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Biomedical subjects

D Reinhardt

Publications and source records attributed to D Reinhardt.

At least 127 records · Page 7Linked to original sources
PubMed1990

Histamine release test in comparison to standard tests in diagnosis of childhood allergic asthma.

An allergen-specific histamine release test (HR) was investigated in 93 children with a history of extrinsic asthma and suspected allergy to house dust mite or fungi. For both allergy groups the correlations between HR and the bronchial provocation test were better than those between the inhalation test and prick test or RAST. It is concluded that, especially in childhood where performance of a bronchial provocation should be avoided because of its potential risk and required hospitalization, the HR test can represent a significant diagnostic aid.

Adolescent↗
PubMed1990

[IgG subclasses in healthy children and in children with frequent respiratory tract infections].

A group of 130 children presenting with frequent respiratory tract infections was examined for serum levels of IgG-subclasses IgG1, IgG2, IgG3 and IgG4 using radial immunodiffusion according to Mancini. Additionally a control group of 175 children not prone to infections was investigated. Both, low and high levels compared to controls were observed for IgG3 and IgG4. 11.5% of the children with frequent airway infections had IgG3 values below 2 SD below the mean for age compared to 2.8% in the control group (p less than 0.01). Likewise a low IgG4 level was observed more frequently in children prone to airway infections (9.8% versus 2.8% in control; p less than 0.05). IgG4 was undetectable (level less than 3.4 mg/dl) in 5 of the 175 control children. Despite an accumulation of low or undetectable IgG3 or IgG4 levels in children with frequent respiratory tract infections, no correlation between low IgG subclass-levels and the degree of the individual disease could be detected. Based on this lack of a simple causal relationship between frequent respiratory tract infections and the finding of low or undetectable IgG-subclass levels, an immunoglobulin replacement therapy has to be considered with reserve.

Adolescent↗
PubMed1989

The adrenergic system in lymphocytes from children with cystic fibrosis.

Several in vivo and in vitro studies have suggested that children suffering from cystic fibrosis (CF) might have a general defect of beta-adrenoceptors on the cell surface which might account for an unbalanced secretory process. In order to investigate if this view holds true, we determined the beta-adrenoceptor density and affinity on lymphocytes by means of radioligand studies using 125-iodo-cyano-pindolol (125-ICYP) in 20 children with CF. Cyclic AMP (cAMP) response was also investigated after specific beta-adrenoceptor stimulation with isoprenaline (IPN) and after direct stimulation of the adenylate cyclase with forskolin in lymphocytes. Children with CF and controls have identical numbers and affinities of beta-adrenoceptors on lymphocytes. The cyclic AMP response was identical in CF- and in age-matched control children regardless whether adenylate cyclase was stimulated directly or via beta-adrenoceptors. In conclusion, the data support the view that no general adrenoceptor or adenylate cyclase defect exists in CF. As several studies have found abnormal reactions to adrenergic stimuli in CF patients, we presume that there is a defect beyond the level of adrenergic receptors and cAMP which remains to be identified.

Adenylyl Cyclases↗
PubMed1989

Adrenoceptors and the lung: their role in health and disease.

alpha- and beta-Adrenoceptors have each been divided into two subgroups (alpha 1, alpha 2, beta 1 and beta 2). The basic mechanisms underlying the adrenoceptor/effector coupling are complex and vary for the alpha-, but not for the beta-subpopulations. Adrenoceptors of the bronchi and the lung show a special pattern of distribution and response, ensuring that the airway system works as a functionary unit. Dysfunctions of adrenoceptor-mediated effects have been suggested to contribute to some important paediatric disorders such as hyaline membrane syndrome, wet lung, bronchial asthma, cystic fibrosis, and pertussis. Drugs which act on the adrenergic system influence some of these disorders directly. Further studies applying modern techniques to receptor research are needed in order to clarify the basic mechanisms involved in receptor-mediated lung disorders and the activity of drugs in lung tissue.

Child↗
PubMed1989

Impaired formation of the second messenger cAMP in mononuclear blood cells of children with pertussis.

To determine the pathophysiologic significance of pertussis toxin (PT) on the human beta-adrenergic system, beta-adrenoceptor (beta-R)-density and cyclic AMP response of peripheral mononuclear blood cells (MN leukocytes) were studied in children during the paroxysmal stage of natural pertussis infection, after vaccination with pertussis monovaccine, and in controls. Isoprenaline-induced cAMP accumulation, measured in a protein-binding assay, was significantly reduced to about 25-50% in children during the first week of paroxysmal pertussis, compared with controls. In contrast, cAMP accumulation after stimulation of the adenylyl cyclase by forskolin was unaffected. The density and affinity of beta-R, estimated by 125I-cyanopindolol-binding studies, were not significantly altered. The suggestion that PT might impair the coupling of the beta-R signals to the adenylyl cyclase was confirmed by parallel in vitro studies on MN leukocytes from adults. These cells, when incubated with purified PT, showed a significantly diminished cAMP response to isoprenaline, whereas that to forskolin remained unaffected. As cAMP accumulation in response to prostaglandin E1 and hydrocortisone was also reduced, it appears that PT may directly affect G-proteins serving as signal transducers for several stimulatory receptors. In contrast to the actual disease, in children treated with pertussis monovaccine, cAMP accumulation as well as the beta-R were unaffected. It is concluded that in MN leukocytes obtained from children during the natural course of pertussis, as well as after incubation of normal MN leukocytes with PT, the stimulatory signal-transducing system for cAMP generation is inhibited.

Adenylate Cyclase Toxin↗
PubMed1989

[Surgical correction of bronchial stenosis: increased somatic development following elimination of the stenosis].

A 5 year old girl suffered from nearly total stenosis of the bronchus intermedius and exspiratory collaps of both main bronchi. Because of preterm birth she was postnatally intubated and mechanically ventilated for 6 weeks. Her somatic development was significantly retarded in comparison with the monozygotic twin, and pulmonary impairment increased again in the last preoperative year. By the combination of latest surgical technics (pericardial patch, interposition of a costal segment, fibrine glue) the bronchial abnormalities could be corrected successfully. In the first year after surgery catch-up growth was observed in the girl.

Aprotinin↗
PubMed1988

Glucocorticoid receptors in mononuclear blood cells and their correlation to endogenous and exogenous corticoids in healthy and asthmatic children.

The number and affinity of glucocorticoid binding sites in peripheral mononuclear cells (MNC) of asthmatic and healthy children were determined by a whole cell (3H)dexamethasone binding assay at 37 degrees C. Using HPLC determination, corresponding serum levels of non-protein-bound (free) cortisol, whole cortisol and cortisone as well as urine excretion of free cortisone and cortisol were assessed. The average number of binding sites (BS) per cell and the dissociation constant (KD) respectively, in atopic asthmatics (7768 +/- 666 BS/MNC resp. KD = 17.2 +/- 2 nM) did not differ from the values measured in our control group (8333 +/- 691 BS/MNC resp. 25.4 +/- 4.8 nM). Within the age range 1 month-15.8 years neither age-dependent changes nor sex-related differences in the number of binding sites or the KD values could be detected. Active or currently inactive asthmatics, and patients under different antiasthmatic drug regimes, had similar binding sites on MNC. No differences in serum levels of cortisol, cortisone and free cortisol or in free cortisol and free cortisone of 24-h urine samples were found between healthy children and asthmatics. After a short course of prednisolone therapy for an acute severe asthmatic attack the number of glucocorticoid binding sites in peripheral MNC decreased to an average of 4632 +/- 421 BS/MNC, whereas the dissociation constant did not change significantly (14.5 +/- 3.6 nM). The corticoid-hormone pattern in the serum, 24-h urine excretion, and the normal number and affinity of glucocorticoid receptors on peripheral MNC suggest that there is no primary, general impairment of glucocorticoid metabolism in asthmatic children.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Beta-adrenoceptor density and resolution of high and low affinity state on B- and T-cells in asthmatic and non-asthmatic children.

Beta-adrenoceptor binding in lymphocytes of asthmatic and non-asthmatic children and healthy adult volunteers was investigated with the radioligand 125-iodocyanopindolol (ICYP). Binding studies were performed with 4 to 5 different concentrations of ICYP. Receptor density and affinity were calculated by Scatchard plots. Resolution of beta-adrenoceptors into those of high and low affinity state was obtained from inhibition curves with salbutamol using Hofstee plots. Receptor density in B-cell enriched fractions was two to three-fold higher than in T-cells for all patients and volunteers studied (P less than 0.025). No difference in beta-adrenoceptor density on B and T-cells occurred neither in age-matched asthmatic and non-asthmatic children nor in adult volunteers. The affinity of beta-adrenoceptors did not differ for B and T-cells nor for the patients or volunteers studied. However, when two distinct binding states for beta-adrenoceptor agonists were obtained using salbutamol displacement curves it appeared that beta-adrenoceptors on T-cells were at a higher affinity state compared to those on B-cells in asthmatic and non-asthmatic children, as well as in adults. Since the ability of an agonist to activate adenylate cyclase correlates closely with the amount of high affinity receptor state formed in the presence of the agonist, increased intrinsic activity of the beta-adrenoceptor agonist on T-cells may be postulated. In conclusion, age-related control groups and determination of the B/T ratio are necessary for interpretation of beta-adrenoceptor changes in bronchial asthma.

Adolescent↗
PubMed1988

Phaeochromocytoma without symptoms: desensitization of the alpha- and beta-adrenoceptors.

A 16-year-old boy is described who had a relapse of a phaeochromocytoma 6 years after an initially successful tumour resection. The relapse was suspected after routine testing of urinary catecholamine excretion and was confirmed by scintigraphy with 123I-meta-iodobenzylguanidine, computed tomography and magnetic resonance imaging. The plasma norepinephrine level was 3082 pg/ml (normal less than 500 pg/ml); the plasma epinephrine level was in the normal range. Surprisingly, our patient had no symptoms, including hypertension. The density of the alpha- and beta-adrenoceptors on circulating blood cells was decreased. Postoperatively the plasma catecholamine levels were in the normal range. Three months after surgery the adrenoceptor density was almost normal. We conclude that the absence of clinical symptoms was probably due to desensitization of the adrenoceptors. After a successful operation to treat phaeochromocytoma, long-term monitoring of catecholamines is necessary to rule out an asymptomatic relapse.

Adolescent↗
PubMed1988

[Residues of active substances after consumption of contaminated food: status report on the evaluation of residues with examples of two drugs].

Pharmacokinetic models are presented for the computation of time courses of blood levels of drugs in man following the consumption of contaminated food. Mathematically, two linear systems of differential equations are set up for the donor organism (e.g., trout) and for the recipient, (e.g., man), where the first system generates the initial conditions for the second. Models of this kind are applied to the transfer of chloramphenicol to man via carp and trout (which had previously been administered this drug) and to the transfer of theophylline to infants via breast milk. Limiting concentration profiles are computed by constructing the most favourable and most adverse combinations of parameters with respect to drug elimination in both the donor and recipient organism.

Animals↗
PubMed1988

Density and agonist-promoted high and low affinity states of the beta-adrenoceptor on human B- and T-cells.

beta-Adrenoceptor binding on peripheral blood mononuclear cells (PBMC) of healthy adult volunteers was investigated using the radioligand 125iodo-cyanopindolol (ICYP). Saturation binding studies were performed with nine different concentrations of ICYP. Receptor density and affinity were calculated by Scatchard plots. Resolution of beta-adrenoceptors into those with high and low affinity state of the beta-adrenoceptor was obtained from inhibition curves with salbutamol using Hofstee plots. Receptor density on enriched B-cells ('B-cells') was two-fold higher than on enriched T-cells ('T-cells') (P less than 0.025). Affinity (KD values) of beta-adrenoceptors did not differ for B- and T-cells. However, when two distinct binding states for beta-adrenoceptor agonists were identified using salbutamol displacement curves, beta-adrenoceptors on T-cells presented more receptors in a high affinity state than those on B-cells (P less than 0.01). Since the ability of an agonist to activate adenylate cyclase is closely correlated with the ratio of low to high affinity states formed in the presence of the agonist, increased intrinsic activity for the beta-adrenoceptor agonist on T-cells may be postulated. In conclusion, determination of the B/T ratio is a prerequisite for interpretation of beta-adrenoceptor changes on peripheral lymphocytes in various diseases.

Adolescent↗
PubMed1988

Effects of the antiallergic drug ketotifen on bronchial resistance and beta-adrenoceptor density of lymphocytes in children with exercise-induced asthma.

In a parallel, double-blind, placebo-controlled study we investigated the effect of the antiallergic drug Ketotifen on bronchial resistance (determined body plethysmographically) and beta 2-adrenoceptor density of lymphocytes (determined by 125-iodo-cyano-pindolol binding) in asthmatic children suffering from exercise-induced asthma (EIA). In order to provoke EIA a test which involved running for 7 min was performed with 22 asthmatic children. 13 age-matched children not suffering from asthma served as controls. Control children showed a 30% increase in the number but not in the affinity of beta-adrenoceptors in response to a 7-min run. Asthmatic children with EIA showed no difference in the number and affinity of beta-adrenoceptors under resting conditions when compared with the controls. In contrast to what has been observed with control children, however, no increase in the number of beta-adrenoceptors in response to exercise was observed. A 1-week treatment with placebo neither affected the bronchoconstriction nor the number of lymphocyte beta 2-adrenoceptors. Ketotifen (2 X 1 mg/day for 1 week) protected asthmatic children from EIA, at least in part, and restored the up-regulation of beta-adrenoceptors in response to exercise in 9 of 14 children with EIA. However, no correlation between the serum concentration of Ketotifen and the number of binding sites could be found. It is therefore concluded that the preventive effect of Ketotifen in EIA might also involve mechanisms other than a recovery of the beta-adrenergic system.

Adolescent↗
PubMed1988

Status of plasma and erythrocyte fatty acids and vitamin A and E in young children with cystic fibrosis.

The fatty acid (FA) status in young children with cystic fibrosis (CF) was investigated. The FA composition of the plasma cholesterol esters (CE) and phospholipids (PL) and of the erythrocyte phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was estimated in 11 patients with CF and pancreatic insufficiency (median age, 3.0 years; range, 3 months to 7 years) and in 10 age-matched controls. Linoleic acid values ranged widely but were not significantly reduced in the patients. However, arachidonic acid (20:4w6) and docosahexaenoic acid were decreased in all lipid classes. The ratio of dihomo-gamma-linoleic acid to arachidonic acid (20:3w6/20:4w6) was significantly increased in the patients, indicating an impairment of FA metabolism (delta 5-desaturation). Plasma retinol concentrations were normal and did not differ between the supplemented patients and controls. Plasma total tocopherols and alpha-tocopherol and their ratios to total lipids were significantly reduced in the CF patients, but all values were within the normal ranges for the pediatric age group, and no child met the criterion for vitamin E deficiency.

Child↗
PubMed1987

Steady state pharmacokinetics, metabolism and pharmacodynamics of theophylline in children after unequal twice-daily dosing of a new sustained-release formulation.

This was an open-label study in 19 children aged 9-13 years, weighing 27-44 kg, with bronchial asthma. Twenty-four-hour steady-state concentrations of theophylline and its metabolites 1,3-dimethyl uric acid, 3-methyl xanthine and 1-methyl uric acid were assessed after daily dosing of 600 mg (ca 18 mg/kg/day) of the sustained-release theophylline micro-pellet sprinkle system BY158K, for 4 days. The dosing regimen used was an unequal twice-daily dose of 200 mg in the morning after breakfast and 400 mg in the evening after dinner. Twenty-four-hour peak expiratory flow (PEF) profiles were compared before treatment and at steady-state, along with lung function parameters after bronchial provocation. Mean values +/- SD (n = 16) of the steady-state characteristics were Cmin 6.8 +/- 2.1 mg/l, Cmax 14.5 +/- 4.8 mg/l and Cav 10.5 +/- 2.9 mg/l, the plateau time was 11.7 +/- 4.8 hr and peak-trough fluctuation and swing were 72 +/- 21 and 118 +/- 52%, respectively. There was an excellent reproducibility of theophylline pre-dose levels at corresponding time points of the 24-hr sampling period [r = 0.864 (p less than 0.001)]. Mean values +/- SD of the 24 hr average serum metabolite levels were 0.9 +/- 0.2 mg/1 for 1,3-dimethyl uric acid, 0.6 +/- 0.1 mg/1 for 3-methyl xanthine and 0.4 +/- 0.1 mg/1 for l-methyl uric acid. Lung function (n = 17) following bronchial provocation, improved in 10 children after theophylline treatment of 4 days, remained stable in 2 patients and deteriorated in 5 patients. Serum theophylline profiles and PEF profiles ran largely in parallel over the 24-hr period. Six children exhibited typical theophylline induced side-effects, headache (n = 3), nausea (n = 4), dizziness (n = 1), vomiting (n = 4), sleep disturbances (n = 1), pallor (n = 1) and tremor (n = 1), necessitating in 3 children one dose omission/reduction (n = 2) or subsequent dose reduction (n = 1). It has been shown that a twice daily dosing regimen with unequal doses of anhydrous theophylline (BY158K) is well suited to this population of fast metabolisers. The patients were well protected throughout the day, including the critical early morning hours.

Asthma↗
PubMed1987

[Chronic recurrent pneumonias in ossifying bronchial carcinoid tumor].

We describe the case history of a 13 year old boy with recurrent bronchitis and pneumonia over a period of 8 years. Because of the peculiar bronchoscopic finding of an osseous foreign body a chronical foreign body aspiration was considered likely, but not confirmed histologically. A bronchial carcinoid tumor with ossifications proved to be the cause of recurrent chest infections. Tumors arising from bronchial epithelia in childhood and adolescence are very uncommon, ossification in this age group is a rarity. In the eight years following the operation there has been no relapse.

Adolescent↗
PubMed1987

[Causative relations between infections and allergies in obstructive respiratory tract diseases in childhood].

Obstructive bronchitis of young babies and infants is most often caused by respiratory-syncytial (RS)- and parainfluenza viruses, to a certain extent by adenoviruses. In the school age-group rhinoviruses and to a smaller extent mycoplasma pneumoniae gain further importance. All the viruses may cause or deteriorate asthmatic attacks, as well as during common cold or on the basis of documented allergies. Proposed mechanisms of viral-infection-induced obstructive airway disease are distinct lesions of bronchial-epithelium, followed by enhanced allergen-resorption and sensitization of submucosal mast cells, establishing an allergy. Following epithelial discontinuation airway irritant receptors which are raised in sensitivity by viral toxins are exposed and stimulated. Via vago-vagal reflexes this leads to bronchoconstriction. Furthermore, in the development of bronchial hyperresponsiveness there may be participation of virus-induced blockage of adrenoceptors, basophilic and mast-cell release of mediators as well as induction of specific IgE antibodies against RS- and/or Para-influenza-viruses. Viral airway infections are supposed to influence the immunological response of T-lymphocytes and probably macrophages selectively, e.g. to regulate IgE-antibody production. Especially in children with an atopic family history the RS-viruses cause obstructive airway disease. During acute respiratory-virus infections using electron microscopy marked pathological changes of bronchial-epithelium can be demonstrated causing disturbance or even stopage of mucus-transport. These changes are fully reversible within weeks after airway infection. Although there is no doubt about a causative relation between respiratory-tract infection and allergy, hardly any prediction for development of asthma bronchiale in later life, after having suffered from virus-induced obstructive airway disease early in life, can be made.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗