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U Frey

Publications and source records attributed to U Frey.

At least 55 records · Page 3Linked to original sources
PubMed2000

Specification for signal processing and data handling used for infant pulmonary function testing. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/American Thoracic Society.

The aim of this present paper is to define minimal performance criteria for the separate items comprising signal processing and data handling used to measure respiratory function in infants. These guidelines cover numerous aspects including: signal processing, data handling and subsequent analysis, reporting of results, demographics and handling of reference values. Adherence to these guidelines should ensure that infant lung function measurements can be performed with an acceptable degree of safety, precision, and reproducibility. Furthermore, they will facilitate multicentre collection of data and the performance of clinical investigations.

Electronic Data Processing↗
PubMed1999

Airway and tissue resistance in wheezy infants: effects of albuterol.

We partitioned total respiratory system resistance into airway (Raw) and tissue (Rti) resistance in 16 sedated infants (age 15 to 88 wk) with a history of wheezing disorders before and after inhalation of albuterol. Using systems identification methods, airway (Raw-z) and tissue resistance (Rti-z) were extracted from measurements of respiratory system transfer impedance (Ztr[omega]) over a wide frequency range (typically, 4 < f < 140 Hz). Baseline Raw-z (80.6 +/- 31.5 cm H(2)O/L/s) was significantly (p < 0.01) reduced after albuterol inhalation (60.6 +/- 22.2 cm H(2)O/L/s) but pre- and postalbuterol Rti-z were not significantly different (2.3 +/- 1.7 and 2.7 +/- 2.4 cm H(2)O/L/s, respectively). Raw-z was compared with airway resistance measured with whole-body plethysmography (Raw-p) in 10 of the 16 infants. Raw-z and Raw-p were significantly different in baseline as well as postalbuterol conditions (86.4 +/- 36.9 versus 19.0 +/- 7.0, and 60.6 +/- 22.0 versus 22.5 +/- 14.7, respectively) and they were not correlated. There was no significant difference between Raw-p under baseline and postalbuterol conditions. We conclude that airway resistance estimated from Ztr measurements comprises the major portion of total resistance (approximately 97%) in infants with wheezing disorders in baseline as well as post-beta agonist inhalation, and it is significantly reduced by albuterol inhalation.

Administration, Inhalation↗
PubMed1998

[Etiology and therapy of obstructive respiratory tract diseases in infancy and early childhood].

Wheezing disorders in early childhood are frequent, nevertheless little is known about their heterogeneous aetiology. In the last few years there has been increasing evidence of antenatal as well as postnatal influences which can make infants more prone to wheezing episodes. This review tries to classify various groups of wheezing disorders based on risk factors such as allergy, developmental differences in airway mechanics or association with viral infections. On this basis the different therapeutic regimens and particularly the effect of anti-inflammatory treatment with inhaled corticosteroids in this age group are discussed. New concepts of anti-inflammatory treatment for croup syndromes are summarised.

Administration, Inhalation↗
PubMed1998

Synaptic tagging: implications for late maintenance of hippocampal long-term potentiation.

A novel property of hippocampal LTP, 'variable persistence', has recently been described that is, we argue, relevant to the role of LTP in information storage. Specifically, new results indicate that a particular pattern of synaptic activation can give rise, either to a relatively short-lasting LTP, or to a longer-lasting LTP as a function of the history of activation of the neuron. This has led to the idea that the induction of LTP is associated with the setting of a'synaptic tag' at activated synapses, whose role is to sequester plasticity-related proteins that then serve to stabilize temporary synaptic changes and so extend their persistence. In this article, we outline the synaptic tag hypothesis, compare predictions it makes with those of other theories about the persistence of LTP, and speculate about the cellular identity of the tag. In addition, we outline the requirement for aminergic activation to induce late LTP and consider the functional implications of the synaptic tag hypothesis with respect to long-term memory.

Animals↗
PubMed1998

Irregularities and power law distributions in the breathing pattern in preterm and term infants.

Unlike older children, young infants are prone to develop unstable respiratory patterns, suggesting important differences in their control of breathing. We examined the irregular breathing pattern in infants by measuring the time interval between breaths ("interbreath interval"; IBI) assessed from abdominal movement during 2 h of sleep in 25 preterm infants at a postconceptional age of 40.5 +/- 5.2 (SD) wk and in 14 term healthy infants at a postnatal age of 8.2 +/- 4 wk. In 10 infants we performed longitudinal measurements on two occasions. We developed a threshold algorithm for the detection of a breath so that an IBI included an apneic period and potentially some periods of insufficient tidal breathing excursions (hypopneas). The probability density distribution (P) of IBIs follows a power law, P(IBI) approximately IBI-alpha, with the exponent alpha providing a statistical measurement of the relative risk of insufficient breathing. With maturation, alpha increased from 2.62 +/- 0.4 at 41. 2 +/- 3.6 wk to 3.22 +/- 0.4 at 47.3 +/- 6.4 wk postconceptional age, indicating a decrease in long hypopneas (for paired data P = 0.002). The statistical properties of IBI were well reproduced in a model of the respiratory oscillator on the basis of two hypotheses: 1) tonic neural inputs to the respiratory oscillator are noisy; and 2) the noise explores a critical region where IBI diverges with decreasing tonic inputs. Accordingly, maturation of infant respiratory control can be explained by the tonic inputs moving away from this critical region. We conclude that breathing irregularities in infants can be characterized by alpha, which provides a link between clinically accessible data and the neurophysiology of the respiratory oscillator.

Abdominal Muscles↗
PubMed1998

High-frequency respiratory impedance measured by forced-oscillation technique in infants.

Measurements of respiratory input impedance (Zin) in infants using forced oscillations at the airway opening up to 256 Hz have been shown to include a first antiresonance (ar,1). We wondered whether features derived from high-frequency Zin change during methacholine-induced airway obstruction in infants, whether those changes could be explained by a lumped parameter model as in dogs (providing a value for respiratory resistance [Rrs]), or whether they are similar to Zin data in human adults with airway obstruction. In 13 wheezy infants (age 58 +/- 19 wk) Zin(omega) was assessed at baseline, and in nine infants after methacholine challenge, using a provocation dose defined by fall of more than 30% in VmaxFRC (rapid chest-compression technique). Following methacholine challenge, VmaxFRC decreased significantly (p < 0.0005), the frequency at which ar,1 occurred ( far,1) increased significantly (p = 0.0007), and the relative maximum in the real part at far,1 [Zinre( far,1)] increased significantly (p = 0.02), whereas Rrs did not change. We conclude that in wheezy infants ar,1 is highly sensitive to changes in lung mechanics. Although ar,1 cannot be explained by a simple lumped-parameter model, it is likely due to wave propagation phenomena, as in human adults. In either case, far,1 potentially contains information about airway wall compliance, which is important for the understanding of flow limitation in infant wheezing disorders.

Airway Resistance↗
PubMed1998

Differences in airway wall compliance as a possible mechanism for wheezing disorders in infants.

High-frequency input impedance measurements (Z(f)) provide useful noninvasive information on airway geometry and especially airway wall mechanics in the canine and human adult respiratory system. Using the high-speed interrupter technique (HIT), we have shown that it is possible to measure high-frequency Z(f) in infants up to 900 Hz, including antiresonant phenomena which are known to be related to wave propagation velocity. This implies that the first antiresonant frequency (far,1) is a function of airway wall compliance. Since, airway wall mechanics are particularly important for the flow limitation phenomena, we wondered whether we could find evidence that airway wall properties were important for the occurrence of flow limitation during incremental methacholine challenge in infants. We measured Z(f) from 32-900 Hz and maximal flow at functional residual capacity (V'maxFRC) by the rapid chest compression technique in 10 infants (aged 36-81 weeks) with wheezing disorders. far,1 increased significantly at very low doses of mch before any decline could be detected in V'maxFRC. We hypothesize that these changes in far,1 are determined by mch-induced decrease in airway wall compliance. High-speed interrupter technique in combination with rapid chest compression technique can be used to study developmental differences in airway function (particularly of airway wall properties) and their contribution to airway disease and response to bronchodilator therapy in infants.

Adult↗
PubMed1998

High-frequency respiratory input impedance measurements in infants assessed by the high speed interrupter technique.

High-frequency input impedance (Z(f)) measurements, including antiresonances, provide useful noninvasive information on airway geometry and especially airway wall mechanics in the canine and human adult respiratory system. A knowledge of airway wall mechanics would be particularly important in understanding flow limitation phenomena in infants. High-frequency Z(f) has not been measured in infants above 256 Hz, because the high impedance of the infantile respiratory system would be expected to result in low amplitudes of oscillatory flow at higher frequencies. The aim of this study was to develop a technique to measure high-frequency Z(f) in infants and to elucidate the nature of the antiresonance phenomena in the Z(f) spectrum in infants. Z(f) was measured from 32-900 Hz during rapid airflow interruption by the high-speed interrupter technique (HIT) in 18 infants (aged 24-149 weeks) with wheezing disorders. The HIT enables the excitement of higher flow amplitudes at high frequencies using a pseudostep forcing function. In all infants Z(f) showed a mean (SD) first antiresonance (far,1) of 172 (35) Hz (real part of Z(f) at far,1 (Z(f)re(far,1)): 4.9 (1.1) kPa x L(-1) x s) and in five infants a second antiresonance (far,2) of 564 (51) Hz (Z(f)re(far,2): 2.0 (0.7) kPa x L(-1) x s). The antiresonances were found to be related to wave propagation in the airways (acoustic antiresonances), because they increased by a factor of approximately 2 when He-O2 was inhaled. This implies that far,1 and its harmonics are a function of airway wall compliance. In conclusion, the first and second antiresonances may be helpful in understanding flow limitation in wheezing disorders in infants, because flow limitation is related not only to airway diameter but also to airway wall compliance.

Adult↗
PubMed1997

Hippocampal synaptic plasticity: role in spatial learning or the automatic recording of attended experience?

Allocentric spatial learning can sometimes occur in one trial. The incorporation of information into a spatial representation may, therefore, obey a one-trial correlational learning rule rather than a multi-trial error-correcting rule. It has been suggested that physiological implementation of such a rule could be mediated by N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) in the hippocampus, as its induction obeys a correlational type of synaptic learning rule. Support for this idea came originally from the finding that intracerebral infusion of the NMDA antagonist AP5 impairs spatial learning, but studies summarized in the first part of this paper have called it into question. First, rats previously given experience of spatial learning in a watermaze can learn a new spatial reference memory task at a normal rate despite an appreciable NMDA receptor blockade. Second, the classical phenomenon of 'blocking' occurs in spatial learning. The latter finding implies that spatial learning can also be sensitive to an animal's expectations about reward and so depend on more than the detection of simple spatial correlations. In this paper a new hypothesis is proposed about the function of hippocampal LTP. This hypothesis retains the idea that LTP subserves rapid one-trial memory, but abandons the notion that it serves any specific role in the geometric aspects of spatial learning. It is suggested that LTP participates in the automatic recording of attended experience': a subsystem of episodic memory in which events are temporarily remembered in association with the contexts in which they occur. An automatic correlational form of synaptic plasticity is ideally suited to the online registration of context event associations. In support, it is reported that the ability of rats to remember the most recent place they have visited in a familiar environment is exquisitely sensitive to AP5 in a delay-dependent manner. Moreover, new studies of the lasting persistence of NMDA-dependent LTP, known to require protein synthesis, point to intracellular mechanisms that enable transient synaptic changes to be stabilized if they occur in close temporal proximity to important events. This new property of hippocampal LTP is a desirable characteristic of an event memory system.

2-Amino-5-phosphonovalerate↗
PubMed1997

Endogenous serine protease inhibitor modulates epileptic activity and hippocampal long-term potentiation.

Protease nexin-1 (PN-1), a member of the serpin superfamily, controls the activity of extracellular serine proteases and is expressed in the brain. Mutant mice overexpressing PN-1 in brain under the control of the Thy-1 promoter (Thy 1/PN-1) or lacking PN-1 (PN-1-/-) were found to develop epileptic activity in vivo and in vitro. Theta burst-induced long-term potentiation (LTP) and NMDA receptor-mediated synaptic transmission in the CA1 field of hippocampal slices were augmented in Thy 1/PN-1 mice and reduced in PN-1-/- mice. Compensatory changes in GABA-mediated inhibition in Thy 1/PN-1 mice suggest that altered brain PN-1 levels lead to an imbalance between excitatory and inhibitory synaptic transmission.

Amyloid beta-Protein Precursor↗
PubMed1997

Synaptic tagging and long-term potentiation.

Repeated stimulation of hippocampal neurons can induce an immediate and prolonged increase in synaptic strength that is called long-term potentiation (LTP)-the primary cellular model of memory in the mammalian brain. An early phase of LTP (lasting less than three hours) can be dissociated from late-phase LTP by using inhibitors of transcription and translation, Because protein synthesis occurs mainly in the cell body, whereas LTP is input-specific, the question arises of how the synapse specificity of late LTP is achieved without elaborate intracellular protein trafficking. We propose that LTP initiates the creation of a short-lasting protein-synthesis-independent 'synaptic tag' at the potentiated synapse which sequesters the relevant protein(s) to establish late LTP. In support of this idea, we now show that weak tetanic stimulation, which ordinarily leads only to early LTP, or repeated tetanization in the presence of protein-synthesis inhibitors, each results in protein-synthesis-dependent late LTP, provided repeated tetanization has already been applied at another input to the same population of neurons. The synaptic tag decays in less than three hours. These findings indicate that the persistence of LTP depends not only on local events during its induction, but also on the prior activity of the neuron.

Animals↗
PubMed1997

NMR identification of hydrophobic cavities with low water occupancies in protein structures using small gas molecules.

Magnetization transfer through dipole-dipole interactions (nuclear Overhauser effects, NOEs) between water protons and the protons lining two small hydrophobic cavities in hen egg-white lysozyme demonstrates the presence of water molecules with occupancies of approximately 10-50%. Similarly, NOEs were observed between the cavity protons and the protons of hydrogen, methane, ethylene or cyclopropane applied at 1-200 bar pressure. These gases can thus be used as general NMR indicators of empty or partially hydrated hydrophobic cavities in proteins. All gases reside in the cavities for longer than 1 ns in marked contrast to common belief that gas diffusion in proteins is not much slower than in water. Binding to otherwise empty cavities may be a major aspect of the anesthetic effect of small organic gas molecules.

Algorithms↗
PubMed1997

Human respiratory input impedance between 32 and 800 Hz, measured by interrupter technique and forced oscillations.

Respiratory input impedance (Zin) over a wide range of frequencies (f) has been shown to be useful in determining airway resistance (Raw) and tissue resistance in dogs or airway wall properties in human adults. Zin measurements are noninvasive and, therefore, potentially useful in investigation of airway mechanics in infants. However, accurate measurements of Zin at these f values with the use of forced oscillatory techniques (FOT) in infants are difficult because of their relatively high Raw and large compliance of the face mask. If pseudorandom noise pressure oscillations generated by a loudspeaker are applied at the airway opening (FOT), the power of the resulting flow decreases inversely with f because of capacitive shunting into the volume of the gas in the speaker chamber and in the face mask. We studied whether high-frequency respiratory Zin can be measured by using rapid flow interruption [high-speed interrupter technique (HIT)], in which we expect the flow amplitude in the respiratory system to be higher than in the FOT. We compared Zin measured by HIT with Zin measured by FOT in a dried dog lung and in five healthy adult subjects. The impedance was calculated from two pressure signals measured between the mouth and the HIT valve. The impedance could be assessed from 32 to 800 Hz. Its real part at low f as well as the f and amplitude of the first and second acoustic resonance, measured by FOT and by HIT, were not significantly different. The power spectrum of oscillatory flow when the HIT was used showed amplitudes that were at least 100 times greater than those when FOT was used, increasing at f > 400 Hz. In conclusion, the HIT enables the measurement of high-frequency Zin data ranging from 32 to 800 Hz with particularly high flow amplitudes and, therefore, possibly better signal-to-noise ratio. This is particularly important in systems with high Raw, e.g., in infants, when measurements have to be performed through a face mask.

Adult↗
PubMed1997

Oscillatory pressure transients after flow interruption during bronchial challenge test in children.

The measurement of the conventional interrupter resistance (Rint) is dependent on pressure equilibration between alveolar and airway opening pressure, which is often not achieved in the presence of severe airways obstruction or in small children. The damping properties (d) of postocclusional oscillatory pressure transients after rapid flow interrruption can be assessed independent of complete pressure equilibration, and we have previously shown them to be correlated to resistive properties of the respiratory system. We wanted to determine whether these transients were an expression of acoustic properties of the air in the airways, or whether they were caused by an interaction of gas and lung tissue, and whether d was more sensitive than Rint to changes in airway mechanics. Bronchial challenge tests were carried out with cumulative doses of inhaled carbachol in 10 healthy children (aged 7-14 yrs) and 50 asthmatic children (aged 5-15 yrs). The airflow interruptions were performed with a combined nebulizer-shutter head, allowing resistance measurements with each breath. The frequency, and the damping factor of the postocclusional pressure transients changed significantly during carbachol challenge in both groups of children. The provocation dose (PD) at which the damping factor (d) of the oscillatory pressure transients increased more than 2 SD above the baseline mean ("variance-based", PDvb) was lower than the PDvb of the end-interruption resistance (Rint, EI). These changes in frequency and damping factor were reversible after inhaling salbutamol. These findings suggest that the damping properties of the postocclusional pressure transients after flow interruption can be used as a sensitive parameter to assess changes in airway mechanics during bronchial challenge test in children in whom pressure equilibration is frequently not achieved during airflow interruption due to airways obstruction.

Acoustics↗
PubMed1996

A different form of long-lasting potentiation revealed in tissue plasminogen activator mutant mice.

The establishment of hippocampal long-term (LTP) requires protein and mRNA synthesis, suggesting that neuronal activity resulting in LTP initiates a cascade of gene expression. The expression of the gene for the extracellular serine protease tissue plasminogen activator (t-PA) is induced during LTP. Here we analyze long-lasting LTP (L-LTP,>4 hr)in CA1 hippocampal slices of mice homozygous for disrupted t-PA genes. Although mutant mice appear to exhibit long-term potentiation, we provide evidence that these mice are devoid of conventional homosynaptic L-LTP at the Schaffer collateral-CA1 pyramidal cell synapse. Most remarkably, t-PA-deficient mice exhibit a different form of long-lasting potentiation that is characterized by an NMDA receptor-dependent modification of GABA transmission in the CA1 region.

2-Amino-5-phosphonovalerate↗