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Biomedical subjects

T Wagner

Publications and source records attributed to T Wagner.

At least 253 records · Page 14Linked to original sources
PubMed1986

[Fibrinolytic therapy of massive pulmonary embolism on the 1st postoperative day following cholecystectomy].

Two patients, aged 64 and 47 years, had a massive pulmonary embolism one day after cholecystectomy. Ultra-short fibrinolysis was undertaken with 1.5 million units of streptokinase. Both patients rapidly improved, with a fall in heart rate, pulmonary artery or central-venous pressure, and a rise in arterial pO2. There were no significant bleedings. Ultra-short fibrinolysis (maximally over one hour) can thus successfully lyse emboli--consisting of fresh plasminogen-rich coagulation thrombi in the early postoperative period--without re-opening wound- and capillary beds during this short period.

Cholecystectomy↗
PubMed1986

Comparison of the opioid activity of CAM and kappa agonists.

CAM has been shown to produce opiate agonist and antagonist activities. Based on its potent agonist activity in rabbit vas deferens and the low potency of naloxone to antagonize its agonist effect in the guinea pig ileum and mouse vas deferens, CAM can be considered as kappa agonist. It is further supported by its diuretic effect and the estimated "apparent pA2" values with naloxone and Mr-2266BS. However, in the rabbit ear artery and cat nictitating membrane, ethylketazocine (EK) produced agonist activity, while CAM produced antagonist activity. Also, EK differs from CAM in mouse vas deferens in the presence of 4-aminopyridine. It is concluded, that CAM might be an agonist on kappa type (subtype) of opiate receptors, although its spectrum of activity was found to be different from EK or bremazocine.

Animals↗
PubMed1986

Intracavitary chemotherapy with activated cyclophosphamides and simultaneous systemic detoxification with protector thiols in Sarcoma 180 ascites tumor.

Activated cyclophosphamides such as 4-sulfoethylthiocyclophosphamide (mafosfamide) are suitable for a local intracavitary chemotherapy, whereas cyclophosphamide requires a metabolic activation. Mafosfamide administered i.p. in mice was less toxic (50% lethal dose, 640 mg/kg) than its i.v. application (50% lethal dose, 480 mg/kg). A further remarkable reduction of toxicity with an increase of the 50% lethal dose of mafosfamide to 1500 mg/kg was obtained by the simultaneous i.v. application of the protector thiol cysteine (mafosfamide:cysteine ratio, 1:5 on molar weight basis). In comparison with the i.v. injection of mafosfamide, the local i.p. application resulted in a 20 times higher concentration versus time product of peritoneal drug levels. The molar ratio of sulfhydryl groups to activated cyclophosphamide (resorbed from the peritoneal cavity) remained high in blood. Therapy studies on Sarcoma 180 ascites tumor of mice revealed that the coadministration of cysteine i.v. in mafosfamide i.p. treatment is superior to mafosfamide i.p. application alone. On the contrary, the simultaneous i.p. application of cysteine is accompanied by a loss of antitumor efficacy. The regimen of local i.p. chemotherapy with activated cyclophosphamide and simultaneous systemic detoxification by an appropriate thiol allows the reduction of the systemic toxicity of treatment without influence on the cancerotoxic activity at the site of local injection and the exposing of the intraabdominal tumor to a much higher concentration of the cytostatic agent.

Animals↗
PubMed1986

Pharmacokinetics and bioavailability of oral ifosfamide.

The bioavailability of oral N,3-bis(2-chloroethyl) tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide (ifosfamide) (500-mg gelatine capsules) was investigated in 18 patients with bronchogenic carcinoma. Oral and intravenous (Holoxan) ifosfamide was applicated in a randomized sequence on days 1 and 3 at a dose of 1 g/m2 (n = 12) and 2 g/m2 (n = 6). Ifosfamide determination was performed with N/P flame ionization gas chromatography following derivatization with heptafluorobutyric acid. Orally administered ifosfamide showed relatively fast absorption kinetics. Peak levels were reached within 1 h in both dosage groups. With exception of the absorption phase blood level curves of orally and i.v. administered ifosfamide were identical. The average half-life of ifosfamide was 5.5 h (2 g/m2) and 5.8 h (1 g/m2) with a considerable individual variation in both dosage groups. The bioavailability of oral ifosfamide calculated as ration AUCp.o./AUCi.v. was 1.04 after 1 g/m2 ifosfamide and 0.95 in the 6 patients receiving 2 g/m2 ifosfamide. According to our results i.v. administration of ifosfamide especially in fractioned dosage regimes can be replaced by oral application of the same ifosfamide dose.

Administration, Oral↗
PubMed1985

Distribution of albumin in normal and regenerating livers of mice. A light microscopic immunohistochemical and autoradiographic study.

The conditions affecting the immunohistochemical identification of albumin in livers of male NMRI-mice were investigated by light microscopy. In normal livers albumin is randomly distributed, revealing a pancytoplasmic nearly homogen reaction in groups of hepatocytes or single parenchymal cells. However, combined autoradiographic studies after pulse labelling with 3H-valine and perfusion experiments with human albumin indicate that this distribution is caused by albumin from blood plasma and does not reflect true protein synthesis. After perfusion of the livers followed by immunohistochemical amplification techniques which allowed to dilute the primary antibody up to 1:30,000, albumin could be detected nearly in all liver parenchymal cells as granular deposits decreasing in its density from periportal fields towards the terminal hepatic venules. In regenerating livers due to partial hepatectomy no remarkable differences in granular albumin deposits between G1- and S-phase of the cell cycle could be detected as was demonstrated by combined immunohistochemistry and 3H-dThd-autoradiography. However, during mitosis the content of albumin was often considerably reduced.

Albumins↗
PubMed1984

Pharmacokinetics of "activated" cyclophosphamide and therapeutic efficacies.

Estimation of "activated" cyclophosphamide (4-OH-CP) in blood of cancer patients and laboratory animals has revealed significant differences between pharmacokinetics of cyclophosphamide (CP) in man and laboratory animals after CP treatment. Whereas in blood of mice and rats relatively high concentrations of 4-OH-CP were found to exist for a relatively short time, in blood of humans only low, but longer-lasting, blood levels were detected after administration of comparable CP doses. In order to examine whether these different pharmacokinetic behaviors might account at least in part for the known differences of antitumor activity and toxicity of CP between humans and laboratory animals, the authors studied the influence of pharmacokinetics of activated CP on therapeutic efficacy and toxicity after injection of 4-(S-ethanol)-sulfido-cyclophosphamide (P1), a pro drug of activated CP, into nude mice bearing heterotransplanted human bladder sarcoma. With P1, which hydrolyzes quickly in blood to yield 4-OH-CP, different blood level shapes of 4-OH-CP could be established either by single bolus injection of P1 or by repetitive injection of a loading dose followed by several maintenance doses which caused nearly constant levels of activated CP for a longer time period. With these models it was found that 4-OH-CP showed more therapeutic efficacy when present in blood at relatively low levels for longer times than after bolus injection of the same dose resulting in a sharp peak level of activated CP. So after single intraperitoneal (IP) injection of 300 mg/kg P1 which caused a bioavailability of 36 mumol/ml-1/minute a 67% inhibition of tumor growth was achieved, whereas a tumor growth reduction of 83% was obtained after injection of the same dose in 6 fractions resulting in constant blood levels with a bioavailability of only 17 mumol/ml-1/minute. In contrast to the significant influence on antitumor efficacy of activated CP, practically no effect of pharmacokinetics on toxicity of 4-OH-CP could be observed. Therefore, the bioavailability of activated CP, which killed 50% of the animals, was determined to be approximately 89 mumol/ml-1/minute after adjustment of pharmacokinetics to yield constant levels and approximately 79 mumol/ml-1/minute after single bolus injection. The experiments presented show that by adjustment of pharmacokinetics the therapeutic index of P1, defined as bioavailability causing 50% of animals to die, referred to bioavailability causing 90% tumor growth inhibition, could be more than doubled.

Animals↗
PubMed1984

Isoleucyl initiator tRNA does not initiate eucaryotic protein synthesis.

Initiator tRNA from yeast (tRNAMeti) was quantitatively misaminoacylated with L-isoleucine using isoleucyl-tRNA synthetase from Escherichia coli. Surprisingly the misaminoacylated Ile-tRNAMeti neither participates in nor inhibits the initiation of globin synthesis in a rabbit reticulocyte lysate, whereas Met-tRNAMeti readily initiates protein synthesis in the same system. The incompetent behavior of Ile-tRNAMeti may be related to the observation that in vitro it does not form a stable complex with eucaryotic initiation factor 2 (eIF-2) and GTP, under conditions which lead to a stable eIF-2 X GTP X Met-tRNAMeti ternary complex. This indicates that eIF-2 can discriminate between the side chains of the aminoacyl adducts of the tRNAMeti during ternary complex formation, the first essential step in initiation of eucaryotic protein synthesis.

Animals↗
PubMed1984

Bioavailability of cyclophosphamide from oral formulations.

Cyclophosphamide (CP) is an alkylating cytostatic compound, which is activated to its cytotoxic form in the liver [1]. Since the therapeutic range of CP in the treatment of human tumours, is small like other cytostatics, a constant high bioavailability is essential for its oral administration. Although CP has become one of the most widely used cytostatics [2], there do not appear to have been any bioavailability investigations providing the necessary information. The development of a very sensitive gas chromatographic analytical method has now permitted investigation of the pharmacokinetics of oral CP in conventional clinical doses [3, 4, 5, 6].

Biological Availability↗
PubMed1984

Investigations concerning the correlation between liver cell proliferation, production of alpha-fetoprotein, and DNA-synthesis of lymphocytes in the spleen of NMRI-mice. An autoradiographic and immunohistochemical study.

To obtain more information concerning the correlation between liver cell proliferation, production of alpha-Fetoprotein (AFP) and DNA-synthesis of lymphocytes in the central and peripheral parts of periarteriolar lymphatic sheaths ( PALS ) of the spleen, these parameters were monitored in intervals of 12h after CCl4-poisoning of NMRI-mice using autoradiographic and immunohistochemical methods. The results indicate that synthesis of AFP is not linked closely to proliferation of hepatocytes because in contrast to DNA-synthesis the production of AFP was only detectable in a very small subpopulation of liver parenchymal cells reaching a peak before the majority of hepatocytes was found to enter the S-phase of the cell cycle. Beyond this, in vivo no general suppressive effect of AFP on proliferation of lymphocytes in preferably T-dependent areas of the spleen could be detected since the 3H-TdR-labeling index in these compartments increased, reaching a peak 48h after the maximum of hepatocytes producing AFP had occurred.

Animals↗
PubMed1984

[Pharmacokinetics of 5-fluorouracil and its permeation in pleural effusions in the therapy of metastatic breast cancer].

The pharmacokinetic of 5-Fluorouracil and its permeation into malignant pleural effusion was investigated in 9 patients with breast carcinoma who received 600 mg/m2 5-Fluorouracil i.v. within the CMF protocol. Despite the short plasma halflife of 5-Fluorouracil (16,8 min) distinct concentrations with peak levels up to 115 nmol/ml after 30 min were observed in the effusions. In consequence of the rapid elimination of 5-Fluorouracil from the plasma and the comparatively slow retrograde diffusion (t 1/2 55 min) from the pleural space, the drug levels persisted longer in the effusions, than in the blood. Thus the area under the curve of the pleural level (AUC) reached 50% (27-85%) of the corresponding plasma AUC (10,9 +/- 2,3 mumol x min x ml-1). From a pharmacokinetic point of view, no additional local instillations of 5-Fluorouracil are necessary during a systemic therapy of breast cancer with pleural effusions.

Aged↗