Endothelial dysfunction following coronary artery bypass grafting : Influence of patient and procedural factors.

BACKGROUND: Angiopoietin-2 (Angpt2) mediates endothelial dysfunction (ED) following coronary artery bypass grafting (CABG). Its triggers are, however, poorly understood. METHODS: We examined the time course of ED beyond the early phase of postoperative recovery in 75 patients following CABG with a special focus on different cardiopulmonary bypass (CPB) modes as potential triggers of Angpt2 release. RESULTS: Nine patients (12.0%) underwent off-pump coronary artery bypass (OPCAB), 31 patients (41.3%) received minimized extracorporeal circulation (MECC), and 35 patients (46.6%) were operated on with (conventional) CPB. Angpt2 levels steadily increased across the observation period (1.7 [1.4-2.1] to 3.4 [2.5-6.1] ng/ml, p < 0.001). Angpt2 levels did not differ between the MECC and CPB groups (p = 0.564). There was no difference between MECC and CPB patients regarding net fluid balance (p = 0.821) and other surrogate markers of postoperative ED. The magnitude of Angpt-2 increase correlated more strongly with baseline C­reactive protein (r = 0.459, p < 0.001) than with any other parameter. Hospital length of stay correlated more strongly with baseline Angpt2 levels (r = 0.512, p = 0.005) than with follow-up Angpt2 levels and appeared not to be influenced by CPB mode (p = 0.428). CONCLUSION: CABG is associated with prolonged ED, which is determined by the patient's preoperative inflammatory state rather than by CPB modifications.

Fibre type composition in the lumbar perivertebral muscles of primates: implications for the evolution of orthogrady in hominoids.

The axial musculoskeletal system is important for the static and dynamic control of the body during both locomotor and non-locomotor behaviour. As a consequence, major evolutionary changes in the positional habits of a species are reflected by morpho-functional adaptations of the axial system. Because of the remarkable phenotypic plasticity of muscle tissue, a close relationship exists between muscle morphology and function. One way to explore major evolutionary transitions in muscle function is therefore by comparative analysis of fibre type composition. In this study, the three-dimensional distribution of slow and fast muscle fibres was analysed in the lumbar perivertebral muscles of two lemuriform (mouse lemur, brown lemur) and four hominoid primate species (white-handed gibbon, orangutan, bonobo, chimpanzee) in order to develop a plausible scenario for the evolution of the contractile properties of the axial muscles in hominoids and to discern possible changes in muscle physiology that were associated with the evolution of orthogrady. Similar to all previously studied quadrupedal mammals, the lemuriform primates in this study exhibited a morpho-functional dichotomy between deep slow contracting local stabilizer muscles and superficial fast contracting global mobilizers and stabilizers and thus retained the fibre distribution pattern typical for quadrupedal non-primates. In contrast, the hominoid primates showed no regionalization of the fibre types, similar to previous observations in Homo. We suggest that this homogeneous fibre composition is associated with the high functional versatility of the axial musculature that was brought about by the evolution of orthograde behaviours and reflects the broad range of mechanical demands acting on the trunk in orthograde hominoids. Because orthogrady is a derived character of euhominoids, the uniform fibre type distribution is hypothesized to coincide with the evolution of orthograde behaviours.

Colloid volume loading does not mitigate decreases in central blood volume during simulated haemorrhage while heat stressed.

Heat stress results in profound reductions in the capacity to withstand a simulated haemorrhagic challenge; however, this capacity is normalized if the individual is volume loaded prior to the challenge. The present study tested the hypothesis that volume loading during passive heat stress attenuates the reduction in regional blood volumes during a simulated haemorrhagic challenge imposed via lower-body negative pressure (LBNP). Seven subjects underwent 30 mmHg LBNP while normothermic, during passive heat stress (increased internal temperature ∼1◦C), and while continuing to be heated after intravenous colloid volume loading (11 ml kg⁻¹). Relative changes in torso and regional blood volumes were determined by gamma camera imaging with technetium-99m labelled erythrocytes. Heat stress reduced blood volume in all regions (ranging from 7 to 16%), while subsequent volume loading returned those values to normothermic levels. While normothermic,LBNP reduced blood volume in all regions (torso: 22 ± 8%; heart: 18 ± 6%; spleen: 15 ± 8%). During LBNP while heat stressed, the reductions in blood volume in each region were markedly greater when compared to LBNP while normothermic (torso: 73 ± 2%; heart: 72 ± 3%; spleen: 72 ± 5%, all P<0.001 relative to normothermia). Volume loading during heat stress did not alter the extent of the reduction in these blood volumes to LBNP relative to heat stress alone (torso: 73 ± 1%; heart: 72 ± 2%; spleen: 74 ± 3%, all P>0.05 relative to heat stress alone). These data suggest that blood volume loading during passive heat stress (via 11 ml kg⁻¹ of a colloid solution) normalizes regional blood volumes in the torso, but does not mitigate the reduction in central blood volume during a simulated haemorrhagic challenge combined with heat stress.

Recovery after long-term summer drought: Hydraulic measurements reveal legacy effects in trunks of Picea abies but not in Fagus sylvatica.

Climate change is expected to increase the frequency and intensity of summer droughts. Sufficient drought resistance, the ability to acclimate to and/or recover after drought, is thus crucial for forest tree species. However, studies on the hydraulics of mature trees during and after drought in natura are scarce. In this study, we analysed trunk water content (electrical resistivity: ER) and further hydraulic (water potential, sap flow density, specific hydraulic conductivity, vulnerability to embolism) as well as wood anatomical traits (tree ring width, conduit diameter, conduit wall reinforcement) of drought-stressed (artificially induced summer drought via throughfall-exclusion) and unstressed Picea abies and Fagus sylvatica trees. In P. abies, ER indicated a strong reduction in trunk water content after 5 years of summer drought, corresponding to significantly lower pre-dawn leaf water potential and xylem sap flow density. Vulnerability to embolism tended to be higher in drought-stressed trees. In F. sylvatica, only small differences between drought-stressed and control trees were observed. Re-watering led to a rapid increase in water potentials and xylem sap flow of both drought-stressed trees, and to increased growth rates in the next growing season. ER analyses revealed lower trunk water content in P. abies trees growing on throughfall-exclusion plots even 1 year after re-watering, indicating a limited capacity to restore internal water reserves. Results demonstrated that P. abies is more susceptible to recurrent summer drought than F. sylvatica, and can exhibit long-lasting and pronounced legacy effects in trunk water reserves.

[Disability assessment for the statutory pension insurance: significance, need for research, and opportunities]. / Sozialmedizinische Begutachtung im Rentenverfahren: Stellenwert, Forschungsbedarf und Chancen.

Disability assessment is a complex and multifaceted process of exploration and evaluation, which in terms of legal evidence can be of far-reaching consequence for the claimant, the statutory pension insurance and finally for society as well. In the article the specifics of the assignment, the assessment situation, and the process of evaluation are described. Based upon an analysis of the so far only little research activities, the future need for research is subdivided into 4 thematic groups: 1 Operationalization and validation of central dimensions of evaluation; 2 Investigation of the structure of the expert decision-making process and the factors influencing it; 3 Investigation of the influence of sociopolitical, labour market-related and economical aspects on the evaluation; 4 Quality assurance. On the other hand the article describes the special quality of disability assessment. In a unique way it offers an integrated reflection of the medical history, limitation in capacity and participation and options for treatment and rehabilitation. Beyond the assessment of functional capacity, it could be of use for the development of innovative forms of support for the rehabilitation of working capacity.

One-day or two-day procedure for sentinel node biopsy in melanoma?

PURPOSE: We compared the outcome of a 1-day and a 2-day sentinel node (SN) biopsy procedure, evaluated in terms of lymphoscintigraphic, surgical and pathological findings. METHODS: We studied 476 patients with melanoma from two melanoma centres using static scintigraphy and blue dye. A proportional odds model was used for statistical analysis. RESULTS: The number of SNs visualized at scintigraphy increased significantly with time from injection to scintigraphy and activity left in the patient at scintigraphy, and depended on the melanoma location. The number of SNs removed at surgery increased with the number of SNs visualized at scintigraphy and time from injection to surgery. The frequency of nodal metastasis increased with increasing thickness and Clark level of the melanoma, and was highest for two SNs visualized at scintigraphy. CONCLUSION: This study showed that early vs. late imaging and surgery do make a difference on the outcome of the SN procedure and confirmed the importance of the scintigraphic visualization of all true SNs.

EA-1, a novel adhesion molecule involved in the homing of progenitor T lymphocytes to the thymus.

The mouse progenitor T lymphocyte (pro-T) cell line FTF1 binds in vitro to thymus blood vessels, the thymic capsule, and liver from newborn mice. A mAb, EA-1, raised against an embryonic mouse endothelial cell line, blocked adhesion. The antibody also interfered with pro-T cell adhesion to a thymus-derived mouse endothelial cell line; it had no effect on the adhesion of mature T lymphocytes and myeloid cells. The antigen recognized by EA-1 is located on the vascular endothelium of various mouse tissues and absent on pro-T cells. EA-1 antibody precipitates molecules with apparent molecular weights of 110,000, 140,000, 160,000, and 200,000. Immunoclearing and binding-inhibition studies with antibodies against known adhesion molecules suggest that the EA-1 antigen is a novel adhesion molecule involved in colonization of the embryonic thymus by T cell progenitors.

The initial domestication of goats (Capra hircus) in the Zagros mountains 10,000 years ago.

Initial goat domestication is documented in the highlands of western Iran at 10,000 calibrated calendar years ago. Metrical analyses of patterns of sexual dimorphism in modern wild goat skeletons (Capra hircus aegagrus) allow sex-specific age curves to be computed for archaeofaunal assemblages. A distinct shift to selective harvesting of subadult males marks initial human management and the transition from hunting to herding of the species. Direct accelerator mass spectrometry radiocarbon dates on skeletal elements provide a tight temporal context for the transition.

Sentinel node detection in melanomas using contrast-enhanced ultrasound.

BACKGROUND: Sentinel node (SN) biopsy has proven to be a useful clinical method based on the combination of radionuclide tracer principles and the dye technique. Contrast-enhanced ultrasound (CEUS) has been used successfully for detection of SN in animals, but the use of CEUS has not been reported in humans. PURPOSE: To investigate the possible use of CEUS in detecting SN in patients with malignant melanomas (MM), and to improve the method by using different concentrations of contrast agent and various positions of the extremity. MATERIAL AND METHODS: Ten patients with MM on an extremity and one healthy volunteer were included. One milliliter of a contrast agent (Sonovue; Bracco, Milan, Italy) was injected subcutaneously on both sides of the scar from the excised tumor. Contrast-enhanced lymph channels and lymph nodes (LNs) were searched for using low-mechanical-index CEUS and by stimulated acoustic emission. Afterward, lymphoscintigraphy was performed and the patient operated. During surgery, the SNs were located via scintigraphic findings, gamma-probe signals, and blue-dye visualization of lymph channels and LNs. Before the human study, a study of 10 mice was performed to exclude possible tissue damage, as the contrast agent was not registered for subcutaneous administration. RESULTS: In one patient, two contrast-enhanced inguinal LNs were visualized by CEUS, corresponding to two inguinal SNs found by scintigraphic imaging. No contrast-enhanced lymph channels or LNs were visualized in any other patients or in the volunteer. No tissue damage was observed in the 10 mice. CONCLUSION: This study does not support the use of CEUS for detection of SNs in humans. However, the application of CEUS for the investigation of SNs is still not fully explored in humans, and an alternative setup and/or contrast agent might provide better results.

Nuclear cardiology and coronary surgery.

Rising age, repeated percutaneous coronary revascularizations, and co-morbidity such as overweight, diabetes, and hypertension, characterize a change over the last 20-30 years in coronary patients referred to coronary artery bypass grafting (CABG). This patient group represents a great part of today's large and increasing patient population with heart failure, and their treatment remains a limited success. CABG may lead to symptomatic and prognostic improvement, but the limited risk of operative complications has to be balanced against the chances of symptomatic and prognostic benefit from the operation. Identification of culprit lesions and estimation of the severity of coronary stenoses of intermediate or uncertain degree are important in preoperative decision-making. Location and extent of a perfusion abnormality must reflect the anatomical distribution of an angiographic stenosis, supporting or arguing against the decision to revascularize . Myocardial perfusion imaging by single photon emission computed tomography or positron emission tomography before surgery will increase the level of information about coronary hemodynamics and myocardial viability before surgical intervention and is therefore highly recommended to increase the chances of successful coronary surgery, as well as to reduce the small risk of operative complications.

Recent advances in nuclear cardiology.

Nuclear cardiology is an essential part of functional, non-invasive, cardiac imaging. Significant advances have been made in nuclear cardiology since planar (201)thallium ((201)TI) scintigraphy was introduced for the evaluation of left ventricular (LV) perfusion nearly 40 years ago. The use of nuclear cardiology has been steadily increasing over the last 20 years with important steps being the introduction of (99m)technetium- ((99m)Tc)-labelled perfusion radiotracers, the change from only planar to now much more single photon emission computed tomography (SPECT) and positron emission tomography (PET), electrocardiogram gating of nuclear perfusion imaging, and finally introducing nuclear hybrid imaging using either SPECT or PET together with either computed tomography or magnetic resonance imaging. The indications have extended from nearly only coronary artery diseases to several non-coronary cardiac diseases. The advances in nuclear cardiology are discussed under the four headlines of: 1) myocardial perfusion, 2) cardiac performance including LV and right ventricular (RV) function, 3) myocardial metabolism, and 4) experimental nuclear cardiology.

Diagnosis of ovarian tumour tissues by SR-FTIR spectroscopy: A pilot study.

Ovarian cancer is the seventh most common cancer among women across the world with very high mortality rates. Histology is considered the gold standard for tumour diagnosis. FTIR spectroscopy is relies on registering biochemical differences in the samples analysed, including biological specimens. Therefore, the Synchrotron radiation based-Fourier transform infrared spectroscopy (SR-FTIR) was used for the preliminary investigation of the molecular composition of the human, non-fixed ovarian neoplastic tissues with different type of biological potential. The study that was carried out on thin tissue sections, placed on barium fluoride infrared windows, was focused on investigating spatial distribution of the biochemical markers in various ovarian tumours. Since the structural constituents of tissues accumulate different molecules which may correspond to the specific type of ovarian tumours, the main goal of this study was to check if the mean intensities of the spectral lines of some bio-molecules can be treated as ovarian cancer bio-indicators. Moreover, an attempt to identify and understand the underlying biochemical changes associated with the disease was carried out. The major spectral differences in the frequency and intensities were identified as bonds of lipids, protein massif and nucleic acids. The results obtained suggest that Fourier transform infrared spectroscopy can be used as a supporting tool in the analysis of neoplastic ovarian tissue.

[Protocolized cognitive-behavioural group therapy for inflammatory bowel disease]. / Tratamiento cognitivo-conductual protocolizado en grupo de las enfermedades inflamatorias intestinales.

INTRODUCTION: patients affected by inflammatory bowel disease have a high rate of psychiatric disorders such as depression and anxiety. OBJECTIVE: the main goal of this study was to design, to put into practice, and to validate a protocolized psychological treatment program based on the coping model, and a psycho-educational methodology in which the following intervention modules were included- illness information, coping model, problem solving techniques, relaxation, social skill training, distraction, and cognitive restructuring techniques. All these techniques were adapted to the characteristic features of inflammatory bowel disease. METHOD: the sample included 57 patients with inflammatory bowel disease from the Spanish Crohn s Disease and Ulcerative Colitis Association. The sample was randomly assigned to one of the two experimental groups -33 were assigned to the treatment group, and 24 were assigned to the waiting list control group. RESULTS: the results reflected a significant clinical and statistical improvement in anxiety (p < 0.001) and depression (p < 0.001) variables when compared to the waiting list control group. Likewise, improvement was sustained at 3, 6, and 12 months during follow-up. CONCLUSION: the protocolized psychological treatment program, administered in group sessions, is effective in reducing emotional symptoms arising as a result of inflammatory bowel disease.

The regulatory background of nuclear cardiology in Europe: a survey by the European Council of Nuclear Cardiology.

PURPOSE: Nuclear cardiology is a well-validated, non-invasive imaging modality that is highly cost-effective as a diagnostic and prognostic tool in the evaluation of patients with known or suspected coronary artery disease. However, the number of procedures in Europe is very far from that which would be expected on the basis of epidemiological data, particularly when comparison is made with the USA. As a preliminary step for future action aimed at improving and increasing nuclear cardiology practice in Europe, the European Council of Nuclear Cardiology performed a survey to identify the regulatory issues and the training components pertaining to the practice of nuclear cardiology. METHODS: a questionnaire was sent to 31 national nuclear medicine societies and to 40 national cardiology societies. The main areas covered by the survey were: (1) the license requirements, (2) the theoretical and practical aspects of training and (3) supervision of the stress test during a nuclear cardiology study. RESULTS: The results show that, in a setting of wide heterogeneity of national regulations, education and professional practice, nuclear medicine is a restricted and closely regulated specialty. This situation guarantees the quality and safe use of radionuclides; at the same time, however, it limits integration of nuclear medicine into the clinical arena. CONCLUSION: Cardiologists should become more involved in nuclear cardiology, to further stimulate the use of this powerful diagnostic and prognostic imaging modality.

Systemic two-stage carcinogenesis in the epithelium of the forestomach of mice using 7,12-dimethylbenz(a)anthracene as initiator and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate as promoter.

In a modified two-stage carcinogenesis experiment, the effectiveness of the initiator 7,12-dimethylbenz(a)anthracene (DMBA) and the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) in the epithelium of the forestomach of the mouse has been investigated. Fifty mice were treated intragastrically with a single dose of DMBA (50 mg/kg body weight), followed by repeated intragastric administration of TPA (10 mg/kg body weight) over a period of 35 weeks. In comparison with the corresponding control groups (no treatment, DMBA initiation only, and TPA treatment only), the initiated and promoted group clearly showed the highest tumor incidence in the target organ (45 tumor-bearing animals of 50 animals). No tumors of the forestomach were found in the untreated control group and the TPA-treated group, whereas in the DMBA-initiated group, ten animals had developed tumors of the forestomach. In addition to the mouse skin model for two-stage carcinogenesis, the mouse forestomach appears to respond to DMBA initiation-TPA promotion. This organ provides an additional tissue with which to investigate tumor promotion and further to ascertain specific parameters of the promotion step.

Magnesium from bioresorbable implants: Distribution and impact on the nano- and mineral structure of bone.

Biocompatibility is a key issue in the development of new implant materials. In this context, a novel class of biodegrading Mg implants exhibits promising properties with regard to inflammatory response and mechanical properties. The interaction between Mg degradation products and the nanoscale structure and mineralization of bone, however, is not yet sufficiently understood. Investigations by synchrotron microbeam x-ray fluorescence (µXRF), small angle x-ray scattering (µSAXS) and x-ray diffraction (µXRD) have shown the impact of degradation speed on the sites of Mg accumulation in the bone, which are around blood vessels, lacunae and the bone marrow. Only at the highest degradation rates was Mg found at the implant-bone interface. The Mg inclusion into the bone matrix appeared to be non-permanent as the Mg-level decreased after completed implant degradation. µSAXS and µXRD showed that Mg influences the hydroxyl apatite (HAP) crystallite structure, because markedly shorter and thinner HAP crystallites were found in zones of high Mg concentration. These zones also exhibited a contraction of the HAP lattice and lower crystalline order.

Hydrolytic degradation of phosphatidylethanolamine and phosphatidylcholine by isolated rat-liver lysosomes.

Lysosomal catabolism of radioactively labelled phosphatidylethanolamine, phosphatidylcholine and several potential metabolites of these diacylphospholipids was studied using rat-liver lysosomes which had been isolated from Triton WR-1339-treated animals. Hydrolysis of these lipids seems to be restricted to the soluble lysosomal compartment. The initial intralysosomal degradation is predominantly catalysed by phospholipase A1 (EC 3.1.1.32) followed by lysophospholipase (EC 3.1.1.5). The end products of this pathway are free fatty acids and glycerophosphorylethanolamine or glycerophosphorylcholine. These phosphodiesters are not hydrolysed further in lysosomes, as has been shown previously (Fowler, S. and De Duve, C. (1969) J. Biol. Chem. 144, 471-481). The intermediary lysophospholipids, however, are also hydrolysed by an alternative pathway, i.e. by a lysophospholipase which catalyses the hydrolysis of the glycerophosphate ester bond, followed by a monoacylglycerol lipase and a phosphomonoesterase (EC 3.1.3.2), respectively. Besides these two catabolic routes of intralysosomal hydrolysis of phosphatidylethanolamine and phosphatidylcholine, additional pathways are possible, which seem, however, to be of minor importance, at least in the substrate concentration ranges employed in these studies. These additional reactions include attack by a phospholipase A2 (EC 3.1.1.4) and--as discovered recently (Matsuzawa, Y. and Hostetler, K.Y. (1980) J. Biol. Chem. 255, 646-652)--by a phospholipase C (EC 3.1.4.3). Cations such as Mg2+, Ca2+, K+ and Na+ inhibit preferentially deacylation reactions.

Effects of antimalarial drugs on several rat-liver lysosomal enzymes involved in phosphatidylethanolamine catabolism.

The effects of three cationic amphiphilic antimalarial drugs (chloroquine, mepacrine and primaquine) on the intralysosomal catabolism of phosphatidylethanolamine and several of its metabolites were studied with rat-liver lysosomes which had been isolated from animals previously treated with Triton WR-1339. The activities of each of the various enzymes involved in the main pathways of intralysosomal phosphatidylethanolamine degradation (Kunze, H., Hesse, B. and Bohn, E. (1982) Biochim. Biophys. Acta 711, 10-18) exhibited almost identical inhibitory sensitivities towards mepacrine and primaquine. In contrast, chloroquine inhibited the activities of the various enzymes to different extents, lysophospholipid acylhydrolase (EC 3.1.1.5) being the most sensitive enzyme, followed by phospholipase A1 (EC 3.1.1.32) and monoacylglycerol lipase, and eventually lysophospholipid monoacylglycerol hydrolase as the least sensitive enzyme. The relative inhibitory potencies towards phospholipase A1 activity of chloroquine were increased with increasing pH, and the mode of inhibition was competitive. In contrast, the inhibitory potencies towards monoacylglycerol lipase activity of chloroquine increased only up to pH 5 but decreased above this value, and the mode of inhibition was noncompetitive.

Effects of antimalarial drugs on phospholipase A and lysophospholipase activities in plasma membrane, mitochondrial, microsomal and cytosolic subcellular fractions of rat liver.

Activities of membrane-associated phospholipases A1 and A2, and membrane-associated as well as soluble lysophospholipases were measured in different subcellular fractions of rat liver, using suspensions of stereospecifically labelled radioactive phospholipids as substrates. Plasma membranes and endoplasmic reticulum were shown to contain phospholipase A1 and lysophospholipase activities, both of which could be stimulated by Ca2+, mitochondria Ca2+-dependent phospholipase A2 and cytosol Ca2+-independent lysophospholipase activities. Each of these lipolytic enzymes could be inhibited by antimalarial drugs (chloroquine, mepacrine, primaquine) at concentrations above 1 x 10(-4) M. Inhibition of the alkaline cytosolic lysophospholipase by these drugs was noncompetitive with respect to the substrate, and the inhibitory potency increased, when the pH was raised.