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Biomedical subjects

T Wagner

Publications and source records attributed to T Wagner.

At least 271 records · Page 15Linked to original sources
PubMed1984

[Sonographic study of the effect of hyoscin-N-butylbromide on cholecystokinin stimulated gallbladder motility].

The influence of the spasmolytic agent Hyoscine-N-butylbromide on the Cholecystokinin induced gallbladder contraction was investigated by ultrasonography in 25 volunteers. Even at a dosage of 0.15 mg/kg i.v. administered Hyoscine-N-butylbromide inhibited significantly the gallbladder emptying. In the investigated dosage range up to 0.6 mg/kg Hyoscine-N-butylbromide a strong response relationship was found. Since after the application of Hyoscine-N-butylbromide 30 min. before Cholecystokinin injection no loss of efficacy was observed, a considerably longer duration of the spasmolytic effect can be assumed. Also the oral form of the spasmolytic (dragees, mean dosage 0.6 mg/kg, application 30 min. before Cholecystokinin) showed a significant inhibition of gallbladder motility.

Adult↗
PubMed1984

Pharmacokinetics and bioavailability of cyclophosphamide from oral formulations.

The bioavailability of three administration forms of cyclophosphamide (CP) was determined by comparison with the i.v. application in 12 female patients with breast cancer. CP charges were given on four consecutive days at a dosage of 175 mg/m2 (50-mg dragees) in a randomized sequence. CP blood levels were measured with N/P flame ionization gas chromatography. The average half-life of intravenously applicated CP and for all three oral formulations was about 4 h. The ratio AUC p.o./AUC i.v. was 0.896 with the gastric juice-resistant formulation of CP, and 0.914 and 0.958 with the two "rapid release" formulations (soluble in gastric juice). The slight differences in the bioavailability and in the peak concentration (19.1; 22.1; 22.8 nmol/ml) were not significant. However, the gastric juice-resistant formulation displayed delayed peak times (2.5 h as compared to 1.13 and 1.42 h) as well as an irregular absorption phase with several maxima in the blood level curves in a few patients. When a first-pass effect of approximatively 8% is added to the bioavailability of the nonmetabolized CP, an almost complete absorption results for all CP formulations. Since the first-pass effect by hepatic metabolism of CP represents no detoxication, but a conversion of inactive CP into the actual cytostatically active form, a cytostatic bioavailability of likewise almost 100% can also be assumed.

Administration, Oral↗
PubMed1983

Inhibition of ribosomal translocation by peptidyl transfer ribonucleic acid analogues.

The activity of peptidyl-tRNALys-CpCp2'dA was measured in an in vitro poly(A)-dependent polypeptide synthesizing system derived from Escherichia coli. It has already been shown that Lys-tRNALys-CpCp2'dA is active as an acceptor and Ac2-Lys-tRNALys-Cp2'dA can donate its peptidyl residue but that the overall poly(A)-dependent synthesis of polylysine does not take place with Lys-tRNALys-CpCp2'dA [Wagner, T., Cramer, F., & Sprinzl, M. (1982) Biochemistry 21, 1521-1529]. This is due to the efficient inhibition of the EF-G-dependent translocation of the peptidyl-tRNA CpCp2'dA from the ribosomal A to the ribosomal P site. In addition, the EF-G-dependent release of the deacylated tRNALys-CpCp2'dA from the ribosomes is also inhibited. The action of the elongation factor G or some other ribosomal component participating in the translocation process requires the presence of the 2'-hydroxyl group on the terminal adenosine of tRNA. If this hydroxyl group is not present on the tRNA, the ribosomes remain locked in their pretranslocational state.

Deoxyadenosines↗
PubMed1982

[Endocrine reaction pattern in the course of a one-phase tramadol-N2O combination anesthesia].

The effects of Tramadol-N2O-anaesthesia on the per- and postoperative change in blood concentrations of cortisol, prolactin, thyroxine, triiodothyronine, cyclic AMP, glucagon, antidiuretic hormone, PTH-peptide (44-68), glucose, lactate, pyruvate and free fatty acids (FFA) were investigated in connection with elective orthopaedic surgery. Anaesthesia in man with Tramadol and nitrous oxide were found to be associated with a significant elevation of plasma cortisol and plasma prolactin in man. However, cortisol secretion during anaesthesia is associated with an inhibition in T4-T3 conversion. No significant alterations in plasma glucagon concentrations were observed. Generally, surgical trauma induced a significant increase in plasma cyclic AMP with intraoperative levels between 26.4 and 34.3 pmol/ml. At the end of surgery a significant fall in plasma PTH-peptide (44-68) occurred. There was also a significant change in plasma ADH levels following induction of anaesthesia. During surgery we found plasma ADH levels up to 56 pg/ml. In addition stress and surgical trauma increased blood glucose and FFA while plasma pyruvate and plasma lactate nearly remained unchanged. The data would suggest that the non-specific stress response attributed to anaesthesia may in fact be reflecting a response to relatively light anaesthesia.

Adult↗
PubMed1982

[Differential diagnosis of pancreatitis: metastasis to the pancreas].

A case report is given of a patient with a metastasizing teratocarcinoma of the testis (ripe teratoma and embryonal carcinoma), which was misinterpreted in the beginning as acute pancreatitis. At post mortem, metastases of this tumour were found in the pancreas, which apparently had led to inflammatory lesions of this organ, which could not explain however all of the clinical symptoms seen before. The literature dealing with cases suffering from acute pancreatitis induced by tumours is reviewed. A list of possible associations between pancreatitis and tumours is given.

Acute Disease↗
PubMed1982

[Effective levels of cyclophosphamide and metabolites in pleural effusions during intravenous therapy (author's transl)].

Levels of cyclophosphamide (CP, Endoxan) and metabolites were determined in blood and pleural effusions of 5 cancer patients receiving 20 mg/kg CP i.v. The pleural concentrations of CP and its stable deactivated metabolites as 4-keto-CP and carboxyphosphamide increased slowly and even after 4 to 6 an equilibrium with plasma levels was not achieved completely. Plasma peak levels of activated CP (4-hydroxy-CP + aldophosphamide) determined after conversion into the stable derivative 4-(S-benzyl)sulfido-CP or by a fluorometric test were in the range of 1 to 2 nmol/ml. Using these techniques, as two independent methods, amounts of activated CP in pleural effusion were found to be below the limit of detection (0.1-0.2 nmol/ml). Also the alkylating rates of proteins in the pleural effusions were only 20% of those measured in blood samples. The relatively short plasma half-life (approx. 15 min) of 4-hydroxy-CP, when compared with the slow passage of CP-metabolites from blood to the pleural space, is assumed to be the reason for the failure of detection of activated CP and low levels of alkylating material observed in the pleural effusions.

Biotransformation↗
PubMed1981

Comparative study on human pharmacokinetics of activated ifosfamide and cyclophosphamide by a modified fluorometric test.

The activated metabolites of ifosfamide and cyclophosphamide (4-hydroxy-ifosfamide and 4-hydroxy-cyclophosphamide) were analysed fluorometrically by condensation of liberated acrolein with m-aminophenol yielding 7-hydroxyguinoline. Interfering fluorescence of blood and urine was eliminated by extraction with dichlormethane and determination of blanks in which the liberated acrolein reacted with hydrazine to non-fluorescent pyrazoline. The modified test proved effective in identifying low levels of activated metabolites in man. After i.v. injection of 20 mg/kg cyclophosphamide or ifosfamide peak levels of activated cyclophosphamide (4.7 nmol/ml) and the area under the curve (c.t = 16.7 nmol.ml/h) showed mean values three times higher than those found for activated ifosfamide. One per cent of the applied dosis of cyclophosphamide vs. 0.3% of ifosfamide was excreted as activated metabolites. Due to the high stability of activated cyclophosphamide and ifosfamide in urine a low liberation rate of acrolein was found, the concentration of which in urine was below 0.5 nmol/ml. Acrolein, which was directly liberated from activated cyclophosphamide or ifosfamide, does not seem to play an important role in the urotoxicity of these cytostatics.

Acrolein↗
PubMed1981

Synthesis of alpha-fetoprotein (AFP) and cell proliferation in regenerating livers of NMRI mice after partial hepatectomy. An immunohistochemical and autoradiographic study with 3H-thymidine.

To get more information concerning the relation between cell proliferation and the synthesis of alpha-fetoprotein (AFP), liver regeneration and AFP production was followed simultaneously in short intervals in NMRI mice after two-thirds hepatectomy using autoradiographic and immunohistochemical methods. The results indicate that AFP synthesis is not linked closely to cell proliferation in the sense that each proliferating hepatocyte synthesizes AFP during a definite phase of the cell cycle. However, AFP production, as measured by the index of anti-AFP positive hepatocytes, occurs in a very small population of parenchymal cells when the bulk of the hepatocytes has just passed the S-phase and is considered to be in the G2-, M or early G1-phase of the cell cycle when the cells are still in an undifferentiate state.

Animals↗
PubMed1981

[Leukocyte-adherence-inhibition reactivity in patients with colorectal and pancreatic cancer (author's transl)].

The immunoreactivity of patients with colorectal or pancreatic cancer was investigated by a modified leukocyte adherence inhibition test (LAI). The microcapillary-LAI-test was easy to practise and measurements had a low intra-assay coefficient of variation. The number of false positive results was low, only 1 of 39 patients with benign disease and not one of 13 healthy volunteers reacted in the presence of colorectal carcinoma extracts. In 43 patients with colorectal cancer 17 of 25 (68%) with Dukes' B & C and 15 of 18 (83%) with Dukes' D cancer were LAI positive. Of the 19 patients with colon polyps 6 positive results were observed, exclusively in case of large villous adenomas, polyposis coli and one polyp with a focal carcinoma. 10 of 11 patients with pancreatic cancer reacted in the test. Leukocytes from patients with limited cancer of other source, when tested with colorectal or pancreatic carcinoma extracts, showed a negative LAI response. However, in case of metastatic diseases some crossreactions were observed, which resulted in false positive tests. Following our results, the LAI test could be of value in the diagnosis of gastrointestinal carcinoma.

Aged↗
PubMed1980

[Blood level and urinary excretion of activated cyclophosphamide and its deactivation products in man (author's transl)].

Blood levels and urinary excretion of cyclophosphamide and its metabolites were determined in cancer patients receiving cyclophosphamide. Activated cyclophosphamide (4-hydroxycyclophosphamide aldophosphamide) was assayed by TLC after derivatisation to stable 4-(S-benzyl)-sulfido-cyclophosphamide. Twenty minutes after injection of 10(20) mg/kg cyclophosphamide mean peak levels of activated cyclophosphamide were found to be 1.4(2.6) nmol/ml. The rate constant for biotransformation (=activation) of cyclophosphamide in man (km = 0.132 h-1) was only 1/50 of the value found in the mouse whereas the elimination rate constant of activated cyclophosphamide (ke[M] approximately 6.78 h-1) was much higher equalling that of laboratory animals. 4-ketocyclophosphamide, carboxyphosphamide, and phosphoramidemustard reached their peak levels between 4 and 6 h after cyclophosphamide injection. Increasing quantities of cyclophosphamide metabolites were bound to plasma proteins reaching a constant level after 24 h lasted for several days. Fifty per cent of those metabolites were reversibly bound to plasma proteins. Within 24 h, the cumulative excretion of cyclophosphamide and its metabolites amounted to 50% of the dose applied. The main metabolites excreted were phosphoramide-mustard and carboxyphosphamide whereas only 2% consisted of activated cyclophosphamide. The significance of the different pharmacokinetics of cyclophosphamide in laboratory animals and man for the therapeutic index is discussed.

Aged↗
PubMed1980

The complex formation between Escherichia coli aminoacyl-tRNA, elongation factor Tu and GTP. The effect of the side-chain of the amino acid linked to tRNA.

The interaction between Escherichia coli aminoacyl-tRNAs and elongation factor Tu (EF-Tu) x GTP was examined. Ternary complex formation with Phe-tRNAPhe and Lys-tRNALys was compared to that with the respective misaminoacylated Tyr-tRNAPhe and Phe-tRNALys. There was no pronounced difference in the efficiency of aminoacyl-tRNA x EF-Tu x GTP complex formation between Phe-tRNAPhe and Tyr-tRNAPhe. However, Phe-tRNALys was bound preferentially to EF-Tu x GTP as compared to Lys-tRNALys. This was shown by the ability of EF-Tu x GTP to prevent the hydrolysis of the aminoacyl ester linkage of the aminoacyl-tRNA species. Furthermore, gel filtration of ternary complexes revealed that the complex formed with the misaminoacylated tRNALys was also more stable than the one formed with the correctly aminoacylated tRNALys. Both misaminoacylated aminoacyl-tRNA species could participate in the ribosomal peptide elongation reaction. Poly(U)-directed synthesis of poly(Tyr) using Tyr-tRNAPhe occurred to a comparable extent as the synthesis of poly(Phe) with Phe-tRNAPhe. In the translation of poly(A) using native Lys-tRNALys, poly(Lys) reached a lower level than poly(Phe) when Phe-tRNALys was used. It was concluded that the side-chain of the amino acid linked to a tRNA affects the efficiency of the aminoacyl-tRNA x EF-Tu x GTP ternary complex formation.

Amino Acyl-tRNA Synthetases↗
PubMed1980

[Effect of damaged liver parenchyma, renal insufficiency and hemodialysis on the pharmacokinetics of cyclophosphamide and its activated metabolites].

Patients with impaired liver function have a reduced biotransformation rate of the cytostatic agent cyclophosphamide. With pathologically reduced serum cholinesterase activity the half-life of the drug increases from normally 4.3 h to 6.7 h. These patients show significantly lower peak levels of activated cyclophosphamide (4-hydroxy-cyclophosphamide + aldophosphamide). Because of the low renal clearance of cyclophosphamide (16 ml/min) and equally low renal excretion of activated cyclophosphamide amounting to only 1% of the applied dose more than 80% of the drug is still metabolized and the area under the curve of activated cyclophosphamide (cXt) remains relatively constant. No change in the pharmacokinetics of cyclophosphamide and its activated metabolite is observed in an anuric patient. However, an accumulation of toxic, directly alkylating metabolites with a fourfold alkylation rate of plasma proteins is found in this case. Hemodialysis sufficiently eliminated the toxic alkylating metabolites without a measurable influence on the pharmacokinetics of activated cyclophosphamide.

Aged↗