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Biomedical subjects

H A Wagner

Publications and source records attributed to H A Wagner.

7 recordsLinked to original sources

Serum and tissue levels of platinum after cisplatinum instillation of the rat bladder.

The absorption of chemotherapeutics after local application in the urinary bladder is important for optimum therapy. We therefore investigated the absorption of Cisplatinum (Pt) through the bladder wall in 100 female Sprague-Dawley-rats after instillation under different clinical and pharmacological conditions. Only low platinum (Pt)-concentrations of about 1 microgram/ml could be detected in the serum using unmodified Cisplatinum solutions for instillation in the rat bladder indicating a rather low absorption rate for Cisplatinum. The extent of the absorption of Cisplatinum through the instilled bladder increased with the instilled volume. The absorption rate also increased after electrocoagulation and during cystitis with a maximum concentration of about 2.64 micrograms/ml. Correspondingly the vesicoplasmatic gradient factor clearly decreased. On addition of the detergent Tween 80, the serum Pt-concentration increased rapidly during the initial 30 min. Under these conditions Cisplatinum penetrated the bladder wall, about three times more effectively than in the absence of Tween while entering the systemic circulation only at about twice the normal rate without Tween 80. On addition of the polar organic solvent dimethylsulfoxide (DMSO) serum Pt-concentration increased continuously during the following 2 to 3 h reaching maximum values of about 13.3 micrograms/ml. The greatest accumulation of Pt in the bladder tissue (about 1,600 micrograms Pt/g tissue) was also observed under these conditions. A comparison of the Pt-concentration in serum with that in the bladder wall showed the most favourable relation of high tissue penetration and low serum concentration using Tween 80.

Animals↗

[Laboratory diagnosis and practical treatment of patients].

The practical treatment of patients requires a reliable diagnosis and prognosis followed by therapy. Laboratory medicine is an essential scientific basis to rational treatment in each of these three phases. The significance, usefulness and extent of laboratory tests are largely dependent upon the disease spectrum. The possibilities and aims of laboratory medicine are: 1. Knowledge of and research into both the pathobiochemical and statistical connections between biochemical data and diseases leading to the selection of diagnostically reliable and relevant parameters. 2. Knowledge of the sensitivity, specificity and predictive values of relevant biochemical parameters and their application to the different clinical problems. 3. Evaluation of reliable analytical methods with details of their accuracy and precision. 4. Critical evaluation of pre-analytical factors. The translation of accurate laboratory data into clinically relevant information must always be coupled with a critical assessment of its diagnostic value, validity and range of error. An uncritical "consumption" of laboratory data is dangerous for both the patient and the clinician as is the suppression of these data when it does not fit the supposed diagnosis. Laboratory medicine is indispensible in proper patient care since it guarantees adequate medical action. The information that it delivers is binding and therefore offers help as well as protection.

Clinical Laboratory Techniques↗

Isolation of apolipoprotein-B-48 from chylomicrons by high-performance liquid chromatography.

Apolipoprotein-B-48 (B-48) is a component of chylomicrons and chylomicron remnants and originates in the human gut wall. Its molecular weight represents 48% of the hepatic apolipoprotein-B-100 (B-100). So far, immunochemical assays are only available for B-100 and do not permit the specific determination of B-48. As a convenient immunochemical method is necessary for clinical and biochemical investigations of chylomicron remnants, we isolated B-48 in amounts sufficient to permit the production of monoclonal antibodies. After delipidation of the chylomicron fraction from 3 1 of human chylous ascites, size-exclusion chromatography was performed by using two serially connected TSK columns. B-48 was eluted as a second peak at about 35% of the total volume, well separated from B-100 (eluted as a first peak). After detection by UV absorption at 280 nm, the fractions collected from 25 automated runs were combined, ultrafiltered and examined for their protein composition by sodium dodecyl sulphate polyacrylamide gel electrophoresis. This indicated that we were able to isolate rapidly 3.4 mg of B-48 in a purity sufficient to perform immunization.

Apolipoprotein B-48↗

Effects on prostanoid formation and pharmacokinetics of dazmegrel (UK-38,485), a novel thromboxane synthase inhibitor, in man.

The pharmacokinetics of dazmegrel (UK-38,485), a novel selective thromboxane synthase inhibitor, and its effects on in vivo prostanoid formation were studied in a 2 weeks, multiple dose, placebo controlled, double blind trial in man. The drug was well tolerated. After dazmegrel 50-200 mg p.o. peak plasma levels of 0.7-3 mu/ml were reached within 1 hr. Elimination was of first order with a half life of 0.88 +/- 0.17 hr. Platelet count and bleeding time were unchanged by all regimes of dazmegrel used (100 and 200 mg b.i.d.; 50, 100 and 200 mg t.i.d.). Serum thromboxane (TXB2) was more than 95% suppressed one hour after all doses studied, but 200 mg t.i.d. were needed suppress circadian serum TXB2 profiles more than 90% at all times. Urinary excretion of 2,3-dinor-TXB2 (TXA2-M) fell by over 90%. An increase in the excretion of 2,3-dinor-6-keto-PGF1 alpha (PGI2-M), the major metabolite of prostacyclin, was largely transient and fell short of significance at all times. The ratio of TXA2-M to PGI2-M was lowered from about 5.0 to 0.2 and sustained throughout treatment. Dazmegrel selectively blocks in vivo and ex vivo TXA2 formation. Redirection of endoperoxides from total body TXA2 formation into prostacyclin formation is only minor under basal conditions.

Adult↗

[Muscular carnitine-palmityl-transferase deficiency].

Deficiency in carnitine-palmityl-transferase (CPT) was demonstrated in a 20-year-old man with paroxysmal myoglobinuria, after failure to discover another cause. It is concluded that muscular CPT deficiency must be excluded before a recurrent myoglobinuria is classified as "idiopathic".

Acyltransferases↗

[Early detection and incidence of iron deficiency in pregnancy].

For early detection of iron deficiency during pregnancy ferritin, transferrin, serum iron, transferrin saturation and red blood cell (RBC) parameters were measured in 156 pregnant women. The geometric mean of ferritin-concentration was 11.7 +/- 2.7 ng/ml (mean +/- 1 s) which is about 46 ng/ml lower than that in non pregnant women. The duration of pregnancy, the number of pregnancies and the interval from the preceding pregnancy were all considered: 67% had iron deficiency, 18% prelatent, 27% latent and 22% manifest. On the basis of RBC analysis only 30% could be detected correctly. Ferritin detected 90% whereas serum iron, transferrin, transferrin saturation only detected 45% of the cases. The serum ferritin level did not correlate with the number of previous pregnancies but it did correlate with the interval to the last pregnancy. Serum ferritin declined sharply until the 28th week of pregnancy but only slightly thereafter. These data suggest at least one determination of serum ferritin concentration in pregnant women for a sufficient prophylaxis of iron deficiency during pregnancy. The latest time for the measurement should be between the 20th and 23rd week. An additional determination of serum ferritin during the early pregnancy is indicated if the time interval to the preceding pregnancy is shorter than three years.

Adolescent↗