Search PubMed⌕ Search

Biomedical subjects

R Lange

Publications and source records attributed to R Lange.

At least 109 records · Page 6Linked to original sources

Domain organization and molecular characterization of 13 two-component systems identified by genome sequencing of Streptococcus pneumoniae.

In bacteria, adaptive responses to environmental stimuli are often initiated by two-component signal transduction systems (TCS). The prototypical TCS comprises two proteins: a histidine kinase (HK, hk) and a response regulator (RR rr). Recent research has suggested that compounds that inhibit two-component systems might have good antibacterial activity. In order to identify TCS that are crucial for growth or virulence of Streptococcus pneumoniae, we have examined the genomic sequence of a virulent S. pneumoniae strain for genes that are related to known histidine kinases or response regulators. Altogether 13 histidine kinases and 13 response regulators have been identified. The protein sequences encoded by these genes were compared with sequences deposited in public databases. This analysis revealed that two of the 13 pneumococcal TCSs have been described before (ciaRH and comDE) and two are homologous to the yycFG and the phoRP genes of Bacillus subtilis. All the pneumococcal response regulators contain putative DNA binding motifs within the C-terminal output domain, implying that they are involved in transcriptional control. Two of these response regulators are obviously the first representatives of a new subfamily containing an AraC-type DNA-binding effector domain. To assess the regulatory role of these transcription factors, we disrupted each of the 13 response regulator genes by insertional mutagenesis. All the viable mutant strains with disrupted response regulator genes were further characterized with regard to growth in vitro, competence, and experimental virulence. Two response regulator genes could not be inactivated, indicating that they may regulate essential cellular functions. The possibility of using these systems as targets for the development of novel antibacterials will be discussed.

Amino Acid Motifs↗

The individual tyrosines of proteins: their spectra may or may not differ from those in water or other solvents.

The overall derivative spectrum of a protein is the sum of the individual derivative spectra just as the overall ultraviolet spectrum of a protein is the sum of its component parts. The RNase and DNA binding protein Sso7d has two tyrosines and one tryptophan. We used two mutant forms of the protein to show that the individual aromatics contribute derivative spectra that can be explained on the basis of their environments. We used mutant forms of iso-1-cytochrome c to estimate the contributions of the single tryptophan and three of the five tyrosines to the overall derivative spectrum. The tryptophan spectrum is not exceptional. The comparable tyrosine spectra are more complex. The derivative spectrum of individual tyrosines does not correspond to that expected on the basis of concentration. This is a reflection of two factors: (1) the extent to which mutations are sensed distally through the introduction and compression of packing defects; and (2) the extent to which electronic transitions of tyrosine are influenced by nearby atoms. This influence could take the form of tyrosine residing in an area where the dielectric coefficient is not uniform; it could also result from tyrosine bumping into neighboring atoms with lower frequency than it does in solution.

Proteins↗

[Surgical treatment of cardiovascular manifestations of Marfan's syndrome].

Patients with Marfan's syndrome suffer mainly from the cardiovascular manifestations of the disease, in particular the acute dissection or rupture of the dilated aorta. Due to improved diagnostic and early surgical intervention the life expectancy of these patients could be considerably improved. However, rupture is still the most frequent and dissection the second frequent cause of death. Life threatening complications of aortic dissection are pericardial effusion, aortic insufficiency and malperfusion syndrome, due to obstruction of aortic branches. Dissection of the ascending aorta is treated by implantation of a valved conduit with reimplantation of the coronary arteries. Some surgeons favor the complete replacement of the ascending aorta with preservation of the aortic valve, although long-term results show some development of aortic insufficiency after this procedure. Based on the experience of the last years, most surgeons prefer the prophylactic replacement of the aorta in Marfan patients, i.e. before complications have occurred. A special treatment algorithm helps to define the indication for the operative treatment in different manifestations of the disease. The low mortality of the elective replacement of the ascending aorta in contrast to replacement in emergency cases speaks in favor of the early operative treatment. For the long-term prognosis of the patient a closed and continuous cardiologic surveillance is mandatory. The patient should be close to a center with the necessary diagnostic tools and with sufficient experience with the medical and surgical treatment, in order to further improve the life expectancy in the future.

Aortic Dissection↗

[A new concept for treatment of supraventricular tachycardia after heart operations: low energy internal cardioversion using a temporary atrial electrode].

Supraventricular tachycardia (SVT) is a common complication early after cardiac surgery. A novel temporary atrial patch electrode (TAPE) for low energy atrial defibrillation was first implanted for intraoperative testing and subsequently removed during open heart surgery in 10 patients (Phase I). After the intraoperative testing period, the TAPE was implanted in 20 patients for postoperative termination of spontaneous episodes of supraventricular tachycardia (Phase II). In case of supraventricular tachycardia (SVT), biphasic shocks (1.2-5.0 J) were applied, measuring the atrial defibrillation thresholds. Phase I: The mean intraoperative atrial defibrillation threshold was 1.6 +/- 1.4 J with a mean shock-impedance of 64.0 +/- 7.3 Ohms. Phase II: Postoperatively, 6 out of 20 patients (30%) developed 7 episodes of atrial fibrillation (n = 6) and atrial flutter (n = 1). In 5 patients, SVT could be converted to sinus rhythm (n = 5) or junctional rhythm (n = 1). The mean postoperative defibrillation threshold (DFT) was 2.7 +/- 2.1 J with a mean shock-impedance of 50.2 +/- 6.8 Ohms. In conclusion, the TAPE allows low-energy defibrillation of atrial fibrillation. It seems to be a useful alternative in the treatment of supraventricular tachycardia.

Adult↗

Auxiliary liver transplantation in acute liver failure in the rat -- an illustrated description of a new surgical approach.

INTRODUCTION: To investigate auxiliary liver transplantation successfully in rats suffering from acute liver failure, we developed a new surgical approach. METHODS: A 70% hepatectomized liver graft was implanted into the right upper quadrant of the abdomen. The donor portal vein was anastomosed with the recipient's right renal artery using the splint technique. The donor infrahepatic vena cava was attached onto the recipient vena cava end to side. The bile duct was implanted into the duodenum.

Anastomosis, Surgical↗

Outcome and management of blunt liver injuries in multiple trauma patients.

BACKGROUND: In Germany, abdominal trauma in multiple- trauma patients can be observed in about 25-35% of all cases. Due to major bleeding complications, the initial treatment of blunt abdominal trauma in multiple-trauma patients has high priority. The aim of this study was to discuss management, treatment and outcome of blunt liver injury in multiple-trauma patients treated in our department. METHODS: The clinical records of 1192 multiple-trauma patients [injury severity score (ISS) 3-18] treated at the Surgical Department of the University Clinic of Essen from January 1975 to February 1998 were reviewed. Seventy-five patients with an ISS above 18 operated on due to a blunt liver injury could be included. The mean age was 29.82+/-1.80 years (60 males and 15 females). The degree of injury in this group was high (ISS 37.12+/-1.06). RESULTS: Twenty-three of the 75 (30.6%) patients died during their hospital stay. Deceased patients were older (27+/-2 years versus 37+/-4 years; P<0.01) and had a higher ISS (ISS=34.5+/-1 versus 43.2+/-2; P<0.01). In nine cases, death was strongly related to liver injury. Operational blood loss was higher in the group of multiply injured patients with liver injury and in those patients who did not survive (P<0.05). An increased mortality could be seen in this selected patient group when compared with our large collective of multiply injured patients. The age of the patients, the ISS and operative blood loss were the significant factors that influenced the operative mortality after blunt hepatic injuries in our study.

Adult↗

Simulation of arterial hemodynamics after partial prosthetic replacement of the aorta.

BACKGROUND: Replacing parts of the aorta with a non-compliant vascular prosthesis results in marked alterations of the aortic input impedance and influences arterial hemodynamics. We propose a mathematical model of circulation that can predict hemodynamic changes after simulation of vascular grafting. METHODS: A new mathematical model of the human arterial system was developed on a 75-MHz Pentium personal computer using Matlab software. The human arterial tree was delineated according to a 128-branch design encompassing bifurcations and physical properties of the arterial wall. A digitized aortic flow wave was chosen as the input signal to the system. After determination of the modules of elasticity of native vascular tissue and standard prostheses in technical experiments, replacement of any part of the aorta with a prosthesis was simulated by increasing the elasticity in the parts desired. RESULTS: During control conditions, the model displayed a physiologic distribution of flow and pressure waves throughout the arterial system. Simulated replacement of the aorta resulted in an increase in pressure amplitude and a partial loss of the aortic "Windkessel" function. Calculation of the aortic input impedance showed an increase in the characteristic impedance, whereas the peripheral resistance remained unaltered. CONCLUSIONS: This mathematical model of the arterial circulation is useful for simulating hemodynamic changes after implantation of vascular grafts. The results of the model analysis are consistent with those in previous experimental work.

Aorta↗

Pectoral implantation of single-lead implantable cardioverter-defibrillators in patients without transvenous access.

With the introduction of the single-lead "Active-Can" implantable cardioverter-defibrillators, the implantation of the internal defibrillators has become a technically easy procedure. With these systems lowest defibrillation thresholds are achieved with a very low complication rate. For patients with thrombosis of both subclavian veins, however, a transvenous implantation technique is not possible. These patients are still equipped with epicardial patch electrodes. This article describes an alternative technique for implantation of this system in such patients, eliminating the need for epicardial patches and related complications.

Defibrillators, Implantable↗

Monitoring of soluble HLA class I size variants after liver transplantation.

To monitor soluble HLA class I (sHLA-I) and their size variants after liver transplantation (LTX) plasma samples from 22 LTX patients were studied by sHLA-I ELISA, SDS-PAGE, and densitometry. Samples collected were classified into three groups: Group 1 comprised samples taken during episodes without complications, group 2 during episodes of cholangitis/cholestasis (CC), and group 3 during episodes of acute rejection (AR). Compared to group 1 (0.27 +/- 0.03 SEM microg/ml) mean sHLA-I increments in groups 2 and 3 were with 0.53 +/- 0.05 SEM microg/ml and 0.47 +/- 0.04 SEM microg/ml increased (p < 0.001). The same samples were studied by SDS-PAGE and the 43, 39, and 35 kD sHLA-I variants were quantified densitometrically. In samples of group 1 ratios of 43 vs. 39 kD bands revealed a mean of 2.1 +/- 0.3, whereas in group 2 and 3 these were only 0.8 +/- 0.1 SEM and 0.9 +/- 0.1 SEM, respectively, (p < 0.001). For the relation between 43 and 35 kD variants a reduced ratio of 1.1 +/- 0.2 SEM was confined to group 3 samples (p < 0.001), as groups 1 and 2 had ratios of 13.4 +/- 2.3 SEM and 8.4 +/- 2.9 SEM, respectively. This indicates that elevated sHLA-I levels during CC or AR are mainly caused by increases of 39 and/or 35 kD sized molecules. Therefore, our study demonstrates, that after LTX the contribution of sHLA-I size variants to total sHLA-I amounts changes drastically during immune activation pointing to different mechanisms of sHLA-I release.

Acute Disease↗

Pharmacokinetics, induction of anaesthesia and safety characteristics of propofol 6% SAZN vs propofol 1% SAZN and Diprivan-10 after bolus injection.

AIMS: In order to avoid the potential for elevated serum lipid levels as a consequence of long term sedation with propofol, a formulation of propofol 6% in Lipofundin(R) MCT/LCT 10% (Propofol 6% SAZN) has been developed. The pharmacokinetics, induction of anaesthesia and safety characteristics of this new formulation were investigated after bolus injection and were compared with the commercially available product (propofol 1% in Intralipid(R) 10%, Diprivan-10) and propofol 1% in Lipofundin(R) MCT/LCT 10% (Propofol 1% SAZN). METHODS: In a randomised double-blind study, 24 unpremedicated female patients received an induction dose of propofol of 2.5 mg kg-1 over 60 s which was followed by standardized balanced anaesthesia. The patients were randomized to receive propofol as Propofol 6% SAZN, Propofol 1% SAZN or Diprivan-10. RESULTS: For all formulations the pharmacokinetics were adequately described by a tri-exponential equation, as the propofol concentrations collected early after the injection suggested an additional initial more rapid phase. The average values for clearance (CL), volume of distribution at steady-state (Vd,ss ), elimination half-life (t1/2,z ) and distribution half-life (t1/2, lambda2) observed in the three groups were 32+/-1.5 ml kg-1 min-1, 2. 0+/-0.18 l kg-1, 95+/-5.6 min and 3.4+/-0.20 min, respectively (mean+/-s.e.mean, n=24) and no significant differences were noted between the three formulations (P >0.05). The half-life of the additional initial distribution phase (t1/2,lambda1 ) in all subjects ranged from 0.1 to 0.6 min. Anaesthesia was induced successfully and uneventfully in all cases, and the quality of induction was adequate in all 24 patients. The induction time did not vary between the three formulations and the average induction time observed in the three groups was 51+/-1.3 s which corresponded to an induction dose of propofol of 2.1+/-0.06 mg kg-1 (mean+/-s.e. mean, n=24). The percentage of patients reporting any pain on injection did not vary between the formulations and was 17% for the three groups. No postoperative phlebitis or other venous sequelae of the vein used for injection occurred in any of the patients at recovery of anaesthesia nor after 24 h. CONCLUSIONS: From the above results, we conclude that the alteration of the type of emulsion and the higher concentration of propofol in the new parenteral formulation of propofol does not affect the pharmacokinetics and induction characteristics of propofol, compared with the currently available product. Propofol 6% SAZN can be administered safely and has the advantage of a reduction of the load of fat and emulsifier which may be preferable when long term administration of propofol is required.

Adult↗

[Temporary adjustable defibrillator electrodes: an alternative method for the treatment of postoperative arrhythmias after heart surgery].

INTRODUCTION: Supraventricular and ventricular tachycardias are common and serious postoperative complications early after cardiac surgery. We introduce a new temporary adjustable defibrillation electrode (TADE) for internal low-energy cardioversion/defibrillation of postoperative atrial and ventricular tachyarrhythmias. METHODS: Evaluation of the new electrode was performed in ten open-chest beagles with a mean weight of 25.5 kg. The electrodes were first positioned on the left and right atrium. Atrial fibrillation (AU) was induced via a bipolar temporary heart wire. Atrial defibrillation thresholds (DFT's) were measured according to a step-down shock protocol (5 J-0.4 J). Thereafter, the electrodes were adjusted and positioned on the right and left ventricle. Ventricular fibrillation (VF) was induced and DFT's were recorded the same way. RESULTS: For termination of AF, mean DFT's were 0.4 +/- 0 J (lowest possible shock level) with a mean shock impedance of 70 +/- 7.6 omega. VF was terminated with a mean DFT of 3 +/- 1.1 J with a mean impedance 56.1 +/- 7.9 omega. Complete transcutaneous removal of the electrodes was possible in all animals without any complications. CONCLUSION: Successful low-energy termination of AF and VF is possible with the tested temporary adjustable electrode. A clinical study is planned for further evaluation.

Animals↗

The impact of television on attitudes towards organ donation--a survey in a German urban population sample.

BACKGROUND: The stagnation or decrease in organ donation rates since 1992 in Germany has partly been attributed to the negative impact of reports about organ donation periodically presented by German television between 1992 and 1997. This study was performed to elucidate the impact of the media on the public's attitudes towards organ donation. METHODS: A questionnaire concerning different aspects of organ donation was sent to the parents of pupils of a high school in a German city in 1994 and 1998. RESULTS: In 1994, 940 adults could be identified who had (TV+, n = 546) or had not (TV-, n = 394) followed at least one television discussion about the topic. In 1998, the group consisted of 756 (TV+, n = 443 and TV-, n = 313) adults. The discriminating question was of sufficient strength to reveal significant differences between TV(+) and TV(-) respondents. Contrary to an assumed negative impact of TV, differences between the groups were detectable mainly in questions regarding information, but not in those which dealt with personal fears and concerns. The main results obtained in both surveys were identical. Furthermore, from 1994 to 1998 there was a trend in favour of information and organ donation for TV(+) but not for TV(-) respondents. CONCLUSION: The assumption that TV has had a negative impact on donation rates must be rejected. Therefore, the stagnation/decline in donation rates must be attributed to other factors.

Attitude↗

The role of fear in delusions of the paranormal.

Based on an extended process model derived from attribution theory, we hypothesized that pervasive and persistent delusions of the paranormal are characterized by the existence of a positive (self-reinforcing), rather than a negative (self-correcting), feedback loop involving paranormal beliefs, fears, and experiences, as moderated by gender and tolerance of ambiguity. A cross-cultural sample of "international" students who reported poltergeist-like experiences showing high fear of the paranormal was identified. As in earlier research, path analysis showed statistically significant and positive effects of belief on experience and/or fear on belief. However, paranormal experience now had a positive effect on fear as well. Thus, as predicted, increased fear removes the option of neutralizing ambiguous events by labeling them as "paranormal." Although female subjects showed significantly greater fear of the paranormal than male subjects, there is no evidence that the nature of the delusional process is gender specific.

Acculturation↗

Adjustable atrial and ventricular temporary electrode for low-energy termination of tachyarrhythmias early after cardiac surgery.

Supraventricular and ventricular tachycardias are common and serious postoperative complications early after cardiac surgery. We introduce a completely removable temporary adjustable defibrillation electrode (TADE) for low energy cardioversion/defibrillation of postoperative atrial and ventricular tachyarrhythmias. The electrode consists of three loops of steel wires connected to one steel wire, which are movable within an isolation sheet for adjusting the active surface to the individual size of the heart chambers. Evaluation of the electrode was performed in 10 open-chest beagles with a mean weight of 25.5 kg. The electrodes were first positioned on the left and right atrium. Atrial fibrillation (AF) was induced via a bipolar temporary heart wire. Atrial defibrillation thresholds (DFTs) were measured according to a step-down shock protocol (5-0.4 J). Thereafter, the electrodes were adjusted and positioned on the right and left ventricle. Ventricular fibrillation (VF) was induced and DFTs were recorded the same way. Aortic flow and pressure and left ventricular pressure were continuously monitored throughout the experiment. For termination of AF, mean DFTs were 0.4 +/- 0 J (lowest possible shock level) with a mean shock impedance of 70 +/- 7.6 ohms. VF was terminated with a mean DFT of 3 +/- 1.1 J with a mean impedance 56.1 +/- 7.9 ohms. Complete transcutaneous removal of the electrodes was possible in all animals without any complications. In conclusion, successful low energy termination of AF and VF is possible with the tested temporary adjustable electrode. A clinical study is planned for further evaluation.

Animals↗

Aortic input impedance and ventriculoarterial coupling following cardioversion/defibrillation.

Defibrillation shocks are commonly used after cardiac surgery or during defibrillator implantation. The hemodynamic consequences of countershocks on circulatory dynamics are not completely understood, and there is a lack of information concerning the effects on ventriculoarterial interaction. The study presented here was performed to assess the influence of defibrillation shocks on arterial hemodynamics and ventriculoarterial coupling. Eight mongrel dogs (weight 15-18 kg) were anesthetized and median thoracotomy was performed. Pressure in the ascending aorta and the left ventricle and flow in the ascending aorta were continuously monitored. After induction of atrial or ventricular fibrillation, termination was achieved by epicardial low energy shocks (atrium, 3J; ventricle, 51). In an additional attempt ventricular fibrillation was terminated by a high energy shock (34J). Aortic input impedance was calculated by fast-Fourier-transformation of aortic flow and pressure signals, while ventriculoarterial coupling was expressed by the ratio of aortic and ventricular end systolic elastance (Ea/Ees). Defibrillation by low energy shocks of atrial or ventricular fibrillation did not result in changes of the aortic impedance spectrum, and ventriculoarterial coupling remained unaltered compared to control conditions. High energy defibrillation, however, resulted in a marked rise in total peripheral resistance (P < 0.03). The ratio of Ea/Ees increased significantly (P < 0.005). These effects were reversible within 15 minutes. Low energy defibrillation does not alter arterial hemodynamics and ventriculoarterial coupling in this experimental setup. High energy defibrillation, however, results in a temporary increase of ventricular load. This finding may be of particular interest in patients with poor left ventricular function.

Animals↗

Mathematical modelling of extracorporeal circulation: simulation of different perfusion regimens.

Computer- and sensor-aided control of the heart-lung machine is considered a major goal for perfusion sciences for the next few years. At present, control of perfusion is achieved by surgeons, anaesthesiologists and perfusionists making short-term decisions, which leads to variations of the perfusion regimens between different centres and even between different teams in the operating theatre. As the basis for an integrated control of extracorporeal circulation (ECC), we proposed a mathematical model for simulating haemodynamics during pulsatile perfusion. This model was then modified to allow it to simulate the effects of different perfusion regimens on arterial haemodynamics and whole body oxygen consumption. The model was constructed on a PC using MATLAB/SIMULINK. The human arterial tree was divided into a multibranch structure consisting of 128 segments characterized by their particular physical properties. Peripheral branches were terminated by a resistance term representing smaller vessels like arterioles and capillaries. Flow and pressure were expressed by the intensity of current and voltage in an electrotechnical analogon; inductivity, resistance and capacitance were implemented according to the physical properties of the arterial tree and the rheology of blood. The effects of different perfusion regimens (pulsatility, flow amount, acid-base regulation) were studied. After introducing an input signal to the model, flow and pressure waves established themselves throughout the simulated arterial tree. During the simulation experiments, marked differences among different perfusion regimens were displayed by the model. Variations in acid-base management mainly influenced the distribution of perfusion: during simulation of low-flow perfusion (1.2 l/min/m2), cerebral blood flow was 6.2 ml/s using an alpha-stat regimen, while it was increased to 9.4 ml/s during pH-stat, caused by an implementation of reduced cerebral resistance. Whole body oxygen consumption was predominantly regulated by the perfusion rate. While central venous oxygen saturation was calculated to be 84.7% during simulation of high-flow perfusion (2.4 l/min/m2), it dropped to 70% during simulation of low-flow perfusion regimens. The model proved to be useful for a realistic simulation of different perfusion regimens. Therefore it can be considered a continuing step for the derivation of a 'state' observer leading to the realization of an automatically controlled heart-lung machine.

Blood Transfusion↗