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Biomedical subjects

A Lohmann

Publications and source records attributed to A Lohmann.

At least 19 recordsLinked to original sources

[Surgical intervention in severe acute pancreatitis--retrospective study of 79 patients of the RWTH Aachen Surgical Clinic].

This is a report on the surgical intervention in 79 patients with acute pancreatitis, who were operated in the Department of Surgery of the University Clinic RWTH Aachen in the period from 1986 to 1993. The main objective was the stratification of pancreatitis according to the Ranson-Score, the analysis of the surgical treatment and the timing of operation depending on the clinical condition. The average Ranson-score was 3.3 (median 3). 56 patients had necroses, which were removed because of the deteriorating clinical condition. In these cases the average Ranson-score was 4.2 (median 4). Seven patients (8.9% of the total number and 12.5% of the patients with necroses of the pancreas) died. This small number is the result of a severity-adapted management in a modern intensive care-unit and the good cooperation with the Department of Internal Medicine.

Adult↗

[Simultaneous retroperitoneal operation of juxtarenal abdominal aortic aneurysm and ischemic vertebral body necrosis].

The combination of abdominal aortic aneurysm (AAA) and necrosis of the lumbar vertebral bodies is often the consequence of ischemia of the lumbar arteries and local compression from the aneurysm. A patient with necrosis of lumbar vertebral bodies 2 to 4 was admitted for abdominal aneurysm repair. CT scanning revealed almost complete destruction of the second and fourth lumbar vertebral bodies. In a combined operation an orthopedic and a vascular surgical team implanted two carbonic cages with autogenous splinter of the pelvic bone and an aortic vascular graft, using a retroperitoneal approach. Three months after the operation the 61-year-old man is entirely well and without any signs of back pain. He could be fully mobilized within 3 weeks postoperatively. This case study depicts the surgical techniques and discusses the advantages of the simultaneous operation and retroperitoneal exposure.

Aortic Aneurysm, Abdominal↗

Comparison of the stimulus properties of ethanol and the Ca2+ channel antagonist nimodipine in rats.

A variety of L-type Ca2+ channel antagonists, including the dihydropyridine derivative nimodipine, have been shown to be effective in reducing ethanol intake and preference in animal models of alcoholism. The behavioral mechanism involved in the anti-alcohol effects of nimodipine are, however, not clear yet. The aim of the present study was to investigate the possibility that the effects of nimodipine on ethanol intake are based on stimulus substitution. Therefore, rats were trained to discriminate ethanol (12.5% w/v, 1000 mg/kg i.p.) from saline in a two-lever food-reinforced drug discrimination procedure (dose range of ethanol tested: 125-1000 mg/kg i.p., ED50 value: 488 mg/kg). In cross-generalization tests with nimodipine (0.15-15 mg/kg i.p.), stimulus substitution was not noted. In addition, a cross-familiarization conditioned taste aversion paradigm was utilized. In rats, 1000 mg/kg i.p. ethanol was used as the reference drug producing a conditioned taste aversion. Effects of preexposure to ethanol (500-1500 mg/kg i.p.) and nimodipine (7.5-30 mg/kg i.p.) on the magnitude of the ethanol-induced conditioned taste aversion were investigated as an index for stimulus similarity between preexposure and reference drug. Preexposure to both ethanol and nimodipine prevented the development of a conditioned taste aversion. Contrary to the drug discrimination results, these latter findings suggest that there may be similarities between the stimulus properties of nimodipine and ethanol. Moreover, the apparent discrepancy between the results obtained in drug discrimination and cross-familiarization conditioned taste aversion suggests that different stimulus properties of ethanol control behavior in both procedures. The finding that, under particular conditions, ethanol and nimodipine appear to share common stimulus properties needs to be further evaluated, as this may be related to the reported anti-alcohol effects of nimodipine and other Ca2+ channel antagonists.

Analysis of Variance↗

The calcium channel agonist BAY k 8644 reduces ethanol intake and preference in alcohol-preferring AA rats.

Applying a 12-h limited access, two-bottle choice procedure, antialcohol effects of the 1,4-dihydropyridine (DHP) L-type calcium (Ca2+) channel agonist BAY k 8644 were investigated in alcohol-preferring AA rats. In this Wistar line, selectively bred for a high 10% v/v ethanol (EtOH) preference in a free choice situation, effects on EtOH preference and intake, as well as on food and total fluid intake were evaluated for racemic BAY k 8644 (0.1-1 mg/kg IP; 0.25-2 mg/kg PO), its agonistic (-)-enantiomer (0.1-1 mg/kg IP and PO) and its antagonistic (+)-enantiomer (10-50 mg/kg IP and PO). Irrespective of route of application, BAY k 8644 was found to be effective in reducing both EtOH intake and preference (minimal effective dose: 0.5 mg/kg; maximum effect: approximately 60% of baseline levels). The (+)-enantiomer, acting as a low-potency Ca2+ channel antagonist, also reduced EtOH intake and preference, but the effects were not very selective as food intake was also substantially reduced. Moreover, the effects were only obtained at relatively high doses (50 mg/kg). The essential enantiomer involved in the antialcohol effects of BAY k 8644 seems to be the (-)-enantiomer, acting as a strong Ca2+ channel agonist. This latter compound was potent (minimal effective dose: 0.3 mg/kg), very effective in reducing EtOH intake (maximum effect: 29% of baseline level) and preference (26% of baseline) and apparently more selective. Although slightly decreasing over days, effects of (-)-BAY k 8644 on EtOH intake and preference were shown to remain after repeated treatment (10 successive days, 0.3 mg/kg IP). Interestingly, the acute antialcohol effects of (-)-BAY k 8644 (0.3-1 mg/kg IP) could not be antagonized with the DHP L-type Ca2+ channel antagonists nimodipine (0.01-1 mg/kg IP) and (-)-nimodipine (1-30 mg/kg IP). The present results suggest that a mechanism of action other than L-type Ca2+ channel agonism is involved in the antialcohol effects of (+/-)- and (-)-BAY k 8644. Alternatively, it is possible that the previously described antialcohol effects of DHP Ca2+ channel antagonists are not related to antagonistic activity at Ca2+ channels. Finally, it cannot be excluded that a mechanism unrelated to Ca2+ channels is responsible for the antialcohol effects of both DHP Ca2+ channel agonists and antagonists.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Ethanol intake-reducing effects of ipsapirone in rats are not due to simple stimulus substitution.

The present series of experiments was conducted to investigate whether the previously reported ethanol intake reducing effects of the 5-HT1A receptor agonist ipsapirone could be based on possible stimulus similarities between both compounds. Rats were trained to discriminate ethanol (12.5% w/v, 1000 mg/kg, IP) from saline in a two-lever food-reinforced drug discrimination (DD) procedure. Discrimination criterion was reached after a mean number of training sessions of 42. In subsequent generalization sessions, a dose-response curve was established for ethanol (125-1000 mg/kg, IP, ED50 value: 355 mg/kg). In additional cross-generalization tests with ipsapirone (1-30 mg/kg, IP), stimulus substitution for the ethanol cue was not noted (maximal degree of generalization: 33%, at 10 and 30 mg/kg). To confirm the DD findings that ipsapirone does not substitute for ethanol, an alternative cross-familiarization conditioned taste aversion paradigm (CF-CTA) was utilized. In rats, 1000 mg/kg IP ethanol was used as the reference drug producing a conditioned taste aversion (CTA). It was found that preexposure to ethanol (500-1500 mg/kg, IP) dose-dependently attenuates the CTA produced by this same drug. Full familiarization was noted with 1000 and 1500 mg/kg. In contrast with this, ipsapirone (1-30 mg/kg, IP) failed to abolish ethanol-induced CTA, suggesting again that the ipsapirone stimulus complex is dissimilar to that produced by ethanol. Because the present findings indicate that, in rats, ipsapirone does not substitute for ethanol, it is suggested that the reported ethanol intake-reducing effects of ipsapirone in animal models of alcoholism are not due to simple stimulus substitution.

Alcohol Deterrents↗

Conditioned taste aversion and place preference induced by the calcium channel antagonist nimodipine in rats.

It has become clear that various calcium channel antagonists are able to suppress excessive intake of ethanol in rats. With respect to these findings, it has become of interest whether these drugs can act as rewarding and/or aversive stimulus. Therefore, such affective stimulus effects of the L-type calcium channel antagonist nimodipine and its enantiomers were studied in Wistar rats in a series of conditioned taste aversion (CTA; two-bottle choice procedure) and conditioned place preference (CPP; two-compartment procedure) experiments. Racemic nimodipine (0.95-15 mg/kg IP) was found to induce a dose-dependent CTA, 7.5 mg/kg being the lowest effective dose. Subsequent studies with both enantiomers revealed that the CTA effects of nimodipine are completely dependent on the activity of (-)-nimodipine. With (+)-nimodipine (0.25-90 mg/kg IP), none of the doses tested induced a significant CTA, whereas with (-)-nimodipine clear and dose-dependent CTA effects were noted (0.5-30 mg/kg IP). For this enantiomer, the lowest effective dose was 15 mg/kg. In additional CPP experiments, it was confirmed that (+/-)-nimodipine and (-)-nimodipine have affective stimulus properties, whereas (+)-nimodipine was again an ineffective stimulus (dose used for all drugs: 15 mg/kg IP). Interestingly, the affective stimulus effects as measured with CPP of (+/-)- and (-)-nimodipine turned out to be rewarding, as it was found that both drugs produced a significant place preference. It is concluded from these studies that nimodipine possesses intrinsic affective stimulus effects which are rewarding in nature. Furthermore, these stimulus effects are mediated by the activity of the (-)-enantiomer. Possibly, these rewarding effects of nimodipine may play a role in the reported attenuating effects of this drug on voluntary ethanol intake in rats.

Animals↗

Effect of long-term angiotensin-converting enzyme inhibition on vascular function in patients with chronic congestive heart failure.

The present study demonstrates that peripheral vasodilatory capacity is impaired in patients with chronic congestive heart failure not treated with aspirin, but preserved in patients taking aspirin. This decreased peripheral vasodilatory capacity can be restored by chronic angiotensin-converting enzyme inhibition, indicating that locally acting cyclooxygenase-dependent factors contribute to peripheral vasoconstriction in chronic congestive heart failure.

Adult↗

Determination of apovincaminic acid in serum by means of high-performance liquid chromatography.

A high-performance liquid chromatographic method for the determination of low concentrations in serum of apovincaminic acid, the main metabolite of vinpocetine, is reported. The assay includes a two-step ion-pair extraction with tetrabutylammonium as counter ion. Recovery is ca. 40%. Separation is performed on a narrow-range 5 microns particle size octadecylsilane modified silica packing. Heptanesulphonic acid is the pairing ion in the eluent, and the ultraviolet detection wavelength is 224 nm. Yohimbine serves as the internal standard. The assay is fast, accurate and sensitive quantifying at least 5 ng/ml apovincaminic acid in serum. The method was applied to the analysis of serum samples from aged subjects, treated with a 20-mg dose of vinpocetine.

Chromatography, High Pressure Liquid↗

Bioavailability of vinpocetine and interference of the time of application with food intake.

In a pilot study based on an open cross-over design involving four phases, the relative bioavailability of the eburnamenine derivative vinpocetine (CAS 42971-09-5) was investigated in 8 healthy volunteers in relation to different times of drug administration relative to food intake. The substance was applied orally as 10 mg film tablets. The areas under the plasma concentration-time curves (AUC) amounted to 27.3 +/- 18.1 ng.h/ml (fasting) and 42.8 +/- 27.4 up to 54.3 +/- 38.4 ng.h/ml (non-fasting, intake before and after meal, resp.). The relative bioavailability under non-fasting conditions was found to be approx. 60 to 100% higher than under fasting conditions.

Adult↗

Development of a sensitive enzyme immunoassay for the determination of vinpocetine in human plasma.

An Enzyme immunoassay for the quantitative determination of vinpocetine (CAS-42971-09-5) in human plasma has been developed. The lower limit of quantification is 0.1 ng/ml plasma. The assay shows no cross reactivity with the major metabolite apovincaminic acid. Because of a strong unspecific binding of vinpocetine to plasma proteins an extraction step was necessary. The inter- and intra-assay reproducibility of the test (coefficient of variation) is in a range of 1.1 and 18.3%.

Antibody Specificity↗

Determination of bencyclane in human plasma by means of capillary gas chromatography and nitrogen-phosphorus selective detection.

A sensitive and specific method for the determination of bencyclane in human plasma is presented. Bencyclane was extracted from human plasma with two 3-ml volumes of isooctane and was shaken for 10 min. The organic phase was separated and evaporated to dryness at 40 degrees C under a nitrogen stream. The residue was dissolved and an aliquot was injected into the gas chromatograph. The separation was performed with a DB-17 column with helium as the carrier gas. Nitrogen-selective detection was performed. The quantification was performed with the signal output. The limit of detection was 1 ng/ml.

Bencyclane↗

Determination of fendiline in human plasma by means of capillary gas chromatography and nitrogen-phosphorus selective detection.

A sensitive and specific method for the determination of fendiline in human plasma is presented. Fendiline was extracted from human plasma after the addition of phosphate buffer two times with 4 ml of n-hexane. The organic phase was separated and evaporated to dryness at 40 degrees C under a stream of nitrogen. The residue was dissolved and an aliquot was injected into the gas chromatograph. Chromatographic separation was performed with a DB-1 column with helium as carrier gas. Nitrogen-selective detection was performed. Quantification was performed with the signal output. The limit of detection was 1 ng/ml of plasma.

Chromatography, Gas↗

Influence of food on the bioavailability of theophylline from a sustained-released theophylline preparation.

In a single-dose cross-over study with 12 healthy male volunteers the relative bioavailability of theophylline (CAS 58-55-9) in a dosage of 700 mg (sustained-release preparation) under fasting- and non-fasting conditions was investigated. The areas under the plasma concentration-time curves AUC amounted to 184.2 +/- 42.7 micrograms.h/ml (fasting) and 157.9 +/- 32.9 micrograms.h/ml (non-fasting, p = 0.031). The bioavailability was reduced by approx. 15% by concomitant food intake. The 95% confidence intervals for AUC and Cmax were 76-99% and 78-105%, respectively, and therefore narrowly outside the usual 80-120% limits. There were no therapeutically relevant changes with regard to the parameters Cmax, tmax and MRT. The MRT values of 13.4 and 13.9 h respectively showed furthermore that theophylline represents a twice-daily formulation. No "dose-dumping effect" was observed.

Administration, Oral↗

Investigation of the possible influence of the absorption of vinpocetine with concomitant application of magnesium-aluminium-hydroxide gel.

The concomitant application of magnesium-aluminium-hydroxide gel does not influence the absorption of vinpocetine (CAS 42971-09-5). The pharmacokinetics of vinpocetine under the influence of a concomitant application of magnesium-aluminium-hydroxide gel was investigated. 18 healthy male volunteers were included in the study. Vinpocetine was administered in the galenic form of a film-coated tablet in a dosage of 20 mg t.i.d. over 10 days. On days 5 and 6 of the study, blood samples were taken at 16 different moments over 24 h and analyzed as to their vinpocetine content. Starting with the 6th day of the study, the patients were administered in addition 1 sachet of an magnesium-aluminium-hydroxide gel 4 times a day. On day 9 of the trial, blood samples were taken again over 24 h. The parameters examined were AUC, Cmin, Cmax, tmax and Mean Residence Time. The results as to these parameters of day 5 were compared with those of day 9. As a further parameter, apovincaminic acid plasma levels were determined. There was no difference as to the vinpocetine amount absorbed with or without concomitant application of magnesium-aluminium-hydroxide gel. Apovincaminic acid plasma levels were lowered by approx. 11% when associated with the antacid.

Adult↗

[Nasal concentrations of fusafungin following administration of a dosage aerosol (Locabiosol)].

Following investigations on content uniformity and of the drug content delivered per each dose from a pressurised aerosol (Locabiosol) the concentration of the locally acting antibiotic fusafungin was determined in nasal secretions of volunteers. Quantitative HPLC-assay of fusafungin was performed following the extraction of cotton swabs used to collect nasal secretions. The volume of the nasal secretions results from the mass difference of the swabs before and after application. The concentrations of fusafungin measured on 41 volunteers over a period of 3 hrs were evidently higher than the minimum inhibitory concentrations reported in literature. The results of controlled clinical studies of other authors are in agreement with these results.

Adult↗