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Biomedical subjects

R Kraemer

Publications and source records attributed to R Kraemer.

At least 19 recordsLinked to original sources
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↗
PubMed1990

Ventilatory inequalities, pulmonary function and blood oxygenation in advanced states of cystic fibrosis.

In 36 patients with cystic fibrosis (CF), aged 6.2-26.4 years, the relationship between functional lung deterioration and gas exchange characteristics was studied by backward stepwise discriminant analysis of 22 dependent variables, within 3 clinically defined severity degrees of the disease. The stratification was based on a general clinical score, a chest X-ray score and the relative underweight of the patients. Lung function testing included whole body plethysmography and multibreath nitrogen washouts (MBNW). Blood gas analyses were performed under room air (FiO2 = 0.21) and 100% oxygen breathing (FiO2 = 1.0). The clinical score correlated best with vital capacity (r = 0.776) and PaO2 at room air (r = 0.829); the X-ray score correlated best with PaO2 at room air (r = 0.768). Impairment of oxygenation characteristics was closely related to the degree of ventilation inequalities (MBNW) and the amount of trapped gases, both increasingly present from severity group I to III. In addition the calculated arterial-alveolar oxygen ratio (group I 0.47; group II 0.38; group III 0.29) as an estimate of intrapulmonary gas exchange deficiency revealed that only patients with mild lung involvement (group I) fulfil the functional conditions to achieve a paO2 of 70 mm Hg at room air, whereas patients with severer lung involvement (groups II and III) would need a FiO2 of 26.0 or 39.6, respectively, in order to have a sufficient oxygenation.

Adolescent↗
PubMed1990

Improvement from pulmonary hyperinflation and bronchial obstruction following sympathomimetics systemically given in infants with broncho-pulmonary diseases.

Functional disorders and efficacy of treatment with a beta-2-agonist salbutamol (Ventolin), 0.225 mg/kg bodyweight, systemically given, were evaluated by infant whole-body plethysmography in 60 infants (64 data sets) with broncho-pulmonary disease belonging to three diagnostic groups: 24 survivors after respiratory distress syndrome, 21 patients with recurrent wheezing, and 15 infants with cystic fibrosis. The values of thoracic gas volume (IGV) and airway resistance (Raw) prior to the drug administration showed a scattered distribution, which was unrelated to the 3 diagnostic groups. Therefore, stratification into 4 functional groups was performed. In 25 tests (22 infants) normal lung function (TGV less than 130% pred., Raw less than 130% pred.); in 16 tests pulmonary hyperinflation (TGV greater than 130% pred., Raw less than 130% pred.); in 10 tests hyperinflation and bronchial obstruction (TGV and Raw greater than 130% pred.); and in 13 tests (12 patients) bronchial obstruction (TGV less than 130% pred; Raw greater than 130% pred.) were found. The response to beta-2-agonists was evaluated by vector analysis (circular statistics) revealing different response groups. With respect to the initial lung function abnormality and due to a stratification into different "response groups", beta adrenoreceptor agonists showed a volume-response (decrease in end-expiratory level) in 63% of infants with pulmonary hyperinflation, a flow response (improvement of airway resistance) in 54% of infants with predominantly bronchial obstruction and a mixed-response (decrease of TGV and Raw) in 70% of infants with mixed functional abnormalities, at least if the drug is given systemically. However, distinction into functional groups and its response to a sympathomimetic agent is only possible when both, changes in TGV and concomitant changes in Raw are accurately assessed.

Airway Resistance↗
PubMed1989

[Effect of air pollutant burden on healthy children and children with lung diseases in southern Ticino].

To investigate the effects of air pollution on the respiratory health of children, a study was undertaken in the southern part of Switzerland covering 312 school children who lived in two zones with significantly different concentrations of NO2. In the more urban area the mean NO2 measured over a period of 10 months was 36.2 +/- 9.5 micrograms/m3 (25 14-day values greater than 40) compared to the mean of the second, rural area of 26.2 +/- 10.4 micrograms/m3 (6 14-day values greater than 40). Respiratory health was evaluated by determination of bronchial reactivity to Carbachol in 5 diagnostic groups (healthy: 109; healthy with positive family history of atopy: 60; allergic but not asthma: 59; asthma: 55; and "unclear cough": 29) by the technique of group specific sampling. The study shows differences in the incidence of bronchial hyperreactivity in children (PD65 less than 900 micrograms Carbachol). Within the 5 diagnostic groups, however, this distinction was significant only in the group of healthy subjects (p less than 0.005). In the other diagnostic groups the influence of the various trigger factors such as respiratory tract infections, allergen exposure, parental smoking and (last but not least) drug treatment seems to be as important as that of air pollution.

Adolescent↗
PubMed1989

[Characteristics of inspiratory flow-volume curves in children with bronchial asthma and patients with cystic fibrosis].

The characteristics of the inspiratory and expiratory flow-volume curves were measured in 77 children with bronchial asthma and 30 patients with cystic fibrosis (CF) in comparison with 19 healthy children. The aim was to explore how for children with lung diseases fulfil the physiological conditions to generate sufficient flow for optimal use of "breath actuated inhalation devices" such as the Spinhaler, Rotahaler, Turbuhaler and Diskhaler. No correlation was found between the values of inspiratory flow-volume curves and conventional lung function parameters either in healthy children or in those with lung diseases. The majority of the patients (78.6%) showed a maximal inspiratory flow, at 50% of vital capacity, (MIF50) of more than 1 l/sec, irrespective of the type of functional disorder (pulmonary hyperinflation, bronchial obstruction or both). The remaining patients (21.4%), comprising mainly patients with CF, did not reach this limit. The flows needed for correct use of the different inhalation devices vary greatly (0.4-1.6 l/sec) and the criterion of a flow lower than 1 l/sec is only fulfilled by the Turbuhaler (0.4 l/sec), the Rotahaler (0.65 l/sec) and the Diskhaler (0.8 l/sec). In contrast, the Spinhaler needs a flow of at least 1.6 l/sec. For practical purposes it seems that an MIF50 of more than 1 l/sec could be used as criterion in the indication for such inhalation devices.

Adolescent↗
PubMed1989

Antipseudomonal therapy in cystic fibrosis: aztreonam and amikacin versus ceftazidime and amikacin administered intravenously followed by oral ciprofloxacin.

In order to determine the optimal antipseudomonal therapy in patients with cystic fibrosis aztreonam plus amikacin was compared to ceftazidime plus amikacin, and these two-week hospital regimens were followed by oral ciprofloxacin given for four weeks. Fifty-six cases of acute pulmonary exacerbation of the disease in 42 patients associated with isolation of Pseudomonas aeruginosa from the sputum were randomly treated with either aztreonam or ceftazidime (300mg/kg/day i.v.; maximum daily dose 12g) in combination with amikacin (36mg/kg/day i.v.; maximum daily dose 1,500mg). Other aspects of the two-week treatment were constant. The two therapy groups were comparable in all respects. Both regimens were well tolerated and resulted in similar improvements in clinical, bacteriologic, radiologic and laboratory findings, and pulmonary function. Fifty patients could be reevaluated after subsequent outpatient therapy consisting of oral ciprofloxacin (30mg/kg/day; maximum daily dose 1,500mg) given for four weeks. During this period, the clinical and laboratory improvements persisted, and the rate of eradication of Pseudomonas aeruginosa from sputum decreased from 62% to 34%. Ciprofloxacin was well tolerated and there was no drug toxicity or serious adverse effect. In the 25 prepubertal patients there was neither subjective nor objective evidence of skeletal drug toxicity. In patients with cystic fibrosis, aztreonam or ceftazidime in combination with amikacin represents an effective and safe systemic anti-pseudomonal therapy. Subsequent oral ciprofloxacin therapy for four weeks prolongs the beneficial effects and is well tolerated.

Adolescent↗
PubMed1989

Neutrophils delay functional recovery of the post-hypoxic heart of the rabbit.

A postischemic contractile dysfunction termed myocardial stunning has been described in vivo and is attributed, in part, to the generation of oxygen-derived free radicals and the presence of neutrophils. An analogous contractile derangement occurs in the posthypoxic heart in vitro. This study determined the role of neutrophils in hypoxia/reoxygenation-induced cardiac dysfunction in the isolated buffer-perfused rabbit heart utilizing a recirculating system with or without neutrophils present. In control hearts perfused with a neutrophil-free buffer, reoxygenation after 20 min of hypoxia was associated with a slow recovery of contractility which returned to prehypoxic values by 30 to 45 min. Although perfusion with buffer-containing neutrophils did not affect the hypoxia-induced decrease in myocardial contractility, the recovery of contractile function during subsequent reoxygenation was significantly diminished (P less than .01 vs. control), remaining depressed by 30 to 35% at 45 min. The myocardial neutrophil content increased approximately 2-fold in response to hypoxia and reoxygenation, as assessed using 51Cr-labeled neutrophils. The deleterious effects of neutrophil perfusion on cardiac function could not be attributed to neutrophil-mediated plugging of coronary vessels or enhanced myocellular damage. These results support the concept that neutrophils contribute to the cardiac dysfunction described in this model.

Animals↗
PubMed1989

Osmolality changes in nebulizer solutions.

Paradoxical effects (bronchoconstriction instead of bronchodilatation) have been reported after inhalation of beta2-mimetics in asthmatic children, and it has been suggested that this was due to osmolality and pH changes of the nebulizer solution. We tested commercially available nebulizer solutions and found osmolality changes after 5, 10 and 15 min of nebulization. Osmolality was measured in the nebulizer chamber and the airsteam of two types of jet nebulizers. When normal saline was nebulized chamber, from 282 +/- 7 mmol.kg-1 to 432 +/- 18 mmol.kg-1 resulted. Salbutamol ready made solution, and terbutaline respules were isotonic, whereas fenoterol, disodium cromogylcate (DSCG), beclomethasone dipropionate (BDP) and salbutamol (respirator solution 0.5%) were hypotonic (60-100 mmol.kg-1). When a mixture of sodium chloride (NaCl) and the drug solution (salbutamol, terbutaline, fenoterol) was nebulized for 10-15 min, the osmolality in the nebulizer cup increased to 420-500 mmol.kg-1. However, mixtures of the same beta 2-agonists with DSCG or with BDP remained hypo-osmolar. The same osmolality changes were present in the airstream. This study shows that after 10-15 min of nebulization osmotic changes occur in the nebulizer cup and airstream and that these changes differ according to the drug mixtures and the amount of the solution in the nebulizer chamber.

Adrenergic beta-Agonists↗