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R Valkema

Publications and source records attributed to R Valkema.

At least 37 records · Page 2Linked to original sources

Safety, hemodynamic profile, and feasibility of dobutamine stress technetium myocardial perfusion single-photon emission CT imaging for evaluation of coronary artery disease in the elderly.

OBJECTIVES: Cardiovascular disease is the leading cause of morbidity and mortality in the elderly. The evaluation of coronary artery disease by exercise stress testing is frequently limited by the patient's inability to exercise. Although pharmacologic stress testing with dobutamine is an alternative, the safety of dobutamine myocardial perfusion scintigraphy in the elderly has not been previously studied. PATIENTS AND METHODS: We studied the safety and feasibility of dobutamine (up to 40 microg/kg/min)-atropine (up to 1 mg) stress myocardial perfusion scintigraphy using technetium single-photon emission CT imaging in 227 patients > or = 70 years old (mean +/- SD age, 75 +/- 4 years). A control group of 227 patients < 70 years old (mean age, 55 +/- 11 years; matched for gender, prevalence of previous infarction, beta-blocker therapy, and severity of resting perfusion abnormalities) was studied to assess age-related differences in the safety and the hemodynamic response. A feasible test was defined as the achievement of the target heart rate and/or an ischemic end point (angina, ST-segment depression, or reversible perfusion abnormalities). RESULTS: No myocardial infarction or death occurred during the test. The target heart rate was achieved more frequently in the elderly patients (87% vs 79%; p < 0.05). The elderly patients had a higher prevalence of supraventricular tachycardia (7% vs 1%; p < 0.005) and premature ventricular contraction (74% vs 32%; p < 0.005) during the test, as compared to the younger patients. There was a trend to a higher prevalence of ventricular tachycardia (5% vs 2%) and atrial fibrillation (3% vs 0.4%) in the elderly patients. Arrhythmias were terminated spontaneously by termination of dobutamine infusion or by administration of metoprolol. Independent predictors of supraventricular tachyarrhythmias and ventricular tachycardia were older age (p < 0.001; chi(2), 9.8) and myocardial perfusion defect score at rest (p < 0.01; chi(2), 6.8) respectively, by using a multivariate analysis of clinical and stress test variables. Elderly patients had a higher prevalence of systolic BP drop > 20 mm Hg during the test (37% vs 12%; p < 0.05). The test was terminated due to hypotension in 2% of the elderly patients and in 1% of the control group. Age was the most powerful predictor of hypotension (p < 0.005; chi(2), 10.3). The test was considered feasible in 216 elderly patients (95%) and in 209 patients of the control group (92%). CONCLUSION: Dobutamine-atropine stress myocardial perfusion scintigraphy is a highly feasible method for the evaluation of coronary artery disease in the elderly. Elderly patients have a higher risk for developing hypotension and supraventricular tachyarrhythmias during a dobutamine stress test. However, dobutamine-induced hypotension is often asymptomatic and rarely necessitates the termination of the test.

Adult↗

Dobutamine stress echocardiography and technetium-99m-tetrofosmin/fluorine 18-fluorodeoxyglucose single-photon emission computed tomography and influence of resting ejection fraction to assess myocardial viability in patients with severe left ventricular dysfunction and healed myocardial infarction.

The purpose of this study was to compare 2 different techniques--dobutamine-atropine stress echocardiography (DSE) and dual-isotope simultaneous acquisition (technetium-99-m-tetrofosmin/fluorine 18-fluorodeoxyglucose) single-photon emission computed tomography (DISA-SPECT)--for assessment of viable myocardium. One hundred ten patients (mean age 55 +/- 9 years) with left ventricular (LV) dysfunction (mean LV ejection fraction 27 +/- 13%) underwent both DISA-SPECT and DSE. A 16-segment scoring model was adopted for both techniques. Four types of wall motion during DSE were assessed: (1) biphasic, improvement at low dose (10 microg/kg/min) with worsening at high dose; (2) worsening, deterioration without initial improvement; (3) sustained, persistent or late improvement; and (4) no change. Viability criteria were biphasic, worsening, and sustained improvement with DSE. Viability criteria with DISA-SPECT were normal perfusion and metabolism (normal), concordantly mildly reduced perfusion and metabolism (subendocardial scar), or severely reduced perfusion and increased metabolism (mismatch). Myocardium was considered nonviable with DSE in case of unchanged wall motion, or moderate reduction or absence in both technetium-99m-tetrofosmin perfusion and fluorodeoxyglucose uptake with DISA-SPECT. Of 1,756 of 1,760 analyzable LV segments, 1,373 (78%) had severe wall motion abnormalities at baseline (severe hypokinesia, akinesia, or dyskinesia). Of these abnormal segments, 282 (21%) were considered viable during DSE (63 [5%] with biphasic response, 47 [3%] with ischemia, and 172 [13%]) with sustained improvement, whereas 1,091 (79%) were considered nonviable. With DISA-SPECT, 396 (29%) segments were considered viable (312 [23%] with matched perfusion/metabolism and 84 [6%] with mismatch), whereas 977 segments (71%) were considered nonviable. Both techniques showed agreement for viability in 201 segments and 896 were concordantly classified as nonviable. Disagreement was present in 276 segments of which 195 (71%) were nonviable with DSE and viable with DISA-SPECT. Overall agreement between the 2 techniques was 81% (kappa 0.46) in a subgroup of patients with an ejection fraction <25% 78% (kappa 0.39). Thus, DSE and DISA-SPECT show good agreement for assessing viable myocardium not influenced by resting ejection fraction. DSE underestimated the amount of viable tissue compared with DISA-SPECT.

Blood Pressure↗

Dobutamine stress thallium-201 single-photon emission tomography versus echocardiography for evaluation of the extent and location of coronary artery disease late after myocardial infarction.

Dobutamine stress echocardiography and thallium-201 myocardial perfusion scintigraphy are clinically useful methods for the evaluation of coronary artery disease (CAD). However, the relative merits of these imaging modalities in the evaluation of the extent of CAD after myocardial infarction have not been well studied. The aim of this study was to compare the accuracy of dobutamine stress echocardiography and simultaneous 201Tl single-photon emission tomography (SPET) imaging for the diagnosis and localization of CAD late after acute myocardial infarction. Dobutamine (up to 40 micrograms kg-1 min-1)-atropine (up to 1 mg) stress echocardiography in conjunction with stress-reinjection 201Tl SPET was performed for the evaluation of myocardial ischaemia in 90 patients with previous myocardial infarction who underwent coronary angiography. Significant CAD was predicted on bases of myocardial ischemia (new or worsening wall motion abnormalities on echocardiography and reversible perfusion defects on 201Tl SPET). Significant CAD (> or = 50% luminal diameter stenosis) was detected in 73 (81%) patients. The sensitivity, specificity and accuracy of echocardiography in detecting remote ischaemia for the diagnosis of remote CAD (present in 53 patients) were, respectively, 79% (CI 70%-88%), 85% (CI 77%-93%) and 81% (CI 73%-90%), while the corresponding figures for 201Tl SPET were 75% (CI 66%-85%), 78% (CI 69%-87%) and 76% (CI 67%-86%) respectively (P = NS vs echocardiography). The sensitivity, specificity and accuracy of echocardiography in detecting peri-infarction ischaemia for the diagnosis of infarct-related artery stenosis (present in 70 patients) were, respectively, 77% (CI 68%-86%), 85% (CI 78%-92%) and 79% (CI 70%-87%) while the corresponding figures for 201Tl SPET were 73% (CI 64%-82%), 85% (CI 78%-92%) and 76% (CI 67%-84%) respectively (P = NS vs echocardiography). The agreement between the two methods for the diagnosis of peri-infarction and remote ischaemia was 70% (kappa = 0.37) and 80% (kappa = 0.59) respectively. It is concluded that dobutamine stress echocardiography and 201Tl SPET have comparable accuracy for the diagnosis of infarct related and remote CAD in patients with previous myocardial infarction. The agreement between the methods is higher for the diagnosis of remote CAD than for that of peri-infarction ischaemia.

Cardiotonic Agents↗

Radiolabelled somatostatin analogue(s) for peptide receptor scintigraphy and radionuclide therapy.

BACKGROUND: Peptide receptor scintigraphy with the radioactive somatostatin analogue, [111In-DTPA0]octreotide, is a sensitive and specific technique to show in vivo the presence and abundance of somatostatin receptors on various tumours. AIM: With this technique primary tumours and metastases of neuroendocrine cancers as well as of many other cancer-types can be localised. This technique is currently used to assess the possibility of peptide receptor radionuclide therapy (PRRT) with repeated administrations of high doses of [111In-DTPA0)octreotide. 111In emits Auger and conversion electrons having a tissue penetration of 0.02-10 microns and 200 to 500 microns, respectively. PATIENTS AND METHODS: Thirty end-stage patients with mostly neuroendocrine progressing tumours were treated with [111In-DTPA0]octreotide, up to a maximal cumulative patient dose of about 74 GBq, in a phase I trial. RESULTS: There were no major clinical side effects after up to two years treatment, except that in a few patients a transient decline in platelets counts and lymphocyte subsets occurred. Promising beneficial effects on clinical symptoms, hormone production and tumour proliferation were found. Of the 21 patients who received a cumulative dose of more than 20 GBq, eight patients showed stabilisation of disease and six other patients a reduction in size of tumours. There is a tendency towards better results in patients whose tumours have a higher accumulation of the radioligand. CONCLUSIONS: PRRT is feasible, also with 111In as radionuclide. Depending on the homogeneity of distribution of tumour cells expressing peptide receptors and the size of the tumour, beta-emitting radionuclides, e.g., 90Y, labelled to DOTA-chelated peptides, are also attractive candidates for PRRT. The first PRRT trials with [90Y-DOTA0,Tyr3]octreotide started recently.

Animals↗

Scintigraphy and radionuclide therapy with [indium-111-labelled-diethyl triamine penta-acetic acid-D-Phe1]-octreotide.

Peptide receptor scintigraphy with [111In-DTPA-D-Phe1]-octreotide is a sensitive and specific technique to show in vivo the presence and abundance of somatostatin receptors on various tumours. With this technique primary tumours and metastases of neuroendocrine cancers as well as of many other cancer types can be localised. This technique is currently used to assess the possibility of peptide receptor radionuclide therapy with repeated administrations of high doses of [111In-DTPA-D-Phe1]-octreotide. 111In emits Auger and conversion electrons having a tissue penetration of 0.02 to 10 microns and 200 to 500 microns, respectively. Twenty end-stage patients, mostly with neuroendocrine progressing tumours, were treated with [111In-DTPA-D-Phe1]-octreotide, up to a maximal cumulative patient dose of about 74 GBq, in a phase I trial. Results showed there were no major clinical side-effects after up to 2 years treatment, except that in a few patients a transient decline in platelet counts and lymphocyte subsets occurred. Promising beneficial effects on clinical symptoms, hormone production and tumour proliferation were found. Of the 16 patients who received a cumulative dose of more than 20 GBq, 5 patients showed stabilisation of disease and 5 other patients a reduction in size of tumours. There is a tendency towards better results in patients whose tumours have a higher accumulation of the radioligand. In conclusion, peptide receptor radionuclide therapy is feasible, also with 111In as radionuclide. Theoretically, depending on the homogeneity of distribution of tumour cells expressing peptide receptors, beta-emitting radionuclides, e.g. 90Y, labelled to DOTA-chelated peptides may be more effective than 111In for peptide receptor radionuclide therapy. The first peptide receptor radionuclide therapy trials with [90Y-DOTA-Tyr3]-octreotide started recently.

Antineoplastic Agents, Hormonal↗

Preclinical and initial clinical evaluation of 111In-labeled nonsulfated CCK8 analog: a peptide for CCK-B receptor-targeted scintigraphy and radionuclide therapy.

UNLABELLED: The presence of cholecystokinin (CCK)-B (gastrin) receptors has been shown in more than 90% of medullary thyroid cancers (MTCs) and in a high percentage of small cell lung cancers, stromal ovarium cancers and several other tumor types. METHODS: The aim of this study was to evaluate in vitro and in vivo whether 111In-labeled CCK-B receptor-specific CCK8 analog [D-Asp26,Nle28,31]CCK26-33 (D-Asp-Tyr-Nle-Gly-Trp-Nle-Asp-Phe-NH2) is suitable for CCK-B receptor scintigraphy based on the finding that unlabeled nonsulfated diethylenetriamine pentaacidic acid [DTPA0]CCK8 and tetraazacyclododecanetetraacetic acid [DOTA0]CCK8 analogs show high and specific binding for CCK-B receptors in human tumors. Fifty percent inhibitory concentrations were in the low nanomolar range. RESULTS: In vitro, [111In-DOTA0]CCK8 showed specific internalization in CCK-B receptor-positive rat pancreatic tumor cells AR42J. Internalization of the analog appeared to be time and temperature dependent and receptor specific. From the data obtained with [111In-DOTA0]CCK8 and (125I)I-gastrin, the latter being a specific ligand for the CCK-B receptor, the rat pancreatic cell line CA20948 also appeared to be CCK-B receptor positive. This provides an in vitro and in vivo rat tumor model because this cell line can be grown to solid tumors in Lewis rats. In vivo biodistribution experiments in CA20948 tumor-bearing Lewis rats showed rapid clearance of [111In-DOTA0]CCK8, and specific uptake was found in the CCK-B receptor-expressing stomach and tumor. Furthermore, comparing [111In-DOTA0]CCK8 with the radioiodinated nonsulfated CCK10 analog (D-Tyr-Gly-Asp-Tyr-Nle-Gly-Trp-Nle-Asp-Phe-NH2), both ligands having high affinity for the CCK-B receptor, tumor-to-blood ratios were significantly higher for [111In-DOTA0]CCK8 than for 125I-CCK10, analogous to the findings with radioiodinated and 111In-labeled octreotide. The study in humans with [111In-DTPA0]CCK8 showed receptor-specific uptake in the CCK-B receptor-positive stomach and in metastases in the neck region up to 48 h after injection. CONCLUSION: [111In-DOTA0]CCK8 is most promising for scintigraphy and, after coupling to therapeutic radionuclides, for radionuclide therapy of human CCK-B receptor-positive tumors such as MTC and small cell lung cancer.

Animals↗

Therapy of neuroendocrine tumors with radiolabeled somatostatin-analogues.

UNLABELLED: Peptide receptor scintigraphy with the radioactive somatostatin-analogue [111In-DTPA0]octreotide (DTPA = diethylenetriaminepentaacetic acid) is a sensitive and specific technique to show in vivo the presence and abundance of somatostatin receptors on various tumors. With this technique primary tumors and metastases of neuroendocrine cancers as well as of many other cancer types can be localised. A new application is the use of peptide receptor radionuclide therapy, administrating high doses of 111In- or 90Y-labeled octreotide-analogues. PRECLINICAL: We investigated the radiotherapeutic effect of 90Y- and 111In-labeled [DOTA0,Tyr3]octreotide (DOTA = tetraazacyclododecanetetraacetic acid) or [111In-DTPA0]octreotide in Lewis rats bearing the somatostatin receptor-positive rat pancreatic tumor CA20948 in A) the flank or B) in the liver. PATIENTS: Thirty end-stage patients with mostly neuroendocrine progressing tumors were treated with [111In-DTPA0]octreotide, up to a maximal cumulative patient dose of about 74 GBq, in a phase 1 trial. PRECLINICAL RESULTS: A) Flank model: at least two 111MBq injections of [111In-DOTA0,Tyr3]octreotide were needed to reach tumor response, in 40% of the animals complete tumor remission was found after a follow-up period of 10 months. One or two injections of [90Y-DOTA0,Tyr3] octreotide yielded transient stable disease. B) Liver model: we found that peptide receptor radionuclide therapy is only effective if somatostatin receptors are present on the tumors, and is therefore receptor-mediated. High radioactive doses of 370 MBq [111In-DTPA0]octreotide or 93 MBq [90Y-DOTA0,Tyr3]octreotide can inhibit the growth of somatostatin receptor-positive metastases. CLINICAL RESULTS: There were no major clinical side effects after up to 2 years treatment, except that a transient decline in platelet counts and lymphocyte subsets can occur. Promising beneficial effects on clinical symptoms, hormone production and tumor proliferation were found. Of the 21 patients with progressive disease at baseline and who received a cumulative dose of more than 20 GBq [111In-DTPA0]octreotide, 8 patients showed stabilisation of disease and 6 other patients a reduction in size of tumors. There is a tendency towards better results in patients whose tumors have a higher accumulation of the radioligand. CONCLUSION: Radionuclide therapy with octreotide-derivatives is feasible, both with 111In and 90Y as radionuclides.

Animals↗

Comparison of dobutamine stress echocardiography and technetium-99m sestamibi single-photon emission tomography for the diagnosis of coronary artery disease in hypertensive patients with and without left ventricular hypertrophy.

Stress echocardiography has been considered an accurate method for the diagnosis of coronary artery disease in hypertensive patients and in patients with left ventricular hypertrophy. In contrast, the specificity of myocardial perfusion scintigraphy in these patients has been questioned. The aim of this study was to compare the accuracy of these two imaging modalities in conjunction with dobutamine stress test for the diagnosis of coronary artery disease in hypertensive patients with and without left ventricular hypertrophy. Dobutamine (up to 40 microg kg-1min-1) stress echocardiography in conjunction with sestamibi (MIBI) single-photon emission tomography (SPET) was performed in 84 patients with the diagnosis of systemic hypertension who had been referred for evaluation of myocardial ischaemia. Ischaemia was defined as new or worsened wall motion abnormalities at echocardiography and reversible perfusion defects at SPET. Significant coronary artery disease (>/=50% luminal diameter stenosis) was detected in 66 patients (79%). The sensitivity, specificity and accuracy of the ischaemic pattern at echocardiography for the diagnosis of coronary artery disease were 73% (CI 63%-82%), 83% (CI 75%-91%) and 75% (CI 66%-84%), those for MIBI were 67% (CI 57%-77%), 83% (CI 75%-91%) and 70% (CI 60%-80%) respectively (P = NS vs echocardiography). Significant stenosis was detected in 123 (49%) of the 252 analysed coronary arteries. The sensitivity, specificity and accuracy of echocardiography for the regional diagnosis of coronary artery disease were 63% (CI 56%-69%), 90% (CI 86%-94%) and 77% (CI 72%-82%). Those for MIBI were 58% (CI 51%-64%), 91% (CI 87%-94%) and 75% (CI 69%-80) respectively (P = NS vs echocardiography). Left ventricular hypertrophy was detected in 59 patients (70%) by echocardiography and did not influence the overall or regional specificity of echocardiography or MIBI SPET. It is concluded that in hypertensive patients, dobutamine stress echocardiography and MIBI SPET have a comparable accuracy for the overall and regional diagnosis of coronary artery disease. Hypertensive patients with or without left ventricular hypertrophy should not be considered unsuitable candidates for stress myocardial perfusion scintigraphy.

Adrenergic beta-Agonists↗

Safety and utility of atropine addition during dobutamine stress echocardiography for the assessment of viable myocardium in patients with severe left ventricular dysfunction.

OBJECTIVE: To assess the feasibility safety and side effects of the addition of atropine to dobutamine stress echocardiography for the detection of viable myocardium in patients with left ventricular dysfunction (ejection fraction < or = 35%) prior to coronary revascularization. BACKGROUND: The assessment of viable and/or ischaemic myocardium has high prognostic value as regards improvement of function and survival after coronary revascularization. The addition of atropine to dobutamine during echocardiographic testing for the presence of viable myocardium is not common practice. Consequently, no data exist on the safety and additional diagnostic value of this practice. METHODS: Two hundred patients with left ventricular ejection fraction < or = 35% were studied. RESULTS: Test end-points were: target heart rate in 164 (82%) of the patients, severe angina in 18 (9%), maximum dobutamine-atropine dose in six (3%), severe ST segment changes in five (2%), cardiac arrhythmias in four (2%), and hypotension in three (1%). Viability could be assessed echocardiogaphically in 105/200 (53%) from a biphasic response (improvement of wall motion with low dose dobutamine and worsening with high dose), in 93 from ischaemia and in 12 from sustained or late improvements. In 36/105 (34%) patients, ischaemic myocardium could only be assessed after the addition of atropine. Cardiac arrhythmias occurred in 11/200 (6%) and hypotension (decrease of systolic blood pressure >30 mmHg) in 21/200 (11%). Neither the use of atropine nor the induction of ischaemia were associated with an increased incidence of cardiac arrhythmias or hypotension. CONCLUSIONS: In a large group of patients with severe left ventricular dysfunction, dobutamine stress echocardiography is feasible and safe in 186/200 (93%); the addition of atropine was necessary in 34% to assess myocardial viability. Hypotension and cardiac arrhythmias were the most frequent side effects, but were not related to the induction of ischaemia or addition of atropine.

Adult↗

Myocardial viability: known and unknown.

The assessment of myocardial viability has gained a lot of attention over the past few years. Various imaging techniques, mainly nuclear and echocardiographic approaches, have been developed for this purpose. From the existing data, it has become clear that the presence of dysfunctional yet viable myocardium can predict improvement of regional and global left ventricular (LV) function after revascularization. This issue is most relevant in patients with severely depressed LV function, since in these patients revascularization carries a high (peri-)procedural risk on the one hand, but may substantially improve LV function in some patients. Besides the improvement of resting LV function after revascularization, other end-points may also be clinically relevant, including the response during stress, improvement of exercise capacity, the quality of life and the prevention of LV remodeling. These issues have not been studied extensively thusfar. Finally, several retrospective studies have shown the prognostic value of viability assessment; patients with viable but jeopardized myocardium were significantly more prone to experience cardiac events than patients with viability who underwent revascularization. The different aspects of viability assessment (including pathophysiology, available techniques, current implications and unresolved issues) will be addressed in this manuscript.

Cardiomyopathies↗

Safety of dobutamine-atropine stress myocardial perfusion scintigraphy.

UNLABELLED: Dobutamine stress testing is increasingly used for the diagnosis and functional evaluation of coronary artery disease. However, the relationship between myocardial perfusion abnormalities and complications of the test has not been studied. METHODS: We studied the hemodynamic profile, safety and feasibility of dobutamine (up to 40 microg/kg/min)-atropine (up to 1 mg) stress myocardial perfusion SPECT imaging (with 201TI, 99mTc-MIBI or tetrofosmin) in a consecutive series of 1076 patients (age = 59 +/- 11 yr, 50% with previous myocardial infarction) referred for evaluation of myocardial ischemia. RESULTS: No infarction or death occurred during the test. The test was considered feasible (achievement of 85% of the target heart rate or an ischemic endpoint) in 1005 patients (94%). Hypotension (systolic blood pressure drop > or = 40 mm Hg) occurred in 37 patients (3.4%). Independent predictors were higher baseline systolic blood pressure (p < 0.0001), number of ischemic segments (p < 0.05) and age (p < 0.05). Supraventricular tachyarrhythmias occurred in 48 patients (4.4%). Independent predictors were fixed perfusion defect (infarction) score (p < 0.005) and age (p < 0.05). Ventricular tachycardia occurred in 41 patients (3.8%). Independent predictors were infarction score (p < 0.01) and male gender (p < 0.05). All arrhythmias terminated spontaneously or after metoprolol administration. CONCLUSION: Dobutamine-atropine myocardial perfusion scintigraphy is a feasible method for the evaluation of coronary artery disease with a safety profile and feasibility comparable to those reported for dobutamine stress echocardiography. Patients with more severe fixed perfusion abnormalities are at a higher risk of developing tachyarrhythmias during the test.

Atropine↗

Phosphorylation of chemoattractant receptors is not essential for chemotaxis or termination of G-protein-mediated responses.

In several G-protein-coupled signaling systems, ligand-induced receptor phosphorylation by specific kinases is suggested to lead to desensitization via mechanisms including receptor/G-protein uncoupling, receptor internalization, and receptor down-regulation. We report here that elimination of phosphorylation of a chemoattractant receptor of Dictyostelium, either by site-directed substitution of the serines or by truncation of the C-terminal cytoplasmic domain, completely prevented agonist-induced loss of ligand binding but did not impair the adaptation of several receptor-mediated responses including the activation of adenylyl and guanylyl cyclases and actin polymerization. In addition, the phosphorylation-deficient receptors were capable of mediating chemotaxis, aggregation, and differentiation. We propose that for chemoattractant receptors agonist-induced phosphorylation regulates surface binding activity but other phosphorylation-independent mechanisms mediate response adaptation.

Actins↗

FDG SPECT in the assessment of myocardial viability. Comparison with dobutamine echo.

The use of 18F-fluorodeoxyglucose (FDG) imaging with single photon emission computed tomography (SPECT) has been introduced recently to assess myocardial viability. Several centres have now gained experience with cardiac FDG SPECT imaging, and this report is a summary of the currently available FDG SPECT data. Three studies have compared FDG SPECT with FDG positron emission tomography and demonstrated good agreement between them. Initial results in patients undergoing revascularization suggest that FDG SPECT can predict improvement in contractile function after revascularization. Although the initial results are promising, larger studies are needed to determine the precise role of FDG SPECT in the assessment of myocardial viability.

Cardiotonic Agents↗

Single radionuclide scintigraphy with 99mtechnetium-sestamibi and ultrasonography in hyperparathyroidism.

OBJECTIVE: Assessment of 99mTechnetium-sestamibi scintigraphy and ultrasonography as methods of locating enlarged parathyroid glands before operation. DESIGN: Retrospective analysis. SETTING: University hospital, The Netherlands. SUBJECTS: 21 patients with primary hyperparathyroidism and 6 patients with persistent or recurrent hyperparathyroidism. INTERVENTIONS: Single radionuclide scintigraphy with 99mTc-sestamibi, ultrasonography of the neck, and parathyroidectomy. MAIN OUTCOME MEASURES: Operative findings, postoperative serum calcium concentrations. RESULTS: 99mTc-sestamibi scintigraphy correctly identified 17 of 21 parathyroid tumours in patients who were about to undergo their first parathyroidectomy (sensitivity = 81%) with a positive predictive value of 94% and all 6 in patients with persistent or recurrent hyperparathyroidism. Ultrasonography correctly identified 13 parathyroid tumours in 18 patients about to undergo their first parathyroidectomy (sensitivity = 72%) with a positive predictive value of 93%, but only 3 among the 6 patients with persistent or recurrent hyperparathyroidism. CONCLUSION: Single radionuclide scintigraphy with 99mTc-sestamibi seems to identify the sites of parathyroid tumours accurately in patients with persistent or recurrent hyperparathyroidism but is not recommended for patients with primary hyperparathyroidism. Combining scintigraphy with ultrasonography does not improve the accuracy.

Adult↗

Detection of myocardial viability with F-18-fluorodeoxyglucose and single photon emission computed tomography.

The application of 18-F-fluorodeoxyglucose (FDG) imaging with single photon emission computed tomography (SPECT) to detect tissue viability has been introduced recently in several centers, both in Europe and the USA. This paper summarizes the available data on FDG SPECT. Three studies have performed a direct comparison between FDG SPECT and FDG PET, showing good agreement between these techniques. Preliminary data in patients with poor left ventricular function undergoing revascularization suggest that FDG SPECT can predict improvement of ventricular function after revascularization. Comparative studies between FDG SPECT and low-dose dobutamine echocardiography also showed close agreement. Although the initial results are promising, larger studies are needed to determine the precise role of FDG SPECT in the assessment of myocardial viability.

Cardiotonic Agents↗

Increased bone mass with pamidronate treatment in rheumatoid arthritis. Results of a three-year randomized, double-blind trial.

OBJECTIVES: Osteoporosis is a frequent complication of rheumatoid arthritis (RA). We therefore investigated the effect of oral pamidronate therapy as a specific bone-sparing agent in RA. METHODS: The study design was a 3-year randomized, double-blind trial of 300 mg oral pamidronate/day compared with placebo in 105 RA patients. Bone mineral density (BMD) measured at 12-month intervals was the primary efficacy parameter. RESULTS: In 3 years, lumbar spine and forearm BMD increased significantly in the pamidronate-treated group (by 8.4 +/- 6.9% [mean =/- SEMI] [P < 0.00011 and 5.2 =/- 6.5% [P < 0.005], respectively), compared with nonsignificant changes in the placebo-treated patients (increase of 0.6 =/- 5.2% and decrease of 1.2 =/- 5.8%, respectively). Femoral neck BMD increased in the pamidronate-treated group (by 2.6 =/- 8.6%) and decreased significantly in the placebo-treated group (by 4.0=/- 1.3% [P < 0.005]). The changes in BMD with time at all 3 measurement sites were significantly different between the treatment groups (P < 0.0001). Changes in radiographic signs of joint damage and in disease activity were similar in the 2 groups. CONCLUSION: The present study provides the first evidence that long-term treatment with an orally administered bisphosphonate overcomes bone loss and increases bone mass when compared with placebo. This finding may have significance with regard to the treatment of patients with RA.

Adult↗

The diagnostic utility of somatostatin receptor scintigraphy in oncology.

Somatostatin receptor scintigraphy (SRS) with the diethylenetriaminopentaacetic-acid-conjugated somatostatin analogue [111In-DTPA-D-Phe1] octreotide, also known as 111In-pentetreotide, is a new non-invasive modality for the evaluation of tumours that express receptors for somatostatin. These receptors are present on neuroendocrine and other tumours, including lymphomas and some breast cancers. In oncology SRS is a promising diagnostic tool for localizing primary tumours, staging, control and follow-up after therapy, and for identification of patients who may benefit from therapy with unlabelled octreotide or, in the future, with radiolabelled octreotide. In the past few years many small and large studies investigating various aspects of SRS have been reported. In this review the value of SRS in the management of individual tumour types is explored. For many tumours the best sensitivity in lesion detection is only achieved by very careful imaging after the administration of at least 200 MBq 111In-pentetreotide. On the basis of the current experience the main value of SRS in oncology is in the staging and evaluation of gastroenteropancreatic tumours, paragangliomas, small-cell lung cancer and lymphomas. Promising areas for SRS are the evaluation of breast cancer, non-medullary thyroid cancer and melanoma, and initial results with targeted radionuclide therapy using radiolabelled octreotide have been reported.

Amino Acid Sequence↗

Somatostatin receptor: scintigraphy and radionuclide therapy.

Peptide receptor scintigraphy is more sensitive at the biological than anatomical level, in contrast to conventional imaging, which it complements. Neuroendocrine tumours have the most somatostatin receptors in vitro and their metastases are somatostatin receptor positive in vitro, so that [111In-DTPA-D-Phe1]octreotide (OCT) can be used to image them. OCT was compared with conventional imaging techniques (CON) in a European Multicentre Trial. In 350 evaluable patients, CON detected 88%, and OCT 80% (glucagonomas 100%, VIPomas 88%, carcinoids 87%, non-functioning islet cell tumours 82%, insulinomas 46%) of tumour sites but there was no systematic use of abdominal single-photon-emission computerised tomography. OCT demonstrated multiple tumour sites in 62 of 178 patients in whom CON had found only 1 lesion, with 60% confirmed. 12/16 lesions detected by OCT in 11 patients with no lesions according to CON were also confirmed. The impact of OCT on management was evaluated in 235 patients and affected 40%: it determined 29 surgical decisions, led to octreotide therapy in 47, and modified octreotide dose in 18. Six end-stage patients with neuroendocrine tumours were treated with OCT radionuclide therapy (up to a cumulative dose of 53 GBq per patient) in a phase I trial. There were no major side-effects after up to 2 years treatment, with impressive effects on hormone production and a likely anti-proliferative effect.

Humans↗