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Biomedical subjects

U Stephan

Publications and source records attributed to U Stephan.

At least 19 recordsLinked to original sources

Effect of antigens from Nippostrongylus brasiliensis and cytokines on the ongoing IgE synthesis in vitro.

The modulation of an ongoing IgE-mediated immune response induced by the infection of mice with the nematode Nippostrongylus brasiliensis (N.b.) was investigated in vitro. In previous experiments antigens derived from the homogenate of adult worms (WH) and third stage larvae (LH) were characterized by immunoblotting. Our results demonstrate that only antigens of the WH were recognized by IgE antibodies. The effect of worm antigens and cytokines (IL-2, IL-4, IL-5, IFN gamma) on the IgE and IgG synthesis in different culture systems was studied. The IgG synthesis of B cells was stimulated by WH or WH/cytokines. The IgE production of B cells was enhanced only by WH/cytokines or when T cells were present. Individual antigen fractions (WH 5, 8, 9, 10, 13) increased the IgE production, which was enhanced in the presence of IL-4 2- to 3.5-fold) but had no significant effects on the IgG production.

Animals

Effects of 2 quinolone antibacterials, temafloxacin and enoxacin, on theophylline pharmacokinetics.

Certain quinolone and naphthyridone antibacterial agents reduce the clearance of theophylline, posing potential clinical risks for patients maintained on this bronchodilator. Whether temafloxacin also affects theophylline pharmacokinetics was assessed in a randomised double-blind 3-way crossover study in 12 healthy volunteers, using placebo and enoxacin as controls. Each volunteer participated in all 3 phases of the study, receiving theophylline plus daily divided doses of temafloxacin 800mg, enoxacin 800mg, or placebo, orally for 7 days. Aminophylline 200mg (containing 146mg theophylline) was given orally twice daily on the first 4 days. On the fifth morning, theophylline 200mg was administered intravenously, and serial blood and urine samples were collected for the following 72h. Coadministration of enoxacin significantly reduced the metabolic clearance of theophylline (approximately 65%). In contrast, during coadministration of temafloxacin, theophylline pharmacokinetics did not differ significantly from those during coadministration of placebo. No clinically significant adverse events occurred; total reported adverse events during enoxacin-theophylline administration (n = 33) were higher than those reported during temafloxacin-theophylline administration (n = 22) and theophylline alone (n = 23). Administration of temafloxacin to patients on long term theophylline therapy appears to be a safe and rational choice when treatment with a broad spectrum antibiotic is indicated.

Administration, Oral

Effect of cimetidine on the pharmacokinetics of temafloxacin.

Cimetidine, a widely prescribed histamine H2-receptor antagonist, is known to interact with a variety of drugs; consequently, it is important to determine its potential for interaction with any new drug. The interaction between cimetidine and a new quinolone, temafloxacin, has been examined in an open randomised 2-period crossover study in 12 healthy adults. Half the volunteers received cimetidine 400mg 3 times daily for 8 days. On day 5, a single temafloxacin 400mg dose was administered. No other drugs were allowed during this period. The other volunteers did not receive cimetidine (or any other drugs) for an 8-day period except for temafloxacin 400mg on day 5. Blood and urine were sampled serially after temafloxacin administration and daily thereafter until the last day of the study. A 2-week washout period preceded crossover. Pharmacokinetic analyses showed that cimetidine did not affect the rate or extent of temafloxacin absorption, as evidenced by unchanged peak plasma concentration, time to peak plasma concentration, and terminal-phase volume of distribution. However, renal and total clearance values for temafloxacin were reduced by 19%, and elimination half-life and area under the concentration vs time curve were increased in the presence of cimetidine. The most likely mechanism underlying these effects is inhibition by cimetidine of tubular secretion of temafloxacin in the kidney. The lack of clinically significant adverse effects and the small magnitude of the reduction in temafloxacin clearance suggest that the interaction is of little clinical consequence.

Administration, Oral

Effect of antacid medication on the pharmacokinetics of temafloxacin.

The effect of an antacid drug (Maalox 70) on the pharmacokinetics of temafloxacin was studied in 12 healthy young volunteers. The study was designed as a randomised open 2-period crossover trial in which temafloxacin was administered alone and with Maalox 70. In both treatments, temafloxacin was administered as a single oral 400mg dose on the morning of day 2. In the antacid regimen, 8 doses of Maalox 70 were administered every 2h on day 1, starting at 8am and ending with the last dose at 10pm; 5 doses were given on day 2, at 2.5 and 1h before administration of temafloxacin and 1, 3 and 5h after the temafloxacin dose. With coadministration of Maalox 70, peak plasma temafloxacin concentrations (Cmax) were reduced to 44.6% (+/- 24.5), and AUC(0-infinity) was reduced to 39.8% (+/- 17.4) of the corresponding values obtained when temafloxacin was given alone. Urinary excretion of temafloxacin was reduced to 46.0% (+/- 13.7) of that observed when temafloxacin was administered alone. Time to peak plasma concentration (tmax = 1.8h) was not affected by antacid administration. Comparable or greater antacid-associated reductions in relative bioavailability have been reported for other quinolones. As with other quinolones, the concurrent administration of temafloxacin and antacids should be avoided.

Adult

Effects of temafloxacin and ciprofloxacin on the pharmacokinetics of caffeine.

A number of quinolone antibacterial agents, particularly enoxacin, pefloxacin, pipemidic acid and ciprofloxacin, are known to decrease the clearance of methylxanthines. The effects of temafloxacin and ciprofloxacin on the pharmacokinetics of caffeine were therefore compared in a 3-way crossover study in 12 healthy young volunteers. Each volunteer received 183mg once-daily doses of caffeine in conjunction with twice-daily placebo, temafloxacin 600mg and ciprofloxacin 750mg in 3 separate phases according to a randomised sequence. A doubling of the area under the plasma concentration-time curve (77.8 vs 31.8 mg/L.h) and terminal-phase half-life (9.7 vs 4.5h) of caffeine were observed in the presence of ciprofloxacin. The magnitude of the reduction in the intrinsic clearance of caffeine produced by ciprofloxacin was greater than that described in the literature for ciprofloxacin and theophylline. This may partly be explained by intertrial differences in dosage and study design. Coadministration of temafloxacin did not have any effect on the pharmacokinetics of caffeine, confirming results of other studies suggesting that this agent does not affect methylxanthine clearance. Accordingly, it appears that restriction of caffeine intake during temafloxacin therapy is not necessary.

Adult

Characterization of allergenic components of rye and wheat flour (Secale, Triticum vulgaris) by western blot with sera of bakers: their effects on CD23 expression.

The allergenic components of water-soluble rye flour extract were studied by immunoblotting. Sera from 100 bakers were analyzed for their IgG, IgG4 and IgE binding pattern. Two allergens with molecular weights of 35 and 14 kD were detected. Previously, the major allergens of wheat flour extract were identified. The wheat flour components at a MW of 15/17 kD and the rye flour component at a MW of 14 kD were purified and isolated. The modulation of the low affinity receptor for IgE (Fc epsilon RII/CD23) on monocytes by separated allergenic components was studied. Depending on the allergen concentration the CD23 expression on isolated cells increased after stimulation with the rye flour component (MW 14 kD). The combined addition of the rye flour component (14 kD) with IL-4 induced a significant CD23 expression as compared to IL-4 alone.

Allergens

Staphylococcus aureus modifies the cytokine-induced immunoglobulin synthesis and CD23 expression in patients with atopic dermatitis.

The influence of Staphylococcus aureus on peripheral blood lymphocytes (PBL) of patients with atopic dermatitis (AD) was analysed. The parameters studied were spontaneous and interleukin-inducible immunoglobulin (IgA, IgE, IgG) synthesis, as well as CD23 expression. Various heat-killed, clinical isolates of S. aureus were analysed. PBL from non-atopic donors served as controls. The time-course of co-cultured PBL with S. aureus showed a dose-dependent increase in immunoglobulin (Ig) synthesis from PBL of normal donors, whereas the Ig synthesis of atopic cells was significantly depressed. Additional stimulation with interleukin-4 (IL-4) also led to a pronounced suppression of the IgE and IgA synthesis in normal donor cells, while the effect of S. aureus on PBL of atopic donors was not markedly affected by IL-4. Transwell cultures of bacteria separated from PBL by a semi-permeable membrane induced stimulation of IgA and IgE synthesis in patients with AD. The Ig synthesis in the control group was not altered. Co-stimulation of S. aureus and IL-4 in this system led to a suppression of IgA with cells of both atopic and normal donors. IgE synthesis from atopic PBL was significantly stimulated. The CD23 expression of atopic PBL was increased by S. aureus and IL-4. Our data indicate that S. aureus may modulate the cytokine-dependent humoral immunity in patients with AD and that chronic colonization of the skin may be responsible for allergic skin reactions in AD.

Antigens, Bacterial

Pharmacokinetic disposition of quinolones in human body fluids and tissues.

The unique pharmacokinetic properties as well as the body fluid and tissue penetration of quinolones are discussed. Quinolones are well absorbed from the gastrointestinal tract and are eliminated with considerable differences in their terminal half-lives. The major elimination pathways of quinolones are renal excretion and hepatic metabolism. Renally, these drugs undergo the potential excretion mechanisms (glomerular filtration, tubular secretion, reabsorption). In the liver, they are metabolised primarily by oxidation as well as by conjugative pathways. However, the metabolic pattern and extent of metabolism differ significantly between individual agents. Alterations in the pharmacokinetic disposition of these agents in liver and renal failure as well as in elderly patients are observed as predicted from their excretion pattern. In addition, quinolones can interact with a number of other compounds at hepatic (e.g. with xanthine derivatives), renal (with probenecid) and gastrointestinal (with antacids) sites. The volume of distribution of quinolones is considerably higher than body volume, which suggests intracellular penetration. Studies on tissue penetration show that concentrations exceeding plasma levels are obtained in most tissues. The highest tissue/plasma concentration ratios are achieved in lung and kidney, whereas concentrations in fat are considerably lower than in plasma. Body fluid penetration is introduced as a new approach to evaluate distribution kinetics of quinolones. With the exception of those in nasal secretions and ejaculate, body fluid levels of these drugs rarely reach plasma levels. The body fluid penetration model allows for differentiation among individual agents. There is no apparent relationship between differences in body fluid penetration of quinolones and differences in volume of distribution. For the clinical use of these drugs it is important that the concentrations achieved in body fluids and tissues are sufficient to kill most pathogens. A discussion on the relationship between plasma and tissue levels and the MICs of quinolones is, however, beyond the scope of this article.

4-Quinolones

[Sonographic findings in the gallbladder in mucoviscidosis patients].

The improved survival time of patients with mucoviscidosis has revealed some new complications. 137 patients were studied by sonography. The findings in the gall bladder have been compared with liver echogenicity. A micro-gall bladder was found in 37 patients (27%). 74 patients had a normal gall bladder (54%). Concretions were found in 22 (16%) of patients. 10 out of the 22 patients with concretions showed sonographic changes in the liver. In view of the frequent abdominal symptoms in patients with mucoviscidosis, sonography should be used routinely as a non-invasive method of investigation.

Adolescent

[Supplementary intravenous nutrition in term and preterm neonates (author's transl)].

16 term and preterm neonates received intravenous nutriton for at least three days. The dosage was 1--2 g amino acids, 1 g of fat, and 8--10 g glucose per kg body weight and day. Compatibility was investigated by daily determinations of the amino acid pattern in the serum and measurement of free fatty acids and triglycerides. All results were compared to five neonates who were fed completely orally from the first day of life. Leucine, methionine, proline, and valine levels were elevated during intravenous nutrition, but only the high methionine levels were regarded as a nutrional imbalance. Free fatty acids and triglycerides showed no significant differences as compared to the control group.

Amino Acids

[Vaccination in childhood. Indications towards change].

Indications of vaccinations in childhood are changing due to the development of new vaccines and to changes of the epidemiological situation. In Germany one of the most controversial vaccinations is the BCG-immunization. Regarding our own experiences in the northern part of Bavaria we recommend the BCG-vaccination of all newborn infants. Indication of vaccination against tetanus remains unchanged. All children should be immunized against diphtheria. To protect against measles and parotitis epidemica we use the combined measles-parotitis-vaccine in the second year of life. The indication of vaccination against smallpox changed meanwhile due to the changed legal situation and the nearly complete eradication of smallpox in the world. Before puberty all girls should be vaccinated against rubella. To fight poliomyelitis oral vaccination is necessary.

Age Factors