Search PubMed⌕ Search

Biomedical subjects

W Lindner

Publications and source records attributed to W Lindner.

At least 19 recordsLinked to original sources
PubMed1998

Tension pneumopericardium in a preterm infant without mechanical ventilation: a rare cause of cardiac arrest.

A preterm infant with a gestational age of 32 weeks developed a tension pneumopericardium during the second day of life. The infant was treated with nasal continuous positive airway pressure and was not mechanically ventilated before pneumopericardium occurred. After emergency pericardiocentesis, two recurrences of pneumopericardium without clinical deterioration were diagnosed by X-ray during a 2-d observation period. A continuous pericardial drainage was positioned and was successfully removed on the seventh day of life after weaning from the ventilator. Tension pneumopericardium may occur even in non-ventilated newborns and should be considered as a rare but important differential diagnosis of cardiac arrest.

Disease-Free Survival↗
PubMed1997

Computerized optimization of the high-performance liquid chromatographic enantioseparation of a mixture of 4-dinitrophenyl amino acids on a quinine carbamate-type chiral stationary phase using DRYLAB.

A method is proposed for the sensitive chiral analysis of amino acid enantiomers by high-performance liquid chromatography (HPLC). Thus the enantiomers of a mixture of seven racemic amino acids were resolved as their DNP derivatives from each other and from the peak of the hydrolyzed reagent, employing a quinine carbamate-based chiral anion exchange-type chiral stationary phase (CSP) and aqueous buffered mobile phases. However, the initial isocratic chromatogram yielded many peak overlaps although the corresponding enantiomers were well resolved. Therefore, the separation of the complex mixture had to be optimized; we utilized the commercial computer method development software DRYLAB. First, the influence of the manifold mobile phase parameters and chromatographic conditions (pH, type and content of organic modifier, buffer concentration, temperature, type of co-ion, etc.) on retention and resolution was studied by isocratic elution. Furthermore, with such optimized conditions linear and multi-segmented organic modifier and buffer salt gradients, respectively, were simulated with the computer program and experimentally verified. Average errors of prediction of retention times lay between 2 and 8%. Finally, a highly improved HPLC gradient method resulted in almost all components being baseline separated and equally spaced and accelerated by a factor of more than 3 compared to the initial run.

Amino Acids↗
PubMed1996

Comparison of the Hummel-Dreyer method in high-performance liquid chromatography and capillary electrophoresis conditions for study of the interaction of (RS)-, (R)- and (S)-carvedilol with isolated plasma proteins.

The Hummel-Dreyer method in capillary zone electrophoresis was compared with the corresponding high-performance liquid chromatographic (HPLC) variant in order to study the interaction of racemic carvedilol and its individual enantiomers with isolated human plasma proteins [alpha 1-acid glycoprotein (AGP) and human serum albumin (HSA)]. The binding parameters characterizing the high-affinity binding site of AGP evaluated by using capillary electrophoresis [Ka(RS) = (3.01 +/- 1.15).10(6) l/mol; Ka(S) = (2.13 +/- 0.53).10(6) l/mol; Ka(R) = (4.88 +/- 1.57).10(6) l/mol] were in good accordance with those obtained by HPLC [Ka(RS) = (3.88 +/- 1.74).10(6) l/mol: Ka(S) = (1.80 +/- 0.53) x 10(6) l/mol; Ka(R) = (5.43 +/- 2.53).10(6) l/mol]. Relatively small quantitative differences have been observed considering the attachment of (R)-carvedilol to the secondary low-affinity binding sites on alpha 1-acid glycoprotein by comparing these two methods. In general, the Hummel-Dreyer method applied to capillary zone electrophoresis conditions was verified to be an efficient and fast technique for reliable description of quantitative binding parameters of hydrophobic drugs.

Adrenergic beta-Antagonists↗
PubMed1996

Drug-protein binding sites. New trends in analytical and experimental methodology.

In the last few years, continuous progress in instrumental analytical methodology has been achieved with a substantial increase in the number of new, more specific and more flexible methods for ligand-protein assays. In general, the methods used for drug-protein binding studies can be divided into two main groups: separation methods (enabling the calculation of binding parameters, i.e. the number of binding sites and their respective affinity constants) and non-separation methods (describing predominantly qualitative parameters of the ligand-protein complex). This review will be focussed particularly on recent trends in the development of drug-protein binding methods including stereoselective and non-stereoselective aspects using chromatography, capillary electrophoresis and microdialysis as compared to the "conventional approach" using equilibrium dialysis, ultrafiltration or size exclusion chromatography. The advantages and limitations of various methods will be discussed including a focus on "optimal" experimental strategies taking into account in vitro, ex vivo and/or in vivo studies. Furthermore, the importance of some particular aspects concerning the drug binding to proteins (covalent binding of drugs and metabolites, stereoselective interactions and evaluation of binding data) will be outlined in more detail.

Animals↗
PubMed1996

Organochlorine pesticide analysis in oil seeds and vegetable oil: simplification of silica gel clean-up and elimination of chlorinated solvents.

For the determination of organochlorine pesticides (OCPs) in vegetable oils and oil seed samples, a solid-phase extraction method is described, modified from that developed by Steinwandter, with silica gel columns activated with a 10% water content. In comparison to the method developed by Steinwandter, we reduced the amount of solvents and chemicals required for sample preparation and substituted dichloromethane by the much less toxic tert-butylmethyl ether in the eluent mixture. In this manner the sample preparation technique becomes more convenient, cheaper and ecologically more justifiable. Under the specified sample preparation and elution conditions 1 g silica gel retained about 16 mg triglycerides whereas the OCPs were quantitatively eluted. The recoveries for hexachlorobenze, (HCB) alpha-HCH, Lindane (gamma-HCH) gamma-HCH, Heptachlor, Heptachlorepoxid, o,p'-DDE, p,p'-DDE, Dieldrin, o,p'-DDT, p,p'-DDT were between 75 and 90%. The reproducibility of the total method was excellent as well as its ruggedness.

Chromatography, Gas↗
PubMed1996

Are there stereoselective electrophysiologic effects of intravenously administered (S)- or (R)-propafenone hydrochloride in patients with supraventricular tachycardia?

OBJECTIVE: The electrophysiological effects of intravenously administered pure (S)- and (R)-propafenone hydrochloride has been determined for the first time in humans-12 patients with supraventricular tachycardia. METHODS: Measurements were performed before and during drug therapy. RESULTS: (S)- and (R)-propafenone prolonged the AH interval from 82 to 107 ms and 75 to 84 ms, respectively, and significantly increased the V nodal Wenckebach cycle length by 58 ms and 37 ms, respectively. The AV nodal effective refractory period in both groups was increased significantly to the same extent (45 vs 42 ms). Sinus node recovery times were not significantly influenced by either enantiomers. Both (S)- and (R)-propafenone significantly prolonged the HV interval to the same extent (from 41 to 51 ms, and 42 to 53 ms). Changes in the electrophysiological characteristics of the myocardium were more pronounced in the atria than in the ventricles. Only (S)-propafenone significantly increased the atrial effective refractory period from 204 to 230 ms, and the ventricular effective refractory period from 225 to 241 ms compared to (R)-propafenone (from 221 to 239 ms, and from 219 to 222 ms, respectively). There was a more pronounced electrophysiological effect on AV nodal conduction of (S)- than (R)-propafenone, probably as a result of its beta-blocking activity. CONCLUSION: The electrophysiological effects of (S)-compared to (R)-propafenone were not very pronounced, so it still remains questionable whether one of the enantiomers might be clinically superior to the other, or to the racemic mixture.

Adult↗
PubMed1996

Exercise increases plasma concentrations of (R)- and (S)-propranolol.

OBJECTIVE: We recently reported a highly stereoselective increase in plasma concentrations of (S)-atenolol during exercise which is most likely due to a release of the drug from adrenergic cells. The objective of the present study was to investigate the influence of physical exercise on plasma concentrations of the (R)- and (S)-enantiomers of propranolol. METHODS: Blood samples were taken immediately before and at the end of exercise in 12 patients receiving chronic treatment with racemic (R, S)-propranolol. Plasma concentrations of (R)- and (S)-propranolol were determined by HPLC. RESULTS: In contrast to atenolol, mean plasma concentrations of (S)-propranolol were significantly higher (+20%) than those of (R)-propranolol at rest. During exercise there was an increase in plasma concentrations of both (R)-propranolol (+129%) and (S)-propranolol (+109%). CONCLUSION: Based on information from in vitro studies we conclude that the increase in plasma concentrations of (S)-propranolol during exercise is caused by a release of the drug from adrenergic nerves, whereas the reason for the increase in (R)-propranolol remains to be determined. This release of the beta-adrenoceptor blocking (S)-enantiomer directly at the synaptic gaps might be one reason for the poor correlation between plasma concentration and effect of beta-adrenoceptor antagonists repeatedly described in the literature.

Adrenergic beta-Antagonists↗
PubMed1996

Quantification of rate-dependent effects of verapamil, diltiazem, and digoxin on atrioventricular conduction.

The calcium channel blocking agents, verapamil and diltiazem, and the digitalis compound, digoxin, caused drug specific rate-dependent changes of the atrioventricular conduction time (AVCT). The purpose of this study was to investigate this rate adaptation of the AVCT in isolated guinea pig hearts perfused by the method of Langendorff to get an insight in drug-specific binding kinetic to the respective channel. In the presence of 10 nM verapamil, 30 nM diltiazem, or 0.6 nM digoxin, the atrioventricular conduction time was prolonged to a comparable degree during sinus rhythm. The drug-specific time constant, characterizing the rate-dependent adaptation of the AVCT, in the presence of a substance was comparable if evaluated after abruptly changing the heart rate from the pacing cycle length of 240 ms to 180 ms (tau-on) or from 180 to 240 ms (tau-off). The adaptation of the AVCT in the presence of verapamil (tau-on = 178 +/- 45 beats, tau-off = 125 +/- 33 beats, mean +/- SEM) was more pronounced than in the presence of digoxin (tau-on = 144 +/- 24 beats, tau-off = 98 +/- 15 beats) or diltiazem (tau-on = 70 +/- 11 beats, tau-off = 98 +/- 15 beats). In conclusion, the differences in the rate adaptation of the AVCT may be explained by the drug-specific association and dissociation kinetic to the calcium channel, slow in the case of verapamil, and fast in the case of dilitiazem, whereas this phenomenon in the presence of digoxin may be explained by its direct effects on passive membrane properties.

Adaptation, Physiological↗
PubMed1995

Stereoselective increase of plasma concentrations of the enantiomers of propranolol and atenolol during exercise.

OBJECTIVE: In vitro studies have shown that, like catecholamines, both propranolol and atenolol are taken up by and released from adrenergic cells. We performed this study to investigate whether this may also play a role in humans and whether stereoselective aspects are important. METHODS: This was a randomized, double-blind, placebo-controlled, crossover study of two groups of 12 healthy volunteers. Subjects received single oral doses of 80 mg (R,S)-, 40 mg (R)-, and 40 mg (S)-propranolol; 100 mg (R,S)-, 50 mg (R)-, and 50 mg (S)-atenolol; and placebo at intervals of 1 week. Exercise was performed at 4 and 9 hours after drug intake, and blood samples were taken before and at the end of each exercise period. The plasma concentrations of the (R)- and (S)-enantiomers of propranolol and atenolol, as well as those of epinephrine and norepinephrine, were determined by HPLC. RESULTS: Effects of exercise on the plasma levels of the enantiomers of propranolol and atenolol were similar. When the optically pure enantiomers were administered, exercise caused a marked and significant increase of the plasma concentrations of the (S)- but not of the (R)-enantiomers. When the drugs were administered in the racemic form, the plasma levels of both the (R)- and (S)-enantiomers were elevated to the same extent. The increase of norepinephrine levels during exercise was more pronounced than that of epinephrine and paralleled that of the (S)-enantiomers of the beta-blockers. CONCLUSION: Bearing the in vitro data in mind, we conclude that (S)-propranolol and (S)-atenolol are taken up into and released from adrenergic cells together with norepinephrine during exercise. The reason why the plasma concentrations of (R)-propranolol and (R)-atenolol are increased only during exercise in the presence of the corresponding (S)-enantiomers remains to be determined.

Administration, Oral↗
PubMed1995

Stereoselective vascular effects of the (R)- and (S)-enantiomers of propranolol and atenolol.

All beta-adrenergic antagonists have an asymmetric carbon atom, and most commercially available beta-blockers consist of (R)- and (S)-enantiomers in a fixed 1:1-ratio. The drugs are believed to be contraindicated when peripheral vascular disease exists, presumably due to unopposed alpha-adrenergic vasoconstriction. However, little is known about direct vascular effects of beta-blockers or of stereoselective effects on peripheral arteries. Therefore, we investigated the effects on forearm blood flow (FBF) of brachial artery infusions of the (R)- and (S)- enantiomers of propranolol and atenolol (2, 10, and 50 micrograms/min each) and their inhibitory effects on isoprenaline (Iso)-induced vasodilatation by forearm venous occlusion plethysmography in 12 healthy subjects. Only (R)-propranolol caused an increase in FBF (+21%, p < 0.05), whereas (S)-propranolol and (R)- and (S)-atenolol had no direct effect on peripheral arteries. Vasodilatation induced by Iso was abolished by (S)-propranolol and reduced by (R)-propranolol (-56%, p < 0.05) and (S)-atenolol (-68%, p < 0.05), whereas (R)-atenolol had no effect. Our results indicate that the optically pure (R)- and (S)-enantiomers of propranolol and atenolol do not exert direct vasoconstrictive effects. Furthermore, our results confirm that predominantly (S)-enantiomers have beta-adrenoceptor blocking effects, but they also show that neither the non-beta-blocking (R)-enantiomer of propranolol nor the (S)-enantiomer of the beta 1-selective agent atenolol is completely devoid of blocking effects on vascular beta 2-adrenoceptors.

Adult↗
PubMed1994

Stereoselective high-performance liquid chromatographic assay of (+/-)-delmopinol in plasma using solid-phase extraction, a chiral derivatizing agent and electrochemical detection.

An enantioselective HPLC bioanalytical method for (+/-)-delmopinol was established in order to elucidate the pharmacokinetic behaviour of this chiral drug. (+/-)-Delmopinol and (+/-)-M1652, a structurally related compound used as internal standard, were extracted from plasma by a solid-phase extraction procedure using CN cartridges. The enantiomers were derivatized with a chiral derivatizing agent (R,R)-O,O'-di-p-toluoyl tartaric acid anhydride yielding diastereomeric derivatives which were separated on a reversed-phase column with acetonitrile-0.1 M ammonium acetate buffer (65:35, v/v) pH 5.7 as mobile phase. The resolution values of the diastereomeric derivatives of (-)- and (+)-M1652 and of the derivatives of (-)- and (+)-delmopinol were 1.03 and 1.46, respectively. The limit of quantitation was approximately 3 pmol (1 ng)/enantiomer per 0.5 ml plasma using electrochemical detection (+0.75 V versus Pd/PdO reference electrode). The effectiveness of the derivatization was > 98% and the total recovery of (+/-)-delmopinol and of (+/-)-M1652 from plasma or serum was found to be approximately 50%. The assay was applied to enantioselective pharmacokinetic investigations in humans, rats and dogs but showing here only one concentration time curve of the (+)- and (-)-delmopinol in a human subject after administering (+/-)-delmopinol in form of an aqueous mouth wash solution for 60 s.

Anhydrides↗
PubMed1994

Direct enantioselective determination of (R)- and (S)-propranolol in human plasma. Application to pharmacokinetic studies.

In order to examine possible drug interactions of (R)- and (S)-propranolol a randomized, double blind, crossover study has been performed, administering orally single doses of 40 mg (R,S)- and of 20 mg (S)-propranolol. HCl three times daily over a week to reach steady state conditions. After the first single dose of 40 mg (R,S)-propranolol. HCl, the AUC0-infinity and Cmax values of the (S)-isomer were greater than those of the (R)-isomer: the ratio of AUC(S) over AUC(R) was 1.77 (P < 0.05) and that of Cmax 1.57 (P < 0.01). When (S)-propranolol.HCl was given as a single 20 mg dose, the AUC(S) value was a factor of 0.55 lower than that administration of 40 mg (R,S)-propranolol.HCl. At steady state, the AUC of (S)-propranolol was 1.52 times higher (P < 0.01) than that of the (R)-isomer after administration of 40 mg racemate, and comparing the (S)-isomer, the ratio was 1.21. Following administration of the first single dose of 40 mg of the racemate, the mean (SD) clearance of the (R)- and (S)-isomers was 110 (84) and 61 (37) ml min-1 kg-1, respectively; at steady state these values were 89 (55) and 57 (37) ml min-1 kg-1, respectively. Respective values for (S)-propranolol after single isomer administration (20 mg) were 86 (36) and 57 (25) ml min-1 kg-1 in single dose and steady state situations. The data are based on the quantitative analysis of (R)- and (S)-propranolol in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗
PubMed1993

Stereoselective features of (R)- and (S)-atenolol: clinical pharmacological, pharmacokinetic, and radioligand binding studies.

In a randomized, double-blind, cross-over study in 12 healthy volunteers, the effects of single oral doses of 100 mg rac-atenolol were compared during exercise to those of equal amounts of the optically pure enantiomers, i.e., 50 mg (R)- and 50 mg (S)-atenolol. The mean rate pressure product decreased with rac-atenolol (-37%; P < 0.01) and half-dosed (S)-atenolol (-35%; P < 0.01) to the same extent, whereas (R)-atenolol caused no effect. Radioligand binding studies in beta-adrenergic receptors of the guinea pig heart yielded a eudismic ratio of 46 for (S)- to (R)-atenolol. The mean AUCs, maximal plasma concentrations, and plasma half-lives of the enantiomers were similar regardless of whether they were administered as optically pure enantiomers or as racemic mixture. On the other hand, the AUC of (R)-atenolol was 1.08-fold greater (P < 0.01) than that of the (S)-enantiomer. The reason for this finding remains unclear. We conclude that only (S)-atenolol, but not (R)-atenolol, contributes to the beta-blocking effect of currently used rac-atenolol since the same effect can be elicited with the (S)-enantiomer alone.

Adult↗