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Unlabelled: General practitioners (GPs) are responsible for 70% (or roughly 30 billion DM) of the entire medication prescribed by practising doctors. Pharmacotherapy circles (PTC) are a further education, which focuses on the optimisation of prescription behaviour (best therapy possible in clinical pharmacology, the translatability into daily practice and guides the concept and contents of the further education. The concept of further education in pharmacotherapy circles developed by us follows the rules of quality assurance in medical care:, Assessment: Recording prescriptions in one quarter for evaluation of prescription problems. Problem selection: Medicine groups, whose prescription frequency give an indication of prescription quality, i.e. vein and rheumatism ointments (as little as possible) and proton pump inhibitors and lipid reducers (as many as necessary). The problem analysis takes place as peer review by a group of physicians from the same field, and under the moderation of two doctors from the same field, who have been for at last one year, carefully instructed, in pharmacology and the moderations of groups. The formulation of guidelines shall be shown for an indication area, for which there is no robust therapy (e.g. venous medicaments). The purpose of theses guidelines shall be to optimise the treatment, strengthen the health consciousness of the patient and reduce the prescription of medicaments, whose efficacy has not been proven. The evaluation proves that these goals have been reached. The total reduction in costs is different for individual physicians depending on the original prescription level of the underlying medicament costs. Only the third of "high prescribers" showed economy reserves. There were savings in medicaments with non-proven efficacy among the lower and middle prescribers, however, there were increased expenditures and therapy improvements in other areas.

Purpose: To reproduce and investigate in a primate animal model the phenomenon of the red carotenoid canthaxanthin (beta, beta-carotene-4'4'-dione) to induce crystal-like retinal deposits as they have been observed in the ocular fundus of humans after high canthaxanthin intake (i.e., more than 30 mg/day)., Methods: Groups of four cynomolgus monkeys (Macaca fascicularis) per gender and dose were administered 5.4, 16.2, or 48.6 mg canthaxanthin/kg body weight daily by oral gavage for 2.5 years. Eight control animals received placebo. In vivo ophthalmoscopy was performed at intervals of 3 months along with electroretinography after 12 and 24 months and retinal biomicroscopy just before the monkeys were killed. Retinal wholemounts or frozen sections were investigated postmortem by polarization, bright field, and differential interference contrast microscopy. Retinal and preterminal plasma canthaxanthin concentrations were determined by high-performance liquid chromatography (HPLC)., Results: By ophthalmoscopy and retinal biomicroscopy in vivo, no crystals or other light-reflecting particles were observed in the central paramacular retina. However, postmortem polarization microscopy of all 24 canthaxanthin-treated animals showed a circular zone in the peripheral retina containing birefringent, polymorphous red, orange, or white inclusions. The density of these inclusions was diminished within 1 to 8 mm posterior to the ora serrata. These inclusions were located mainly in the inner retinal layers, that is the nerve fiber layer and ganglion cell layer, inner plexiform layer, and inner nuclear layer. Twelve of the 24 canthaxanthin-treated animals showed yellow, golden birefringent inclusions in the macula. Retinas of placebo-treated monkeys were free of birefringent, crystal-like inclusions. The HPLC confirmed the presence of all-trans canthaxanthin, and 4-OH-echinenone and isozeaxanthin as well, in the retinas of all canthaxanthin-treated animals. Neither electroretinography nor histopathology indicated any adverse effects of the canthaxanthin-induced retinal inclusions seen in this study., Conclusions: A high intake of canthaxanthin for 2.5 years led to the deposition of crystal-like birefringent inclusions in the inner layers of the peripheral retina and, to some extent, the central retina of cynomolgus monkeys. The presence of these deposits did not interfere with morphology nor with retinal function.

Purpose: To isolate and characterize a monomethioninesulfoxide variant of the commercially available therapeutic protein interferon alpha-2b., Methods: The methionine (Met)-oxidized variant was isolated by reverse-phase high performance liquid chromatography and characterized by SDS-PAGE, peptide mapping and mass spectrometric analysis of the trypsin/V8-generated peptide fragments. The biological and immunological activities of the isolated variant were also evaluated., Results: The rHuIFN alpha-2b variant was found to contain a Met sulfoxide residue at position 111 of the rHuIFN alpha-2b molecule. The far-UV CD spectra showed a slight loss of alpha-helical content and an increase in the beta-sheet contribution. The CD spectra indicate that both chromatographic conditions and Met oxidation contribute to the observed secondary structure changes. Both interferon alpha-2b main component and its methionine-oxidized variant showed different reactivity to monoclonal antibodies employed in immunoassays for the protein., Conclusions: A monomethioninesulfoxide rHuIFN alpha-2b variant was found to be present in the rHuIFN alpha-2b bulk drug substance in solution. The Met(111) residue was identified as Met sulfoxide by comparative tryptic/V8 mapping and mass spectrometric analysis. Nevertheless, the oxidation of the Met(111) residue did not seem to have a detectable effect on the biological activity of the molecule.

Rational and efficient pharmacotherapy in a particular quality may be achieved by work in quality control seminars. During the last couple of years, seminars for pharmacotherapy have taken place at the Society of Panel Physicians of the German state Hessen under the supervision and scientific guidance of Lieselotte von Ferber, MD, University of Cologne. The kind of work in these seminars is demonstrated as well as the evaluated results. It can be proven that the quality of the pharmacotherapy is improved together with considerable savings in the costs of drugs without a decrease in the pharmaceutical care of the patients. The seminars for pharmacotherapy may be a suitable method to avoid legal actions for those physicians which may become liable of for compensation because of their high average of prescription costs.

In order to ensure the stability of protein pharmaceuticals, human serum albumin (HSA) is often added as an excipient, frequently in large excess. This makes chromatographic analysis of the stability of the active protein difficult. In the case of interleukin-4 (IL-4), separation from HSA can be achieved to some degree by size exclusion chromatography, but some HSA co-elutes with the IL-4. Hydrophobic ion pairing provides a method for selective precipitation of IL-4 from HSA. Hydrophobic ion pairing involves the electrostatic interaction of ionic detergents with oppositely charged polypeptides. Even when HSA is present in fifty-fold excess (w/w), the resulting precipitate contains greater than 70% of the IL-4. Selective precipitation with SDS produces enhancements in IL-4 over HSA of more than 2000-fold. This approach permits subsequent facile analysis of IL-4 by conventional reverse phase HPLC.

The Dutch Dental Association (NMT) feels very involved in dental schooling and advocates as broad an education as possible with explicit attention to the 'gatekeeper' function of the dentist in general practice, diagnostics and the development of motor skills for complex, restorative treatments. Attention is demanded to place individual professional practice in a wider context of dental staff and a network of opportunities of referral. The NMT wishes to develop a system for the profession in which guidelines, intercollegial testing and effective accredited provision of further training, systemic opportunities and guidelines for the promotion of expertise are given in the areas of technical methods, organisation of practices and professional attitude. They wish to support the newly-qualified dentist through the introduction of a year of practical training linked to study, so that an 'educational continuum' of education, training and continual further training develops, and to make a contribution not just organizationally, but also regarding the content of the curriculum, certainly where it concerns the sociological aspects and the needs of the professional group.

HPLC analyses of GM-CSF in solution mixtures containing both GM-CSF and HSA showed losses of GM-CSF which could not be accounted for using conventional electrophoretic and/or RP-HPLC techniques. Further investigation of these mixtures by immunoblotting and by immunoaffinity chromatography demonstrated the presence of high molecular weight (> 67,000 GM-CSF related species. No such species was detectable in solutions of GM-CSF alone. This experiment pointed to the formation of an adduct between GM-CSF and HSA in the solution mixtures. To probe further the hypothesis of a GM-CSF/HSA adduct, an immunologically based test was conceived which could react only with this type of hybrid molecule. A sandwich enzyme-linked immunosorbent assay (ELISA) was developed using two antibodies, anti-GM-CSF (capture antibody) and anti-HSA (detection antibody), as part of the quantitation of GM-CSF/HSA adducts. After confirming its existence by ELISA, a GM-CSF/HSA adduct was isolated from the solution mixture containing both GM-CSF and HSA. This isolate served as a primary reference standard in the ELISA assay. The immunoassay has a subnanogram sensitivity and is highly specific for GM-CSF/HSA adducts in the presence of either free GM-CSF or free HSA. As a verification, conjugates of GM-CSF/HSA were synthesized using a cross-linking reagent. These covalent conjugates reacted positively in the ELISA and are employed as a convenient alternative reference standard.

The pathomechanism of diseases in the field of oto-rhino-laryngology caused by an hormonal contraceptive therapy are presented on base of a critical literature survey. Complications of oral contraception are proved only for the oral tissue (hyperplastic gingivitis) the larynx and the eustachian tube. Otological (otosclerosis, acute deafness, slowly progressive deafness) and rhinological diseases (Rhinopathia vasomotorica) in women under oral contraception cannot be attributed exclusively to this therapy.

By means of a case report, we show that the general classification of different forms of osteofibrous skull tumours does not always agree with the clinical, pathological and roentgenological findings. A classification based on these requirements is discussed.

Mouse mammary tumor cells were cultured on a three-dimensional bundle of semipermeable hollow fibers as a prototype system for large-scale in vitro production of mammary tumor-associated antigens. Cells were seeded onto the surface of the hollow fibers that served as an artificial capillary network. The cells grew to tissue-like densities within 3 weeks, achieving the high density and three-dimensional intercellular relationships known to potentiate expression of murine mammary tumor virus (MuMTV) antigens. Significant levels of a 52,000-relative-molecular-weight (Mr) glycoprotein antigen of MuMTV (gp52) were detected on the cell side of the semipermeable membrane of the hollow fibers in a yield at least fiftyfold greater than that produced by monolayer cultures. Antigen could be collected from capillary cultures for 6-12 weeks, rather than days from monolayer cultures. Further, gp52 was collected in an undegraded state. Perfusates contained lesser amounts of cross-reactive antigenic species that were predominantly smaller than 50,000 Mr, which suggests that the fibers may be used to separate antigens from their degradation products. The production of nonviral, mammary tumor-associated antigens by cells on artificial capillaries was also demonstrated. Artificial capillary cell culture systems provide a means to obtain significant quantities of tumor-relevant antigens in a semipurified natural state.

Affinity-purified Maclura pomifera lectin (MPL) elutes from a gel filtration column as a single symmetrical peak with characteristics expected for a single protein of approximately 40 000 daltons. This material can be dissociated into two dissimilar polypeptide chains of approximately 10 000 daltons. Ion-exchange chromatography on DEAE-cellulose resolves affinity-purified MPL into five components. These proteins are structurally related and contain varying proportions of the two polypeptide chains. Two of these tetrameric lectins, each composed solely of one of these chains, display differences in mobility during discontinuous polyacrylamide gel electrophoresis and ion-exchange chromatography, but display no detectable differences in hemagglutination of human erythrocytes and interactions with carbohydrates.

Changes of the static-dynamical balance inside the thorax by pressure or traction of pathologic processes effect dislocation of the trachea and the larynx. Basing on the clinical symptoms of 45 patients the results are stated of experiments on cadavers and on isolated, at the hyoid bone fixed laryngotracheal preparations. Opposite displacements of the larynx and the trachea, especially in mediastinal processes, are to be observed among predominant equilateral dislocations to the side of the thorax process, concerning primarily the trachea and only in increasing pressure or traction also the larynx. The findings are collated with earlier researches to the same subject. They have a bearing on the interpretation and the attachment of the symptoms of stenosis.

The possible excretion of biocytin or biotinyl-peptides was investigated in urines of children with congenital biotinidase deficiency. Treatment of urine samples of affected children with normal plasma (as source of biotinidase) liberated additional free biotin (L. plantarum assay), indicating the presence of biotinyl-compounds. Using thin-layer chromatography the occurrence of biocytin was demonstrated in all urine samples of the affected children. In contrast, no biocytin could be detected in urines of healthy subjects.

Maclura promifera seeds contain a protein which agglutinates human erythrocytes at concentrations as low as 4 ng/mL. This property is related to its ability to bind with high specificity various alpha-D-galactopyranosides. The agglutinin, which was pruified by affinity adsorption, exhibits one band on immunoelectrophoresis and displays one peak during ultracentrifugation, isoelectric focusing, and gel permeation chromatography. The active protein has a molecular weight of 40 000-43 000 and contains two dissimilar polypeptide chains of 12 000 and 10 000, respectively.

Clinical and biochemical investigations in six patients with congenital biotinidase deficiency are presented. The time course of biotin depletion in relation to carboxylase activities and clinical onset of symptoms was studied after withdrawal of biotin supplementation. Renal biotin clearance studies were performed in patients and controls. Renal loss of biocytin and biotin itself are shown to be a major cause for the increased biotin requirement in patients with congenital biotinidase deficiency.

In a cross-over experiment, 46 young healthy volunteers consumed in succession a high-fiber and a low-fiber diet for 3 weeks at two levels of dietary cholesterol. Half of the dietary fiber came from fruits and vegetables, and the rest from bread and other cereal products. On the high-fiber diet, concentrations of serum cholesterol decreased on average by 0.44 mmole/liter with high-cholesterol and 0.31 mmole/liter with low-cholesterol regimes; high density lipoprotein-cholesterole decreased by 0.1 mmole/liter; on average fecal weight increased by 115 g/day and mean transit time through the gut was decreased by 18 hr. Only part of the decrease in serum cholesterole may be due directly to the high intake of dietary fiber components. The remainder is due to differences in fat intake: during the high-fiber period subjects consumed less fat and cholesterol than had been planned.

A specific method for the quantitative determination of biocytin from urine of biotinidase deficient patients is described using HPLC-separation and quantitative determination by an avidin binding method. Partial purification of biocytin from urine was achieved with an anion exchange resin and concentration of the eluate by lyophilization. The recovery of biocytin from urines was 95.3 +/- 5.9 (mean +/- SD). The precision of biocytin estimation in patients urines including the HPLC-sample preparation procedure varied between 5.9% and 10.5% (CV). Biocytin concentrations were measured in urine samples of 5 patients obtained during and/or before biotin therapy. Before treatment biocytin excretion ranged from 6.2-28.8 nmol/mmol creatinine. During therapy biocytin excretion increased to the 1.3 to 4-fold level in 3 out of 4 patients. However, there was no dose-related increase of biocytin excretion when pharmacological doses were administered. Apart from biocytin and biotin, patients excrete additional biotin derivatives. Some of these have been preliminary identified as bisnorbiotin and oxidation products of bisnorbiotin, biocytin and biotin.