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Biomedical subjects

G Wagner

Publications and source records attributed to G Wagner.

At least 433 records · Page 24Linked to original sources

Is prostaglandin E2 really of therapeutic value for postoperative urinary retention? Results of a prospectively randomized double-blind study.

In a prospectively randomized double-blind study 28 patients with urinary retention after anterior colporrhaphy were administered either placebo or prostaglandin E2 in different doses (0.75 mg, 1.5 mg, or 2.25 mg) intravesically on postoperative days 6 and 7. Urodynamic assessment was performed before and after treatment. A moderate but not significant decrease of maximum bladder capacity, bladder compliance, and maximum urethral closure pressure was found in patients treated with 2.25 mg of prostaglandin E2. These urodynamic changes did not correspond to the clinical outcome: Residual urine decreased and effective bladder capacity increased significantly in all four groups uninfluenced by the type of therapy. The rate of success (defined by the amounts of residual urine after therapy) was similar in the four groups. A long-term effect of prostaglandin E2 could also be excluded, since the mean time interval from operation to the first day without residual urine was similar in the four groups. Therefore the therapeutic value of intravesically administered prostaglandin E2 in doses from 0.75 to 2.25 mg must be seriously questioned.

Clinical Trials as Topic↗

Orgasm in women in the laboratory--quantitative studies on duration, intensity, latency, and vaginal blood flow.

Sexual arousal by clitoral self-stimulation was used by healthy, young adult women volunteers (n = 28) to induce orgasm in the laboratory. The duration of the orgasm was obtained using the subject's verbal indication of its start and finish. The estimated duration and the subjective experience of the orgasm self-graded on a 5-point scale were also obtained in a number of subjects. Vaginal blood flow was assessed by the power consumption needed to keep a heated oxygen electrode, held on the vaginal wall by suction, at a constant temperature. The mean measured orgasm duration was 19.9 seconds (SD, +/- 12, n = 26). For 14 subjects, their estimate of the duration of their orgasms (12.2 +/- 9.8 seconds, mean +/- SD) was greatly underestimated compared with the measured duration (26 +/- 14.6 seconds). This result indicates that data obtained on the duration of orgasm from questionnaires or interviews have suspect validity. The measured duration of the orgasms was not significantly correlated with the subjective grading. The increase in vaginal blood flow at orgasm was not significantly correlated with the subjective gradings of orgasm (n = 18), the orgasm latency (time taken to induce orgasm, n = 18), or the measured duration of orgasm (n = 14).

Adult↗

[Results of the first Austrian multicenter ovarian cancer study: prospective randomized comparison of sequential chemotherapy (adriamycin/cisplatin--vincristine/cyclophosphamide--methotrexate) with 2 standard protocols (adriamycin/cyclophosphamide or adriamycin/cisplatin) in stage III and IV patients].

From June 1980 to December 1982 164 patients with ovarian cancer stage III and IV were randomized into the three-legged Austrian Ovarian Cancer Study. A new polychemotherapy, known as the "changing-scheme" (adriamycin/cisplatinum--vincristine/cyclophosphamide--high dose methotrexate), developed in Vienna, was compared with adriamycin/cyclophosphamide and adriamycin/cisplatinum. The risk factors were stratified by means of special computer-assisted randomization. The first study evaluation in 1982 showed a significant advantage for the changing-scheme with regard to recurrence-free interval and survival (Mantel test: p less than 0.01, Breslow test: p less than 0.03). No difference was found between the combinations of adriamycin/cyclophosphamide and adriamycin/cisplatinum. At the second study evaluation in June 1984 the differences previously observed were no longe present to the same significant extent. The changing-scheme continued to be superior for the subgroups of patients with highly differentiated tumors, without ascites, with larger postoperative tumor burden and with liver metastases. The use of this therapy is be recommended for women with advanced ovarian cancer, especially in consideration of the much lower toxicity caused by the less frequent cisplatinum administrations as compared to the adriamycin/cisplatinum combination.

Antineoplastic Combined Chemotherapy Protocols↗

Alterations of immunologic parameters in pregnancies complicated by EPH-gestosis.

To characterize the cellular and humoral immune situation in pregnancies with EPH-gestosis (n = 44), percentages of peripheral T-lymphocytes, ratio of helper and suppressor T-lymphocytes further circulating immuncomplexes (CIC), beta 2-Microglobulin (beta 2-MG) and lysozyme (Lz) were determined. 50 pregnant women without EPH-gestosis were examined as controls. The mean counts of total lymphocytes decreased with increasing gestosis index in contrast to T-lymphocyte percentages. The mean T-helper/T-suppressorcell ratio indicated a severe imbalance in a few cases with severe gestosis. CIC were present in all serum samples of patients with moderate and severe gestosis. Lz was found to be elevated in EPH-gestosis in correlation to severity of disease. beta 2-MG levels in serum were only increased in women with reduced renal function. This parameter was not strictly correlated to the severity of EPH-gestosis but only to the degree of kidney dysfunctioning. EPH-gestosis represents a heterogeneous group with uniform symptomatology. Only in severe gestosis an imbalance of T-lymphocyte subpopulations as well as CIC and elevated Lz levels were detected. In mild gestosis no alterations of the used parameters were found.

Antigen-Antibody Complex↗

[Synthesis of N-alpha-benzyloxycarbonyl-4-amidinophenylalanine amides as thrombin inhibitors].

Based on 4-cyanophenylalanine, the title compounds had been obtained by benzyloxycarbonylation of the amino group, subsequent formation of the activated ester by 4-nitrophenol, its aminolysis and at least change of the cyano function to the amidine function via thiocarbamides and thioimid acid esters. The inhibitor effect against thrombin of the pyrrolidid 16 is analogous to those of the adequate N alpha-tosyl compound.

Chemical Phenomena↗

[Synthesis of N-alpha-(8-quinolinesulfonyl)-4-amidinophenylalanine amides as thrombin inhibitors].

The compounds mentioned in the title were prepared starting from 4-cyanophenylalanine by sulfonylation using 8-quinoline sulfonic acid chloride, formation of the 4-nitrophenylester, aminolysis of the latter and subsequent transformation of the cyano via the thiocarbamoyl and the thioimid acid ester into the amidine group. The antithrombin effect decreased by substituting the 1-naphthylsulfonyl by the 8-quinolinesulfonyl residue.

Chemical Phenomena↗

[Synthesis of N alpha-(benzoylglycyl)- and N alpha-(benzyloxycarbonylglycyl)-4-amidinophenylalanine amides as thrombin inhibitors].

The 4-nitrophenyl esters of hippuric acid and benzyloxycarbonylglycine had been aminolyzed by racemic 4-cyanphenylalanine into the compounds 3 and 4. After activation as 4-nitrophenyl esters and following reaction with amines the amides 7-14 were formed. These cyano compounds were converted into the amidines via the thioamides 15-22 and the thioimidic esters 23-30. The piperidide 35 was most effective against thrombin.

Antithrombins↗

[Effect of bisoprolol in coronary heart disease. Effect on cardiovascular parameters and ischemic ST depression: studies on the duration of the effect].

A beta-adrenoceptor antagonist, bisoprolol, was given by mouth, 5 and 10 mg doses per 24 hours, in a double-blind randomized cross-over trial to 12 patients with stable coronary-heart disease. Ischaemia criteria proved not reproducible in control ergometry tests on two patients, leaving ten patients for further evaluation. On two days, one week apart, bicycle ergometry was undertaken until the occurrence of ST segment depression of at least 0.3 mV, often associated with angina. Four, eight and 24 hours after the drug had been taken, the ergometry was repeated to the same maximal Watt level and duration of exercise. Heart rate and pressure-rate product at rest, as well as the same parameters including ST segment depressions immediately at the end of exercise, significantly fell after bisoprolol during the entire trial period independently of the dose. There was no sign of reduced effectiveness 24 hours after drug intake. The results indicate that treatment of stable angina with bisoprolol can be achieved with a single daily dose.

Adrenergic beta-Antagonists↗

Two-dimensional 1H NMR of two chemically modified analogs of the basic pancreatic trypsin inhibitor. Sequence-specific resonance assignments and sequence location of conformation changes relative to the native protein.

Two-dimensional nuclear magnetic resonance was used to obtain sequence specific assignments for the 1H NMR spectra of two chemically modified analogs of the basic pancreatic trypsin inhibitor. In one analog the disulfide bond 14-38 was cleaved, in the second derivative the N-terminus was transaminated. From measurements of the chemical shifts and determination of the sequence locations of slowly exchanging backbone amide protons it was found that conformational differences between the native inhibitor and the chemical modifications occur exclusively near the modification sites and that the internal hydrogen bonds are nearly fully preserved. Intriguing conformation differences with respect to the native protein are that for five residues in the transaminated inhibitor and for one residue in the reduced inhibitor multiple local conformers are indicated, and that the four internal water molecules observed in the crystal structure of the native inhibitor appear not to be preserved after reduction of the disulfide bond 14-38.

Amides↗

Amide-proton exchange studies by two-dimensional correlated 1H NMR in two chemically modified analogs of the basic pancreatic trypsin inhibitor.

The backbone amide proton exchange with the solvent was investigated in 2H2O solutions of the basic pancreatic trypsin inhibitor and two chemical modifications thereof, which were obtained by transamination of the N-terminus and by cleavage of the disulfide bond 14-38, respectively. The three proteins have nearly identical conformations, but the stability with respect to thermal denaturation is markedly different. Exchange rates for a large number of individually assigned amide protons located both in central and peripheral parts of the protein structures were measured by two-dimensional correlated spectroscopy (COSY). From analysis of the individual proton exchange rates in the three proteins at different temperatures, an interplay of global and local structure fluctuations was characterized, which promote hydrogen exchange in distinct regions of the molecules. The exchange of particular amide protons may be governed by different motional processes at different temperatures. As a general trend, global fluctuations involving breakage of numerous hydrophilic secondary bonds appear to be dominant at higher temperatures, whereas at lower temperatures the influence of local fluctuations in hydrophobic regions of the protein structures is also clearly noticeable.

Amides↗

Inhibition of bovine and human thrombins by derivatives of benzamidine.

Thirty-four derivatives of benzamidine were tested for their inhibitory activities on bovine and human thrombins using the chromogenic peptide substrate N-D-Phe-Pip-Arg-pNA. The inhibition constants of small molecular size inhibitors of comparatively low affinity as well as those of tight binding inhibitors did not differ significantly with different species. Accordingly, the active site of bovine thrombin seems to correspond largely to that of human thrombin.

Amidines↗