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The renin-angiotensin system plays an important role in the pathogenesis of cardiac hypertrophy and chronic heart failure as angiotensin II has been shown to induce cardiac hypertrophy and fibrosis. Besides these structural alterations, functional effects on cardiomyocytes have been reported in different mammalian species. Angiotensin II is known to produce a positive inotropic effect in some species, and differences in atrial and ventricular myocardium have been described. So far, the molecular events which govern angiotensin II-mediated changes in cardiac contractility are not completely understood. In order to study the dependency of the angiotensin II-induced positive inotropic effect on receptor density, we examined the effect of angiotensin II on cardiac function in atria, papillary muscles and isolated ventricular cardiomyocytes from adult Sprague-Dawley rats and TGR(αMHC-hAT1) transgenic rats, which expressed the human angiotensin AT1 receptor (hAT1) specifically in the heart. In atrial myocardium from adult Sprague-Dawley rats, angiotensin II (30 μmol/l) produced an AT1-mediated positive inotropic effect (38.5% of control), whereas in papillary muscles and isolated ventricular myocytes, no inotropic response was observed. As shown by polymerase chain reaction (PCR) and radioligand binding, the human angiotensin AT1 receptor was exclusively expressed in transgenic animals, which markedly overexpressed the angiotensin AT1 receptor. However, in transgenic rats the positive inotropic effect in atrial preparations was similar to the controls, and neither in papillary muscles nor in isolated cardiomyocytes the increase in receptor density led to an inotropic effect induced by angiotensin II. These data suggest that the existence of functionally uncoupled receptors rather than the low density of receptors at the ventricular site is responsible for the inability of ventricular myocardium to respond to angiotensin II.

Purpose: Positron emission tomography (PET)/computed tomography (CT) measurements on small lesions are impaired by the partial volume effect, which is intrinsically tied to the point spread function of the actual imaging system, including the reconstruction algorithms. The variability resulting from different point spread functions hinders the assessment of quantitative measurements in clinical routine and especially degrades comparability within multicenter trials. To improve quantitative comparability there is a need for methods to match different PET/CT systems through elimination of this systemic variability. Consequently, a new method was developed and tested that transforms the image of an object as produced by one tomograph to another image of the same object as it would have been seen by a different tomograph. The proposed new method, termed Transconvolution, compensates for differing imaging properties of different tomographs and particularly aims at quantitative comparability of PET/CT in the context of multicenter trials. Methods: To solve the problem of image normalization, the theory of Transconvolution was mathematically established together with new methods to handle point spread functions of different PET/CT systems. Knowing the point spread functions of two different imaging systems allows determining a Transconvolution function to convert one image into the other. This function is calculatedmore » by convolving one point spread function with the inverse of the other point spread function which, when adhering to certain boundary conditions such as the use of linear acquisition and image reconstruction methods, is a numerically accessible operation. For reliable measurement of such point spread functions characterizing different PET/CT systems, a dedicated solid-state phantom incorporating {sup 68}Ge/{sup 68}Ga filled spheres was developed. To iteratively determine and represent such point spread functions, exponential density functions in combination with a Gaussian distribution were introduced. Furthermore, simulation of a virtual PET system provided a standard imaging system with clearly defined properties to which the real PET systems were to be matched. A Hann window served as the modulation transfer function for the virtual PET. The Hann's apodization properties suppressed high spatial frequencies above a certain critical frequency, thereby fulfilling the above-mentioned boundary conditions. The determined point spread functions were subsequently used by the novel Transconvolution algorithm to match different PET/CT systems onto the virtual PET system. Finally, the theoretically elaborated Transconvolution method was validated transforming phantom images acquired on two different PET systems to nearly identical data sets, as they would be imaged by the virtual PET system. Results: The proposed Transconvolution method matched different PET/CT-systems for an improved and reproducible determination of a normalized activity concentration. The highest difference in measured activity concentration between the two different PET systems of 18.2% was found in spheres of 2 ml volume. Transconvolution reduced this difference down to 1.6%. In addition to reestablishing comparability the new method with its parameterization of point spread functions allowed a full characterization of imaging properties of the examined tomographs. Conclusions: By matching different tomographs to a virtual standardized imaging system, Transconvolution opens a new comprehensive method for cross calibration in quantitative PET imaging. The use of a virtual PET system restores comparability between data sets from different PET systems by exerting a common, reproducible, and defined partial volume effect.« less

Reinhardt M, Emrich D, Krause T, Bräutigam P, Nitzsche E, Blattmann H, Schümichen C, Moser E. Improved dose concept for radioiodine therapy of multifocal and disseminated functional thyroid autonomy. Eur J Endocrinol 1995;132:550–6. ISSN 0804–4643 The present study analyzes the improvement of the outcome of radioiodine therapy in non-immunogenic hyperthyroidism by adapting the target dose to the 99mTc-pertechnetate thyroid uptake under suppression (TcTUs) prior to radioiodine therapy. The TcTUs is a substitute for the non-suppressible iodine turnover. The 89 patients presented with a basal thyrotropin level of s between 1.6 and 3.2% (group A) and 57 had a TcTUs > 3.2% (group B). Fifty-five patients (three of group A and 52 of group B) were treated previously for overt hyperthyroidism with antithyroid drugs. Target doses of 150 and 200 Gy were used in both groups and 300 Gy in group B only. Six months after radioiodine therapy, a basal TSH level of ≥ mU/l as criterion of therapy success was observed in 94% of group A and in 54% of group B. Further differentiation of group B shows an increasing success rate with the target dose used: 45% after 150 Gy, 50% after 200 Gy and 90% after 300 Gy. In patients with a basal TSH level of s was evaluated again. Persistence of functional thyroid autonomy, defined as TcTUs > 1.6%, was found in 89% (one patient of group A, 24 patients of group B) and still observed a high extent of autonomous function in 25% of them, evidenced by a TcTUs > 3.2% (seven patients of group B, target doses of 150 or 200 Gy). No case of overt hypothyroidism was observed within the first 6 months after radioiodine therapy and no difference was found in therapy outcome between multifocal and disseminated thyroid autonomy. As a consequence, the target dose should be adapted to the TcTUs prior to radioiodine therapy in the range of 150–300 Gy to the total thyroid gland. Michael Reinhardt, Abteilung Nuklearmedizin, Radiologische Universitätsklinik, Hugstetter Straße 55. 79106 Freiburg im Breisgau, Germany

Background The release of endothelium-derived relaxing factors has been shown experimentally to be of pivotal importance for the maintenance of coronary blood flow during increased demand. In humans with coronary atherosclerosis, endothelial vasodilator dysfunction is not confined only to epicardial conductance vessels but may also extend into the coronary microcirculation. We therefore tested the hypothesis that endothelial vasodilator dysfunction of the coronary resistance vasculature is associated with myocardial ischemia during exercise in patients without hemodynamically significant epicardial artery stenoses. Methods and Results Coronary vasodilator function was assessed by subselective infusion of the endothelium-dependent dilator acetylcholine (0.036 to 3.6 μg/mL) and the endothelium-independent dilator papaverine (7 mg). Coronary blood flow responses were evaluated by intracoronary Doppler flow velocity recordings and quantitative angiography. Exercise-induced myocardial perfusion was determined by 201 Tl single photon emission computed tomographic imaging. Thirteen patients had exercise-induced myocardial perfusion defects suggestive of myocardial ischemia, whereas 14 patients had normal thallium imaging during exercise. In patients with exercise-induced thallium perfusion defects, coronary blood flow responses to acetylcholine were significantly ( P P Conclusions Impaired endothelium-dependent vasodilation of the coronary microcirculation is associated with exercise-induced myocardial ischemia in patients without hemodynamically significant epicardial artery lesions. Endothelial vasodilator dysfunction extending into the coronary microcirculation may thus contribute to the ischemic manifestations of coronary artery disease during times of increased myocardial demand.

The Pas1 protein (Pas1p) is required for peroxisome biogenesis in Saccharomyces cerevisiae and contains two putative ATP-binding sites, each within a domain which is conserved among members of the recently characterized AAA-family. To elucidate whether both putative ATP-binding sites are essential for Pas1p function, lysine 467 of the first and lysine 744 of the second putative ATP-binding site were each changed to glutamate by site-directed mutagenesis. While replacement of lysine 744 abolished the function of the Pas1 protein in peroxisome biogenesis, replacement of lysine 467 had no obvious effect.

In a subgroup of 45 patients with acute myocardial infarction (AMI) from the German multicenter trial of anisoylated plasminogen streptokinase activator complex (APSAC) (n = 20) versus heparin (n = 25), simultaneous thallium (TI)-201 technetium (Tc)-99m pyrophosphate (PYP) tomography was initiated to elucidate a possible benefit of APSAC over heparin. Findings in the 2 treatment groups were similar with respect to TI-201 defect score, relative scintigraphic infarct size, and in keeping with the main group coronary artery patency, global ejection fraction and maximal creatine kinase level. However, 2 different TI-201/Tc-99m PYP accumulation patterns within the area of infarction (homogeneous, group A; inhomogeneous, group B) were identified. Both treatment groups were similar with regard to the frequency of the homogeneous and inhomogeneous pattern. In comparing the 2 accumulation patterns, creatine kinase peaked earlier in group A than in group B, and global left ventricular ejection fraction was significantly higher in group A than in group B. In Group A, 30 of 31 patients and in group B 7 of 11 patients had a patent infarct-related vessel (p0.025). TI-201 defect score was lower in group A than in group B. Likewise, relative size of the infarction as determined from Tc-99m PYP images was significantly lower in group A than in group B. Fifteen patients experienced cardiogenic shock or severe heart failure. Patients in group B had a higher incidence of these in-hospital complications than patients in group A (92 vs 12%, p0.0005). Scintigraphic infarct size and TI-201 defect score were greater in patients with the aforementioned clinical events.(ABSTRACT TRUNCATED AT 250 WORDS)

tolerated differences for the oxygen maps. Moreover, the tolerated difference was found to strongly influence the tumor control probability that could be obtained, with tumor control probability decreasing with increasing tolerated difference. Conclusions: Adaptive dose planning depends on the degree of interfraction variability in the dose planning images and thresholds used for deciding when to adapt.

The antiarrhythmic and hemodynamic effects of sotalol (160 to 480 mg/day), a beta-blocking agent that prolongs ventricular repolarization, were examined in 38 patients with complex symptomatic ventricular ectopic activity. During ambulatory monitoring, 24 patients (63%) exhibited a reduction of greater than 75% in single ventricular premature beats (VPBs) and greater than 90% reduction in repetitive arrhythmia. In contrast to the effects of other agents, left ventricular ejection fraction as determined by radionuclide angiography was not impaired, increasing slightly from 45 +/- 14% to 47 +/- 14% during therapy (p less than 0.05). Antiarrhythmic drug efficacy did not correlate with baseline ejection fraction or sotalol-induced changes in ventricular function. Late follow-up studies disclosed that antiarrhythmic efficacy and tolerance were maintained in the majority of patients. Repeat radionuclide angiography at 6 months revealed no late drug-induced depression of left ventricular function. Sotalol appears to be an effective and well tolerated agent for treatment of complex ventricular ectopic activity, even in the setting of compromised cardiac function.

The purpose of this study was to validate different scintigraphic approaches for assessing acute myocardial infarctions. 201Tl, 99Tcm pyrophosphate (PPi) and combined 201Tl/99Tcm PPi tomograms were evaluated in 115 consecutive patients, in 85 of whom clinical examination revealed acute myocardial infarction. The overall sensitivity and specificity for infarct detection was 80% versus 56% for 201Tl alone, 61% versus 97% for 99Tcm PPi alone, and 100% each for the combined 201Tl/99Tcm PPi imaging. The sensitivity for nontransmural infarcts was 57% for 201Tl, 37% for 99Tcm PPi and 100% for combined imaging. The overlay of 201Tl and 99Tcm PPi images increases the observer's confidence in the diagnosis and provides better localization of the infarction. 201Tl alone could localize the infarction in 80%, 99Tcm PPi alone in 49% and 201Tl/99Tcm PPi in 100% of the cases. ECG and 201Tl/99Tcm PPi tomography concurred upon infarct localization in 98% of the patients. Based on the 201Tl/99Tcm accumulation pattern, 94% of the Q-wave infarctions were judged to be transmural and 83% of the non-Q-wave infarctions were judged to be nontransmural. It is concluded that combined 201Tl/99Tcm PPi tomography is highly accurate for determining the presence and location of acute myocardial infarction. This technique appears to be superior to studies where only one radioisotope is used.

Es wurde der Versuch unternommen, durch Umsetzung von Zellstoffen mit Glycidyltrimethylammoniumchlorid im Losungsmittelsystem Dimethylacetamid/Lithiumchlorid kationische Cellulosederivate mit moglichst hohen Substitutionsgraden zu erhalten. Hierzu wurden Temperaturabhangigkeit, Reaktionsdauer und Molverhaltnis der Reaktanden untersucht. Als optimal erwies sich eine Reaktionsdauer von 8 h bei einer Reaktionstemperatur von 70°C. Der Cellulosegehalt in Losung und das Molverhaltnis der Reaktanden mussen dem verwendeten Zellstoff angepast werden. An attempt was made to obtain cationic cellulose derivatives of highest possible degrees of substitution by treating dissolving grade pulps under homogeneous conditions with glycidyltrimethylammonium chloride in the solvent system dimethylacetamide/lithiumchloride. The influence of temperature, reaction time and molar ratio of the reagents was examined. A reaction time of 8 h and a temperature of 70°C have been found to be optimal. The cellulose content in solution and the molar ratio of the reagents have to be adapted to the used pulp.

An uber 20 Derivaten von N'-methylierten Saurehydraziden (1-Methylsemicarbaziden, 3-Methyl-carbazinsaureestern, N'-Methylcarbonsaurehydraziden, N'-Methylsulfonsaurehydraziden) wird die Anwendungsbreite der zu entsprechend acylierten Hexahydro-1,2,4,5-tetrazinen fuhrenden Oxidation mit Blei(IV)-acetat untersucht; als reaktive Zwischenprodukte werden 1,3-dipolare N'-acylierte Carbenium-iminium-N-imide diskutiert. Oxidative Cyclization of N'-Methylhydrazides with Lead Tetraacetate Acylated hexahydro-1,2,4,5-tetrazines are obtained from N'-methylhydrazides by oxidation with lead tetraacetate. The range of application of this reaction was investigated using more than 20 hydrazides. 1,3-Dipolar species of type 3 are discussed as intermediates.

Es wird eine Methode zur Bestimmung der Packungsdichte (Rohdichte) verholzter Zellwande—defintert durch das Gewicht der Holzsubstanz je Volumeneinheit der Zellwand—beschrieben. Die Methode beruht auf der Bestimmung des volumens einer Holzprobe, des Gewichts derselben Probe in absolut trockenem Zustand und der planimetrische Messung des prozentualen Anteils der Zellwande am Gesamtvolumen auf mikroskopischem Wege Aus den erhaltenen Werten wird die Packungsdichte berechnet. Untersucht wurden Pappel-, Buchen-, Birken-, Eukalyptus-und Schirmbaumholz, z. T. an mehreren Proben.

Die rechnerunterstutzte Konstruktion von Spezialrechnern aus Programmen anwendungsorientierter hoherer Programmiersprachen wird motiviert.

Radium Ra-223 dichloride (radium-223, Xofigo®) is a targeted alpha therapy approved for the treatment of castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastatic disease. Radium-223 is the first targeted alpha therapy in this indication providing a new treatment option, with evidence of a significant survival benefit, both in overall survival and in the time to the first symptomatic skeletal-related event. The skeleton is the most common metastatic site in patients with advanced prostate cancer. Bone metastases are a clinically significant cause of morbidity and mortality, often resulting in bone pain, pathologic fracture, or spinal cord compression necessitating treatment. Radium-223 is selectively accumulated in the bone, specifically in areas of high bone turnover, by forming complexes with the mineral hydroxyapatite (the inorganic matrix of the bone). The alpha radiation generated during the radioactive decay of radium-223 produces a palliative anti-tumour effect on the bone metastases. The purpose of this guideline is to assist nuclear medicine specialists in evaluating patients who might be candidates for treatment using radium-223, planning and performing this treatment, understanding and evaluating its consequences, and improving patient management during therapy and follow-up.

PET/CT guidance for percutaneous interventions allows biopsy of suspicious metabolically active bone lesions even when no morphological correlation is delineable in the CT images. Clinical use of PET/CT guidance with conventional step-by-step technique is time consuming and complicated especially in cases in which the target lesion is not shown in the CT image. Our recently developed multimodal instrument guidance system (IGS) for PET/CT improved this situation. Nevertheless, bone biopsies even with IGS have a trade-off between precision and intervention duration which is proportional to patient and personnel exposure to radiation. As image acquisition and reconstruction of PET may take up to 10 minutes, preferably only one time consuming combined PET/CT acquisition should be needed during an intervention. In case of required additional control images in order to check for possible patient movements/deformations, or to verify the final needle position in the target, only fast CT acquisitions should be performed. However, for precise instrument guidance accounting for patient movement and/or deformation without having a control PET image, it is essential to be able to transfer the position of the target as identified in the original PET/CT to a changed situation as shown in the control CT.