[Originators and eponyms of dermatomyositis : Ernst Leberecht Wagner (1821-1888) and Heinrich Unverricht (1853-1912)]. / Erstbeschreiber und Namensgeber der Dermatomyositis : Ernst Leberecht Wagner (1821-1888) und Heinrich Unverricht (1853-1912).

Dermatomyositis is a rare muscle disease that was first described by Ernst Leberecht Wagner and Heinrich Unverricht.After providing a survey on both scientists' life works, this contribution describes the most significant subsequent works on the diagnostics and classification of clinical symptoms and the progress of the disease that the author has been observing for more than three decades.Polymyositis/dermatomyositis (also known as Unverricht-Wagner or Wagner-Unverricht syndrome) was described in two publications by Ernst Leberecht Wagner in 1863 and 1887. Wagner was - probably uniquely in Germany - consecutively professor of pathology and also, as a successor to K. A. Wunderlich, of internal medicine at the University of Leipzig. The most frequently used designation for polymyositis/dermatomyositis today was originated by Heinrich Unverricht in 1891. After his education in his home town of Breslau, Unverricht was first employed as head of the clinic for internal medicine in Jena. From 1886 he was a professor in Dorpat, but he left this university when the language of teaching was changed to Russian in 1892. Unverricht then became the first director of the newly founded Sudenburg Hospital in Magdeburg (Medical Academy from 1954 to 1991).During the subsequent decades, further medical scientists have studied the disease and brought about today's precise classification criteria for diagnostics - based on Wagner's and Unverricht's findings.

Methodological challenges in evaluating performance, impact and ranking of IWRM strategies in the Jordan Valley.

The philosophy of integrated water resource management (IWRM), as formulated in several international summits, yielded numerous interpretations and extensions over the last decade but always focused on the overall objective of maximizing the welfare and livelihood of the people concerned. One of the major constraints of this concept is the gap between the well-defined philosophy and the fuzzy definition of operational and testable indicators for the achievement of its goals. This leads to difficulties in the evaluation of potential contributions from technological and managerial improvements. The experience of the multi-lateral IWRM research initiative SMART in the lower Jordan Valley shows that the evaluation and ranking of alternative IWRM strategies and their elements relies simultaneously on the identification of local goals and their interfaces with the superordinate national water sector policies. The documentation of the, still ongoing, development process of suitable assessment procedures describes their methodological embedding and conclusions drawn for the heterogeneous situation of water-related settings in this transboundary watershed.

[Nursing in the profession of the "sub-surgeons" between 1750 and 1850]. / Krankenpflege im Berufsbild der "Subchirurgen" zwischen 1750 und 1850.

Between 1750 and 1850 surgical training was professionalized as a consequence of newly established technical colleges for surgeons in Germany and Austria led by doctors rather than craftsmen. At first, anatomy, debridement and obstetrics was taught, then a technical knowledge of medical treatment in general was instructed at specific medical/surgical schools. Depending on their years of training, graduates then worked as country doctors or as surgical assistants ("Subchirurgen", second class wound doctors). Nursing care was also on the curriculum; therefore some students worked temporarily as nurses. After graduating, many supervised nursing care in hospitals. This profession died out due to developments in the medical profession of the mid-19th century. However, they never belonged to the proletarian class of orderlies.

[The Karlsruhe Nursing School]. / Das Karlsruher Krankenwärterinstitut.

Systematic education in professional nursing was established during 1782 in Germany by the general practitioner and midwife lecturer Franz Anton Mai. The second institution of this kind was opened in Karlsruhe during 1784 by the general practitioner Christian Ludwig Schweickhard. The archives in Karlsruhe showed that Mai also founded this second institution and gave the first lectures, while Schweickhard continued the lectures until 1811. On the one hand this shows the importance of the foundation of the nursing schools by Franz Anton Mai and on the other hand points out that the first nursing schools in Germany were strongly influenced by already existing schools for midwives.

[Michael Gering's (1918-1969) influence on nursing education in the German Democratic Republic]. / Der Einfluss Michael Gehrings (1918-1969) auf die krankenpflegeausbildung in der DDR.

In 1945, the young physician Michael Gehring returned from captivity to his home in East-Germany. He joined the Liberaldemokratische Partei (LDPD), then went over to the SED. After having played a decisive role in establishing one of the first outpatients' clinics, he was called to the central administration of health in East-Berlin. He transformed the traditional nursing education by integrating it into the state system of medical technical colleges. Didactical and methodical indications were added to the first curriculum for the new nursing course, which had been written by Gehring. He also tried to introduce I.P. Pawlow's physiological theory into nursing-theory. It is true that he ignored older German and American research on the subject. But concerning the history of nursing his performance in improving educational organization in East-Germany has to be highly valued.

[The history of medical nursing schools at the Vienna University (1812 to 1846) and at the Royal Charité Hospital in Berlin since 1832]. / Zur Geschichte der ärztlichen Krankenpflegeschulen an der Wiener Universität (1812 bis 1846) und am Königlichen Charit-Krankenhaus in Berlin seit 1832.

The first examples of nurse training, beginning in Vienna in 1812 and in Berlin in 1832, demonstrate that research in nursing-history must explore primary sources which are still in existence, in order to counteract current cliche and perhaps even develop completely new insights into historical accounts. Nursing literature in Austria did not start will the textbook by Billroth (1st edition 1881), but with the textbook by Maximilian Florian Schmidt, same publisher, 50 years earlier. His professorship was not held in the University but in what would not be a technical school. The textbook by Schmidt, and not that by Franz Anton Mai (1782), provided the submission for the curriculum which Dieffenbach made available to the school opened in Berlin in 1832. Dieffenbach was given the title of "Professor" for his services to "the improvement of nursing" and not for his pioneer work in plastic and orthopedic surgery. It was not Dieffenbach's curriculum but the 1837 revision of the work of Gedike, who was not a pupil of Dieffenbach's, which was used by the ministery responsible for the Board of Trustees of the hospital, for the state controlled course of nursing education. This educational programme was not less optional than that statutorily controlled one from 1907 onwards.

(-)-BM 13.0913: a new oral antidiabetic agent that improves insulin sensitivity in animal models of type II (non-insulin-dependent) diabetes mellitus.

Insulin resistance is one of the key features of non-insulin-dependent diabetes mellitus (NIDDM). Therefore, a drug that causes an improvement in insulin sensitivity would be of great interest for the treatment of NIDDM. In addition to the insulin-sensitizing thiazolidinediones, we have found another class of insulin-sensitizing agents: the alpha-activated carbonic acids. (-)-BM 13.0913, a member of this class, was effective in improving insulin resistance in hyperinsulinemic and hypoinsulinemic insulin-resistant animal models of NIDDM. The 50% effective dose (ED50) for the glucose-lowering action was 4, 2.4, and 8 mg/kg in ob/ob, yellow KK, and db/db mice, respectively. The ED50 for the insulin-lowering action was 14.5, 5, and 26 mg/kg. This rightward shift of the dose-response curve for insulin indicates that improving glucose homeostasis is the primary effect of the drug, followed by an insulin-decreasing action. This effect on glucose homeostasis may be brought about by sensitizing peripheral target tissues to the effects of insulin. An increase in deoxyglucose uptake and glucose oxidation measured in adipocytes from rats that had been treated for 14 days with (-)-BM 13.0913 supports this conclusion. Glucose uptake and oxidation was increased at all insulin concentrations tested, suggesting an improved responsiveness. Insulin sensitivity in adipocytes was not influenced by the drug. Studies in the moderately hypoinsulinemic, low-dose streptozotocin (STZ) diabetic rat with a residual insulin concentration showed a decrease in blood glucose concentrations, as well as a decrease in urinary glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

[Career paths and professional education in the former German Democratic Republic 1949-1989]. / Die Berufs- und Ausbildungswege der Krankenpflege in der ehemaligen Deutschen Demokratischen Republik von 1949 bis 1989.

With the unification of Germany the career structure and the places where nurses were educated and trained were pushed aside, as legislation of the Federal Republic was adopted. Thus they have acquired historical interest. Nevertheless they represent a quasi governmental experiment, the outcome of which should be recognised as a historical experience and should be preserved scientifically, because of the impact on the development of nursing-education, professionalization of nursing and most of all on the preparation of nurse-teachers. The authors of this paper are former nurses and educators in medical subject who were actively involved in developments, as teachers in hospitals and lecturers in teacher training colleges, since 1957 in the former DDR. The paper describes the organisation of nursing-education, the educational institutions in which this took place and the concurrent development of qualification for nurse teaching. What probably has most significance for the future is the experience gained between 1961 and 1974 in attaching nurses' professional training directly, without any time interval, to the 10th year of schooling. The outcome of this should be evaluated.

[Medical use of fetal cells and tissue: ethical aspects]. / Die medizinische Nutzung fetaler Zellen und Gewebe: ethische Aspekte.

After considering the moral status of the living and of the dead human fetus, the article examines various ethical arguments connected with the use of fetal remains following elective abortion: financial or humanitarian incentives for the termination of pregnancy, conflicts of interest between mother and user, authority over fetal remains and modality of donation and utilization of the fetus. To prevent improper use of fetal remains it is recommended: to separate completely the decisions relating to abortion (first) and to the subsequent use of fetal tissues (second); to obtain explicit informed consent from the mother, making it impossible for her to direct any specific use of the fetal tissues; to base decisions on the method and timing of an abortion on the mother's health care needs alone; to exclude those involved in the process of abortion from any use of the fetus; to protect the anonymity of donor and recipient through an intermediary (tissue bank).

Blood-glucose-lowering activity of 2-(3-phenylpropoxyimido)-butyrate (BM 13.677).

A single oral or intraperitoneal application of 2-(3-phenylpropoxyimido)-butyrate (BM 13.677) resulted in a dose-dependent blood-glucose-lowering effect in fasted guinea-pigs. The threshold dose and the EC50 were estimated as 25 mg/kg and 63 mg/kg, respectively, which is between that of the biguanides phenformin and metformin. A rise in blood lactate concentrations was observed only at high doses of BM 13.677, but was not related to an irreversible metabolic inhibition. Among several rodent species studied the potency of the drug decreased in the order guinea-pig much greater than mouse greater than rat = rabbit. Inhibition of hepatic gluconeogenesis by the drug was demonstrated in the perfused liver or hepatocytes of guinea-pigs. Inhibition of glucose production by the perfused liver in the presence of 0.1 mM BM 13.677 was dependent on the substrate and decreased in the order: lactate greater than pyruvate greater than alanine much greater than propionate greater than glycerol = fructose. This suggests a specific interaction of the drug with a mitochondrial key reaction of gluconeogenesis. Stimulation of glucose oxidation in rat diaphragm by the compound (EC50 = 0.85 mM) suggests that besides inhibition of gluconeogenesis also extrahepatic effects contribute to the blood-glucose-lowering effects of the drug.

Irreversible inhibition of the TXA2/PGH2 receptor of human platelets by a photoaffinity ligand.

In order to tag the TXA2/PGH2 receptor of human platelets, we synthesized azido-BSP (= 4-[2-(4-azido-benzenesulfonylamino)-ethyl]phenoxyacetic acid), a photolabile derivative of the specific TXA2/PGH2 receptor antagonist sulotroban (= BM 13.177). If protected from UV light, azido-BSP competitively inhibited the shape change of human washed platelets stimulated by the TXA2 mimetic U 46619. Schild analysis revealed a pA2 = 6.7 (apparent KD = 0.2 mumol/l). Irreversible inhibition of the U 46619-induced platelet activation was achieved by irradiating for 5 min with UV light of 254 nm a platelet suspension containing azido-BSP. After subsequent washing, the platelets were stimulated with U 46619, ADP or PAF. Under these conditions azido-BSP inhibited the shape change, aggregation and [3H]serotonin release induced by U 46619 but not the shape change induced by ADP or PAF. The concentrations of azido-BSP which blocked the U 46619-induced [3H]serotonin release and the aggregation were 0.5 mumol/l and 1.0 mumol/l, respectively, whereas even 50.0 mumol/l of azido-BSP only partially inhibited the U 46619-stimulated shape change. Obviously, increasing numbers of thromboxane receptors have to be blocked in order to inhibit the [3H]serotonin release, the aggregation and the shape change. Even at an azido-BSP concentration equal to 250 times the apparent dissociation constant, enough receptor sites remained active to allow U 46619 to induce the shape change. In sulotroban was added prior to irradiation, the blocking effect of azido-BSP decreased with increasing concentrations of sulotroban. These results show that azido-BSP is a specific and high affinity ligand of the TXA2/PGH2 receptor and that it covalently links to the receptor under irradiation. Azido-BSP is a new tool to identify and characterize the TXA2/PGH2 receptor.

Synthesis and hypoglycemic activity of N-alkylated hydrazonopropionic acids.

A series of N-alkylated 2-hydrazonopropionic acids have been synthesized and evaluated for their hypoglycemic activity. Most of the compounds exhibit a remarkable blood glucose lowering activity in fasted guinea pigs. Some of the structural variables studied were the effects of branching, unsaturation, or substitution on the alkyl side chain and the effect of nuclear substitution on the aralkyl analogues. From these compounds, 2-[[(E)-2-methyl-3-phenyl-2-propenyl]hydrazono]propionic acid (BM 42.304; 42) was selected for further investigation.

The pharmacological profile of the thromboxane A2 antagonist BM 13.177. A new anti-platelet and anti-thrombotic drug.

BM 13.177 (4-[2-(benzenesulfonamido)-ethyl]-phenoxyacetic acid) is a representative of a new class of sulfonamidophenylcarboxylic acids which possess platelet-inhibitory and anti-thrombotic activity and inhibits the contraction of rabbit aorta stimulated by PG endoperoxides and TXA2. BM 13.177 5 mg/kg body weight p.o. protected rabbits from arachidonate-induced sudden death and greater than or equal to 10 mg/kg dose-dependently reduced the experimental thrombus formation induced in the rabbit aorta by perivascular administration of silver nitrate. In guinea-pigs, the collagen-induced bronchoconstriction was inhibited in a dose- and time-dependent fashion. The formation of TXA2 and the TXA2-induced platelet aggregation and smooth muscle contraction are probably crucial events in these experimental models. The protective effect of BM 13.177 may, therefore, be due to the TXA2-antagonizing effect of BM 13.177, which has been conclusively demonstrated in human platelets (PATSCHEKE and STEGMEIER, Thrombosis Res., 33, 277-288 (1984). The antagonism of TXA2 is supported by the observation that BM 13.177 also specifically inhibits the contraction of isolated arterial strips from rabbits which were stimulated with the thromboxane A2 mimetic U 46619. Schild-plot with a slope close to unity suggests a competitive type of antagonism. BM 13.177 exhibited neither anti-inflammatory nor ulcer-inducing activity of cyclooxygenase inhibitors. Furthermore it did not block the TXB2 formation in spontaneously clotting blood from rabbits and did not inhibit the release of prostacyclin-like activity from rabbit aortas. The lack of toxicological effects in long-term toxicity studies in rat and dog, together with the absence of objective and subjective side effects in the first human studies have encouraged us to initiate clinical trials in order to evaluate the therapeutic benefit of this new approach in humans.