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E Alt

Publications and source records attributed to E Alt.

At least 73 records · Page 4Linked to original sources

Coordinate expression of N-myc 2 and insulin-like growth factor II in precancerous altered hepatic foci in woodchuck hepatitis virus carriers.

Over 50% of the hepatocellular carcinomas (HCCs) arising in the livers of woodchucks with persistent woodchuck hepatitis virus (WHV) infection contain integrations of WHV DNA within, or immediately adjacent to, a unique and functional N-myc 2 retroposon [G. Fourel et al., Nature (Lond.), 347: 294-298, 1990; Y. Wei et al., J. Virol., 66: 5265-5276, 1992]. The integrations are believed to activate the expression of N-myc 2 by an enhancer insertion mechanism [Y. Wei et al., J. Virol., 66: 5265-5276, 1992]. Since the fetal growth factor insulin-like growth factor II (IGF-II) is also expressed in woodchuck HCCs [X. X. Fu et al., J. Virol., 62: 3422-3430, 1988; D. Yang and C. E. Rogler, Carcinogenesis (Lond.), 12: 1893-1901, 1991] we sought to determine the earliest stage in hepatocarcinogenesis at which overexpression of N-myc and IGF-II could be detected. The earliest precancerous lesions so far identified in woodchucks are altered hepatic foci (AHFs) [K. Abe et al., Jpn. J. Cancer Res., 79: 466-472, 1988; H. Popper et al., Hepatology (Baltimore), 1: 91-98, 1981]. Using in situ hybridization, we have demonstrated that both the N-myc and IGF-II genes are coordinately overexpressed in nearly all AHFs in precancerous woodchuck livers. In contrast, WHV replication was either repressed or undetectable in the same AHFs. The use of probes selective for N-myc 2 versus N-myc 1 (the normal mammalian homologue) revealed nearly exclusive expression of N-myc 2 in AHFs. Cells within AHFs were generally slow growing, as determined by frequency of histone III-expressing hepatocytes; however, a few fast-growing AHFs, with growth rates nearly equivalent to those of HCCs, were identified. Furthermore, very highly elevated N-myc 2 or IGF-II expression was detected in a few subregions within AHFs which otherwise exhibited a uniformly moderate expression, suggesting that selection for higher levels of N-myc or IGF-II expression may occur within AHFs. These data suggest that coordinate expression of N-myc 2 and IGF-II and repression of WHV replication may be functionally involved in the development of AHFs and that cells expressing very high levels of N-myc and IGF-II may be selectively enriched as AHFs progress to HCC, since high levels of N-myc and IGF-II are common in HCCs.

Animals↗

[Behavior of various activity-controlled cardiac pacemakers in treadmill stress tests with variable slopes].

New activity pacemaker systems with the principle of sensing low-frequency acceleration in the anterior-posterior axis are currently under clinical evaluation. We compared the pacemaker system Relay, which represents this new generation of accelerometer controlled devices, with conventional activity systems sensing pressure and vibration. Ten pacemaker patients with implanted Activitrax, Sensolog or Relay pacemakers and 10 healthy volunteers with externally strapped-on pacemakers were studied. The aim was to evaluate the systems' ability to distinguish different workloads during graded treadmill testing with changes in speed and/or slope. The rate adaption of the new acceleration sensing pacemakers was found to be more adequate compared to vibration and pressure-sensing pacemakers when only the slope of the treadmill was varied. The acceleration-sensing pacemaker adjusted its rate according to the workload largely independent from the type of stress (n.s.). With the vibration and pressure-sensing pacemakers, however, significant differences (p < 0.05) were seen between rate adaption in the two stress test modes. The new generation of acceleration-sensing pacemakers has certain advantages over conventional vibration-sensitive systems in terms of a higher sensitivity to varying workloads and higher specificity to the type of exercise performed.

Adult↗

Feasibility of using intracardiac impedance measurements for capture detection.

Energy consumption and longevity of modern pacemakers are determined by the controlling electronic circuitry and by the stimulation energy. While with technological progress the electronics' energy consumption has been reduced significantly, clinical practice shows that many cardiac pacemakers are programmed to suboptimal settings with regard to minimization of pacing energy consumption. Several methods for optimizing pacemaker output settings have been proposed in the past. The most promising concept is an output parameter optimizing pacemaker with automatic capture detection. We examined whether it is possible to distinguish between effective and ineffective pacemaker stimulus capture by analyzing high pass filtered intracardiac impedance signals that are derived from standard bipolar pacing leads. In one series of 11 patients undergoing replacement or implantation of chronic bipolar pacemakers, four patients during electrophysiology studies, and eight volunteers undergoing invasive electrophysiology trials, we examined intracardiac impedance signals obtained with various stimulation rates and output parameter settings. Additionally we analyzed a series of five patients with implanted pacemakers that can measure and telemeter intracardiac impedance signals. Several evaluation concepts have been analyzed regarding their ability to discriminate between effective and ineffective stimuli. We developed an adequate algorithm that detects capture or loss of capture at different output parameter settings based on intracardiac impedance analysis. The sensitivity is 98.5% and specificity is 91% to loss of capture for the currently investigated algorithm and this can be used to determine the optimal setting of pulse width and amplitude with regard to energy consumption. This concept is currently under realization in the external programmer and in the future an implementation of these algorithms within the pacemaker itself is intended.

Algorithms↗

Comparison of two activity-controlled rate-adaptive pacing principles: acceleration versus vibration.

Activity-guided rate-adaptive pacing is currently the most widely used principle for rate adaptation. Broad experience has been gathered from several hundred thousand pacemakers that adjust the pacing rate according to vibrational forces detected by a piezosensor bonded to the inner side of the pacemaker can. A new generation of accelerometer-based pacemakers has been introduced into clinical practice. The vibrational type detects vibration, pressure, and shock waves traveling through the body with physical stress and using the pacemaker can as a resonator. In contrast, the accelerometer is insulated from the pacemaker housing and is incorporated into electronic hybrid circuitry. The forces detected by an accelerometer are motion and acceleration of the body in an anterior-posterior direction. Clinical studies conducted to date have shown that the accelerometer to be superior to the conventional vibration activity pacemakers, as far as the discrimination of different workloads and rejection of unwanted environmental noise are concerned.

Acceleration↗

[Initial studies of the possibility of selective ablation of arteriosclerotic vascular changes using laser-induced shock waves].

We studied the effect of laser-induced shock waves in 94 arterial segments from freshly obtained autopsy material. In analogy to the well-established method of shock-wave based lithotripsy, the new principle of our treatment depends on an indirect interaction of the laser energy with the arterial wall via laser-induced mechanical shock waves (angiotripsy). We used a Nd:YAG laser, 1064 nm, 8-20 ns pulse-length to create shock waves that effected smooth craters in arteriosclerotically affected arteries. The histological examination found no thermal damage. Shock waves applied to the healthy and normal arterial wall only resulted in focal intimal ablation and in a minor loosening of the medial structures. The examination of the irrigation solution by means of a laser-guided, high-resolution analysis of the particles revealed that, in 97%, the particles created by our shock wave angiotripsy showed a diameter of less than 5 mm and an area of less than 25 mm2. Based on these first in vitro results, it seems possible to ablate arteriosclerotically affected tissue without significant damage to normal wall segments. Further in vitro and in vivo studies are required to evaluate the clinical implications of this new therapeutic approach.

Angioplasty, Laser↗

[Effect of body posture on heart rate and cardiocirculatory parameters in stress--implications for frequency-adapted pacemaker systems].

In order to study the influence of body position on cardiodynamics and the consequences for the regulation of rate-adaptive pacing, we examined variations of cardiocirculatory parameters with passive graded tilt from the erect to the supine position (90 degrees, 75 degrees, 60 degrees, 45 degrees, 30 degrees, 0 degrees) in 25 healthy subjects of both sexes under resting conditions and under conditions of exercise on a bicycle ergometer. Using impedance cardiography combined with phonocardiography, it was possible to record heart rate, cardiac output, contractility (Heather index), and left-ventricular ejection time (LVET). Under the condition of rest, some parameters showed evident tilt dependency: tilting from erect to supine induced a decrease of heart rate (85.1 to 65.7 bpm), an increase of stroke volume (84.4 to 111.4 ml), and a prolongation of LVET (255.8 to 330.3 ms). Cardiac output and the index of contractility were not changed by this manipulation, however. Tilting under the condition of exercise clearly had less influence on all cardiodynamic parameters than tilting under the condition of rest. The only significant increase of heart rate (89.4 to 109.2 bpm), cardiac output (10.4 to 13.1 l/min), and Heather index (24.2 to 29.8 ohm/s2) was found between 30 degrees or 15 degrees, respectively, and the supine position. Thus, in addition to indicators of physical activity, body position respective stroke volume should be taken into consideration. Consequently, rate-adaptive pacing may guarantee optimal physiological hemodynamics.

Adult↗

A new approach towards defibrillation electrodes: highly conductive isotropic carbon fibers.

A new carbon fiber material was studied for its potential benefit in defibrillation electrodes. Miniaturization of the fiber production can result in small strands with extremely large surface areas. Two carbon fiber patches and a single carbon fiber bundle were used for the purposes of this study, and the results were compared to those obtained with conventional titanium/mesh patch electrodes. Tests performed in a saline filled tank revealed considerably lower resistances through the carbon material when compared to standard mesh electrodes. There was also a higher peak current flow with lower voltage. The carbon fibers exhibited lower impedance for defibrillation and this may be related to low polarization known to occur with carbon materials. This new carbon material may prove to be useful and further research is required.

Carbon↗

Effect of different body-exercise modes on the rate response of the temperature-controlled pacemaker Nova MR.

In order to evaluate the effect of different modes of physical exercise on the rate response of the temperature-controlled Nova MR, parameters such as temperature behaviour and correlation of work load to pacing rate were investigated using different types and protocols of stress testing. This study considered 21 patients (age: 66 +/- 12 y). The indications for the Nova MR were AV block (n: 14) and sick sinus syndrome (n: 7). The patients performed two different types of exercise (treadmill n: 13, bicycle n: 14) based on different protocols. We registered the surface ECG, pacing rate, exercise time, and (via data transmission by the RX 2000 programmer) blood temperature and pacing rate. An adequate rate response could be achieved with all the different types of exercise and protocols using more sensitive program settings. The type of stress testing used to adjust or evaluate the Nova MR seems to be secondary, although cycling as compared with treadmill exercise resulted in a slightly weakened reaction of temperature and pacing rate. Our investigations revealed a good correlation between work load and pacing rate independent of the type of stress testing. The initial DIP (48%) is not a constant phenomenon and showed inter- and intraindividual variations. Impressive psychological influences also exhibited an effect on temperature and pacing rate, sometimes preventing a DIP response. During exercise at lower work loads (under 50 watts, shorter than 3-4 min) the rate response of the Nova MR--without any detected DIP--is often delayed due either to a decrease or to a late and flat increase in temperature. An additional fast-reacting sensor could be advantageous in triggering the initial rate response in such cases.

Aged↗

Differences between atrial single chamber pacing (AAI) and ventricular single chamber pacing (VVI) with respect to prognosis and antiarrhythmic effect in patients with sick sinus syndrome.

Several studies suggest different effects of atrial (AAI) and ventricular single chamber pacing (VVI) for sick sinus syndrome with respect to the suppression of atrial tachycardias and to the prognosis. With this aspect in mind, we studied 222 patients with sick sinus syndrome, 110 of whom had been supplied with AAI systems, and 112 with VVI systems, in the period from January 1978 to December 1986. The mean observation period was 53 +/- 28 months. The cumulative 5-year survival rate was not significantly different in the two groups. After subgroups with comparable underlying diseases had been differentiated, patients with coronary heart disease showed a significantly higher survival rate (P less than 0.05) under AAI pacing, and the same was shown for patients with no underlying heart disease (P less than 0.02). The incidence of chronic atrial fibrillation was 6% in the AAI group and 19% in the VVI group. Patients with preexisting atrial tachyarrhythmias showed the lowest incidence of chronic atrial fibrillation under AAI pacing. Under VVI pacing this incidence was a function of the basic rate of the pacemaker systems. In conclusion, the pacing mode seems to have a prognostic importance in spite of all methodological difficulties. A suppressive effect of AAI pacing on atrial dysrhythmias can also be assumed.

Aged↗

[30 years cardiac pacemaker therapy: a status evaluation].

Antibradycardiac pacemaker therapy has become established as one of the most effective forms of cardiological therapy for the indications AV-block, sick sinus syndrome, bradyarrhythmia, and hypersensitive carotid sinus. About 220,000 systems are implanted per year worldwide, about 32,000 in West Germany. Of the pacing modes, the fixed-rate ventricular single chamber systems (VVI) dominate with a share of almost 90%. Prognostic importance: For AV-block, the improvement of the prognosis by pacemaker therapy is unquestionable, since it increases the cumulative survival rates to 81% and 95% after 1 year and 50% to 65% after 5 years. For sick sinus syndrome, VVI-pacing proves to be a symptomatic measure, no prognostic importance can be proven. It is not conclusively clarified at present whether physiological pacing modes (AAI, DDD) have any such importance. Pacemaker therapy also has no prognostic importance for bradyarrhythmia. Hemodynamic importance: Numerous hemodynamic studies show that fixed-rate VVI-pacing fails to produce a long-term hemodynamic improvement for either an AV-block or a sick sinus syndrome. In sick sinus syndrome hemodynamic improvement can only be achieved by physiological pacing modes (AAI, DVI, DDD), whereby the increase in cardiac output is between 11% to 30%. For AV-block a long-term hemodynamic improvement can only be obtained by atrial triggered pacing modes (VAT, VDD, DDD); this is higher than the values of fixed-rate VVI-pacing by 7-25% at rest, or 10-40% under exercise. Similar results with improvements of the exercise hemodynamics between 22% and 66% are reported for rate-modulated single-chamber pacing (VVIR) for AV-block. Future trends: In the fourth decade of pacemaker therapy, developments point toward the "smart pacemaker", toward rate-modulated systems with combinations of parameters, toward rate-modulated dual-chamber systems and universal antibradycardiac and antitachycardiac systems.

Bradycardia↗

[Cardiodynamic determinants of heart perception].

Subjective perception of one's heartbeat is augmented by psychological factors (stress, fear) as well as by physiological influences (e.g., physical work). It is still unclear on which cardiac or circulatory parameters the "signal" for cardiac perception is based. In this study, the relation between cardiac performance and the ability to perceive one's heartbeat was investigated. Sixteen healthy subjects (8 female, 8 male, aged from 21 to 31 years) participated. Cardiac activity was varied by a combination of passive tilt and physical work on a bicycle ergometer. Subjects had to perform physical work (0, 25, 50, 75, 100 W) on the bicycle at seven different angles (90 degrees, 75 degrees, 60 degrees, 45 degrees, 30 degrees, 15 degrees, 0 degrees). A cardiac perception test was carried out after each load. The following cardiodynamic parameters were measured: stroke volume, contractility, and heart rate. The mean correlation coefficient between cardioceptive performance and cardiodynamic parameters was .62 for stroke volume, .45 for contractility, and .12 for heart rate. Obviously, a remarkable relation exists between the mass and--to a lesser degree--the velocity of ejected blood and cardiac perception. From this we infer, tentatively, that the subjectively perceivable heartbeat stimulus is generated by mechanical events that occur close to the left ventricle.

Adult↗

[A new mechanical sensor for activity controlled and body position dependent frequency adaptive pacemaker stimulation].

In the past, the most important feature in the development of rate-responsive pacemaker systems was ensuring an adequate rate response to physical exercise. But there are other variables that modulate the rate of the healthy heart; examples include postural changes in heart rate in order to prevent orthostatic reactions, and the nightly decrease in intrinsic pacemaker rate. Therefore, we developed a sensor that could distinguish, not only rest and activity, but also discriminate between a supine and an upright position. This sensor is a multicontact tilt switch, which contains a small mercury ball. By measuring the number of openings and closures within the sensor as the ball touches the numerous sensor contacts it is possible to discriminate between different levels of exercise; the contact pins are circled around the base plate. There is an almost linear increase in the number of changes per time with increasing exercise. Besides measuring body activity from the number of contact changes per time, it is also possible to determine the body's posture from the count and positioning of the closed contacts within the casing. Based upon the results of 12 volunteers and nine pacemaker patients, a new algorithm is being prepared which enables the pacemaker to decrease stimulation rate in the supine position, to increase it in the upright position, and to correlate pacing rate with the increase in physical exercise. There is a good correlation between number of contact changes and the intrinsic heart rate (r = 0.87).

Adult↗

The basis for activity controlled rate variable cardiac pacemakers: an analysis of mechanical forces on the human body induced by exercise and environment.

We conducted tests on six healthy volunteers and six pacemaker patients. With the aid of three straight line frequency acceleration pickups attached to the body, the mechanical signals were recorded on the three axes during different activities. Along with standardized exercise on bicycle and treadmill ergometers, we tested the influence of household activities and interference influences. The results were analyzed in terms of the amplitude and frequency content of the signals. For walking activities, we found a signal amplitude increasing in a largely linear fashion with the walking speed, the signal amplitudes being approximately twice as high on the vertical axis as on the other two axes. Exercise on the bicycle ergometer produced mechanical signals of clearly lower amplitude than comparable walking activities. The Fast-Fourier analysis showed amplitude peaks in the low frequency range of 1 to 4 Hz for all forms of physiological exercise, while interference influences showed amplitude peaks mainly in the range above 8 Hz. The use of a straight line-frequency acceleration pickup and a corresponding low pass filter might be a way of reducing the effect of unphysiological interference influences on an activity controlled pacemaker system. A sensor measuring on the horizontal axis appears to be the most favorable compromise for the various types of exercise. However, due to the considerable difference in signal amplitude for different types of exercise of the same intensity, an activity controlled pacemaker system cannot entirely meet metabolic conditions and requirements.

Activities of Daily Living↗

[Heart valve surgery: an analysis of the causes and peri- and postoperative course].

From a total of 1,152 consecutive patients with heart valve replacement (1964-87) 108 patients (9.4%) had to be reoperated. Mechanical valves had to be replaced (n = 89) mainly because of perivalvular leakage followed by prosthetic stenosis and dysfunction. The lowest reoperation rate was found with Björk-Shiley prostheses (3.4%). Bioprostheses (reoperation rate 8.2%) had to be reoperated predominantly as a consequence of dysfunction. Ten years following implantation 30% of bioprostheses had to be replaced. Patients with reoperations demonstrated, in comparison to patients with singular valve replacement, no significant change in early mortality during the last 6 years (6.8% vs 5.4%). Furthermore, both patient groups revealed similar survival rates (10 years; 78% vs 76%) and improvement of life quality. However, non-lethal peri- and postoperative complication rates were higher in reoperated patients compared to patients with first valve replacement.

Adolescent↗

[Principle of the activity-controlled rate-adaptive cardiac pacemaker: analysis of stress and environment-induced mechanical effects on the human body].

Rate-adaptive pacemakers are increasingly becoming part of clinical routine, the most widespread systems being activity-controlled. In order to shed more light on the foundations of mechanical forces which can possibly be utilized for controlling rate-adaptive systems, we conducted tests on six healthy volunteers and six pacemaker patients. With the aid of three orthogonal wide-band linear acceleration pick-ups attached to the body, the mechanical signals were recorded from the three axes during different activities. Along with standardized exercise on bicycle and treadmill ergometers, we tested the influence of household activities and interference influences. The results were analyzed in terms of the amplitude and frequency content of the signals. For walking activities we found a signal amplitude increasing in largely linear fashion with the walking speed, the signal amplitudes being approximately twice as high on the vertical axis as on the other two axes. Exercise on the bicycle ergometer produced mechanical signals of clearly lower amplitude than comparable walking activities. The Fast-Fourier analysis showed amplitude peaks in the low frequency range of 1 to 4 Hz for all forms of physiological exercise, while interference influences showed amplitude peaks mainly in the range above 8 Hz. The use of an acceleration pickup and a corresponding low pass filter might be a way of reducing the effect of nonphysiological interference influences on an activity-controlled pacemaker system. A sensor measuring in the horizontal axis appears to be the most favorable compromise for the various types of exercise. However, due to the considerable difference in signal amplitude for different types of exercise of the same intensity, an activity-controlled pacemaker system cannot entirely meet metabolic conditions and requirements.

Adult↗

A new rate-modulated pacemaker system optimized by combination of two sensors.

A new rate-modulated pacemaker system optimized by combination of two sensors is described. The parameter body activity and central venous blood temperature control the pacemaker rate. The specific characteristic of each parameter determines its role within the algorithm. While the motion sensor yields a fast reaction following the onset or a change of stress intensity, central venous blood temperature corresponds better to body metabolism. An indication of increased exercise from the motion sensor results in an accordingly rapid increase in the pacing rate. Unless this increased exercise is confirmed by an increase in central venous blood temperature within 2 or 3 minutes, the new motion level will be assumed to be the new baseline motion value and the pace rate will return to a basic pacing rate. Prolonged inappropriate responses are therefore avoided. Longer lasting exercise, fever and nonphysiological signals are recognized and handled safely. Exercise tests with five volunteers under various conditions showed pacing rate behavior that was close to normal.

Adult↗