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Stefan Fischer

Publications and source records attributed to Stefan Fischer.

At least 73 records · Page 4Linked to original sources
PubMed2002

Interleukin-8 release during early reperfusion predicts graft function in human lung transplantation.

Cytokines have been shown to play an important role in promoting inflammation in the setting of ischemia-reperfusion injury. However, their role in human lung transplantation has not been systematically explored. This study was undertaken to examine the kinetics of cytokine release in 18 consecutive human lung transplantation procedures and to examine the relationships between their levels and donor factors, length of ischemic time, and allograft function. TNF-alpha, IFN-gamma, IL-10, IL-12, and IL-18 were found at higher levels during the ischemic time, whereas IL-8 predominantly increased after reperfusion. IL-8 levels after 2 h of reperfusion correlated with lung function assessed by the Pa(O2 )/FI(O(2)) ratio, the mean airway pressure, and the APACHE score during the first 24 postoperative hours. The length of ICU stay also correlated with IL-8 levels after 2 h of reperfusion. Longer ischemic time was associated with significantly higher levels of IL-18 before reperfusion, and older donors had significantly lower levels of IL-10 after reperfusion. We have demonstrated the importance of IL-8 in predicting early graft function after human lung transplantation. In addition, we showed that donor age and ischemic time may influence release of specific cytokines during ischemia-reperfusion.

APACHE↗
PubMed2002

Can the calculation of ligand binding free energies be improved with continuum solvent electrostatics and an ideal-gas entropy correction?

The prediction of a ligand binding constant requires generating three-dimensional structures of the complex concerned and reliably scoring these structures. Here, the scoring problem is investigated by examining benzamidine-like inhibitors of trypsin, a system for which errors in the structures are small. Precise and consistent binding free energies for the inhibitors are determined experimentally for this test system. To examine possible improvement of scoring methods, we test the suitability of continuum electrostatics to account for solvation effects and use an ideal-gas entropy correction to account for the changes in the degrees of freedom of the ligand. The small observed root-mean-square deviation of 0.55 kcal/mol of the calculated relative to the experimental values indicates that the essentials of the binding process have been captured. Even though all six ligands make the same salt bridge and H-bonds to the protein, the electrostatic contribution varies among the ligands by as much as 2 kcal/mol. Moreover, although the ligands are rigid and similar in size, the entropic terms also significantly affect the relative binding affinities (by up to 2.7 kcal/mol). The present approach to solvation and entropy may allow the ranking of the ligands to be considerably improved at a cost that makes the method applicable to the optimization of lead compounds or to the screening of small collections of ligands.

Journal Article↗
PubMed2002

[Is chronic graft rejection the reason for degenerative changes in allogeneic and xenogeneic heart valve prostheses: immunohistochemical evaluation of inflammatory factors].

OBJECTIVES: After a period of 5 to 10 years, biological heart valve prostheses undergo degenerative processes, which finally lead to dysfunction and complete destruction. Although many efforts have been made to identify underlying mechanisms, many questions remain unanswered. Here we evaluate immunological factors and their potential role in biological heart valve destruction. PATIENTS AND METHODS: Allogeneic (n=10) and xenogeneic (n=3) aortic valvular prostheses, as well as aortic valves retrieved from transplanted human hearts, which had to be replaced because of chronic graft rejection (n=4) were analyzed. Aortic valves from human donor hearts (native) (n=4), which were considered not transplantable served as controls. Endothelial expression patterns of the following adhesion molecules were analyzed by immunohistochemistry: selectin family: ELAM-1, CD62, integrin family: VLA-1, -2, -3, -4, -5, and -6, immunoglobulin supergene family: PECAM-1, ICAM-1, and -2, and class I heavy chain proteins, complementary adhesion molecules: CD34, CD44 and the von Willebrand factor. RESULTS: ELAM-1, ICAM-1 and -2, CD34, CD44 and class I heavy chain proteins, all molecules which play significant roles during inflammatory processes, showed stronger expression patterns in allogeneic and xenogeneic aortic heart valve prostheses compared to native or chronically rejected valves. Furthermore, the von Willebrand factor stained positive only on allogeneic and xenogeneic valves. Only mild differences were observed regarding the expression of integrin molecules and CD62. CONCLUSIONS: Immunological reactions play a major role in the degeneration of biological heart valve prostheses. This is underlined by observations made on aortic valves from chronically rejected cardiac grafts, which did not show any degenerative alterations. Thus, since immunosuppressive therapy after heart valve replacement is no reasonable alternative, novel and future approaches in "tissue engineering" will hopefully help avoid tissue degeneration, while preserving the advantage of biological tissue origin.

Animals↗
PubMed2002

Neuroendocrine carcinoma (carcinoid) of the thymus associated with Cushing's syndrome.

Neuroendocrine carcinoma (carcinoid) of the thymus associated with Cushing's syndrome is a rare disease. Recent evidence suggests that these tumors form part of a continuous spectrum ranging from well-differentiated carcinomas to small cell carcinomas. We report two new cases and review the 23 cases reported in the literature since 1972. The different diagnostic modalities are discussed, and an algorithm for the diagnosis of ectopic secretion of adrenocorticotropin (ACTH) is presented. In the future, the advent of radiologic and nuclear imaging as well as more accurate workup should help to diagnose these tumors at an earlier stage and improve the long-term outcome.

ACTH Syndrome, Ectopic↗
PubMed2002

Bilateral lung transplantation using a donor with a tracheal right upper lobe bronchus.

We report on a case of successful bilateral sequential lung transplantation using a donor with the right upper lobe bronchus arising from the trachea. After en-bloc donor lung retrieval, the right bronchial stump was fashioned to create one lumen including the bronchus intermedius and the aberrant right upper lobe bronchus. A carinoplasty was performed in the recipient with resection of a portion of the lateral wall of trachea. The anastomosis was completed using a telescoping technique without any complication. This case demonstrates the possibility of successfully using donor lungs with such anatomic abnormality for transplantation.

Adult↗
PubMed2002

Solitary fibrous tumors of the pleura.

Solitary fibrous tumor of the pleura is a mesenchymal tumor that has been increasingly recognized over the past few years. The tumor was initially described in the pleura, but it has been reported in many other sites lately. Although the majority of these tumors have a benign course, the malignant form still remains enigmatic. Indeed, the behavior of these tumors is often unpredictable and does not always correlate with histologic findings. In addition, benign tumors may remain unproblematic for several years before changing into a malignant form. In order to define more precisely the clinical behavior of solitary fibrous tumors of the pleura, we reviewed the literature with particular attention to the clinical presentation, histopathologic characteristics, and cytogenetic differentiation of these tumors. A staging system and an algorithm for the management and follow-up of these patients are proposed.

Algorithms↗
PubMed2002

Post-trial administration of vasopressin in humans does not enhance memory formation (vasopressin and memory consolidation).

Many animal studies show an enhancing effect of vasopressin (VP) on memory, but not all human studies could confirm this finding. This study examined the influence of post-learning administration of VP (40 IU, intranasally) on the consolidation of declarative memories in healthy humans during different intervals of sleep and waking. We could not find any effect of VP on memory consolidation, but EEG activity indicated a significant arousing influence of VP. Results suggest that if VP affects memory function it might do so primarily at the stage of encoding of the materials to be learned but it leaves unaffected processes of consolidation.

Administration, Intranasal↗
PubMed2002

Translocation mechanism of long sugar chains across the maltoporin membrane channel.

Maltoporin allows permeation of long maltodextrin chains. It tightly binds the amphiphilic sugar, offering both hydrophobic interactions with a helical lane of aromatic residues and H bonds with ionic side chains. The minimum-energy path of maltohexaose translocation is obtained by the conjugate peak refinement method, which optimizes a continuous string of conformers without applying constraints. This reveals that the protein is passive while the sugar glides screw-like along the aromatic lane. Near instant switching of sugar hydroxyl H bond partners results in two small energy barriers (of approximately 4 kcal/mol each) during register shift by one glucosyl unit, in agreement with a kinetic analysis of experimental dissociation rates for varying sugar chain lengths. Thus, maltoporin functions like an efficient translocation "enzyme," and the slow rate of the register shift (approximately 1/ms) is due to high collisional friction.

Bacterial Outer Membrane Proteins↗
PubMed2002

Intraoperative acute type A dissection caused by an intra-aortic filter (EMBOL-X) in a patient undergoing mitral valve re-replacement for acute endocarditis.

We report on the case of a 60-year-old male patient who underwent mitral valve re-replacement for acute mechanical valve endocarditis. When an intra-aortic filter (EMBOL-X Inc, Mountain View, CA) was inserted through the arterial cannula in order to prevent embolization from a floating thrombus attached to the mitral valve prosthesis, our patient developed acute type A aortic dissection. This, to our knowledge, is the first report on this kind of complication using intra-aortic filter systems. Here we discuss a potential mechanism that might have led to the event of acute type A dissection in our case. Furthermore we point out strategies that might help to prevent this life-threatening complication in the future.

Aortic Dissection↗
PubMed2002

Clinical relevance of intracranial high intensity transient signals in patients following prosthetic aortic valve replacement.

OBJECTIVES: There has been frequent report on transcranially detected microembolic signals (HITS) following cardiac surgery using extracorporeal bypass support. The clinical relevance of HITS, however, has yet to be clarified. The incidence of thromboembolic events is increased following mechanical heart valve replacement. The purpose of this study was to quantify postoperative HITS after implantation of two types of prosthetic aortic valves and to compare both types of mechanical valves with respect to the generation of HITS. In addition, HITS rates were correlated with clinical, echocardiographical and laboratory findings. METHODS: Forty-two patients following implantation of either a Sorin Biomedica heart valve (n=22, group A) or a Tekna Duromedics mechanical valve (n=20, group B) were examined. A group of ten healthy volunteers served as control. Clinical, echocardiographic, carotid artery duplex and laboratory examinations were performed in all patients. A 60 min bilateral transcranial doppler monitoring of the medial cerebral artery (MCA) was also carried out in order to evaluate cerebral blood flow. RESULTS: In group A 14 of 22 patients were positive for HITS (53%), with an average of 16.4+/-19 HITS/pt.h. In group B 15 of 20 patients were HITS positive (75%) with an average amount of 14.4+/-24 HITS/pt.h. The incidence of HITS was not significantly different between the two groups. No correlation was seen between the HITS-rate/h and neurological findings, duplex sonographic results, mechanical valve size and anticoagulation regimen (P>0.05). However, a negative correlation was observed between patient age and HITS-rate (P=0.02) as well as between the NYHA degree and HITS-rate (P=0.018). The HITS-rate also correlated with postoperative time (P=0.042). No HITS were detected in the control group. CONCLUSIONS: HITS do not correlate with the individual clinical status and, thus, cannot predict the occurrence of neurological deficits in patients following mechanical aortic valve implantation.

Aged↗
PubMed2002

Anticoagulation for prosthetic heart valves during pregnancy: is low-molecular-weight heparin an alternative?

We report on the treatment failure of low molecular weight heparin (LMWH) for anticoagulation in a pregnant woman that underwent artificial mitral valve replacement 10 years prior to her pregnancy. Until she became pregnant warfarin was administered for anticoagulation, but due to the often mentioned increased risk for warfarin-induced maternal and fetal complications, at gestational week 5 the anticoagulation regimen was switched to subcutaneous application of low molecular weight heparin. At gestational week 24 our patient developed acute life-threatening pulmonary edema and hemodynamic instability due to acute mitral valve thrombosis and underwent emergency valve re-replacement with a biological porcine valve. She recovered uneventfully and gave birth to a healthy child at gestational week 35. In addition to our case presentation we review the sparse evidence in the literature regarding anticoagulation in pregnant women with mechanical heart valves and discuss the rational of different anticoagulation regimens with regards to maternal and fetal outcome. Special consideration is directed towards LMWH administration as an alternative to oral anticoagulation during pregnancy in women with mechanical heart valves.

Adult↗
PubMed2002

A novel bioartificial myocardial tissue and its prospective use in cardiac surgery.

BACKGROUND: Congenital heart defects such as atrial septal defect, ventricular septal defect, double outlet ventricles and the hypoplastic left heart syndrome as well as ischemic heart disease are associated with aplastic, defective or necrotic myocardial structures. In many of these instances patch closure, reconstruction of the defect or revascularization is required. We have developed a contractile bioartificial myocardial tissue, which offers new perspectives for various reconstructive surgical interventions, including congenital heart surgery. METHODS: Neonatal rat cardiomyocytes were seeded in vitro in a commercially available collagen scaffold. Histological examination and ultrastructural evaluation were performed. Protein and mRNA analysis were carried out by two-dimensional electrophoresis and reverse transcription-polymerase chain reaction (RT-PCR). Force measurements of contractions from the spontaneously beating or the pharmacologically stimulated bioartificial myocardial patch were obtained. RESULTS: A solid matrix of 20 x 15 x 2 mm with spontaneous contractions resulted 36 h after cardiomyocyte seeding. Histology showed a tight mesh of collagen fibrils. Two-dimensional electrophoresis and RT-PCR revealed cardiotypical proteins (actin, tropomyosin, creatine kinase, ventricular light chain) and mRNA (myosin heavy chain, Connexin 43). The elasticity curve during passive stretch was similar to that of myocardium. Contractile force increased after topical administration of Ca(2+) and adrenaline. However, stretch led to the highest levels of contractile force. CONCLUSIONS: Our novel contractile bioartificial tissue can be engineered in vitro and may open novel avenues for myocardial tissue replacement in congenital and reconstructive heart surgery. From the current standpoint autologous or allogeneic cells would be preferred over xenogeneic sources.

Animals↗
PubMed2002

Paradoxic aortic arch embolization with occlusion of the supraaortic arteries.

Pulmonary embolization usually occurs when thrombotic material that originates from deep venous thrombosis of the lower extremities is washed out into the pulmonary vasculature via the blood stream. However, in the presence of a patent foramen ovale (PFO), systemic paradoxic embolization may also occur (Am J Surg 176 (1998) 158). Here, we report on the case of a patient with a PFO, who developed paradoxic embolization of the aortic arch following deep venous thrombosis and massive pulmonary embolism.

Aorta, Thoracic↗
PubMed2002

Massive postoperative rhabdomyolysis following combined CABG/abdominal aortic replacement: a possible association with HMG-CoA reductase inhibitors.

OBJECTIVE: The beneficial effects of the treatment of hyperlipidemia in the secondary prevention of ischemic heart disease are well established. Pravastatin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor often prescribed for the treatment of hypercholesterolemia. Occasional side effects include increased creatine kinase levels and myalgias worsened by exertion, rarely presenting with severe myopathy and rhabdomyolysis resulting in myoglobinuria and renal failure. PATIENTS AND METHODS: We report on a case of a 68-year-old male patient who developed rhabdomyolysis, severe myoglobinuria, and acute renal failure following uneventful coronary bypass grafting surgery (CABG) combined with infrarenal replacement of the abdominal aorta. The patient presented with numerous risk factors for development of rhabdomyolysis following surgical intervention. We underscore important contributory factors and discuss differential diagnostic considerations e.g., malignant hyperthermia and neuroleptic malignant syndrome in such patients. CONCLUSIONS: Considering the high risk of perioperative mortality in patients that routinely take fat lowering substances, we suggest to discontinue the intake prior to surgical interventions.

Acute Kidney Injury↗
PubMedDate not supplied

Injurious mechanical ventilation and end-organ epithelial cell apoptosis and organ dysfunction in an experimental model of acute respiratory distress syndrome.

CONTEXT: Recent clinical trials have demonstrated a decrease in multiple organ dysfunction syndrome (MODS) and mortality in patients with acute respiratory distress syndrome (ARDS) treated with a protective ventilatory strategy. OBJECTIVE: To examine the hypothesis that an injurious ventilatory strategy may lead to end-organ epithelial cell apoptosis and organ dysfunction. DESIGN AND SETTING: In vivo animals: 24 rabbits with acid-aspiration lung injury were ventilated with injurious or noninjurious ventilatory strategies. In vitro: rabbit epithelial cells were exposed to plasma from in vivo rabbit studies. In vivo human: plasma samples from patients included in a previous randomized controlled trial examining a lung protective strategy were analyzed (lung protection group, n = 9 and controls, n = 11). MAIN OUTCOME MEASURES: In vivo animals: biochemical markers of liver and renal dysfunction; apoptosis in end organs. In vitro: induction of apoptosis in LLC-RK1 renal tubular epithelial cells. In vivo human: correlation of plasma creatinine and soluble Fas ligand. RESULTS: The injurious ventilatory strategy led to increased rates of epithelial cell apoptosis in the kidney (mean [SE]: injurious, 10.9% [0.88%]; noninjurious, 1.86% [0.17%]; P<.001) and small intestine villi (injurious, 6.7% [0.66%]; noninjurious, 0.97% [0.14%]; P<.001), and led to the elevation of biochemical markers indicating renal dysfunction in vivo. Induction of apoptosis was increased in LLC-RK1 cells incubated with plasma from rabbits ventilated with injurious ventilatory strategy at 4 hours (P =.03) and 8 hours (P =.002). The Fas:Ig, a fusion protein that blocks soluble Fas ligand, attenuated induction of apoptosis in vitro. There was a significant correlation between changes in soluble Fas ligand and changes in creatinine in patients with ARDS (R = 0.64, P =.002). CONCLUSIONS: Mechanical ventilation can lead to epithelial cell apoptosis in the kidney and small intestine, accompanied by biochemical evidence of organ dysfunction. This may partially explain the high rate of MODS observed in patients with ARDS and the decrease in morbidity and mortality in patients treated with a lung protective strategy.

Animals↗