Marcel P Stokkel

Leiden University Medical Centre, Leiden, South Holland, Netherlands

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Publications (42)188.54 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to systematically review literature, exploring the role of radioguided surgery with iodine-labeled metaiodobenzylguanidine (MIBG) in resection of neuroendocrine tumors. PubMed, EMBASE, Web of Science, COCHRANE, CINAHL, Academic Search Premier, ScienceDirect, Wiley, and references of key articles were searched to identify potentially relevant studies. Twenty studies were included. A total of 130 procedures in 120 patients were performed. Ninety percent of included studies concerned case reports or case series. It is described that radioguided surgery with iodine-labeled MIBG can improve the quality of macroscopic resection of neuroendocrine tumors in selected cases, ie, in cases where the tumor is small, nonpalpable, difficult to visualize on conventional imaging studies, or located in an area with adhesional scar tissue from previous surgery. However, in a substantial number of cases the gamma probe failed due to technical problems. Since there is limited evidence that radioguided surgery contributes substantially in resection of neuroendocrine tumors, we cannot advocate its use in general. However, we can conclude that it can seemingly improve the quality of resection in selected cases. When radioguided surgery is performed in neuroendocrine tumors, we advocate the use of I to label MIBG.
    Clinical nuclear medicine 09/2012; 37(11):1083-8. · 3.92 Impact Factor
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    ABSTRACT: Radioactive MIBG can be used in radioguided surgery for neuroendocrine tumors. We report the case of a man with a mutation in the succinate dehydrogenase subunit B (SDHB) gene, in which an abdominal MRI scan identified two 5-mm left para-aortic nodules, suspect for paragangliomas. Subsequent SPECT revealed increased uptake of tracer. 123I MIBG probe-guided resection was scheduled. During surgery, 2 small nodules with elevated activity in between the superior mesenteric artery and the left adrenal gland were identified by the detection probe and were resected. Histopathologic examination revealed mature ganglioneuromas.
    Clinical nuclear medicine 08/2012; 37(8):768-71. · 3.92 Impact Factor
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    ABSTRACT: The canonical Wnt pathway plays a key regulatory role in osteoblastogenesis and bone mass acquisition through its main effector, β-catenin. Adenomatous polyposis coli (APC) represents the key intracellular gatekeeper of β-catenin turnover, and heterozygous germ-line mutations in the APC gene cause familial adenomatous polyposis (FAP). Whether APC mutations affect bone mass has not been previously investigated. We conducted a cross-sectional study evaluating skeletal status in FAP patients with a documented APC mutation. Twenty-two FAP patients with a mean age of 42 years (54.5% women) were included in this study. Mean bone mineral density (BMD) Z-scores were significantly increased above normal at all measured sites: lumbar spine (p < .01), total hip (p < .01), femoral neck (p < .05), and trochanter (p < .01). Z-scores were +1 or greater in 14 patients (63.6%) and +2 or greater in 5 (22.7%). Mean values of bone turnover markers were within normal ranges. There was a significant positive correlation between procollagen type I N-terminal propeptide (P1NP) and β-crosslaps (β-CTX) (r = 0.70, p < .001) and between these markers and sclerostin and BMD measurements. We demonstrate that FAP patients display a significantly higher than normal mean BMD compared with age- and sex-matched healthy controls in the presence of a balanced bone turnover. Our data suggest a state of "controlled" activation of the Wnt signaling pathway in heterozygous carriers of APC mutations, most likely owing to upregulation of cytoplasmic β-catenin levels.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 12/2010; 25(12):2624-32. · 6.04 Impact Factor
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    ABSTRACT: previous studies have shown that the presence of stenosis alone on multislice computed tomography (MSCT) has a limited positive predictive value for the presence of ischemia on myocardial perfusion imaging (MPI). The purpose of this study was to assess which variables of atherosclerosis on MSCT angiography are related to ischemia on MPI. both MSCT and MPI were performed in 514 patients. On MSCT, the calcium score, degree of stenosis (≥ 50% and ≥ 70% stenosis), and plaque extent and location were determined. Plaque composition was classified as noncalcified, mixed, or calcified. Ischemia was defined as a summed difference score (≥ 2 on a per-patient basis. Ischemia was observed in 137 patients (27%). On a per-patient basis, multivariate analysis showed that the degree of stenosis (presence of (≥ 70% stenosis, odds ratio=3.5), plaque extent and composition (mixed plaques (≥3, odds ratio=1.7; calcified plaques ≥ 3, odds ratio=2.0), and location (atherosclerotic disease in the left main coronary artery and/or proximal left anterior descending coronary artery, odds ratio=1.6) were independent predictors for ischemia on MPI. In addition, MSCT variables of atherosclerosis, such as plaque extent, composition, and location, had significant incremental value for the prediction of ischemia over the presence of ≥70% stenosis. in addition to the degree of stenosis, MSCT variables of atherosclerosis describing plaque extent, composition, and location are predictive of the presence of ischemia on MPI.
    Circulation Cardiovascular Imaging 11/2010; 3(6):718-26. · 5.80 Impact Factor
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    ABSTRACT: Timing of acquisition is a factor that may influence the subdiaphragmatic activity in myocardial perfusion scintigraphy (MPS). According to the instructions of tetrofosmin, scintigraphy may already be started 15 minutes postinjection. The aim of the present study was to compare the image quality and the functional parameters between early and late scanning. Eventually, 49 consecutive patients underwent a 2-day MPS protocol in which 15 and 45 minutes after the injection of 500 MBq of technetium-99m-tetrofosmin scintigraphy both at stress and rest were performed. The amount of subdiaphragmatic tracer activity was scored from "no tracer activity" to "severe." Moderate and severe subdiaphragmatic tracer activity was considered relevant for the interpretation of the myocardial perfusion scan. Two-thirds of the patients (64%) showed a considerable amount of subdiaphragmatic activity on the 15 minutes rest images, whereas only 9 patients (18%) had considerable subdiaphragmatic activity on the late images. Stress imaging showed comparable results, however, subdiaphragmatic activity was generally less frequent and less prominent following stress. The value of the ejection fraction was significantly lower during early imaging comparing with late imaging. Lower ejection fraction was exclusively noticed in imaging with moderate and severe subdiaphragmatic tracer activity related wrong border estimation. Acquisition 15 minutes after the injection of Tetrofosmin shows a significant and clinically relevant subdiaphragmatic activity in most myocardial perfusion scans leading to poorer image quality and to an erroneous measurement of the ejection fraction. Therefore, early acquisition in MPS is not recommended in clinical practice.
    Clinical nuclear medicine 10/2010; 35(10):764-9. · 3.92 Impact Factor
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    ABSTRACT: The purpose of this study was to evaluate the prevalence of cardiac autonomic neuropathy (CAN) in a cohort of patients with type 2 diabetes, truly asymptomatic for coronary artery disease (CAD), using heart rate variability (HRV) and (123)I-metaiodobenzylguanidine ((123)I-mIBG) myocardial scintigraphy. The study group comprised 88 patients with type 2 diabetes prospectively recruited from an outpatient diabetes clinic. In all patients myocardial perfusion scintigraphy, CAN by HRV and (123)I-mIBG myocardial scintigraphy were performed. Two or more abnormal tests were defined as CAN-positive (ECG-based CAN) and one or fewer as CAN-negative. CAN assessed by (123)I-mIBG scintigraphy was defined as abnormal if the heart-to-mediastinum ratio was <1.8, the washout rate was >25%, or the total defect score was >13. The prevalence of CAN in patients asymptomatic for CAD with type 2 diabetes and normal myocardial perfusion assessed by HRV and (123)I-mIBG scintigraphy was respectively, 27% and 58%. Furthermore, in almost half of patients with normal HRV, (123)I-mIBG scintigraphy showed CAN. The current study revealed a high prevalence of CAN in patients with type 2 diabetes. Secondly, disagreement between HRV and (123)I-mIBG scintigraphy for the assessment of CAN was observed.
    European Journal of Nuclear Medicine 08/2010; 37(9):1698-705. · 4.53 Impact Factor
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    ABSTRACT: The purpose of this study was to evaluate whether 123-iodine metaiodobenzylguanidine (123-I MIBG) imaging predicts ventricular arrhythmias causing appropriate implantable cardioverter-defibrillator (ICD) therapy (primary end point) and the composite of appropriate ICD therapy or cardiac death (secondary end point). Although cardiac sympathetic denervation is associated with ventricular arrhythmias, limited data are available on the predictive value of sympathetic nerve imaging with 123-I MIBG on the occurrence of arrhythmias. Before ICD implantation, patients underwent 123-I MIBG and myocardial perfusion imaging. Early and late 123-I MIBG (planar and single-photon emission computed tomography [SPECT]) imaging was performed to assess cardiac innervation (heart-to-mediastinum ratio, cardiac washout rate, and 123-I MIBG SPECT defect score). Stress-rest myocardial perfusion imaging was performed to assess myocardial infarction and perfusion abnormalities (perfusion defect scores). During follow-up, appropriate ICD therapy and cardiac death were documented. One-hundred sixteen heart failure patients referred for ICD therapy were enrolled. During a mean follow-up of 23 +/- 15 months, appropriate ICD therapy (primary end point) was documented in 24 (21%) patients and appropriate ICD therapy or cardiac death (secondary end point) in 32 (28%) patients. Late 123-I MIBG SPECT defect score was an independent predictor for both end points. Patients with a large late 123-I MIBG SPECT defect (summed score >26) showed significantly more appropriate ICD therapy (52% vs. 5%, p < 0.01) and appropriate ICD therapy or cardiac death (57% vs. 10%, p < 0.01) than patients with a small defect (summed score </=26) at 3-year follow-up. Cardiac sympathetic denervation predicts ventricular arrhythmias causing appropriate ICD therapy as well as the composite of appropriate ICD therapy or cardiac death.
    Journal of the American College of Cardiology 06/2010; 55(24):2769-77. · 14.09 Impact Factor
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    ABSTRACT: (123)I-meta-iodobenzyl-guanidine ((123)I-MIBG) scintigraphy is used to visualize and quantify the sympathetic nerve activity. Although it has been used since 1980 to identify myocardial innervation, it is not yet regarded a routine sympathetic imaging agent in this respect. The lack of large multicentre studies and the presence of variations in the protocols that are used for planar MIBG acquisition confines the comparability of study results and application of normal values. Therefore, the aim of this study was to assess the variations in mathematical methods that are currently used to quantify the heart-to-mediastinum ratio and washout rate (WOR). In addition, normal values were evaluated in concordance with these methods. A systematic literature search yielded 169 unique manuscripts, of which 30 contained a complete description of the acquisition protocol for planar MIBG acquisition, image analysis and quantification of the parameters. The results indicate not only large variations in mathematical methods, but also in various aspects of the protocols that are used during acquisition. In many manuscripts method-specific normal values were used; however, these values were generally generated from small, single-centre studies. This study stresses the need to produce guidelines to achieve a standardized method for MIBG acquisition, image analysis and methods to quantify parameters.
    Nuclear Medicine Communications 03/2010; 31(7):617-28. · 1.38 Impact Factor
  • Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2010; 55(10).
  • Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2010; 55(10).
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    ABSTRACT: Identification of asymptomatic patients with type 2 diabetes at increased risk for coronary artery disease (CAD) remains a challenge. We evaluated the potential of carotid intima-media thickness (CIMT) for prediction of abnormal myocardial perfusion in this population. CIMT and SPECT myocardial perfusion imaging were assessed in 98 asymptomatic patients with type 2 diabetes. An increased CIMT was defined as > or =75th percentile of reference values. RESULTS Increased CIMT was an independent predictor of the extent of abnormal perfusion (P < 0.001). In patients with increased CIMT as compared with patients with normal CIMT, abnormal perfusion (75 vs. 9%) and severely abnormal perfusion (28 vs. 3%) were observed more frequently. Increased CIMT was significantly related to the presence and extent of abnormal myocardial perfusion. Assessment of CIMT may be useful to identify asymptomatic patients with type 2 diabetes at higher risk for CAD.
    Diabetes care 11/2009; 33(2):372-4. · 7.74 Impact Factor
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    ABSTRACT: In patients with diabetes mellitus, myocardial perfusion defects are often observed in the absence of obstructive epicardial coronary artery disease (CAD), thereby presenting a diagnostic problem. We hypothesized that these perfusion abnormalities may be explained by endothelial dysfunction or occult coronary atherosclerosis. Prospectively, 130 asymptomatic patients with diabetes mellitus underwent cardiovascular screening by coronary artery calcium (CAC) scoring, multislice CT coronary angiography, and myocardial perfusion imaging by SPECT. Multislice CT images were evaluated for the presence of obstructive epicardial CAD (>or=50% luminal narrowing). To quantify abnormal myocardial perfusion on SPECT images, we determined the summed stress score for each patient. The presence of abnormal myocardial perfusion was defined as a summed stress score of 3 or more. In addition, flow-mediated dilatation of the brachial artery, a marker of endothelial function, was determined using ultrasonography. In 35 patients (27%), obstructive epicardial CAD was observed on multislice CT, and these patients were excluded from further analysis. In the remaining 95 patients, abnormal myocardial perfusion was observed in 30 (32%) of patients. Flow-mediated dilatation was significantly lower in patients with abnormal myocardial perfusion (3.6% +/- 2.4%) than in those with normal myocardial perfusion (6.4% +/- 2.6%) (P < 0.001). Importantly, flow-mediated dilatation remained a significant predictor of the extent of abnormal myocardial perfusion after correction for cardiovascular risk factors and CAC score (P < 0.001). In contrast, no association was observed between nonobstructive plaque burden as reflected by CAC scores and extent of abnormal myocardial perfusion. In patients with diabetes mellitus, myocardial perfusion abnormalities in the absence of obstructive epicardial CAD are associated with endothelial dysfunction.
    Journal of Nuclear Medicine 11/2009; 50(12):1980-6. · 5.77 Impact Factor
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    ABSTRACT: Treatment options for patients with radioactive iodine (RaI) refractory metastases of differentiated thyroid carcinoma (DTC) are limited. We studied the effects of the multitarget tyrosine kinase inhibitor sorafenib on the reinduction of RaI uptake and tumor progression. Open, single center, single arm 26-week prospective phase II study with open-ended extension. We treated 31 patients with progressive metastatic or locally advanced RaI refractory DTC with sorafenib 400 mg b.i.d. The primary endpoint was reinduction of RaI uptake at 26 weeks. Additional endpoints were the radiological response and the influence of bone metastases. At 26 weeks of sorafenib therapy, no reinduction of RaI uptake at metastatic sites was observed, but 19 patients (59%) had a clinical beneficial response, eight of whom had a partial response (25%) and 11 had stable disease (34%). Seven patients had progressive disease (22%). Sorafenib was significantly less effective in patients with bone metastases. The estimated median progression free survival was 58 weeks (95% confidence interval, CI, 47-68). In general, thyroglobulin (Tg) response (both unstimulated and TSH stimulated) reflected radiological responses. The median time of the nadir of Tg levels was 3 months. Responses were not influenced by histological subtype, mutational status or other variables. No unusual side effects were observed. Sorafenib has a beneficial effect on tumor progression in patients with metastatic DTC, but was less effective in patients with bone metastases. Diagnostic whole body scintigraphy did not reveal an effect of sorafenib on the reinduction of RaI uptake.
    European Journal of Endocrinology 09/2009; 161(6):923-31. · 3.14 Impact Factor
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    ABSTRACT: The aim of this study was to assess the effects of replacement with recombinant human growth hormone (rhGH) in patients with GH deficiency (GHD) after treatment of acromegaly. Intervention study. Sixteen patients (8 men, age 56 years), treated for acromegaly by surgery and radiotherapy, with an insufficient GH response to insulin-induced hypoglycaemia, were treated with 1 year of rhGH replacement. Study parameters were assessed at baseline and after 1 year of rhGH replacement. Study parameters were cardiac function, body composition, bone mineral density (BMD), fasting lipids, glucose, bone turnover markers, and Quality of Life (QoL). During rhGH replacement IGF-I concentrations increased from -0.4 +/- 0.7 to 1.0 +/- 1.5 SD (P = 0.001), with a mean daily dose of 0.2 +/- 0.1 mg in men and 0.3 +/- 0.2 mg in women. Nonetheless, rhGH replacement did not alter cardiac function, lipid and glucose concentrations, body composition or QoL. Bone turnover markers (PINP and beta crosslaps) levels increased (P = 0.005 and P = 0.021, respectively), paralleled by a small, but significant decrease in BMD of the hip. The beneficial effects of rhGH replacement in patients with GHD during cure from acromegaly are limited in this study.
    Pituitary 07/2009; 12(4):339-46. · 2.67 Impact Factor
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    ABSTRACT: Dosimetry studies have shown that activities of 131I as small as 10-20 MBq may cause a stunning effect. A result of this stunning effect may be a lower success rate of the ablative 131I therapy for differentiated thyroid carcinoma (DTC). The aim of this study was to determine whether pre-therapeutic uptake measurement with 40 MBq 131I causes a lower success rate of ablation. retrospective chart review study. In two hospitals the ablation protocols differed in one respect only: in the one hospital no diagnostic 131I was applied before ablation (group 1, n = 48), whereas in the other hospital a 24-h uptake-measurement with 40 MBq 131I was performed (group 2, n = 51). Included were all DTC patients without distant metastases who had undergone 131I ablation between July 2002 and December 2005, and who had returned for 131I follow-up. Successful ablation was defined as absence of pathological 131I uptake on diagnostic whole-body scintigraphy and undetectable thyroglobulin-levels under TSH stimulation. Overall, ablation was successful in 31/48 patients (65%) in group 1 and in 17/51 patients (33%) in group 2 (p=0.002). Multivariate analysis showed that pre-therapeutic uptake measurement using 40 MBq 131I was an independent determinant for success of ablation (p = 0.002). After applying a diagnostic activity of 40 MBq 131I before ablation, the success rate of ablation is severely reduced. Consequently, the routine application of 131I for diagnostic scintigraphy or uptake measurement prior to 131I ablation is best avoided.
    Nuklearmedizin 05/2009; 48(4):138-42; quiz N19-20. · 1.32 Impact Factor
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    ABSTRACT: The significance of left ventricular (LV) dyssynchrony for the prediction of response to cardiac resynchronization therapy (CRT) has been demonstrated. Parameters reflecting LV dyssynchrony (phase SD, histogram bandwidth) can be derived from gated myocardial perfusion SPECT (GMPS) using phase analysis. The feasibility of LV dyssynchrony assessment with phase analysis on GMPS using Quantitative Gated SPECT (QGS) software has not been demonstrated in patients undergoing CRT. The aim of the present study was to validate the QGS algorithm for phase analysis on GMPS in a direct comparison with echocardiography using tissue Doppler imaging (TDI) for LV dyssynchrony assessment. Also, prediction of response to CRT using GMPS and phase analysis was evaluated. Patients (n = 40) with severe heart failure (New York Heart Association class III-IV), an LV ejection fraction of no more than 35%, and a QRS complex greater than or equal to 120 ms were evaluated for LV dyssynchrony using GMPS and echocardiography with TDI. At baseline and after 6 mo of CRT, clinical status, LV volumes, and LV ejection fraction were evaluated. Patients with functional improvement were classified as CRT responders. Both histogram bandwidth (r = 0.69, r(2) = 0.48, SEE = 25.4, P < 0.01) and phase SD (r = 0.65, r(2) = 0.42, SEE = 26.8, P < 0.01) derived from GMPS correlated significantly with TDI for assessment of LV dyssynchrony. At baseline, CRT responders showed a significantly larger histogram bandwidth (94 degrees +/- 23 degrees vs. 68 degrees +/- 21 degrees , P < 0.01) and a larger phase SD (26 degrees +/- 6 degrees vs. 18 degrees +/- 5 degrees , P < 0.01) than did nonresponders. Receiver-operating-characteristic curve analysis identified an optimal cutoff value of 72.5 degrees for histogram bandwidth to predict CRT response, yielding a sensitivity of 83% and a specificity of 81%. For phase SD, sensitivity and specificity similar to those for histogram bandwidth were obtained at a cutoff value of 19.6 degrees . QGS phase analysis on GMPS correlated significantly with TDI for the assessment of LV dyssynchrony. Moreover, a high accuracy for prediction of response to CRT was obtained using either histogram bandwidth or phase SD.
    Journal of Nuclear Medicine 05/2009; 50(5):718-25. · 5.77 Impact Factor
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    ABSTRACT: The aim of this study was to assess the prognostic value of technetium-99m tetrofosmin gated SPECT imaging in women using quantitative gated single photon emission computed tomography (SPECT) imaging. We followed 453 consecutive female patients. Average follow-up was 1.33 years (max. 2.55). Hard endpoints were cardiac death, acute myocardial infarction, or documented ventricular fibrillation. Event-free survival curves were obtained. Optimal cutoff values for left ventricular (LV) volumes, LV ejection fraction (LVEF), and perfusion data to predict outcome were determined by ROC curve analysis. A total of 236 patients had an abnormal study, of whom 27 patients experienced hard events (16 deaths) and 47 patients soft events. For hard events summed stress score (SSS) and LVEF, and for any cardiac event SSS showed independent incremental prognostic value. The survival curves were maximally separated when using cutoff values for SSS of > or = 22 and LVEF < 52% (P < 0.001, HR 4.61 and P < 0.001 HR 5.24 for SSS and LVEF resp.), and SSS > or = 14 (P < 0.001 HR 3.76) for any cardiac event. In women, perfusion and functional parameters derived from quantitative gated technetium-99m tetrofosmin SPECT imaging can adequately be used for cardiac risk assessment. Using quantitative gated SPECT, female patients with an LVEF < 52% or an SSS > or = 22 are at increased risk for subsequent hard events. Furthermore, patients with an SSS > or = 14 are at increased risk for any cardiac events.
    Journal of Nuclear Cardiology 02/2009; 16(1):10-9. · 2.85 Impact Factor
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    ABSTRACT: The purpose of this study was to compare contrast-enhanced MRI and nuclear imaging with (99m)Tc-tetrofosmin and (18)F-fluorodeoxyglucose ((18)F-FDG) single photon emission computed tomography (SPECT) for assessment of myocardial viability. Included in the study were 60 patients with severe ischaemic left ventricular (LV) dysfunction who underwent contrast-enhanced MRI, (99m)Tc-tetrofosmin and (18)F-FDG SPECT. Myocardial segments were assigned a wall motion score from 0 (normokinesia) to 4 (dyskinesia) and a scar score from 0 (no scar) to 4 (76-100% transmural extent). Furthermore, (99m)Tc-tetrofosmin and (18)F-FDG segmental tracer uptake was categorized from 0 (tracer activity >75%) to 3 (tracer activity <25%). Dysfunctional segments were classified into viability patterns on SPECT: normal perfusion/(18)F-FDG uptake, perfusion/(18)F-FDG mismatch, and mild or severe perfusion/(18)F-FDG match. Minimal scar tissue was observed on contrast-enhanced MRI (scar score 0.4+/-0.8) in segments with normal perfusion/(18)F-FDG uptake, whereas extensive scar tissue (scar score 3.1+/-1.0) was noted in segments with severe perfusion/(18)F-FDG match (p < 0.001). High agreement (91%) for viability assessment between contrast-enhanced MRI and nuclear imaging was observed in segments without scar tissue on contrast-enhanced MRI as well as in segments with transmural scar tissue (83%). Of interest, disagreement was observed in segments with subendocardial scar tissue on contrast-enhanced MRI. Agreement between contrast-enhanced MRI and nuclear imaging for assessment of viability was high in segments without scar tissue and in segments with transmural scar tissue on contrast-enhanced MRI. However, evident disagreement was observed in segments with subendocardial scar tissue on contrast-enhanced MRI, illustrating that the nonenhanced epicardial rim can contain either normal or ischaemically jeopardized myocardium.
    European Journal of Nuclear Medicine 01/2009; 36(4):594-601. · 4.53 Impact Factor
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    ABSTRACT: The purpose of this study was to evaluate the prevalence of an abnormal stress myocardial perfusion study in a cohort of truly asymptomatic patients with type 2 diabetes mellitus using myocardial perfusion imaging by means of single photon emission computed tomography (SPECT). Secondly, we determined which clinical characteristics may predict an abnormal stress myocardial perfusion study in this population. A total of 120 asymptomatic patients (mean age 53+/-10 years) with type 2 diabetes mellitus and one or more risk factors for coronary artery disease were prospectively recruited from an outpatient diabetes clinic. All patients underwent myocardial perfusion imaging by means of adenosine (99m)Tc sestamibi SPECT. Images were evaluated for the presence of perfusion abnormalities as well as other nonperfusion abnormalities that may indicate extensive ischaemia, including left ventricular dysfunction (defined as a left ventricular ejection fraction <45%), transient ischaemic dilatation and adenosine-induced ST segment depression. Multivariable analysis was performed using a backward selection strategy to identify potential predictors for an abnormal stress myocardial perfusion study. Finally, all patients were followed up for 12 months to determine the occurrence of cardiovascular events: (1) cardiac death, (2) nonfatal myocardial infarction, (3) unstable angina requiring hospitalization, (4) revascularization, or (5) stroke. Of the 120 patients, 40 (33%) had an abnormal stress study, including myocardial perfusion abnormalities in 30 patients (25%). In 10 patients (8%), indicators of extensive (possibly balanced ischaemia) were observed in the absence of abnormal perfusion. The multivariable analysis identified current smoking, duration of diabetes and the cholesterol/high-density lipoprotein (HDL) ratio as independent predictors of an abnormal stress study. During a follow-up period of 12 months six patients (5%) had a cardiovascular event. The current study revealed a high prevalence of abnormal stress myocardial perfusion studies in patients with type 2 diabetes mellitus despite the absence of symptoms. In contrast to earlier studies, current smoking, duration of diabetes and the cholesterol/HDL ratio were identified as independent predictors of an abnormal study.
    European Journal of Nuclear Medicine 12/2008; 36(4):567-75. · 4.53 Impact Factor
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    ABSTRACT: It has been proposed that TSH has thyroid hormone-independent effects on bone mineral density (BMD) and bone metabolism. This concept is still controversial and has not been studied in human subjects in detail. We addressed this question by studying relationships between serum TSH concentration and indicators of bone turnover, after controlling for triiodothyronine (T(3)), free thyroxine (FT(4)), and non-thyroid factors relevant to BMD and bone metabolism. We also studied the contribution of the TSH receptor (TSHR)-Asp727Glu polymorphism to these relationships. We performed a cross-sectional study with 148 patients, who had been thyroidectomized for differentiated thyroid carcinoma. We measured BMD of the femoral neck and lumbar spine. FT(4), T(3), TSH, bone-specific alkaline phosphatase, procollagen type 1 aminoterminal propeptide levels, C-cross-linking terminal telopeptide of type I collagen, and urinary N-telopeptide of collagen cross-links were measured. Genotypes of the TSHR-Asp727Glu polymorphism were determined by Taqman assay. We found a significant, inverse correlation between serum TSH levels and indicators of bone turnover, which was independent of serum FT(4) and T(3) levels as well as other parameters influencing bone metabolism. We found that carriers of the TSHR-Asp727Glu polymorphism had an 8.1% higher femoral neck BMD, which was, however, no longer significant after adjusting for body mass index. We conclude that in this group of patients, serum TSH was related to indicators of bone remodeling independently of thyroid hormone levels. This may point to a functional role of the TSHR in bone in humans. Further research into this mechanism needs to be performed.
    European Journal of Endocrinology 08/2008; 159(1):69-76. · 3.14 Impact Factor