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Biomedical subjects

R J Gibbons

Publications and source records attributed to R J Gibbons.

At least 55 records · Page 3Linked to original sources
PubMed2000

The impact of time to thrombolytic treatment on outcome in patients with acute myocardial infarction. For the CORE investigators (Collaborative Organisation for RheothRx Evaluation).

OBJECTIVES: To examine the impact of time to thrombolytic treatment on multiple acute outcome variables in a single trial of thrombolysis in acute myocardial infarction. DESIGN AND PATIENTS: Mortality and reinfarction rate were measured in 2770 patients with acute myocardial infarction who received thrombolysis within 12 hours in CORE, an international, dose ranging trial of poloxamer 188. Tc-99m sestamibi infarct size and radionuclide angiographic ejection fraction substudies included 1099 and 1074 patients, respectively. RESULTS: Time to thrombolysis, subgrouped by intervals (< 2, 2-4, > or = 4-6, and > or = 6 hours), was significantly associated with infarct size (median 15.0%, 18.5%, 22.0%, 18.5% of left ventricle; p = 0.033), mean (SD) ejection fraction (51.5 (12.0)%, 48. 3 (13.9)%, 48.2 (13.3)%, 48.2 (15.0)%; p = 0.006), 35 day mortality (5.7%, 7.1%, 7.9%, 12.5%; p = 0.0004), six month mortality (7.3%, 8. 6%, 10.4%, 15.5%; p < 0.0001), and 35 day reinfarction rate (6.1%, 3. 2%, 4.0%, 0.9%; p = 0.0001). CONCLUSIONS: In this single large trial, the beneficial effect of time to thrombolysis on infarct size and ejection fraction was restricted to treatment given within two hours of symptom onset, while the effect on mortality was evident over all time intervals. Reinfarction rate was higher in patients treated with earlier thrombolysis.

Humans↗
PubMed2000

Is rest or exercise hypertension a cause of a false-positive exercise test?

STUDY OBJECTIVES: To determine if a history of hypertension or an exaggerated rise in exercise systolic BP is associated with a false-positive exercise ECG. DESIGN, SETTING, AND PATIENTS: Retrospective analysis of the associations between exercise-induced ST-segment depression and a history of hypertension, exercise systolic BP, and several other clinical and exercise test variables. Among 20,097 patients referred for exercise tomographic thallium imaging in a nuclear cardiology laboratory at a tertiary care center, 1,873 patients met inclusion criteria for this study, which included no history of myocardial infarction or coronary artery revascularization, a normal resting ECG, and normal exercise thallium images. RESULTS: False-positive ST-segment depression occurred in 20% of the population. A history of hypertension was actually associated with a lower likelihood of ST-segment depression (odds ratio, 0.70; 95% confidence interval [CI], 0.55 to 0.89; p = 0. 004). A higher peak exercise systolic BP was associated with a higher likelihood of ST-segment depression (odds ratio, 1.08 for each 10-mm Hg increase in systolic BP; 95% CI, 1.03 to 1.14; p < 0. 001). However, the association between peak exercise systolic BP and ST-segment depression was so weak that this measurement could not be predictive in the individual patient (R(2) = 0.2%). For every 20-mm Hg increase in peak exercise systolic BP, the percentage of patients with ST-segment depression increased by only 3%. CONCLUSIONS: In patients with normal resting ECGs, we conclude the following: (1) a history of hypertension is not a cause of a false-positive exercise test, and (2) higher exercise systolic BP is a significant but weak predictor of ST-segment depression.

Blood Pressure↗
PubMed2000

A nonsense mutation of the ATRX gene causing mild mental retardation and epilepsy.

Mutations in the X-encoded gene ATRX are known to give rise to profound syndromal mental retardation (MR). Here, we describe a pedigree, including 4 affected family members with a 324C-->T nonsense mutation in the ATRX gene. Although 2 patients have moderate to profound MR and the typical facial features of ATR-X syndrome, the other 2 patients presented with mild MR and epilepsy but without the characteristic facial dysmorphism. Mutations in the ATRX gene should be considered as a cause of mild MR in male patients lacking specific diagnostic features.

Adolescent↗
PubMed2000

Assessment of infarct size and severity by quantitative myocardial SPECT: results from a multicenter study using a cardiac phantom.

UNLABELLED: The aim of this study was to determine the reproducibility of measurements of the size and severity of myocardial defects from 99mTc sestamibi cardiac phantom studies performed on multiple different gamma camera systems. METHODS: A total of 250 gamma camera systems were evaluated over a 5-y period as part of the validation process of multiple multicenter trials. Each laboratory performed 9 acquisitions of a cardiac phantom. Small myocardial defects (0%-30% of myocardial mass) were placed in the inferobasal region, whereas larger defects (40%-70%) were located in the anterior wall. Five representative short-axis slices were analyzed to determine defect size and severity (i.e., contrast in defect region) using circumferential short-axis count profiles. Defect size and severity were analyzed as a function of the type of collimator, gamma camera system, and type of orbit (180degrees versus 360degrees). RESULTS: Of the 250 systems, image data were acquired correctly and showed an acceptable correlation between true and measured defect size in 198 systems. For these systems, the slope of the regression line between true and measured defect size was 1.03 +/- 0.03, with an average absolute error in estimating defect size of 1.7% +/- 0.5% and a correlation coefficient r = 0.99 +/- 0.01. Results were independent of the gamma camera system, type of collimator, and orbit. Contrast in the defect region (minimum count/maximum count) showed a small dependence on collimator resolution and pixel size but was altered significantly by the type of acquisition orbit, with a 360 degrees orbit showing better contrast for defects located in the inferobasal wall than a 180degrees orbit. CONCLUSION: Measurement of defect size is independent of the gamma camera system, type of collimator, and orbit. Contrast in small defects located in the inferobasal wall of the heart is affected significantly by the type of acquisition orbit but not by the type of collimator.

Gamma Cameras↗
PubMed1999

Threshold values for preserved viability with a noninvasive measurement of collateral blood flow during acute myocardial infarction treated by direct coronary angioplasty.

BACKGROUND: Quantitative measures of myocardial perfusion defect severity from acute (99m)Tc-sestamibi tomographic images (nadir) have correlated closely with collateral and residual antegrade blood flow during acute myocardial infarction. The purpose of this study was to determine whether a viability threshold could be identified from this measure in patients with acute myocardial infarction treated in a homogeneous manner with successful reperfusion therapy. METHOD AND RESULTS: The study group consisted of 61 patients with acute myocardial infarction with a risk area of >6% LV treated with primary angioplasty between 120 and 240 minutes after symptom onset. All patients were injected with 20 to 30 mCi of (99m)Tc-sestamibi before primary angioplasty and imaged after the procedure. Acute myocardium at risk (MAR) and subsequent infarct size (IS) were quantified by a threshold program. Severity (nadir) from the acute image was the lowest ratio of minimal/maximum counts from 5 short-axis slices. Infarct location was anterior in 22 and inferior in 39 patients. MAR was 33+/-15% LV and IS was 13+/-15% LV: 23 patients had no infarction despite MAR similar to those with infarction. Receiver-operator characteristic curve analysis identified a nadir value of 0.26 as providing the best separation of patients with and without infarction (sensitivity, 74%; specificity, 74%). This nadir threshold varied by infarct location: anterior defect, 0.21; inferior defect, 0.31. The sensitivity and specificity for absent infarction for these values were anterior, 69% and 67%, and inferior, 88% and 84%, respectively. CONCLUSIONS: In a time frame in which the presence of residual blood flow is important, the severity of the acute (99m)Tc-sestamibi defect can be used to predict whether infarction will develop despite successful reperfusion.

Aged↗
PubMed1999

Long-term prognostic value of Duke treadmill score and exercise thallium-201 imaging performed one to three years after percutaneous transluminal coronary angioplasty.

The value of exercise nuclear perfusion imaging performed beyond the 6-month restenosis window for percutaneous transluminal coronary angioplasty (PTCA) has not been explored. This study evaluates the long-term prognostic value of exercise thallium (Tl)-201 imaging after PTCA. We studied the late outcome of a series of 211 patients with tomographic Tl-201 exercise studies performed between 1 to 3 years after PTCA. Follow-up was 96% complete at a median duration of 7.3 years. Most (73%) had 1- or 2-vessel coronary artery disease and normal left ventricular function and 193 (91%) had successful PTCA. Two thirds of the patients were symptomatic at the time of testing. The mean Duke score was 5+/-6 and 125 (60%) patients had a low-risk Duke score. Mean summed stress score was 50+/-9 and mean summed reversibility score was 3+/-4. The 5-year overall survival was 95%, yielding a low annual mortality rate of 1%/year. The summed stress score exhibited a significant association (p = 0.047) with the end point of cardiac death or myocardial infarction. The Duke score was predictive of the combination end point of hard and soft cardiac events (p = 0.002). This study demonstrates that exercise Tl-201 perfusion imaging performed 1 to 3 years after PTCA was predictive of cardiac events.

Angioplasty, Balloon, Coronary↗
PubMed1999

Localization of a putative transcriptional regulator (ATRX) at pericentromeric heterochromatin and the short arms of acrocentric chromosomes.

ATRX is a member of the SNF2 family of helicase/ATPases that is thought to regulate gene expression via an effect on chromatin structure and/or function. Mutations in the hATRX gene cause severe syndromal mental retardation associated with alpha-thalassemia. Using indirect immunofluorescence and confocal microscopy we have shown that ATRX protein is associated with pericentromeric heterochromatin during interphase and mitosis. By coimmunofluorescence, ATRX localizes with a mouse homologue of the Drosophila heterochromatic protein HP1 in vivo, consistent with a previous two-hybrid screen identifying this interaction. From the analysis of a trap assay for nuclear proteins, we have shown that the localization of ATRX to heterochromatin is encoded by its N-terminal region, which contains a conserved plant homeodomain-like finger and a coiled-coil domain. In addition to its association with heterochromatin, at metaphase ATRX clearly binds to the short arms of human acrocentric chromosomes, where the arrays of ribosomal DNA are located. The unexpected association of a putative transcriptional regulator with highly repetitive DNA provides a potential explanation for the variability in phenotype of patients with identical mutations in the ATRX gene.

Animals↗
PubMed1999

Long-term outcome of patients with intermediate-risk exercise electrocardiograms who do not have myocardial perfusion defects on radionuclide imaging.

BACKGROUND: The appropriate management of patients with intermediate-risk Duke treadmill scores is not established. The purpose of this study was to determine the long-term risk of subsequent cardiovascular events in patients with an intermediate-risk treadmill score who do not have myocardial perfusion defects on radionuclide imaging. METHODS AND RESULTS: The existing databases of the nuclear cardiology laboratories of 4 academic institutions were searched retrospectively. A total of 4649 patients were identified who had intermediate-risk Duke treadmill scores (-10 to 4), normal or near-normal exercise single photon-emission computed tomographic myocardial perfusion images using either thallium-201 or technetium-99m sestamibi, and no previous coronary revascularization. Follow-up was 95% complete. Cardiovascular survival was 99.8% at 1 year, 99.0% at 5 years, and 98.5% at 7 years. Cardiac survival free of myocardial infarction was similarly high at 96.6% at 7 years. Cardiac survival free of myocardial infarction or revascularization was 87.1% at 7 years. Near-normal scans and cardiac enlargement were independent predictors of time to cardiac death. Seven-year cardiac survival was still high at 97.0% in the 357 patients with near-normal scans and normal cardiac size and somewhat lower, at 89.0%, in the 167 patients with cardiac enlargement. CONCLUSIONS: Patients with an intermediate-risk treadmill score but with normal or near-normal exercise myocardial perfusion images and normal cardiac sizes are at low risk for subsequent cardiac death and can be safely managed medically until their symptoms warrant revascularization. The appropriate management of patients with cardiac enlargement will remain a matter of clinical judgment.

Adult↗
PubMed1999

Comparison of acute myocardial infarct size to two-year mortality in patients <65 to those > or =65 years of age.

Older patients have higher in-hospital and longer term mortality after myocardial infarction. To determine if larger infarct size correlates with this observation, myocardium at risk was measured on arrival to the hospital in 347 patients with acute myocardial infarction, and final infarct size was measured at hospital discharge in a subset of 274 of these patients. Myocardium at risk and final infarct size were quantified by tomographic technetium-99m sestamibi imaging. Statistical analyses examined the associations between age, myocardium at risk, final infarct size, and both in-hospital and postdischarge mortality. Median value for age was 64 years, and myocardium at risk was 24% and final infarct size was 12% of the left ventricle. There was no correlation between age and myocardium at risk (r = 0.04, p = NS) or final infarct size (r = 0.06, p = NS). In-hospital mortality was 4% overall and was 2% for patients <65 years old versus 6% for those > or =65 years old (chi-square 11.3, p<0.001). In-hospital mortality was not associated with myocardium at risk (chi square <1, p = NS). For the subset of 274 patients in whom final infarct size was measured, the subsequent 2-year mortality rate was 3% and was independently associated with both age (chi-square 15.6, p<0.001) and final infarct size (chi-square 9.7, p = 0.002). Survival was excellent for patients who were either <65 years old (2-year mortality 1%) or had an infarct size <12% (2-year mortality 0%). For patients > or =65 years old with infarct size > or =12%, 2-year mortality was 13%. These results demonstrate that older patients do not have larger infarcts. Advanced age is associated with higher in-hospital and postdischarge mortality, independent of infarct size.

Adult↗
PubMed1999

Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: results of a multicenter, randomized, placebo-controlled trial: the Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial.

OBJECTIVES: The Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial was designed to test the hypothesis that adenosine as an adjunct to thrombolysis would reduce myocardial infarct size. BACKGROUND: Reperfusion therapy for acute myocardial infarction (MI) has been shown to reduce mortality, but reperfusion itself also may have deleterious effects. METHODS: The AMISTAD trial was a prospective, open-label trial of thrombolysis with randomization to adenosine or placebo in 236 patients within 6 h of infarction onset. The primary end point was infarct size as determined by Tc-99 m sestamibi single-photon emission computed tomography (SPECT) imaging 6+/-1 days after enrollment based on multivariable regression modeling to adjust for covariates. Secondary end points were myocardial salvage index and a composite of in-hospital clinical outcomes (death, reinfarction, shock, congestive heart failure or stroke). RESULTS: In all, 236 patients were enrolled. Final infarct size was assessed in 197 (83%) patients. There was a 33% relative reduction in infarct size (p = 0.03) with adenosine. There was a 67% relative reduction in infarct size in patients with anterior infarction (15% in the adenosine group vs. 45.5% in the placebo group) but no reduction in patients with infarcts located elsewhere (11.5% for both groups). Patients randomized to adenosine tended to reach the composite clinical end point more often than those assigned to placebo (22% vs. 16%; odds ratio, 1.43; 95% confidence interval, 0.71 to 2.89). CONCLUSIONS: Many agents thought to attenuate reperfusion injury have been unsuccessful in clinical investigation. In this study, adenosine resulted in a significant reduction in infarct size. These data support the need for a large clinical outcome trial.

Adenosine↗
PubMed1999

Prognostic value of a treadmill exercise score in symptomatic patients with nonspecific ST-T abnormalities on resting ECG.

CONTEXT: Exercise testing of patients with ST-T abnormalities on the resting electrocardiogram (ECG) is problematic because in the presence of pre-existing ST-T abnormalities, the exercise test is less specific for the diagnosis of coronary artery disease. The prognostic capability of the Duke treadmill score in patients with ST-T abnormalities vs those with normal findings on resting ECG has, to our knowledge, not been evaluated. OBJECTIVE: To compare the prognostic accuracy of the Duke treadmill score in patients with nonspecific ST-T abnormalities vs those with normal results on resting ECG. DESIGN: Inception cohort study with 7 years of follow-up. SETTING: Nuclear cardiology laboratory of a US referral center. PATIENTS: All symptomatic patients who underwent exercise thallium testing between 1989 and 1991,939 of whom had nonspecific ST-T abnormalities and 1466 of whom had normal findings on resting ECG. Exclusion criteria included congenital, valvular, or cardiomyopathic heart disease; prior coronary artery revascularization; resting ECG with secondary ST-T abnormalities; or missing data. MAIN OUTCOME MEASURES: Rates of overall mortality and cardiac death for subjects classified by Duke treadmill score risk group. RESULTS: For the end point cardiac death, 7-year survival in the study population in the low-, intermediate-, and high-risk groups was 97%, 92%, and 76%, respectively (P<.001). Compared with the control group, the study group had lower 7-year survival (94% vs 98%; P<.001), fewer low-risk patients (426 [45%] vs 811 [55%]; P<.001) with worse 7-year survival (97% vs 99%; P= .008), and more high-risk patients (49 [5%] vs 34 [2%];P<.001) with a nonsignificant trend toward worse 7-year survival (76% vs 93%; P= .36). CONCLUSIONS: The Duke treadmill score can effectively risk-stratify patients with ST-T abnormalities on the resting ECG. In classified risk categories, patients with ST-T abnormalities have a worse prognosis than those with normal results on resting ECG.

Aged↗
PubMed1999

Determinants of infarct size after thrombolytic treatment in acute myocardial infarction.

Both experimental and single-center clinical studies have shown that myocardium at risk, residual collateral flow, and duration of coronary occlusion are important determinants of final infarct size. The purpose of this study was to replicate these results on a multicenter basis to demonstrate that perfusion imaging using different camera and computer systems can provide reliable assessments of myocardium at risk and collateral flow. Sequential tomographic myocardial perfusion imaging with technetium-99 (Tc-99m) sestamibi was performed in 74 patients with first time myocardial infarction, who were enrolled in a multicenter, randomized, double-blind, placebo-controlled pilot study of poloxamer 188 as ancillary therapy to thrombolysis. All patients underwent thrombolysis within 6 hours of the onset of chest pain. Tc-99m sestamibi was injected intravenously at the initiation of thrombolytic therapy, and tomographic imaging was performed 1 to 6 hours later to assess myocardium at risk. Collateral flow was estimated noninvasively from the acute sestamibi images by 3 methods that assess the severity of the perfusion defect. Final infarct size was determined at hospital discharge by a second sestamibi study. Myocardium at risk (r = 0.61, p <0.0001) and radionuclide estimates of collateral flow (r = 0.58 to 0.66, all p <0.0001) were significantly associated with final infarct size. These associations were independent of the treatment center. On a multivariate basis, myocardium at risk (p = 0.003), the radionuclide estimate of collateral flow (p = 0.03), and treatment arm (p = 0.04) were all independent determinants of infarct size. Time to thrombolytic therapy showed only a trend (p = 0.10). The treatment center was not significant (p = 0.42). Myocardium at risk and collateral flow are important determinants of infarct size that are independent of treatment center. Tomographic imaging with Tc-99m sestamibi can provide noninvasive assessments of these parameters in multicenter trials of thrombolytic therapy.

Adult↗