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Peter Bernhardt

Publications and source records attributed to Peter Bernhardt.

At least 19 recordsLinked to original sources
PubMed2006

Detection of cardiac small vessel disease by adenosine-stress magnetic resonance.

BACKGROUND: Patients testing positive for myocardial ischemia but without significant coronary artery (CA) stenosis in coronary angiography (CXA) are characterized as having "small vessel disease" (SVD). The aim of our study was to identify these patients by stress perfusion cardiac magnetic resonance (CMR). METHODS: 317 patients with suspected myocardial ischemia and clinical indication for CXA were scanned < 72 h before CXA in a whole-body 1.5T scanner. After 3 min of adenosine infusion (140 microg/kg/min), a myocardial first-pass perfusion sequence in 4-5 contiguous short-axis orientations using a Gadolinium-based contrast agent (0.1 mmol/kg) was performed. Images were analyzed qualitatively by two independent and blinded investigators. RESULTS: Perfusion deficits were detected in 93% of our patients. In 78% of patients with relevant perfusion delay, perfusion deficits extended to > 1/3 of the wall thickness in > or = 2 myocardial segments, persisted for > 5 heartbeats and were regarded as relevant coronary macroangiopathy. All of these patients had significant CA stenosis (60% had luminal narrowing > 70% and 18% had 50-70%). 22% of the patients had perfusion deficits affecting < or = 1/3 of wall thickness with persistence for < or = 5 heartbeats and were regarded as having SVD. None of these patients had a CA stenosis of > 50% or received CA revascularization. These patients more frequently had hypertension (p<0.0001), diabetes (p<0.05) and circumferential perfusion deficits (p<0.0001) than other patients. CONCLUSION: Stress perfusion CMR allows non-invasive differentiation between patients with significant CA stenosis and patients with SVD caused by hypertension and/or diabetes based on the temporal and spatial extent of perfusion deficits. Patients with SVD more often have diffuse perfusion deficits with shorter persistence than patients with significant CA disease.

Adenosine↗
PubMed2006

Administered activity and metastatic cure probability during radioimmunotherapy of ovarian cancer in nude mice with 211At-MX35 F(ab')2.

PURPOSE: To elucidate the therapeutic efficacy of alpha-radioimmunotherapy of ovarian cancer in mice. This study: (i) estimated the minimum required activity (MRA), giving a reasonable high therapeutic efficacy; and (ii) calculated the specific energy to tumor cell nuclei and the metastatic cure probability (MCP) using various assumptions regarding monoclonal-antibody (mAb) distribution in measured tumors. The study was performed using the alpha-particle emitter Astatine-211 (211At) labeled to the mAb MX35 F(ab')2. METHODS AND MATERIALS: Animals were inoculated intraperitoneally with approximately 1 x 10(7) cells of the cell line NIH:OVCAR-3. Four weeks later animals were treated with 25, 50, 100, or 200 kBq 211At-MX35 F(ab')2 (n = 74). Another group of animals was treated with a nonspecific mAb: 100 kBq 211At-Rituximab F(ab')2 (n = 18). Eight weeks after treatment the animals were sacrificed and presence of macro- and microscopic tumors and ascites was determined. An MCP model was developed and compared with the experimentally determined tumor-free fraction (TFF). RESULTS: When treatment was given 4 weeks after cell inoculation, the TFFs were 25%, 22%, 50%, and 61% after treatment with 25, 50, 100, or 200 kBq (211)At-MX35 F(ab')2, respectively, the specific energy to irradiated cell nuclei varying between approximately 2 and approximately 400 Gy. CONCLUSION: As a significant increase in the therapeutic efficacy was observed between the activity levels of 50 and 100 kBq (TFF increase from 22% to 50%), the conclusion was that the MRA is approximately 100 kBq (211)At-MX35 F(ab')2. MCP was most consistent with the TFF when assuming a diffusion depth of 30 mum of the mAbs in the tumors.

Animals↗
PubMed2006

Clinical implication of adenosine-stress cardiac magnetic resonance imaging as potential gatekeeper prior to invasive examination in patients with AHA/ACC class II indication for coronary angiography.

BACKGROUND: Real world cardiology is faced with a low diagnostic yield of coronary angiography (CXA) in patients presenting with ACC/AHA class II CXA indication. Our aim was to analyze the clinical implication of a Cardiac MR (CMR) protocol including adenosine stress perfusion in this patient population. We examined whether CMR could enhance appropriate CXA indication and thus reduce the rate of pure diagnostic CXA. In addition, we compared the relative impact of CMR exam components (perfusion, function and viability assessment) in achieving this target. METHODS: 176 patients were referred for CXA with class II indication. 171 underwent complete additional CMR exam in a 1.5-T whole body CMR-scanner for myocardial function, ischemia and viability prior to CXA. The routine protocol for assessment of CAD consisted of functional imaging (long and short axes), adenosine stress- and rest-perfusion in short axis orientation and "late enhancement" imaging in long and short axes. Images were analyzed by two independent and blinded investigators. Interobserver differences were resolved by a third reader. RESULTS: There was a high association between CMR results and subsequent invasive findings (chi square for CMR perfusion deficit and stenosis >70% in CXA: 113.7, p<0.0001). 109 (63.7%) of our patients had relevant perfusion deficits as seen by CMR and matching coronary artery stenosis >70%. Four (2.3%) patients had false negative CMR findings. In 58 patients (33.9%) no relevant coronary artery stenosis could be observed, correctly predicted by CMR in 48 cases; in 10 (5.8%) patients CMR provided false positive results. Sensitivity of CMR to detect relevant CAD (>70% luminal narrowing) was 0.96, specificity 0.83, positive predictive value 0.92 and negative predictive value 0.92. Of the CMR components, perfusion deficit was the strongest independent predictor (odds ratio 132.3, p < 0.0001). CONCLUSION: In a great number of patients being referred to cath lab with ACC/AHA class II indication for CXA, CMR provides a high accuracy for decision making regarding appropriateness of the invasive exam. CMR prior to CXA could substantially reduce pure diagnostic coronary angiographies in patients with intermediate probability for CAD, in our patient-cohort from approximately 34% to 6%. Further studies are warranted to identify rare false negative CMR results.

Adenosine↗
PubMed2006

Antitumoural effects of the pyridyl cyanoguanidine CHS 828 on three different types of neuroendocrine tumours xenografted to nude mice.

CHS 828, a cyanoguanidine with potent experimental antitumoural activity, inhibits activation of nuclear factor-kappaB. In the present study, marked antitumoural activity of peroral CHS 828 was shown against three different human neuroendocrine tumours, midgut carcinoid (GOT1), pancreatic carcinoid (BON), and medullary thyroid carcinoma (GOT2), transplanted in nude mice. Our results indicate that CHS 828 can be a candidate drug for treatment of neuroendocrine tumours.

Animals↗
PubMed2006

Radiation-induced up-regulation of somatostatin receptor expression in small cell lung cancer in vitro.

BACKGROUND: The internalization of radiolabeled somatostatin analogs into tumor cells is of great importance for radionuclide therapy. It has previously been shown that some radiolabeled somatostatin analogs are internalized through receptor-mediated endocytosis. The development of methods that increase the number of receptors on tumor cells is important to further improve the internalization of radionuclides. The aim of this study was to investigate the possibility of inducing up-regulation of the somatostatin receptor (sstr) expression on tumor cells by external-beam irradiation. METHODS: Human small cell lung cancer (SCLC) cells were irradiated to absorbed doses of 2-8 Gy, and the uptake of 177Lu-DOTA-Tyr3-octreotate was measured 1-7 days after irradiation. The sstr2 mRNA expression was determined by quantitative reverse transcriptase-polymerase chain reaction. RESULTS: The uptake of 177Lu-DOTA-Tyr3-octreotate was 1.5-3 times higher in cells irradiated to 4 Gy than in nonirradiated cells, and the highest uptake occurred 1 and 3-5 days after irradiation. The uptake of 177Lu-DOTA-Tyr3-octreotate was similar for cells irradiated to 2, 4, 6 and 8 Gy. The sstr2 mRNA expression was twice as high in the cells irradiated to 4 Gy than in the nonirradiated cells. CONCLUSIONS: The uptake of 177Lu-DOTA-Tyr3-octreotate increased in SCLC cells after exposure to irradiation, probably due to up-regulation of sstr expression. These results may be important in optimizing the treatment of tumors expressing sstr using radiolabeled somatostatin analogs.

Carcinoma, Small Cell↗
PubMed2006

Safety of adenosine stress magnetic resonance imaging using a mobile cardiac magnetic resonance system.

BACKGROUND: Contrast-enhanced magnetic resonance imaging (ceMRI) allows for the detection of ischemic heart disease. Aim of this prospective study was to show feasibility, practicability and safety of adenosine stress ceMRI in routine outpatients with a mobile scanner. METHODS: Consecutive patients were scanned in six different cardiac outpatient centers with a 1.5 T mobile ceMRI scanner. First-pass wash-in patterns of gadolinium chelate were evaluated after three minutes of adenosine infusion. After a second bolus of gadolinium chelate myocardial late enhancement (MLE) images of the left ventricle were acquired to visualize myocardial necrosis. RESULTS: Five hundred seventy-four patients were enrolled to the study. No major complications during examination and adenosine infusion were observed. One hundred seventy-three minor complications as temporary atrio-ventriculare blockade, mild chest pain or dyspnea and nausea were noticed. None of the complications led to further special treatment CONCLUSION: This ceMRI protocol is suitable for application in outpatient settings. CeMRI stress testing using a mobile scanner in an outpatient setting is feasible and safe.

Adenosine↗
PubMed2006

Atrial thrombi-a prospective follow-up study over 3 years with transesophageal echocardiography and cranial magnetic resonance imaging.

BACKGROUND: Patients with atrial fibrillation (AF) and atrial thrombi have an increased risk for cerebral embolism. However, there is little knowledge about the long-term fate of atrial thrombi and the incidence of cerebral embolism in patients under oral anticoagulation. METHODS: Consecutive patients with persistent or permanent AF and left atrial (LA) thrombi were included in the study. We performed serial and prospective transesophageal echocardiography, cranial magnetic resonance imaging, and clinical examinations during a period of 3 years. Oral anticoagulation was continued or initiated in all patients. A target INR of 2.5 was intended in all patients. RESULTS: Forty-three patients with LA thrombi and persistent or permanent AF were included. During the follow-up period 31(72%) of the thrombi disappeared. Patients with disappearance of thrombi had significantly smaller thrombi (P < 0.01), a lower echogenicity of thrombi (P < 0.01), and a lower LA volume (P = 0.02). Twenty-two (51%) patients suffered from cerebral embolism and/or death during the observation period. Five patients died due to embolic events. The only independent predictors of cerebral embolism were an elevated peak emptying velocity of the LA appendage (P < 0.001) and a history of previous thromboembolism (P < 0.01). CONCLUSIONS: Patients with persistent or permanent AF and atrial thrombi have a high long-term risk of cerebral embolism and/or death (51%) even despite the oral anticoagulation therapy. Thrombus size may predict thrombus resolution under continued anticoagulation.

Aged↗
PubMed2006

Dosimetric characterization of radionuclides for systemic tumor therapy: influence of particle range, photon emission, and subcellular distribution.

Various radionuclides have been proposed for systemic tumor therapy. However, in most dosimetric analysis of proposed radionuclides the charged particles are taken into consideration while the potential photons are ignored. The photons will cause undesirable irradiation of normal tissue, and increase the probability of toxicity in, e.g., the bone marrow. The aim of this study was to investigate the dosimetric properties according to particle range, photon emission, and subcellular radionuclide distribution, of a selection of radionuclides used or proposed for radionuclide therapy, and to investigate the possibility of dividing radionuclides into groups according to their dosimetric properties. The absorbed dose rate to the tumors divided by the absorbed dose rate to the normal tissue (TND) was estimated for different tumor sizes in a mathematical model of the human body. The body was simulated as a 70-kg ellipsoid and the tumors as spheres of different sizes (1 ng-100 g). The radionuclides were either assumed to be uniformly distributed throughout the entire tumor and normal tissue, or located in the nucleus or the cytoplasm of the tumor cells and on the cell membrane of the normal cells. Fifty-nine radionuclides were studied together with monoenergetic electrons, positrons, and alpha particles. The tumor and normal tissue were assumed to be of water density. The activity concentration ratio between the tumor and normal tissue was assumed to be 25. The radionuclides emitting low-energy electrons combined with a low photon contribution, and the alpha emitters showed high TND values for most tumor sizes. Electrons with higher energy gave reduced TND values for small tumors, while a higher photon contribution reduced the TND values for large tumors. Radionuclides with high photon contributions showed low TND value for all tumor sizes studied. The radionuclides studied could be divided into four main groups according to their TND values: beta emitters, Auger electron emitters, photon emitters, and alpha emitters. The TND values of the beta emitters were not affected by the subcellular distribution of the radionuclide. The TND values of the Auger electron emitters were affected by the subcellular radionuclide distribution. The photon emitters showed low TND values that were only slightly affected by the subcellular radionuclide distribution. The alpha emitters showed high TND values that were only slightly affected by the subcellular radionuclide distribution. This dosimetric characterization of radionuclides may be valuable in choosing the appropriate radionuclides for specific therapeutic applications.

Body Burden↗
PubMed2006

Can quantification of VMAT and SSTR expression be helpful for planning radionuclide therapy of malignant pheochromocytomas?

Tumor-specific uptake of the radio-iodinated norepinephrine analogue meta-iodobenzylguanidine (MIBG) or uptake of radiolabeled somatostatin analogues via somatostatin receptors (SSTRs) are possibilities to diagnose and treat malignant pheochromocytomas/paragangliomas (PCs/PGs). The aims of this study were to investigate the quantitative expression of vesicular monoamine transporters (VMAT 1, 2) and all five SSTRs in malignant pheochromocytoma/paraganglioma (PC/PG) to evaluate the possibilities for tumor-specific radionuclide therapy. High scintigraphic 123I-MIBG uptake was found in two malignant PGs with high VMAT expression (500-730 copies of VMAT 1, 1,500-1,700 copies of VMAT 2 per 1,000 beta-actin), while no 123I-MIBG uptake was found in the malignant PG with low VMAT expression (330 copies of VMAT 1, 350 copies of VMAT 2 per 1,000 beta-actin). The two patients with high VMAT expression and high 123I-MIBG uptake were treated with 131I-MIBG (2-3x8 GBq). In vitro, the VMAT antagonist, reserpine, and the membrane pump inhibitor, clomipramine, inhibited the uptake of 123I-MIBG into tumor cells equally well (48% and 53% reduction respectively, P<0.001). SSTR2 was the most abundant receptor subtype, but in the two malignant PGs its expression was only 110-260 copies/1,000 beta-actin. The transporters at the cell membrane and in the vesicular membrane both appear to be of importance for the uptake of 123I-MIBG into malignant PC/PG. Quantitative determination of VMAT expression may be helpful in selecting patients suitable for radionuclide therapy with 131I-MIBG. The present data indicate that SSTR-mediated radionuclide therapy will not be effective treatment of malignant PC/PG.

3-Iodobenzylguanidine↗
PubMed2006

Aspects on radionuclide therapy in malignant pheochromocytomas.

Malignant pheochromocytomas/paragangliomas (PCs/PGs) often have distant metastases to the skeleton, liver, and lungs. Radionuclide therapy is valuable for treatment of disseminated tumor disease and could be used as adjuvant therapy after surgery. Patients with local and/or distant metastases of PC/PG should be investigated preoperatively by scintigraphy using both 123I-MIBG and 111In-DTPA-D-Phe1-octreotide, to evaluate the possibilities for radionuclide therapy (i.e., a dosimetric estimation of radiation dose to the tumor tissue versus critical normal tissues). Individual patient dose-planning should be performed. For patients in whom positive therapeutic effects are anticipated radionuclide therapy can be applied. Therapy with both 131I-MIBG and 177Lu-octreotate might be favorable in individual patients with lesions visualized by both metaiodobenzylguanidine (MIBG) and octreotide scintigraphy with enhanced therapeutic effects and reduced side effects.

3-Iodobenzylguanidine↗
PubMed2006

Electron- and positron-emitting radiolanthanides for therapy: aspects of dosimetry and production.

UNLABELLED: All lanthanides have similar chemical properties regarding labeling. Therefore, radiolanthanides that have been used for therapy, such as (153)Sm and (177)Lu, might easily be replaced with other radiolanthanides. The aim of this work was to investigate the suitability of electron- and positron-emitting radiolanthanides for radionuclide therapy with reference to dosimetry and production possibilities. METHODS: Radiolanthanides with half-lives of 1 h to 15 d, stable or long-lived daughters, and limited photon emission were selected. The ratio of the absorbed dose rate to the tumors and the normal tissue (TND) was calculated for different tumor sizes and compared with the TND values for (90)Y and (131)I. The normal tissue and tumors were simulated as an ellipsoid and spheres, respectively. The TND values depend on the physical parameters of the radionuclides, the tumor size, and the ratio between the activity concentrations in the tumor and normal tissue (TNC). RESULTS: (153)Sm, (161)Tb, (169)Er, (175)Yb, and (177)Lu had the highest TND values for most of the tumor sizes studied. Among these radiolanthanides, (161)Tb and (177)Lu are the only ones that can be produced no-carrier-added (nca) and with high specific activities. The Auger-electron emitters (161)Ho and (167)Tm had high TND values for tumors weighing less than 1 mg and can be produced nca and with high specific activities. (142)Pr, (145)Pr, and (166)Ho showed TND values similar to those of (90)Y. (166)Ho is generator produced and can be obtained nca and at high specific activities. (143)Pr, (149)Pm, (150)Eu, (159)Gd, (165)Dy, (176m)Lu, and (179)Lu had higher TND values than did (90)Y for all tumor sizes studied, but only (149)Pm can be produced nca and at high specific activities. The other electron-emitting radiolanthanides and the positron-emitting radiolanthanides showed low TND values for all tumor sizes because of the high photon contribution. CONCLUSION: The low-energy electron emitters (161)Tb, (177)Lu, and (167)Tm might be suitable for radionuclide therapy. The Auger-electron emitter (161)Ho might not be suitable for systemic radionuclide therapy (intravenous injection) because of its short half-life but might be suitable for local therapy (e.g., in body cavities). If higher electron energy is needed, (149)Pm or (166)Ho might be suitable for radionuclide therapy.

Electrons↗
PubMed2005

Prediction of necessity for coronary artery revascularization by adenosine contrast-enhanced magnetic resonance imaging.

BACKGROUND: Assessing myocardial first-pass wash-in during pharmacological induced stress allows detection of perfusion deficits and indicates stenotic coronary arteries (CA). The aim of our study was to demonstrate clinical relevance of contrast-enhanced stress magnetic resonance imaging (CMR) by predicting necessity of CA intervention. METHODS: 738 patients with scheduled coronary angiography (CXA) were scanned in a 1.5 Tesla CMR scanner. After 3 min of adenosine infusion (140 microg/kg/min), first-pass kinetic of contrast agent was evaluated. Myocardial necrosis was visualized with "myocardial late enhancement (MLE)". Perfusion deficits were described as either "ischemia in viable myocardium", or "no relevant ischemia in viable myocardium" or as "ischemia in chronic myocardial infarction (CMI)" based on spatial and temporal extent of ischemia and of MLE. CXA was performed in all patients within 48 h after CMR and revascularization, if applicable, was performed. Angiograms were read by two independent and blinded investigators and matched with CMR findings. RESULTS: 539 patients (73%) showed "ischemia in viable myocardium" and revascularization was performed in 513 patients (95%). In 111 patients with "no relevant ischemia in viable myocardium", revascularization was performed in only 5 patients (5%). In 88 patients classified as "ischemia in CMI", revascularization was performed in 14 patients (16%). Positive predictive value of CMR for CA intervention was 0.95, negative predictive value was 0.89, sensitivity was 0.96, and specificity was 0.87. CONCLUSION: CMR allows clinical useful prediction of relevant CA disease with need for revascularization prior to CXA and may be used as non-invasive test for myocardial ischemia and viability to guide further therapy.

Adenosine↗
PubMed2005

Cardiac magnetic resonance in outpatients in Germany--indications, complications and protocol suggestions from a high-volume center.

BACKGROUND: Cardiac magnetic resonance (CMR) has developed into a routine examination in many centers in cardiology. However, there is little knowledge about its applicability in outpatients as a diagnostic tool for cardiovascular diseases. We report about the experiences in a high-volume cardiac imaging center and in a "mobile setting" in Germany and provide routinely used examination protocols. METHODS: 8976 patients referred for CMR from cardiologists, internal medicine practices and from general practitioners and 2200 patients examined in a "mobile" system by outpatient cardiologists were included in the study. Indications were as follows: 7672 (69%) examinations for myocardial ischemia and viability, 1313 (12%) for cardiac and pericardial inflammatory disease and cardiac mass, 976 (9%) for detection and quantification of heart valve disease and 466 (4%) for congenital heart disease. 697 (6%) were referred for other indication. Two independent readers performed image analysis of the 8976 patients in our center. RESULTS: Image quality was rated "excellent" in 90.6%, "good" in 8%, "fair" in 1.2% and "poor" in 0.2%. 0.0002% of all examinations were not assessable due to low image quality. Minor complications (temporarily, asymptomatic AV-blockade; mild chest pain and/or dyspnea; nausea) could be observed in 12% and resolved within few minutes. One patient experienced a grand mal seizure due to hyperventilation. 0.9% examinations had to be terminated untimely due to claustrophobia. CONCLUSION: CMR in outpatients is a widely used imaging modality in cardiology in Germany. A large variety of clinical questions may be answered by CMR with excellent image quality and without major complication. With user-adapted protocols, a rapid diagnosis is achieved even in outpatients in a "mobile" setting. Hence, CMR will increase its applicability as a routine imaging tool.

Clinical Protocols↗
PubMed2005

Patients with atrial fibrillation and dense spontaneous echo contrast at high risk a prospective and serial follow-up over 12 months with transesophageal echocardiography and cerebral magnetic resonance imaging.

OBJECTIVES: We sought to assess the prognosis of patients with atrial fibrillation (AF) and dense spontaneous echo contrast (SEC) and to determine the incidence of cerebral embolism under continued oral anticoagulation. BACKGROUND: Patients with AF and dense SEC have an increased risk of cerebral embolism. However, there is little knowledge about the long-term fate and the rate of clinical silent cerebral embolism under continued oral anticoagulation. METHODS: Between 1998 and 2001, all consecutive patients with AF and dense SEC were included in the study. We performed serial and prospective transesophageal echocardiography, cranial magnetic resonance imaging, and clinical examinations during a period of 12 months. RESULTS: A total of 128 patients with dense SEC and AF were included. The control group consisted of 143 patients with faint SEC and AF. During the follow-up period, three patients (2%) had cerebral embolism with neurologic deficits. A total of eight patients (6%) died due to embolic events, and 19 (15%) patients had silent embolism, as documented on cerebral magnetic resonance imaging. Patients with an event had significantly lower left atrial appendage peak emptying velocities and more commonly had a history of previous thromboembolism and denser SEC, as compared with patients without an event. CONCLUSIONS: Patients with AF and dense SEC have a high likelihood of cerebral embolism (22%) and/or death, despite oral anticoagulation. Low peak emptying velocities of the left atrial appendage and dense SEC are independent predictors of an event.

Anticoagulants↗
PubMed2005

Incidence of cerebral embolism after cardioversion of atrial fibrillation: a prospective study with transesophageal echocardiography and cerebral magnetic resonance imaging.

BACKGROUND: After cardioversion of atrial fibrillation the risk for cerebral embolism is increased. There is little knowledge about the incidence of cerebral embolism for patients with transesophageal echocardiography (TEE)-guided cardioversion under oral anticoagulation. METHODS: Consecutive patients with atrial fibrillation and TEE-guided cardioversion were included in the study. We performed serial TEE studies, Holter electrocardiography, cranial magnetic resonance imaging, and clinical examinations during a period of 4 weeks before and after cardioversion. Oral anticoagulation was continued or initiated in all patients. RESULTS: During the observation period 6 of 127 (4.7%) patients had new embolic lesions after cardioversion documented on cerebral magnetic resonance imaging. Patients with an event were significantly older (P = .04) and had a larger left atrium (P = .04) than patients without event. CONCLUSION: Patients with atrial fibrillation and oral anticoagulation have a low rate of clinical apparent cerebral embolism after TEE and anticoagulation-guided cardioversion. The rate of silent cerebral embolism is almost 5%. Age and left atrial size are predictors for an event.

Administration, Oral↗