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Biomedical subjects

R Mrowka

Publications and source records attributed to R Mrowka.

At least 19 recordsLinked to original sources

Time of measurement influences the variability of tidal breathing parameters in healthy and sick infants.

The aim of this study was to investigate the influence of the time, when measuring tidal breathing parameters 1 min (epoch 1) and 5 min (epoch 2) after application of the facemask in healthy infants and infants with bronchopulmonary dysplasia (BPD), using the dead space free flow-through technique. In both patient groups, there were no statistically significant differences between epoch 1 and 2, in most of the tidal breathing parameters, except an increased VE and increased correlation dimension of the respiratory signal in the BPD infants in epoch 1. However, in nearly all parameters the coefficient of variation (CV) was significantly higher in epoch 1 compared with epoch 2, and in some infants, we found very high CVs (>50%) in epoch 1, which disappeared in epoch 2. The study shows that after having applied the facemask, a sufficient amount of adaptation time is necessary in order to reduce the within-subject variability and improve the reproducibility and interpretation of tidal breathing measurements in infants.

Adaptation, Physiological↗

A Java applet for visualizing protein-protein interaction.

UNLABELLED: A web applet for browsing protein-protein interactions was implemented. It enables the display of interaction relationships, based upon neighboring distance and biological function. AVAILABILITY: The Java applet is available at http://www.charite.de/bioinformatics

Algorithms↗

Is there a bias in proteome research?

Advances in technology have enabled us to take a fresh look at data acquired by traditional single experiments and to compare them with genomewide data. The differences can be tremendous, as we show here, in the field of proteomics. We have compared data sets of protein-protein interactions in Saccharomyces cerevisiae that were detected by an identical underlying technical method, the yeast two-hybrid system. We found that the individually identified protein-protein interactions are considerably different from those identified by two genomewide scans. Interacting proteins in the pooled database from single publications are much more closely related to each other with respect to transcription profiles when compared to genomewide data. This difference may have been introduced by two factors: by a selection process in individual publications and by false positives in the whole-genome scans. If we assume that the differences are a result of false positives in the whole-genome data, the scans would contain 47%, 44%, and 91% of false positives for the UETZ, ITO-core, and ITO-full data, respectively. If, however, the true fraction of false positives is considerably lower than estimated here, the data from hypothesis-driven experiments must have been subjected to a serious selection process.

False Positive Reactions↗

[Heart rate variability--physiology, methods of registration and application in pediatric sleep laboratory].

Heart rate variability (HRV) has become the focus of interest of a multitude of investigations being a parameter that can easily be recorded. Accepted clinical indications in adults include evaluation of diabetic neuropathy and prediction of prognosis after myocardial infarction in adults. In children, HRV is regularly being registered in the pediatric sleep laboratory in sleep related breathing disorders, after apparent life threatening events, or in infants with assumed increased risk for sudden infant death syndrome. However, uniform interpretation criteria have not been established in these situations, at least partially due to insufficient understanding of physiology and pathophysiology of HRV in this age group. In this overview, current knowledge on HRV in infants and children is summarized and its clinical relevance discussed. In addition, technical requirements and methods of analysis which have a major impact on calculated parameters are being presented.

Austria↗

Blood pressure control in eNOS knock-out mice: comparison with other species under NO blockade.

Changes in arterial blood pressure (ABP) lead to changes in vascular shear stress. This mechanical stimulus increases cytosolic Ca2+ in endothelial cells, which in turn activates the endothelial isoform of the nitric oxide synthase. The subsequently formed NO reaches the adjacent vascular smooth muscle cells, where it reduces vascular resistance in order to maintain ABP at its initial level. Thus, NO may play an important role as a physiological blood pressure buffer. Previous data on the importance of eNOS for blood pressure control are reviewed with special emphasis on the fact that endogenous nitric oxide can buffer blood pressure variability (BPV) in dogs, rats and mice. In previous studies where all isoforms of the nitric oxide synthase were blocked pharmacologically, increases in blood pressure and variability were observed. Thus, we set out to clarify which isoform of the nitric oxide synthase is responsible for this BPV controlling effect. Hence, blood pressure control was studied in knock-out mice lacking specifically the gene for endothelial nitric oxide synthase with their respective wild-type controls. One day after surgery, under resting conditions, blood pressure was increased by 47 mmHg (P < 0.05), heart rate was lower (-77 beats min-1, P < 0.05), and BPV doubled (P < 0.05). Based on these results, we conclude that chronic blood pressure levels are influenced by eNOS and that there is a blood pressure buffering effect of endogenous nitric oxide which is mediated by the endothelial isoform of the nitric oxide synthase.

Animals↗

Low-frequency respiratory rhythms in infants during the first six months of life.

The aim of the study was to investigate characteristics of low-frequency components in respiration. Sixteen healthy term infants were examined from the first day up to the 6th month of life. The respirogram, instantaneous respiratory frequency and respiratory amplitude of undisturbed segments of quiet sleep phases and periodic breathing (PB) were analysed via fast Fourier transformation. The peak frequency (PF) in the low-frequency range (0.04-0.2 Hz) was determined. PF for PB ranged from 0.056 to 0.1 Hz. Further, low-frequency rhythms (LFR) of the respirogram, which were stable during the recordings as well as during development, were found ranging from 0.045 to 0.067 Hz. The LFR of the respirogram is correlated with rhythmic changes in the relationship between inspiratory and expiratory amplitudes. The frequency of the LFR was significantly lower than that of the PB. The data indicate that LFR and PB are low-frequency respiratory rhythms which are separately controlled and perform independently.

Child Development↗

Blunted arterial baroreflex causes "pathological" heart rate turbulence.

Sudden cardiac death is the leading cause of cardiovascular mortality in developed countries. Recently, two post-myocardial-infarction risk predictors were introduced that are superior to all other presently available indicators: turbulence onset (TO) and turbulence slope (TS). These parameters characterize the behavior of instantaneous heart rate after a ventricular premature beat, i.e., they describe the reestablishing of heart rate control after an acute perturbation. We propose that the dysfunction of an important cardiovascular control mechanism, the arterial baroreflex, is the mechanism behind these new potent markers. The hypothesis is tested by means of a physiological model involving the excitation generation in the heart, the hemodynamic situation in the aorta, and baroreceptor feedback mechanisms. The data show that a blunted baroreceptor response of the heart resembles patterns of heart rate turbulence that correspond to pathological values of TO and TS. The results of the model suggest that the recently established risk parameters TO and TS characterize baroreflex function, a known risk stratifier in patients.

Adrenergic beta-Antagonists↗

Rhythms and complexity of respiration during sleep in pre-term infants.

The aim of this study is to test rhythmic and complex properties of respiratory control in former ventilated, pre-term infants during quiet and active sleep. The children had a higher risk for sudden infant death due to bronchopulmonary dysplasia (BPD). Twelve infants suffering from BPD and 12 control infants, matched regarding their post-conceptional age, were examined polygraphically during quiet (QS) and active sleep (AS). The respiratory rate (RR), the ratio (LF/HF) between the low-frequency power (LF) and the high-frequency power (HF) of the spectra of the thoracic respiratory effort, and the frequency of the dominant peak within LF (LFF) and HF (HFF) were computed. The correlation dimension (D2) of the respiratory signal was calculated to determine the complexity of the respiratory control. The transcutaneous pO2 (tcpO2) and pCO2 and the oxygen saturation (sO2) were analysed. Infants with BPD had significantly higher RR and HFF during QS (median: BPD 48 breaths min-1; control 32 breaths min-1). tcpO2 and sO2 were significantly lower in the BPD group. No differences were found in LF/HF, LFF or D2 between groups, either in QS or in AS. D2 ranged between 1.8 and 3.8, showing significantly higher values during AS. LFF was found to be lower during active sleep (AS 0.04-0.05 Hz; QS about 0.06 Hz). We propose that in infants with BPD the lower lung compliance and the higher resistance, and possibly also the hypoxaemia, contribute to the acceleration of breathing. The behaviour of RR, spectral parameters and D2 indicates a specific, functional setting rather than a regulatory impairment in infants with BPD.

Bronchopulmonary Dysplasia↗

Enhanced blood pressure variability in eNOS knockout mice.

It has been shown previously that endogenous nitric oxide can buffer arterial blood pressure variability in dogs and rats. In these former studies, all isoforms of the nitric oxide synthase were blocked pharmacologically and an increased blood pressure variability was observed. Thus the question as to which isoform of the nitric oxide synthase is responsible for the blood pressure buffering effect of endogenous nitric oxide remains unraveled. In the present study, we therefore compared blood pressure variability in knockout mice that lack specifically the gene for endothelial nitric oxide synthase with their respective wild-type controls. One day after carotid artery cannulation, blood pressure was recorded in these conscious mice. During resting conditions, blood pressure variability was markedly enhanced in knockout mice compared with wild-type mice (10.5+/-1.5 mm Hg2 vs 6.0+/-0.8 mm Hg2, P<0.05). Power spectral analysis revealed that this increase in blood pressure variability is manifested at low frequencies that range from 0.05 to 0.40 s-1 (Hz) (5.1+/-1.0 mm Hg2 vs 2.5+/-0.5 mm Hg2, P<0.05). On the basis of these results, we conclude that the blood pressure buffering effect of endogenous nitric oxide is mediated by the endothelial isoform of the nitric oxide synthase. In addition, endothelial nitric oxide is most effective in buffering blood pressure oscillations at frequencies that range from 0.05 to 0.40 s-1 (Hz) in conscious mice.

Animals↗

Genomic difference analysis by two-dimensional DNA fingerprinting reveals typical changes in human low-grade gliomas.

Cytogenetic and molecular analyses such as allelotyping studies have revealed several genetic changes typical for human glial neoplasms. However, most studies to date have involved malignant gliomas and thus are likely to reflect late events of tumor progression. To elucidate the initial events of glial tumor growth, we performed a genome-wide search for genetic alterations in the DNA of 43 low-grade gliomas as compared to the constitutional DNA of the patients' peripheral blood leucocytes using the two-dimensional (2D) DNA fingerprint approach. Reliable results were obtained for 28 blood/tumor sample pairs (13 astrocytomas, 9 pilocytic astrocytomas, 1 oligodendroglioma, 3 oligoastrocytomas, and 2 ependymomas). DNA was digested with the restriction enzyme HaeIII and the resulting fragments were separated on 2D gels according to size and sequence in the first and second dimensions, respectively. Patterns of hundreds of spots were generated by hybridization with four different mini- and microsatellite core probes. A total of 655 to 1,122 spots could be visualized per sample. Comparison of blood and tumor spot patterns revealed two to 11 reproducible changes per patient. Most of the differences were spot losses (77.1%), while the others appeared to be gains or amplifications. Exactly the same changes were found in tumor recurrences which lacked histological signs of progression. When comparing different patients, many of the affected spots tended to cluster in particular areas of the gel as revealed by computer-aided comparison of all spot patterns. Eleven different spot clusters were identified which may correspond to several major deletion targets. This study provides the basis for the future molecular cloning of the candidate tumor suppressor genes affected by the common spot losses and will allow new insights into the genetic mechanisms of glial tumorigenesis.

Adolescent↗

A novel standardization method for two-dimensional DNA fingerprints.

Two-dimensional (2-D) DNA fingerprinting is a technique that allows for parallel genome analysis through the simultaneous detection of up to 500 mini- or microsatellite loci on a 2-D gel. Separation is performed according to size and melting temperature in the gel. In the application of this technique in genome analysis, a standardized method for the identification of individual spots is required. However, due to the polymorphic nature of up to 80% of the spots, existing standardization methods that have been primarily developed for 2-D protein patterns are not suitable for this task. We developed a robust method that standardizes 2-D DNA fingerprint spots on the basis of melting temperature - or denaturing gradient position - and fragment size. An external marker was used as a basis for standardization. A normalization surface was calculated over the gel dimensions by adapting an established numerical iteration technique previously used in physics termed "relaxation method". The relaxation method works robustly with the irregularly spaced marker spots. The evaluation of the method for a spot of preknown position derived from the TP53 gene revealed a median observed error below 1% for fragment length and denaturing gradient position. The search for candidate minisatellite loci in genomic difference analysis depends on the reliable identification of alleles of this locus in different individuals. We proved experimentally that alleles of a single minisatellite locus cloned from a 2-D gel cluster on an isothermal line can be reliably identified using the presented standardization method. In conclusion, a standardization tool for a broader application of 2-D DNA fingerprinting in both tumor analysis and possibly parallel mutation screening is now available.

Alleles↗

Linear and nonlinear properties of heart rate control in infants at risk.

The aim of this study was to test whether the heart rate (HR) control in infants at risk differs in comparison with healthy infants. Twelve former preterm infants suffering from bronchopulmonary dysplasia and 18 control infants, matched for their postconceptional age, were examined polygraphically during quiet and active sleep. HR, low-frequency (LF) power, high-frequency (HF) power, total power, and the ratio of LF to HF power (LF/HF) of the instantaneous HR spectra were calculated for linear analysis. The largest Lyapunov exponent (LLE) of the R-R interval time series was calculated to determine a nonlinear property of HR. Infants at risk had significantly lower LF power (median: 0.51 x 10(-3) vs. 1.16 x 10(-3) Hz2) and lower LF/HF (median: 1.05 vs. 1.94) during quiet sleep. LLE was positive, revealing low-dimensional chaotic behavior of HR control, and did not differ between both groups (median: quiet sleep, 0.05 bit/s vs. 0.06 bit/s; active sleep, 0.16 bit/s vs. 0.15 bit/s). Sleep state-related changes in spectral parameters and LLE were similar in both groups. In infants at risk, the lower LF/HF during quiet sleep can be interpreted in terms of changes in the rhythmic components of the sympathovagal balance of the autonomic system, which is an expression of linear properties of HR control. Conversely, the lack of differences in LLE between both groups indicates similar nonlinear properties of the control system.

Bronchopulmonary Dysplasia↗

Interaction of heart-rate fluctuations and respiration in 12 to 14-year-old children during sleeping and waking.

Our study was designed to investigate and quantitatively characterise the interaction of breathing and instantaneous heart rate. Comparisons were made during consciousness at rest, and during non-REM sleep. 31 12-14-year-old healthy children were subjected to a 24-h polygraphic electrocardiogram, respirogram, electrooculogram and actogram measurements. The data were analysed by means of power spectral analysis and coherence spectra. The peak frequency of high-frequency heart rate fluctuations was always clearly related to the breathing frequency, i.e., respiratory sinus arrhythmia is present in both states. Moving squared coherence analysis demonstrates the stability of the cardiorespiratory coupling to remain constant during wakefulness or non-REM sleep. However, coherence increases from waking state to non-REM sleep. The lower coherence during waking state may be explained by greater additional central and peripheral influences on the cardiorespiratory coupling or by increased non-linear properties of the transfer system due to operating point shifting.

Adolescent↗

Development of heart rate power spectra reveals neonatal peculiarities of cardiorespiratory control.

Postnatal adaptation should be associated with changes in cardiac rhythmic behavior. To examine the development of heart rate variability, instantaneous heart rate (IHR) and the corresponding breathing signals of 16 healthy infants were analyzed. This was pursued by use of fast Fourier transformation beginning with the 1st day until the 6th mo of life. Power in the low-frequency range (LF, 0.02-0.2 Hz) and high-frequency range (HF, 0.2-1.5 Hz), total power (TP), the quotient LF/HF, and the frequency of the peak in LF and HF (LFF and HFF, respectively) were derived from the IHR spectrum. The peak frequency in HF (RF) was detected in the respiratory spectrum. Power and frequency of IHR rhythms undergo a marked development. TP, LF, and HF are lowest from the end of the 1st mo until the 2nd mo. LF predominates over HF, with LF/HF reaching its peak during 1- to 2-mo period. HF, recording respiratory related rhythms is negatively correlated with the breathing rate (BR). HFF and RF both show an increasing tendency during the 1st mo followed by a decrease down to the 6th mo. However, HFF is lower than RF if BR is high, mainly during the first 2 mo. The distinct changes in BR and its important influence on the IHR spectrum underscore the importance of monitoring respiration as a further measure in the diagnosis of infants. LFF is on average between 0.075 and 0.095 Hz, exhibiting an irregular course with minimum at the 10th, 21st-28th, and 90th day being apparent. The developmental pattern of LFF may by interpreted in terms of the maturation of the nervous system involved in the generation of circulatory rhythms.

Aging↗

Linear and non-linear properties of heart rate in postnatal maturation.

OBJECTIVE: An investigation was made of how postnatal maturation of cardiac control can be described by linear and non-linear methods of time series analysis. METHODS: Sixteen healthy and term newborns were studied during their first 6 months of life. Power spectrum analysis including total power (TP), low frequency power (LF), high frequency power (HF) and LF/HF ratio were performed on the instantaneous heart rate (IHR) time series and mean heart rate (HR) was derived. The largest Lyapunov exponent (LLE) was calculated using a modified Wolf algorithm and checked by means of the surrogate-data test. RESULTS: There is an age dependency for the parameters LLE, HR, TP, HF, LF, LF/HF for active and LLE, HR, TP, HF, LF/HF for quiet sleep. HR is characterised by a steep increase between the 5th and 7th day. HF demonstrates a distinct development with high values around the first week and 90-180th day and low values around the 10-60th day. TP, LF and LF/HF show significantly higher values in active sleep in comparison to quiet sleep. For all ages and sleep stages, positive LLE were found, indicating sensitivity to initial conditions, a hall-mark of chaos. For the period between the 7 and 90th days of life, the LLE for active sleep took on larger values compared with the LLE of quiet sleep. CONCLUSIONS: This study shows that by linear as well as non-linear analysis one can reveal the complexity of the IHR development in humans and may gain insight into the system controlling the heart during the period considered. The positive LLE indicate that there is a non-linear component in the heart rate control. There is no "straight line" development for the parameters analysed within the first 6 months. This may result from manifold influences on the autonomic system, due to structural and functional maturation in this period of life.

Heart↗

Developmental aspects of the interaction between the controls of heart rate and respiratory rhythm--linear and nonlinear components of diverse activity states in childhood.

Heart beat and respiration are rhythmical phenomena with separate intrinsic frequencies which necessarily have to be effectively tuned by a network of interactive processes. Their linear and nonlinear components may ripen in different ways during childhood thus leading to unstable transitions or risk of dangerous events. This study investigates the development from newborns to children mainly between sleep and wakefulness. 42 healthy untrained children underwent a 24 hours monitoring of ECG, respiration, actogram, and EOG. Linear parameters such as respiratory rate, heart period duration (HPD), total and high frequency spectral power (TP, HFP), low/high frequency power quotient (LF/HF) and coherence were calculated in wake state, REM- and non-REM sleep. The largest Lyapunov exponent (LLE) was evaluated as nonlinear parameter and proved by the surrogate data method. The childrendata were compared to newborndata at days 1 and 180. In wake children, all values except TP differ from that in non-REM and except LLE from that in REM. All linear parameters differ between REM and non-REM. Similar differences exist for quiet to active sleep in newborns at day 1. At day 180 only LF/HF and coherence differ. Development from day 1 to 180 exists in quiet sleep for LF/HF and coherence, in active sleep additionally for LLE and from day 180 to children except for LF/HF and coherence. The results show clear differences in the linear parameters of the activity states. Wakefulness, REM- and non-REM sleep, therefore, follow varied rhythmical controls. The behaviour of LF/HF points to changes in the intensity of vagal participation and that of the coherence accentuates the differing tightness of the coupling. The clearly existing nonlinear components have a separate value only in wakefulness hinting at larger complexity at that state. The development within the first 180 days indicates an increase of vagal participation and tightness of coupling in quiet sleep, in active sleep also an increase in complexity. From that day no further development in vagal and coupling effects has been detected among children. The complexity remains unchanged, only the power parameters expressing heart rate variability increase. (Fig. 3, Tab. 3, Ref. 13.)

Adolescent↗

[Nonlinear dynamics in regulation of heart rate in healthy infants].

The aim of this study was to investigate qualitatively and quantitatively non-linear and linear characteristics of heart rate identifying their connection to sleep states during the first 6 months of life. 16 newborns were examined polygraphically in a longitudinal study (first day, first and sixth month). After R-peak detection of a limb lead ECG and R-R interval calculation, time series of the instantaneous heart rate (IHR) were constructed. They were analyzed qualitatively with regard to the structure of the Poincaré maps and the occurrence of bifurcations as well as quantitatively by calculating the correlation dimension (D2) and the Lyapunov exponent (LLE). In some cases, bifurcations in the IHR time series occurred. The Poincaré maps showed mainly clear structures in the shape of limited point clusters. D2 was in the range of 1.5 to 2.5 and was larger in quiet than in active sleep. LLE was always positive, although higher values in active sleep than in quiet sleep were exhibited in the first month of life only. D2 and LLE values during active sleep were age-dependent. The results of the study indicate a non-linear component in the heart rate control of healthy newborns. The change in D2 and LLE in connection with postnatal age and sleep states expresses a modulation of these system components during the postnatal maturation and during vegetative sleep organisation.

Child Development↗