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Biomedical subjects

E Schubert

Publications and source records attributed to E Schubert.

At least 19 recordsLinked to original sources
PubMed2001

NMR characterization of a novel bile acid sequestrant, DMP 504.

DMP 504, a potential bile acid sequestrant for the treatment of hypercholesterolemia, is a highly insoluble, cross-linked polymer which does not lend itself to ordinary means of characterization used for drug substances in the pharmaceutical industry. Therefore, alternative characterization techniques have been sought. As part of an effort into extensive characterization of DMP 504 drug substance, nuclear magnetic resonance (NMR) was employed to provide insight into details of the DMP 504 polymer structure. The primary motivation for determining the structure of the polymer chain is to relate the DMP 504 structure to its performance properties as a bile acid sequestrant. Characterization of the polymer chain and understanding of the structural basis of its properties is essential in optimizing and controlling the manufacture of reproducible drug substance. NMR has proven a versatile tool for the description of polymer structure and dynamics because of the wide range of nuclear interactions affecting the NMR signal. This allows the design of experiments to elicit information about specific polymer interactions or properties. The methods of sample preparation utilized to obtain NMR spectra of the insoluble polymer, as well as a discussion and comparison of results for the characterization of DMP 504 obtained using several different NMR techniques will be presented.

Bile Acids and Salts↗
PubMed2000

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↗
PubMed1998

Detection and characterization of two cytotoxins produced by Campylobacter jejuni strains.

Campylobacter jejuni strains are able to produce at least two different cytotoxins called "cytolethal distending toxin" (CLDT) and "cytolethal rounding toxin" (CLRT). In this study, we investigated the corresponding changes in CHO-K1 cells using the cell counter and analyzer system CASY 1. Determination of the cell volume after toxin treatment of the cells is a useful criterion for differentiation between the cytotoxic activities produced by Campylobacter strains. Incubation of the cells with crude CLDT resulted in a decrease in the cell count combined with a dramatic increase of the mean cell volume in comparison to the control culture. A decrease in the cell count was also seen as a response to CLRT preparations, while this toxin had no effect on the mean cell volume determined. It was shown that only CLDT caused histone-associated DNA fragments in the cytoplasm of CHO-K1 cells indicating an apoptotic pathway of cell death. In addition, the polymerase chain reaction (PCR) was employed to screen Campylobacter strains for the presence of the cdtB gene sequence, which was detectable in all strains investigated.

Animals↗
PubMed1998

Haplotype and phenotype analysis of nine recurrent BRCA2 mutations in 111 families: results of an international study.

Several BRCA2 mutations are found to occur in geographically diverse breast and ovarian cancer families. To investigate both mutation origin and mutation-specific phenotypes due to BRCA2, we constructed a haplotype of 10 polymorphic short tandem-repeat (STR) markers flanking the BRCA2 locus, in a set of 111 breast or breast/ovarian cancer families selected for having one of nine recurrent BRCA2 mutations. Six of the individual mutations are estimated to have arisen 400-2,000 years ago. In particular, the 6174delT mutation, found in approximately 1% of individuals of Ashkenazi Jewish ancestry, was estimated to have arisen 29 generations ago (1-LOD support interval 22-38). This is substantially more recent than the estimated age of the BRCA1 185delAG mutation (46 generations), derived from our analogous study of BRCA1 mutations. In general, there was no evidence of multiple origins of identical BRCA2 mutations. Our study data were consistent with the previous report of a higher incidence of ovarian cancer in families with mutations in a 3.3-kb region of exon 11 (the ovarian cancer cluster region [OCCR]) (P=.10); but that higher incidence was not statistically significant. There was significant evidence that age at diagnosis of breast cancer varied by mutation (P<.001), although only 8% of the variance in age at diagnosis could be explained by the specific mutation, and there was no evidence of family-specific effects. When the age at diagnosis of the breast cancer cases was examined by OCCR, cases associated with mutations in the OCCR had a significantly older mean age at diagnosis than was seen in those outside this region (48 years vs. 42 years; P=.0005).

Adult↗
PubMed1998

Weight of adrenal glands may be increased in persons who commit suicide.

In a previous study, increased weight of the adrenal glands was found in a small group of persons who committed violent suicides. This finding was confirmed in our study, which comprised a group of 42 suicide cases and 37 control cases. Further analysis with special consideration toward a "relative adrenal weight" (weight/body surface) revealed that a relative combined adrenal weight >6 g/m2 may be a morphologic sign of a depressive disorder prior to death if no other disease with a known effect on the adrenals is present. These results are consistent with clinical computed tomographic findings of enlarged adrenals in depressed patients. In all suicide cases the police records were reviewed and a postmortem psychiatric diagnosis conducted to investigate whether a correlation between adrenal weight and the "severity" of depression or type of psychiatric disorder exists. In thirteen cases, psychiatric treatment prior to death was known, and a postmortem severity score of depressive disease was formed. No influence of this score or the postmortem diagnosis on the adrenal weight, however, could be detected. Also, the increase in weight of adrenal glands could not be explained by a suspected or proven preceding drug therapy or use. The effect on the pituitary-adrenal-axis by depressive disorders and changes in serotonin metabolism have been investigated repeatedly; mainly reported are increased levels of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) in the depressive interval, which may lead to a growth of the adrenal glands.

Adrenal Glands↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

The theory of and experimentation into respiratory gas exchange--Carl Ludwig and his school.

Investigations of respiratory functions progressed considerably in the middle of the 19th century. Motive forces for this were the improvement of basic medical sciences due to the progress in science politics, the evolution of exact measuring methods owing to the improvement of natural sciences and the origin of the ideology of antivitalism and organic physics, revealed by the striving of their leading scientists including Carl Ludwig. Formerly, exchange of O2 and CO2 was related merely to the lungs without exact knowledge of data or mechanisms. Ludwig and his pupils improved the analytical methods of G. Magnus and L. Meyer and applied various experimental conditions thus obtaining data allowing the interpretation of the respiratory gas exchange in the organism according to physical laws. It was found that respiratory gases are transported in a chemically bound state; that the binding mechanisms for O2 and CO2 interact; that body tissues extract O2 and release CO2 depending on metabolism, and that partial pressures justify purely physical theories of the gas exchange. These results enabled the investigation of the transporting substance, haemoglobin, by F. Hoppe-Seyler and of the binding and dissociation dynamics by C. Bohr, J.S. Haldane and A. and M. Krogh. Thus Ludwig bridged the gap from qualitative gas analysis to quantitative research into the kinetics of gas binding.

Animals↗
PubMed1996

[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↗
PubMed1996

[Sleep structure in relation to respiration and heart rate in children in puberty].

The different expression of respiratory sinus arrhythmia in REM- versus nonREM-sleep indicates a dependence of cardiorespiratory interaction on patterns of sleep. Investigations of the intensity of respiratory entrainment on heart rhythmicity during various stages of sleep will provide an insight into the coupling of cardiorespiratory interaction and sleep patterns. 42 healthy children (12 to 15 years old) were polygraphically investigated over 24 h. An ECG, EOG, and actogram were performed, respiratory movements were observed, and the skin temperature was taken. The power spectra of the instantaneous heart rate and the respirograms were calculated. The analysis of coherence was carried out to determine how pronounced the cardiorespiratory interaction is. REM-sleep, nonREM-phases, and wakefulness were compared. The spectral parameters of instantaneous heart rate show differences between both stages of sleep and the waking state. Due to a dependence of spectral power on breathing patterns, drawing quantitative conclusions is not possible. The analysis of coherence provides more information about sleep patterns within the cardiorespiratory interaction. It is very pronounced during non-REM-sleep (0.80 +/- 0.07; mean +/- standard deviation). Heart rhythmicity proceeds independent of breathing during REM-sleep (0.52 +/- 0.11). The coupling is weaker than during wakefulness (0.64 +/- 0.09).

Adolescent↗
PubMed1995

[Circadian rhythms in the spectrum of heart rate variability].

Heart rate shows a circadian rhythm. This has not yet been sufficiently investigated for its variability till now, which challenges the analysis of rhythms of the variability and their validity in long time records. For this purpose, time series of heart period duration (HPD) and sinus arrhythmia (SA) were measured in 30 children in a boarding-school (14 male, 16 female, 12 to 14 years of age) from the ECG for 5 min/h during 24 h. Fast Fourier transform provided the spectra and the power density. HPD, SA, power maxima and their frequencies were analyzed for circadian rhythms according to Halberg. Times of meals and sleep were uniform. Power and frequencies of the spectra showed individual patterns, stable throughout the day in 2 diverse groups. SA, high- (HF) and middle frequent (MF) spectral parts show circadian oscillations in frequency or power with acrophases during day or night, often in contrast to HF and MF. This proves the existence of circadian rhythms of heart rate variability for SA, HF and MF. In some cases, the individual 24-h patterns are superimposed by effects of external zeitgeber, e.g. meals.

Adolescent↗
PubMed1995

[Correlation between respiration and heart rate in 12- to 14-year-old children during sleep and wakefulness].

The coupling of respiratory and cardiac rhythm is determined by interactions of oscillating brain stem centers and external physical and psychical influences. Not well known are effects of sleep and wakefulness which will be investigated over the day. From the ECG and respirogram of 42 healthy children (11 female, 31 male, 12 to 14 years) during 24 h the time series of instantaneous heart rate (HR) and respiratory rhythm and from this by FFT the density spectra of power, the maximal power and related frequency in the respiratory range were ascertained. Differences between nonREM sleep and wakefulness and the strength of coupling were determined by coherence analysis. In all probands the maximal power of HR and of the coherence were higher during nonREM sleep than in wakefulness. Both values were stable during each state. The maximum related frequencies of HR and respiration shifted parallel between sleep and wakefulness. The results mean augmentation in nonREM sleep following to improved transfer of respiratory activity to the control of HR. The increased coherence hints at a stronger linear coupling which is stable during each state. The changes of cardiorespiratory coupling may be effected by stronger non-linear parts in the interactions during wakefulness.

Adolescent↗
PubMed1995

[Development of heart rate in newborn infants during quiet sleep].

The small number of investigations of the development of heart rhythm during the first half year of life provide only rough ideas regarding the maturation of heart rate control. In the present study, in 10 newborns, ECG and respiratory effort were recorded in 13 sessions from birth up to the sixth month. The total power (TP), power in the low (LF) and high frequency range (HF), and the ratio LF/HF were used from the heart rate power spectra. All parameters reveal no linear developmental patterns: TP, LF, and HF increase during the first days to a maximum, then decrease subsequently and remain low until the second month. TP and HF increase between the second and sixth month. LF/HF increases up to the second month followed by a decrease down to the sixth month. The developmental courses of TP, HF and LF/HF correlate with the course of breathing rate (BR), whereby high BR is associated with low HF and TP. The results hint at a maturated cardiorespiratory system.

Child Development↗