Polyacrylonitrile complement activation attenuated by simultaneous ultrafiltration and adsorption.

The highly permeable synthetic polyacrylonitrile (PAN) membrane (Filtral; Hospal, Basle) is regarded as biocompatible for its slight complement activation and leucocyte sequestration. The low C3a and C5a concentrations during PAN dialysis may be due to a lack of complement activation potential of this polymer, but also to elimination of activated complement components by the dialyser through adsorption and/or ultrafiltration (mol wt of C3a and C4a 9000 daltons; of C5a 11,000 daltons). Comparing arteriovenous differences throughout the study, higher concentrations of C3a (+23%; n.s.) and C5a (+80%; P less than 0.05) were measured in the efferent blood lines, suggesting a slight complement activation by the alternate pathway. A significantly lower C4a concentration in the efferent blood lines (-30%, P less than 0.05) indicates an elimination within the dialyser. Significantly higher arteriovenous concentration differences at the beginning of dialysis and increasing sieving coefficients suggest elimination by adsorption, mainly in the first 20 min of haemodialysis. The continuous decrease of C3a and C4a plasma concentrations in the afferent blood line suggests transport across the membrane and removal by the dialysate. Accordingly, measurable amounts of these complement components were detected in ultrafiltrate.

Permeability and secondary membrane formation of a high flux polysulfone hemofilter.

It has been assumed that the molecular weight (MW) cut-off of a newly fabricated polysulfone capillary dialyzer (F60, Fresenius, FRG) is similar to that of the human glomerulus. We recently tested the device in vivo and found this not to be so, based on the device's ability to eliminate substances of a MW of 10,000 to 60,000 daltons. One of the reasons for this discrepancy was found to be the influence of secondary membrane formation on solute permeability. Endogenous marker substances of a defined MW (beta 2-microglobulin, myoglobin, RBP, alpha 1-microglobulin, acid alpha 1-glycoprotein, alpha 1-antitrypsin, prealbumin, and albumin were measured by laser nephelometry or radioimmune assay; sieving coefficients (SC) and protein eliminations were calculated for each low MW protein.

Pharmacokinetics of bisoprolol and influence on serum thyroid hormones in hyperthyroid patients.

Nine hyperthyroid patients (FT4 greater than or equal to 20 ng/L; FT3 greater than or equal to 6 ng/L) were given 1 X 10 mg bisoprolol/day p.o. for a period of 7 days. Pharmacokinetic data were derived from measurements of plasma bisoprolol concentrations after the first dose and at steady state after 7 days treatment. The thyroid hormones FT4, FT3, and rT3 were determined in the serum before and after bisoprolol treatment. In addition, subjective and objective parameters of thyroid function were recorded during the course of the therapy. The maximum bisoprolol concentrations measured after the first dose and after 7 days were 54.3 +/- 2.1 and 70.3 +/- 3.8 ng/ml, respectively, the minimum concentrations being 9.6 +/- 1.0 ng/ml and 11.9 +/- 1.7 ng/ml, respectively. This yields an accumulation factor of 1.2. At steady state, the plasma elimination half-life of bisoprolol was 9.8 +/- 0.9 h. No significant changes in serum thyroid hormones were observed during bisoprolol treatment. There was, however, an improvement in the subjective and objective clinical symptoms of hyperthyroidism. In comparison with the findings in healthy volunteers, the pharmacokinetics of bisoprolol remained unaltered in mild to moderate hyperthyroid patients. After oral application of bisoprolol, only small variations in the plasma concentration were observed inter- and also intraindividually in the course of treatment. This finding reflects the high absolute bioavailability of bisoprolol.

Treatment of severe Graves' ophthalmopathy with cyclosporin A.

Ten patients with severe Graves' ophthalmopathy, resistant to other therapeutic regimens were treated with cyclosporin A (CyA) over a period of 6 months. Clinically, 9 patients improved, 2 of them only after addition of corticosteroids. Intra-ocular tension on upward gaze decreased in all of these 9 patients (P less than 0.01). In 6 patients there was a significant decrease in eye muscle thickness under the treatment (P less than 0.05) as determined by computerized tomography. Side effects (e.g., paraesthesia, proteinuria) which were observed under higher doses of CyA, disappeared after lowering the dose. In only one out of 3 patients with hypertension an antihypertensive medication became necessary. CyA appears to be a valuable drug for treatment of severe Graves' ophthalmopathy when previous therapeutic regimens turned out to be unsuccessful.

[Improved diagnostic evaluation of prostatic neoplasms using radioimmunoassay for prostatic acid phosphatase]. / Bessere diagnostische Beurteilung des Prostataneoplasmas durch den Radioimmunoassay für die saure Prostataphosphatase?

Better diagnosis of prostatic cancer by RIA of serum prostatic acid phosphatase? The results of serum determination of RIA prostatic acid phosphatase (PAP) and enzymatic serum phosphatase were compared in 267 patients with the clinical diagnosis to reveal the diagnostic value of the RIA-PAP in prostatic carcinomata. In 33 of the investigated patients (12.4%) we found elevated values of the PAP over the normal range of 0--5 ng/ml. In these 33 patients with pathologic PAP-values those with adenomata and in adenomata intracapsulated prostatic cancers had normal serum values measured enzymatically. There was no correlation between PAP-RIA results and the stage of the prostatic carcinoma. In nearly 20% we found better information by RIA-PAP than enzymatic laboratory tests, but combined with a digital investigation.

[Hypoferraemia and serum ferritin (author's transl)]. / Hypoferrämie und Serumferritin.

The wide use of serum iron determination by automatic analysers may lead to low values being taken as evidence of iron deficiency. Determining serum ferritin concentration in such cases provides rapid and reliable information to distinguish between reactive hypoferraemia and iron deficiency hypoferraemia, as demonstrated in tests on 71 patients with reproducible hypoferraemia. In 31 patients there was reactive hypoferraemia, in 40 iron deficiency hypoferraemia.

The 3'-amido and 5'-amido analogues of adenosine 3':5'-monophosphate; interaction with cAMP-specific proteins.

The sensitivity for recognition of adenosine 3:5'-monophosphate (cAMP) by its coordinate proteins towards chemical changes in the six-membered cyclic phosphate ring has been investigated. A comparison of the interaction parameters of the 3' and 5'-amido analogues (I, II) and of unsubstituted cAMP has been made using two different protein kinases and the phosphodiesterase from bovine heart. Binding affinity and the capacity of the amido analogues to stimulate the phosphotransferase activity of the kinases is greatly reeuced relative to cAMP, the 3'-position being more sensitive towards the modification than the 5'-position. The coordinate noncyclic derivatives, 3'-deoxy-3'-amino-5'-AMP (IV) and 5'-deoxy-5'-amino-3'-amp (iii), were also tested. Surprisingly activity towards protein kinases was found to be considerable for the 5'-deoxy-5'-amino-3'-AMP (III), while the 3'-deoxy-3'-amino-5'-AMP (IV) is practically inactive. A possible reason for this is that the noncylic 5'-analogue (III) may be able to assume a cyclic structure maintained by internal salt formation. The phosphodiesterase splits both cyclic amido analogues but with reduced rates compared to that of natural cAMP. Kinetic data obtained from different methods reveal a stronger affinity for the 5'-analogue (I) than the 3'-analogue (II) for the active site, although the reaction rate at saturated substrate concentration is significantly higher with II than with I. The properties of the amido and the noncyclic amino analogues are discussed with available data from chemotaxis of the cellular slime moulds. Furthermore data of the respective methylene cyclic derivatives are used for a more comprehensive comparison. The above is interpreted in terms of the electronic features of the substitutions and of the changes in bond distances or angles upon replacement of O by NH or CH2 in the cyclic phosphate ring (obtained from X-ray work).