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Biomedical subjects

P Novak

Publications and source records attributed to P Novak.

At least 55 records · Page 3Linked to original sources
PubMed1995

Slow cardiovascular rhythms in tilt and syncope.

The cardiovascular oscillations during orthostasis were analyzed by time-frequency mapping in 23 patients with history of vasodepressor (VD) syncope and in 10 control subjects. Syncope was induced by head-up tilt (80 degrees, 25 min) alone in 11 patients (VD-1). Twelve patients remained asymptomatic (VD-2) during this tilt, but presented VD syncope or presyncope during tilt with an isoproterenol infusion. Data from the first tilt without isoproterenol infusion are presented here. Amplitude of sympathetically-mediated nonrespiratory fluctuations [0.01 Hz-respiratory frequency (Rf)] in blood pressure was greater at the beginning of the tilt in both (VD-1 and VD-2) groups compared to controls. Nonrespiratory oscillations were present throughout the tilt and their amplitude increased toward its end (p < 0.001) in VD-2 and control groups. In contrast, in the VD-1 group, the amplitude of 0.01-0.05 Hz rhythm in blood pressure diminished shortly after the beginning of tilt and continued to decline toward the syncope. Nonrespiratory fluctuations in R-R intervals were greatest in VD-1 group. The slow blood pressure rhythms reflect an integrity of feedback loops, and their disappearance is an early sign of an impending syncope.

Adult↗
PubMed1994

Time-frequency analysis of slow cortical activity and cardiovascular fluctuations in a case of Alzheimer's disease.

The dynamics and relationship of slow cortical activity (amplitude modulation of electroencephalograph at 0.02-0.05 Hz) and cardiovascular fluctuations (0.01-0.05 Hz range) was studied by time-frequency mapping (modified Wigner distribution) in a patient with Alzheimer's disease. The amplitude modulating at rest basal alpha and theta activity (lead Oz) was exaggerated compared with control subjects. Fluctuations at respiratory and nonrespiratory (0.01-0.05 Hz) frequencies in R-R intervals and blood pressure were present and within normal range. Spontaneous hypotension (by 20 to 80 mmHg lasting 15-20 s) accompanied by cardioacceleration occurred repeatedly in the supine position and during hyperventilation. Slow cortical activity and nonrespiratory fluctuations (0.01-0.05 Hz) in blood pressure increased concurrently with hypotensions. No signs of peripheral autonomic dysfunction or malfunction of baroreceptors were observed and the vasomotor instability appeared to be of central origin. The results suggested that slow cortical activity was functionally related to the central autonomic nervous system and reflected cortico-thalamo-brainstem interaction.

Alpha Rhythm↗
PubMed1994

Accuracy of beat-to-beat noninvasive measurement of finger arterial pressure using the Finapres: a spectral analysis approach.

OBJECTIVE: Our objective was to test the accuracy of noninvasive recordings of finger arterial pressure (FAP) using the Ohmeda Finapres (Ohmeda Monitoring Systems, Englewood, CO). METHODS: Twenty patients, aged 20 to 78 years, requiring admission to the intensive care unit and placement of intraarterial catheters participated in the study. Systolic and diastolic pressures were derived from 1-hr recordings of beat-to-beat FAP and from ipsilaterally recorded intraarterial pressure (IAP) signals. In all 20 cases, we analyzed beat-to-beat discrepancies between the actual magnitude of FAP and IAP, as well as the distribution of the consecutive differences within each of the two signals. In 10 cases, spectral analysis of the frequency content of both signals was performed. RESULTS: The average systolic FAP (128.1 +/- 22.4 mm Hg) did not differ from IAP (127.1 +/- 19.7 mm Hg), whereas diastolic FAP (78.1 +/- 11.9 mm Hg) was greater (71.5 +/- 10.3 mm Hg) (p < 0.001). No differences in the linear trends of FAP and IAP were observed. Overall, systolic FAP and IAP were discrepant by 0.84 +/- 13.3 mm Hg (-21.82 to 25.8 mm Hg); diastolic FAP and IAP were discrepant by 6.67 +/- 5.23 mm Hg (2.68 to 13.05 mm Hg). Despite discrepancies in the magnitude of the two signals, the contour of IAP approximated that of FAP. Spectral analysis demonstrated good reproducibility and coherence between diastolic IAP and FAP fluctuations in both low-frequency (0.01 to 0.15 Hz) and high-frequency (0.15 to 0.33 Hz) bands. The low-frequency fluctuations in FAP systolic pressure were significantly amplified (p < 0.001) (gain 1.75), whereas the high-frequency fluctuations were not. CONCLUSIONS: Over the course of 1 hr, FAP followed the contour and frequency content of IAP.

Adult↗
PubMed1994

Time-frequency mapping of the QRS complex in normal subjects and in postmyocardial infarction patients.

The effect of myocardial infarction upon the frequency content of the QRS complex was analyzed. Three bipolar signal-averaged surface electrograms, recorded during the early (10-15 days) and late (6 months) chronic phases of myocardial infarction, were analyzed in 61 patients and 11 healthy subjects. All patients were free of ventricular arrhythmia during 6 months of follow-up examinations. Time-frequency analysis of the QRS complex was based on the modified Wigner distribution, which is well suited to examine nonstationary character of data. Standard time-domain analysis for the presence of late potentials was used for comparison. High-frequency (> or = 90 Hz) components, separable from the dominant low-frequency components (< 90 Hz), were found in all groups. They were present throughout the QRS complex and were peaking in its middle portion. The high-frequency components were found significantly higher in postinfarction patients in both early (P < .007) and late chronic stage myocardial infarction (P < .05) compared to healthy subjects. Patients who tested positive for late potentials (24%) also had elevated high-frequency components; however, a comparable increase was also observed in late potential negative patients. Furthermore, the high-frequency component increase occurred in all patients earlier in the QRS than in its terminal 40 ms, where late potentials are traditionally evaluated. It is concluded that high-frequency components are an integral part of the QRS complex under physiologic conditions and persist in variable amount throughout its duration. The high-frequency components are increased in patients after myocardial infarction not associated with ventricular arrhythmia, and their elevation is not limited to the terminal QRS complex.

Adult↗
PubMed1994

5-Chloro-2',3'-dideoxy-3'-fluorouridine (935U83), a selective anti-human immunodeficiency virus agent with an improved metabolic and toxicological profile.

5-Chloro-2',3'-dideoxy-3'-fluorouridine (935U83) is a selective anti-human immunodeficiency virus (HIV) agent. When tested in phytohemagglutinin-stimulated normal human peripheral blood lymphocytes against fresh clinical isolates of HIV type 1 (HIV-1) obtained from patients naive to AZT (3'-azido-3'-deoxythymidine [zidovudine]), 935U83 inhibited virus growth with an average 50% inhibitory concentration (IC50) of 1.8 microM; corresponding IC50s were 0.10 microM for FLT (3'-deoxy-3'-fluorothymidine) and 0.23, 0.49, and 0.03 microM for the approved agents AZT, ddI (2',3'-dideoxyinosine), and ddC (2',3'-dideoxycytosine), respectively. Importantly, 935U83 retained activity against HIV strains that were resistant to AZT, ddI, or ddC. Of additional interest, we were unable to generate virus which was resistant to 935U83 by passaging either HXB2 (AZT-sensitive) or RTMC (AZT-resistant) strains in the presence of high concentrations of 935U83. The anabolic profile of 935U83 was similar to that of AZT, and 935U83 triphosphate was a potent inhibitor of HIV-1 reverse transcriptase. Pharmacokinetic evaluation showed good oral bioavailability (86% in mice and 60% in monkeys) and less extensive metabolism to the glucuronide relative to AZT. 935U83 showed low toxicity. In an in vitro assay for toxicity to a human erythrocyte progenitor, erythroid burst-forming unit (BFU-E), the IC50 for 935U83 (> 400 microM) was more than 1,000-fold those of FLT (0.07 microM) and AZT (0.30 microM). Mild reversible reductions in erythrocytes and associated parameters were seen in mice dosed orally with 2,000 mg of 935U83 per kg per day for 1 and 6 months. In monkeys dosed orally with up to 700 mg/kg/day for 1 and 6 months, the only possible treatment-related finding was cataracts in 1 of 12 animals given the intermediate dose of 225 mg/kg/day. At the highest doses in mice and monkeys, maximal concentrations in plasma were more than 100-fold the anti-HIV IC50s against clinical isolates. This safety profile in animals compares very favorably with that of any of the anti-HIV drugs approved to date and has led us to begin evaluation of 935U83 in patients with HIV infection.

Animals↗
PubMed1994

Altered cardiorespiratory transfer in hypertension.

The effect of continuously slowing respiration (from 0.46 to 0.05 Hz, eg, from 30 to 3 breaths per minute) on cardiovascular variables was studied in 14 hypertensive patients and 16 normotensive subjects. Beat-to-beat time-frequency (Wigner) distributions were used for dynamic analysis of RR interval and systolic and diastolic pressures. Dominant breathing frequency at rest did not differ in hypertensive patients from the control group (0.21 versus 0.19 Hz). However, in the hypertensive group it was disturbed 34.4% of the time by slow breathing and apneas, which evoked transient blood pressure instability and increased spectral powers at low frequencies (range, 0.01 to 0.1 Hz). The nonrespiratory fluctuations (NONRFs) and respiratory fluctuations (RFs) in RR interval and NONRFs in systolic pressure were smaller in hypertensive patients (P < .001). In both groups, slowing of respiratory frequency from 0.46 to 0.05 Hz entrained RFs in the RR interval and systolic and diastolic pressures. RFs in the RR interval remained diminished in hypertensive patients (P < .001), but RFs in systolic pressure increased higher at maximum, corresponding to breathing frequencies from 0.07 to 0.09 Hz (P < .001). A dynamic cardiorespiratory index (ratio of RFs in RR interval and systolic pressure) was smaller (P < .01) in hypertensive patients than in normotensive subjects. Irregular breathing at rest was found in hypertensive patients. The transfer from respiration into RR interval was diminished, suggesting an impaired parasympathetic responsiveness in mild hypertension.

Adult↗
PubMed1993

Time/frequency mapping of the heart rate, blood pressure and respiratory signals.

The discrete Wigner distribution (DWD) was implemented for the time/frequency mapping of variations of R-R interval, blood pressure and respiratory signals. The smoothed cross-DWD was defined and the modified algorithm for the smoothed auto- and cross-DWD was proposed. Spurious cross-terms were suppressed using a smoothing data window and a Gauss frequency window. The DWD is easy to implement using the FFT algorithm. Examples show that the DWD follows well the instantaneous changes of spectral content of cardiovascular and respiratory signals which characterise the dynamics of autonomic nervous system responses.

Blood Pressure↗
PubMed1993

Influence of respiration on heart rate and blood pressure fluctuations.

The dynamics of the respiratory and cardiovascular systems were studied by continuously slowing respiration from 0.46 to 0.05 Hz. The time-frequency distribution and global spectral analysis were used to assess the R-R interval (R-R) and the systolic and diastolic blood pressure fluctuations in 16 healthy subjects. During rest, the nonrespiratory-to-respiratory frequency ratios were not affected by occasional slow breathing, whereas the low- (0.01-0.15 Hz) to high- (0.15-0.3 Hz) frequency indexes for blood pressure were increased (P < 0.05). The respiratory fluctuations in R-R and the systolic and diastolic pressures were paced over the 0.46- to 0.05-Hz range. As respiration slowed to 0.07-0.09 Hz, the frequency content of the respiration and cardiovascular variables increased sharply and nonlinearly to a maximum that exceeded values at higher frequencies (P < 0.001). The nonrespiratory frequency content remained stable in the 0.01- to 0.05-Hz range and did not significantly differ from that at rest. In contrast, the nonstable 0.05- to 0.1-Hz component was suppressed. A slow 0.012- to 0.017-Hz rhythm modulated respiration and hemodynamic fluctuations at both respiratory and nonrespiratory frequencies. The study indicated that respiration input should be considered in the interpretation of global spectra. Furthermore the time-frequency distributions demonstrated that a close nonlinear coupling exists between the respiratory and cardiovascular systems.

Adult↗
PubMed1992

Periodic amplitude modulation of EEG.

Time variation of the EEG spectral parameters was analyzed during a 10 min resting period in 40 healthy subjects. Spectral band powers over the theta and alpha bands were calculated for each non-overlapping 2.5 s long EEG segment. The time variation of the band powers was further analyzed by computing the power spectra. The results showed that both theta and alpha band powers oscillate at an average frequency 0.024 Hz and 0.057 Hz. This indicates, that the background EEG activity is modulated by periodical slow components. We hypothesize that this modulation reflects spontaneous periodic changes of cortical excitability with control at the brainstem level.

Adolescent↗
PubMed1992

Positive pressure on neck reduces baroreflex response to apnoea.

This study was designed to evaluate the arterial blood pressure and heart rate responses to positive pressure applied to the neck during repetitive inspiratory apnoea. Twenty-five subjects (aged 20-40 years) were trained to exert a positive pressure on the neck by actively contracting the neck muscles and pressing the chin in the jugular notch. Blood pressure and heart rate were evaluated during 5-min long periods at rest, at the beginning and end of a 25-min period of apnoea with and without positive pressure and after a second period of rest. Positive pressure diminished the initial hypotensive and bradycardiac reactions to apnoea and augmented the heart rate and blood pressure increase towards the end of apnoea. Both systolic and diastolic pressures and heart rate were significantly elevated during both apnoeic sequences, and also remained significantly elevated after the release of pressure. Spectral analysis (FFT) and auto-regressive model showed the entrainment of the slow 0.03 Hz oscillations by repetitive apnoea and the occurrence of 0.1 Hz and respiratory 0.2 Hz components in the heart rate and blood pressure in both types of apnoea. It is suggested, since the positive pressure decreases the baroreflex and the increased sympathetic tone persists after apnoea, that such effects may contribute to the development of cardiac complications in prediposed individuals with obstructive apnoea syndrome.

Adult↗
PubMed1992

Time-frequency dynamics in neurally mediated syncope.

In this study, the responses during syncope were determined by noninvasive beat-to-beat analysis during passive orthostasis. Twenty patients with recurrent unexplained syncope (13 men and seven women) and ten healthy aged-matched control subjects were studied during 80 degrees head-up tilt for 25 min. Time-frequency mapping of R-R intervals, systolic and diastolic pressures and respiration was used to determine the responses to tilt. The spectral estimation was based on a modified Wigner distribution and the frequency content was evaluated on a beat-to-beat basis. Ten patients developed syncope (tilt-positive group) during tilt, while the remaining ten were asymptomatic (tilt-negative group). Control subjects reacted to tilt by the immediate shortening of R-R intervals to a plateau with an accompanying moderate increase in diastolic pressure. In the tilt-negative group the responses to tilt were similar, but of greater amplitude. In contrast, in the tilt-positive group, R-R intervals gradually and continuously decreased with tilt while systolic and diastolic pressures increased until shortly before syncope, when an abrupt fall in blood pressure followed by R-R intervals lengthening occurred. Furthermore, the R-R intervals fluctuations at both respiratory and nonrespiratory frequencies were the highest at rest as well as during tilt in the tilt-positive group. Nonrespiratory fluctuations in blood pressure increased more during tilt in both tilt-positive and negative groups compared to the control group. The nonrespiratory fluctuations in R-R intervals and blood pressure reached a maximum at syncope, simultaneously with hypotension and bradycardia. Time-frequency mapping has demonstrated that an elevated parasympathetic tone at rest which persists during orthostasis identifies patients prone to vasodepressor syncope. The counteracting sympathetic activation is not sustained and results in hypotension followed by cardioinhibition and loss of consciousness.

Adolescent↗
PubMed1992

Slow modulation of EEG.

Time variation of the successive 2.5 s long EEG theta and alpha band powers during 5 min rest and 4 min hyperventilation (HV) was analyzed by modified Wigner distribution (WD) in 22 subjects. Two main peaks at frequency 0.02 Hz and 0.068 Hz were detected in the WDs of both alpha and theta powers at rest. The HV increased the magnitude of the faster (0.068 Hz) component of both theta and alpha WD's while the slower (0.02 Hz) component was increased only in the theta WD. We hypothesize that this slow brain activity reflects spontaneous periodic changes of cortical excitability with control at the brain stem level.

Adult↗
PubMed1992

[Phases in the rehabilitation of male and female bone marrow transplant patients].

Teamwork is essential when investigating the long-term adoption of such medical intervention that are highly demanding on patients, physicians and nursing staff. Bone marrow transplantation represent such an intervention for a series of well defined hematological diseases. The contribution demonstrates the multiple perspective approach of the Ulm team. A case report illustrates the multiplicity of clinical issues. The state of research allows the sketching of a process model on rehabilitation.

Adaptation, Psychological↗
PubMed1990

Minimum substrate sequence for signal peptidase I of Escherichia coli.

The minimum substrate sequence recognized by signal peptidase I (SPase I or leader peptidase) was defined by measuring the kinetic parameters for a set of chemically synthesized peptides corresponding to the cleavage site of the precursor maltose binding protein (pro-MBP). The minimum sequence of a substrate hydrolyzed by SPase I at a measurable rate was the pentapeptide Ala-Leu-Ala decreases Lys-Ile. The rates of hydrolysis of this substrate, however, were several hundred-fold lower than those observed for the maturation of MBP in Escherichia coli, suggesting that in addition to these minimal sites involved in recognition, other features of pro-MBP are also needed for the optimal rate of signal peptide cleavage by SPase I. One parameter may be the length of the polypeptide chain. Studies of the synthetic peptides showed that decreasing the length of the polypeptide chain of substrates decreased the substrate efficiency measured as kcat/Km. However, in one case a decrease in the length of a peptide corresponding to -7 to +3 positions of pro-MBP to a nonapeptide (-7 to +2) increased the substrate efficiency by about 900-fold. The nonapeptide is the most efficient substrate for the enzyme in vitro so far reported. It is speculated that better peptide substrates are the ones which are able to adopt folded structures.

Amino Acid Sequence↗
PubMed1989

Blood glucose measurement by infrared spectroscopy.

For the development of an implantable artificial endocrine pancreas, a sensor for blood glucose measurement is needed providing a long-term stability. This goal can be achieved by the application of infrared spectroscopy which, unlike electrochemical sensors, responds directly to the glucose molecule. An investigation under physiological conditions revealed five glucose absorption bands in the near and middle infrared range. These are 1040, 1085, 1109, 1160 and 1365 cm-1. Only the 1040 cm-1 frequency coincides with none of the other infrared-active blood substances like proteins, lipids and urea. Nevertheless, the other absorption bands too, especially the 1109 cm-1 frequency, can be used for blood glucose measurement, if the superimposed absorptions are compensated. Methods for the compensation have been found. Technically feasible embodiments of an infrared glucose sensor are described.

Blood Glucose↗
PubMed1988

Degradation of a signal peptide by protease IV and oligopeptidase A.

The degradation of the prolipoprotein signal peptide in vitro by membranes, cytoplasmic fraction, and two purified major signal peptide peptidases from Escherichia coli was followed by reverse-phase liquid chromatography (RPLC). The cytoplasmic fraction hydrolyzed the signal peptide completely into amino acids. In contrast, many peptide fragments accumulated as final products during the cleavage by a membrane fraction. Most of the peptides were similar to the peptides formed during the cleavage of the signal peptide by the purified membrane-bound signal peptide peptidase, protease IV. Peptide fragments generated during the cleavage of the signal peptide by protease IV and a cytoplasmic enzyme, oligopeptidase A, were identified from their amino acid compositions, their retention times during RPLC, and knowledge of the amino acid sequence of the signal peptide. Both enzymes were endopeptidases, as neither dipeptides nor free amino acids were formed during the cleavage reactions. Protease IV cleaved the signal peptide predominantly in the hydrophobic segment (residues 7 to 14). Protease IV required substrates with hydrophobic amino acids at the primary and the adjacent substrate-binding sites, with a minimum of three amino acids on either side of the scissile bond. Oligopeptidase A cleaved peptides (minimally five residues) that had either alanine or glycine at the P'1 (primary binding site) or at the P1 (preceding P'1) site of the substrate. These results support the hypothesis that protease IV is the major signal peptide peptidase in membranes that initiates the degradation of the signal peptide by making endoproteolytic cuts; oligopeptidase A and other cytoplasmic enzymes further degrade the partially degraded portions of the signal peptide that may be diffused or transported back into the cytoplasm from the membranes.

Amino Acid Sequence↗