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Biomedical subjects

G Heimann

Publications and source records attributed to G Heimann.

At least 55 records · Page 3Linked to original sources
PubMed1992

Neonatal theophylline intoxication: pharmacokinetics and clinical evaluation.

The pharmacokinetics of theophylline and its metabolites, caffeine, 1,3-dimethyluric acid, 1-methyluric acid and 3-methylxanthine were studied in a 5-day old 1.3 kg premature neonate who accidentally received 180 mg theophylline in 26 h during treatment for bradycardia. Tachycardia, hyperventilation, increased diuresis, central nervous system excitation, an increase in blood glucose concentrations followed by a prolonged decrease and hypercalcaemia were the predominant clinical and laboratory manifestations. The patient responded to supportive care and survived without sequelae. The concentration time course of theophylline and its metabolites in plasma and the pattern of urinary and gastric elimination were determined over 95 h. Theophylline showed, in contrast to its metabolites, a log linear decline in plasma. Elimination of theophylline and caffeine, calculated from their urinary excretion rates, were both exponential during the entire observation period. Urine flow dependence of renal clearance was obvious for theophylline and caffeine. Implications of theophylline disposition in neonates are discussed with special regard to theophylline poisoning.

Drug Overdose↗
PubMed1992

[Juvenile optic neuropathy caused by Km variants of biotinidase].

A patient with a newly recognised variant of biotinidase deficiency presented with acute bilateral visual loss at the age of 10 years. A progressive optic neuropathy, a predominantly motor type neuropathy and spastic paraparesis developed over the following 5 years. Metabolic investigations revealed biotin depletion causing multiple biotin dependent carboxylase deficiency. The basic defect was a biotin recycling disorder due to a biotinidase Km variant with residual colorimetric activity of 4.4% of normal. Further investigations on plasma biotinidase showed biphasic kinetics with two different reduced Vmax values and two Km-values, one being almost normal and the other highly elevated. After a period of 2 months of oral substitution with biotin 10 mg per day the visual field defects improved as well as the distal spastic parapareses and motor neuropathy. We conclude that the differential diagnosis of unexplained bilateral optic neuropathy of juvenile onset, particularly when associated with upper and lower motor neuron disease should include biotinidase deficiency.

Adolescent↗
PubMed1992

A biotinidase Km variant causing late onset bilateral optic neuropathy.

A patient with a newly recognised variant of biotinidase deficiency presented with acute loss of vision at the age of 10 years. Progressive bilateral optic neuropathy, spastic paraparesis, and a predominantly motor type neuropathy developed over the next five years. Metabolic investigations revealed biotin depletion causing multiple carboxylase deficiency. The basic defect was a biotin recycling disorder due to a mutant biotinidase with residual activity of 4.4% assayed routinely. Biocytin excretion in urine was only slightly increased. Further investigations on plasma biotinidase revealed biphasic kinetics with two different reduced values for maximum reaction velocity (Vmax) and two for the Michaelis constant (Km), one being almost normal and the other considerably raised. In contrast to this patient, two age matched children with partial biotinidase deficiency (2.8% and 2.9% of normal), but with a normal Km for biocytin, remained asymptomatic. After six months of oral substitution with 10 mg biotin per day the coecocentral and peripheral scotomata regressed, the pyramidal signs in the lower limbs disappeared, and further progression of the motor neuropathy arrested. We conclude that the differential diagnosis of unexplained bilateral optic neuropathy of juvenile onset, particularly when associated with upper and lower motor neuron disease, should include biotinidase deficiency.

Adolescent↗
PubMed1992

Pharmacokinetics and antibacterial activity of daily gentamicin.

Twenty full term neonates with suspected bacterial infection were randomly assigned to a once daily or a twice daily dosage regimen with gentamicin (4 mg/kg/day). Concomitantly all patients were treated with ampicillin (200 mg/kg/day). The gentamicin concentration time curves were analysed by an open two compartment model under steady state conditions on day 4 of treatment. The mean theoretical maximum serum concentration in the group taking gentamicin once daily (10.9 micrograms/ml) was significantly higher than in the group taking it twice daily (7.4 micrograms/ml). Potentially toxic serum concentrations were never reached. Mean trough concentrations were comparable in both groups (once daily 0.8 micrograms/ml; twice daily 1.0 micrograms/ml). Urinary alanine aminopeptidase excretion increased during and even two days after end of treatment in both groups without any significant differences. The results of the dynamic in vitro model revealed that both dosage schedules showed comparable bactericidal effects on pathogens inhibited by low concentrations of gentamicin like Escherichia coli and Staphylococcus aureus. However the once daily regimen was significantly superior in isolates with high minimal inhibitory concentrations.

Aminopeptidases↗
PubMed1992

Concentrations in serum of IgG, IgM and IgA and their age-dependence in beagle dogs as determined by a newly developed enzyme-linked-immuno-sorbent-assay (ELISA).

The concentrations of immunoglobulins IgG, IgM and IgA and their age dependence were determined in the serum of normal, untreated beagle dogs by a newly developed sandwich enzyme-linked-immuno-sorbent-assay (ELISA). A clear age-dependent increase between approximately 0.8 and 1.6 years of age was observed for the immunoglobulin IgA, whereas IgG and IgM showed only a slight tendency to an age-dependent increase. For immunotoxicological characterization of various compounds especially in long term studies, this IgA age-dependence has to be considered in the planning and interpretation of studies with beagle dogs.

Age Factors↗
PubMed1992

[Cardiopulmonary capacity in patients with mucoviscidosis. Comparison of ergospirometry findings with clinical and radiological scores].

AIM OF STUDY: Shwachman-Kulczycki- and Chrispin-Norman-Scores are widely used scoring systems for CF-patients. Maximum bicycle exercise testing was performed in 15 patients (medium age 13.4 years) to investigate whether clinical and radiographic scores or pulmonary function testing could predict cardiorespiratory fitness. METHODS: A progressive exercise test was used to determine maximum working capacity (Wmax). Prior to exercise testing, lung function and blood gases were investigated. Chest radiographs were scored by an independent radiologist (G.B.) applying the Chrispin-Norman-Score. The Shwachman-Kulczycki-Score was determined by two observers (F.F., H.S.). RESULTS: Chrispin-Norman-Score, Schwachman-Kulczycki-Score, results of lung function testing and blood gas values were significantly correlated to each other. However no significant correlation was found to the degree of exercise limitation. CONCLUSION: Clinical, radiographic scores and lung function testing cannot predict exercise tolerance. Exercise testing is mandatory to evaluate cardio-respiratory fitness in CF-patients.

Adolescent↗
PubMed1991

[Pharmacokinetics and pharmacodynamics of twice-daily unequal administration of theophylline retard pellets in children of various age groups].

To assess the pharmacokinetic parameters of theophylline (Euphylong as retard pellets) children were studied belonging to age groups between 9 to 13 and 5 to 9 years in twice-daily dosage with unequal distribution of the daily doses. For the older children the dose was 400 + 200 mg and for the younger ones 300 + 150 mg theophylline (these quantities represent the evening and morning doses). 16 and 14 children, respectively, completed the studies regularly. Pharmacokinetic evaluation resulted in a markedly parallel course of the individual serum theophylline profiles around the mean value. The average nocturnal concentration from 200 to 600 hours in the morning was higher than the average daytime concentration (11.4 to 10.5 mg/l or 12.3 to 11.4 mg/l). Due to the relatively stable baseline values the clinical parameters improved only slightly, but there were in particular significant changes in the peak-flow profile. In the older children we could also prove that they had a better protection against metacholine provocation. The side effects were generally mild and were in accordance with previous experiences collected with the studied preparation. The dosage scheme with unequal distribution of the total daily dose is recommended, on the basis of the present study, for all patients with rapid theophylline metabolism, i. e. children, habitually strong smokers or if the clearance is accelerated due to endogenous factors.

Adolescent↗
PubMed1991

[Gastrointestinal symptoms in disseminated Langerhans cell histiocytosis. Case report and review of the literature].

Symptoms of gastrointestinal disease are variable in Langerhans' cell histiocytosis (LCH). The incidence of gastrointestinal involvement is estimated to be approximately 5% in disseminated LCH. This report focuses on a 10.5 months old female infant who suffered from relapsing diarrhea and intermittent anal blood loss since the second week of life and from weight loss later in the course of disease. Definite diagnosis of LCH was not established before the patient developed additional characteristic symptoms. Analysis of large series of patients and a retrospective histopathological study reveals that an involvement of the gastrointestinal tract must be anticipated in about 50% of all cases with disseminated LCH.

Biopsy↗
PubMed1990

[Effect of methylxanthines on periodic respiration and acid gastroesophageal reflux in newborn infants].

The treatment of neonatal apnea and bradycardia with methylated xanthines--theophylline and caffeine--is generally accepted. Besides the desired effects of these drugs they induce a wide range of side effects including relaxation of smooth muscles and increased gastric secretion. The aims of this study were, at first to investigate the coincidence of periodic breathing (PA) and acid gastro-esophageal reflux (GER) in neonates (n = 15) without therapy; at second to examine the influence of the consecutive medication with theophylline and caffeine on these parameters in patients (n = 10) with recurrent episodes of bradycardia and apnea. A 24 h esophageal pH-monitoring and 24 h cardiorespirography were performed simultaneously under standarized conditions. In the 15 neonates studied a weak correlation was found between the time spent breathing periodically and the duration of GER; the overlap of PB and GER was minimal. Theophylline and caffeine medication resulted in a marked reduction of PB which was more pronounced than it could be expected from maturation. The total time of a 24 h esophageal pH-monitoring was subdivided in an early postprandial time (FPP: first two hours after the beginning of a meal) and a late postprandial time (SPP: remaining time until the following meal). An increased duration of acid GER was observed during the SPP under therapy with theophylline and even more distinct with caffeine treatment.

Bradycardia↗
PubMed1987

Total theophylline clearance in childhood: the influence of age-dependent changes in metabolism and elimination.

Theophylline metabolism and elimination during childhood are age-dependent. The total clearance, which is the sum of metabolic and renal clearances is highest in infants and young children. To differentiate between the two pathways, theophylline concentrations were measured in both serum and urine in 16 children aged 2 weeks-16 years using the fluorescence polarization immunoassay. It was found that both partial clearances assume maximal values at about the same age, but the fraction of total clearance attributable to the renal route decreases continuously.

Adolescent↗
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↗
PubMed1984

[Peculiarities of the pharmacokinetics and pharmacodynamics of theophylline in children].

Pharmacologically relevant factors such as enteral absorption, distribution, metabolism and excretion are age-dependent. The absorption of theophylline given in aqueous solution to prenatal infants with apnoea is markedly reduced when administered along with the infant's feed. The metabolic pathway of theophylline depends on the age group. Newborn and older infants form the pharmacodynamically active metabolite, caffeine. The main metabolites 1.3-dimethyl-uric acid and 3-methylxanthine are detectable, as in adults, but 1-methyl-uric acid remains below the demonstrable serum concentration level in infants of our study. The elimination velocity of theophylline is also dependent on the age. In order to achieve effective theophylline concentrations in the serum with oral preparations the galenic properties of the sustained-release products are decisive. By contrast, there was no difference between intravenous administration as permanent infusion or bolus injection. The data presented underline that in the treatment of apnea in premature infants as well as in the treatment of asthma in older children individual controls of serum concentrations are required to achieve further improvement of therapeutic success.

Adolescent↗
PubMed1984

[Pharmacotherapy of acute infant enteritis].

The management of acute diarrhea in infants with drugs is justified only where these drugs have specific interactions with the pathophysiologic mechanisms involved. Most of the infectious diarrheas are self-limited, many patients recover spontaneously. Antimicrobial drugs are only indicated if mucosal destruction takes place and symptoms of dysentery respectively inflammation are observed. Some authors propose to treat newborn and young infants in case of doubt. If antimicrobial drugs are given uncritically a selection of not obligatory microorganisms can occur, or the number of asymptomatic carriers increases. There is no confirmation that drugs like adsorbents (kaolin, pectin, charcoal) or lyophilized microorganisms have a therapeutic effect. In contrast morphine derivatives like loperamide act not only by slowing the intestinal motility but also by inhibiting the secretion mechanisms of the enterocyts. Nevertheless these drugs can not be recommended for infants since ileus symptoms have been observed.

Anti-Bacterial Agents↗
PubMed1983

Pharmacokinetics and clinical aspects of azlocillin in paediatrics.

A pharmacokinetic and clinical study was done in 25 newborn infants suffering predominantly from pseudomonas infections treated with azlocillin. After a single iv dose of 50 mg azlocillin per kg bodyweight in biphasic concentration time course suggested an open two compartment body model. There was a rapid diffusion between the peripheral and the central compartment. The elimination half life calculated from the beta-slope was 2.5-2.6 h, and differences between premature neonates with more than 2000 g body weight and mature neonates were absent. To maintain a median steady state concentration of 50-80 mg/l in the serum 100-200 mg azlocillin/kg body weight per day must be given. Using this dosage non-linear kinetics and an accumulation of the drug would not occur. Bacteriological and clinical results confirm that in neonatal reinfection, and bronchopulmonary and local infection caused by pseudomonas strains, azlocillin has favourable properties.

Azlocillin↗
PubMed1983

Renal toxicity of aminoglycosides in the neonatal period.

Renal toxicity of aminoglycosides seems to be less frequent in newborn infants compared to adults even though glomerular filtration rate and tubular secretion and reabsorption mechanisms are subjected to adaptive processes during the neonatal period. In 14 infants, kinetic parameters of gentamicin were determined using an open three-compartment body model. According to the lower glomerular filtration rate, the beta-elimination phase is longer in the newborn infant compared to adults, while the gamma-elimination phase is quite similar to adult values. The calculated drug accumulation in the deep compartment (kidney) under steady-state conditions is lower in newborns compared to infants. The excretion of urinary enzymes of tubular origin, that is the lysosomal NAG (N-acetyl-beta-D-glucosaminidase), beta-glucuronidase, and the brush-border-associated AAP (alanine-aminopeptidase), GGT (gamma-glutamyl-transpeptidase), are lower in healthy newborn infants compared to older ones. The increase of AAP, for instance, during aminoglycoside therapy is less pronounced in newborn infants, especially in prematures, if compared to adult values. After end of therapy the AAP excretion decreases to normal. The calculated rate of this decrease takes place in a fashion similar to the release of drugs from the kidney (gamma-elimination phase). The data indicate that there may be a lower renal accumulation of aminoglycosides in newborn infants, which can be explained by the morphometric and functional characteristics of the newborn kidney.

Acetylglucosaminidase↗