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Biomedical subjects

W Kirch

Publications and source records attributed to W Kirch.

At least 19 recordsLinked to original sources
PubMed1996

Determination of scopolamine in human serum by gas chromatography-ion trap tandem mass spectrometry.

The objective of this study was to develop a very sensitive and selective method for the determination of scopolamine in serum with a rapid and simple sample preparation. A capillary column gas chromatographic-ion trap tandem mass spectrometric technique has been applied. Scopolamine and the internal standard mexiletine were extracted from serum samples and cleaned up by using a single step liquid-liquid extraction. Derivatization was carried out using 2,2,2-trifluoro-N-methyl-N-trimethylsilylacetamide. The mass spectrometer was operated with positive ions in the selected reaction mode with chemical ionisation using methane. The sum of peak height of two daughter ions was used for quantification. The detection limit was 50 pg/ml in serum.

Cholinergic Antagonists↗
PubMed1996

Characterization of Meibomian gland innervation in the cynomolgus monkey (Macaca fascicularis).

To characterize the innervation of the cynomolgus monkey (Macaca fascicularis) Meibomian (tarsal) glands, upper lids of six cynomolgus monkeys were investigated with electronmicroscopical and double-labeling immunocytochemical methods. Antibodies against calcitonin gene-related peptide (CGRP), dopamine-beta-hydroxylase (DBH), neuropeptide Y (NPY), nitric oxide synthase (NOS), protein gene product 9.5 (PGP 9.5), substance P (SP), tyrosine hydroxylase (TH), and vasoactive intestinal peptide (VIP) were used. In addition, sections were processed for NADPH-diaphorase (NADPH-d) histochemistry. Staining for PGP 9.5 and electron microscopy showed that Meibomian gland acini were surrounded by a network of unmyelinated nerves and terminal varicose axons. The terminals contained small agranular (30-60 nm) and large granular vesicles (65-110 nm), and were observed in close contact with the basal lamina of the acini, but never internally to the basal lamina. Meibomian axons showed like-immunoreactivity (LI) for the neuropeptides SP, CGRP, NPY, and VIP. In addition, the axons stained for TH, DBH, NOS, and NADPH-d. VIP-LI, NOS- and NADPH-d-positive axons appeared to be more numerous, TH- and DBH-positive axons more rare than others. Most SP-LI axons were double-labelled for CGRP-LI, some for VIP-LI or NPY-LI. In addition, some VIP-LI axons were double-labeled for NPY-LI. NPY/VIP-LI and NPY/SP-LI axons were only observed close to the Meibomian acini. Conversely, NPY-LI colocalized with TH-IR or DBH-IR predominated in perivascular nerves of Meibomian gland vasculature. The close association of varicose axons with the acini of Meibomian glands indicates that nervous signals modulate meibomian secretion. Meibomian gland nerve fibers in the cynomolgus monkey appear to utilize various neuropeptides, catecholamines and nitric oxide as transmitter substances, and seem to derive from the pterygopalatine, superior cervical and trigeminal ganglion respectively.

Animals↗
PubMed1996

Direct demonstration of small intestinal secretion and site-dependent absorption of the beta-blocker talinolol in humans.

OBJECTIVE: To examine the relevance of site-dependent small intestinal absorption for incomplete intestinal absorption of the poorly metabolized beta 1-adrenergic receptor antagonist talinolol. METHODS: The intestinal steady-state perfusion technique (triple lumen tubing system with a 30 cm test segment) for intraluminal measurements was combined with simultaneous determination of talinolol serum concentrations. Dissolved talinolol was perfused over 160 minutes into different parts of the small intestine. The middle of the test segment was located between 25 and 235 cm beyond the teeth. Each of the six healthy subjects was studied twice with a proximal and a more distal site of perfusion to allow for comparisons within an individual subject. RESULTS: The area under the curve for serum concentrations from 0 to 480 minutes [AUC(0-480 min)] and the maximum serum concentration after distal perfusions corresponded to only 15% to 73% and 7% to 90% of the proximal values, respectively. AUC decreased with increasing distance from the teeth. The mean amount of talinolol absorbed from the test segment per unit time (intestinal transport rate) corresponds to only one-tenth of the amount of drug offered to the test segment (perfusion rate). There was a direct correlation between the perfusion rate of talinolol and its transport rate for both regions and in all subjects investigated. However, to achieve the same transport rate in the distal region a higher perfusion rate is required, compared to the proximal small intestine. At perfusion rates lower than 600 micrograms/min, net secretion of talinolol into the intestinal lumen occurred against a steep concentration gradient blood: lumen of about 1:4200. CONCLUSION: Talinolol oral bioavailability of 55% is due to a low absorption rate and a decrease of absorption capabilities along the small intestine. Net absorption of talinolol is reduced by the involvement of active intestinal secretion.

Administration, Oral↗
PubMed1996

Misdiagnosis at a university hospital in 4 medical eras.

In the present study 100 randomly selected autopsies from each of the years 1959, 1969, 1979, and 1989 at a German university hospital were analyzed to determine whether advances in diagnostic procedures have reduced the misdiagnosis rate. We define misdiagnosis as occurring when a disease that does not exist is assumed to be present and when the failure to recognize the true existing disease leads to a worsened patient prognosis. In all years analyzed, about 10% of the autopsies revealed a misdiagnosis; another 25% disclosed a false negative diagnosis; which did not influence the patient's prognosis; and about 10% disclosed a false-positive diagnosis, which again did not influence the patients prognosis. The most common diagnostic errors were pulmonary emboli, myocardial infarctions, neoplasms, and infections. The introduction of new diagnostic procedures such as ultrasound, computerized tomography, and radionuclide scans has not reduced the rate of misdiagnoses. Misinterpretation, technical errors, and overreliance on these new procedures occasionally contributed directly to diagnostic errors. By contrast, the patient's medical history and physical examination played an important role in the diagnostic process, leading to a correct final diagnosis in 60%-70% of cases.

Adult↗
PubMed1995

Immunohistochemical localization of neuropeptides in the human ciliary ganglion.

In human ciliary ganglia, 18% of neurons were in contact with substance P (SP) and 12% with calcitonin gene-related peptide (CGRP) like-immunoreactive (LI) varicose axons. CGRP was colocalized with SP. Numerous SP-LI and CGRP-LI non-varicose nerve fibers were found between the ganglion cells and in nerve trunks that entered the ganglia. Axons immunoreactive for neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), tyrosine hydroxylase (TH) or dopamine-beta-hydroxylase (DBH) never contacted neuronal cell bodies. Perikarya of ciliary neurons neither stained for any of the neuropeptides nor for DBH. 23% of ciliary perikarya were TH-immunoreactive. These observations suggest an innervation of human ciliary ganglion neurons by peptidergic primary afferent collaterals presumably of trigeminal origin.

Adult↗
PubMed1995

Clinical aspects of cardiovascular effects of H2-receptor antagonists.

In vitro studies and animal experiments as well as clinical observations in humans concerning cardiovascular effects of H2-receptor antagonists have been published shortly after the development. Thus, clinical studies were performed to investigate these effects. The following review summarizes the results from in vitro studies up to the clinical investigations performed.

Animals↗
PubMed1995

Hemolysis on intravenous administration of a new calcium antagonist.

Hemolysis-inducing properties of the new calcium antagonist Ro 40-5967 administered intravenously to 39 healthy male subjects were investigated in a placebo-controlled study. The volunteers were randomized into five parallel groups of 9 subjects each: three groups, receiving infusions of 40 mg Ro 40-5967 in 60, 30, and 15 min, respectively; one group receiving 80 mg Ro 40-5967 in 30 min as two simultaneous doses of 40 mg in the cubital veins of both arms; and one group receiving 80 mg Ro 40-5967 in 30 min in one arm. Within each group, 3 subjects received placebo under randomized double-blind conditions. Plasma haptoglobin decreased by 67% after 3.5 h in 2 subjects who received 80 mg Ro 40-5967 in one arm (treatment schedule thereupon discontinued). Serum bilirubin levels also increased in a dose-dependent manner in all groups as compared with placebo. Other parameters of hemolysis remained unchanged; no hemoglobinuria was observed. The intravascular hemolysis observed on infusion limits the therapeutic application of Ro 40-5967 to oral use only.

Adult↗
PubMed1995

The interaction of the calcium antagonist RO 40-5967 with digoxin.

1. The interaction of the newer calcium antagonist Ro 40-5967 with digoxin was investigated in 42 healthy subjects under steady state conditions. 2. After an adequate loading dose digoxin 0.375 mg once daily was given alone for 1 week. Afterwards three different doses (50, 100, 150 mg daily) of the calcium antagonist Ro 40-5967 were administered to three groups of 14 subjects each for 1 week concurrently with digoxin 0.375 mg daily. 3. Ro 40-5967 led to an increase of mean maximum digoxin plasma concentrations (Cmax) and AUC. For AUC this effect was significantly dose-dependent. 4. Increasing doses of the calcium antagonist led to a stepwise rise of the PQ-time in ECG. 5. A slight fall of heart rate was seen after a 7 day treatment of digoxin alone. This effect was more pronounced when Ro 40-5967 was added to the medication. No significant changes of stroke volume and blood pressure were noted. 6. In conclusion Ro 40-5967 led to a significant elevation of the plasma concentration-time curve (AUC) of digoxin. This effect was dose-dependent.

Administration, Oral↗
PubMed1995

Day-night variations in the renal excretion of the antiarrhythmic agent tiracizine and its metabolites.

Daytime and nighttime urinary recovery as well as morning and evening trough serum levels of the antiarrhythmic agent tiracizine and three of its metabolites (M1, M2, and M3) were assessed during a 7-day multiple-dose study period (50 mg tiracizine twice daily) in eight healthy volunteers. A significantly lower mean steady-state urinary recovery was observed during the daytime as compared with during the nighttime (Ae (tot tau d)=42.0 +/- 15.7% vs. Ae (tot tau n)=51.2 +/- 19.6%). This difference is mainly due to a substantial increase of M1 and a smaller increase of M2 urinary recovery by night. Results of additional in vitro investigations showed the ratio of the nonionic/ionic forms of M1 and M2 to be highly dependent on pH in the range of pH 5-pH 7. Therefore, the observed day-night variations might be attributed to alterations of ionization, i.e., nonionic tubular reabsorption of the metabolites due to circadian differences in urinary pH. Trough serum levels of M1 and M2 tended to be higher at 7 P.M. as compared with 7 A.M. Due to the narrow therapeutic index of class I antiarrhythmics, the present results indicate the need for further investigations concerning the effect of urinary pH on the pharmacokinetics of tiracizine and its metabolites.

Adult↗
PubMed1995

Hemodynamic effects of extracardiac drugs.

Almost all types of drugs which primarily exert extracardiac effects may cause adverse cardiovascular reactions. This may apply to such frequently prescribed drugs as antihistamines, antidepressants and neuroleptic agents, antibiotics, lipid lowering drugs, and many others. Negative chronotropic, inotropic or dromotropic effects, changes in pre- and afterload with a decrease in stroke volume and cardiac output, or the occurrence of cardiac arrhythmias have all been reported upon treatment with extracardiac drugs. Physicians mostly fail to consider that these adverse events may well be related to drug effects, but rather ascribe them to the underlying disease or variations in the course of the patient's illness. Recent characteristic examples of the cardiovascular effects of extracardiac drugs are the cardiac arrhythmias (torsades de pointes) caused by the H1-receptor antagonists terfenadine and astemizole. These observations were made only many years after the availability of these drugs on the market-- in some countries even as over-the-counter drugs. In general, both the number of drugs causing undesired cardiac events and the different types of adverse cardiovascular reactions ascribable to these drugs appear to be on the increase.

Antidepressive Agents↗
PubMed1994

[Reversible thrombocytopenia due to digitoxin overdose].

A 65-year-old woman, known to have peptic ulcers, developed nausea and retching. Clinical examination demonstrated pain on pressure in the epigastrium with otherwise normative findings for age. Two gastric ulcers and gastritis with erosions were seen at endoscopy. The patient, who was being treated with digitoxin for heart failure, reported having taken up to four digitoxin tablets (0.07 mg each) daily because she had insomnia. The plasma digitoxin level was between 150 and 160 nmol/l (therapeutic range 17-33 nmol/l), while the ECG showed no signs of digitalis intoxication. Initially the platelet count was 40,000/microliter: there had been no history of thrombocytopenia or symptoms of abnormal haemostasis. Other laboratory tests were within normal limits. After digitoxin had been discontinued, the platelet count rose without further treatment to 373,000/microliter 3 weeks after hospital admission by which time the digitoxin level had fallen to 48.9 nmol/l. The gastrointestinal symptoms regressed completely on treatment with omeprazole (40 mg three times daily for 8 days) and ranitidine (150 mg twice daily).

Aged↗
PubMed1994

Elucidation of the structure of talinolol metabolites in man. Determination of talinolol and hydroxylated talinolol metabolites in urine and analysis of talinolol in serum.

The objective of this study was to determine the structure of talinolol metabolites formed and the amounts excreted in urine. Talinolol metabolites in urine were identified by comparing their HPLC retention times and their GC-MS profile with those of previously characterized reference compounds. The metabolites were quantified by HPLC with a normal-phase silica column, a single chloroform extraction and UV detection. Less than 1% of an administered dose was found in urine as hydroxylated talinolol. Other metabolites could be excluded. A sensitive method to determine talinolol in serum and a simple method for analysis of talinolol in urine are described. These methods were found to be precise and accurate for the measurement of talinolol in samples obtained from patients during chronic talinolol treatment as well as from healthy volunteers after a single dose of talinolol.

Adrenergic beta-Antagonists↗