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R Kraemer

Publications and source records attributed to R Kraemer.

At least 37 records · Page 2Linked to original sources
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

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↗
PubMed1998

Genotype-phenotype association in infants with cystic fibrosis at the time of diagnosis.

The relationship between the most common disease-causing mutations, the clinical manifestation, and lung function was prospectively assessed in 60 infants (33 females, 27 males) with cystic fibrosis at time of diagnosis (age: 7.2 months; range: 0.8-23.8 months). Lung function was assessed by infants whole-body plethysmography. Age at time of diagnosis was independent from the genotype. Weight gain from birth until the time of diagnosis expressed in percent predicted of a normal population was lower in the 3905insT group (57.9 +/- 19.0%) compared with deltaF508 homozygotes (62.5 +/- 20.6%; n.s.) and the R553X group (85.9 +/- 10.9%; p < 0.005). Differences regarding lung function within the genetic groups are mainly related to pulmonary hyperinflation, measured by thoracic gas volume (TGV), present in 8 of 9 infants with 3905insT, differentiating this frameshift mutation (TGV of 7.0 +/- 3.6 SD-S) from the R553X mutation (TGV 2.1 +/- 4.6 SD-S; p < 0.02). It is concluded that the variable disease findings in infants with cystic fibrosis is clinically and functionally reflected by features already present at time of diagnosis. The degree of pulmonary hyperinflation is, at least partly, influenced by the genotype.

Bacteria↗
PubMed1997

Ciprofloxacin as antipseudomonal treatment in patients with cystic fibrosis.

OBJECTIVE: The efficacy and safety of oral ciprofloxacin as a maintenance antipseudomonal therapy were evaluated in 44 patients with cystic fibrosis who had completed a 14-day regimen of intensive hospital therapy with intravenous ceftazidime and amikacin, supplemented by amikacin inhalation therapy. METHODS: Twenty-one patients were randomly assigned to oral ciprofloxacin alone (Group I) and 23 received ciprofloxacin plus inhaled amikacin (Group II). RESULTS: Negative sputum cultures were achieved in 34 patients (77%) at the end of intensive therapy (19 Group I and 15 Group II) and were sustained after 3 months of maintenance therapy in 5 of the 19 responders in Group I (26%) and in 8 of the 15 responders in Group II (53%). Resistance to ciprofloxacin was found in 7 of 31 (23%) sputum isolates at the end of ciprofloxacin therapy. During maintenance therapy, continued improvement in clinical symptoms was observed in 14 patients in both treatment groups; 6 in each group had further improvements whereas only 4 patients were clinical failures. There was no correlation between clinical outcome and either elimination of Pseudomonas aeruginosa from sputum culture or development of ciprofloxacin resistance. Both maintenance regimens were well-tolerated by this population of patients which included 28 children younger than 15 years of age. There were no severe or serious adverse events, no signs of quinolone-related arthropathy and no growth impairment. CONCLUSION: Ciprofloxacin was efficacious, safe and well-tolerated as maintenance antipseudomonal therapy in cystic fibrosis patients. These results suggest further evaluation of ciprofloxacin as an oral maintenance therapy is warranted.

Adolescent↗
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

Clinical and physiological improvement after inhalation of low-dose beclomethasone dipropionate and salbutamol in wheezy infants.

UNLABELLED: Twenty-nine of initially 42 infants with recurrent wheeze (20 male and 9 female) with an age range of 2.1-25.2 months were randomly assigned to receive either 100 micrograms beclomethasone dipropionate (BDP) combined with 200 micrograms salbutamol (group BDP-S, n = 9), 200 micrograms salbutamol (group S, n = 8), or placebo (group P, n = 6) 3 times daily for a 6 weeks' treatment period. Six infants had to be treated openly with BDP-S (group O, n = 6) because of deterioration in the disease state. Ten babies were excluded because of incomplete data and poor drug compliance and further 3 because of needed rescue medication. The drugs were inhaled from a metered dose inhaler through a baby-adapted spacer device, the Babyhaler. Control was assessed by symptom diaries, and infant whole-body plethysmography. Values of thoracic gas volume (TGV), airway conductance (Gaw) and specific airway conductance (sGaw) were calculated numerically independent of age and body length in percent predicted and in standard deviation scores using regression equations taken from healthy infants previously evaluated. Functional improvement was considered to have occurred when either TGV, and/or Gaw improved more than 2 SD from baseline. There was a significant improvement in the symptom score (p < 0.05), particularly concerning cough, in addition to a significant decrease in pulmonary hyperinflation (TGV: p < 0.05) and improvement of Gaw (p < 0.01) and sGaw (p < 0.01) in the BDP-S group when compared to the P group. No significant differences were found between the BDP-S and S group and/or between the S and P groups. CONCLUSIONS: In wheezy infants BDP improves clinical status and lung function, when given in combination with salbutamol by a baby-adapted spacer device.

Administration, Inhalation↗
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↗
PubMed1995

Interrelationship between postocclusional oscillatory pressure transients and standard lung function in healthy and asthmatic children.

We studied the correlation between characteristics of the postocclusional oscillatory airway opening pressure transients after flow interruption and body height, the degree of pulmonary hyperinflation [measured by thoracic gas volume (TGV)], and the degree of airway obstruction [measured by airway resistance (Raw)] and maximal expiratory flow at 50% vital capacity (MEF50) in 10 healthy and 50 asthmatic children age 7-16 years. Focusing on the damped oscillatory change in pressure, the first derivative of the shutter curve was analyzed, featuring a natural frequency fO and damping factor d in the time domain, and frequency FFS and power AFS in the frequency domain. A maximal frequency was found at approximately 80 Hz without a two peak distribution as described in dogs. Multiple linear forward step analysis revealed that omega O (the undamped, natural frequency) and AFS were related to body height (P < 0.001). The damping factor d (independent of body height) was related to TGV and MEF50 (P < 0.001), and FFS to Raw (P < 0.001). The analysis of the postocclusional pressure transients after airflow interruption provides information on the resistive, elastic and inertive properties of the thoraco-pulmonary system. The measurements obtained are influenced by the end-expiratory resting level (or the degree of pulmonary hyperinflation) and the degree of airway obstruction.

Adolescent↗
PubMed1995

The age at onset of chronic Pseudomonas aeruginosa colonization in cystic fibrosis--prognostic significance.

To evaluate the prognostic significance of the age at onset of chronic Pseudomonas aeruginosa colonization (OPCP) with respect to pulmonary disease progression in patients with cystic fibrosis (CF), a retrospective long-term analysis using annual chest radiographs was performed on 54 CF patients. Thirty-seven patients (68%) were chronically colonized before the age of 12 years (group 1), 17 patients (32%) thereafter (group 2). These two groups did not significantly differ in terms of mean duration of follow up (16.2 +/- 5.9 years), sex, CF genotypes, colonization with other respiratory pathogens, supportive medical treatment and death rate during the study period. Chest radiographs were evaluated according to the Chrispin-Norman score, increasing scores representing increasing severity of respiratory disease. In both groups, progression of score means was not accelerated of score means was not accelerated up to 6 years after OCPC (Scores at OCPC set 0; mean score +/- SEM 6 years prior to OCPC -5.6 +/- 2.0; 10 years after OCPC +3.6 +/- 0.7 points). Patients chronically colonized prior to age 12 years (group 1) scored significantly higher between age 2 and 11 years (maximum difference at age 8 years [mean +/- SEM]: 9.4 +/- 0.7 vs. 4.3 +/- 1.3 points; P = 0.002) as compared to group 2. After age 11 years, mean scores were similar in both groups, since in group 2 scores increased rapidly after age 8 years. We conclude that OCPC did not cause an immediate acceleration of CF lung disease judged by serial chest radiographs. Rapid progression in group 2 (OCPC after age 12 years) was independent of OCPC since it occurred earlier. These data indicate that OCPC may be a marker rather than the cause of respiratory disease progression.

Adolescent↗
PubMed1995

Pressure oscillations after flow interruption in relation to lung mechanics.

The value of interrupter resistance measurements has been questioned because these depend on equilibration between alveolar (PA) and mouth pressure (PAO), which may not occur during airway obstruction or in measurements in children. In order to determine whether airway geometry and its interaction with the lung volume can be obtained without complete pressure equilibration, the postocclusional oscillatory airway opening pressure transients PAO(t) after flow interruption were studied in comparison to airway resistance (RAW), lung volumes (TGV, VC) and MEF50 in 9 healthy children (7-14 y) and 5 adults (28-37 y) in both time and frequency domains. The frequency of pressure oscillations was correlated to TGV (p < 0.01). Its damping properties (d) were correlated to MEF50 (p < 0.005). Performing airflow interruptions in the same subject showed that d increased at low lung volumes. During bronchial challenge test, d significantly increased with carbachol and decreased with salbutamol, whereas the frequency decreased with carbachol and increased with salbutamol. Therefore, the analysis of postocclusional pressure oscillations can be used to assess relative changes in airway mechanics and its interaction with lung volume during bronchial challenge tests in patients such as children with poor cooperation.

Adolescent↗
PubMed1995

Babyhaler--a new paediatric aerosol device.

Nebulizers have, until recently, been the mainstay of drug delivery by inhalation in babies and young children. The willingness of a young child to cooperate, however, is limited and the 10-12 mins needed to deliver drug using a nebulizer often limits the compliance with this mode of administration in infants. Therefore, drug delivery systems using the metered-dose inhaler (MDI) as the aerosol generator attached to valved holding chambers were developed. The breathing pattern of a baby with lung disease is quite different from that of older children and adults, for whom most large-volume devices were developed. Infants have a high respiratory frequency, small tidal volume, and low inspiratory airflow rate. Therefore, specific conditions for optimal drug use in this particular group of patients have to be met. Efficacy of topical drug delivery depends on the generation of aerosol particles with an adequate size distribution (technical prerequisites), the breathing pattern of the child (physiological requirements), and the willingness of a young child to cooperate with parental drug administration (practicality and compliance). Infants with lung disease have a tidal volume of 8-10ml/kg body weight. The volume of a spacer device must be such that about 5-10 breaths would be needed to provide an adequate dose. In addition, the dimensions of a spacer device must be such that sufficient drug particles of optimal size will be generated to minimize impaction and deposition within the device. The Babyhaler consists of a tubular chamber 230mm long, with a volume of 350ml and low-resistance inspiratory and expiratory valves.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1995

Cystic fibrosis mutations and immotile cilia syndrome.

The immotile cilia syndrome (ICS) presents with autosomal recessive inheritance and is a chronic respiratory disease supposed to be caused by different genetic determinants. The hypothesis that cystic fibrosis (CF) heterozygotes may have a predisposition to develop bronchial or respiratory diseases other than CF prompted us to look for CF mutations in patients with ICS. Five patients, as well as the parents and two healthy brothers of one patient were tested for 12 CF mutations, for the polymorphic GATT repeat in intron 6a and for the CF gene flanking markers XV-2c, KM19, MP6d-9, J3.11. None of the 12 mutations at the CF locus have been detected in the ICS patients and no linkage was found between ICS and the polymorphic markers. Thus, based on our data, ICS and CF seem to be two different clinical entities.

Adult↗
PubMed1995

Chronic metabolic alkalosis: not uncommon in young children with severe cystic fibrosis.

The acid-base balance of 199 patients with cystic fibrosis, seen from 1987 through 1992 at the Bern Outpatient Clinic, were evaluated. Simple metabolic alkalosis was demonstrated in 16 and mixed metabolic alkalosis and respiratory acidosis in 9 patients. When compared with 10 patients with simple respiratory acidosis and 16 with normal hydrogen ion balance, those with simple metabolic alkalosis were significantly younger. The need for pancreatic enzymes was significantly higher and the relative underweight significantly more severe in patients with either simple or mixed metabolic alkalosis and respiratory acidosis. The results indicate the rather common occurrence of chronic metabolic alkalosis in cystic fibrosis. It is observed in young patients, in patients who need high doses of pancreatic enzymes and in the those with poor nutritional status.

Acidosis, Respiratory↗
PubMed1995

Plethysmographic measurements in the clinical assessment of infants with bronchopulmonary disease.

Whole-body plethysmography makes it possible, to measure, during the same test sequence, the end-expiratory resting level (thoracic gas volume (TGV)), and, hence, an estimate of lung volume, and its close inter-relationship to airway function (airway resistance (Raw), or its reciprocal value airway conductance (Gaw). An overview is given of the physiological background and some equipment required for this technique. Furthermore, the attractive usefulness of whole-body plethysmography in clinical routine is discussed. Based on plethysmographic data obtained in 118 infant survivors of respiratory distress syndrome (RDS), in wheezy infants and infants with cystic fibrosis (CF), the important inter-relationship between changes in end-expiratory resting level (TGV) and the deficit in airway mechanics (Gaw) is shown, and special emphasis is given to the absolute need to obtain these measurements simultaneously. It can be shown that this recommendation is of even greater clinical importance in view of the fact that the younger the child the more frequent and severe the pulmonary hyperinflation present. Finally, this inter-relationship has to be borne in mind when reversibility of functional abnormalities on adrenoceptor agonists is assessed by lung function measurements.

Airway Resistance↗
PubMed1995

Neurotrophin and neurotrophin receptors in vascular smooth muscle cells. Regulation of expression in response to injury.

The neurotrophins, a family of related polypeptide growth factors including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3 and NT-4/5 promote the survival and differentiation of distinctive sets of embryonic neurons. Here we define a new functional role for neurotrophins, as autocrine or local paracrine mediators of vascular smooth muscle cell migration. We have identified neurotrophins, and their cognate receptors, the trk tyrosine kinases, in human and rat vascular smooth muscle cells in vivo. In vitro, cultured human smooth muscle cells express BDNF; NT-3; and trk A, B, and C. Similarly, rat smooth muscle cells expressed all three trk receptors as well as all four neurotrophins. Moreover, NGF induces cultured human smooth muscle cell migration at subnanomolar concentrations. In the rat aortic balloon deendothelialization model of vascular injury, the expression of NGF, BNDF, and their receptors trk A and trk B increased dramatically in the area of injury within 3 days and persisted during the formation of the neointima. In human coronary atherosclerotic lesions, BDNF, NT-3, and NT-4/5, and the trk B and trk C receptors could be demonstrated in smooth muscle cells. These findings suggest that neurotrophins play an important role in regulating the response of vascular smooth muscle cells to injury.

Animals↗
PubMed1995

Cholesterol enrichment enhances expression of sterol-carrier protein-2: implications for its function in intracellular cholesterol trafficking.

Cholesterol enrichment of vascular smooth muscle cells, as occurs under conditions of hypercholesterolemia and atherosclerosis, is accompanied by specific changes in cholesterol metabolism and in intracellular cholesterol trafficking. Sterol-carrier protein-2 (SCP2), an intracellular lipid binding protein, enhances the activation of enzymes involved in cholesterol metabolism. It may also enhance cholesterol efflux by regulating the size of the "fast" cholesterol pool available for efflux to high density lipoproteins. However, a definitive role for SCP2 in arterial cholesterol metabolism is unclear. Therefore, we examined the expression of SCP2 (13.1 kD), SCPx (58 kD), and p30 (30.8 kD) in cultured arterial smooth muscle cells under conditions of cholesterol enrichment. We found that SCP2, SCPx, and p30 are localized principally in the cytosolic fraction, with lesser amounts associated with the nuclear/peroxisomal fraction; the expression of SCP2 protein and mRNA, but not SCPx, is increased after exposure of smooth muscle cells to cationized LDL. In contrast to the increased expression of SCP2, the expression of p30 decreases after cholesterol enrichment of smooth muscle cells. Coupled with previous studies demonstrating enhanced cholesterol efflux from cholesterol-enriched smooth muscle cells in response to high density lipoproteins, our results suggest that increased expression of SCP2 may partly mediate the cholesterol trafficking process.

Animals↗
PubMed1994

A pressurized injection/suction system for ventilation in the presence of complete airway obstruction.

OBJECTIVE: To describe the design and ventilatory characteristics of a new mode of ventilation (pressurized injection/suction ventilation). DESIGN: Descriptive and analytical laboratory study. SETTING: Laboratory study. SUBJECTS: Simulated lung model and dogs. INTERVENTIONS: We tested the ability to maintain ventilation through a 2.5-mm internal diameter ventilating stylet in the setting of simulated complete airway occlusion. A microprocessor-controlled ventilator mode was used wherein injection of oxygen under high pressure (flow rate 95 L/min) alternates with suction of expired gas (flow rate 18 L/min) through the ventilating stylet. MEASUREMENTS AND MAIN RESULTS: In a lung model, we achieved a maximum minute ventilation of 12.9 L/min. In two dogs, we maintained stable oxygenation (mean PaO2 603 +/- 47 torr [80.4 +/- 6.3 kPa]) and ventilation (mean PaCO2 19 +/- 3 torr [2.5 +/- 0.4 kPa]) for 15 mins at maximum minute ventilation settings. No clinically important deleterious effects on the tracheal mucosa were observed. The ventilator system's safety-abort feature prevented overinflation or excessive deflation of the dogs' lungs in every test of simulated malfunction of the pressure-monitoring mechanism. CONCLUSIONS: Pressurized injection/suction ventilation can maintain adequate gas exchange in an animal model with near-complete airway obstruction. Further work is needed to develop the safety and clinical applications of pressurized injection/suction ventilation in the management of patients with near-complete airway occlusion.

Airway Obstruction↗