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Biomedical subjects

D Reinhardt

Publications and source records attributed to D Reinhardt.

At least 145 records · Page 8Linked to original sources
PubMed1986

A new radiographic method for cardiac output and cardiac shunt determination in vivo.

The present paper describes a new method for the measurement of cardiac output (CO) and cardiac shunt (CS). The CO method is based on the accurate determination of the concentration of the indicator in large vessels. For the measurement of the left to right shunting volumes, a double tracer technique is used by which radioactively labeled transferrin or erythrocytes are applied together with radioactively labelled human-serum-albumin (HSA) microspheres. The results obtained using these methods were compared with the data obtained by invasive methods. High correlation of both sets of data suggests that the proposed methods might provide an excellent extension of noninvasive procedures in the first months of a childs life.

Adult↗
PubMed1986

[Postnatal development of the sympathoadrenergic system in premature and newborn infants].

Autonomic regulatory mechanisms and some metabolic functions are predominantly influenced by the sympathetic nervous system. Premature and mature newborns show a high variability and a low adaptability of the sympathetic nervous system. In order to investigate whether sympathetic systems are completely developed at birth or underly a postnatal maturation process we have determined plasma levels of adrenaline and noradrenaline as well as the density and affinity of alpha- and beta-adrenoceptors on thrombocytes and lymphocytes in pre- and mature newborns and adults. Catecholamines were determined by means of a radioenzymatic method, number and affinity of adrenoceptors by use of the radioactive labelled antagonists 3-H-Yohimbine and 125-I-Cyano-Pindolol. Beta-adrenoceptor responsiveness was assessed by measurement of cyclic AMP in lymphocytes before and after stimulation of beta-adrenoceptors by isoprenaline. A linear relationship occurred between the gestational age and the number of adrenoceptors on lymphocytes, whereas the alpha-adrenoceptors on thrombocytes showed no age dependency. The basal content of cyclic AMP and the accumulation in response to beta-adrenoceptor stimulation by isoprenaline was significantly lower in newborns than in adults. Since noradrenaline and adrenaline plasma levels were not significantly different in newborns and adults it is assumed that the low density of beta-adrenoceptors in premature and mature newborns is due to a postnatal maturation and not to a "down regulation" by circulating catecholamines. Our results suggest that an immaturity of beta-adrenoceptors is involved in the poorly developed adaptive control in newborns.

Adult↗
PubMed1986

[Defects of IgG subclasses as a cause of severe, recurrent respiratory tract infection].

IgG Immunoglobulins can be differentiated into four subclasses with different structures and functions. Partial or complete defects of one or two subclasses can be related to an impaired immune defence. We describe four children with severe recurrent bacterial airway infections. Two children had developed bronchiectasia following recurrent bronchopulmonary inflammation. Prior to diagnosis of IgG subclass deficiency other common causes of recurrent airway infections were excluded. Defects of IgG 2 or IgG 4 antibodies as well as of both classes were found with compensatory elevation of IgG 1 and IgG 3. In repeated sputum cultures haemophilus influenzae and staphylococcus aureus were isolated. This might be due to an impaired antibody production against special antigens as alpha-toxin of staphylococcus or capsular polysaccharide of haemophilus influenzae. The four cases demonstrate that in children with severe recurrent airway infections including bronchiectasia and otitis media defects of IgG subclasses have to be considered. Diagnosis should be proved by repeated determinations of blood levels after exclusion of other common causes for infections. Diminution of IgG subclasses without clinical symptoms of airway infections is also possible. If diagnosis seems to be certain intravenous substitution with 7 s gammaglobulin beside symptomatic antibiotic therapy is recommended.

Child↗
PubMed1986

[Peculiarities of drug therapy in childhood].

The age of the patient is one of the major determinants of drug efficacy due to certain anatomical, physiological, biochemical and behavioral characteristics of different age groups of the pediatric population. Qualitative and quantitative differences in pharmacokinetics and pharmacodynamics of drugs should be considered before dosage regimens can be established. Differences may occur in each age group, but may be even greater in newborns. Nevertheless, the maturation from the newborn towards adulthood proceeds through a continuum and thus involves also other age groups. Pediatricians are aware of this situation. But only for a small fraction of drugs used in newborns and infants clinical-pharmacological data are available, and drug instructions often contain disclaimer statements against the use in children. In pediatric intensive care units newborns and infants often receive drugs which have not been evaluated before within this age group. According to epidemiological data it has to be assumed that 30% of neonates in neonatal care units develop adverse side effects, which may originate from the drug itself or from drug interactions. Drug trials are completed or underway when new approaches to therapeutic interventions are developed for pediatric disease states. Examples for the development of new therapeutic interventions are for instance the use of theophylline for the prevention of apnoes in prematures, the use of indomethacin for the closure of a patent ductus arteriosus, or the specific advances of cancer chemotherapy in childhood. However, there is no doubt that a complete interplay between clinical, ethical and legal aspects renders the task of studying the effects of drugs in children more difficult than in the case of adults.

Apnea↗
PubMed1985

[Is the use of adriamycin (doxorubicin) limited by its cardiotoxicity?].

Adriamycin (doxorubicin), one of the most active cytotoxic antineoplastic agents, can cause heart failure. This side effect is dose-dependent, the frequency of heart failure being 3% at a cumulative Adriamycin dose of 400 mg/m2 and 18% at 700 mg/m2. It is assumed that Adriamycin, or other anthracycline derivatives, are still active when the cardiotoxic level is reached. In this retrospective study of 171 patients with various metastatic malignant tumors, the total dose of Adriamycin given to the patients and the reasons for withholding the treatment have been analyzed. Overall, among the 171 patients treated by Adriamycin-containing combination chemotherapy, 54 objective remissions (31%) were observed. Remissions were more frequent in untreated patients (52%) than in previously treated patients (20%). In 36 of 54 patients the disease progressed before the cumulative cardiotoxic level was reached. Adriamycin could be discontinued in only 18 patients still in remission. 8 of 171 patients received more than 450 mg/m2 Adriamycin without cardiotoxic side effects being observed. Among the 171 patients, cardiotoxicity probably related to anthracyclines developed in 5 cases (3%), in all cases at a level below 450 mg/m2. These results suggest that in most cases Adriamycin becomes inactive before the dose-limiting cumulative cardiotoxic level is reached.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Comparison of the serum protein binding of digoxin in premature and mature newborns, infants and adults.

Infants require higher therapeutic doses (per unit body weight and surface area) and also tolerate higher doses of digoxin than adults. In contrast premature and even mature newborns are more susceptible to digoxin intoxications. Serum protein binding contributes to the apparent volume of distribution. Since the volume of distribution for digoxin shows an age-dependency, the present study was designed to determine the plasma protein binding of digoxin in premature and mature newborns as well as in infants and adults. Using the equilibrium dialysis method the fraction of digoxin bound to serum protein averages 30% in all groups studied. Thus protein binding could not account for the differences in dosage and susceptibility of digoxin in newborns and infants as compared to adults.

Adult↗
PubMed1985

[Pharmacokinetics and pharmacodynamics of proxyphylline in asthmatic children].

In 15 asthmatic children and 3 healthy adult volunteers the pharmacokinetics and pharmacodynamics of proxyphylline under oral treatment, and the pharmacokinetics after intravenous administration were determined. The concentration-time-courses after intravenous application could best be fitted to an open 2-compartment model whereas the pharmacokinetics after oral treatment followed an open 1-compartment model. Under oral administration great inter- and intraindividual variances of the serum levels occurred. These differences which showed no age-dependency were suggested to be due to variations of the absorption velocity and the elimination half-lifes. In order to evaluate the curative efficacy of proxyphylline on lung function parameters all children had to undergo a whole body-plethysmography. No significant antiobstructive effects on the relevant baseline ventilation parameters could be observed. The protective efficacy of proxyphylline was determined in asthmatic children who developed an exercise induced asthma after a 7 minutes run. Only in 3 of 11 children a significant reduction of the enhanced airway resistance occurred. No correlation between serum levels and the protective effects was found. The present results show that there is no positive association between pharmacokinetics and pharmacodynamics of proxyphylline in asthmatic children. A safe antiobstructive therapy appears to be impossible within the dose range recommended so far.

Administration, Oral↗
PubMed1984

Age-dependency of alpha- and beta-adrenoceptors on thrombocytes and lymphocytes of asthmatic and nonasthmatic children.

Among the possible mechanisms which may cause wheezing or asthmatic episodes a genetically determined beta-adrenoceptor blockade and a hyperresponsiveness of alpha-adrenoceptors has been postulated. Evidence to support this hypothesis stems from an increased bronchial sensitivity to beta-blockers, a reduced formation of cyclic AMP in response to beta-adrenergic stimulation and enhanced alpha-adrenergic responses in asthmatic subjects. The recent development of techniques for measuring the specific, high-affinity binding of radiolabeled alpha- and beta-adrenergic antagonists made it possible to study alpha- and beta-adrenoceptors in vitro. Based upon the assumption that a change in the number and/or affinity of adrenergic receptors might be a general phenomenon, we have performed alpha- and beta-receptor binding studies on lymphocytes and platelets from wheezing infants and asthmatic children as well as of infants, children, and adults not suffering from these diseases. Using 125[I]-cyanopindolol (ICYP) and 3[H]-yohimbine (HYOH) as highly specific ligands for alpha- and beta-adrenoceptors, the following results were obtained: Lymphocytes and platelets from control subjects and asthmatics bound similar amounts of ICYP and HYOH and thus showed no differences either in the number or the affinity of alpha- and beta-adrenoceptors. Lymphocytes and platelets of wheezing and nonwheezing infants also bound the same amounts of the radioligands. In asthmatic children receiving 4 X 2 puffs salbutamol beta-adrenoceptors were down-regulated and this may mimic beta-adrenoceptor blockade. When subjects were divided into four categories according to age (0-5, 5-10, 10-20 years, adults) the number of beta-adrenoceptor binding sites showed an age-dependent increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

The dyskinetic cilia syndrome in childhood. Modifications of ultrastructural patterns.

The syndrome of cilia dyskinesia is known as a heterogenous ciliary dysfunction caused by morphological defects of the dynein arms, the nexin links, the radial spokes and by the transposition of microtubules. Supernumerary tubules have been regarded as acquired morphological defects on the background of other bronchopathies. The report of a 9-year-old girl with the clinical signs of ciliary dyskinesis is considered to be an attribution to the clinical and pathological features of this syndrome. The girl's history of chronic bronchopulmonary infections and nasal polyposis resistant to therapy made her suspected to be ill of Kartagener's syndrome. The results of ultrastructural investigations of the mucosa from ciliated epithelium revealed a ciliary structural defect in the bronchi as well as in the nose and the sinuses with supernumerary microtubular doublets and singles, a decentration of the central tubules and shortened dynein arms. The regularity of the electron optical abnormalities implicates a systemic disorder of ciliated epithelium, which is to be summarized to the syndrome of cilia dyskinesis.

Bronchi↗
PubMed1984

[Pulmonary dysplasia in infancy. Pathogenesis, pneumologic course studies and therapy possibilities].

Some premature and mature newborns who require intermittent positive airway pressure (IPPV) and high oxygen concentrations for respiratory distress syndrome develop characteristic damage of bronchi and bronchioles termed broncho-pulmonary dysplasia (BPD). According to the radiographic findings the changes are categorized into four progressive stages. Stage 1 describes a radiographic feature with a pattern of fine, faint granularity as it is characteristic for the hyaline-membrane-syndrome. Stages 2 to 4 represent diffuse interstitial emphysema, a bubbly appearance of the lung, atelectasis and a progressive fibrosis. Electronmicroscopic investigations of bronchial imprints could demonstrate a rarefication of the cilia and a ciliary damage which took the form of compound cilia. In addition, a marked increase of goblet cells in the bronchial mucosa as well as a metaplasia of the epithelial cells was present. These findings may be a prerequisite for chronic infections, and perpetuate a cycle which may result in chronic obstructive airway disease. The significance of bronchial and bronchiolar injury in children with BPD is said to be due to IPPV, high inspiratory oxygen concentrations, high fluid intake, vitamin E deficiency or an increased intrapulmonary pressure secondary to a patent ductus arteriosus. When pulmonary mechanics were measured in a baby-body-plethysmograph a high pulmonary resistance and a low dynamic compliance occurred at the first investigation after IPPV or oxygen administration. On re-examination there was a strong tendency to normalisation of x-ray findings and pulmonary mechanics, depending upon the time which elapsed between ventilation and re-examination. Current therapy has to be symptomatic and may include secretolytics, glucocorticoids and bronchodilators. The preventive interventions have to take into consideration ventilation techniques, restrictions in O2 and fluid intake.

Bronchi↗
PubMed1984

The relationship between pharmacodynamics and pharmacokinetics in asthmatic children receiving a sustained-release formulation of theophylline.

Pharmacodynamic response as well as serum and saliva concentrations of theophylline were monitored in 15 children under a long term theophylline treatment. Respiratory parameters, such as vital capacity and total bronchial resistance all related to bronchodilatation, were measured by use of a bodyplethysmograph. Measurements were performed before treatment and during the steady state with respect to serum levels. Due to small differences between peak and trough concentrations, no correlations between serum concentrations and respiratory parameters were found during the steady state. However, some important respiratory parameters exhibit considerable differences with respect to pretreatment values. In conclusion, one can state that during the steady state, theophylline exerts a constant influence on bronchodilatation which depends only slightly on the concentration range achieved.

Adolescent↗
PubMed1983

Capillary gas chromatography of fatty acid methyl esters from human milk lipid subclasses.

The fatty acid (FA) composition of the human milk lipid subclasses sphingomyelin, phosphatidylcholine, phosphatidylethanolamine and cholesterol esters (CE) were analysed by capillary gas chromatography (GC) on wall-coated open-tubular glass columns. Compared with GC on packed columns, capillary GC was found to be ten times more sensitive (0.1 microgram of each individual FA methyl ester could be quantified), and the time needed for the analysis could be reduced by a factor of five. The reproducibility of the analysis was good relative standard deviation (4-7%) and comparable to that obtained by packed column GC.

Cholesterol Esters↗
PubMed1983

Influence of beta-receptor-agonists and glucocorticoids on alpha- and beta-adrenoceptors of isolated blood cells from asthmatic children.

The most attractive "adrenergic theory" has proposed that in asthmatic patients the bronchial hyperreactivity might be caused by a decreased beta-receptor and an increased alpha-receptor responsiveness. Based upon the assumption that an abnormality of adrenergic receptors might be a general phenomenon, we have performed receptor-binding studies on lymphocytes and thrombocytes from asthmatic children who had and had not undergone treatment with beta-receptor agonists and/or glucocorticoids. Iodo-cyano-pindolol and tritium-labeled yohimbine were used as beta- and alpha-receptor ligands. The following results have been obtained: 1) The number and affinity of alpha- and beta-adrenoceptors on thrombocytes and lymphocytes showed no significant differences in asthmatic children and their age-matched controls. 2) In vivo treatment of asthmatic children with beta-receptor agonists immediately reduced the number of beta-receptors ("down regulation"). A reversal of the number of beta-receptors occurred within 1 day after cessation of the therapy. Although it appeared that some asthmatics with severe asthma have a reduced number of beta-receptors, in vivo treatment with beta-receptor agonists thus might mimic a beta-receptor blockade. 3) High-dose treatment with glucocorticoids increased the number of beta-receptors but left the alpha-receptors unaffected.

Adolescent↗
PubMed1983

Modified pharmacokinetics of I-asparaginase from E coli by formation of specific antibodies to I-Asparaginase of different immunoglobulin classes in children with acute lymphocytic leukemia.

Twenty-four children (2-15 years old) with acute lymphocytic leukemia (ALL) were treated intravenously with 1-Asparaginase (1-Asp) isolated from E coli at a dose of 3,000 U/kg body weight four times every third day as part of a standard chemotherapy protocol. Sera of patients were obtained prior to each infusion, immediately following each infusion, and at defined intervals (2, 4, 12, 24, 36, and 48 hours postinfusion) and assayed for 1-Asp enzymatic activity.1-Asp antigen, and anti-1-Asp antibodies. Results indicate that the in-vivo elimination half-life of 1-Asp activity in patients with no demonstrable specific antibody is approximately 5.5 hours. Half-life of enzymatic activity in patients with a moderately high level of specific antibodies (pre-infusion) was prolonged (approximately 7.0 hours) in comparison to the group with no specific antibodies. In patients with very high levels of specific antibodies several infusions could not be completed because of apparent anaphylactic reactions. In-vitro studies showed that experimental immune complexes made of 1-Asp and the IgG-fraction of a rabbit-anti-1-Asp antibody under conditions of antigen excess still exhibit enzymatic activity. On the basis of this observation we conclude that specific antibodies to 1-Asp in vitro and, most likely, in vivo do not inactivate the drug but may lead to either delayed elimination of enzyme activity or, in the presence of high levels of specific antibodies, anaphylactic reaction.

Adolescent↗