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Biomedical subjects

C Fischer

Publications and source records attributed to C Fischer.

At least 271 records · Page 15Linked to original sources
PubMed1988

Pharmacokinetics and pharmacodynamics of nitrendipine in healthy subjects and patients with kidney and liver disease.

Nitrendipine [3-ethyl-5-methyl-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine dicarboxylate] is a calcium antagonist with a dihydropyridine structure that has a great structural resemblance to nifedipine. Instead of a methyl group in position 3, it has an ethyl group and the NO2 group is in the meta instead of in the ortho position. These minor structural differences have a pronounced impact with respect to both the pharmacokinetics and pharmacodynamics of nitrendipine as compared to nifedipine. Based on equimolar plasma concentrations, nitrendipine is on average three times more potent than nifedipine with regard to the reduction of peripheral vascular resistance, arterial blood pressure, and increased leg blood flow. The terminal half-life is on average 8 h, and thus substantially longer than the terminal half-life of 2-3 h for nifedipine. Despite its almost complete absorption, bioavailability is on average 15-25% and shows great interindividual variability ranging from 7 to 40%. The systemic plasma clearance of the drug is on average 18 ml/min/kg and thus approaches the liver blood flow. In patients with liver cirrhosis, the half-life is prolonged to 19.6 h, the total plasma clearance is decreased by 50%, and the bioavailability is more than doubled to 54%. No data are available if liver disease alters the pharmacodynamic response of the drug. Kidney disease has some effect on the disposition of the drug. Systemic clearance is not changed but the terminal elimination half-life is slightly prolonged to 10.5 h. This increase in half-life is due to an increased volume of distribution. Bioavailability, which is 21.2%, is not grossly altered in renal failure.

Humans↗
PubMed1988

Lack of effect of nitrendipine on the pharmacokinetics and pharmacodynamics of midazolam during steady state.

1. The possible interaction (as indicated by rat experiments) between calcium channel blocking agents and benzodiazepines has been evaluated in nine healthy subjects. 2. Subsequently to an intravenous loading dose (0.07 mg kg-1) midazolam was infused for 6 h (0.035 mg kg-1 h-1) and steady state plasma levels between 54 to 114 micrograms l-1 were achieved. Two hours after the bolus of midazolam a solution of 20 mg nitrendipine or placebo was administered in a randomized, double-blind crossover fashion. 3. The marked sedative-hypnotic effects of midazolam as assessed by visual analogue scales (about four fold increase in the sedation index) and choice reaction time (100% prolongation) indicated some form of adaptation or tolerance towards the end of the infusion. However, the midazolam-induced impairments were not affected by nitrendipine. 4. EEG-data indicated stabile benzodiazepine-like effects during the complete infusion period of midazolam (e.g. decrease in alpha activity, increase in sigma, delta 2 and beta 1 activity). Again, these alterations were not modified by nitrendipine. 5. There was also no pharmacokinetic interaction between both agents, since elimination of midazolam (t 1/2 = 2.5 +/- 0.8 h; CL = 548 +/- 143 ml min-1) was in close agreement with control values (t 1/2 = 2.4 +/- 0.6 h; CL = 512 +/- 102 ml min-1). Likewise, plasma levels of nitrendipine were comparable to literature data. 6. Thus, it could be concluded that nitrendipine does not affect the action of midazolam and therefore a direct involvement of calcium at the benzodiazepine receptor site is unlikely under our clinical conditions.

Adult↗
PubMed1988

Treatment of advanced, progressive epidemic Kaposi's sarcoma (EKS): a phase-II study.

The design of a prospective phase-II study on the treatment of Kaposi's sarcoma (KS) in patients with HIV infection is described. In this study the toxicity and antineoplastic activity of high-dose alpha-interferon (20 x 10(6) U/m2 s.c. daily) will be investigated in patients with advanced and progressive KS. Patients with progressing KS during IFN treatment or with relapsing KS after IFN will be treated with vinblastine (4 mg/m2 i.v., days 1, 8, and 15) and bleomycin (15 mg i.v., days 1 + 8). The study was only recently activated; results are so far not available.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Epidermoid cyst of the fourth ventricle.

The case of a 52-year-old patient with a fourth ventricle epidermoid is reported. The initial presentation included long-standing headaches, progressive anomalies of gait and slight impairment of mentation. CT showed a hypodense mass enhancing peripherally after contrast infusion. Brain auditory evoked responses (BAER) showed asymmetric increased latencies. At operation, total removal of an extensive fourth ventricle epidermoid was achieved. A delayed meningitis occurred postoperatively. Physical examination was normal at the 2 year follow-up and BAER were improved. The etiological and clinical features of fourth ventricular epidermoids are briefly reviewed. The diagnostic value of CT is emphasised but the possibility of CT-dense epidermoid cysts deserves a special mention. Total removal of the neoplasm is the theoretical aim of operative treatment, but this purpose may be harmful when the ventricular floor is involved by the capsule.

Brain Diseases↗
PubMed1988

St. Louis University.

Explore the source record for details and available documents.

Academic Medical Centers↗
PubMed1987

Identification of novel arachidonic acid metabolites formed by prostaglandin H synthase.

The metabolism of [1-14C]arachidonic acid by microsomal and purified prostaglandin (PG) H synthase was investigated. HPLC analysis confirmed that arachidonic acid (20:4) was extensively converted into prostaglandin G2 (PGG2) and/or prostaglandin H2 (PGH2) but several minor labelled products were formed in addition. Their formation, mediated by PGH synthase was established by inhibition with aspirin and indomethacin [Hecker, M., Hatzelmann, A. & Ullrich, V. (1987) Biochem. Pharmacol. 36, 851-855]. Upon comparison with authentic reference material these unknown PGH synthase metabolites were identified with respect to chromatographic properties, ultraviolet spectroscopy and mass spectrometry as 11 (R)-hydroperoxy-5Z,8Z,12E,14Z-eicosatetraenoic acid (11-OOH-20:4), 12(S)-hydroperoxy-5Z,8E,10E-heptadecatrienoic acid (OOH-17:3), 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (OH-17:3), 15(RS)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoi c acid (15-OOH-20:4), 15(RS)-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (15-OH-20:4), 13-hydroxy-5Z,14Z-prostaglandin H2, 15(S)-hydroxy-8-iso-5Z,13E-prostaglandin H2 and 15-oxo-prostaglandin H2. Unlike PGG2 and PGH2, 8-iso-PGH2, 13-hydroxy-PGH2 and 15-oxo-PGH2 failed to induce aggregation of washed human platelets and to form thromboxane upon incubation with homogeneous human platelet thromboxane synthase. In contrast to the formation of OOH-17:3, 15-oxo-PGH2 and OH-17:3 which can be attributed to the heme-catalyzed decomposition of PGG2 and PGH2, 11-OOH-20:4,15-(O)OH-20:4-,8 iso-PGH2 and 13-hydroxy-PGH2 represent potential side products of arachidonic acid conversion into PG endoperoxides. Their formation allows to conclude on PGH synthase mechanism and its intermediates for which an extended reaction scheme is proposed.

Animals↗
PubMed1987

[Nuclear spin tomography and computerized tomography in malignant hypernephroma].

Forty patients with histologically confirmed hypernephromas were examined by MR and CT. As regards T-staging, MR had an accuracy of 97% and CT of 91%; for N-staging, MR had an accuracy of 85% and CT of 91% and, with regard to infiltration of the renal vein, MR was correct in 88% of cases and CT in 81%. MR was most accurate in the pre-operative assessment of tumour spread, demonstrating caval involvement in 100% and lymph node metastases in 97%. On the other hand, infiltration of the renal pelvis could be assessed in only 65% of cases; in 27% the assessment was not possible and in 8% one could not be certain. CT proved to be at its best for staging of lymph nodes, but in 15% it was not possible to identify infiltration of the renal vein. MR was not greatly superior to CT in the preoperative diagnosis and staging of hypernephromas.

Carcinoma, Renal Cell↗
PubMed1987

Application of stable isotope methodology to study the pharmacokinetics, bioavailability and metabolism of nitrendipine after i.v. and p.o. administration.

1. The pharmacokinetics, bioavailability and metabolism of nitrendipine were studied in six healthy volunteers (three females, three males) using [13C4]-nitrendipine as a biological internal standard. In the first study the drug was administered simultaneously by the i.v. [13C4] and p.o. (solution) routes and in a second study two oral preparations (13C4-solution and commercial tablet) were administered, also simultaneously. 2. The mean terminal elimination half-life was 8.3 +/- 3.2 h (range 3.4 to 16 h) with no differences between the intravenous and oral route of administration. Total plasma clearance averaged 18.7 +/- 0.6 ml min-1 kg-1 and volume of distribution at steady state 5.4 +/- 2.4 1 kg-1. 3. Following oral administration of nitrendipine solution the percentage of dose absorbed was 88.4 +/- 16.0% based on urinary excretion of metabolites. Despite its almost complete absorption, absolute bioavailability of the solution was only 22.6 +/- 6.7% due to extensive presystemic elimination. The bioavailability of the commercial tablet relative to the solution was 82.2 +/- 20.3%. 4. Both after i.v. and oral administration the drug was extensively metabolized with less than 0.5% of the dose excreted as unchanged drug in urine. Cleavage of the two ester functions in position 3 and 5, respectively, to carboxylic acids and further hydroxylation of the methyl groups in position 2 and 6 of the pyridine ring to the corresponding hydroxymethyl carboxylic acids constituted the major urinary metabolites accounting for 35.0 +/- 16.5% (i.v.) and 32.8 +/- 20.4% (p.o.), respectively, of the dose administered. 5. Binding of nitrendipine to plasma proteins was high with a fraction unbound of only 0.02 +/- 0.012 (range 0.011 to 0.036).

Administration, Oral↗
PubMed1987

[Complete excision of acoustic neurinoma. Preservation of the facial nerve and hearing].

Using microtechniques, total removal of acoustic neuromas with facial nerve preservation is possible today in most cases. The next barrier of operative treatment is hearing preservation which is routinely attempted, with the help of intraoperative brainstem auditory evoked responses monitoring. The present series deals with 176 operations performed sub-occipitally in 159 patients from 1970 up to 1985. Twelve patients were operated upon 29 times. According to the W.T. Koos classification, there were 16 type II, 39 type III and 121 type IV neuromas. Ten patients died postoperatively. In seven of these, death was related to surgery, in two it was caused by respiratory failure. In the last patient unexplained sudden death occurred. 169 patients had no facial weakness preoperatively, in 158 of these the facial nerve was anatomically preserved (93.5%). Facial nerve function was judged by evaluation of function of face at least 12 months after operation. Up to 36 months after surgery, a good facial result may be expected in cases where the facial nerve was macroscopically spared at completion of removal. Functional results have been reviewed in 151 patients according to the J.W. House's International Evaluation System, with an excellent or good result in 66 (44%), fair in 65 (43%), bad or poor in 20 (13%). The anatomical preservation of the cochlear nerve could be achieved in 80 patients of the group of 169 in whom the auditory function had not been damaged by a previous operation. In fact, the auditory function preservation could be reasonably attempted in 79 patients: showing a hearing loss below 70 dB on tone audiometry, whatever may be the result of speech discrimination score. 59 patients (75%) of this later group had their auditory nerve preserved, 14 (18%) showed preserved hearing function postoperatively, 10 of these with a speech discrimination score over 50%. Two of these showed an improvement of preoperative hearing, two others showed a total recovery of hearing function after removal.

Adolescent↗