Search PubMed⌕ Search

Biomedical subjects

R Kraemer

Publications and source records attributed to R Kraemer.

At least 19 recordsLinked to original sources
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

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↗
PubMed1994

Expression of the v-crk oncogene product in PC12 cells results in rapid differentiation by both nerve growth factor- and epidermal growth factor-dependent pathways.

The transforming gene of the avian sarcoma virus CT10 encodes a fusion protein (p47gag-crk or v-Crk) containing viral Gag sequences fused to cellular sequences consisting primarily of Src homology regions 2 and 3 (SH2 and SH3 sequences). Here we report a novel function of v-Crk in the mammalian pheochromocytoma cell line, PC12, whereby stable expression of v-Crk induces accelerated differentiation, as assessed by induction of neurites following nerve growth factor (NGF) or basic fibroblast growth factor (bFGF) treatment compared with the effect in native PC12 cells. Surprisingly, however, these cells also develop extensive neurite processes after epidermal growth factor (EGF) stimulation, an event which is not observed in native PC12 cells. Following EGF or NGF stimulation of the v-CrkPC12 cells, the v-Crk protein itself became tyrosine phosphorylated within 1 min. Moreover, in A431 cells or TrkA-PC12 cells, which overexpress EGF receptors and TrkA, respectively, a GST-CrkSH2 fusion protein was indeed capable of binding these receptors in a phosphotyrosine-dependent manner, suggesting that v-Crk can directly couple to receptor tyrosine kinase pathways in PC12 cells. In transformed fibroblasts, v-Crk binds to specific tyrosine-phosphorylated proteins of p130 and paxillin. Both of these proteins are also complexed to v-Crk in PC12 cells, as evidenced by their coprecipitation with v-Crk in detergent lysates, suggesting that common effector pathways may occur in both cell types. However, whereas PC12 cellular differentiation can occur solely by overexpression of the v-Src or oncogenic Ras proteins, that induced by v-Crk requires a growth factor stimulatory signal, possibility in a two-step process.

Animals↗
PubMed1994

[Assessment of intrapulmonary ventilation disorders in children with bronchial asthma using the nitrogen elimination technique].

Stratification of functional abnormalities evaluated by whole-body plethysmography in asthmatic children can be characterized into three functional groups: pulmonary hyperinflation (H: TGV > mean + 2SD), bronchial obstruction (O: Raw > mean + 2SD) and a mixed type, group M, including both abnormalities. The multibreath nitrogen washout (MBNW) offers the possibility to measure FRC and calculate the amount of trapped gases (TG = TGV-FRCMBNW). Furthermore ventilation inequalities can be estimated by mathematical analysis of the washout curve from which indexes such as the lung clearance index (LCI), the mean dilution number (MDN) and the moment ratio (m2:m0 = M-ratio) can be obtained. In 69 asthmatic children (age 5-17 y; 38 boys, 31 girls) body plethysmography and MBNW were performed in the symptom free interval. The questions were, at what extend TG are present within the different functional groups, and which parameters best describe ventilation inequalities. The group attribution was H: 23, M: 16, O: 30. The highest amount of TG was found in H (36.4 +/- 22.2% TGV), then in M (26.6 +/- 23.1% TGV) and in O (19.4 +/- 16.0% TGV). In 33/50 cases presenting with normal TGV, TG mainly was at cost of a low FRC (13 in H, 8 im M, 12 in O). In 19 cases FRC was higher than TGV (3 in H, 1 in M 15 in O). TG was closely related with LCI, MDN and M-ratio. Most pronounced ventilation inequalities were found in group M showing a correlation only with FRC, but not with TGV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

[Therapeutic aspects in the treatment of juvenile bronchial asthma].

The most important goal of the treatment for bronchial asthma in infants and children is to avoid structural damage to bronchi and lung by the underlying allergic and immunologic inflammatory process. This inflammation is caused by an inherited predisposition to exaggerated mediator-release in the mucosa. Repeated actions of trigger factors maintain this inflammation and provoke exacerbations of asthmatic symptoms. The protective task of the bronchial mucosa can not be fulfilled anymore. General measures of asthma treatment such as prophylaxis against house-dust mite exposure, improved breathing technique and improvement of lung clearance are indispensable measures of an individually adapted, effective symptomatic (bronchodilators) and protective (cromolyn, topical steroids) drug therapy in infants and children with bronchial asthma. A successful therapy should ensure a physiological development of the child.

Adolescent↗
PubMed1992

A new baby-spacer device for aerosolized bronchodilator administration in infants with bronchopulmonary disease.

The response of salbutamol (Ventolin, Glaxo), topically administered from a metered dose inhaler (MDI) through a new baby-spacer-device (Babyhaler, Glaxo) was studied in 14 infants (8 wheezy infants, 3 infants with cystic fibrosis and 3 infants after respiratory distress syndrome), age 2.9-18.8 months. Changes in thoracic gas volume (TGV) as an estimate of pulmonary hyperinflation and changes in airway conductance (Gaw) as an estimate of bronchial obstruction were assessed by whole-body plethysmography. After baseline measurements, 1 puff of 100 micrograms salbutamol was given repeatedly at 5 min intervals until 600 micrograms have been inhaled and TGV and Gaw were measured after each inhalation at 5, 10, 15, 20, 25 and 30 min. Significant improvement in lung function was achieved in 57.1% of infants after 400 micrograms and in 92.9% of infants after 600 micrograms salbutamol. The study shows usefulness of bronchodilator treatment in infants with bronchopulmonary disease by a system with a MDI and baby-spacer-device. However a special dose-time relationship must be respected.

Albuterol↗
PubMed1992

Genotype/phenotype association in cystic fibrosis: analyses of the delta F508, R553X, and 3905insT mutations.

A striking clinical phenomenon of cystic fibrosis is the heterogeneous disease expression. It must therefore be assumed that the nature of the mutations associated with cystic fibrosis might partly determine the phenotypic manifestations. The relation between the cystic fibrosis mutations delta F508, R553X, and 3905insT and clinical parameters such as sweat test electrolytes, age at chronic Pseudomonas aeruginosa colonization, Chrispin-Norman x-ray scores, and relative underweight have been investigated in 45 patients homozygous for delta F508 (delta F2), in 12 compound heterozygotes for delta F508/R553X (delta F1/RX1), in three R553X homozygotes (RX2), and in 13 patients compound heterozygous for delta F508/3905insT (delta F16). We have found significant differences between the genetically defined subgroups concerning the mean age at onset and the cumulative incidence of chronic P. aeruginosa colonization and Chrispin-Norman x-ray scores. The significant results as well as some trends regarding the relative underweight demonstrate a milder clinical course in R553X heterozygotes and more severe disease in the delta F16 group compared to delta F508 homozygotes. The three patients homozygous for R553X presented with a two-stage course showing mild progression before P. aeruginosa infection and as severe a course as the delta F16 patients after P. aeruginosa colonization at the age of 12 y. The findings presented here indicate that specific mutations can influence the severity and progression of the disease, implicating the importance of mutation and haplotype analyses. However, wide variations within the genetically homogeneous subgroups illustrate that other determinants of the clinical status do exist.

Adolescent↗
PubMed1991

[Cystic fibrosis in changing times. Clinical aspects, basic defect and molecular biology aspects].

Life quality of patients suffering from cystic fibrosis (CF) has been significantly improved by early diagnosis and advanced therapy during the past three decades. Today, an increasing number of severely affected patients reach adult life no longer requiring the care of a pediatrician but of a specialist for internal diseases. The CF gene has recently been cloned and the most common defect defined, thus providing prenatal diagnosis and carrier detection in CF families. Although the identification of the CF gene is expected to have important clinical consequences, including new therapeutic perspectives, in the distant future, the present therapeutic concept must aim at early treatment of lung disease and pancreatic insufficiency. Intensive therapy, however, is for the patient's lifetime and requires adequate individual control.

Adolescent↗
PubMed1991

IgE hidden in immune complexes with anti-IgE autoantibodies in children with asthma.

Serum levels of IgE, anti-IgE autoantibodies (Abs), and IgE/IgG anti-IgE immune complexes (ICs) were measured in 110 children with asthma and 90 healthy control children. Significantly enhanced levels of IgE/anti-IgE IC were detected in children with asthma. However, only a weak correlation was found between anti-IgE auto-Ab serum levels and the degree of lung function abnormalities in children with asthma. However, children with asthma with low serum IgE levels had elevated IC serum levels of IgE/anti-IgE auto-Abs, suggesting that IgE might be hidden within these ICs and is therefore not measurable in vitro. The significant elevation of IgE/anti-IgE IC serum levels raises the question whether IgE within ICs is neutralized or might still be involved in immunologic mechanisms responsible for clinical symptoms of bronchial asthma.

Adolescent↗
PubMed1991

Activated human polymorphonuclear leucocytes reduce rabbit papillary muscle function: role of the CD18 glycoprotein adhesion complex.

STUDY OBJECTIVE: The aim was to determine if human polymorphonuclear leucocytes activated by human recombinant C5a (hrC5a) reduce the contractile function of the isolated papillary muscle and if this response depends upon the functional integrity of the CD18 glycoprotein adhesion complex. DESIGN: Human neutrophils with or without pretreatment with monoclonal antibodies to the CD18 adhesion complex were added to organ baths containing isolated papillary muscles of the rabbit and activated with hrC5a. Changes in papillary muscle function were measured. EXPERIMENTAL MATERIAL: 52 right ventricular papillary muscles isolated from rabbit and neutrophils isolated from human whole blood were used. MEASUREMENTS AND MAIN RESULTS: Neither neutrophils nor hrC5a alone reduced papillary muscle function, but activation of neutrophils with hrC5a provoked reduction in myocardial contractility. This correlated with the degree of neutrophil stimulation, assessed by cell aggregation. Pretreatment of neutrophils with antibodies to the CD18 adhesion complex significantly attenuated the neutrophil induced contractile impairment. CONCLUSIONS: Activated human neutrophils can impair contractile function of papillary muscles, which is dependent upon adhesion of the leucocytes to the muscle via the CD18 complex.

Animals↗
PubMed1991

Short-term effect of albuterol, delivered via a new auxiliary device, in wheezy infants.

In a double-blind, placebo-controlled study, the response of lung function to albuterol, topically administered by a metered-dose inhaler (MD) through a baby-adapted auxiliary device, was evaluated in 36 wheezy infants (1.6 to 25.2 months of age; median 8.1 months). The auxiliary device contains an air chamber of 350 ml and two low-resistant valves separating the inspiratory from the expiratory line. After baseline lung function measurements by infant whole-body plethysmography, the patients were randomly assigned to inhale either three times two puffs albuterol (100 micrograms/puff) or three times two puffs placebo at 5-min intervals. Changes in the degree of pulmonary hyperinflation, estimated by thoracic gas volume (TGV) and/or in the degree of bronchial obstruction, estimated by thoracic gas volume (TGV) and/or in the degree of bronchial obstruction, estimated by airway conductance (Gaw), were measured at 5-min intervals for up to 30 min. TGV and Gaw were expressed as standard deviation scores (SDS) of values predicted, and patients improving TGV and/or Gaw more than 2 SD were considered responders. In comparison with placebo, a significant percentage improvement in TGV (by the mean 26 to 53%) and a significant percentage improvement in Gaw (by the mean 34 to 51%) could be found in the active treatment groups. The study documents the usefulness of a new auxiliary device for the administration of aerosolized bronchodilators to wheezy infants.

Aerosols↗
PubMed1990

Patient education in asthmatic children.

The major goal of all diagnostic and therapeutic efforts in childhood asthma is to prevent progression of lung disease into adulthood. To improve the uncomfortable situation of underdiagnosis and undertreatment and to lower the risk of acquiring irreversible lung damage, an optimal co-working relationship between family doctor and parents, and a patient education program toward that end, is essential.

Asthma↗
PubMed1990

Abnormal 3,4-dihydroxyphenylalanine (dopa) concentrations in plasma and urine of patients with cystic fibrosis.

Plasma and urine concentrations of the free amino acid 3,4-dihydroxyphenylalanine (dopa) were determined in a blind study in 16 children and adolescents with cystic fibrosis (CF), eight heterozygote parents of these children and in 11 healthy subjects who served as controls. To exclude any drug interference with catecholamine metabolism and to evaluate a tentative basic metabolic alteration in cystic fibrosis, the same determinations were done in 11 newly diagnosed infants (age 1-84 months). Free plasma dopa was significantly (P less than 0.01) elevated in CF (27.0 +/- 6.1 nmol l-1 vs. 19.1 +/- 5.0 nmol l-1 in the controls); heterozygotes had the lowest concentration: 11.5 +/- 5.8 nmol l (P less than 0.01 compared with normals). Increased plasma dopa concentrations were measured in the newly diagnosed infants (35.4 +/- 16.9 nmol l-1). Renal dopa clearance was the same in cystic fibrosis (9.26 +/- 5.71 ml min-1 1.73 m-2) and controls (10.87 +/- 2.46 ml min-1 1.73 m-2). A concomitant elevation of metabolic products as dopamine and noradrenaline in plasma and urine was noticed. These data are consistent with a dopa abnormality in this genetic disease.

Adolescent↗
PubMed1990

Polymorphonuclear leukocytes reduce cardiac function in vitro by release of H2O2.

Polymorphonuclear leukocytes (PMNs) have been implicated in postischemic myocardial injury and associated derangements in contractile function. To examine the direct effects of PMNs on cardiac function, isolated right ventricular papillary muscles of the rabbit were exposed to increasing concentrations of purified rabbit PMNs in the presence of cimetidine. PMNs induced a significant concentration-dependent decrease in contractile function, where 5 x 10(5) PMNs/ml reduced contractile force to 75 +/- 2.1% of control (vs. 95 +/- 5% for time control; P less than 0.005). Similar decreases were also observed for peak positive and negative first derivatives of contractile force. The degree of PMN-induced contractile dysfunction correlated with the activity of the PMNs in an aggregation assay (r = 0.82, P less than 0.01). The loss of contractile function in response to PMNs was attenuated by catalase, which metabolizes H2O2, but not by superoxide dismutase, a scavenger of the superoxide anion. PMNs can convert H2O2 to either the hypochlorite anion or the hydroxyl radical, which are removed by methionine or mannitol, respectively. However, these scavengers did not ameliorate the PMN-induced loss of cardiac function. Exposure of papillary muscles to H2O2 resulted in a concentration-dependent decrease in contractile function where 100 microM reduced contractile force to 78 +/- 4%, an effect prevented by catalase. Thus PMNs reduce the contractile function of isolated papillary muscles probably by the release of H2O2.

Animals↗