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Biomedical subjects

T Walther

Publications and source records attributed to T Walther.

At least 19 recordsLinked to original sources
PubMed2006

First experimental test of a new monochromated and aberration-corrected 200 kV field-emission scanning transmission electron microscope.

The first 200 kV scanning transmission electron microscope (STEM) with an imaging energy filter, a monochromator and a corrector for the spherical aberration (Cs-corrector) of the illumination system has been built and tested. The STEM/TEM concept with Koehler illumination allows to switch easily between STEM mode for analytical and TEM mode for high-resolution or in situ studies. The Cs-corrector allows the use of large illumination angles for retaining a sufficiently high beam current despite the intensity loss in the monochromator. With the monochromator on and a 3 microm slit in the dispersion plane that gives 0.26 eV full-width at half-maximum (FWHM) energy resolution we have obtained so far an electron beam smaller than 0.20 nm in diameter (FWHM as measured by scanning the spot quickly over the CCD) which contains 7 pA current and, according to simulations, should be around 0.12 nm in true size. A high-angle annular dark field (ADF) image with isotropic resolution better than 0.28 nm has been recorded with the monochromator in the above configuration and the Cs-corrector on. The beam current is still somewhat low for electron energy-loss spectroscopy (EELS) but is expected to increase substantially by optimising the condenser set-up and using a somewhat larger condenser aperture.

Journal Article↗
PubMed2006

Relation between circulating angiotensin II type 1 receptor agonistic autoantibodies and soluble fms-like tyrosine kinase 1 in the pathogenesis of preeclampsia.

CONTEXT: Placental and circulatory soluble fms-like tyrosine kinase 1 (sFlt1) has proven to be elevated in pregnant women with preeclampsia, a disease characterized by hypertension, proteinuria, and endothelial dysfunction. Recent studies also demonstrated an autoantibody against the angiotensin II type 1 (AT1) receptor (AT1-AA) in that disease. OBJECTIVE: Both factors are discussed as key players in the etiology of preeclampsia. However, it has not yet been clarified whether these two circulating factors correlate and whether synergy determines the severity of pathology. DESIGN: AT1-AA was retrospectively determined by a bioassay and sFlt1 by an ELISA. PATIENTS: Serum from second-trimester pregnancies with normal or abnormal uterine perfusion and in women at term with or without pregnancy pathology was analyzed. RESULTS: Most of the preeclamptic patients were characterized by high sFlt1 levels and the presence of AT1-AA, although the agonistic effects of the antibody did not correlate with the sFlt1 concentrations (P = 0.85). Although AT1-AA was also detected in second-trimester pregnancies evidencing abnormal uterine perfusion without later pathology, sFlt1 was not significantly elevated in these pregnancies, compared with those with normal uterine perfusion. However, whereas women with abnormal perfusion and later pregnancy pathology did not differ in AT1-AA, compared with those with normal outcome, sFlt1 was significantly increased. Again, the two factors did not correlate (P = 0.15). CONCLUSIONS: We conclude that AT1-AA bioactivity and sFlt1 concentrations do not correlate, are not mutually dependent, and are thus probably involved in distinct pathogenetic mechanisms. Both factors in combination may not be causative for the early impaired trophoblast invasion and pathological uterine perfusion.

Adult↗
PubMed2006

Stentless mitral valve implantation in comparison to conventional mitral valve repair or replacement at five years.

OBJECTIVE: A chordally supported stentless mitral valve (SMV) may be a suitable prosthesis for patients with severe degenerative mitral valve disease. We analyzed the five-year results and compared them with results after conventional mitral valve repair or replacement. METHODS: 155 patients, operated on since August 1997, were evaluated. 53 patients (ages, 68 +/- 8 years, 37 female, valve repair not feasible) received a SMV (Quattro), 51 patients (69 +/- 9 years, 32 female) had mitral valve repair (MVR) and 51 patients (66 +/- 9 years, 32 female) had a conventional mitral valve replacement (MVP). There were no significant differences with respect to preoperative NYHA functional class, left ventricular ejection fraction, cardiac index and surgical risk, according to the EuroSCORE. Mean follow-up is 64 +/- 18 (21-89) months. RESULTS: Surgery was performed using a median sternotomy (32 [SMV]/20 [MVR]/34 [MVP]) or a lateral mini-thoracotomy 21/31/17 approach. The SMV was safely attached to the papillary muscles. In-hospital mortality was 1, 2 and 4 respectively; re-operation was required in 6, 2 and 3 patients. Five-year survival rate was 80.6 +/- 4.4 % (SMV), 80.2 +/- 5.6 % (CMV) and 82.6 +/- 5.6 % (MVP), p = n.s. After hospital discharge, there was no significant difference in mortality in comparison to an age-matched control population. Echocardiography revealed acceptable SMV hemodynamics with preservation of left ventricular function. CONCLUSION: Midterm results after SMV implantation are comparable to conventional approaches. Complete preservation of the annulo-ventricular continuity is advantageous and close to physiologic hemodynamics can be achieved. Long term follow-up is required.

Aged↗
PubMed2006

Moderate versus deep hypothermia for arterial switch operation.

BACKGROUND: We evaluated the impact of moderate versus deep intraoperative hypothermia on postoperative morbidity in patients receiving a standard arterial switch operation (ASO). METHODS: 71 newborns underwent ASO from 9/98 onwards. Patients were operated using moderate hypothermia (M, 24 degrees C to 30 degrees C, n=21) or deep hypothermia (D, 16-22 degrees C, n=50). Mean patient age was 9.5 (M) versus 10 (D) days, body weight 3.6+/-0.7 (M) versus 3.8+/-0.9 kg (D), P=n. s. Coronary anatomy was complex in 9.5% (M) versus 16% (D) of patients; additional VSD was present in 23.8 (M) versus 38% (D) of the patients, respectively. Mean follow-up is 2.3+/-1.6 years. RESULTS: Intraoperative rectal temperature was 25+/-2 degrees C (M) and 19+/-2 degrees C (D). Cross-clamping time was 95+/-24 (M) versus 108+/-31 min (D), P=n. s. Conventional ultrafiltration was performed at 114+/-46 (M) versus 129+/-69 ml/kg (D), P=n. s. One patient (D) with complex anatomy suffered myocardial ischemia required ECMO support and died. In-hospital mortality was 1.4%. All other patients were safely weaned from extracorporeal circulation with moderate inotropic support. Secondary chest closure was performed in 33% (M) versus 54 % (D) of the patients. Patients were extubated after 7.4 (M) versus 6 (D) days. There was no renal failure and no other serious complications. CONCLUSIONS: ASO can be safely performed using moderate hypothermia, even with complex anatomy, leading to comparatively good results compared to a conventional approach.

Cardiac Surgical Procedures↗
PubMed2006

A new experimental procedure to quantify annular dark field images in scanning transmission electron microscopy.

A new procedure to quantify the contrast in annular dark field images recorded without lattice resolution in a scanning transmission electron microscope is proposed. The method relies on the use of an in-column energy filter prior to the annular dark field detector and the acquisition of a series of energy-filtered images as a function of the inner detection angle. When the image contrast of an interface between two materials in such energy-filtered annular dark field images is plotted vs. camera length and extrapolated to zero (i.e. infinite scattering angle), the contrast is shown to behave exactly as predicted by Rutherford's scattering formula (i.e. intensity scales proportional, variantZ2). This can then be used to determine the local chemistry at and the effective chemical widths of interfaces or thin films without any additional spectroscopy method for calibration, provided the global chemical composition is known. As examples, the systems SiGe/Si and InGaAs/Ge are considered in detail.

Journal Article↗
PubMed2006

Linear least-squares fit evaluation of series of analytical spectra from planar defects: extension and possible implementations in scanning transmission electron microscopy.

In a previous paper, a new technique was introduced to determine the chemistry of crystallographically well-defined planar defects (such as straight interfaces, grain boundaries, twins, inversion or antiphase domain boundaries) in the presence of homogeneous solute segregation or selective doping. The technique is based on a linear least-squares fit using series of analytical (electron energy-loss or energy-dispersive X-ray) spectra acquired in a transmission electron microscope that is operated in nano-probe mode with the planar defect centred edge-on. First, additional notes on the use of proper k-factors and determination of Gibbsian excess segregation are given in this note. Using simulated data sets, it is shown that the linear least-squares fit improves both the accuracy and the robustness to noise beyond that obtainable by independently repeated measurements. It is then shown how the method originally developed for a stationary nano-probe mode in transmission electron microscopy can be extended to a focused electron beam that scans a square region in scanning transmission electron microscopy. The necessary modifications to scan geometry and corresponding numerical evaluation are described, and three different practical implementations are proposed.

Journal Article↗
PubMed2006

Autopsy findings in patients on postcardiotomy extracorporeal membrane oxygenation (ECMO).

OBJECTIVES: To assess the clinical sensitivity of causes of death, concomitant diseases and postoperative complications including thromboembolic events in ECMO patients. METHODS: Between January 2000 and December 2004 154/202 patients (76.2%) died after postcardiotomy ECMO circulatory support. Autopsy was performed in 78 (50.6%) consecutive patients. Clinical and post-mortem data were prospectively recorded and compared concerning causes of death and postoperative complications including venous and arterial thromboembolisms and significant comorbidities. RESULTS: Mean age was 62.1+/-11.3 years, ejection fraction was 43.4+/-17.3%. 39.7% were emergency operations including acute coronary syndrome in 25.6% and preoperative cardiogenic shock in 28.2%. Successful ECMO weaning rate was 43.6%. Mean postoperative survival was 11.3 days. Premortem unknown concomitant diseases were found in 63 patients (80.8%) with clinical relevance in 9 patients (11.5%). Clinically unrecognized postoperative complications were found in 59 patients (75.6%) including acute cerebral infarction (n=7), acute bowel ischemia (1), intestinal perforation (3), pneumonia (4), venous thrombus formation (25) and systemic thromboembolic events (24). Clinically based causes of death were cardiac in 62.8%, multi-organ failure in 10.3%, cerebral in 5.1%, respiratory in 10.3%, fatal pulmonary embolism in 2.6%, technical in 5.1%, and others in 3.8%. Unexpected causes of death were found by autopsy in 22 patients (28.2%) including myocardial infarction (n=5), acute heart failure (4), fatal pulmonary embolism (2), pneumonia (2), ARDS (1), lung bleeding (1), fatal cerebrovascular event (4) and multiorgan failure (3). CONCLUSIONS: In ECMO patients major discrepancies between clinical and post-mortem examination were found. The true incidence of thromboembolic events is highly underestimated by clinical evaluation.

Aged↗
PubMed2005

Diabetes in patients undergoing coronary artery bypass grafting. Impact on perioperative outcome.

Diabetes mellitus is an established risk factor related to significant morbidity and mortality after coronary artery bypass grafting. Data on 9682 patients undergoing coronary artery bypass grafting either with (n=8917) or without cardiopulmonary bypass (off-pump coronary artery bypass grafting; n=765) were subjected to an univariate analysis to identify potential associations between diabetes mellitus and 26 a priori selected perioperative outcome variables. Those having a significant association with diabetes were then subjected to a stepwise logistic regression model to identify the impact of diabetes as compared to additional 22 different a priori chosen patient related risk factors and treatment variables. Prevalence of outcome variables independently associated with diabetes has been determined in the subgroup of diabetics undergoing coronary artery bypass grafting with cardiopulmonary bypass or off-pump coronary artery bypass grafting surgery to evaluate the effect of avoiding cardiopulmonary bypass on perioperative patient outcome. Diabetes mellitus was defined as glucose intolerance either treated dietary, with oral hypoglycemics or with insulin. According to this definition of diabetes mellitus we found an overall prevalence of 37.1% (coronary artery bypass grafting with cardiopulmonary bypass: 37.5%; off-pump coronary artery bypass grafting: 32.5%). Eleven outcome variables having a significant association with diabetes were identified. Diabetes could be identified as an independent predictor of postoperative delirium, renal dysfunction and respiratory insufficiency. Prevalence of these three variables was lower in diabetics undergoing off-pump coronary artery bypass grafting as in those undergoing coronary artery bypass grafting with cardiopulmonary bypass surgery reaching statistical significance with regard to postoperative delirium and respiratory insufficiency. In conclusion, diabetes mellitus is a significant independent predictor for three postoperative outcome variables in coronary artery bypass surgery. Avoiding cardiopulmonary bypass in diabetics seems to have a beneficial effect.

Age Distribution↗
PubMed2005

Angiotensin-(1-7) enhances LTP in the hippocampus through the G-protein-coupled receptor Mas.

The renin-angiotensin system not only plays a critical role in blood pressure control but is also involved in learning and memory mechanisms. In addition to angiotensin (Ang) II, Ang-(1-7) may also have important biological activities in the brain. Here, we show for the first time that Ang-(1-7) enhances long-term potentiation (LTP) in the CA1 region of the hippocampus. Our studies with AT1 receptor antagonists and selective Ang-(1-7) receptor antagonists demonstrate the existence of a distinct Ang-(1-7) receptor in the brain, the G-protein-coupled receptor Mas, encoded by the Mas protooncogene. We also show that the genetic deletion of this receptor abolishes the Ang-(1-7)-induced enhancement of LTP. Thus, we firstly demonstrate that Ang-(1-7) influences the induction of LTP in limbic structures implicating its distinct function in learning and memory mechanisms; secondly, we have identified Mas as a functional receptor for Ang-(1-7) in the brain.

Angiotensin I↗
PubMed2005

Critical assessment of the speckle statistics in fluctuation electron microscopy and comparison to electron diffraction.

The technique of fluctuation electron microscopy (FEM) is applied to thin films of amorphous germanium and of polycrystalline gold in a transmission electron microscope. Even though the method was introduced as a tool for quantitative analysis of structural fluctuations in amorphous materials, the basic principles are applicable to any disordered specimen independent of the dimension of disorder. Hence, we extended the technique of FEM to a well-known specimen, gold, whereby it was possible to reinterpret the results of the measurements on amorphous germanium. The hollow-cone dark field images, the statistical analysis of which is the basis of FEM, are examined with respect to the effects of frequency filtering, and are compared to electron diffraction. We find that the angular dependence of the normalised variance, as measured by FEM, yields information similar to the average intensity of hollow-cone dark field image series. Both plots are basically identical to a scan through a selected-area diffraction pattern convoluted by the corresponding angular resolution function. Hence, it appears questionable whether standard FEM analysis provides more information than the classical pair distribution function, which is experimentally limited to short-range order. Frequency selective analysis of the normalised variance, however, gives supplementary information on preferred inter-atomic distances related to the medium-range order of the specimen.

Journal Article↗
PubMed2004

Baroreflex sensitivity, heart rate, and blood pressure variability in hypertensive pregnancy disorders.

Hypertensive pregnancy disorders are a leading cause of perinatal and maternal morbidity and mortality. Heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) are relevant predictors of cardiovascular risk in humans. The aim of the study was to evaluate whether HRV, BPV, and BRS differ between distinct hypertensive pregnancy disorders. Continuous heart rate and blood pressure recordings were performed in 80 healthy pregnant women as controls (CON), 19 with chronic hypertension (CH), 18 with pregnancy-induced hypertension (PIH), and 44 with pre-eclampsia (PE). The data were assessed by time and frequency domain analysis, nonlinear dynamics, and BRS. BPV is markedly altered in all three groups with hypertensive disorders compared to healthy pregnancies, whereby changes were most pronounced in PE patients. Interestingly, this increase in PE patients did not lead to elevated spontaneous baroreflex events, while BPV changes in both the other hypertensive groups were paralleled by alterations in baroreflex parameters. The HRV is unaltered in CH and PE but significantly impaired in PIH. We conclude that parameters of the HRV, BPV, and BRS differ between various hypertensive pregnancy disorders. Thus, distinct clinical manifestations of hypertension in pregnancy have different pathophysiological, regulatory, and compensatory mechanisms.

Adult↗
PubMed2004

Requirement for renal replacement therapy in patients undergoing cardiac surgery.

BACKGROUND: Despite refinements in perioperative patient management renal insufficiency requiring renal replacement therapy (RRT) is still a common complication after cardiac surgical procedures associated with impaired patient outcome and increased costs. METHODS: Prospective data on 16,184 patients undergoing different cardiac surgical procedures (CABG, n = 8917; beating heart CABG, n = 1842 [OPCAB, n = 765; MIDCAB, n = 1077]; aortic valve surgery, n = 1830; mitral valve surgery, n = 708; double valve surgery, n = 381; CABG and valve surgery, n = 2506) between April 1996 and August 2001 were subjected to univariate and multivariate logistic regression analysis. Postoperative RRT was defined as any postoperative renal insufficiency requiring first time hemofiltration or dialysis during the postoperative stay. Patients with preoperative dialysis dependent renal insufficiency were excluded from further analysis. RESULTS: The overall prevalence of postoperative RRT was 4.7% which varied according to different surgical procedures. 45 out of 49 selected pre- and intraoperative patient- and treatment-related variables had a significant association with postoperative RRT. 10 of these (renal disease, myocardial infarction, diabetes, cardiogenic shock, urgent operation, NYHA > or = 3, intraoperative hemofiltration, perfusion time > or = 2 hours, intraoperative low cardiac output, perioperative high transfusion requirement) were independent predictors. OPCAB surgery and younger patient age were identified as having a significantly lower predictive value for postoperative RRT. Patients with postoperative RRT were found to have a significantly longer ICU- and total postoperative hospital stay as well as a higher 30-day mortality. CONCLUSION: Identifying perioperative risk factors associated with postoperative RRT will help to reduce the incidence of this complication. Avoiding cardiopulmonary bypass seem to be beneficial with regard to the prevalence of postoperative RRT.

Age Factors↗
PubMed2004

Leiomyosarcoma--an unusual cause of right ventricular outflow tract obstruction.

A 76-year-old female patient was admitted with progressive dyspnea on exertion, signs of right ventricular failure, and severe pulmonary stenosis. Intraoperatively an infiltrating right ventricular outflow tract (RVOT) tumor was found and xenograft conduit replacement was performed successfully. Histological examination revealed primary cardiac leiomyosarcoma, the patient was discharged and is in good health condition at 9 months' follow-up. Unusual causes of RVOT obstruction should be considered.

Aged↗
PubMed2004

Development of a new analytical electron microscopy technique to quantify the chemistry of planar defects and to measure accurately solute segregation to grain boundaries.

A new technique of analytical transmission electron microscopy called ConceptEM has been developed for determining highly accurately small amounts of solute or dopant atoms incorporated into well-defined planar defects such as stacking faults, grain boundaries or interfaces. The method is based on recording series of analytical spectra taken with different electron beam diameters on the same position centred above a defect that is orientated either edge-on or slightly inclined with respect to the electron beam. It can be applied to energy-dispersive X-ray spectroscopy or electron energy-loss spectroscopy and necessitates only a nano-probe modus but no scanning unit. Reliability and accuracy have been tested numerically under various conditions using simulations for a specific geometry, as a function of specimen thickness, material, acceleration voltage, collection angle, random beam displacements and solid solubility. The accuracy has been found to be substantially better (by factors of 5-10) than that of any other current standard technique based on single measurements. Our calculations suggest an accuracy in the determination of the Gibbsian solute excess at a special grain boundary down to +/- 1% of a monolayer, i.e. around +/- 0.1 atoms nm(-2) under typical experimental conditions, with a maximum error about twice as large. The parameter limiting a straightforward analysis is found to be the solid solubility, which itself, however, can be measured accurately by the technique so that it can be taken into account quantitatively and the above-stated precision is retained.

Journal Article↗
PubMed2004

C-type natriuretic peptide in reproduction, pregnancy and fetal development.

C-type natriuretic peptide (CNP) belongs to the natriuretic peptide family that consists of three structurally related peptides with a 17-amino acid ring linked by a disulfide bond. In contrast to atrial and brain natriuretic peptides that are mainly cardiovascular hormones, CNP acts predominantly in an autocrine/paracrine fashion, is commonly considered to be an endothelial hormone with antimitogenic properties, and is characterized as a regulator of endochondral ossification. Its biological effects are mediated by an intracellular cGMP accumulation via specific membrane-bound guanylyl cyclase B (GC-B) activation. There is growing evidence that this peptide is also involved in various reproductive processes as well as in embryonic and fetal development. In rodents, CNP and its receptor are highly expressed in the uterus and ovaries with specific regulation during the estrous cycle. During pregnancy, CNP mRNA is detectable in mice embryos and shows an organ-specific expression in maternal reproductive tIssues with the highest concentration in the placenta. This could indicate a defined biological function of the CNP/GC-B/cGMP axis in gestation e.g. antagonizing vasoconstrictive peptides like angiotensin II. In humans, besides a postulated fetal de novo synthesis of CNP, both the peptide and its receptor are expressed in the placenta and myometrium with opposite regulation of CNP in pregnancies complicated by pre-eclampsia or intrauterine growth retardation. Since the maternal plasma levels do not reflect these alterations, one can conclude that this part of the natriuretic peptide system acts locally suggesting that CNP-stimulated cGMP release exhibits organ-specific effects. Importantly, CNP has also become a peptide with a distinct role in male reproductive processes, since endocrine function of the testis and the regulation of penile erection are regulated by the CNP/GC-B axis. This review gives a comprehensive overview of the multiple functions of CNP in reproduction and pregnancy as well as in embryonic and fetal development.

Animals↗