Monitoring left ventricular dilation in mice with PET.

Molecular imaging by small-animal PET is an important noninvasive means to phenotype transgenic mouse models in vivo. When investigating pathologies of the left ventricular (LV) myocardium, the serial assessment of LV volumes is important. By this, the presence of LV dilation as a sign of developing heart failure can be detected. Whereas PET is usually used to derive biochemical and molecular information, functional parameters such as ventricular volumes are generally measured using echocardiography or MRI. In this study, a novel method to monitor LV dilation in mice with PET is presented and evaluated using cardiac MRI. METHODS: A semiautomatic 3-dimensional algorithm was used to delineate the LV myocardial wall on static PET images depicting myocardial glucose metabolism ((18)F-FDG PET) for 20 mice: 10 wild-type and 10 genetically modified littermates designed to develop a dilative cardiomyopathy phenotype (cardiomyocyte-specific knockout of survivin). The volume enclosed by the 3-dimensional midmyocardial contour was calculated as a measure for LV volume for each mouse. Data were compared with ventricular volumes measured by MRI in the same animals. RESULTS: LV volumes obtained by PET and MRI correlated well (R = 0.89) for hearts with small and large left ventricles. In accordance with the hypothesis, the LV volumes were increased significantly for transgenic mice examined at an older age compared with those examined at a younger age (MRI: 160.5 +/- 25.7 microL vs. 114.7 +/- 15.2 microL [P = 0.012]; PET: 129.3 +/- 15.3 microL vs. 73.8 +/- 15.0 microL [P < 0.001], all values shown as mean +/- SD; for MRI, mean of end-diastolic and end-systolic volumes are given), whereas they did not for their wild-type littermates (MRI: 106.2 +/- 12.3 microL vs. 94.7 +/- 14.6 microL [P = 0.214]; PET: 82.6 +/- 20.9 microL vs. 65.0 +/- 16.9 microL [P = 0.185]). CONCLUSION: Evaluation and quantitation of LV dilation in both control and cardiomyopathic mice can be reliably and serially performed using small-animal PET and (18)F-FDG, yielding useful functional information in addition to metabolic data.     

Diagnostik und Therapiestrategie bei Weichteilsarkomen

Soft tissue sarcomas (STS) represent a rare entity of all malignant tumors (1%). Thus, an in-depth understanding of multidisciplinary treatment strategies may not be sufficiently present at all operative units. Consecutively, optimal diagnostic and therapeutical pathways may not be applied. Magnetic resonance imaging (MRI) is the procedure of choice in diagnosing STS. Biopsies should be performed in specialized centers. Identification of cytogenetic factors has become more important for the typing and prognosis of STS. Management of STS should employ multimodal treatment concepts (Oncology, Radiotherapy, Surgical Oncology). The decision on whether radiotherapy, chemotherapy or another option is indicated should be taken by an interdisciplinary tumor board, which also determines the sequence of treatment in relation to resection. To obtain sufficient information from histopathologic examination of the resected tumor, a clear and distinct definition of critical margins and topography by the surgeon is essential. Following these concepts, optimal local tumor control associated with resections preserving function and limbs is achieved without impairment of overall prognosis. Tumor resection alone, without previous evaluation and where appropriate adopting multimodal treatment strategies, no longer meets modern standards. After primary treatment is complete, patients have to be enrolled in a standardized follow-up program.     

Anterior Cruciate Ligament Reconstruction: State of the Art

Abstract The rupture of the Anterior cruciate ligament (ACL) belongs to the most common ligament injuries of the human knee joint. ACL rupture results in an increased anterior translation and internal rotation of the tibia. Untreated knee instability causes a disintegration of the roll and sliding movement and a high incidence of secondary meniscus and chondral damages with consecutive or advanced arthritic changes. For deciding on a conservative or operative therapy, it is necessary to develop a high-risk profile. Elderly, inactive patients without instability symptoms can be treated conservatively; younger, active people and complex ligament injuries should receive an ACL replacement. The goal is to eliminate instability by maintaining the physiological kinematics of the knee. Anterior cruciate ligament may be reconstructed arthroscopically assisted by autologous tendons. Predominantly, hamstring- and bone-patellar-tendon grafts are used. No significant differences in knee laxity, clinically and functionally, were observed between both grafts. Various reconstruction techniques, single- or double-bundle techniques, were described. Successful replacement depends on a correct tunnel placement and reconstruction of the physiological band tension, a sufficient mechanical stability of fixation, an impingement-free range of motion and an adequate rehabilitation. A high degree of patient satisfaction in clinical and functional outcome could be evaluated.     

Increase in the degree of phosphorylation of circulating fibrinogen under thrombolytic therapy with urokinase

Human fibrinogen is phosphorylated in vivo to an equal extent at two positions, one at Ser 3 located on fibrinopeptide A, the other at Ser 345 of the A alpha-chain. As has been shown previously, the degree of phosphorylation of the circulating fibrinogen pool can be determined in vitro from the ratio between the HPLC peaks formed by phosphorylated and non-phosphorylated fibrinopeptide A which has been cleaved from plasma fibrinogen by thrombin or reptilase. Plasma samples were obtained from patients with venous thrombosis undergoing fibrinolytic therapy with urokinase (n = 8). The degree of phosphorylation increased from about 35% before treatment to values between 50% and 70% within 48 hours. It remained at these high levels as long as urokinase was administered and declined slowly thereafter. This behaviour of the degree of phosphorylation of fibrinogen is explained by a model which assumes that fibrinogen is secreted in the phosphorylated form and then dephosphorylated in the circulation by an up to now unidentified phosphatase by first order kinetics. When this system is in steady state, the degree of phosphorylation is about 25% under normal conditions. If the elimination rate of fibrinogen is greatly enhanced by fibrinogenolysis the system will approach a new steady state with a higher degree of phosphorylation, the magnitude of which will depend on the new ratio of dephosphorylation and elimination.     

Closed-loop feedback control of methohexital anesthesia by quantitative EEG analysis in humans

A combined pharmacokinetic and pharmacodynamic model of methohexital was used to establish and evaluate feedback control of methohexital anesthesia in 13 volunteers. The median frequency of the EEG power spectrum served as the pharmacodynamic variable constituting feedback. Median frequency values from 2-3 Hz were chosen as the desired EEG level (set-point). In 11 volunteers, the feedback system succeeded in maintaining a satisfactory depth of anesthesia (i.e., unresponsiveness to verbal commands and tactile stimuli). During feedback control, 75% of all measured median frequency values were in the preset range of 2-3 Hz. This distribution of median frequency was obtained by applying random stimulation (six different acoustic and tactile stimuli) to the volunteers approximately every 1.5 min. The decrease of median frequency from baseline to anesthetic values was primarily induced by increasing the fractional power in the frequency band of 0.5-2 Hz from 12.6 +/- 4.5% (mean +/- SD) to 46.0 +/- 2.5%. The median time to recovery (as defined by opening eyes on command) after cessation of the feedback control period was 20.6 min (10.7-44.5 min) when median EEG frequency was 5.2 Hz (4.7-8.4 Hz). The average requirement of methohexital (mean +/- SD) during the 2 h was 1.02 +/- 0.16 g. It is concluded that pharmacokinetic-pharmacodynamic models of intravenous anesthetics established previously may be used to form a suitable background for model-based feedback control of anesthesia by quantitative EEG analysis. This approach gives a possible solution to the problem of adapting pharmacokinetic and pharmacodynamic data to individuals when using population mean data as starting values for drug therapy.     

Beitrag zur Frage der Fremdkörperappendicitis

Zusammenfassung Es bleibt für die Bedeutung des Fremdk?rpers in der Appendix nur ein Moment übrig: Der Fremdk?rper kann, ?hnlich wie andere mechanische Ver?nderungen des Wurmes, eine günstige Disposition schaffen, bei der eine eintretende Infektion gut wirksam werden kann. Er ist aber nicht Ursache der Appendicitis. *** DIRECT SUPPORT *** A00EI668 00008