A randomised trial comparing the efficacy and safety of tacrolimus with microemulsified cyclosporine after liver transplantation.
Explore the source record for details and available documents.
Administration, Oral↗
Biomedical subjects
R Lange
Publications and source records attributed to R Lange.
Cell-extracellular matrix interaction and physico-chemical characteristics of titanium surfaces depend on the roughness of the material.
The interaction of cells with the extracellular matrix at the interface of an implant determines the biology of cells and tissues. We analysed components of cell adhesion and measured physico-chemical characteristics of structural modifications of titanium surfaces: polished, machined, glass particle-blasted, corundum-blasted, vacuum plasma-sprayed. Scanning electron microscopy and profilometry revealed a differentiated topography from smooth to rough surfaces, respectively. Osteoblastic MG-63 cells showed an increased spreading on surfaces with low roughness, although without a straight correlation with the surface topography. Integrin expression was increased on structured surfaces compared with polished material, and the organization of the actin cytoskeleton and fibronectin was impaired on extremely rough surfaces. Electrochemical methods, especially the electrochemical impedance spectroscopy (EIS) was used to evaluate physico-chemical characteristics, and the impedance curves revealed a dependence on the roughness of the material surfaces. Further analyses of the EIS results were performed using equivalent circuits which model the electrical flow through the interface. First indications for a correlation between parameters from the equivalent circuits with surface properties were obtained which promise a relevance for the biological response of the cells.
Actins↗
Causative factors, surgical treatment and outcome of incisional hernia after liver transplantation.
BACKGROUND: Little is known about the incidence and causes of herniation, and the results of hernia repair in patients undergoing liver transplantation. Likewise, nothing is known about the best surgical approach for hernia repair. METHODS: A retrospective analysis was conducted of the occurrence of incisional hernia in 290 patients who had liver transplantation between 1990 and 2000, and survived more than 6 months. Follow-up data were obtained from medical records and the outpatient service. Patients were evaluated for various clinical and surgical factors. Hernias were analysed with respect to localization, type of surgical repair and recurrence rate. RESULTS: Some 17 per cent of the transplanted patients experienced an incisional hernia. Risk factors were acute rejection with affiliated steroid bolus therapy (P = 0.025), a low platelet count after transplantation (P = 0.048), and a transverse abdominal incision with upper midline approach (P = 0.04). Hernias were mainly located at the junction of the transverse and midline incision (P < 0.001) and the recurrence rate was highest here (P = 0.007). Prosthetic hernia repair achieved the lowest rate of recurrence and did not increase the incidence of infectious complications. CONCLUSION: Improved immunosuppression should avoid early steroid bolus therapy after transplantation. A low platelet count promotes herniation. Transverse abdominal incision seems to be the best approach for liver transplantation. Prosthetic hernia repair does not increase the complication rate.
Adult↗
Capillary leak syndrome after cardiopulmonary bypass in elective, uncomplicated coronary artery bypass grafting operations: does it exist?
OBJECTIVE: Operations coupled with cardiopulmonary bypass may provoke a systemic inflammatory response, and it has been suggested that this responses causes capillary leakage of proteins, edema formation, and even organ failure. However, capillary leak syndrome is mainly a clinical diagnosis and has not been verified as yet by actual demonstration of protein leakage from the circulation. We have therefore measured the disappearance of labeled plasma protein before and after cardiopulmonary bypass. METHODS: Sixteen patients scheduled for elective coronary artery bypass grafting were enrolled in a prospective controlled study. The cardiopulmonary bypass circuit was primed with crystalloids only. Tumor necrosis factor alpha, interleukin 6, interleukin 8, anaphylatoxin C3a, and terminal complement complex C5b9 levels were determined before, during, and 3 hours after cardiopulmonary bypass. The transvascular escape rate of plasma protein from the intravascular compartment was assessed by measuring the disappearance of intravenously injected Evans blue dye before and during the third hour after cardiopulmonary bypass. RESULTS: A significant inflammatory response could be demonstrated by means of the 5 measured mediators after bypass. The maximal increase, as compared with the baseline value, was found for interleukin 6 (36-fold). The transvascular escape rate of Evans blue dye was similar before and after bypass (7.6 +/- 0.6%/h vs 7.3 +/- 0.6%/h). CONCLUSIONS: The above data confirm the systemic inflammatory response induced by cardiopulmonary bypass. Contrary to expectations, the transvascular escape rate of Evans blue dye did not change when comparing values before and after bypass. The data do not support the concept of increased protein leakage in the exchange vessels after bypass. We were unable to demonstrate a capillary leak syndrome.
Aged↗
Cardiac surgery with deep hypothermic circulatory arrest produces less systemic inflammatory response than low-flow cardiopulmonary bypass in newborns.
OBJECTIVE: We sought to compare low-flow cardiopulmonary bypass with deep hypothermic circulatory arrest in respect to the influence on the systemic inflammatory response. METHODS: Twenty-three infants weighing less than 10 kg and scheduled for repair of congenital malformations were enrolled in a randomized, controlled study. Eleven patients underwent cardiac surgery with deep hypothermic circulatory arrest (the DHCA group). Low-flow cardiopulmonary bypass was used in another 12 patients (the LF group). Interleukin 6 and 8 and anaphylatoxin C3a levels were measured 6 times perioperatively. Also, perioperative weight gain and a radiologic soft-tissue index were compared. RESULTS: All patients had an uneventful clinical course. Duration of deep hypothermic circulatory arrest was 40 +/- 4 minutes; the bypass time was significantly shorter in the DHCA group (85 +/- 8 vs 130 +/- 19 minutes). However, the duration of the operation was similar in both groups (245 +/- 30 vs 246 +/- 30 minutes). During cardiopulmonary bypass (rewarming), the concentration of C3a (3751 +/- 388 vs 5761 +/- 1688 ng/mL, mean +/- SEM) was significantly lower in the DHCA group than in the LF group. The interleukin 8 level was significantly lower, and the interleukin 6 level had a tendency to be lower in the DHCA group compared with levels in the LF group. There was less weight gain on the first postoperative day in the DHCA group (65 +/- 61 vs 408 +/- 118 g). The soft-tissue index suggested reduced edema formation in the DHCA group. CONCLUSION: Deep hypothermic circulatory arrest produces less systemic inflammatory response than low-flow cardiopulmonary bypass. In addition, there is an indication of less fluid accumulation postoperatively.
Blood Pressure↗
Use of high pressure to study elementary steps in P450 and nitric oxide synthase.
Chemical reactions are often highly pressure-dependent. A perturbation of the elementary steps by pressure therefore offers the possibility of a detailed characterization of enzyme mechanisms. We used this method to study distinct steps in the reaction of nitric-oxide synthase (NOS), and compared them to analogous steps in the reaction of cytochrome P450 BM3 (BM3). Our results indicate that, in BM3, electron transfer depends on electrostatic interactions. In NOS, pressure, similarly to chemical denaturants, can mimic the structural effects of Ca/calmodulin. This helps to better understand the structural basis of the regulatory effect of Ca/calmodulin. Furthermore, stopped-flow kinetics under high pressure show that CO binding to the heme iron is hindered by substrate in NOS, but not in BM3. This indicates a relatively large or flexible substrate binding site in BM3, and a more narrow and rigid binding site in NOS.
Bacterial Proteins↗
The poliovirus receptor CD155 mediates cell-to-matrix contacts by specifically binding to vitronectin.
The human receptor for poliovirus (CD155) is an immunoglobulin-like molecule with unknown normal function(s). Here we provide evidence that CD155 binds specifically to vitronectin with a dissociation constant (K(d)) of 72 nM as determined by surface plasmon resonance. Based on sequence homology to the CD155 gene, three poliovirus receptor-related genes (PRR1, PRR2, and PRR3) were cloned recently. PRR proteins were reported by others to mediate homophilic cell adhesion. Neither PRR1 nor PRR2 binds poliovirus and it is assumed that their physiological functions differ from that of CD155. Indeed, mPRR2 was found to bind to vitronectin only weakly, while its self-adhesion activity is characterized by a K(d) of 310 nM. Moreover, there is no evidence for CD155 self-adhesion. Both CD155 and vitronectin colocalize to follicular dendritic cells and B cells inside the germinal centers of secondary lymphoid tissue (tonsils)-an observation suggesting that the CD155/vitronectin interaction is required for the establishment of a proper immune response in this particular context.
Animals↗
Pressure denaturation of phosphorylating glyceraldehyde-3-phosphate dehydrogenase from Bacillus stearothermophilus.
The effects of hydrostatic pressure on apo wild-type glyceraldehyde-3-phosphate dehydrogenase (wtGAPDH) from Bacillus stearothermophilus (B. stearothermophilus) have been studied by fluorescence spectroscopy under pressure from 0.1 to 650 MPa. Unlike yeast GAPDH [Ruan, K. C., and Weber, G. (1989) Biochemistry 28, 2144-2153], denaturation of the tetrameric apo wtGAPDH from B. stearothermophilus is likely to precede dissociation into subunits. As expected, denaturation is accompanied by the loss of enzymatic activity. B. stearothermophilus apo wtGAPDH interfaces are less pressure sensitive than apo yeast GAPDH ones, while NAD does not protect B. stearothermophilus wtGAPDH against denaturation by pressure. The pressure effects on B. stearothermophilus GAPDH whose R and Q-axis interfaces were destabilized by disruption of interfacial hydrogen bonds are similar to that of apo wtGAPDH.
Apoenzymes↗
Myocardial blood flow and flow reserve after coronary reimplantation in patients after arterial switch and ross operation.
BACKGROUND: Coronary reimplantation is used in therapy for congenital heart disease, such as in the arterial switch (ASO) and Ross operations. The adequacy of myocardial perfusion may remain a matter of concern. The aim of the present study was to stratify the effect of coronary reimplantation on myocardial perfusion and to highlight the clinical relevance of any attenuation in myocardial perfusion. METHODS AND RESULTS: A total of 21 children with transposition of the great arteries at a mean interval of 11.2+/-2.9 years after ASO and 9 adolescents at a mean interval of 4.2+/-2.1 years after the Ross procedure were investigated. All patients were asymptomatic and had a normal exercise capacity. On stress echocardiography, 2 of the ASO patients had dyskinetic areas within the left ventricular myocardium, and 5 had adenosine-induced perfusion defects on positron emission tomography. No coronary obstruction was detected on coronary angiography in any patient, but a common finding was right coronary dominance and a small caliber of the distal part of the left anterior descending artery. Coronary flow reserve (CFR) was significantly reduced in all patients after ASO when compared with 10 normal healthy volunteers (age, 25.6+/-5.3 years). CFR was normal in the 9 patients who had the Ross operation (age, 19.2+/-7.6 years); exercise-induced perfusion defects were not detected in the Ross patients. CONCLUSIONS: Children after ASO are asymptomatic, without clinical signs of coronary dysfunction. In contrast to patients who had the Ross operation, stress-induced perfusion defects and an attenuated CFR were documented. The prognostic implications of these findings and the clinical consequences are unclear; nevertheless, close clinical follow-up of ASO patients is mandatory.
Adolescent↗
Unusual sites of malignancy: case 2. Orbital lymphoma.
Explore the source record for details and available documents.
Exophthalmos↗
Frequency and predictors of osteoporotic fractures after cardiac or liver transplantation: a follow-up study.
BACKGROUND: Osteoporosis and related fractures are a major complication after organ transplantation. The aim of this study was to find out the frequency and predictors of osteoporotic fractures after cardiac or liver transplantation. METHODS: 235 consecutive patients who had a cardiac transplant (n=105; 88 men, 17 women) or a liver transplant (130; 75 men, 55 women) were followed. Vertebral fractures were assessed by a standardised analysis of spinal radiographs before and annually after transplantation. Clinical and non-vertebral fracture data were noted from hospital records. FINDINGS: In the first and second years after transplantation, the proportion of patients (Kaplan-Meier estimates) who had at least one vertebral fracture was slightly higher in the cardiac group (first year 21%, second year 27%) than in the liver group (first year 14%, second year 21%). In the third and fourth years, one third of patients from both groups had had one or more vertebral fractures. Non-vertebral fractures occurred in nine patients (7%) after liver transplantation and avascular necrosis of the hip head in three patients (3%) after cardiac transplantation. In both groups, no dose-dependent effect of immunosuppressive therapy on fracture development could be identified. Independent predictors assessed by multivariate analysis were age (hazard ratio [95% CI] increase of 5 years, 1.71 [1.1-2.7]) and lumbar bone-mineral density (decrease of 1 SD t score, 1.97 [1.2-3.2]) in cardiac transplantation patients, and vertebral fractures before transplantation (6.07 [1.7-21.7]) in the liver group. INTERPRETATION: The high frequency of osteoporotic fractures in the 2 years after transplantation and the limitations of reliable fracture-risk predictions, show the need to investigate preventive therapies.
Adult↗
[Acute thrombosis of a mechanical heart valve caused by inadequate anticoagulation with low molecular weight heparin].
CASE REPORT: A 55-year-old woman with a mechanical aortic prosthesis was admitted with pulmonary edema and suspect of valvular malfunction. The patient had a anticoagulation therapy at the time with low-molecular-weight heparin only. Echocardiography confirmed a failing mobility of a prosthetic valve leaflet. Emergency aortic valve replacement was performed. CONCLUSION: According to international approved guidelines an adequate anticoagulation after mechanical prosthetic heart valve replacement is provided either by oral anticoagulants, or, in the case of pregnancy or surgical procedures, by unfractioned heparins. The use of low-molecular-weight heparin as sole anticoagulant remains a matter of controversy in the literature. In recent years low-molecular-weight heparins were mainly administered for prevention and treatment of deep vein thrombosis, pulmonary embolism, stroke, and instable angina.
Acute Disease↗
Serum bile acids in liver transplantation--early indicator for acute rejection and monitor for antirejection therapy.
We studied the course of serum bile acids to investigate its reliability in the diagnosis of acute rejection after liver transplantation in relation to pathohistological findings. Serum bile acid concentration, bilirubin and transaminases were measured in 41 patients who underwent liver transplantation. Their course was correlated to liver biopsy. Group I (n = 19) patients were without acute rejection, whereas group II (n = 22) patients showed acute rejection. Bile acid concentrations in group II showed a statistically highly significant (P < or = 0.001) threefold increase 3 days prior to biopsy. Successful antirejection treatment was correlated with a statistically significant (P = 0.008) decrease of serum bile acid 1 day after initiation of therapy. Patients without acute rejection showed a baseline bile acid concentration at the time of biopsy. Bilirubin and transaminases did not show any statistically significant correlation to acute rejection. Infection did not lead to a significant bile acid increase. Our study shows that serum bile acids monitored after liver transplantation can easily be used to detect acute rejection and at the same time they reflect the success of antirejection therapy.
Acute Disease↗
Relevance of two-stage total hepatectomy and liver transplantation in acute liver failure and severe liver trauma.
Emergency liver transplantation frequently is the only life-saving procedure in cases of acute liver failure. It remains unclear whether emergency hepatectomy with portocaval shunt followed by liver transplantation as a two-stage procedure should be performed in cases in which a donor organ is not yet available. It has been stated that "toxic liver syndrome" could be treated by means of this strategy. From 1990 to 1995 we performed emergency hepatectomies in eight cases of acute liver failure or traumatic liver rupture with exsanguinating bleeding. In six cases we were able to perform a subsequent liver transplantation. Five of the six patients who underwent an emergency hepatectomy died. Emergency hepatectomy led to a significant increase in epinephrine dosage until the transplantation was performed. Only after transplantation did the need for epinephrine therapy decrease. The need for oxygen support did not change during the entire observation period. Plasmatic coagulation was stabilized by substitution, showing significantly higher values at 24 h after transplantation than at 48 h before transplantation. Fibrinogen increased significantly after transplantation in this group of patients. The experiences gathered at our clinic, however, do not show advantages that would allow a recommendation of emergency hepatectomy and subsequent liver transplantation as a two-stage procedure except for situations of severe and uncontrollable hepatic bleeding. Considering the progressive destabilization of our patients, fast procurement of donor organs seems to be of imminent importance for the outcome.
Acute Disease↗
Passive finger movement evoked fields in magnetoencephalography.
We studied neuromagnetic fields during passive finger movements in 11 normal subjects. Activation started 27 ms after the onset of movement and remained for about 100 ms. Four activation maxima occurred within this time range, PM1 at 27 ms, PM2 at 46 ms, PM3 at 85 ms, and PM4 at 125 ms. Not all components were distinguishable in every subject partly due to overlapping effects, but PM3 was present in all subjects. Magnetic source imaging (MSI) revealed dipolar sources within 1 cm of the central sulcus for all four components. The results suggest that studying the integrity of the sensorimotor system in patients regardless of their degree of motor impairment is feasible.
Adult↗
[Dynamic cardiomyoplasty: evaluation of an alternative procedure in the treatment of terminal heart failure].
Dynamic cardiomyoplasty (DCMP) was developed as an alternative treatment for patients with end-stage heart failure. The first clinical application of this technique was in 1985 by Carpentier und Chachques. Since then, DCMP has been performed in more than 1000 patients world-wide. During the initial experience with DCMP, survival for NYHA class IV patients was clearly shown to be much worse than that for class III patients. By careful patient selection, operative mortality has decrease from 31% in the past to less than 5% today. The vast majority of patients have demonstrated significant improvement in NYHA class and overall quality of life with only minor effects on systolic cardiac function. Clinical work, as well as recent animal work supports the hypothesis that by a combination of long-term elastic constraint and active dynamic assist, DCMP decreases myocardial wall stress. This process results in a "reverse remodeling" of the insufficient heart with an improvement of the "contractility reserve". To prove the effectiveness of DCMP versus medical therapy alone, the C-SMART study started in 1994, as the first and only randomized trial. Unfortunately the study was stopped in 1998 due to slow patient recruitment after enrolling 103 patients. The study showed that, from a symptoms standpoint, patients with DCMP were improved over those who were medically treated. However, there was no significant difference for survival between the two groups after 12 months. The lack of a clear survival advantage and the relatively poor and inconsistent hemodynamic benefit of DCMP have hindered its acceptance to date as a treatment alternative for patients with end-stage heart failure. The ultimate role of DCMP in the treatment of heart failure will depend on the outcome of future developments to improve the contractility and the long-term durability.
Cardiomyoplasty↗
[Isolated left ventricular papillary muscle rupture: a rare event after blunt thoracic trauma].
We report about a 20-year old man, who suffered from a car accident under the influence of ecstasy. Although he had no visible injuries at the chest, the accident caused an isolated rupture of a papillary muscle of the mitral valve. A review of the literature shows the rarity of this kind of injury. The mechanisms of traumatic papillary muscle rupture, the diagnosis, therapy and complications are discussed.
Accidents, Traffic↗
Formation of a protonated trihydrobiopterin radical cation in the first reaction cycle of neuronal and endothelial nitric oxide synthase detected by electron paramagnetic resonance spectroscopy.
Nitric oxide synthase (EC 1.14.13.39; NOS) converts L-arginine into NO and L-citrulline in a two-step reaction with Nomega-hydroxy-L-arginine (NOHLA) as an intermediate. The active site iron in NOS has thiolate axial heme-iron ligation as found in the related monooxygenase cytochrome P450. In NOS, tetrahydrobiopterin (BH4) is an essential cofactor for both steps, but its function is controversial. Previous optical studies of the reaction between reduced NOS with O2 at -30 degrees C suggested that BH4 may serve as an one-electron donor in the first cycle, implying formation of a trihydrobiopterin radical. We investigated the same reaction under identical conditions with electron paramagnetic resonance spectroscopy. With BH4-containing full-length neuronal NOS we obtained an organic free radical (g-value 2.0042) in the presence of Arg, and a similar radical was observed with the endothelial NOS oxygenase domain in the presence of Arg and BH4. Without substrate the radical yield was greatly (10x) diminished. Without BH4, or with NOHLA instead of Arg, no radical was observed. With 6-methyltetrahydropterin or 5-methyl-BH4 instead of BH4, radicals with somewhat different spectra were formed. On the basis of simulations we assign the signals to trihydropterin radical cations protonated at N5. This is the first study that demonstrates the formation of a protonated trihydrobiopterin radical with the constitutive isoforms of NOS, and the first time the radical was obtained without exogenous BH4. These results offer strong support for redox cycling of BH4 in the first reaction cycle of NOS catalysis (BH4 <--> BH3.H+).
Animals↗