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Introduction PARP (Poly ADP Ribose Polymerase) inhibitors are an effective maintenance therapy for various entities, such as BRCA (breast cancer gene) mutated or HRD (homologous recombination deficiency) positive primary platin-sensitive advanced ovarian cancer after platin induction therapy and in relapse after responding to carboplatin reinduction. Other entities are metastatic BRCA mutated pancreas, prostate and Her2-negative breast cancer. Therefore, patients with allergic reactions to PARP inhibitors should undergo a desensitization procedure to be able to receive this efficient therapy. Case report We conducted a two-day desensitization on a 45-year-s old patient with advanced ovarian cancer who displayed symptoms of an allergic reaction to Olaparib. Management and outcome Using an Olaparib tablet suspension, we orally administered increasing Olaparib doses, starting with 12.5 mg and reaching a cumulative dose of 387.5 mg on the first day and starting with 100 mg and reaching a cumulative dose of 600 mg on the second day, without concomitant antiallergic medication. Except for mild erythema on day one receding within the hour, no further allergic reactions appeared during desensitization. The patient has since received 300 mg of Olaparib twice a day without further complications or interruptions. Conclusion Desensitization in a two-day suspension protocol is a safe method that ensures effective maintenance therapy for patients with allergic reactions to PARP inhibitors.

Objectives Clinical pharmacy services in German hospitals appear to be underdeveloped compared with other European countries. However, recent developments have increased the interest in expanding these services. Detailed data about the current state of clinical pharmacy services in Germany are lacking. This survey establishes the current level of pharmacy services in Germany and the barriers to implementation. Methods An online survey conducted in 2017 was distributed to directors of all 389 German hospital pharmacies. The survey contained 26 questions addressing hospital and pharmacy characteristics, clinical pharmacy services provided, the number of clinical pharmacists and the frequency as well as the quality assurance of these services. Results There were 133 responses (34%). Of these, 84 (63%) pharmacies provided some form of clinical pharmacy services. Based on the 389 contacted pharmacies, a clinical pharmacy service is available in at least 22% of hospital pharmacies in Germany. On average there are 2.4 full-time equivalent (FTE) clinical pharmacists per hospital employed, although there is a wide variation in numbers (0.3–22 FTE) and service provision between hospitals. Clinical pharmacy services are generally provided on a daily or weekly basis, with a principal focus on general surgery, critical care and general medicine wards. Conclusions This is the first survey providing a detailed picture of clinical pharmacy services in Germany. There is wide variation in clinical service provision among hospitals, with some hospitals having developed a comprehensive range of clinical services. Compared with other countries, particularly the UK where the focus has shifted to provision of 7-day clinical services, the gap in clinical pharmacy services remains large. The focus should be turned to refining clinical pharmacy services in hospital admissions and discharge planning while also improving Health IT, the opportunities for specialisation and aligning education in accordance with the EAHP common training framework.

Platinkomplexe spielen in der zentralen Zytostatikazubereitung der Apotheke eine wesentliche Rolle. Wenn auch die Herstellung applikationsfertiger Infusionslosungen der drei in der Therapie befindlichen Platinkomplexe Cisplatin, Carboplatin und Oxaliplatin aus Fertigarzneimitteln keine grose technologische Herausforderung darstellt, so ist doch ein umfangreiches Wissensspektrum nicht zuletzt uber die Supportivtherapie aller drei Komplexe Voraussetzung fur eine adaquate pharmazeutische Therapiebegleitung durch die Apotheke. Hier kann sich die Apotheke als pharmazeutischer Dienstleister etablieren und Mitverantwortung fur eine optimale Arzneimitteltherapie der Patienten ubernehmen.

DNA is the ultimate target of platinum-based anticancer therapy. Since the N7 of guanine is known to be the major binding site of cisplatin and its analogues, adduct formation with model nucleotides, especially 2'-deoxyguanosine 5'-monophosphate (dGMP), has been studied in detail. During the last few years a coupled capillary eletrophoresis/electrospray-ionization mass spectrometry (CE/ESI-MS) method has been advantageously used in order to separate and identify platinum adducts with nucleotides in submillimolar concentrations in aqueous solutions. Beside the bisadduct, [Pt(NH(3))(2)(dNMP)(2)](2-) (NMP=2'-deoxynucleoside 5'-monophosphate), and the well-known monochloro and monohydroxo adducts, [Pt(NH(3))(2)Cl(dNMP)](-) and [Pt(NH(3))(2)(dNMP)OH](-), respectively, a third kind of monoadduct species with a composition of [Pt(NH(3))(2)(dNMP)](-) can be separated by CE and detected through the m/z values measured with ESI-MS. Different experimental setups indicate the existence of an O(6)-N7 chelate, whereas the formation of N7-alphaPO(4) macrochelates or dinuclear species is unlikely. Additionally, offline MS experiments with 2'-deoxyguanosine (dG) and stabilization of the controversially discussed O(6)-N7 chelate by oxidation with hydrogen peroxide support the assumption of the existence of O(6)-N7 chelation.

Platinum adducts are supposed to be the cytotoxic lesions in DNA after platinum-containing anticancer therapy. Various adducts are formed upon interaction of platinum complexes with nucleotides, but contribution of individual adducts to antitumor activity and toxicity of platinum complexes still remains to be examined. A capillary zone electrophoresis (CZE) method is described that is suitable to separate individual platinum adducts. We investigated the formation of adducts following the reaction of cis-diamminedichloroplatinum (II) (cisplatin) with various DNA nucleotides. Baseline separation of unmodified and modified nucleotides (adducts) was achieved using uncoated fused-silica capillaries and basic separation buffers. In order to elucidate the observed peak pattern, a coupled CZE-electrospray ionization-mass spectrometry (ESI)-MS approach was applied. After incubation of mononucleotides with cisplatin, monochloro, monoaqua and bifunctional adduct species were detected. Consequently, the migration order of nucleotides and individual platinum adducts could be determined. Moreover, the time-dependent conversion from monochloro to monoaqua and subsequently to bifunctional adducts was monitored. In conclusion, individual platinum adducts were separated by CZE and identified by CZE-ESI-MS. Formation and conversion of distinct species were confirmed. Potential applications comprise studies of novel platinum complexes, investigations of platinum-adduct formation with DNA, and determination of platinum-DNA adducts in cells.

PEMF-induced transmembrane transfer of H + ions into blood vessel walls and the electrostriction phenomenon play a major role in the functioning of bioenergetic and receptor systems. This explains the following changes in our measured indicators of effects. 1. The pH is low, and hence p CO 2 is high, in the capillaries where oxygen is separated from hemoglobin, which results in a high p O 2 and dilatation moment in the arteries and veins. 2. A low pH in the cerebrospinal fluid (4th ventricle) and adjacent tissues increases the respiration amplitude. 3. A low pH in the vaguscenter reduces the heart beat frequency, and the pH determines the net charge of proteins and the level of enzyme activity. 4. A low pH in the vessel walls increases the sensitivity of the baroreceptors, which are stimulated by the microvibration due to mechanical electrostriction and which in consequence reduce the central sympathetic tonus. Therefore it appears that the transfer of hydrogen ions from blood to tissue is a primary working mechanism of our type of PEMF with the effects described above.

Zu Zeiten der fruhen arbeitsphysiologischen Untersuchungen war es das Hauptziel, den schwer arbeitenden Menschen durch eine biomechanisch halbwegs angemessene „Schnittstelle“ zur bedienten Maschine mechanisch zu entlasten. So konnte man beipielsweise allein durch Einfuhrung einer geeigneteren Stuhlhohe und einer Ruckenlehne mit optimierter Neigung die (atmungsphysiologisch mesbare) Belastung beim periodischen Drucken eines Fushebels auf die Halfte reduzieren. Aspekte dieser Art gelten heute nur noch im geringen Mas und dienen eher dem Komfort und der feinfuhligen Geratehandhabung. So zeigt die Abbildung 1 A eine klassische Zange in der Hand; die Muskeln arbeiten wegen der symmetrischen Zangenkonstruktion und des asymmetrischen Handbaus nicht optimal. Eine bessere Abstimmung, die einen hoheren Kraftaufwand mit geringere „Belastung“ kombiniert (Abb. 1 B) erreicht man durch eine unsymmetrische Zangenform, die „besser in der Hand liegt“.

The history of bioelectromagnetics, M. Bischof introduction to electromagnetism, F. Popp basic electromagnetic interactions of biological systems, U. Warnke electroception, magnetonavigation and orientation in animals, U. Warnke can weak magnetic fields (or potentials) affect pattern formation?, M.-W. Ho et al electromagnetic fields and biomembranes, R.P. Liburdy the language of cells - molecular processing of electric signal by cell membranes, T.Y. Tsong and C. Grosse biological effects of ELF, microwaves and millimeter waves, C. Smith dielectric and AC electrodynamic properties of cells, R. Pethig electroporation and its biological implications, C. Chang biophotons and biological coherence, W.P. Mei liquid crystalline mesophase in living organisms, M.-W. Ho and P.T. Saunders coherent brain waves in visual perception as detected with the SQUID magnetometer, A.A. laonnides skin conductivity measurements - electroacupuncture and electrodiagnosis, L.Z. Chang and F. Popp promises and perils of electromedicine, U. Warnke can weak magnetic fields have biological effects?, D. Edmonds Frohlich's theory of coherent excitation - a retrospective, T.M. Wu the storage and transport of energy in biological systems, A.S. Davydov what is the relationship between bioelectromagnetism and biocommunication?, M.-W. Ho.

International audience

In the year 1979 we published the results of our preliminary experiments. 1 PEMFs with impulse package frequencies in the ELF-range modify the infrared radiation (3-10 µm) of local areas of the body surface in humans. This occurs in single cases already at magnetic induction values of dB/dt < 500 mT/sec when the field is applied to the head-thorax-area (Fig. 1).