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.     

Emergency Treatment of Multiply Injured Patients with Unstable Disruption of the Posterior Pelvic Ring by Using the “C–Clamp”

Abstract Purpose: Evaluation of the therapeutic usefulness of the “pelvic C–clamp” (PCC) during emergency treatment of multiply injured patients with unstable disruption of the posterior pelvic ring. Patients and Methods: The data of 28 patients with polytrauma in combination with an unstable fracture of the posterior pelvic ring (average Injury Severity Score [ISS]: 49 points; average Polytrauma Score [PTS]: 41 points) were retrospectively analyzed from the moment they were admitted to the emergency room until 48 h after admittance. The PCC was used immediately for primary stabilization of the pelvis after clinical diagnosis of the unstable pelvic fracture. Main outcome measurements: development of mean blood pressure, development of oxygenation level, period of time until the PCC was placed, number of blood units needed, period of time until circulatory stabilization occurred. Results: The PCC was applied in all cases within an average of 64.7 min after trauma. Seven patients (25%) died within the first 45 min after admission. The surviving patients showed:• an increase in mean blood pressure of 25% 20 min after application of the PCC,• a hemodynamic stabilization 6 h after application of the PCC,• a stabilization of the oxygenation level 6 h after application of the PCC,• a decrease in the number of required blood units 6 h after application of the PCC. Conclusion: The present study shows, that the application of the PCC to critically injured patients with unstable pelvic fractures leads to stabilization of the vital parameters within a short period of time.     

Effect of dialysis flux and membrane material on dyslipidaemia and inflammation in haemodialysis patients.

BACKGROUND: Dyslipidaemia, inflammation and oxidative stress are prominent risk factors that potentially cause vascular disease in haemodialysis patients. Dialysis modalities affect uraemic dyslipidaemia, possibly by modifying oxidative stress, but the effects of dialyser flux and membrane material on atherogenic remnant particles and oxidized low-density lipoproteins (LDL) are unknown. METHODS: We performed a randomized crossover study in 36 patients on haemodialysis to analyse the effect of dialyser flux and membrane material on plasma lipids, apolipoproteins and markers of inflammation and oxidative stress. Stable patients on low-flux dialysis with polysulphone for >/=6 weeks were assigned to high-flux polysulphone or high-flux modified cellulose with similar dialyser surface area and permeability characteristics and crossed over twice every 6 weeks. RESULTS: Thirty patients completed the study per protocol. Treatments with high-flux polysulphone and modified cellulose lowered serum triglyceride (by 20% and 10%, respectively; P<0.05) and remnant-like particle cholesterol by 32% (P<0.001) and 11% (NS) after the first 6 weeks of treatment. Oxidized LDL decreased significantly with high-flux polysulphone, but not with modified cellulose. Apolipoproteins CII and CIII were reduced, whereas the ratio CII/CIII was increased (all P<0.05). Acute-phase proteins and LDL and high-density lipoprotein cholesterol remained unaffected. CONCLUSIONS: This randomized crossover study demonstrates a potent effect of high-flux haemodialysis on uraemic dyslipidaemia. Polysulphone membrane material showed superiority on oxidatively modified LDL, an indicator of oxidative stress in haemodialysis patients.     

Phage-displayed recombinant single-chain antibody fragments with high affinity for cholesteryl ester transfer protein (CETP): cDNA cloning, characterization and CETP quantification.

Cholesteryl ester transfer protein (CETP) greatly affects the metabolism of all lipoprotein classes including low-density lipoprotein (LDL) and high-density lipoprotein (HDL), both known to constitute powerful risk factors for coronary artery disease (CAD). We now report the successful first cloning and characterization of single-chain antibody fragments specific for CETP. A recombinant phage display library was generated using spleen mRNA isolated from BALB/c mice that had been immunized with highly purified CETP. Screening of the library yielded two single-chain antibody fragments with high affinity for CETP, termed 1CL8 and 1CL10, displaying respective KD values of 4.36 x 10(-9) M and 4.64 x 10(-9) M as determined by affinity sensor technology. Amino acid sequence comparison indicated the complementarity-determining regions of the respective heavy chains to be responsible for CETP high affinity binding. Fragment 1CL8 was successfully employed in clinical chemical quantification systems that uncovered an association in humans between plasma CETP concentration and total body fat mass (r=0.50, p<0.002). Because of the demonstrated superb CETP capturing capacity, combined with high binding affinity to CETP, ready access and unlimited supply, 1CL8 and 1CL10 are expected to prove powerful tools for studies on the role of CETP in atherogenesis.     

Interdisziplin?re Leitlinien zur Diagnostik und Therapie der extrazerebralen Amyloidosen

Ohne Zusammenfassung     

Short-term lack of cerebral perfusion with good outcome. Advantages of early intracranial pressure monitoring

A 21-year-old man was injured by a tailboard of a truck. He suffered a severe head injury with bilateral depressed skull fractures necessitating surgical decompression. On admission to the hospital the patient showed bending to pain stimuli (Glasgow Coma Score 5). Anisocoria was noticed from the beginning. Initial intracranial pressure (ICP), measured 3 hours after injury, was 30 mm Hg, and the cerebral perfusion pressure (CPP) was 70 mm Hg. During surgical elevation of the skull fracture on the right side an unexplainable rise of ICP to values of 100 mm Hg occurred, which corresponded to the mean arterial blood pressure (MAP). At the same time both pupils were dilated and fixed indicating a lack of cerebral perfusion. Due to immediate trephination of the opposite side, the ICP was lowered to values below 20 mm Hg, and sufficient cerebral perfusion (above 50 mm Hg) was regained. The patient showed a good recovery and was transferred to a rehabilitation center 5 weeks after injury.This case report emphasizes the importance of early and continuous intracranial pressure monitoring for adequate therapy in neurosurgical emergencies.