algorithm in patients with anterior myocardial infarction. "Floating" endocardial or epicardial centroid algorithms, commonly used in tomographic imaging methods to assess regional motion, may misrepresent left ventricular regional myocardial function in the presence of markedly asymmetric left ventricular contraction. METHODS: A new centroid algorithm based on regional myocardial mass distribution was tested in 29 patients with a first anterior myocardial infarction and was compared with conventional centroid algorithms. Direct comparisons in 60 equal sectors at one midventricular level per patient were performed between electron beam computed tomography and technetium-99m sestamibi single-photon emission computed tomography. The thresholds of regional myocardial function used to define infarction were varied for regional ejection fraction from 20% to 40% and for regional wall thickening from 0 to 4 mm. Regression and Bland-Altman analysis were used to compare infarct size by regional myocardial function with infarct size by sestamibi single-photon emission computed tomography. RESULTS: The new myocardial centroid showed the least shift toward infarcted myocardium from diastole to systole and had the highest amplitudes of the measurement curves for regional ejection fraction and regional wall thickening. The optimal regional myocardial function thresholds for each centroid algorithm for regional ejection fraction were endocardial, 30% (R = 0.62; mean difference to sestamibi, -0.5% +/- 22.1% tomographic infarct size points); epicardial, 30% (R = 0.79; mean difference, 2.2% +/- 13.1% tomographic infarct size points); and new myocardial, 25% (R = 0.88; mean difference, -0.6% +/- 9.5% tomographic infarct size points). The optimal thresholds for regional wall thickening were endocardial, 1 mm (R = 0.70; mean difference, -2.2% +/- 14.3% tomographic infarct size points); epicardial, 1 mm (R = 0.78; mean difference, -4.6% +/- 12.7% tomographic infarct size points); and new myocardial, 2 mm (R = 0.71; mean difference, 2.1% +/- 14.1% tomographic infarct size points). The best agreement (R = 0.88) between electron beam computed tomography infarct size and sestamibi single-photon emission computed tomography infarct size was achieved with regional ejection fraction and the new myocardial centroid algorithm. CONCLUSIONS: In asymmetrically contracting left ventricles, the new myocardial centroid algorithm is superior to conventional methods for tomographic analysis of regional myocardial function.

Algorithms↗
PubMed2000

Management of coronary risk factors by registered nurses versus usual care in patients with unstable angina pectoris (a chest pain evaluation in the emergency room [CHEER] substudy).

This study examined whether nurses could manage coronary risk factors in patients with unstable angina more effectively than physicians practicing usual care. Three hundred twenty-six patients were randomized in the emergency room to a 6-month program of risk factor management by a registered nurse versus participation in usual care. The nurse intervention consisted of a 30-minute counseling visit at 6 to 10 days after the chest pain episode and a second 30-minute session 1 month later. Multiple risk factors were assessed and addressed: smoking, blood lipids, blood pressure, blood glucose, physical inactivity, weight, psychological stress, and social isolation. Compared with usual care, nurse intervention patients significantly reduced both triglycerides (-29 +/- 8 vs 5 +/- 6 mg/dl; p <0.0004) and weight (-0.9 +/- 3.3 vs +0.1 +/- 2.1 kg; p = 0.0071), and had corresponding improvements in self-reported diet compliance and exercise (+34 +/- 106 vs +9 +/- 98 minutes, p = 0.0491). No significant differences between groups were observed in terms of 6-month changes in total, high-density lipoprotein, or low-density lipoprotein cholesterol, blood pressure, fasting blood glucose, percent body fat or waist-hip ratio, or psychological distress scores. The 6-month rate of recurrent events (cardiac death, out-of-hospital cardiac arrest, myocardial infarction) and/or revascularizations (coronary artery bypass surgery or coronary angioplasty) was lower in the nurse intervention group (1% vs 9%; p = 0.002). We conclude that a nurse-delivered risk factor intervention program for patients with chest pain is feasible and more effective than usual care in terms of fostering lifestyle changes that may lower coronary risk.

Aged↗
PubMed2000

Molecular-clinical spectrum of the ATR-X syndrome.

Since the identification of the ATRX gene (synonyms XNP, XH2) in 1995, it has been shown to be the disease gene for numerous forms of syndromal X-linked mental retardation [X-linked alpha thalassemia/mental retardation (ATR-X) syndrome, Carpenter syndrome, Juberg-Marsidi syndrome, Smith-Fineman-Myers syndrome, X-linked mental retardation with spastic paraplegia]. An attempt is made in this article to review the clinical spectrum associated with ATRX mutations and to analyse the evidence for any genotype/phenotype correlation.

Abnormalities, Multiple↗
PubMed2000

The effect of collateral flow and myocardial viability on the distribution of technetium-99m sestamibi in a closed-chest model of coronary occlusion and reperfusion.

Myocardial uptake of technetium-99m sestamibi at low coronary flow rates overestimates blood flow, but the relative impact of flow and viability on 99mTc-sestamibi kinetics is unclear. The objective of this study was to determine the effect of myocardial viability and the degree of collateral blood flow on the uptake and retention of 99mTc-sestamibi by examining three animal models of coronary occlusion and reperfusion, each reflecting a different state of viability and collateral blood flow. Three closed-chest animal models were studied: canine (high collateral flow, preserved viability), porcine (low collateral flow, absent viability) and porcine with slowly occlusive coronary stents producing infarction and enhanced collateral blood flow (high collateral flow, absent viability). There were seven dogs, seven pigs and six pigs, respectively, in each animal model. Animals from all three models were subjected to a 40-min total left anterior descending artery (LAD) occlusion followed by 2 h of reperfusion. 99mTc-sestamibi and radiolabelled microspheres were injected during LAD occlusion 10 min prior to reperfusion. Animals were sacrificed after 2 h of reperfusion flow. Ex situ heart slice imaging to determine risk area was followed by viability staining to determine infarct size. Slices were subsequently sectioned into equally sized radial segments and placed in a gamma well counter. Risk area as determined by ex situ 99mTc-sestamibi imaging was not significantly different by model. Pathological infarct size differed significantly by model [canine = 1%+/-1% of the left ventricle (LV); porcine = 13%+/-8% LV; porcine with stent = 14%+/-7% LV; P = 0.002)]. Collateral blood flow by microspheres during occlusion tended to differ among models (overall P = 0.08), with the canine and porcine with stent models having relatively high flow rates compared with the acute porcine model. 99mTc-sestamibi activity correlated with microsphere blood flow in all three models, with r values for individual animals (n = 20) ranging from 0.86 to 0.96 (all P<0.0001). There was a significant difference in the regression line intercepts (P<0.0001) and slopes (P<0.01) among the three models comparing 99mTc-sestamibi uptake with myocardial blood flow. 99mTc-sestamibi uptake overestimated blood flow to a greater extent in the canine model (high flow with viability) than in the porcine model (low flow, absent viability). Despite enhanced collateral flow, there was significantly less overestimation of flow in the porcine stent model (high flow, absent viability). In conclusion, at low flow rates 99mTc-sestamibi activity overestimates myocardial blood flow. This effect is most pronounced in myocardium with significant collateral flow and preserved viability, consistent with over-extraction or redistribution of the tracer. The effect is markedly decreased in non-viable myocardium regardless of blood flow.

Animals↗
PubMed2000

Identification of severe coronary artery disease in patients with a single abnormal coronary territory on exercise thallium-201 imaging: the importance of clinical and exercise variables.

OBJECTIVES: The aim of this study was to determine which clinical, exercise and thallium variables can aid in the identification of three-vessel or left main coronary artery disease (3VLMD) in patients with one abnormal coronary territory (either a reversible or fixed defect) on exercise thallium testing and to test the prognostic value of these variables. BACKGROUND: Although the sensitivity of detection of coronary artery disease by thallium-201 imaging is high, the actual detection of 3VLMD by thallium tomographic images alone is not optimal. METHODS: A multivariate model for prediction of 3VLMD was developed from several clinical, exercise and thallium-201 variables in a training population of 264 patients who had one abnormal coronary artery territory on exercise thallium testing and had undergone coronary angiography. Using this model, patients were stratified into risk groups for prediction of 3VLMD. A separate validation cohort of 474 consecutive patients who were treated initially with medical therapy and who had one abnormal coronary territory were divided into identical risk groupings by the variables derived from the training population, and they were followed for a median of 7.0 years to evaluate the prognostic value of this model. RESULTS: The prevalence of 3VLMD was 26% in the training population despite one abnormal thallium coronary territory. Four clinical and exercise variables--diabetes, hypertension, magnitude of ST segment depression, and exercise rate-pressure product-were found to be independent predictors of 3VLMD. In the training population, the prevalence of 3VLMD in low-, intermediate- and high-risk groups was 15%, 22% and 51%, respectively. When the multivariate model was applied to the validation population, the eight-year overall survival rates in the low-, intermediate- and high-risk groups were 89%, 73% and 75%, respectively (p < 0.001). CONCLUSIONS: A substantial proportion of patients with one abnormal thallium coronary territory have 3VLMD with subsequent divergent outcomes based upon risk stratification by clinical and exercise variables. Consequently, the finding of only a single abnormal coronary territory by thallium-201 perfusion imaging does not necessarily confer a benign prognosis in the absence of consideration of nonimaging variables.

Coronary Angiography↗
PubMed2000

A systematic analysis of factors which may impact upon tomographic perfusion imaging measurements: implications for the use of Tc-99m sestamibi in acute myocardial infarction.

BACKGROUND: The use of acute Tc-99m sestamibi imaging has provided a valuable methodology to assess myocardium at risk and collateral blood flow. OBJECTIVE: The purpose of this study was to determine the impact of physical, physiologic, and reconstruction factors on the extent and severity of Tc-99m sestamibi images in a porcine model of coronary occlusion and reperfusion. METHODS AND RESULTS: Eleven pigs underwent 40 min of coronary occlusion using a balloon catheter followed by reperfusion. Radiolabeled microspheres were injected during occlusion for blood flow determination and 20-30 mCi of Tc-99m sestamibi was injected intravenously for cardiac imaging. Each animal underwent four modes of gamma camera imaging: a cardiac and respiratory gated SPECT study, an ungated SPECT study, a post-mortem SPECT study and an ex-situ study where the heart was sliced into five short axis slices and directly imaged. All animals had extensive wall motion abnormalities at the time of imaging. Myocardial risk area by ex-situ imaging was 32 +/- 9% LV and did not significantly change with the addition of a chest cavity and tomographic reconstruction (post-mortem and gated imaging) or cardiac and respiratory motion (ungated imaging). Defect severity was significantly underestimated with the addition of a chest cavity and tomographic reconstruction but was unaltered by cardiac and respiratory motion. CONCLUSIONS: The assessment of risk area acutely by SPECT Tc-99m sestamibi imaging is unaffected by cardiac motion obviating the necessity for gated imaging. Estimated defect severity (which has been used as a measure of collateral flow) is significantly reduced by the chest wall and tomographic acquisition and reconstruction suggesting a role for scatter and attenuation algorithms for this measure.

Animals↗
PubMed2000

Mutations in ATRX, encoding a SWI/SNF-like protein, cause diverse changes in the pattern of DNA methylation.

A goal of molecular genetics is to understand the relationship between basic nuclear processes, epigenetic changes and the numerous proteins that orchestrate these effects. One such protein, ATRX, contains a highly conserved plant homeodomain (PHD)-like domain, present in many chromatin-associated proteins, and a carboxy-terminal domain which identifies it as a member of the SNF2 family of helicase/ATPases. Mutations in ATRX give rise to characteristic developmental abnormalities including severe mental retardation, facial dysmorphism, urogenital abnormalities and alpha-thalassaemia. This circumstantial evidence suggests that ATRX may act as a transcriptional regulator through an effect on chromatin. We have recently shown that ATRX is localized to pericentromeric heterochromatin during interphase and mitosis, suggesting that ATRX might exert other chromatin-mediated effects in the nucleus. Moreover, at metaphase, some ATRX is localized at or close to the ribosomal DNA (rDNA) arrays on the short arms of human acrocentric chromosomes. Here we show that mutations in ATRX give rise to changes in the pattern of methylation of several highly repeated sequences including the rDNA arrays, a Y-specific satellite and subtelomeric repeats. Our findings provide a potential link between the processes of chromatin remodelling, DNA methylation and gene expression in mammalian development.

Blotting, Southern↗
PubMed2000

Infarct size determination by technetium 99m sestamibi single-photon emission computed tomography predicts survival in patients with chronic coronary artery disease.

BACKGROUND: The prognostic value of infarct size quantification by technetium 99m sestamibi single-photon emission computed tomography (SPECT) in patients with chronic coronary artery disease (CAD) has not been established. Methods And Results Between September 1994 and May 1995, 1323 patients with known or suspected CAD were referred for perfusion imaging for clinical reasons and had infarct size determined by quantitative SPECT imaging. Patients underwent exercise stress (61%), pharmacologic stress (37%), and rest imaging (3%). Patients were excluded if they had cardiomyopathy, valvular heart disease, or myocardial infarction within 3 weeks of the SPECT study. There were 1224 patients who formed the study group. Follow-up was 94% complete at a median of 1.9 +/- 0.4 years. Sixty-five percent of patients had no measurable infarct. Among the patients with measurable infarcts, the mean infarct size by sestamibi imaging was 15.0% +/- 14.5% of the left ventricle (25% of infarcts </=5% of the left ventricle and 25% of infarcts >/=19% of the left ventricle). By using stepwise regression analysis, age, diabetes, and hypercholesterolemia were all clinical predictors of overall death (P <.05). For cardiac death, only age and diabetes were significant. After adjusting for these clinical variables, infarct size remained an independent predictor of overall death (P =. 001) and survival free of cardiac death (P =.0002). However, when first-pass left ventricular ejection fraction was added to the models, infarct size was no longer significant. CONCLUSIONS: Infarct size determination by SPECT (99m)Tc sestamibi can predict subsequent death in patients with chronic CAD, although ejection fraction appears to have greater prognostic value.

Adult↗
PubMed2000

Specificity of the stress electrocardiogram during adenosine myocardial perfusion imaging in patients taking digoxin.

BACKGROUND: In patients taking digoxin, the exercise electrocardiogram has a lower specificity for detecting coronary artery disease. However, the effect of digoxin on adenosine-induced ST-segment depression is unknown. The purpose of this study was to evaluate the specificity of the electrocardiogram during adenosine myocardial perfusion imaging in patients taking digoxin. METHODS: Between May 1991 and September 1997, patients (n = 99) taking digoxin who underwent adenosine stress imaging with thallium-201 or technetium-99m sestamibi and coronary angiography within 3 months were retrospectively identified. Exclusion criteria included prior myocardial infarction, coronary artery angioplasty or bypass surgery, left bundle branch block, paced ventricular rhythm, or significant valvular disease. Twelve-lead electrocardiograms were visually interpreted at baseline, during adenosine infusion, and during the recovery period. The stress electrocardiogram was considered positive if there was > or =1 mm additional horizontal or downsloping ST-segment depression or elevation 0.08 seconds after the J-point compared with the baseline tracing. RESULTS: ST-segment depression and/or elevation occurred in 24 of 99 patients. There were only 2 false-positive stress electrocardiograms, yielding a specificity of 87% and positive predictive value of 92%. All 8 patients with > or =2 mm ST segment depression had multivessel disease by coronary angiography. CONCLUSIONS: ST-segment depression or elevation during adenosine myocardial perfusion imaging in patients taking digoxin is highly specific for coronary artery disease. Marked (> or =2 mm) ST-segment depression and/or ST-segment elevation is associated with a high likelihood of multivessel disease.

Adenosine↗