[Show abstract][Hide abstract] ABSTRACT: Iterative reconstruction techniques for coronary CT angiography have been introduced as an alternative for traditional filter back projection (FBP) to reduce image noise, allowing improved image quality and a potential for dose reduction. However, the impact of iterative reconstruction on the coronary artery calcium score is not fully known. In 112 consecutive stable patients with suspected coronary artery disease, the coronary calcium scores were assessed. Comparisons were made between the Agatston, volume and mass scores obtained with traditional FBP, and by using adaptive statistical iterative reconstruction (ASIR). A significant reduction of the Agatston score, volume score and mass score was observed for ASIR when compared to FBP, with median differences of resp. 26, 5 mm(3) and 1 mg. Using the ASIR reconstruction, the number of patients with a calcium score of zero increased by 13 %. Iterative CT reconstruction significantly reduces the Agatston, volume and mass scores. Since the calcium score is used as a prognostic tool for coronary artery disease, caution must be taken when using iterative reconstruction.
The international journal of cardiovascular imaging 03/2014; 30(5). DOI:10.1007/s10554-014-0409-9 · 1.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Coronary artery calcium (CAC) scores influence the pre-test likelihood of ischemia in patients undergoing myocardial perfusion imaging (MPI). We investigated the influence of CAC score knowledge on the visual interpretation of MPI in patients referred for the diagnostic work-up of suspected coronary artery disease.
We retrospectively analyzed symptomatic patients who were referred for MPI. For the current analysis, we selected 151 patients who underwent SPECT MPI with simultaneous CAC scoring. MPI was visually interpreted in two separate sessions, first without and then with knowledge of the CAC score. MPI results were classified into four groups: normal, fixed defects, ischemia, and equivocal.
Mean age of the patients was 64 ± 11 years, 56 % were male. Without knowledge of the CAC score MPI was evaluated as normal in 36 %, compared to 40 % with knowledge of the CAC score (P = 0.636). Overall, the addition of the CAC score changed the interpretation of MPI in 56 patients (37 %). Importantly, the frequency of equivocal MPI interpretations decreased from 21 % without knowledge of CAC score to 9 % with knowledge of CAC score (P = 0.002).
Knowledge of the CAC score has a major impact on the interpretation of MPI, increasing the interpretative certainty.
[Show abstract][Hide abstract] ABSTRACT: Recently introduced ultrafast cardiac SPECT cameras with cadmium zinc telluride-based (CZT) detectors may provide superior image quality allowing faster acquisition with reduced radiation doses. Although the level of concordance between conventional SPECT and invasive fractional flow reserve (FFR) measurement has been studied, that between FFR and CZT-based SPECT is not yet known. Therefore, we aimed to assess the level of concordance between CZT SPECT and FFR in a large patient group with stable coronary artery disease.
Both invasive FFR and myocardial perfusion imaging with a CZT-based SPECT camera, using Tc-tetrofosmin as tracer, were performed in 100 patients with stable angina and intermediate grade stenosis on invasive coronary angiography. A cut-off value of <0.75 was used to define abnormal FFR.
The mean age of the patients was 64 ± 11 years, and 64 % were men. SPECT demonstrated ischaemia in 31 % of the patients, and 20 % had FFR <0.75. The concordance between CZT SPECT and FFR was 73 % on a per-patient basis and 79 % on a per-vessel basis. Discordant findings were more often seen in older patients and were mainly (19 %) the result of ischaemic SPECT findings in patients with FFR ≥0.75, whereas only 8 % had an abnormal FFR without ischaemia as demonstrated by CZT SPECT.
Only 20 - 30 % of patients with intermediate coronary stenoses had significant ischaemia as assessed by CZT SPECT or invasive FFR. CZT SPECT showed a modest degree of concordance with FFR, which is comparable with previous results with conventional SPECT. Further investigations are particularly necessary in patients with normal SPECT and abnormal FFR, especially to determine whether these patients should undergo revascularization.
European Journal of Nuclear Medicine 12/2013; 41(5). DOI:10.1007/s00259-013-2630-5 · 5.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: High coronary artery calcium (CAC) scores are associated with a high likelihood of ischaemia and obstructive coronary disease. Myocardial perfusion imaging (MPI) is a key investigation to determine the need for revascularization. However, the value of MPI in presence of extensive CAC has so far only been demonstrated in asymptomatic patients, whereas its value in symptomatic patients remains largely unclear. Therefore, we studied the impact of MPI in symptomatic patients with a CAC score ≥1,000.
We included 282 patients (mean age 69 ± 9 years, 63 % men) without a history of coronary disease with suspected stable angina referred for MPI and with a CAC score ≥1,000. On follow-up at 18 months invasive angiography, coronary revascularization, nonfatal myocardial infarction and death were recorded.
MPI was normal in 54 %, equivocal in 10 % and abnormal in 37 % (fixed defect 9 % and ischaemia 28 %) of patients. More abnormal MPI findings were observed in men, smokers and those with even higher CAC scores. During follow-up, 1 patient (with nonischaemic MPI) died from a cardiac cause, 1 patient (with ischaemic MPI) suffered a myocardial infarction and 92 patients (33 %) underwent revascularization. Ischaemia on MPI was a strong predictor of coronary revascularization (odds ratio 13.1; 95 % CI 7.1-24.3; p < 0.001).
Ischaemia on MPI is observed in approximately 30 % of patients with a CAC score ≥1,000, and is a strong predictor of coronary revascularization. However, nonischaemic MPI does not exclude revascularization, and patients with persisting complaints should be considered for invasive angiography.
European Journal of Nuclear Medicine 08/2013; 41(1). DOI:10.1007/s00259-013-2539-z · 5.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To assess the capability of a zero coronary artery calcium (CAC) score to help exclude flow-limiting coronary artery disease (CAD) in a homogeneous population with stable anginal complaints and a low-to-intermediate pretest likelihood.
Materials and methods:
The study protocol had institutional ethics committee approval, with written informed consent from all patients. Between 2009 and 2011, a total of 3501 consecutive stable patients without known CAD underwent prospectively simultaneous myocardial perfusion imaging and CAC scoring on a hybrid, 64-section single photon emission computed tomography (SPECT)/computed tomography (CT) scanner. In 868 (25%) of 3501 patients, the CAC score was zero, and these patients constituted the current study population. When feasible, additional coronary CT angiography was performed in those with abnormal SPECT findings. Clinical follow-up was recorded with regard to invasive coronary angiography, coronary revascularization, nonfatal myocardial infarction, or death. Results were analyzed by using descriptive statistics.
In 868 patients (mean age, 54 years ± 11 [standard deviation]; 610 [70%] female, 258 [30%] male), SPECT findings were normal in 766 (88%) and abnormal in 102 (12%), with equivocal results in 41 (5%), persistent defect in 35 (4%), and ischemia in 26 (3%). In the group with abnormal SPECT findings, additional coronary CT angiography was performed in 93 patients (91%), showing nonobstructive CAD in eight patients (9%) and normal coronary arteries in 85 patients (91%). In the other nine patients (9%), invasive angiography was used to exclude obstructive CAD. At a median follow-up of 17 months (25th percentile, 11; 75th percentile, 24 months), no coronary events were recorded.
A CAC score of zero in stable patients at low or intermediate risk excludes flow-limiting CAD. These findings support the possibility of CAC scoring as a simple and safe tool to select patients for additional testing or discharge, as recommended in the literature.
[Show abstract][Hide abstract] ABSTRACT: The new ultrafast cardiac single photon emission computed tomography (SPECT) cameras with cadmium-zinc-telluride (CZT)-based detectors are faster and produce higher quality images as compared to conventional SPECT cameras. We assessed the need for additional imaging, total imaging time, tracer dose and 1-year outcome between patients scanned with the CZT camera and a conventional SPECT camera.
A total of 456 consecutive stable patients without known coronary artery disease underwent myocardial perfusion imaging on a hybrid SPECT/CT (64-slice) scanner using either conventional (n = 225) or CZT SPECT (n = 231). All patients started with low-dose stress imaging, combined with coronary calcium scoring. Rest imaging was only done when initial stress SPECT testing was equivocal or abnormal. Coronary CT angiography was subsequently performed in cases of ischaemic or equivocal SPECT findings. Furthermore, 1-year clinical follow-up was obtained with regard to coronary revascularization, nonfatal myocardial infarction or death.
Baseline characteristics were comparable between the two groups. With the CZT camera, the need for rest imaging (35 vs 56%, p < 0.001) and additional coronary CT angiography (20 vs 28%, p = 0.025) was significantly lower as compared with the conventional camera. This resulted in a lower mean total administered isotope dose per patient (658 ± 390 vs 840 ± 421 MBq, p < 0.001) and shorter imaging time (6.39 ± 1.91 vs 20.40 ± 7.46 min, p < 0.001) with the CZT camera. After 1 year, clinical outcome was comparable between the two groups.
As compared to images on a conventional SPECT camera, stress myocardial perfusion images acquired on a CZT camera are more frequently interpreted as normal with identical clinical outcome after 1-year follow-up. This lowers the need for additional testing, results in lower mean radiation dose and shortens imaging time.
European Journal of Nuclear Medicine 03/2012; 39(6):1048-55. DOI:10.1007/s00259-012-2086-z · 5.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Myocardial necrosis is a time-dependent event. Nevertheless, clinical studies on association between ischemic time and left ventricle function showed inconsistent findings. Aim of current study is to evaluate the association between ischemic time and the post-infarction left ventricular function in ST-elevation myocardial infarction treated with primary PCI. METHODS: In 2529 patients treated with primary PCI, left ventricular ejection fraction (LVEF) was measured before discharge (median day 4) by radionuclide ventriculography or by echocardiography if patients had atrial fibrillation. Ischemic time was calculated from symptom onset to first balloon inflation. RESULTS: The correlation between ischemic time as continuous variable and LVEF was significant but weak (P=0.002, r=-0.062). The LVEF of patients in ischemic time intervals of >6, >3-6, and ≤3h was 45.1±11.7%, 44.6±11.9%, and 43.2±12.2%, respectively (P=0.029). Adjusted odds ratio of the ischemic time intervals for LVEF<40% was 1.14 (95% CI 1.00-1.30). TIMI flow 0 before and TIMI flow 3 after PCI were related with both longer ischemic time and low LVEF. CONCLUSION: Ischemic time was associated with post infarction LVEF in patients treated with primary PCI, although this association was weak. Initial TIMI flow and post-PCI TIMI flow played important role in impact of the ischemic time on the LVEF.
International journal of cardiology 10/2011; 165(3). DOI:10.1016/j.ijcard.2011.09.082 · 4.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the present study we sought to determine the long-term prognostic value of left ventricular ejection fraction (LVEF), assessed by planar radionuclide ventriculography (PRV), after ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI).
In total 925 patients underwent PRV for LVEF assessment after PPCI for myocardial infarction before discharge from the hospital. PRV was performed with a standard dose of 500 Mbq of 99mTc-pertechnetate. Average follow-up time was 2.5 years.
Mean (+/- SD) age was 60 +/- 12 years. Mean (+/- SD) LVEF was 45.7 +/- 12.2 %. 1 year survival was 97.3 % and 3 year survival was 94.2 %. Killip class, multi vessel-disease, previous cardiovascular events, peak creatin kinase and its MB fraction, age and LVEF proved to be univariate predictors of mortality. When entered in a forward conditional Cox regression model age and LVEF were independent predictors of 1 and 3 year mortality.
LVEF assessed by PRV is a powerful independent predictor of long term mortality after PPCI for STEMI.
[Show abstract][Hide abstract] ABSTRACT: Decreased left ventricular (LV) function is a strong predictor of mortality. Although current guidelines recommend prophylactic implantable cardioverter-defibrillator (ICD) implantation after ST-elevation myocardial infarction and a depressed LV ejection fraction for 1 month, the prognoses of these patients may be better than those observed in randomized trials of ICDs (1-year mortality 6.8% to 19%), particularly because reperfusion treatment has improved, and the use of life-saving drugs is higher. To assess 1-year mortality in patients with depressed LV ejection fractions after primary percutaneous coronary intervention, a prospective, observational study was performed. Data from all patients who survived >/=30 days after primary percutaneous coronary intervention and had LV ejection fractions </=30% from 1994 to 2004 were recorded. Of 2,544 patients, 342 (13%) had LV ejection fractions </=30%. One-year mortality was 5.8%. Sudden death was the most common cause of death (40%). Patients who died more often had multivessel disease and a higher incidence of recurrent myocardial infarction within 1 year. In conclusion, current mortality in patients with depressed LV ejection fractions after primary percutaneous coronary intervention is much better than that observed in previous ICD trials, and the benefits of ICD therapy in these patients should be further evaluated.
The American Journal of Cardiology 09/2007; 100(5):793-7. DOI:10.1016/j.amjcard.2007.03.101 · 3.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Favorable clinical outcomes have been observed with glucose-insulin-potassium infusion (GIK) in acute myocardial infarction (MI). The mechanisms of this beneficial effect have not been delineated clearly. GIK has metabolic, anti-inflammatory and profibrinolytic effects and it may preserve the ischemic myocardium. We sought to assess the effect of GIK infusion on infarct size and left ventricular function, as part of a randomized controlled trial.
Patients (n = 940) treated for acute MI by primary percutaneous coronary intervention (PCI) were randomized to GIK infusion or no infusion. Endpoints were the creatinine kinase MB-fraction (CK-MB) and left ventricular ejection fraction (LVEF). CK-MB levels were determined 0, 2, 4, 6, 24, 48, 72 and 96 hours after admission and the LVEF was measured before discharge.
There were no differences between the two groups in the time course or magnitude of CK-MB release: the peak CK-MB level was 249 +/- 228 U/L in the GIK group and 240 +/- 200 U/L in the control group (NS). The mean LVEF was 43.7 +/- 11.0 % in the GIK group and 42.4 +/- 11.7% in the control group (P = 0.12). A LVEF < or = 30% was observed in 18% in the controls and in 12% of the GIK group (P = 0.01).
Treatment with GIK has no effect on myocardial function as determined by LVEF and by the pattern or magnitude of enzyme release. However, left ventricular function was preserved in GIK treated patients.
BMC Medicine 06/2005; 3(1):9. DOI:10.1186/1741-7015-3-9 · 7.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In patients with acute myocardial infarction, estimation of infarct size by cumulative lactate dehydrogenase release at 72 h (LDHQ(72)) is a simple and widely used method. Our objective was to study the value of estimating infarct size, by the cumulative release of LDH over 72, 60, 48 and 36 h in predicting left ventricular ejection fraction (LV(ef)) and cardiac death at 1 year.
In the Zwolle Infarction Study infarct size estimated as LDHQ was calculated in 1224 patients treated with primary percutaneous coronary intervention for acute myocardial infarction between December 1993 and June 2001. Patients were categorized as having small (LDHQ(72)<800 U/L), medium (LDHQ(72) 800-2500 U/L) or large (LDHQ(72)>2500 U/L) myocardial infarction.
LDHQ(72) was closely correlated with LDHQ(60), LDHQ(48) and LDHQ(36) (r = 0.998, 0.993 and 0.987, respectively, P <0.0001). The relations between LDHQ infarct size classification and mean LV(ef) (51% vs 45% vs 35%, P <0.001) or cardiac death at 1 year (0-0.3% vs 0.7-1% vs 6-8%) showed a similar pattern, irrespective of whether LDH was measured up to 36, 48, 60 or 72 h.
Infarct size classification based on LDHQ(36) is an objective and widely available method for early risk stratification in patients treated with primary angioplasty for acute ST-segment elevation myocardial infarction.
[Show abstract][Hide abstract] ABSTRACT: Preinfarction angina is associated with reduced myocardial infarct size in patients treated with thrombolysis. Our objective was to assess the relation between preinfarction angina and infarct size, left ventricular function and clinical outcome in patients treated with primary angioplasty (PTCA) and compare this with patients treated with thrombolysis.
In the Zwolle Infarction Study, 953 patients were treated for acute myocardial infarction between 1990 and 1996; 761 patients underwent primary PTCA and 192 patients received thrombolysis as reperfusion therapy.
Preinfarction angina was present in about 50% of the patients, who were categorised into angina ≤24 hours and angina >24 hours before infarction. Patients in both treatment groups have a longer ischaemic time when preinfarction angina is present. In patients treated with thrombolysis, preinfarction angina ≤24 hours results in a smaller enzymatic infarct. Thrombolysis seems to be more effective when preinfarction angina occurs within the 24 hours prior to myocardial infarction. Collateral filling of the infarct-related artery is more often seen in patients with preinfarction angina. In the primary PTCA group, a longer ischaemic time in patients with preinfarction angina does not result in increased infarct size, and this effect remains after excluding patients with collateral filling.
The protective effect of preinfarction angina is likely to be due to better collateral filling of the infarct-related artery and to ischaemic preconditioning of the myocardium.
[Show abstract][Hide abstract] ABSTRACT: To compare long-term clinical outcome after acute myocardial infarction treated with primary coronary angioplasty or thrombolytic therapy, and to study the determinants of survival.
Primary coronary angioplasty results in a higher patency rate and a better short-term survival when compared with thrombolytic therapy, but so far limited information has been available regarding long-term clinical outcome.
Patients with acute myocardial infarction (n=395) were randomised to treatment with either intravenous streptokinase or primary angioplasty, and were followed for up to eight years.
A total of 105 patients died, 42 patients in the primary coronary angioplasty group compared with 63 patients in the streptokinase group (p=0.03). Death and nonfatal reinfarction occurred in 53 patients in the angioplasty group, compared with 94 patients in the streptokinase group (p<0.001). The major cause of long-term mortality is sudden death. Multivariate analysis showed that left ventricular function was the most important predictor for both total mortality and sudden death.
The benefits of primary coronary angioplasty compared with streptokinase are well sustained during long-term follow-up.
[Show abstract][Hide abstract] ABSTRACT: To investigate changes in left ventricular function in the first 6 months after acute myocardial infarction treated with primary angioplasty. To assess clinical variables, associated with recovery of left ventricular function after acute myocardial infarction.
Changes in left ventricular function were studied in 600 consecutive patients with acute myocardial infarction, all treated with primary angioplasty. Left ventricular ejection fraction was measured by radionuclide ventriculography in survivors at day 4 and after 6 months. Patients with a recurrent myocardial infarction within the 6 months were excluded.
Successful reperfusion (TIMI 3 flow) by primary angioplasty was achieved in 89% of patients. The mean ejection fraction at discharge was 43.7%+/-11.4, whereas the mean ejection fraction after 6 months was 46.3%+/-11.5 (P<0.01). During the 6 months, the mean relative improvement in left ventricular ejection fraction was 6%. An improvement in left ventricular function was observed in 48% of the patients; 25% of the patients had a decrease, whereas in the remaining patients there was no change. After univariate and multivariate analysis, an anterior infarction location, an ejection fraction at discharge < or =40% and single-vessel disease were significant predictors of left ventricular improvement during the 6 months.
After acute myocardial infarction treated with primary angioplasty there was a significant recovery of left ventricular function during the first 6 months after the infarction. An anterior myocardial infarction, single-vessel coronary artery disease, and an initially depressed left ventricular function were independently associated with recovery of left ventricular function. Multivessel disease was associated with absence of functional recovery. Additional studies, investigating complete revascularization are needed, as this approach may potentially improve long-term left ventricular function.
European Heart Journal 05/2001; 22(9):785-90. DOI:10.1053/euhj.2000.2316 · 15.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: As compared with thrombolytic therapy, primary coronary angioplasty results in a higher rate of patency of the infarct-related coronary artery, lower rates of stroke and reinfarction, and higher in- hospital or 30-day survival rates. However, the comparative long-term efficacy of these two approaches has not been carefully studied. Methods: We randomly assigned a total of 395 patients with acute myocardial infarction to treatment with angioplasty or intravenous streptokinase. Clinical information was collected for a mean (±SD) of 5±2 years, and medical charges associated with the two treatments were compared. Results: A total of 194 patients were assigned to undergo primary angioplasty, and 201 to receive streptokinase. Mortality was 13 percent in the angioplasty group, as compared with 24 percent in the streptokinase group (relative risk, 0.54; 95 percent confidence interval, 0.36 to 0.87). Nonfatal reinfarction occurred in 6 percent and 22 percent of the two groups, respectively (relative risk, 0.27; 95 percent confidence interval, 0.15 to 0.52). The combined incidence of death and nonfatal reinfarction was also lower among patients assigned to angioplasty than among those assigned to streptokinase, with a relative risk of 0.13 (95 percent confidence interval, 0.05 to 0.37) for early events (within the first 30 days) and a relative risk of 0.62 (95 percent confidence interval, 0.43 to 0.91) for late events (after 30 days). The rates of readmission for heart failure and ischemia were also lower among patients in the angioplasty group than among patients in the streptokinase group. Total medical charges per patient were lower in the angioplasty group ($16,090) than in the streptokinase group ($16,813, P=0.05). Conclusions: As compared with thrombolytic therapy with streptokinase, primary coronary angioplasty is associated with better clinical outcomes over five years.
New England Journal of Medicine 12/1999; 341(19):1413-9. DOI:10.1056/NEJM199911043411901 · 55.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To establish the prevalence of 'silent ischaemia' of the myocardium in male patients with type 1 diabetes mellitus using a non-invasive cardiac examination, and to determine what clinical variables are related to silent ischaemia.
Males aged 20-69 years who visited the outpatient department of Internal Medicine of the De Weezenlanden Hospital in Zwolle between 1 February 1992 and 31 January 1995, and who showed no symptoms of ischaemic cardiopathy (angina pectoris, myocardial infarction or arrhythmias) or of chronic obstructive pulmonary disease, were examined for cardiac ischaemia by means of a 24-hour Holter registration and a perfusion scintigram after administration of dipyridamol. In order to demonstrate a possible connection between cardiovascular risk factors and silent ischaemia, the patients with an abnormal and those with a normal scintigram were compared by means of multivariate analysis.
Data were collected on 92 successive patients, with a median age of 40 years (range 22-69). There were 19 patients (21%) with an abnormal myocardial scintigram. On average they were older and had a longer history of diabetes mellitus. An abnormal Holter registration was observed in 14 patients (15%), abnormality of either the Holter registration or the myocardial scintigram in 28 patients (30%) and abnormality of both the myocardial scintigram and the Holter registration in 5 patients (5%). The duration of the diabetes mellitus, and a diastolic blood pressure > or = 90 mm Hg were statistically significant and independent predictors of an abnormal myocardial scintigram (relative risks 1.08 and 3.4 per year, respectively).
The prevalence of cardiac ischaemia in males with type 1 diabetes mellitus without cardiac symptoms is approximately 20%. Abnormal test results were associated with a longer duration of the diabetes mellitus and a diastolic blood pressure > or = 90 mm Hg.
Nederlands tijdschrift voor geneeskunde 11/1999; 143(40):2001-6.
[Show abstract][Hide abstract] ABSTRACT: Left ventricular function is an important outcome measure in patients with coronary artery disease, in particular in patients after myocardial infarction. It is reliably assessed by radionuclide angiography, but echocardiographic wall motion scoring might be an attractive alternative.
Four days after reperfusion therapy for acute myocardial infarction both radionuclide angiography and echocardiography were performed in 90 patients. Segmental wall motion scoring (WMSI) and visual estimation of the left ventricular ejection fraction (LVEF) was done by 2 independent observers. Repeated analysis was performed 1 month after the first reading. In 41 patients the LVEF was assessed quantitatively by tracing of endocardial outlines of the left ventricle.
Both correlation with radionuclide angiography (estimated LVEF: r = 0.71, WMSI: r = -0.68, Tracing: r = 0.59) and inter- and intra-observer variability (estimated LVEF: 19% and 15%, WMSI: 65% and 59%) were in favour of the LVEF estimation method. Correlation with radionuclide angiography measurements was related to the quality of the echocardiogram and to the extent of coronary artery disease.
Simple echocardiographic estimation of left ventricular ejection fraction in patients after reperfusion therapy for acute myocardial infarction proved to be superior to quantitative assessment of ejection fraction and to segmental wall motion scoring in comparison with radionuclide angiography.
International Journal of Cardiac Imaging 01/1999; 14(6):413-8. DOI:10.1023/A:1006082214191