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We hypothesized that (1) acute arterial hypertension increases myocardial microvascular fluid filtration and (2) the combination of acute arterial hypertension and coronary sinus pressure elevation may increase myocardial microvascular filtration sufficiently to estimate the osmotic reflection coefficient of the myocardial exchange vessels.In nine mechanically ventilated dogs we cannulated the prenodal major cardiac lymph trunk. With the use of central venous phenylephrine infusion, mean arterial pressure (MAP) was raised progressively to 120, 160, and 180 mm Hg. In five dogs we additionally raised coronary sinus pressure (CSP) to 20 and 40 mm Hg. At each manipulation of MAP and/or CSP, we measured indexes of myocardial lymphatic function and lymph-to-plasma concentration ratios for total protein (CL(TP)/CP(TP) and albumin (CL(alb)/CP(alb)).Myocardial lymph flow rate (QL; microL/min) increased exponentially (QL = 10.9.e0.014.(MAP) and myocardial lymph driving pressure (PL; mm Hg) increased linearly (PL = 2.30 + 0.20 + 0.20 . MAP) following increases, whereas CL(TP)/CP(TP) and CL(alb)/CP(alb) decreases from 0.67 +/- 0.07 (SD) to 0.56 +/- 0.10 and from 0.91 +/- 0.05 to 0.75 +/- 0.11, respectively. Adding CSP elevation increased QL up to 12 times control associated with further CL(TP)/C(TP) and CL(alb)/CP(alb) decreases to 0.49 +/- 0.05 and 0.59 +/- 0.02, respectively.We conclude that hypertensive arterial pressures are, at least in part, transmitted to the myocardial microvascular exchange vessels in the intact animal leading to increased microvascular fluid filtration. However, the combination of acute arterial hypertension and coronary sinus pressure elevation is not sufficient to produce filtration independence required for myocardial osmotic reflection coefficient determination.

Oral anticoagulation in mechanical heart valve recipients remains crucial, and vitamin K antagonists (VKA) are still the gold standard. Polymorphisms of vitamin K epoxide oxidase reductase (VKORC) and cytochrome p450 (CYP2C9) were recently found to influence VKA metabolism. We retrospectively investigated the prevalence of these genotypes and associated anticoagulation-related complications in our patients.Between August 1998 and August 2008, 563 patients received mechanical heart valve replacement in our institution. Of these, 179 completed a questionnaire on anticoagulation-related complications and consented to genetic analysis. We analysed polymorphisms of VKORC (-1639 GA; 1173 CT) and of CYP2C9 (*2, 144 CT; *3, 359 AC) by PCR and restriction analysis.For VKORC-1639/1173 alleles, there were 62 (35%) patients with the combination GG/CC, 91 (51%) with GA/CT, 25 (14%) with AA/TT and 1 (1%) with AA/CT. Phenprocoumon (PC) dosage was related to VKORC polymorphism (P0.001) with lower doses required for AA/TT patients. Overall, there were 27 severe bleedings and 11 thromboembolic events. For GG/CC, the incidence of major bleeding events and thromboembolic events was 13 and 6%, respectively, and for AA/TT, it was 27 and 12%, respectively. Variation in international normalized ratio (INR)1.5 was associated with severe bleeding complications (P = 0.025) and GA/CT patients were predisposed to INR variations1.5 (P = 0.028). No influence of CYP2C9 polymorphism on PC dosage and anticoagulation-related complications was found.VKORC polymorphism affects PC dosage and anticoagulation-related complication rates in mechanical heart valve recipients. Genotyping may help to identify patients at particular risk of anticoagulation-related complications.

This study examined the characteristics of homeless women with substance abuse problems. Data were collected on a sample of 323 homeless substance abusers. First, 49 women and 274 men were compared to demonstrate distinct problems and treatment needs of the women. Results showed that the women were more likely than the men to abuse drugs, but less likely to receive substance abuse treatment. In addition, women spent more time in doubled-up living arrangements, and were more likely to receive outpatient psychiatric treatment. Second, two subgroups of women were compared: those who had been homeless for 6 months or less, and those who had been homeless longer than 6 months during their lifetime. The women who had been homeless longer were less educated, younger when they first became homeless, and were more likely to abuse alcohol, to have been assaulted, and to have attempted suicide. Implications for research and treatment are discussed.

Aortic crossclamp may increase the risk for acute aortic dissection and embolic stroke in patients with severe aortic calcification. Additionally, in CABG re-operation aortic crossclamp may necessitate extensive dissection of fibrous adhesions which may intensify the potential risk of injury to the aorta, pulmonary artery or patent bypass grafts. Therefore, it appears to be advantageous in patients undergoing re-do CABG or with aortic calcification to minimize surgical manipulation of the aorta by abandonment of aortic crossclamp. Adequate myocardial protection and convenient surgical exposure without aortic crossclamp max be achieved by intraaortic administration of the short acting ß-blocker esmolol.

X-ray magnetic circular dichroism measurements in the hard and soft x-ray region have been performed at Mn K and L2,3 edges of the ruthenium (with x=0.05, 0.1 and 0.5) doped Ruddlesden–Popper-phase La1.2Sr1.8Mn2−xRuxO7. In combination with magnetometry, clear evidence of unexpected antiferromagnetic sublattice coupling between manganese and ruthenium was found. A simple coupling model of Mn+3/Mn+4 and Ru+3/Ru+4 ions in the high-spin state is proposed which explains the antiparallel alignment and the technological interesting increase of the Curie temperature.

Legume growers and extension agents require advice on optimum conditions under which inoculants may be stored without deterioration of rhizobia or the effectiveness of the inoculant. This study was conducted to determine effects of storage duration and temperature on survival of Rhizobium meliloti in two inoculant carriers, one with a peat base and the other with a clay base. Inoculant subsamples were placed in polyethylene bags, then packaged into plastic containers and stored in wooden boxes at either −23 °C (freezer), 4 °C (refrigerator), or room temperature (21–33 °C). Before and after storage for 0.5, 3, 6, 9, 12, 15 and 20 mo, samples were analyzed for surviving rhizobia by most probable number (MPN) plant-infection technique using plastic pouches with seedlings of alfalfa (Medicago sativa L. ’Algonquin’). These counts showed no significant reduction of rhizobial viability in either inoculant at any temperature over the 20-mo study. The surprising lack of population decreases was attributed partly to the wide span between the confidence limits of MPN estimates (at P = 0.05) and partly to the effectiveness of the protective packaging in preventing any desiccation or acidification of the inoculants. Throughout the experiment pH remained unchanged at 6.8 and 8.5 and moisture content at 12.3 and 3.0% in the peat-base and clay-base inoculants, respectively. Nodule color and size indicated that symbiotic effectiveness was not affected by storage temperature. Counts, when averaged across temperatures, showed rhizobial populations remained constant around 1.3 × 109 cells g−1 peat and 1.1 × 108 cells g−1 clay. Re-testing of R. meliloti inoculants stored for up to 10 yr at 4 °C, after earlier regulatory testing, showed no significant viability reductions in any product stored < 7 yr and in some products stored for as long as 10 yr. The results indicated that rhizobial populations could be maintained at levels much above the regulatory minimum MPN (103 seed−1), which would be of critical importance when forage legumes are grown under adverse soil conditions and inoculation is required. Key words: Rhizobium meliloti, inoculant storage, temperature effects, carrier effects, MPN plant-infection technique, inoculant quality control

The neurofibromatosis type 2 gene product merlin is known to provoke gliogenic tumors as a result of its mutagenic loss. Merlin's physiological anti-mitogenic function makes it unique among its ezrin–radixin–moesin (ERM) family members. Although ERM proteins and merlin are known to be expressed in glial cells of the peripheral nervous system and CNS, the neuronal expression pattern and function of merlin have been less well investigated. We report here expression of merlin in developing and mature neurons of the murine CNS. Within cerebellar Purkinje cells (PCs), merlin was localized in the soma, sprouting dendrites and axons. Merlin expression in PCs was high during the period of initial dendrite regression and declined during later phases of dendrite elongation. Consistently, merlin expressionin vivowas increased in Engrailed-2-overexpressing PCs, which are characterized by a reduced dendritic extension. Furthermore, overexpression of merlin in dissociated cerebellar cultures and in neurogenic P19 cells caused a significant decline in neurite outgrowth, while, conversely, inhibition of merlin expression increased process formation. This effect was dependent on phosphorylation of serine 518 and involved the inactivation of the growth-promoting GTPase Rac. We thus provide evidence that merlin plays a pivotal role in controlling the neuronal wiring in the developing CNS.

The heart, perhaps more than any other organ, is exquisitely sensitive to increases in microvascular permeability and the accumulation of myocardial interstitial oedema fluid. Whereas some organs can cope with profound increases in the interstitial fluid volume or oedema formation without a compromise in function, heart function is significantly compromised with only a few percent increase in the interstitial fluid volume. This would be of little consequence if myocardial oedema were an uncommon pathology. On the contrary, myocardial oedema forms in response to many disease states as well as clinical interventions such as cardiopulmonary bypass and cardioplegic arrest common to many cardiothoracic surgical procedures. The heart's inability to function effectively in the presence of myocardial oedema is further confounded by the perplexing fact that the resolution of myocardial oedema does not restore normal cardiac function. We will attempt to provide some insight as to how microvascular permeability and myocardial oedema formation compromise cardiac function and discuss the acute changes that might take place in the myocardium to perpetuate compromised cardiac function following oedema resolution. We will also discuss compensatory changes in the interstitial matrix of the heart in response to chronic myocardial oedema and the role they play to optimize myocardial function during chronic oedemagenic disease.

Acute rejection after kidney transplantation was found to be associated with increased recipient-derived lymph angiogenesis. However, the relation of lymph angiogenesis to acute rejection in lung transplantation has not yet been investigated.Transbronchial biopsies from 23 lung transplant recipients (47 + or - 15 years old, 15 male, 19 double lungs, 4 single lungs), taken at 14 and 90 days after transplantation were investigated. Immunohistostaining for PROX-1 (an lymphatic endothelial marker) and for vascular endothelial growth factor receptor (VEGFR) 1 and 2 (blood capillary markers) was performed. Biopsies with no sign of rejection (International Society for Heart and Lung Transplantation [ISHLT] grade A0, n = 27) were compared with biopsies with rejection grade A1/A2 (n = 19).Biopsies with ISHLT rejection grade A1 or A2 showed a significantly higher density of PROX-1 marked lymphatics in comparison with biopsies of grade A0 at 14 days (p0.001) and at 90 days (p0.001) after transplantation, and in the collective comparison (all biopsies with ISHLT grade A1 or A2 versus all biopsies with grade A0, p0.001). For VEGFR-1 and VEGFR-2, no difference was found between ISHLT grade A1 or A2 compared with grade A0, neither at 14 or 90 days nor in the collective comparison.Increased lymphatic angiogenesis after lung transplantation, demonstrated by increased density of the PROX-1 lymphatic endothelial marker, was associated with histologically evident acute organ rejection in humans. Although the exact role of lymphatic angiogenesis in acute organ rejection remains to be determined, further study of the interaction between the microvasculature and acute rejection seems warranted. Pending further investigation, analysis of PROX-1 density may develop into a new tool for rejection monitoring, supplementing conventional rejection grading.

Terminal heart failure is associated with chronic myocardial edema, which in part is compensated by increased myocardial lymph flow. However, little is known about the impact of terminal heart failure on lymphangiogenesis. The purpose of the study was to investigate the morphological and quantitative changes of the initial myocardial lymphatics in terminal heart failure.Paraffin-embedded left ventricular endomyocardial biopsies, taken during heart transplantation from 7 heart transplant recipients (failing heart) and 8 heart transplant donors (control), were investigated by immunohistostaining and triple immunofluorescence for lymphatic endothelial markers LYVE-1, PROX-1, and VEGFR-3. The vessel density was calculated and the ratio of open versus collapsed vessels was estimated by analyzing randomly selected marked vessels.The absolute densities of lymph vessels in failing and control myocardium were not significantly different for all investigated markers. The ratio of open LYVE-1 positive lymph vessels in failing heart was significantly higher than in control (64+/-12.5 vs. 44.3+/-9.3, p0.008). There was no difference for the ratio of open VEGFR-3 vessels between groups (69.0+/-17.5 vs. 70.7+/-17.2). Triple fluorescent immunohistostaining revealed in failing hearts LYVE-1 and PROX-1 positive open vessels, which were VEGFR-3 negative. VEGFR-3 positive, but LYVE-1 and PROX-1 negative vessels could also be seen.Myocardial initial lymphatics in patients with terminal heart failure undergo significant morphological changes in comparison to normal hearts. The ratio of open LYVE-1 vessels was higher in failing hearts by no difference in absolute densities for all markers. These findings suggest that appositional growth of initial lymphatics, rather than "de novo" genesis from pluripotent stem cells or sprouting from preexisting venous vessels, may be the predominant mechanism of lymphangiogenesis in terminal heart failure.

Ezrin, radixin and moesin are a family of proteins that provide a link between the plasma membrane and the cortical actin cytoskeleton. The regulated targeting of ezrin to the plasma membrane and its association with cortical F-actin are more than likely functions necessary for a number of cellular processes, such as cell adhesion, motility, morphogenesis and cell signalling. The interaction with F-actin was originally mapped to the last 34 residues of ezrin, which correspond to the last three helices (alphaB, alphaC and alphaD) of the C-terminal tail. We set out to identify and mutate the ezrin/F-actin binding site in order to pinpoint the role of F-actin interaction in morphological processes as well as signal transduction. We report here the generation of an ezrin mutant defective in F-actin binding. We identified four actin-binding residues, T576, K577, R579 and I580, that form a contiguous patch on the surface of the last helix, alphaD. Interestingly, mutagenesis of R579 also eliminated the interaction of band four-point one, ezrin, radixin, moesin homology domains (FERM) and the C-terminal tail domain, identifying a hotspot of the FERM/tail interaction. In vivo expression of the ezrin mutant defective in F-actin binding and FERM/tail interaction (R579A) altered the normal cell surface structure dramatically and inhibited cell migration. Further, we showed that ezrin/F-actin binding is required for the receptor tyrosine kinase signal transfer to the Ras/MAP kinase signalling pathway. Taken together, these observations highlight the importance of ezrin/F-actin function in the development of dynamic membrane/actin structures critical for cell shape and motility, as well as signal transduction.

A variety of potential substrates has been tested for use in the RAFT (ramp assisted foil casting technique) process. The best results were obtained for graphite ramps coated with pyrolitic carbon (PyC). The interaction mechanism between the silicon melt and the PyC surface is explained in terms of a SiC interface layer which governs the crystallization of the melt film and the separation of the RAFT foil from the ramp.

The introduction of minimum provider volumes for certain medical procedures has been the subject of scientific investigation and political controversy for quite a while. The core of the discussion focuses on the hypothesis that minimum provider volumes could significantly improve operative results and cost efficiency. In Germany the Fifth Volume of Social Law (Sozialgesetzbuch V) set the legal stage for the implementation of minimum provider volumes. This article is a brief review on the experience with minimum provider volumes in cardiac surgery. The main focus is on coronary artery bypass surgery, as this happens to be the most frequently investigated procedure.

Spinal cord injury (SCI) results in a pathophysiology characterized by multiple locomotor and sensory deficits, resulting in altered nociception and hyperalgesia. SCI triggers an early and prolonged inflammatory response, with increased interleukin-1beta levels. Transient changes are observed in subunit populations of the transcription factor nuclear factor-kappaB (NF-kappaB). There were decreases in neuronal c-Rel levels and inverse increases in p65 and p50 levels. There were no changes in neuronal p52 or RelB subunits after SCI at any time point tested. Similarly, SCI had no effect on oligodendroglial levels of any NF-kappaB subunit. There were significant early increases in COX-2 and inducible nitric oxide synthase mRNA and protein levels after SCI. We used synthetic double-stranded "decoy" deoxyoligonucleotides containing selective NF-kappaB protein dimer binding consensus sequences. Decoys targeting the p65/p50 binding site on the COX-2 promoter decreased SCI-induced cell losses, NF-kappaB p65/p50 DNA-binding activity, and COX-2 and iNOS protein levels. NF-kappaB p65/p50 targeted decoys improved early locomotor recovery after moderate but not severe SCI, yet ameliorated SCI-induced hypersensitization after both moderate and severe SCI. To determine whether changes in GABA activity played a role in decreased hypersensitivity after SCI and p65/p50 targeted decoy, we counted gamma-aminobutyric acid (GABA)-containing neurons in laminae 1-3. There were significantly more GABAergic neurons in the p65/p50 targeted decoy-treated group at the level of injury.

Gastrointestinal complications (GI-complications) after CPB are rare, but are associated with high mortality and hospital cost. This retrospective analysis investigates the incidence, patient profile and post-operative course of GI-complications after CPB. The charts of 8869 adult patients, operated on CPB between 1995 and 2002, were reviewed. Patients with post-OP GI-complications were compared to a control group of 1057 consecutive patients operated on CPB between 05/2000 and 04/2001. The incidence of GI-complications was 0.79% with an overall mortality of 21.5% (vs. 3% in controls, P

Die intraaortale Ballonpumpe (IABP) ist das derzeit am haufigsten eingesetzte mechanische Herzunterstutzungssystem, aktuell werden weltweit mehr als 100.000 IABP pro Jahr implantiert. Nach ihrem ersten klinischen Einsatz 1967 durch Adrian Kantrowitz et al. (14) wurde die IABP zunachst bei Patienten im kardiogenen Schock nach akutem Myokardinfarkt eingesetzt (2, 13). Trotz initial sehr enttauschender Ergebnisse mit hoher Letalitat dieser Patienten konnten jedoch die positiven hamodynamischen Effekte der IABP gezeigt werden, und die IABP wurde in der Folgezeit hauptsachlich von Herzchirurgen zur Behandlung des postoperativen Low-cardiac-output-Syndroms angewandt (1, 18). Seit Mitte der 80er Jahre sind 2 Trends in der IABP-Anwendung zu beobachten: einerseits der deutlich zunehmende Einsatz seitens der interventionellen Kardiologen (20; Abb. 1) - der „Benchmark Outcomes Counterpulsation Registry“Abb.1 zufolge werden aktuell 63,7% aller IABP bei kardiologischen gegenuber 29,1% bei herzchirurgischen Patienten eingesetzt (11) - andererseits der liberalere praoperative Einsatz bei herzchirurgischen Hochrisikopatienten (3, 4, 7, 9, 10, 12, 20)

Objective: The lymphatic system plays an important role in interstitial fluid balance, lipid metabolism, and immune response. The recent introduction of specific lymphatic endothelial cell markers has made the investigation of lymphangiogenesis under various conditions and from small tissue samples feasible. It was the purpose of the study to investigate the changes of myocardial lymphatic endothelial markers during the first 12 months after heart transplantation and to analyze if a correlation between lymphatic markers and rejection can be found.Methods:Right ventricular endomyocardial biopsies taken for routine rejection monitoring from 26 heart transplant recipients were investigated. Selected time points were 0.5, 1, 1.5, 6, and 12 months after human heart transplantation (HTX). Immunohistostaining was performed for VEGFR-3, the receptorforlymphangiogenicvascularendothelialgrowthfactorsCandD, forLYVE-1,anovelhyaluronanreceptor, restrictedto lymhatic vessels, and PROX-1, a homeobox gene product, which plays a key role in lymph vessel development and differentiation. Results: Density of VEGFR-3 positive lymphatics did not change during the first 12 months after transplantation. However, in comparison to the 0.5-month biopsy, density of LYVE-1 and PROX-1 positive lymphatics was significantly decreased at 1 month after transplantation (p < 0.03) and at the subsequent time points (p < 0.01). Patients with only moderate rejection during the first 12 months (ISHLT < IIIa) had a significantly higher density of VEGFR-3 at 0.5 month in comparison to patients with at least one episode of clinically relevant rejection (ISHLT IIIa or worse, p < 0.03). Conclusion: Myocardial lymphatics show a significant change of endothelial phenotype after transplantation, as demonstrated by significant quantitative changes of lymphaticendothelial markerdensity. Patientswithat least one rejectionofISHLTIIIa or higher hada significantlylowerdensityof VEGFR-3at 0.5 month after transplantation. The results of this study warrant further investigation on the impact of transplantation on the lymphatic endothelium. The cause—effect relation between rejection and lymphatic endothelium remains to be investigated. # 2005 Elsevier B.V. All rights reserved.

Children with cancer often have fever during chemotherapy-induced neutropenia, but only some develop serious infectious complications. Mannose-binding lectin (MBL) deficiency might increase infection susceptibility in these children. MBL genotype and phenotype were prospectively determined in 110 paediatric oncology patients. During febrile neutropenia, MBL concentrations were measured longitudinally in time. MBL genotype and phenotype were correlated to clinical and laboratory parameters. Structural exon-1 MBL2 mutations and the LX promoter polymorphism lead to deficient MBL concentrations. The capacity to increase MBL concentrations during febrile neutropenia was associated with MBL2 genotype. Infectious parameters did not differ between MBL-deficient and MBL-sufficient neutropenic children (n = 66). In contrast, MBL-sufficient patients had a greater risk of Intensive Care admittance (Relative Risk 1.6, 95% Confidence Interval 1.3-2.0, P = 0.04). MBL-deficient neutropenic children did not have more severe infections. However, most patients (61%) were severely neutropenic (

Objective: Myocardial ischemia and reperfusion induced by cardioplegic arrest subjects the heart to free radical-mediated stress. The purpose of our study was to investigate the effect of cardioplegia-induced ischemia and reperfusion on myocardial formation and distribution of (1) nitrotyrosine as an indicator for peroxynitrite-mediated tissue injury resulting from increased nitric oxide release and (2) 8-isoprostane as an indicator for oxygen-derived free radical-mediated lipid peroxidation. Methods: In 10 patients undergoing coronary artery operations (64 ± 6 [mean ± SD] years, 3 women and 7 men) subjected to cardiopulmonary bypass and intermittent cold blood cardioplegia, we collected transmural left ventricular biopsy specimens before and at the end of cardiopulmonary bypass. Specimens were cut at 10 μm and subjected to immunocytochemical staining against the nitric oxide-producing enzyme constitutive nitric oxide synthase, cyclic guanosine monophosphate (intracellular second messenger of nitric oxide), nitrotyrosine, and 8-isoprostane by using polyclonal antibodies. For global left ventricular function determination, we measured the fractional area of contraction using transesophageal echocardiography. Results: Nitric oxide synthase activity in cardiac myocytes increased from 34 ± 10 gray units before cardiopulmonary bypass to 47 ± 12 gray units at the end of bypass ( P =.015), and all hearts showed increased cyclic guanosine monophosphate content in both myocytes and endothelial cells at the end of bypass. The number of nitrotyrosine-positive capillaries increased from 36 ± 29/mm 2 before bypass to 82 ± 47/mm 2 at the end of bypass ( P =.012), and 8-isoprostane-positive capillaries increased from 92 ± 72/mm 2 before bypass to 209 ± 108/mm 2 at the end of bypass ( P =.005). The fractional area of contraction was 53% ± 12% before bypass and 56% ± 12% after bypass ( P =.47) but was slightly decreased to 45% ± 14% at 4 hours after bypass ( P =.121). Conclusions: Our data show that cardioplegia-induced myocardial ischemia and reperfusion is associated with nitrotyrosine and 8-isoprostane formation mainly in the coronary endothelium, indicating injury mediated by both peroxynitrite and oxygen-derived free radicals. Because nitric oxide synthase activation was accompanied with increased cyclic guanosine monophosphate, these data suggest that direct effects of nitric oxide on cardiac myocytes, as well as nitric oxide-mediated coronary endothelial injury, might contribute to injury associated with cardioplegia and cardiopulmonary bypass. J Thorac Cardiovasc Surg 2003;125:178-83

Aspects and limits of the ramp-assisted foil-casting technique (RAFT) have been studied in a continuously operating. prototype. Information on the practicability and technical feasibility of RAFT has been obtained for large-scale operation. In order to facilitate this transfer, a standard ramp system is defined together with pertinent process parameters. >

Background Myocardial ischemia reperfusion injury may be reduced by beta-blockade. However, how myocardial salvage is affected when beta-blockade is limited to the reperfusion period is unknown. We investigated the impact of CPB and esmolol during reperfusion on infarct size and left ventricular function in two different experimental models of acute myocardial ischemia. Methods In open-chest dogs, myocardial ischemia was induced by LAD occlusion in both studies. In study 1, infarct size (TTZ stain) and myocardial water content (MWC, microgravimetry) were determined, comparing reperfusion with blood and esmolol to blood without additives. Study 2 investigated the impact of esmolol on LV function (sonomicrometry, echocardiography) and MWC (microgravimetry) compared to warm blood cardioplegia in a more clinically oriented model. Results Infarct size and MWC in reperfused myocardium were significantly reduced by esmolol during reperfusion. Global LV function was better preserved in the esmolol group, whereas no difference was seen regarding regional function. Conclusions Myocardial salvage may be significantly enhanced by CPB and esmolol, even when treatment with esmolol is initiated as late as with the onset of reperfusion.

The Pt magnetization depth profile at a single buried Pt/Co interface was investigated by x-ray resonant magnetic reflectivity measurements. The asymmetry as function of angle of incidence has been measured in the Pt ${L}_{3}$-near-edge absorption region at two energies. Observed asymmetry ratios in the order of 0.5% are described on the basis of a magnetically modified Parratt algorithm. Excellent agreement between simulations and experiment was achieved for a Pt magnetic moment of $0.21{\ensuremath{\mu}}_{B}$ at the rough interface followed by an exponential decay of the induced polarization within 1 nm.

X-ray magnetic circular dichroism (XMCD) measurements of the Ruddlesden-Popper Phase La1.2Nd0.2Sr1.6Mn2O7 are reported. The Mn K, La and Nd L2,L3 edges have been measured on a powder sample at two different magnetic fields at low temperature. The analysis of the spectra at B = 1T indicates a large orbital moment of the Nd 5d-states and a significant spin-polarization of the La 5d-band. Furthermore at the Mn K-edge a XMCD-signal is observed, showing a polarization of the Mn 4p-band. At lower field (0.2T) all XMCD-signals are about two times smaller corresponding to the lower total magnetization. The signal at the Nd L2 edge vanishes completely at 0.2T.

A retrospective study comparing clinical and computerized tomography (CT) in 11 patients diagnosed as having schizencephaly was conducted. Seven of these patients were girls and four boys. Six of them had tetraparesis, three hemiparesis and one no motor deficits. Six had epilepsy and ten developmental delay. On CT examinations, 7 patients were found as having bilateral clefts and four unilateral defect. Eight had opened lip clefts and four had a closed lip defect. The commonest associated anomaly was an absent septum pellucidum (n=9), followed by subependymal nodules (n=4), hydrocephalus (n=2) and microcephaly (n=1). Despite magnetic resonance image is the gold-standard to diagnose neuronal migration anomalies, CT can be useful in showing typical aspects of schizencephaly.

In this paper, we will emphasize that XMCD is a universal tool for studies of magnetism with atomic sensitivity. A quantitative analysis of spin and orbital momenta is possible, which could be extracted using sum rules developed by Thole and Carra. For magnetic investigations, it is possible to measure atomic hysteresis loops with high resolution. We will also show that it is feasible to study quantitatively magnetocrystalline anisotropy in complex magnetic structures and to understand their microscopic origin in terms of projected orbital momentum distributions and spin–orbit coupling. We demonstrate that a cubic like anisotropy is present in the colossal magneto resistance Lanthanummanganates. This could be quantitatively addressed to changes in the measured projected orbital moments. In addition, a cubic like anisotropy was observed in oxygen K edge XMCD hysteresis loops. It is also possible to measure quantitatively site selective magnetization profiles in multilayer systems. Therefore, we have developed a magnetic specular hard X-ray diffraction technique. Using the Parratt algorithm, we could extract the platinum L 3 moment magnetization profile as a function of distance to a ferromagnetic cobalt thin layer.

Various risk scores have been developed for the assessment of operative risk in cardiac surgery. Although risk stratification has been acknowledged as a useful tool to analyze trends in therapy and changes in patient populations, its relevance in assessing the indication for surgery has been questioned. It was the goal of this prospective study to compare 6 common risk scores with regard to the predictive value for mortality in individual patients. Between September 1998 and February 1999 all adult patients undergoing heart surgery were prospectively scored according to the following scores: initial Parsonnet, Cleveland Clinic, French, Euro, Pons, and the Ontario Province Risk score. Early lethality was assessed within 30 days postoperatively. Follow-up was completed in 504 patients. With the exception of the Ontario Province Risk score, lethality in the high risk group was overestimated by all scores, whereas lethality in low to moderate risk groups was underestimated by several scores. Mean scores of surviving and deceased patients showed a broad overlap with high standard deviations. Preoperative risk scores are effective tools for stratification of patient populations and the analysis of surgical outcome. With the aid of risk scores, operative risk can be sufficiently predicted for patient populations or subpopulations. The Euro score best predicted the outcome of our patients. However, when the indication for surgery is to be determined in an individual patient, risk scores should be only considered as an orientation in the decision process.

Myocardial edema occurs in many pathological conditions. We hypothesized that protein washdown at the myocardial microvascular exchange barrier would change the distribution of interstitial proteins from large to small molecules and diminish the effect of washdown on the colloid osmotic pressure (COP) of interstitial fluid and lymph. Dogs were instrumented with coronary sinus balloon-tipped catheters and myocardial lymphatic cannulas to manipulate myocardial lymph flow and to collect lymph. Myocardial venous pressure was elevated by balloon inflation to increase transmicrovascular fluid flux and myocardial lymph flow. COP of lymph was measured directly and was also calculated from protein concentration. Decreases occurred in both protein concentration and COP of lymph. The proportion of lymph protein accounted for by albumin increased significantly, whereas that accounted for by β-lipoprotein decreased significantly. The change in the calculated plasma-to-lymph COP gradient was significantly greater than the change in the measured COP gradient. We conclude that the change in the distribution of interstitial fluid protein species decreases the effect of protein washdown on interstitial fluid COP and limits its effectiveness as a defense mechanism against myocardial edema formation.

The mechanism by which chronic myocardial edema causes cardiac dysfunction is poorly understood. We hypothesized that myocardial edema triggers cardiac fibrosis development resulting in cardiac dysfunction. Since collagen is the most abundant constituent of the interstitial matrix, we examined the effects of edema development on cardiac collagen metabolism.We utilized a chronic pulmonary artery banded rat model that produces right ventricular hypertrophy with myocardial edema and left ventricular edema without hypertrophy or hyperplasia. Wet to dry ratios (index of edema), collagen type I and III concentrations, prolyl 4-hydroxylase (P4-H) and collagen type I and III mRNA levels, collagenase activity and transforming growth factor-beta were measured in both ventricles.Right and left ventricular wet to dry ratios were significantly elevated from 1 to 28 days after pulmonary artery banding compared to sham rats. Right and left ventricular collagen types I and III and P4-H mRNA levels increased significantly at 3 days followed by significant increases in right and left ventricular collagen concentration 7 days after pulmonary artery banding. Right ventricular collagenase activity increased at 3 days while left ventricular collagenase activity decreased 7 days after PA banding.We conclude that myocardial edema preceded the observed increase in collagen deposition and that edema may have triggered increased collagen synthesis by fibroblasts. leading to fibrosis development.

Objective: Risk scores have become an important tool in patient assessment, as age, severity of heart disease, and comorbidity in patients undergoing heart surgery have considerably increased. Various risk scores have been developed to predict mortality after heart surgery. However, there are significant differences between scores with regard to score design and the initial patient population on which score development was based. It was the purpose of our study to compare six commonly used risk scores with regard to their validity in our patient population. Methods: Between September 1, 1998 and February 28, 1999, all adult patients undergoing heart surgery with cardiopulmonary bypass in our institution were preoperatively scored using the initial Parsonnet, Cleveland Clinic, French, Euro, Pons, and Ontario Province Risk (OPR) scores. Postoperatively, we registered 30-day mortality, use of mechanical assist devices, renal failure requiring hemodialysis or hemofiltration, stroke, myocardial infarction, and duration of ventilation and intensive care stay. Score validity was assessed by calculating the area under the ROC curve. Odds ratios were calculated to investigate the predictive relevance of risk factors. Results: Follow-up was able to be completed in 504 prospectively scored patients. Receiver operating characteristics (ROC) curve analysis for mortality showed the best predictive value for the Euro score. Predictive values for morbidity were considerably lower than predictive values for mortality in all of the investigated score systems. For most risk factors, odds ratios for mortality were substantially different from ratios for morbidity. Conclusions: Among the investigated scores, the Euro score yielded the highest predictive value in our patient population. For most risk factors, predictive values for morbidity were substantially different from predictive values for mortality. Therefore, development of specific morbidity risk scores may improve prediction of outcome and hospital cost. Due to the heterogeneity of morbidity events, future score systems may have to generate separate predictions for mortality and major morbidity events. q 2000 Elsevier Science B.V. All rights reserved.

Objective: The risk of postoperative cardiac dysfunction is markedly increased by emergency coronary artery bypass grafting in the presence of acute myocardial ischemia. High dose b-blockade during continuous coronary perfusion has been suggested as an alternative to conventional cardioplegia and this technique has been applied successfully in high risk patients for coronary artery bypass grafting (CABG) surgery. This study compared high dose b-blockade with esmolol to continuous warm blood cardioplegia in a clinically oriented model of acute left ventricular (LV) ischemia and reperfusion. Methods: Twelve dogs were subjected to 60 min of regional LV ischemia by left anterior descending branch (LAD) ligation. Cardiopulmonary bypass (CPB) and aortic crossclamp were applied after 45 min of ischemia. Thereafter, high dose b-blockade during continuous coronary perfusion (ESMO, na 6) or antegrade continuous warm blood cardioplegia (WBC, na 6) were maintained for 60 min. Myocardial water content (measured from endomyocardial biopsies using a microgravimetric technique), global LV function (preload recruitable stroke work: PRSW), and regional LV function (echocardiographic wall motion score) were determined at baseline and after weaning from CPB. Results: During aortic crossclamp interstitial edema formation was significantly higher in the WBC group with an average water gain of 2.2 ^ 0.49 vs. 0.76 ^ 0.12% in the ESMO group. Thereafter, edema resolved in both groups, but myocardial water gain remained significantly higher in the WBC group at 60 and 120 min post CPB (0.98 ^ 0.19 and 1.13 ^ 0.32% vs. 0.07 ^ 0.25 and 0.04 ^ 0.08%). Global LV function was significantly higher in the ESMO group at 60 and 120 min post CPB (PRSW 103 ^ 6 and 94.7 ^ 4.6% of baseline vs. 85.3 ^ 4.9 and 74.7 ^ 7.6% of baseline). However, regional LV function showed no significant difference between groups. Conclusions: High-dose b-blockade during continuous coronary perfusion may allow the surgeon to utilize the advantages of warm heart surgery, while avoiding the interstitial edema formation and temporary cardiac dysfunction associated with continuous warm blood cardioplegia. In high risk patients such as patients with unstable angina or after failed PTCA, high-dose bblockade may be an applicable alternative to cardioplegic arrest. q 2000 Elsevier Science B.V. All rights reserved.

gamma-Glutamylcysteine synthetase (GCS) catalyzes the initial and rate-limiting step in the biosynthesis of glutathione. gamma-GCS consists of a heavy and a light subunit encoded by separate genes. Hereditary deficiency of GCS has been reported in 6 patients with hemolytic anemia and low erythrocyte levels of glutathione and gamma-glutamylcysteine. In addition, 2 patients also had generalized aminoaciduria and developed neurologic symptoms. We have examined a Dutch kindred with 1 suspected case of GCS deficiency. The proband was a 68-year-old woman with a history of transient jaundice and compensated hemolytic anemia. One of her grandchildren was also GCS deficient; he was 11 years old and had a history of neonatal jaundice. The enzyme defect was confirmed and GCS activity was found to be less than 2% of normal in the erythrocytes of both patients. The complementary DNA (cDNA) for the heavy subunit of GCS was sequenced in these patients and in several members of the family. The proband and her GCS- deficient grandson were identified as homozygous for a 473C--T substitution, changing codon 158 from CCC for proline into CTC for leucine. Several family members with half-normal GCS activity in their erythrocytes were heterozygous for the mutation.

We report on a 12 years old girl with ulcerative colitis, who after a two years course of her disease developed a concomitant idiopathic pancreatitis. We discuss the causes of acute pancreatitis in childhood in view of the presented case summarizing the current literature. In the literature we found only two other children with ulcerative colitis and idiopathic pancreatitis. Both patients were colectomised as our patient did. Six months after colectomy she is still free of symptoms.

Although myocardial edema is associated with cardiopulmonary bypass (CPB) and cardioplegic arrest (CPA), interventions to expedite edema removal have not been investigated. The primary mechanism for the removal of excess interstitial fluid in the heart is myocardial lymphatic drainage, but lymphatic function can be impaired by decreased contractility because of edema. The purpose of this study was to determine whether enhancing cardiac contractility would increase myocardial lymphatic function and hasten edema resolution after CPB. Sixteen dogs were subjected to CPB and 1 h of hypothermic CPA. After weaning from CPB, 10 dogs received an intravenous dobutamine infusion and 6 dogs received no inotropic support. We determined myocardial lymph driving pressure from the major cardiac lymphatic, myocardial water content by using microgravimetry, and the peak rate of left ventricular pressure increase (dP/dt,,,) by using micromanometry. Measurements were taken at baseline, during CPA, and 60 min after CPB. Compared with controls, dobutamine-treated dogs had an increased dP/ dt,,, (P < 0.05), which was associated with higher lymph driving pressures (P < 0.05), resulting in lower myocardial water gain 1 h after CPB (P < 0.05). We conclude that the resolution of myocardial edema after CPB was hastened by dobutamine. Organized ventricular contraction and myocardial contractility seem to be important determinants of myocardial lymphatic function and myocardial edema removal. These findings suggest that the administration of inotropic drugs after CPB may hasten cardiac recovery. Implications: Myocardial edema, which develops during cardiopulmonary bypass and cardioplegic arrest, contributes to cardiac dysfunction after heart surgery. This study demonstrated that enhancement of cardiac contractility by the administration of dobutamine after cardiopulmonary bypass and cardioplegic arrest was associated with increased myocardial lymphatic function and hastened edema resolution in dogs. (Anesth Analg 1997;85:987-92)

Previous studies demonstrated gas emboli formation during rewarming from hypothermia on cardiopulmonary bypass when the temperature gradient exceeded a critical threshold. It also has been suggested that formation of arterial gas emboli may occur during cooling on cardiopulmonary bypass when cooled oxygenated blood exiting the heat exchanger is warmed on mixture with the patient's blood. The purpose of this study was to determine under what circumstances gas emboli formation would occur during cooling on cardio-pulmonary bypass.Eight anesthetized mongreal dogs were placed on cardiopulmonary bypass using a roller pump, membrane oxygenator, and arterial line filter. For emboli detection, we positioned a transesophageal echocardiographic probe at the aortic arch distal to the aortic cannula and Doppler probes at the common carotid artery and the arterial line. Cooling gradients between normothermic blood and cooled arterial perfusate of 5 degrees, 10 degrees, 15 degrees, 20 degrees, and 0 degree C (isothermal controls) were investigated. In addition to preestablished temperature gradients, we investigated the effect of rapid cooling (maximal flow through the heat exchanger at a water bath temperature of 4 degrees C) after the initiation of normothermic cardiopulmonary bypass.Minimal gas emboli were detected at the aortic arch at gradients of 10 degrees C or greater. The incidence of emboli was related directly to the magnitude of the temperature gradient (p0.01). No emboli were detected at the carotid artery. During rapid cooling, no emboli were observed either at the aorta or at the carotid artery.Cooling gradients of 10 degrees C or greater may be associated with gas emboli formation, but they may be of limited clinical significance because no emboli were detected distal to the aortic arch. During the application of rapid cooling, no emboli formation was observed.

Current therapy for massive venous air embolism (VAE) may include the use of the left lateral recumbent (LLR) position, although its effectiveness has been questioned. This study used transesophageal echocardiography to evaluate the effect of body repositioning on intracardiac air and acute cardiac dimension changes.Eighteen anesthetized dogs in the supine position received a venous air injection of 2.5 ml/kg at a rate of 5 ml/ s. After 1 min the dogs were repositioned into either the LLR, LLR 10 degrees head down (LLR-10 degrees), right lateral recumbence, or remained in the supine position.Repositioning after VAE resulted in relocation of intracardiac air to nondependent areas of the right heart. Peak right ventricular (RV) diameter increase and mean arterial pressure decrease were greater in the repositioned animals compared with those in the supine position (P0.05). Right ventricular diameter and mean arterial pressure showed an inverse correlation (r = 0.81). Peak left atrial diameter decrease was greater in the LLR and LLR-10 degrees positions compared with the supine position (P0.05). Repositioning did not influence peak pulmonary artery pressure increase, and no correlation was found between RV diameter and pulmonary artery pressure. All animals showed electrocardiogram and echocardiographic changes reconcilable with myocardial ischemia.In dogs, body repositioning after VAE provided no benefit in hemodynamic performance or cardiac dimension changes, although relocation of intracardiac air was demonstrated. Right ventricular air did not appear to result in significant RV outflow obstruction, as pulmonary artery pressure increased uniformly in all groups and was not influenced by the relocation of intracardiac air. The combination of increased RV afterload and arterial hypotension, possibly with subsequent RV ischemia rather than RV outflow obstruction by an airlock appeared to be the primary mechanism for cardiac dysfunction after VAE.

Adolescents and adults with congenital heart disease have become a new, continuously growing group of patients, because currently improved diagnostics and therapy allow the majority of newborns with congenital heart disease to survive to adulthood. The objective of this retrospective study was to investigate lethality and morbidity after surgery for congenital heart disease in adolescents and adults. Between 1989 and 1994, we operated 137 patients (age between 15 and 75 years; mean 33.8 +/- 15.1) because of congenital heart disease. This was equivalent to 2.7% of all patients, who were operated during this period of time. 101 cases were primary operations, in 36 cases (26.3%) a reoperation was performed. The most frequent diagnoses were ostium-secundum-defect (37.9%), anomalies of the aortic valve including sub- and supravalvular stenoses (9.5%), anomalies of the mitral valve (8%), ventricular septal defect (7.3%) and aortic coarctation (7.3%). Overall lethality was 5.8%, including emergency cases and all late deaths, which have been reported so far. Evaluation of morbidity showed an intraoperative cardiac low-output-syndrome in 3.7%, pulmonary failure in 5.8%, postoperative renal failure in 4.4% and postoperative bleeding complications in 7.3% of cases. Mean duration of postoperative ventilation and intensive care treatment were 2.3 +/- 5.3 and 3.6 +/- 7.3 d, respectively. In comparison to their preoperative status, 71% of patients had improved by one or two NYHA classes. We found that the higher perioperative risk related to reoperation had no impact on the operation's functional result, as evaluation of postoperative functional class showed no difference between primary and re-do cases. The general term congenital heart disease describes a very inhomogeneous group of patients with a broad spectrum of different diagnoses. The variable morphology and pathophysiology of the different congenital heart defects require an individual surgical strategy for each patient, in rare cases even the decision for a heart- or heart-lung-transplantation. Furthermore, adequate follow-up and competent ambulatory treatment of these patients require the cooperation of pediatric and adult cardiologists and cardiac surgeons in interdisciplinary outpatient clinics.

In order to fulfill in the field of cardiothoracic surgery the obligations of patient-care and research in a university facility according to the international standard it is nowadays absolutely necessary to run a homograft bank. Implantation of an allograft is a preferable choice for a number of different operations, i.e. in aortic valve endocarditis, complex congenital heart disease, Ross' operation and others. Furthermore, in children, women of childbearing age and patients in whom anticoagulation is contraindicated, heart valve replacement with allografts has become routine. The most important advantages of allografts are the excellent hemodynamic qualities and the low risk endocarditis. Anticoagulation is not necessary, because there is no risk for thromboembolism or hemolysis. For the patients mentioned above, these factors are decisive for their quality of life and their prognosis. Because of the shortage of donor organs and the priority of heart transplantation over allograft harvesting, the use of allografts should be limited to the above mentioned indications, mechanical and bioprothetic valves and, just lately available, bioprothetic valves from autogenous pericardium are appropriate.

Background Receptor tyrosine kinases (RTKs) participate in a multitude of signaling pathways, some of them via the small G-protein Ras. An important component in the activation of Ras is Son of sevenless (SOS), which catalyzes the nucleotide exchange on Ras. Principal Findings We can now demonstrate that the activation of Ras requires, in addition, the essential participation of ezrin, radixin and/or moesin (ERM), a family of actin-binding proteins, and of actin. Disrupting either the interaction of the ERM proteins with co-receptors, down-regulation of ERM proteins by siRNA, expression of dominant-negative mutants of the ERM proteins or disruption of F-actin, abolishes growth factor-induced Ras activation. Ezrin/actin catalyzes the formation of a multiprotein complex consisting of RTK, co-receptor, Grb2, SOS and Ras. We also identify binding sites for both Ras and SOS on ezrin; mutations of these binding sites destroy the interactions and inhibit Ras activation. Finally, we show that the formation of the ezrin-dependent complex is necessary to enhance the catalytic activity of SOS and thereby Ras activation. Conclusions Taking these findings together, we propose that the ERM proteins are novel scaffolds at the level of SOS activity control, which is relevant for both normal Ras function and dysfunction known to occur in several human cancers.

Silent myocardial ischaemia seems to be of prognostic value in coronary artery disease. We examined 47 patients with coronary artery disease: 1. 20 patients with a history of myocardial infarction (MI), 2. 15 patients with chronic stable angina pectoris without a history of myocardial infarction (sAP), and 3. twelve patients with unstable angina with or without a history of myocardial infarction (uAP). Horizontal and downsloping ST-segment-depressions greater than or equal to 1 min and greater than or equal to 0.1 mV were defined as significant. There were 132 ST-segment-depressions, the relation between symptomatic and asymptomatic being 1:7.3, in MI 1:6.2, in sAP 1:5.3, in uAP 1:14. Heart rate increased before beginning of ST-segment-depression in 74% in MI, in 86% in sAP, but only in 38% in uAP. In sAP ST-segment-depressions were smaller (14% greater than 0.2 mV, none greater than 0.3 mV) than in patients with MI (42% greater than 0.2 mV, 12% greater than 0.3 mV) and uAP (25% greater than 0.2 mV, 9% greater than 0.3 mV). Mean duration of ST-segment-depression was 15.3 +/- 11.7 min in sAP (2 to 49 min), 28.5 +/- 35.6 min in MI (2 to 168 min), and 41.2 +/- 40 min in iAP (2 to 140 min). ST-segment-depressions in MI and sAP showed a circadian rhythm with a peak at midday and in the early evening and a small amount of ST-segment-depressions at night. In uAP ST-segment-depressions did not show that circadian variation. The number of ST-segment-depressions was higher in uAP than in MI and sAP.(ABSTRACT TRUNCATED AT 250 WORDS)

K. Hekmat, U. Mehlhorn, W. Bloch, Department of Cardiac Surgery, University of Cologne, Cologne, Germany; Institute for Experimentel Medicine, University of Cologne, Cologne, Germany; Department of Cardiac Surgery, University of Freiburg, Freiburg, Germany; Department of Cardiac Surgery, University of Ulm, Ulm, Germany; Institute for Molecular and Cellular Sports Medicine, German Sports Medicine, Cologne, Germany