Inzidenz von bullösen Autoimmunerkrankungen in Serbien: eine retrospektive Studie über 20 Jahre.

PubMed

Milinković, Mirjana; Janković, Slavenka; Medenica, Ljiljana; Nikolić, Miloš; Reljić, Vesna; Popadić, Svetlana; Janković, Janko

2016-10-01

Die meisten früheren Arbeiten zu den klinisch-epidemiologischen Merkmalen von bullösen Autoimmunerkrankungen (AIBD) konzentrierten sich vor allem auf eine einzige Krankheitsentität oder nur eine Krankheitsgruppe; nur in wenigen Studien wurde die Inzidenz verschiedener AIBD untersucht. Bei der vorliegenden Studie war es unser Ziel, das gesamte Spektrum der AIBD zu betrachten, die Inzidenz der häufigsten AIBD zu ermitteln und die zeitlichen Trends ihres Auftretens in Zentralserbien über einen Zeitraum von 20 Jahren zu untersuchen. Wir rekrutierten retrospektiv 1161 AIBD-Fälle, die in Zentralserbien von Januar 1991 bis Dezember 2010 neu diagnostiziert wurden. Die Diagnose stützte sich auf eine strikte klinische, histologische und immunhistologische Beurteilung. Folgende Inzidenzraten wurden für die einzelnen Erkrankungen ermittelt: 4,35 pro eine Million Einwohner/Jahr (pME/Jahr) für Pemphigus, 4,47 pME/Jahr für Pemphigoid, 1,42 pME/Jahr für Dermatitis herpetiformis (DH), 0,25 pME/Jahr IgA-Dermatose und 0,08 pME/Jahr für Epidermolysis bullosa acquisita. Im betrachteten Zeitraum stieg die altersbereinigte Inzidenzrate für Pemphigus und insbesondere für Pemphigoid signifikant an, während sie für DH, allerdings nicht signifikant, abnahm. Unsere Studie befasst sich zum ersten Mal mit den Inzidenzraten des gesamten Spektrums der AIBD in Serbien und untersucht die zeitlichen Trends ihres Auftretens über einen Zeitraum von 20 Jahren. Nach unserem besten Wissen wurde ein ähnlicher Befund wie der unsere, dass nämlich die Inzidenzraten von Pemphigus und Pemphigoid vergleichbar sind, bisher noch nicht publiziert. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Transfer factor - hypotheses for its structure and function.

PubMed

Shifrine, M; Scibienski, R

1975-01-01

Transfer factor (TF) is a dialyzable extract from primed lymphocytes that is able to transfer specific delayed hypersensitivity from one animal to another. On the basis of available data we suggest that TF is a polypeptide with a molecular weight below 15,000 daltons. We hypothesize that TF is the variable light or heavy chain domain of immunoglobulin: such a molecule conforms with the accepted properties of TF and also has the necessary specificity requirements. We also hypothesize that TF is part of a receptor site. beta-2-microglobulin, a molecule that is an integral part of cell surfaces, could be the anchor for TF. beta-2-microglobulin has homologies with the constant portion of immunoglobulin light or heavy chain and thus would combine with the variable domain (TF) to form a complete receptor site for a specific antigen. The properties of TF suggest its mode of action, which is discussed in detail in the text. The biologic advantages of TF is its ability to confer immediate (immunologie specific) protection while the 'normal' immune response develops.

Intraläsionale Therapie niedrig maligner primär kutaner B-Zell-Lymphome mit Anti-CD20-Antikörper: Nebenwirkungen korrelieren mit gutem klinischen Ansprechen.

PubMed

Eberle, Franziska C; Holstein, Julia; Scheu, Alexander; Fend, Falko; Yazdi, Amir S

2017-03-01

Die intraläsionale Gabe von Anti-CD20-Antikörpern (Rituximab) wurde als effektive Therapieoption für Patienten mit niedrig malignen primär kutanen B-Zell-Lymphomen beschrieben. Bis heute wurden allerdings keine Parameter identifiziert, welche reproduzierbar ein gutes klinisches Ansprechen dieser Therapie vorhersagen. Ziel dieser Studie ist, sowohl das klinische Ansprechen und die unerwünschten Nebenwirkungen als auch die Patientenwahrnehmung hinsichtlich intraläsionaler Injektionen von anti-CD20-Antikörpern zur Behandlung indolenter primär kutaner B-Zell-Lymphome im Vergleich mit anderen Therapien zu evaluieren. Elf Patienten mit einem primär kutanen B-Zell-Lymphom, namentlich primär kutanes Keimzentrumslymphom (n = 9) und primär kutanes Marginalzonenlymphom (n = 2), welche mittels intraläsionalem Anti-CD20-Antikörper behandelt wurden, wurden retrospektiv evaluiert hinsichtlich der Ansprechrate und unerwünschter Nebenwirkungen sowie in Bezug auf deren Selbsteinschätzung dieser und anderer Therapien des primär kutanen B-Zell-Lymphoms. Patienten, deren primär kutanes B-Zell-Lymphom mittels intraläsionaler Gabe von Anti-CD20-Antikörper behandelt wurde, zeigten ein komplettes oder partielles Ansprechen in 45 % beziehungsweise 27 % aller Patienten. Speziell Patienten mit grippeähnlichen Symptomen nach erfolgter Injektion zeigten ein gutes Ansprechen. Die Mehrheit der Patienten empfand die Therapie mit Rituximab als die beste Therapie im Vergleich zu anderen Therapien wie beispielsweise chirurgische Exzision oder Radiotherapie. Intraläsionales Rituximab ist eine effektive Therapie mit hoher Patientenzufriedenheit. Starke therapiebedingte Nebenwirkungen wie Fieber, Schüttelfrost und Kopfschmerzen nach Gabe von Rituximab könnten als Indikator für gute Wirksamkeit dienen. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Antibakterielle In-vitro-Wirksamkeit ätherischer Öle gegen veterinärmedizinisch relevante Keime klinischer Isolate von Hunden, Katzen und Pferden.

PubMed

Bismarck, Doris; Schneider, Marianne; Müller, Elisabeth

Einleitung: Ätherische Öle sind die Grundlage der Aromatherapie. Unter anderem wird ihnen eine antibakterielle Wirkung zugeschrieben. In dieser Studie sollte die In-vitro-Wirksamkeit ätherischer Öle gegen ein breites Spektrum veterinärmedizinisch relevanter Erreger getestet werden. Methoden: Die antibakterielle Aktivität von 16 ätherischen Ölen wurde mittels Agardiffusionstest bestimmt. Getestet wurden grampositive und gramnegative Erreger, die aus klinischen Isolaten von Hunden, Katzen und Pferden aus der veterinärmedizinischen Routinediagnostik stammten. Die Einteilung der Wirksamkeit in nicht, gering-, mittel- und hochgradig wirksam erfolgte anhand der Größe der Hemmhofradien des Bakterienwachstums. Ergebnisse: Generell zeigten sich sowohl grampositive als auch gramnegative Erreger empfindlich gegen einige der getesteten ätherischen Öle. Nicht nur gegen Staphylokokken, sondern auch gegen Methicillin-resistente Stämme der Staphylokokken wiesen die ätherischen Öle in vitro eine nicht zu vernachlässigende Wirkung auf. Pasteurella multocida stellte sich als eher sensibler Keim heraus, während Pseudomonas aeruginosa als vollkommen resistenter Keim eine Ausnahme bildete. Teebaum-, Oregano-, und Bergbohnenkrautöl waren die potentesten Öle. Zusätzlich zeigten sich bei den grampositiven Erregern Lemongrasöl und bei den gramnegativen Erregern Thymianöl als gut wirksam. Schlussfolgerung: Ätherische Öle verfügen in vitro über eine antibakterielle Aktivität gegen klinische Isolate von Hunden, Katzen und Pferden. Diese Studie bietet eine Grundlage für die Anwendung ätherischer Öle in der Veterinärmedizin. Es zeichneten sich Tendenzen im Wirkspektrum einzelner ätherischer Öle bzw. im Grad der Wirksamkeit ätherischer Öle hinsichtlich einzelner Erregerspezies ab, allerdings lässt sich keine sichere Vorhersage über ihre Wirksamkeit gegen einen spezifischen Keim eines individuellen Patienten treffen. Deswegen sollte vor einer Therapie mit ätherischen Ölen deren individuelle Wirksamkeit mittels Aromatogramm getestet werden. © 2017 The Author(s). Published by S. Karger GmbH, Freiburg.

[The Coordinating Centers for Clinical Trials (KKS) and the KKS Network: competence for clinical research].

PubMed

Ohmann, Christian; Bruns, Insa; Wolff, Stephanie

2010-01-01

The Network of the Coordination Centers for Clinical Trials (CTCs; Koordinierungszentren für Klinische Studien(KKS)) comprises 17 institutions working as scientific service provider for universities, study groups, the pharmaceutical and medical devices industry as well as additional clients associated with clinical research. The CTCs have established planning and conduct of clinical trials according to Good Clinical Practice (GCP) guidelines,with a wide range of study support in academia. One focus according to indications is cancer. Expertise in hematological/oncological research can be requested nationwide and cross-institutional. The KKS network currently cooperates with medical societies and other, even European networks in 20 countries and has been established as a strong platform for oncological trials. Copyright © 2010 S. Karger AG, Basel.

[Distant healing and diabetes mellitus. A pilot study].

PubMed

Ebneter, M; Binder, M; Kristof, O; Walach, H; Saller, R

2002-02-01

The Institut für Grenzgebiete der Psychologie und Psychohygiene, Freiburg (IGPP) in cooperation with the Abteilung Naturheilkunde, University Hospital, Zürich investigated whether Distant Healing has a beneficial effect on patients with diabetes mellitus regarding the state of the disease and quality of life. The goal of the pilot study was to observe the progression of the disease with various medical and psychological measures and to explore which of them might be sensitive for measuring possible treatment effects. 14 diabetic patients were observed for a period of 16 weeks. Within this time they underwent a treatment of 4 consecutive weeks (weeks 9-12) by 5 experienced and trustworthy healers each. Patients were informed about the duration of the treatment but not about the time point of its beginning. Patients and healers never met and there was no contact between researchers and patients during the study period. With regard to medical parameters, reduction in fructosamine level was observed during the healing period, increasing fructosamine level after the end of the healing period. Sensitivity, measured only at the beginning and at the end of the study period, decreased significantly. The other parameters showed some significant changes but there was no correlation to the Distant Healing intervention. Regarding the psychological data, only improvements were observed. The results indicate the possibility that a Distant Healing intervention could have certain effects on patients with diabetes mellitus. Copyright 2002 S. Karger GmbH, Freiburg

A review of Edward Flatau's 1894 Atlas of the Human Brain by the neurologist Sigmund Freud.

PubMed

Triarhou, Lazaros C

2011-01-01

In 1894, the Polish neurologist Edward Flatau (1868-1932), working in Berlin, published an exquisite photographic atlas of the unfixed human brain, preceding by 2 years Das Menschenhirn, the reference work of Gustaf Retzius (1842-1919) in Stockholm. In his early career as a neuroanatomist and neurologist, Sigmund Freud (1856-1939) wrote a review of Flatau's atlas for the Internationale klinische Rundschau, which has not been included in the 'Standard Edition of the Complete Psychological Works'. The aim of the present paper is twofold: to document Freud's review, and to revive the largely forgotten atlas of Flatau. The full text of Freud is presented in translation. Further, one element Flatau, Retzius and Freud had in common is discussed: their early role as protagonists and firm supporters of Ramón y Cajal's neuron theory, the cornerstone of modern neuroscience. Copyright © 2010 S. Karger AG, Basel.

[Willy Hellpach's (1877-1955) Medical Psychology].

PubMed

Huppmann, Gernot

2004-01-01

In Germany Medical Psychology was commonly understood as Psychopathology until the mid-20th century. Especially Ernst Kretschmer (1888-1964) and Paul Schilder (1886-1964) can be named as authors who contributed to this particular field representing a basis of psychiatry. With his textbook 'Klinische Psychologie' published in 1946, Willy Hellpach (1877-1955), a neuropsychiatrist and professor of psychology, established a new understanding of this part of Applied Psychology. His statement: "All forms of mental behaviour in somatic diseases are subject of Clinical Psychology " has fallen into oblivion. Although presented as Clinical Psychology has conception is basically medical-psychological. We intend to outline Hellpach's biography and to describe - thereafter - the development of his Clinical, i.e. Medical Psychology and its subjects. We hope that medical psychologists, especially in Germany, but in other countries, too, will absorb Hellpach's ideas and will begin to appreciate his importance for the configuration of a modern Medical Psychology.

Bildanalyse in Medizin und Biologie

NASA Astrophysics Data System (ADS)

Athelogou, Maria; Schönmeyer, Ralf; Schmidt, Günther; Schäpe, Arno; Baatz, Martin; Binnig, Gerd

Heutzutage sind bildgebende Verfahren aus medizinischen Untersuchungen nicht mehr wegzudenken. Diverse Methoden - basierend auf dem Einsatz von Ultraschallwellen, Röntgenstrahlung, Magnetfeldern oder Lichtstrahlen - werden dabei spezifisch eingesetzt und liefern umfangreiches Datenmaterial über den Körper und sein Inneres. Anhand von Mikroskopieaufnahmen aus Biopsien können darüber hinaus Daten über die morphologische Eigenschaften von Körpergeweben gewonnen werden. Aus der Analyse all dieser unterschiedlichen Arten von Informationen und unter Konsultation weiterer klinischer Untersuchungen aus diversen medizinischen Disziplinen kann unter Berücksichtigung von Anamnesedaten ein "Gesamtbild“ des Gesundheitszustands eines Patienten erstellt werden. Durch die Flut der erzeugten Bilddaten kommt der Bildverarbeitung im Allgemeinen und der Bildanalyse im Besonderen eine immer wichtigere Rolle zu. Gerade im Bereich der Diagnoseunterstützung, der Therapieplanung und der bildgeführten Chirurgie bilden sie Schlüsseltechnologien, die den Forschritt nicht nur auf diesen Gebieten maßgeblich vorantreiben.

Lupus systémique et atteinte rénale: apport des anticorps anti-SSA

PubMed Central

Baline, Kenza; Zaher, Karim; Fellah, Hassan; Benchikhi, Hakima

2015-01-01

Le but de notre travail est de déterminer le profil des auto-anticorps chez 30 patients ayant un lupus systémique avec ou sans atteinte rénale afin d’établir une corrélation clinico-immunologique entre la néphropathie lupique et ces auto-anticorps. Il s'agit d'une étude transversale de 30 patients atteints de lupus érythémateux systémique diagnostiqués au service de dermatologie durant la période de Décembre 2010 à Décembre 2012 et réalisée conjointement avec le laboratoire d'immunologie. Les anticorps anti-ADN étaient retrouvés chez 17 patients (56.7%) suivis des anti-SSA dans 12 cas (40%). Cinq patients (62.5%) ayant une atteinte rénale avaient des anticorps anti DNA négatifs. Parmi ces patients avec atteinte rénale, 37.5% avaient des anticorps anti SSA sans anticorps anti DNA. La moitié des patients ayant une atteinte rénale (50%) avaient des anticorps anti SSA positifs. Notre série montre l'importance des anticorps anti-SSA surtout chez des patients avec des anticorps anti-DNA négatifs non seulement pour le diagnostic du lupus systémique mais aussi pour déceler certaines manifestations systémiques comme l'atteinte rénale. PMID:26029328

Biomedical program of the ALTAIR french russian flight onboard the MIR station.

PubMed

Andre-Deshays, C; Haignere, J P; Guell, A; Marsal, O; Suchet, L; Kotovskaya, A; Gratchev, V; Noskin, A; Grigoriev, A

1995-01-01

One year after the achievement of the 2 weeks ANTARES french-russian mission in the MIR station in July 1992, a 22 days ALTAIR mission with a french cosmonaut has been performed in July 1993, making use of the scientific payload remaining on board. Taking benefit of the analysis of the previous mission, the experimental protocols were adapted to refine scientific objectives and gave to the scientists the opportunity to enhance quantitatively and qualitatively their results. The french biomedical program, conducted in close scientific cooperation with IMBP and associated laboratories, was composed of 8 experiments out of which 2 were new with regards to the ANTARES program. In the field of cardio-vascular physiology and fluid regulation, the experiments: ORTHOSTATISME, DIURESE have been renewed and complemented by the TISSU experiment (proposed by a german scientist) and a real-time tele-assistance program using US echography technic and ground support from the french CADMOS support control center located in Toulouse. With respect to neurosciences objectives, to the experiments VIMINAL (cognitive processes) and ILLUSIONS (study of proprioceptives cues), was added the SYNERGIES experiment to analyse the postural adjustments during movement. The IMMUNOLOGIE experiment carried on and the radiobiological experiment BIODOSE ended. Adding the results of the 2 missions ANTARES and ALTAIR, and the data obtained in between onboard with russian cosmonauts, the scientists have received a wealth of physiological data and gained reproducibility and confidence in their results.

Biomedical program of the ALTAÏR french russian flight onboard the MIR station

NASA Astrophysics Data System (ADS)

André-Deshays, C.; Haigneré, J. P.; Guell, A.; Marsal, O.; Suchet, L.; Kotovskaya, A.; Gratchev, V.; Noskin, A.; Grigoriev, A.

One year after the achievemant of the 2 weeks ANTARES french-russian mission in the MIR station in July 1992, a 22 days ALTAÏR mission with a french cosmonaut has been performed in July 1993, making use of the scientific payload remaining on board. Taking benefit of the analysis of the previous mission, the experimental protocols were adapted to refine scientific objectives and gave to the scientists the opportunity to enhance quantitatively and qualitatively their results. The french biomedical program, conducted in close scientific cooperation with IMBP and associated laboratories, was composed of 8 experiments out of which 2 were new with regards to the ANTARES program. In the field of cardio-vascular physiology and fluid regulation, the experiments: ORTHOSTATISME, DIURESE have been renewed and complemented by the TISSU experiment (proposed by a german scientist) and a real-time tele-assistance program using US echography technic and ground support from the french CADMOS support control center located in Toulouse. With respect to neurosciences objectives, to the experiments VIMINAL (cognitive processes) and ILLUSIONS (study of proprioceptives cues), was added the SYNERGIES experiment to analyse the postural adjustements during movement. The IMMUNOLOGIE experiment carried on and the radiobiological experiment BIODOSE ended. Adding the results of the 2 missions ANTARES and ALTAÏR, and the data obtained in between onboard with russian cosmonauts, the scientists have received a wealth of physiological data and gained reproducibility and confidence in their results.

Transplantate und Implantate im Mittelohrbereich - Teil 1 (Stand 2002)

NASA Astrophysics Data System (ADS)

Kempf, Hans-Georg; Lenarz, Thomas; Eckert, Karl-Ludwig

In Deutschland leben ungefähr 12 Millionen Menschen, die an einer ein- oder beidseitigen Schwerhörigkeit leiden. Diese kann angeboren oder im Laufe des Lebens erworben sein. Klinisch und therapeutisch wichtig ist die Unterscheidung, ob die Ursache der Schwerhörigkeit im Bereich des Mittelohres, d. h. der Schallübertragung, oder im Bereich des Innenohres, der Hörnerven und der zentralen Hörbahnabschnitte, d. h. der Schallempfindung, liegt. 2,5 Millionen Schwerhörige haben dabei das Problem der Schallübertragung, d.h. die Störung liegt im Mittelohrbereich, und hier kann man in der Regel mit operativen, mikrochirurgisch durchgeführten Massnahmen helfen [1, 2]. Im Vordergrund steht als Ursache hier die chronische Mittelohrentzündung, die sich als Perforation des Trommelfells, als Defekt oder Unterbrechung der Gehörknöchelchen oder auch als Cholesteatom, einer sogenannte Knocheneiterung äussern kann [3]. Therapeutisch und damit als Prinzip der operativen Hörverbesserung steht primär der Verschluss des Trommelfells oder eine Rekonstruktion der Gehörknöchelchen an.

[Officer in charge, that unknown being - an explorative, qualitative study of unconscious fears, wishes, and defense mechanisms].

PubMed

Beck, Thomas; Kumnig, Martin; Breuss, Margit; Mitmansgruber, Horst; Schusser, Sandra; Andreatta, Pia; Mader, Maria; Schüßler, Gerhard

2013-01-01

The stress and coping strategies found among emergency relief personnel have been studied in detail but without considering their function in the team. However, specifically officers in charge have to be addressed and investigated separately. This study focuses on the unconscious desires, fears, and defense mechanisms present in order to improve our understanding of the stress experienced during operations. Four officers in charge were interviewed concerning their stressful experiences during operations. These interviews were then coded and analysed using the JAKOB Narrative Analysis ("Klinische Erzählanalyse JAKOB", Boothe et al. 2002). The recorded unconscious desires included solidarity, phallic integrity, generativity, unconscious fears destruction, loss of power/influence, and social hostility, and as defense strategies rationalism, repression/denial, and idealization. The analysis of the interviews shows a high reliability between the raters (0.74-0.79). The greatest burden for officers in charge is a loss of safety. Especially being confronted with strains in their own team leads to stress, which shows that the methods used for stress management following critical incidents is not sufficient.

[Prevalence of extra-hepatic manifestations in infection with hepatitis C virus: study of 140 cases].

PubMed

Kahloun, A; Babba, T; Fathallah, B; Ghozzi, M; Ezzine, H; Said, Y; Azzouz, M M

2011-06-01

To determine the extrahepatic manifestations (EHM) in chronic hepatitis C and to correlate signs with age, sex, degree of fibrosis and genotype of hepatitis C virus. One hundred forty cases of chronic infection by hepatitis C virus were investigated in a period of 10 years. By interrogation, clinical examination and laboratory tests, the EHM were determined. Correlations with age, sex, viral genotype and degree of fibrosis were determined by the chi2 test. Mean age of our patients was 59 years (16-85 years). 74% were women. The genotype 1b was found in 75% of cases. The clinical EHM were found in 62% of cases: buccal dryness in 17.1% of cases, arthralgias in 33% of cases and fatigue in 65% of cases. 25% of patients had at least one biological EHM associated with chronic hepatitis C: proteinuria in 3 cases, cryoglobulinemia in 4 cases, dysthyroidism in 8 cases and more frequently a positive immunologie test. During the follow-up, we found one case of breast cancer, one case of rectal cancer, 2 cases of MALT lymphoma and one case pf splenic lymphoma. A positive correlation was found between the prevalence of EHM in chronic hepatitis C and the female sex. A degree of fibrosis ³ 2 in METAVIR classification was significantly associated with more important frequency of EHM. EHM should be screened systematically in chronic infection with HCV. Pathogenic mechanisms in a B lymph node proliferation or diabetes and outcome of these abnormalities under antiviral therapy should be further investigated.

[Osteopathie bei gastroösophagealem Reflux mit Hiatushernie: Ein Fallbericht gemäß der CARE-Leitlinie].

PubMed

Rotter, Gabriele; Brinkhaus, Benno

2017-01-01

Hintergrund: Das Vorhandensein einer Hiatushernie kann das Auftreten einer gastroösophagealen Refluxerkrankung (GERD) als Komplikation bedingen. Konventionelle medizinische Therapiemaßnahmen können zu unerwünschten Ereignissen und Rezidiven führen. Bisher sind die Effekte von osteopathischen Behandlungen bei Hiatushernie und GERD nicht bekannt. Fallbericht: Eine 59-jährige Patientin mit endoskopisch diagnostizierter chronischer Gastritis, GERD und Hiatushernie beklagte einen persistierenden gastroösophagealen Reflux trotz konventionell-medizinischer konservativer Therapie. Die osteopathische Diagnostik ergab eine funktionelle Störung im Bereich des Magens und der Kardia mit einer Beteiligung zugehöriger Reflexzonen. Nach einer osteopathischen Behandlung als individuelle, befundorientierte Therapie ließen die Beschwerden erheblich nach. Die Hiatushernie war nach einer dieser Behandlung endoskopisch nicht mehr nachweisbar. Schlussfolgerungen: Dieser Fallbericht schildert die Symptomreduktion einer GERD nach osteopathischer Behandlung. In der endoskopischen Folgeuntersuchung fand sich die initial diagnostizierte Hiatushernie nicht mehr, diese Befund änderung könnte jedoch auf die unterschiedlichen Untersucher zurückgeführt werden. Prospektive kontrollierte klinische Studien sind notwendig, um den Stellenwert von osteopathischen Behandlungen bei GERD mit Hiatushernie zu untersuchen. © 2017 The Author(s). Published by S. Karger GmbH, Freiburg.

Einleitung

NASA Astrophysics Data System (ADS)

Ha, Suk-Woo; Wintermantel, Erich

Der Aufbau des menschlichen Körpers ist derart komplex, dass die vollständige funktionelle Substitution seiner Strukturen mit künstlichen Werkstoffen und Bauteilen unwahrscheinlich ist. Die meisten heute klinisch eingesetzten Implantate ersetzen in der Regel einfache mechanische oder andere physikalische Funktionen des menschlichen Körpers, die aufgrund eines singulären Defektes im Gewebe oder als Ergebnis einer chronischen Erkrankung substituiert werden müssen. Gelenkprothesen beispielsweise übertragen Lasten, eine künstliche intraokulare Linse ermöglicht Lichttransmission und eine künstliche Arterie sorgt für die Aufrechterhaltung der Blutversorgung. Neben der Funktionserfüllung müssen die medizinisch eingesetzten Werkstoffe zusätzlich den Anforderungen der Körperverträglichkeit genügen, die die vollständige und dauerhafte Aufnahme des Implantates im Körper zum Ziel hat. Die Erkenntnisse der Werkstoffwissenschaft und deren Umsetzung in neue Produkte hat die Entwicklung und Fortschritte in der Medizin und in der Chirurgie entscheidend geprägt. Werkstoffe stehen in ihrem klinischen Einsatz als Temporärimplantate (z. B. Kathetersysteme) sowie als Langzeitimplantate (z. B. Hüftgelenksimplantate oder Herzschrittmacher) in direktem Kontakt mit den Geweben des Körpers und müssen deshalb biokompatibel sein.

Medizintechnik in der Tumororthopädie

NASA Astrophysics Data System (ADS)

Burgkart, Rainer; Gollwitzer, Hans; Holzapfel, Boris; Rudert, Maximilian; Rechl, Hans; Gradinger, Reiner

Die Behandlung der Knochentumoren unterlag in den letzten 20 Jahren einem raschen und stetigen Wandel, was zum einen auf die verbesserten Therapieerfolge durch den Einsatz von neoadjuvanten Therapieformen zurückzuführen ist, und andererseits von medizintechnischen Entwicklungen bezüglich moderner Schnittbilddiagnostik, neuer 3D Operationsplanungsverfahren wie das Rapid Prototyping und adaptiv modularer Tumorendoprothesensystemen u. a. begleitet wurde. Gerade die technischen Entwicklungen haben dazu geführt, daß im Bereich der Extremitäten und der Wirbelsäule radikalere Eingriffe durchgeführt werden können, was die lokale Tumorkontrolle wesentlich verbessert hat. In zunehmenden Maße werden deshalb nicht nur Kurzzeiterfolge sondern auch mittel- und langfristige Fortschritte bei der Behandlung der malignen Knochentumoren einschließlich der Metastasenbehandlung erreicht. Grundlage der Therapie ist dabei immer primär die Sicherung der Diagnose mittels Biopsie und die bildgebende sowie histologische Stadieneinteilung des malignen Tumors. Nach der Tumorresektion kann die Rekonstruktion biologisch oder mit Endoprothesensystemen erfolgen. Gerade die weiterentwickelten modularen Systeme führen zu guten funktionellen Ergebnissen mit langen Standzeiten und einer reduzierten Komplikationsrate. Individuell angefertigte Implantate sind vor allem im Bereich der Rekonstruktion komplexer Beckentumoren von großer klinischer Bedeutung.

Implantate für den Bandscheibenersatz (Stand 1993)

NASA Astrophysics Data System (ADS)

Mathey, Michael; Wintermantel, Erich

Die Bandscheiben sind besonders betroffen von Fehlhaltungen und -stellungen der Wirbelsäule. Sie unterliegen als grösstes zusammenhängendes, nicht vaskularisiertes Gewebe im Menschen, statisch und dynamisch extrem belastet, besonders der Alterung. Um die teilweise sehr starken Schmerzen bei Bandscheibenschädigungen zu lindern, ist eine Operation vielfach die einzige Hilfe. Bei dieser Operation (Nukleotomie) entfernt man das aus der Bandscheibe ausgetretene Gewebe des Gallertkerns (nucleus pulposus), welches durch Druck auf die Nervenstränge im Bereich der Wirbelsäule die Beschwerden (Ischias-Schmerz) verursacht hat. Nach der Entfernung des Gallertkerns werden die auftretenden Kräfte bei veränderter Biomechanik übertragen. Dabei erhalten die Zwischenwirbelgelenke (Facettengelenke) eine erheblich grössere Flächenpressung als dies bei intakter Bandscheibe der Fall war. Die höhere Flächenpressung kommt durch die Verringerung des Abstandes zwischen den oberen und unteren Deckplatten der benachbarten Wirbelkörper zustande, zwischen denen sich der Gallertkern befand. Durch geeignetes Training der Rückenmuskulatur kann eine Stabilisierung des operierten Bandscheibensegmentes erreicht werden, jedoch ist es eine klinische Erfahrung, dass die meisten Patienten, die momentan durch die Operation schmerzfrei geworden sind, keine adäquate zusätzliche sportliche Betätigung auf sich nehmen.

[Franz Josef Kallmann (1897-1965) and the transfer of psychiatric-genetic scientific concepts from national socialist Germany to the U.S.A].

PubMed

Cottebrune, Anne

2009-01-01

The founding of the German Research Institute for Psychiatry and its Genealogic-Demographic Department (Genealogisch-Demographische Abteilung; GDA) in 1918 gave the world the first institutional platform for the field of psychiatric genetics. The years between the two World Wars saw the GDA grow in importance with much international respect. The close collaboration between the GDA's protagonist Ernst Rüdin and the National Socialist regime was certainly not an inhibiting factor for the worldwide recognition of the eugenic research conducted in Munich. Around the mid-1930s, the German psychiatrist émigré Franz Josef Kallmann brought the field of study which had been put into practice in Munich to the United States. He fought an uphill battle to be accepted by the North American scientific community, but finally he was able to establish himself as the main researcher in the field of psychiatric genetics. Interestingly enough, the fact that his kind of research had been heavily supported by the National Socialist regime was not a barrier to his acceptance. The fact that it took him a long time to establish the field of eugenics in the U.S.A. is better explained by the psychoanalytic research methods at the time, which gave hereditary transmission short shrift. At the New York State Psychiatric Institute he was able to continue his research, including the examination of race-hygienic motifs, where he designed a research program that was directly based on concepts and methods from Ernst Rüdin's team of researchers in Munich. The only deviation from the original research was in terms of the use of eugenic prophylaxis where he aligned his research in the context of North American democracy in the post-war era. However, the eugenic goal of elimination of certain categories of peoples remained unchanged.

„3D-augmented-reality“-Visualisierung für die navigierte Osteosynthese von Beckenfrakturen

PubMed Central

Befrui, N.; Fischer, M.; Fuerst, B.; Lee, S.-C.; Fotouhi, J.; Weidert, S.; Johnson, A.; Euler, E.; Osgood, G.; Navab, N.; Böcker, W.

2018-01-01

Zusammenfassung Hintergrund Trotz großer Fortschritte in der Entwicklung der Hard- und Software von Navigationssystemen finden diese aufgrund ihrer vermeintlichen Komplexität, umständlichen Integration in klinische Arbeitsabläufe und fraglichen Vorteilen gegenüber konventionellen bildgebenden Verfahren bisher wenig Einsatz in den heutigen Operationssälen. Ziel der Arbeit Entwicklung einer „Augmented-reality“(AR)-Darstellung zur chirurgischen Navigation ohne Infrarot(„IR“)-Tracking-Marker und Vergleich zum konventioneller Röntgen in einem simulierten Eingriff. Material und Methoden Navigationssystem bestehend aus „Cone-beam-CT“(CBCT)-fähigem C-Bogen und „Red-green-blue-depth“(RGBD)-Kamera. Testung durch Kirschner(K)-Draht-Platzierung in Modellen unter Berücksichtigung der benötigten Zeit, der Strahlendosis und der Benutzerfreundlichkeit der Systeme. Ergebnisse Eine signifikante Reduktion der benötigten Zeit, der Röntgenbilder und der gesamten Strahlendosis bei der AR-Navigation gegenüber dem konventionellen Röntgen bei gleichbleibender Präzision. Schlussfolgerung Die AR-Navigation mithilfe der RGBD-Kamera bietet flexible und intuitive Darstellungsmöglichkeiten des Operations-situs für navigierte Osteosynthesen ohne Tracking-Marker. Hiermit ist es möglich, Operationen schneller, einfacher und mit geringerer Strahlenbelastung für Patient und OP-Personal durchzuführen. PMID:29500506

Biokompatible Metalle

NASA Astrophysics Data System (ADS)

Ha, Suk-Woo; Wintermantel, Erich

Metalle als Implantatwerkstoffe werden in der Medizin für zwei Hauptanwendungen eingesetzt: für Prothesen des totalen Gelenkersatzes wie beispielsweise Hüft-, Knie- und Schulterprothesen und für Fixationselemente zur Stabilisierung von Frakturen. Beispiele hierfür sind Osteosyntheseplatten, Marknägel, Schrauben, Drähte und Stents. Eine der ersten Anwendungen von Metallen im menschlichen Körper war die Fixation von Fragmenten eines gebrochenen Humerus (Oberarmknochen) mit einem Metalldraht durch zwei französische Physiker im Jahr 1775 [1]. Ausführliche Untersuchungen zur Verträglichkeit von Metallen im menschlichen Körper wurden bereits im frühen 19. Jahrhundert durchgeführt. Von den untersuchten Werkstoffen verursachten die edlen Metalle wie Gold, Silber und Platin aufgrund ihrer Korrosionsbeständigkeit und Körperverträglichkeit die geringsten Reizungen im menschlichen Körper. Die klinische Anwendung der Edelmetalle war jedoch wegen der geringen mechanischen Eigenschaften beschränkt. Andere Metalle wie Messing, Kupfer oder Eisen wiesen vergleichsweise höhere Festigkeitswerte auf, sie waren jedoch aufgrund der geringen Korrosionsbeständigkeit und Biokompatibilität nicht für den klinischen Einsatz geeignet. Ein weiteres Problem stellte die Gefahr der Infektion durch unsterile Instrumente und Implantate dar. Gegen Ende des 19. Jahrhunderts hielt die antiseptische Operationsmethode Einzug in die Kliniken, die z. B. erfolgreiche Operationen mit Silberdraht ermöglichte.

50th anniversary of Clinical Chemistry and Laboratory Medicine--a historical overview.

PubMed

Körber, Friedrich; Plebani, Mario

2013-01-01

In the early 1960s, Joachim Brugsch, one of the founders of Clinical Chemistry and Laboratory Medicine (CCLM) (then Zeitschrift für Klinische Chemie), had the idea to found a journal in the upcoming field of clinical chemistry. He approached Ernst Schütte, who was associated with the De Gruyter publishing house through another journal, to participate, and Schütte thus became the second founder of this Journal. The aim was to create a vehicle allowing the experts to express their opinions and raise their voices more clearly than they could in a journal that publishes only original experimental papers, a laborious and difficult, but important endeavor, as the profession of clinical chemistry was still in the early stages of development at this time. The first issue of this Journal was published in early 1963, and today, we are proud to celebrate the 50th anniversary of CCLM. This review describes the development of this Journal in light of the political situation of the time when it was founded, the situation of the publisher Walter De Gruyter after the erection of the Berlin Wall, and the development of clinical chemistry, and later on, laboratory medicine as a well-acknowledged discipline and profession.

Frühe Stresserfahrungen und Krankheitsvulnerabilität

PubMed Central

Entringer, Sonja; Buss, Claudia; Heim, Christine

2016-01-01

Zusammenfassung Hintergrund Das stetig wachsende Forschungsgebiet der “Frühe[n] Programmierung von Krankheit und Gesundheit” untersucht, inwieweit die individuelle Vulnerabilität für die Entstehung verschiedenster Erkrankungen über die Lebensspanne bereits während der frühen Entwicklung beeinflusst wird. Ziele der Arbeit In der vorliegenden Übersichtsarbeit werden das Konzept der frühen Programmierung von Krankheitsvulnerabilität erläutert sowie Befunde zu den Folgen frühkindlicher Traumatisierung und pränataler Stressexposition zusammenfassend dargestellt. Es werden außerdem biologische Mechanismen diskutiert, die das erhöhte Krankheitsrisiko nach lebensgeschichtlich früher Stresserfahrungen vermitteln. Die Möglichkeit der transgenerationalen Transmission frühkindlicher Erfahrungen an die nächste Generation und die zugrundeliegenden Mechanismen dieser Übertragung werden ebenfalls vorgestellt. Fazit Die Befundlage zu Stresserfahrungen im frühen Leben und der Entstehung von psychischen und körperlichen Störungen über die Lebensspanne wächst stetig. Die Mechanismen werden derzeit weiter bis hin zur molekularbiologischen und epigenetischen Ebene erforscht. Hier ergeben sich ganz neue Perspektiven, welche die Präzision klinischer Diagnostik und den Erfolg von Interventionen erheblich verbessern könnten. Momentan existiert jedoch noch ein erheblicher Mangel an Translation zwischen diesen Forschungserkenntnissen und deren Anwendung in der klinischen Versorgung. PMID:27604117

[The effect of mood-stabilising drugs on cytokine levels in bipolar disorder: a systematic review].

PubMed

Van Den Ameele, S; van Diermen, L; Staels, W; Coppens, V; Dumont, G; Sabbe, B; Morrens, M

Veranderde cytokineconcentraties bij personen met een bipolaire stoornis ten opzichte van controle-personen suggereren een rol van het immuunsysteem in de pathofysiologie van bipolaire stoornis. Farmacotherapie is een belangrijke verstorende factor in klinisch onderzoek naar cytokineconcentraties.
DOEL: Evalueren van cytokineconcentraties bij medicatievrije patiënten met een bipolaire stoornis en van het effect van stemmingsstabiliserende geneesmiddelen op deze concentraties.
METHODE: We doorzochten systematisch PubMed en Embase naar klinische studies die cytokineconcentraties bij medicatievrije patiënten met een bipolaire stoornis beschrijven of het effect van een individueel stemmingsstabiliserend geneesmiddel op deze concentraties evalueren.
RESULTATEN: Van de 564 gescreende artikelen werden er 17 geïncludeerd. Resultaten bij medicatievrije patiënten toonden stemmingsgerelateerde cytokineveranderingen. Hoewel geen data over de kortetermijneffecten van lithium beschikbaar waren, was lithiumgebruik langer dan 2 maanden geassocieerd met normale cytokineconcentraties. Twee studies rapporteerden geen effect van valproïnezuur. We vonden geen studies over carbamazepine, lamotrigine of antipsychotica.
CONCLUSIE: Dit systematisch literatuuroverzicht toont stemmingsgerelateerde cytokineveranderingen bij medicatievrije patiënten met een bipolaire stoornis met de meeste evidentie voor een pro-inflammatoire immuunrespons tijdens manie. Euthymie en langdurig lithiumgebruik zijn geassocieerd met normale cytokineconcentraties. Er is een belangrijke methodologische heterogeniteit en onvoldoende replicatie tussen studies. Longitudinale studies met medicatievrije beginmetingen, gerandomiseerde monotherapeutische behandelprotocollen en nauwkeurige monitoring van stemming zijn noodzakelijk.
BACKGROUND: Alterations of the cytokine level in persons with bipolar disorder - when compared to controls - suggest that the immune system plays a role in the pathophysiology of bipolar disorder. Pharmacotherapy is an important confounding factor in clinical research on cytokine levels.
AIM: To evaluate the evidence on cytokine levels in medication-free bipolar disorder and to study the effects that single mood-stabilising drugs have on these levels.
METHOD: We searched PubMed and Embase systematically in order to single out clinical studies that reported on cytokine levels in medication-free bipolar disorder or that commented on the effects of single mood-stabilising drugs on cytokine levels.
RESULTS: Of the 564 articles that we screened, we detected 17 that were particularly relevant for our investigation. Results for medication-free patients point to mood-related alterations in cytokine levels. Although we found no data relating to short-term effects of lithium, the use of lithium in euthymic populations was associated with normal cytokine levels. Two studies reported no effect of valproate. We did not find any studies relating to carbamazepine, lamotrigine or antipsychotics.
CONCLUSION: Our systematic review of the literature suggests the presence of mood-related changes in cytokine levels in medication-free patients with bipolar disorder, with the most evidence for a proinflammatory response during a manic episode. Euthymia and long-term use of lithium use are associated with normal cytokine levels. There is considerable heterogeneity in the methods used in these studies and too little replication. Future research will have to include longitudinal studies with medication-free baseline measurements. It will also be necessary to draw up single-drug treatment protocols and to conduct intensive mood-related monitoring.

Implantate im Mittelohrbereich - Teil 2 (Ergänzungen 2007)

NASA Astrophysics Data System (ADS)

Stieve, M.; Lenarz, Thomas

In Deutschland leben ca. 12 Millionen Menschen, die an einer ein- oder beidseitigen Schwerhörigkeit leiden. Diese kann angeboren oder im Laufe des Lebens erworben sein. Klinisch und therapeutisch wichtig ist die Unterscheidung hinsichtlich des Schädigungsortes im Bereich des Mittelohres, d. h. eine Schalleitungsschwerhörigkeit, oder im Bereich des Innenohres, d. h. eine Schallempfindungsschwerhörigkeit, wobei hier der Schädigungsort auch am Hörnerven oder in den zentralen Hörabschnitten liegen kann. Therapeutisch lassen sich sowohl Schwerhörigkeiten im Bereich des Mittelohres als auch im Innenohr und sogar im Hirnstammbereich (Hirnstammimplantat) behandeln. 1,9 Millionen Schwerhörige haben eine Erkrankung im Mittelohrbereich, d. h. der Schall kann nur ungenügend auf das Innenohr übertragen werden. Die Ursache besteht meist in einer chronischen Mittelohrentzündung, die zu einer Zerstörung des Trommelfells und der Gehörknöchelchenkette geführt haben. Therapeutisch und damit als Prinzip der operativen Hörverbesserung steht primär der Verschluß des Trommelfells oder eine Rekonstruktion der Gehörknöchelchen. Mittelohroperationen werden mikrochirurgisch unter dem Operationsmikroskop durchgeführt, wobei zunächst durch eine sanierende Operation der Entzündungsprozeß entfernt wird und nach einer Ausheilungszeit die Gehörknöchelchenkette durch künstliche Prothesen rekonstruiert werden kann.

Update zum klinischen Einsatz von Inhibitoren mutierter Phosphokinasen beim Melanom.

PubMed

Cosgarea, Ioana; Ritter, Cathrin; Becker, Jürgen C; Schadendorf, Dirk; Ugurel, Selma

2017-09-01

Die Behandlungsstrategie beim metastasierten Melanom hat sich mit der Identifizierung therapeutisch angreifbarer molekularer Zielstrukturen innerhalb zellulärer Signalwege radikal geändert. Durch die Zulassung von Substanzen, die gezielt an den zentralen Schaltmolekülen, den Phosphokinasen, angreifen, können diese Signalwege selektiv abgeschaltet werden. Dies ist insbesondere bei denjenigen Tumoren von Interesse, deren Signalwege durch aktivierende Mutationen der für die Schaltmoleküle kodierenden Gene konstitutiv aktiviert sind. Aktuell ist diese therapeutische Strategie insbesondere für Patienten bedeutsam, deren Melanome eine Mutation im BRAF-Gen aufweisen. Diese Patienten können durch eine Kombinationstherapie aus Inhibitoren der Phosphokinasen BRAF und MEK langfristig mit sehr guter Krankheitskontrolle behandelt werden. Unter dieser Kombinationstherapie wird aktuell ein progressionsfreies Überleben von über zehn Monaten und ein Gesamtüberleben von mehr als zwei Jahren bei guter Lebensqualität erzielt. Da unter längerfristiger Therapie mit Kinaseinhibitoren jedoch bei einem Großteil der Patienten eine Resistenzbildung auftritt, sind aktuelle klinische Therapiestudien auf die Suche nach geeigneten Kombinationspartnern unter Blockierung anderer Signalwege oder unter Aktivierung der T-Zell-vermittelten Immunantwort ausgerichtet. Der vorliegende Übersichtsartikel stellt sowohl die aktuell verfügbaren als auch die in der klinischen Testung befindlichen zukünftigen Optionen der zielgerichteten Therapie des Melanoms dar. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Predictive Validity of the HKT-R Risk Assessment Tool: Two and 5-Year Violent Recidivism in a Nationwide Sample of Dutch Forensic Psychiatric Patients.

PubMed

Bogaerts, Stefan; Spreen, Marinus; Ter Horst, Paul; Gerlsma, Coby

2018-06-01

This study has examined the predictive validity of the Historical Clinical Future [ Historisch Klinisch Toekomst] Revised risk assessment scheme in a cohort of 347 forensic psychiatric patients, which were discharged between 2004 and 2008 from any of 12 highly secure forensic centers in the Netherlands. Predictive validity was measured 2 and 5 years after release. Official reconviction data obtained from the Dutch Ministry of Security and Justice were used as outcome measures. Violent reoffending within 2 and 5 years after discharge was assessed. With regard to violent reoffending, results indicated that the predictive validity of the Historical domain was modest for 2 (area under the curve [AUC] = .75) and 5 (AUC = .74) years. The predictive validity of the Clinical domain was marginal for 2 (admission: AUC = .62; discharge: AUC = .63) and 5 (admission: AUC = .69; discharge: AUC = .62) years after release. The predictive validity of the Future domain was modest (AUC = .71) for 2 years and low for 5 (AUC = .58) years. The total score of the instrument was modest for 2 years (AUC = .78) and marginal for 5 (AUC = .68) years. Finally, the Final Risk Judgment was modest for 2 years (AUC = .78) and marginal for 5 (AUC = .63) years time at risk. It is concluded that this risk assessment instrument appears to be a satisfactory instrument for risk assessment.

B-Zell-Lymphome der Haut - Pathogenese, Diagnostik und Therapie.

PubMed

Nicolay, Jan P; Wobser, Marion

2016-12-01

Primär kutane B-Zell-Lymphome (PCBCL) beschreiben reifzellige lymphoproliferative Erkrankungen der B-Zell-Reihe, die primär die Haut betreffen. Die Biologie und der klinische Verlauf der einzelnen PCBCL-Subtypen variieren untereinander stark und unterscheiden sich grundsätzlich von primär nodalen und systemischen B-Zell-Lymphomen. Primär kutane Marginalzonenlymphome (PCMZL) und primäre kutane follikuläre Keimzentrumslymphome (PCFCL) werden auf Grund ihres unkomplizierten Verlaufs und ihrer exzellenten Prognose zu den indolenten PCBCL gezählt. Demgegenüber stellen die diffus großzelligen B-Zell-Lymphome, hauptsächlich vom Beintyp (DLBCL, LT) die aggressiveren PCBCL-Varianten mit schlechterer Prognose dar. Für die Ausbreitungsdiagnostik und die Therapieentscheidung sind eine genaue histologische und immunhistochemische Klassifizierung sowie der Ausschluss einer systemischen Beteiligung in Abgrenzung zu nodalen oder systemischen Lymphomen notwendig. Die Diagnostik sollte dabei durch molekularbiologische Untersuchungen unterstützt werden. Therapeutisch stehen für die indolenten PCBCL primär operative und radioonkologische Maßnahmen im Vordergrund sowie eine Systemtherapie mit dem CD20-Antikörper Rituximab bei disseminiertem Befall. Die aggressiveren Varianten sollten in erster Linie mit Kombinationen aus Rituximab und Polychemotherapieschemata wie z. B. dem CHOP-Schema oder Modifikationen davon behandelt werden. Auf Grund der in allen seinen Einzelheiten noch nicht vollständig verstandenen Pathogenese und Biologie sowie des begrenzten Therapiespektrums der PCBCL besteht hier, speziell beim DLBCL, LT, noch erheblicher Forschungsbedarf. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Gerbstoffe aus Potentilla officinalis wirken entzündungshemmend im UV-Erythem-Test und bei Anwendung auf atopischer Haut.

PubMed

Hoffmann, Julia; Wölfle, Ute; Schempp, Christoph M; Casetti, Federica

2016-09-01

Das Rhizom von Potentilla officinalis (PO) ist reich an Gerbstoffen und wird traditionell zur äußerlichen Behandlung von Entzündungen der Haut und der Schleimhäute verwendet. Ziel der vorliegenden Arbeit war die Bestätigung der antiinflammatorischen Eigenschaften von PO mittels eines UV-Erythem-Tests und einer klinischen Anwendungsstudie bei atopischer Haut. Die antiinflammatorische Wirkung eines PO-Extrakts (standardisiert auf 2 % Trockensubstanz) wurde in einer prospektiven, randomisierten, placebokontrollierten Doppelblindstudie mit 40 gesunden Erwachsenen im UV-Erythem-Test im Vergleich zu 1 % Hydrocortisonacetat untersucht. Im Rahmen einer prospektiven nicht kontrollierten Studie wurde die Wirkung und Verträglichkeit der 2 % PO-Creme an zwölf Erwachsenen und zwölf Kindern mit atopischer Haut nach Anwendung über zwei Wochen in einem definierten Testareal anhand eines Teil-SCORAD untersucht. Zusätzlich wurde die Beeinflussung der Hautrötung im Testareal photometrisch gemessen. Im UV-Erythem-Test zeigte die PO-Creme eine signifikante Reduktion des Erythemindex im Vergleich zum Vehikel. Die antiinflammatorische Wirkung des Verums entsprach der der 1 % Hydrocortisonacetat-Creme. Die klinische Studie bei Atopikern zeigte eine signifikante Abnahme des Teil-SCORAD und des Erythems im Testareal. Es wurden keine Unverträglichkeitsreaktionen beobachtet. PO als 2%ige Zubereitung besitzt entzündungshemmende Eigenschaften und ist wirksam und gut verträglich auf atopischer Haut. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Tufa and travertine of the Lesser Caucasus: a light on the Quaternary palaeoenvironment of the Circumcaspian regions

NASA Astrophysics Data System (ADS)

Ollivier, V.; Roiron, P.; Nahapetyan, S.; Joannin, S.; Chataigner, C.

2012-04-01

In the course of the International Associated Laboratory HEMHA (Humans and Environment in Mountainous Habitats : the case of Armenia), the French Foreign Affair Ministry Caucasus Mission (CNRS-UMR 5133 Archéorient, Lyon University) and the French-German research program Ancient Kura (CNRS-UMR 7192 PrOCauLAC, Paris, France, Deutsches Archäologisches Institut, Eurasien-Abteilung, Berlin, Germany with ANR-CNRS and DFG funding) numerous sites of the Lesser Caucasus territory are under geomorphological, palaeoenvironmental and archaeological investigations. Through comparisons between the tufa/travertine system and the detrital formation morphosedimentary evolution, one of our research interests is to define the Late Quaternary landscape mutations as well as the origin and rhythmicity of the major morphogenic trends reversals. The impacts of the environmental changes highlighted on the human occupation modes are also debated. A total of 14 travertine and tufa formations were studied (8 Pleistocene and 6 Postglacial formations) on a Northwest-Southeast transect of more than 300 km across the Lesser Caucasus. Each of these carbonated system development are correlated with high global relative sea levels and interstadial climates on a range between the Marine Isotopic Stage 11 and 1 (ca. 335 to 1.5 Ky BP). The absolute chronology is constrained by a series of U/Th and 14C dating. A total of 24 dating was performed (6 radiocarbon and 18 U/Th datings), allowing a high quality overview of the travertinization process over the time at a regional scale. Jointly with the measurement of the late Quaternary interglacial series impact on the tufas development in the Caucasus, the geomorphological position of some travertinous formations and their absolute dating gives some clues about the neotectonic evolution of the studied valleys. In some area, the uplift rate has been determined (ca. 8 mm/year) and discretized from the alluvial incision signal. The analysis of the carbonated deposits (faciological determinations, palaeobotanical and palynological identifications of leave imprints and pollens), which are the expression of specific climatic conditions, and the comparative approach with the general morphosedimentary evolution, give a complete reading grid of the regional landscape mutation expressions and origins (Caspian Sea eustatism or exclusive climatic impact), necessary to understand the magnitude of the changes and their influence on the Circumcaspian societies.

Impact of High-Intensity-NIV on the heart in stable COPD: a randomised cross-over pilot study.

PubMed

Duiverman, Marieke Leontine; Maagh, Petra; Magnet, Friederike Sophie; Schmoor, Claudia; Arellano-Maric, Maria Paola; Meissner, Axel; Storre, Jan Hendrik; Wijkstra, Peter Jan; Windisch, Wolfram; Callegari, Jens

2017-05-02

Although high-intensity non-invasive ventilation has been shown to improve outcomes in stable COPD, it may adversely affect cardiac performance. Therefore, the aims of the present pilot study were to compare cardiac and pulmonary effects of 6 weeks of low-intensity non-invasive ventilation and 6 weeks of high-intensity non-invasive ventilation in stable COPD patients. In a randomised crossover pilot feasibility study, the change in cardiac output after 6 weeks of each NIV mode compared to baseline was assessed with echocardiography in 14 severe stable COPD patients. Furthermore, CO during NIV, gas exchange, lung function, and health-related quality of life were investigated. Three patients dropped out: two deteriorated on low-intensity non-invasive ventilation, and one presented with decompensated heart failure while on high-intensity non-invasive ventilation. Eleven patients were included in the analysis. In general, cardiac output and NTproBNP did not change, although individual effects were noticed, depending on the pressures applied and/or the co-existence of heart failure. High-intensity non-invasive ventilation tended to be more effective in improving gas exchange, but both modes improved lung function and the health-related quality of life. Long-term non-invasive ventilation with adequate pressure to improve gas exchange and health-related quality of life did not have an overall adverse effect on cardiac performance. Nevertheless, in patients with pre-existing heart failure, the application of very high inspiratory pressures might reduce cardiac output. The trial was registered in the Deutsches Register Klinischer Studien (DRKS-ID: DRKS00007977 ).

Effects of OK-432 (picibanil) on the estrogen receptors of MCF-7 cells and potentiation of antiproliferative effects of tamoxifen in combination with OK-432.

PubMed

Aoyagi, H; Iino, Y; Takeo, T; Horii, Y; Morishita, Y; Horiuchi, R

1997-01-01

OK-432 (picibanil), a streptococcal preparation, has a strong biological response modifier (BRM) function and is expected to produce clinical improvement and prolongation of survival in treated cancer patients in Japan. We were interested in whether OK-432 augments estrogen receptor (ER) levels in breast cancer. To investigate the effect of the BRMs on cellular growth and the characteristics of ER and progesterone receptors (PgR) in the human breast cancer cell line MCF-7, we used OK-432, Krestin (PSK), a protein-bound polysaccharide extracted from Coriolus versicolor, and lentinan, a fungal branched (1...3)-beta-D-glycan. OK432 and PSK dose dependently inhibited DNA synthesis of MCF-7 cells, and the 50% inhibitory concentrations of OK-432 and PSK were 1.2 KE (klinische Einheit, clinical unit)/ml and 200 micrograms/ml, respectively. Lentinan showed no direct anticancer effect in vitro. We found that OK-432 induced a 2-fold increase in ER levels in MCF-7 cells at 0.005 KE/ml, but not in PgR. Lentinan and low-dose PSK did not change ER or PgR levels, but high-dose PSK decreased ER and PgR. We also studied the combined effect of OK-432 and antiestrogens, tamoxifen (TAM) and DP-TAT-59. The combined treatment with OK-432 and TAM showed an additive inhibitory effect on MCF-7 cells. These results suggest that OK-432 may augment the therapeutic effect of TAM in breast cancer.

Immediate versus delayed loading of strategic mini dental implants for the stabilization of partial removable dental prostheses: a patient cluster randomized, parallel-group 3-year trial.

PubMed

Mundt, Torsten; Al Jaghsi, Ahmad; Schwahn, Bernd; Hilgert, Janina; Lucas, Christian; Biffar, Reiner; Schwahn, Christian; Heinemann, Friedhelm

2016-07-30

Acceptable short-term survival rates (>90 %) of mini-implants (diameter < 3.0 mm) are only documented for mandibular overdentures. Sound data for mini-implants as strategic abutments for a better retention of partial removable dental prosthesis (PRDP) are not available. The purpose of this study is to test the hypothesis that immediately loaded mini-implants show more bone loss and less success than strategic mini-implants with delayed loading. In this four-center (one university hospital, three dental practices in Germany), parallel-group, controlled clinical trial, which is cluster randomized on patient level, a total of 80 partially edentulous patients with unfavourable number and distribution of remaining abutment teeth in at least one jaw will receive supplementary min-implants to stabilize their PRDP. The mini-implant are either immediately loaded after implant placement (test group) or delayed after four months (control group). Follow-up of the patients will be performed for 36 months. The primary outcome is the radiographic bone level changes at implants. The secondary outcome is the implant success as a composite variable. Tertiary outcomes include clinical, subjective (quality of life, satisfaction, chewing ability) and dental or technical complications. Strategic implants under an existing PRDP are only documented for standard-diameter implants. Mini-implants could be a minimal invasive and low cost solution for this treatment modality. The trial is registered at Deutsches Register Klinischer Studien (German register of clinical trials) under DRKS-ID: DRKS00007589 ( www.germanctr.de ) on January 13(th), 2015.

Detection of Pneumonia Associated Pathogens Using a Prototype Multiplexed Pneumonia Test in Hospitalized Patients with Severe Pneumonia

PubMed Central

Schulte, Berit; Eickmeyer, Holm; Heininger, Alexandra; Juretzek, Stephanie; Karrasch, Matthias; Denis, Olivier; Roisin, Sandrine; Pletz, Mathias W.; Klein, Matthias; Barth, Sandra; Lüdke, Gerd H.; Thews, Anne; Torres, Antoni; Cillóniz, Catia; Straube, Eberhard; Autenrieth, Ingo B.; Keller, Peter M.

2014-01-01

Severe pneumonia remains an important cause of morbidity and mortality. Polymerase chain reaction (PCR) has been shown to be more sensitive than current standard microbiological methods – particularly in patients with prior antibiotic treatment – and therefore, may improve the accuracy of microbiological diagnosis for hospitalized patients with pneumonia. Conventional detection techniques and multiplex PCR for 14 typical bacterial pneumonia-associated pathogens were performed on respiratory samples collected from adult hospitalized patients enrolled in a prospective multi-center study. Patients were enrolled from March until September 2012. A total of 739 fresh, native samples were eligible for analysis, of which 75 were sputa, 421 aspirates, and 234 bronchial lavages. 276 pathogens were detected by microbiology for which a valid PCR result was generated (positive or negative detection result by Curetis prototype system). Among these, 120 were identified by the prototype assay, 50 pathogens were not detected. Overall performance of the prototype for pathogen identification was 70.6% sensitivity (95% confidence interval (CI) lower bound: 63.3%, upper bound: 76.9%) and 95.2% specificity (95% CI lower bound: 94.6%, upper bound: 95.7%). Based on the study results, device cut-off settings were adjusted for future series production. The overall performance with the settings of the CE series production devices was 78.7% sensitivity (95% CI lower bound: 72.1%) and 96.6% specificity (95% CI lower bound: 96.1%). Time to result was 5.2 hours (median) for the prototype test and 43.5 h for standard-of-care. The Pneumonia Application provides a rapid and moderately sensitive assay for the detection of pneumonia-causing pathogens with minimal hands-on time. Trial Registration Deutsches Register Klinischer Studien (DRKS) DRKS00005684 PMID:25397673

Retrospektive Analyse von Zufallsbefunden, die bei Patienten mit kutanem malignen Malignom durch (18) F-Fluordeoxyglucose-PET/CT erhoben wurden.

PubMed

Conrad, Franziska; Winkens, Thomas; Kaatz, Martin; Goetze, Steven; Freesmeyer, Martin

2016-08-01

Bei der (18) F-Fluordeoxyglucose-Positronenemissionstomographie/Computertomographie (FDG-PET/CT) ergeben sich häufig Zufallsbefunde. In der vorliegenden Studie konzentrierten wir uns auf mittels FDG-PET/CT erhaltene Zufallsbefunde bei Patienten mit kutanem Melanom und überprüften deren Relevanz hinsichtlich weiterer diagnostischer Maßnahmen und Interventionen. Die Krankenakten von 181 konsekutiven Melanom-Patienten wurden retrospektiv ausgewertet, um das Management von Zufallsbefunden zu dokumentieren. Der Schwerpunkt lag dabei auf den histologischen Befunden. Bei 33 von 181 (18 %) Patienten lagen 39 relevante Zufallsbefunde vor, und zwar im Kolorektalbereich (n = 15 Patienten), in der Schilddrüse (n = 8), der Prostata (n = 2), dem Bewegungsapparat (n = 2), in Lymphknoten (n = 2), der Parotis (n = 1), den Mandeln (n = 1), den Nieren (n = 1) und der Gallenblase (n = 1). Bei 25 Patienten schlossen sich weitere diagnostische Verfahren an, wobei in 21 Fällen ein klinisches Korrelat nachgewiesen wurde. Bei 16 von 21 Patienten ergab sich eine Neoplasie, darunter fünf maligne Läsionen (vier Kolonkarzinome und ein Prostatakarzinom). Die Malignome wurden frühzeitig diagnostiziert und in der Mehrzahl der Fälle erfolgreich entfernt. Der Einsatz der FDG-PET/CT als Routine-Diagnostik wird in den Leitlinien empfohlen und ist indiziert bei malignem Melanom ab Stadium IIC. In dieser Studie wurden auf effektive Weise ansonsten nicht erkannte Krebserkrankungen, insbesondere Kolonkarzinome, detektiert. In den meisten Fällen war eine frühe Intervention möglich. Zufallsbefunde durch FDG-PET/CT sollten, unter Berücksichtigung des Zustands und der Wünsche des Patienten, mit den geeigneten diagnostischen Maßnahmen abgeklärt werden. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Utility of nociceptive flexion reflex threshold and bispectral index to predict movement responses under propofol anaesthesia.

PubMed

Jakuscheit, Axel; Posch, Matthias J; Gkaitatzis, Stefanos; Neumark, Lisa; Hackbarth, Mark; Schneider, Martin; Lichtner, Gregor; Baars, Jan H; von Dincklage, Falk

2017-06-01

The nociceptive flexion reflex threshold (NFRT) is a promising tool to monitor analgesia during general anaesthesia. Clinical studies have shown that the NFRT allows to predict movement responses to painful stimuli under a combined anaesthetic regime of sedative and opioid agents. Experimental studies indicated that the NFRT is also able to predict such movement responses under an exclusively sedative regime like propofol mono-anaesthesia. Therefore, we performed this study to investigate the ability of the NFRT to predict movement responses to painful stimuli in patients during a clinical propofol mono-anaesthesia. We investigated 140 cardiac surgery patients during their postoperative phase under propofol mono-anaesthesia. NFRT and bispectral index (BIS) were determined in each patient right before endotracheal suctioning or painful electrical test stimulation. Prediction probabilities were calculated to quantify how accurate each measure is able to predict movement responses to the stimuli. The 124 patients included in the analysis received a median propofol dosage of 3.2 (2.5-3.9) [median (IQR)] mg/kg/h. The included patients showed 287 movement responses after a total of 725 investigated stimuli. The prediction probabilities for positive movement responses were 0.63 (95%CI: 0.59-0.67) for the NFRT and 0.69 (95%CI: 0.65-0.73) for the BIS. The NFRT allows the prediction of movement responses under propofol mono-anaesthesia, which confirms its utility as a monitor to predict movement responses under general anaesthesia. The BIS allows an even more accurate prediction, although it does not reflect the physiological structures of movement suppression, but correlates closely with the dose of propofol. German clinical trial register (DRKS00003062, Deutsches Register Klinischer Studien).

Vernarbende Alopezien.

PubMed

Kanti, Varvara; Röwert-Huber, Joachim; Vogt, Annika; Blume-Peytavi, Ulrike

2018-04-01

Primär vernarbende Alopezien (PVA) werden nach der Klassifikation der North American Hair Research Society nach ihrem prominenten entzündlichen Infiltrat in vier Gruppen eingeteilt: PVA mit lymphozytärem, neutrophilem, gemischtzelligem oder unspezifischem Entzündungsmuster. Der Haarausfall kann subklinisch beginnen und langsam fortschreiten, so dass der genaue Erkrankungsbeginn oft schwer nachzuvollziehen ist. Die Diagnose wird häufig verzögert gestellt. Während die meisten vernarbenden Alopezien bei vollständiger Ausprägung anhand des klinischen Bildes klar zugeordnet werden können, ist die Diagnosestellung in der Frühphase oder im Endstadium häufig schwierig. Bei Erstvorstellung sollte eine ausführliche Anamnese und dermatologische Ganzkörperuntersuchung, inklusive Trichoskopie durchgeführt werden. In klinisch unklaren Fällen sollte eine Biopsie erfolgen. Aufgrund der Seltenheit der PVA gibt es bisher nur eine niedrige Evidenz über die Wirksamkeiten der Vielzahl der verschiedenen angewandten Therapien. Ziele der Therapie einer PVA sind, den Haarausfall zu stoppen oder zumindest zu verzögern, die klinischen Entzündungszeichen zu reduzieren, weitere Vernarbung zu verhindern sowie die subjektiven Symptome zu lindern. Ein Nachwachsen in bereits vernarbten Arealen sollte nicht erwartet werden. Eine antientzündliche Therapie mit topischen Kortikosteroiden der Klasse III-IV und/oder mit intrakutanen intraläsionalen Triamcinolonacetonid-Injektionen kommt bei den meisten PVA in Betracht. Die Wahl der systemischen Therapie hängt von der Art des prädominierenden entzündlichen Infiltrates ab und umfasst antimikrobielle/antibiotische oder immunmodulatorische/immunsuppressive Ansätze. Psychologische Unterstützung und Camouflage-Techniken sollten den Patienten angeboten werden. © 2018 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

The effects of a pulsed Nd:YAG laser on subgingival bacterial flora and on cementum: an in vivo study.

PubMed

Ben Hatit, Y; Blum, R; Severin, C; Maquin, M; Jabro, M H

1996-06-01

The purpose of this study was to compare the effects of scaling and Nd:YAG laser treatments with that of scaling alone on cementum and levels of Actinobacillus actinomycetemcomitans, Bacteroides forsythus, Porphyromonas gingivalis, and Treponema denticola. Study samples consisted of 14 patients, age 30 to 75 years, 8 females and 6 males, with a total of 150 periodontally involved sites with probing depth > or = 5 mm. Group A consisted of 100 pockets that were subdivided into 4 equal groups that were treated with conventional scaling and pulsed Nd:YAG laser using an optic fiber of 300 microns and 4 different power levels as follows: Group 1: P = 0.8 W, f = 10 Hz, E = 100 mJ/pulse; Group 2: P = 1.0 W, f = 1.0 Hz, E = 100 mJ/pulse; Group 3: P = 1.2 W, f = 12 Hz, E = 100 mJ/purse; and Group 4: P = 1.5 W, f = 15 Hz, E = 100 mJ/pulse. The time of each treatment was 60 sec per pocket in all 4 groups. Group B consisted of 50 pockets that were treated by conventional scaling alone and served as a control group. Microbiological samples from group A were collected before scaling; after scaling = before laser, just after laser, 2 weeks later, 6 weeks later, and 10 weeks later. Microbiological samples from group B were collected before scaling, after scaling, 6 weeks later, and 10 weeks later. Microbiological analysis of all samples was done by the Institute Für Angewandte Immunologie (IAI) method. The effects of laser on root surfaces were assessed by SEM examination and the sample consisted of 13 teeth from 5 different patients. Four sets of 3 teeth each were treated with Nd:YAG laser using 0.8, 1.0, 1.2, and 1.5 W, respectively. One tooth was just scaled and not treated with laser to serve as a control. Microbiological analysis of Group A samples indicated posttreatment reduction in levels of all 4 bacterial types tested compared to pretreatment levels and Group B controls. SEM examination of the specimens treated with Nd:YAG laser at different levels exhibited different features of root surface alterations.

Replication of endometriosis-associated single-nucleotide polymorphisms from genome-wide association studies in a Caucasian population.

PubMed

Sundqvist, J; Xu, H; Vodolazkaia, A; Fassbender, A; Kyama, C; Bokor, A; Gemzell-Danielsson, K; D'Hooghe, T M; Falconer, H

2013-03-01

Is it possible to replicate the previously identified genetic association of four single-nucleotide polymorphisms (SNPs), rs12700667, rs7798431, rs1250248 and rs7521902, with endometriosis in a Caucasian population? A borderline association was observed for rs1250248 and endometriosis (P = 0.049). However, we could not replicate the other previously identified endometriosis-associated SNPs (rs12700667, rs7798431 and rs7521902) in the same population. Endometriosis is considered a complex disease, influenced by several genetic and environmental factors, as well as interactions between them. Previous studies have found genetic associations with endometriosis for SNPs at the 7p15 and 2q35 loci in a Caucasian population. Allele frequencies of SNPs were investigated in patients with endometriosis and controls. Blood samples and peritoneal biopsies were taken from a Caucasian female population consisting of 1129 patients with endometriosis and 831 controls. DNA was extracted for genotyping. The study was performed at a University hospital and research laboratories. A weak association with endometriosis (all stages) was observed for rs1250248 (P = 0.049). No significant associations were observed for the SNPs rs12700667, rs7798431 and rs7521902. A non-significant trend towards the association of rs1250248 with moderate/severe endometriosis was observed (odds ratio 1.18, 95% confidence interval 0.97-1.44). The inability to confirm all previous findings may result from differences between populations and type II errors. Our result demonstrates the difficulty of identifying common genetic variants in complex diseases. This study was supported by grants from the Karolinska Institutet and Stockholm City County/Karolinska Institutet (ALF), Stockholm, Sweden, Swedish Medical Research Council (K2007-54X-14212-06-3, K2010-54X-14212-09-3), Stockholm, Sweden, Leuven University Research Council (Onderzoeksraad KU Leuven), the Leuven University Hospitals Clinical Research Foundation (Klinisch onderzoeksfonds) and by the National Scientific Foundation (Fonds voor Wetenschappelijk Onderzoek, FWO). The authors have no conflict of interest.

Evaluation of OK-432 Injection Therapy as Possible Primary Treatment of Intraoral Ranula.

PubMed

Kono, Michihide; Satomi, Takafumi; Abukawa, Harutsugi; Hasegawa, On; Watanabe, Masato; Chikazu, Daichi

2017-02-01

A ranula is a pseudocyst caused by mucous extravasation from the sublingual gland. Recently, a sclerosing agent, OK-432 (picibanil), has been reported to be highly effective for treating lymphangioma and cervical cystic lesions. The present study assessed the effectiveness of OK-432 injection therapy for intraoral ranula to clarify whether it can be used as the primary treatment. The present study was a retrospective clinical study of patients with intraoral ranula who received OK-432 injection therapy from 2005 to 2015. The ranula size was measured on computed tomography or magnetic resonance imaging studies. We dissolved 1 Klinische Einheit (KE) unit of OK-432 powder in normal saline equal to the aspiration volume. The primary endpoint was the treatment results. The secondary endpoints were the relation between the treatment results and the lesion length and aspiration volume. A total of 23 patients received OK-432 injection therapy for an intraoral ranula. The mean lesion size was 19.96 mm. The mean aspiration volume was 2.14 mL. The number of injections was 1 to 4 (mean 1.70). The treatment results were complete regression (CR) in 18 (78.2%), partial regression (PR) in 3 (13.0%), and no response (NR) in 2 (8%) patients after the last injection. The overall efficacy rate was 91.2% (21 of 23). No serious complications were observed. The lesion length and aspiration volume of the CR group was 17.38 mm and 1.40 mL, respectively. The lesion length and aspiration volume of the PR/NR group was 29.20 mm and 4.80 mL, respectively. The PR/NR group lesions were significantly larger than the CR group lesions. OK-432 injection therapy for intraoral ranula is safe and effective compared with other surgical therapies. This therapy could potentially become a primary treatment of intraoral ranula. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Effects of a team-based assessment and intervention on patient safety culture in general practice: an open randomised controlled trial.

PubMed

Hoffmann, B; Müller, V; Rochon, J; Gondan, M; Müller, B; Albay, Z; Weppler, K; Leifermann, M; Mießner, C; Güthlin, C; Parker, D; Hofinger, G; Gerlach, F M

2014-01-01

The measurement of safety culture in healthcare is generally regarded as a first step towards improvement. Based on a self-assessment of safety culture, the Frankfurt Patient Safety Matrix (FraTrix) aims to enable healthcare teams to improve safety culture in their organisations. In this study we assessed the effects of FraTrix on safety culture in general practice. We conducted an open randomised controlled trial in 60 general practices. FraTrix was applied over a period of 9 months during three facilitated team sessions in intervention practices. At baseline and after 12 months, scores were allocated for safety culture as expressed in practice structure and processes (indicators), in safety climate and in patient safety incident reporting. The primary outcome was the indicator error management. During the team sessions, practice teams reflected on their safety culture and decided on about 10 actions per practice to improve it. After 12 months, no significant differences were found between intervention and control groups in terms of error management (competing probability=0.48, 95% CI 0.34 to 0.63, p=0.823), 11 further patient safety culture indicators and safety climate scales. Intervention practices showed better reporting of patient safety incidents, reflected in a higher number of incident reports (mean (SD) 4.85 (4.94) vs 3.10 (5.42), p=0.045) and incident reports of higher quality (scoring 2.27 (1.93) vs 1.49 (1.67), p=0.038) than control practices. Applied as a team-based instrument to assess safety culture, FraTrix did not lead to measurable improvements in error management. Comparable studies with more positive results had less robust study designs. In future research, validated combined methods to measure safety culture will be required. In addition, more attention should be paid to evaluation of process parameters. Implemented actions and incident reporting may be more appropriate target endpoints. German Clinical Trials Register (Deutsches Register Klinischer Studien, DRKS) No. DRKS00000145.

Development and testing of culturally sensitive patient information material for Turkish, Polish, Russian and Italian migrants with depression or chronic low back pain (KULTINFO): study protocol for a double-blind randomized controlled trial.

PubMed

Hölzel, Lars P; Ries, Zivile; Zill, Jördis M; Kriston, Levente; Dirmaier, Jörg; Härter, Martin; Bermejo, Isaac

2014-07-04

Many of the approximately 15 million people with a migration background living in Germany (19% of the population) are inadequately reached by existing healthcare provision. In the literature, the necessity for cultural adaptation of information material for patients with a migration background is often cited as a measure for improving healthcare.In this study, culturally sensitive information material will be developed and evaluated for patients with a migration background and depression or chronic low back pain. In this respect, it will be examined whether culturally sensitive information material is judged as more useful by the patients than standard translated patient information without cultural adaptation. The implementation and evaluation of culturally sensitive patient information material will occur in the framework of a double-blind randomized controlled parallel-group study in four study centres in Germany. Primary care patients with a Turkish, Polish, Russian or Italian migration background with a diagnosis of depressive disorder or chronic low back pain will be included and randomly allocated to the intervention group or the control group. In the intervention group, culturally sensitive patient information will be handed to the patient at the end of the physician consultation, while in the control group, standard translated patient information material will be provided. The patients will be surveyed by means of questionnaires following the consultation as well as after 8 weeks and 6 months. In addition to the primary outcome (subjective usefulness), several patient- and physician-rated secondary outcomes will be considered. The study will provide an empirical answer to the question of whether persons with a migration background perceive culturally sensitive patient information material as more useful than translated information material without cultural adaptation. Deutsches Register Klinischer Studien (DRKS-ID) DRKS00004241 and Universal Trial Number (UTN) U1111-1135-8043.

Epidemiologie, Prävention und Früherkennung des Zervixkarzinoms

PubMed Central

Wentzensen, Nicolas

2016-01-01

Zusammenfassung Hintergrund Persistierende Infektionen mit humanen Papillomviren sind die notwendige Ursache des Zervixkarzinoms. Die Entwicklung von HPV-basierten Präventionsverfahren, der HPV Impfung und der HPV-Testung, führt derzeit zu umfangreichen Veränderungen von Zervixkarzinom-Vorsorgeprogrammen. Eine Dekade nach Einführung der HPV-Imfpung in vielen Ländern werden bereits Reduktionen von HPV-Infektionen und Krebsvorstufen in jungen Frauen beobachtet. Der Fokus liegt jetzt auf der Integration von neuen Testverfahren im Screening von Populationen mit zunehmenden Impfraten. Ergebnisse und Schlussfolgerung Ein erfolgreiches Zervixkarzinom-Vorsorgeprogramm besteht aus verschiedenen Komponenten, vom primären Screening über die Triage zur Kolposkopie mit Biopsie, um Frauen mit Kresbvorstufen zu identifizieren, die eine therapeutische Intervention benötigen. Im primären Screening wird eine kleine Gruppe von Frauen mit erhöhtem Risiko für eine Krebsvorstufe identifiziert, während die grosse Mehrheit kein erhöhtes Risiko hat. Je nach primärem Testverfahren werden in screen-positiven Frauen zusätzliche Triage-Tests durchgeführt, um zu entscheiden, wer zur Kolposkopie überwiesen werden sollte. Derzeit gibt es drei verschiedene Ansätze für das primäre Zervixkarzinomscreening: Die Zervix-Zytologie, die HPV-Testung, und die HPV-Zytologie Ko-Testung. Zahlreiche Triage-Tests für HPV-positive Frauen werden derzeit untersucht, darunter sind die Zytologie, HPV-Genotypisierung, p16/Ki-67 Zytologie, und diverse Methylierungstests. Die steigende Anzahl an Optionen für die Früherkennung des Zervixkarzinoms stellt eine Herausforderung für klinische Leitlinien dar. Die zunehmende Komplexität von Vorsorgeprogrammen kann zur Verunsicherung von Ärzten und von am Screening teilnehmenden Frauen führen. Die Präzisions-Prävention des Zervixkarzinoms ist eine neuer Ansatz, der umfangreiche Risikodaten basierend auf der individuellen Vorgeschichte und von Testergebnissen integriert und einheitliche, Risiko-basierte Managementempfehlungen gibt. PMID:28265177

EMPOWER-support of patient empowerment by an intelligent self-management pathway for patients: study protocol.

PubMed

Mantwill, Sarah; Fiordelli, Maddalena; Ludolph, Ramona; Schulz, Peter J

2015-03-20

Diabetes education together with patient empowerment has shown to be key to effective self-management behavior. When delivered through information and communication technologies (ICT), this solution has shown to lead to better health outcomes. However, the potential of ICT and their integration into the healthcare environment have not yet been fully exploited. ICT should be in particular used to facilitate communication and information exchange between patient and healthcare providers. In addition, systems should include components facilitating behavior change using empowerment approaches such as goal-setting. Funded by the European Commission (FP7-ICT-2011-288209) a web/mobile based platform (EMPOWER) has been developed, which aims at supporting self-management activities of diabetes patients and their treating physicians in Germany and Turkey. The platform semantically integrates multiple information sources, such as electronic and personal health records (EHR/PHR). Patients can register patterns of daily living, record blood glucose levels, design disease management plans and set long- and short-term goals. The project actively involves the treating physician, who has the possibility to set recommendations for the patient and to monitor his/her progress on the platform. In the test-phase of EMPOWER, patients will be assigned to an intervention group and a control group. Data will be collected at baseline and three months after the intervention started. In addition, qualitative interviews will be conducted to collect extra information on usability and usefulness. Outcome measures include amongst others the Problem Areas in Diabetes questionnaire (PAID), the Summary of Diabetes Self-Care Activities and scales evaluating doctor-patient interaction. Physiological parameters, such as physical activity or blood glucose levels will be collected via the platform. Further, log files and number of logins will serve as independent variables. The interplay between multiple sources, including EHR, patients' own registered information and physicians' recommendations on one platform can have important practice implications. It might not only improve self-management activities in diabetes patients but it will also facilitate physician's work, and ultimately the physician patient relationship. The trial has been registered with Deutsches Register Klinischer Studien (German register of clinical trials) under DRKS00007699 on January 30, 2015.

Impact of preoperative Vitamin D3 administration on postoperative hypocalcaemia in patients undergoing total thyroidectomy (HypoCalViD): study protocol for a randomized controlled trial.

PubMed

Wolak, Stefanie; Scheunchen, Mandy; Holzer, Katharina; Busch, Mirjam; Trumpf, Esra; Zielke, Andreas

2016-02-20

Total thyroidectomy is increasingly used as a surgical approach for many thyroid conditions. Subsequently, postoperative hypocalcaemia is observed with increasing frequency, often resulting in prolonged hospital stay, increased use of resources, reduced quality of life and delayed return to work. The administration of vitamin D is essential in the therapy of postoperative hypocalcaemia; calcitriol is most commonly used. What has not been examined so far is whether and how routine preoperative vitamin D prophylaxis using calcitriol can help to prevent postoperative hypocalcaemia. This study evaluates routine preoperative calcitriol prophylaxis for all patients who are to undergo a total thyroidectomy, compared with the current standard of post-treatment, i.e., selective vitamin D treatment for patients with postoperative hypocalcaemia. This clinical observational (minimal interventional clinical trial) trial is a multicentre, prospective, randomized superiority trial with an adaptive design. Datasets will be pseudonymized for analysis. Patients will be randomly allocated (1:1) to the intervention and the control groups. The only intervention is 0.5 μg calcitriol orally twice a day for 3 days prior to surgery. For the primary endpoint measure (number of patients with hypocalcaemia), hypocalcaemia is defined as serum calcium of less than 2.1 mmol/l on any day during the postoperative course; this measure will be analyzed using a Chi-square test comparing the two groups. Secondary endpoint measures, such as number of days to discharge, quality of life, and economic parameters will also be analyzed. By virtue of the direct comparison of clinically and economically relevant endpoints, the efficacy as well as efficiency of preoperative calcitriol prophylaxis of hypocalcaemia will be clarified. These results should be available 24 months after the first patient has been enrolled. The results will be used to inform a revised practice parameter guideline of whether or not to recommend preoperative calcitriol for all patients in whom total thyroidectomy is planned. Deutsches Register Klinischer Studien, DRKS00005615 (Feb.12.2016).

Whole body vibration compared to conventional physiotherapy in patients with gonarthrosis: a protocol for a randomized, controlled study.

PubMed

Stein, Gregor; Knoell, Peter; Faymonville, Christoph; Kaulhausen, Thomas; Siewe, Jan; Otto, Christina; Eysel, Peer; Zarghooni, Kourosh

2010-06-21

Osteoarthritis (OA) is the most common degenerative arthropathy. Load-bearing joints such as knee and hip are more often affected than spine or hands. The prevalence of gonarthrosis is generally higher than that of coxarthrosis.Because no cure for OA exists, the main emphasis of therapy is analgesic treatment through either mobility or medication. Non-pharmacologic treatment is the first step, followed by the addition of analgesic medication, and ultimately by surgery.The goal of non-pharmacologic and non-invasive therapy is to improve neuromuscular function, which in turn both prevents formation of and delays progression of OA. A modification of conventional physiotherapy, whole body vibration has been successfully employed for several years. Since its introduction, this therapy is in wide use at our facility not only for gonarthrosis, but also coxarthrosis and other diseases leading to muscular imbalance. This study is a randomized, therapy-controlled trial in a primary care setting at a university hospital. Patients presenting to our outpatient clinic with initial symptoms of gonarthrosis will be assessed against inclusion and exclusion criteria. After patient consent, 6 weeks of treatment will ensue. During the six weeks of treatment, patients will receive one of two treatments, conventional physiotherapy or whole-body-vibration exercises of one hour three times a week. Follow-up examinations will be performed immediately after treatment and after another 6 and 20 weeks, for a total study duration of 6 months. 20 patients will be included in each therapy group.Outcome measurements will include objective analysis of motion and ambulation as well as examinations of balance and isokinetic force. The Western Ontario and McMaster Universities Arthritis Index and SF-12 scores, the patients' overall status, and clinical examinations of the affected joint will be carried out. As new physiotherapy techniques develop for the treatment of OA, it is important to investigate the effectiveness of competing strategies. With this study, not only patient-based scores, but also objective assessments will be used to quantify patient-derived benefits of therapy. Deutsches Register Klinischer Studien (DRKS) DRKS00000415Clinicaltrials.gov NCT01037972EudraCT 2009-017617-29.

Primary palliative Care in General Practice - study protocol of a three-stage mixed-methods organizational health services research study.

PubMed

Ewertowski, Helen; Tetzlaff, Fabian; Stiel, Stephanie; Schneider, Nils; Jünger, Saskia

2018-01-30

The focus of this project is on improving the provision of primary palliative care (PC) by general practitioners (GPs). While approximately 10-15% of the incurable, seriously ill or dying people will be in need of specialist PC, the vast majority can be adequately treated within generalist care. The strengthening of the GP's role in PC, as well as ensuring close collaboration between specialist PC services and GPs have been identified as top priorities for the improvement of PC in Germany. Despite healthcare policy actions, diverse obstacles still exist to successful implementation of primary PC on a structural, process, and economic level. Therefore, this project aims at addressing barriers and facilitators to primary PC delivery in general practice in Germany. The study follows a three-step approach; first, it aims at systematically analyzing barriers and facilitators to primary PC provision by GPs. Second, based on these outcomes, a tailored intervention package will be developed to enhance the provision of primary PC by GPs. Third, the intervention package will be implemented and evaluated in practice. The expected outcome will be an evidence-based model for successful implementation of primary PC delivery tailored to the German healthcare system, followed by a strategic action plan on how to improve current practice both on a local level and nationally. The first step of the project has been partly completed at the time of writing. The chosen methodologies of four sub-projects within this first step have opened up different advantages and disadvantages for the data collection. In sum of all sub-projects, the different methodologies and target groups contributed valuable information to the systematic analysis of barriers and facilitators to primary PC provision by GPs. The study (BMBF-FK 01 GY 1610) was retrospectively registered at the German Clinical Trials Register (Deutsches Register Klinischer Studien) (Registration N° DRKS00011821 ; date of registration: December 04th 2017) and at the German Register of health care research (Versorgungsforschung Deutschland - Datenbank) (Registration N° VfD_ALLPRAX_16_003817 ; date of registration: March 30th 2017).

Single dental implant retained mandibular complete dentures – influence of the loading protocol: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Over the years, there has been a strong consensus in dentistry that at least two implants are required to retain a complete mandibular denture. It has been shown in several clinical trials that one single median implant can retain a mandibular overdenture sufficiently well for up to 5 years without implant failures, when delayed loading was used. However, other trials have reported conflicting results with in part considerable failure rates when immediate loading was applied. Therefore it is the purpose of the current randomized clinical trial to test the hypothesis that immediate loading of a single mandibular midline implant with an overdenture will result in a comparable clinical outcome as using the standard protocol of delayed loading. Methods/design This prospective nine-center randomized controlled clinical trial is still ongoing. The final patient will complete the trial in 2016. In total, 180 edentulous patients between 60 and 89 years with sufficient complete dentures will receive one median implant in the edentulous mandible, which will retain the existing complete denture using a ball attachment. Loading of the median implant is either immediately after implant placement (experimental group) or delayed by 3 months of submerged healing at second-stage surgery (control group). Follow-up of patients will be performed for 24 months after implant loading. The primary outcome measure is non-inferiority of implant success rate of the experimental group compared to the control group. The secondary outcome measures encompass clinical, technical and subjective variables. The study was funded by the Deutsche Forschungsgemeinschaft (German research foundation, KE 477/8-1). Discussion This multi-center clinical trial will give information on the ability of a single median implant to retain a complete mandibular denture when immediately loaded. If viable, this treatment option will strongly improve everyday dental practice. Trial registration The trial has been registered at Deutsches Register Klinischer Studien (German register of clinical trials) under DRKS-ID: DRKS00003730 since 23 August 2012. (http://www.germanctr.de). PMID:24884848

Report of the 1st meeting of the "Vienna Initiative to Save European Academic Research (VISAER)".

PubMed

Druml, Christiane; Singer, Ernst A; Wolzt, Michael

2006-04-01

The European Directive 2001/20/EC ("Clinical Trials Directive") was aimed at simplifying and harmonising European clinical research. The directive's attempt represents an important step because many European Member States lack national laws that specifically address details of research, but the goal has been only partly achieved. For academic investigators doing national or multi-national research the new European law and the requirements following its implementation are likely to have the opposite effect. Some areas seem to be of particular concern: trial sponsorship, the ethical review process, the participation of patients who are temporarily not able to consent in clinical trials, in particular the informed consent process, an accepted European registry for all clinical trials, insurance and pharmacovigilance. Furthermore there are fundamental problems of the conduct of clinical trials that could have been foreseen at the time of implementation of the new law, which are impeding academic basic clinical research. The bureaucratic burden for academic investigators has tremendously increased without representing any contribution to patients' safety or to the scientific value of research. Furthermore some large European academic trials cannot be conducted anymore due to the new regulations. This result in a reduction in the number of trials and additionally in a reduction in the number of patients enrolled in a study. European research and thus European patients will suffer from the loss of potential benefits of research. The Vienna Initiative to Save European Academic Research (VISEAR) brings together leading stakeholders from academic research groups and interested parties from industry, international organisations and regulatory authorities to focus on the issues of concern regarding the organisational and funding of academic clinical research in order to improve the development and use of medicines in Europe. The first step of the initiative was a meeting held on May 30, 2005 in Vienna. The resumés of the six parallel working groups are presented in this supplement of the Wiener Klinische Wochenschrift, a position paper with recommendations in relation to the EU Clinical Trials Directive and medical research involving incapacitated adults has been published separately.

Calculation of former ELA depressions in the Himalaya - a comparative analysis

NASA Astrophysics Data System (ADS)

Wagner, M.

2009-04-01

For the reconstruction of former Equilibrium Line Altitudes (ELA) and ELA depressions in the Himalaya, the group of the Toe-to-Summit-Altitude-Methods (TSAM) is most suited. In this investigation the Kuhle (1986) method that is particularly tailored to the extreme high mountain relief, as well as the widely used Höfer (1879) method and Louis (1954/55) method, have been applied. Applying the relief specific correction factor FSD (Factor for snowline deviation) in the Kuhle method, it is thereby possible to simulate the shifting position of the ELA within the vertical extension of the glacier in dependence on the relief characteristics and glacial type. The results of this work, carried out along the Kali Gandaki in central Nepal, illustrate that as a rule, the Louis method results in the highest ELAs and the lowest ELA depressions, while the Höfer method yields the lowest ELAs and the highest ELA depressions. In affirmation of the literature, the Louis method tends to overestimate the ELA, since using the maximum peak height, especially for large glaciers in mountain ranges with high relief energy, leads to an overly high position of the glacier upper limit. With respect to the Höfer method, the suspicion already voiced by Höfer (1879) himself, that with the use of his method, the for the Himalaya typically high elevated, and with marginal gradient toward the valley moving ridge progressions, would lead to a too low ELA, can be affirmed. Clearly to be disputed, however, is the statement of Gross et al. (1976) that the Höfer method leads to an overestimation of the ELA. The reason for this can be found in a wrong computation of the mean ridge height above the ELA and consequently of the ELA itself within the Höfer method, based on the erroneous assumption that otherwise the ELA could not be calculated due to a circular conclusion (Gross et al. 1976). As is evidenced by this study, the Kuhle method mediates between the empiric overly high values of the Louis method and the overly low values of the Höfer method, because of a mediating definition of the accumulation zone upper limit. Additionally, over the FSD, Kuhle allows for a high degree of adaptation to the extreme Himalaya relief, and within limitations from the change of the relief constellation, which stems from transverse valley's characteristics of the Kali Gandaki. Therefore, the results of the Kuhle method must be affirmed as reflecting the greatest conformity with the actual values of the ELA and the ELA depression. References: Gross, G., H. Kerschner, G. Patzelt (1976): Methodische Untersuchungen über die Schneegrenze in alpinen Gletschergebieten. Zeitschrift für Gletscherkunde und Glazialgeologie 12 (2): 223-251. Höfer von Heimhalt, H. (1879): Gletscher- und Eiszeitstudien. Sitzungsberichte der Akademie der Wissenschaften in Wien, Mathematisch-Naturwissenschaftliche Klasse, Abteilung I, Biologie, Mineralogie, Erdkunde 79: 331-367. Kuhle, M. (1986): Schneegrenzberechnung und typologische Klassifikation von Gletschern anhand spezifischer Reliefparameter. Petermanns Geographische Mitteilungen 130: 41-51. Louis, H. (1954/55): Schneegrenze und Schneegrenzbestimmung. Geographisches Taschenbuch 1954/55: 414-418.

The Pedotopia Project: A Transdisciplinary Experiment in Soil Education

NASA Astrophysics Data System (ADS)

Toland, A.; Wessolek, G.

2012-04-01

In the absence of every-day interactions with the land, a hands-on, comprehensive soil education across disciplines and ages is necessary. Soil education is usually integrated into earth science and geography curricula and only rarely into social science, arts and humanities programs. Furthermore, an emphasis on measurement and modeling in conventional classroom science often neglects aesthetic, moral and other non-quantifiable values, precluding a broader cultural context in which soil education could take place. The arts play a vital role in communicating environmental issues to the greater public and represent a dynamic approach to help students discover soil complexity in new and unexpected ways. Artistic methods have recently been introduced as pedagogical tools in soil awareness-raising programs for children and youth. Painting with soil has become an interesting new approach to soil education from Kindergarten to University levels (SZLEZAK 2008). And a growing amount of literature describes artists who have undertaken different soil issues, suggesting that such artistic focus may improve wider understanding and appreciation of soil conservation issues (FELLER et al 2010, TOLAND & WESSOLEK 2010, WAGNER 2002). How can art contribute to soil science, policy and education - both with the aim of generating greater public understanding, but also by honing creative methods to confront problems such as contamination, erosion, and urban sprawl? What artistic approaches exist to protect and restore soils as well as our relationship to the land? And how can these approaches support current soil education goals? These questions were addressed in the transdisciplinary soil seminar, "Pedotopia - Re-sourcing Urban Soils" from September 2010 to September 2011 in Berlin. A cooperation between the Technical University of Berlin's Department of Soil Protection and the Berlin University of Arts' Institute for Art in Context, the project served as a teaching experiment as well as a platform for the production of new soil-oriented artworks. An exhibition of the resulting works as well as a symposium on the cultural values of soil conservation was held at the annual meeting of the German Soil Science Society (DBG) in 2011 in Berlin. In the following paper we will present the Pedotopia project as a case study in transdisciplinary soil education. We will highlight main points of the curriculum, present the results of the project and address challenges and future considerations of transdisciplinary soil education. SOURCES FELLER, LARDY and UGOLINI (2010): The Representation of Soil in the Western Art: From Genesis to Pedogenesis. In: Feller and Landa (Hrsg.) Soil and Culture. Dordrecht, Heidelberg, London and New York: Springer Science + Business Media B.V.: 3-21 SZLEZAK, E. (2009) "Soilart with the Colours of the Earth". In: Amt der NÖ LandesregierungAbteilung Landentwicklung. Stand 2009. http://www.soilart.eu/1-0-Home.htm (abgerufen am 20. Dezember 2011) TOLAND, A. & WESSOLEK, G. (2010): Merging Horizons - Soil Science and Soil Art. In: Feller and Landa (Hrsg.) Soil and Culture. Dordrecht, Heidelberg, London and New York: Springer Science + Business Media B.V.: 45-66 WAGNER, M. (2002): Erde als Material künstlerische Gestaltung. In: BUSCH, B. (2002) (Hrsg.): Erde. Schriftenreihe Forum, Bd. 11, Elemente des Naturhaushalts III. Kunst- und Ausstellungshalle der Bundesrepublik Deutschland GmbH, Köln, 246-260

The preventive effect of sensorimotor- and vibration exercises on the onset of Oxaliplatin- or vinca-alkaloid induced peripheral neuropathies - STOP.

PubMed

Streckmann, Fiona; Balke, Maryam; Lehmann, Helmar C; Rustler, Vanessa; Koliamitra, Christina; Elter, Thomas; Hallek, Michael; Leitzmann, Michael; Steinmetz, Tilman; Heinen, Petra; Baumann, Freerk T; Bloch, Wilhelm

2018-01-10

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and clinically relevant side effect of chemotherapy. Approximately 50% of all leukemia, lymphoma, colorectal- and breast cancer patients are affected. CIPN is induced by neurotoxic chemotherapeutic agents and can manifest with sensory and/or motor deficits. It is associated with significant disability and poor recovery. Common symptoms include pain, altered sensation, reduced or absent reflexes, muscle weakness, reduced balance control and insecure gait. These symptoms not only affect activities of daily living, subsequently reducing patients' quality of life, they have far more become a decisive limiting factor for medical therapy, causing treatment delays, dose reductions, or even discontinuation of therapy, which can affect the outcome and compromise survival. To date, CIPN cannot be prevented and its occurrence presents a diagnostic dilemma since approved and effective treatment options are lacking. Promising results have recently been achieved with exercise. We have revealed that sensorimotor training (SMT) or whole body vibration (WBV) can reduce the symptoms of CIPN and attenuate motor and sensory deficits. We furthermore detected a tendency that it may also have a preventive effect on the onset of CIPN. We are therefore conducting a prospective, multicentre, controlled clinical trial involving 236 oncological patients receiving either oxaliplatin (N = 118) or vinca-alkaloid (N = 118) who are randomized to one of two interventions (SMT or WBV) or a treatment as usual (TAU) group. Primary endpoint is the time to incidence of neurologically confirmed CIPN. Secondary endpoints are pain, maintenance of the functionality of sensory as well as motor nerve fibres as well as the level of physical activity. The baseline assessment is performed prior to the first cycle of chemotherapy. Subsequent follow-up assessments are conducted at 12 weeks, after completion of chemotherapy, and at a 3-month follow-up. Patients who develop CIPN receive an additional assessment at this time point, as it represents the primary endpoint. We hypothesize that SMT and WBV prevent the onset or delay the progression of CIPN, decrease the likelihood of dose reductions or discontinuation of cancer treatment and improve patients' quality of life. Deutsche Register Klinischer Studien ( DRKS00006088 , registered 07.05.2014).

Exploring end-of-life interaction in dyads of parents and adult children: a protocol for a mixed-methods study.

PubMed

Stiel, Stephanie; Stelzer, Eva-Maria; Schneider, Nils; Herbst, Franziska A

2018-04-27

A considerable number of terminally-ill adult children are outlived by at least one parent and receive palliative care prior to their death. At the same time, adult children continue to be confronted with their parents' terminal illnesses and end-of-life situations. The current study explores the specifics of dyadic interaction at the end of life between a) adult children suffering from a life-threatening disease and their parents, and b) terminally ill parents and their adult children. This prospective observational study aims at filling the existing gap on adult child-parent interaction specifics at the end of life using an exploratory mixed-methods framework. The mixed-methods framework combines a qualitative face-to face interview and quantitative self-report questionnaires to study the topic at hand. The qualitative interview will focus on experiences, expectations, and wishes with regard to dyadic communication, information about illness and prognosis, expressed and perceived burden and support as well as caregiving role at the end of life. The questionnaires will cover socio-demographics, loneliness, attachment style, social support, and emotional closeness. The research group is currently adjusting a semi-structured interview guide and questionnaire instructions based on the results of a multiprofessional scientific advisory board meeting (Jan. 2018). In a next step, and prior to qualitative and quantitative data collection, the questionnaires will be piloted on patients and their family members in a palliative care setting. The main expected results are i) a description of the specifics of the interaction within and between both dyads, ii) the development of hypotheses and a theoretical framework on the specifics, similarities, and differences for both study groups, and iii) clinical conclusions on specific psychosocial care needs of both groups. The study was registered prospectively in the Health Services Research Germany register (Versorgungsforschung Deutschland - Datenbank) (Registration N° VfD_Dy@EoL_17_003897; date of registration: November 22, 2017) and in the German Clinical Trials Register (Deutsches Register Klinischer Studien) (Registration N° DRKS00013206 ; date of registration: October 27, 2017). The study is visible in the International Clinical Trials Registry Platform Search Portal of the World Health Organization under the German Clinical Trials Register number.

Effects of heart rate variability biofeedback during exposure to fear-provoking stimuli within spider-fearful individuals: study protocol for a randomized controlled trial.

PubMed

Schäfer, Sarah K; Ihmig, Frank R; Lara H, Karen A; Neurohr, Frank; Kiefer, Stephan; Staginnus, Marlene; Lass-Hennemann, Johanna; Michael, Tanja

2018-03-16

Specific phobias are among the most common anxiety disorders. Exposure therapy is the treatment of choice for specific phobias. However, not all patients respond equally well to it. Hence, current research focuses on therapeutic add-ons to increase and consolidate the effects of exposure therapy. One potential therapeutic add-on is biofeedback to increase heart rate variability (HRV). A recent meta-analysis shows beneficial effects of HRV biofeedback interventions on stress and anxiety symptoms. Therefore, the purpose of the current trial is to evaluate the effects of HRV biofeedback, which is practiced before and utilized during exposure, in spider-fearful individuals. Further, this trial is the first to differentiate between the effects of a HRV biofeedback intervention and those of a low-load working memory (WM) task. Eighty spider-fearful individuals participate in the study. All participants receive a training session in which they practice two tasks (HRV biofeedback and a motor pseudo-biofeedback task or two motor pseudo-biofeedback tasks). Afterwards, they train both tasks at home for 6 days. One week later, during the exposure session, they watch 16 1-min spider video clips. Participants are divided into four groups: group 1 practices the HRV biofeedback and one motor pseudo-task before exposure and utilizes HRV biofeedback during exposure. Group 2 receives the same training, but continues the pseudo-biofeedback task during exposure. Group 3 practices two pseudo-biofeedback tasks and continues one of them during exposure. Group 4 trains in two pseudo-biofeedback tasks and has no additional task during exposure. The primary outcome is fear of spiders (measured by the Fear of Spiders Questionnaire and the Behavioral Approach Test). Secondary outcomes are physiological measures based on electrodermal activity, electrocardiogram and respiration. This RCT is the first one to investigate the effects of using a pre-trained HRV biofeedback during exposure in spider-fearful individuals. The study critically contrasts the effects of the biofeedback intervention with those of pseudo-tasks, which also require WM capacity, but which do not have a physiological base. If HRV biofeedback is effective in reducing fear of spiders, it would represent an easy-to-use tool to improve exposure-therapy outcomes. Deutsches Register Klinischer Studien, DRKS00012278 . Registered on 23 May 2017, amendment on 5 October 2017.

Suitability of current definitions of ambulatory care sensitive conditions for research in emergency department patients: a secondary health data analysis.

PubMed

Frick, Johann; Möckel, Martin; Muller, Reinhold; Searle, Julia; Somasundaram, Rajan; Slagman, Anna

2017-10-22

The aim of this study was to investigate the suitability of existing definitions of ambulatory care sensitive conditions (ACSC) in the setting of an emergency department (ED) by assessing ACSC prevalence in patients admitted to hospital after their ED stay. The secondary aim was to identify ACSC suitable for specific application in the ED setting. Observational clinical study with secondary health data. Two EDs of the Charité-Universitätsmedizin Berlin. All medical ED patients of the 'The Charité Emergency Medicine Study' (CHARITEM) study, who were admitted as inpatients during the 1-year study period (n=13 536). Prevalence of ACSC. Prevalence of ACSC in the study population differed significantly depending on the respective ACSC set used. Prevalence ranged between 19.1% (95% CI 18.4% to 19.8%; n=2586) using the definition by Albrecht et al and 36.6% (95% CI 35.8% to 37.5%; n=4960) using the definition of Naumann et al . (p<0.001). Overall ACSC prevalence (ie, when using all diagnoses used in any of the assessed ACSC-definitions) was 48.1% (95% CI 47.2% to 48.9%; n=6505). Some frequently observed diagnoses such as ' convulsion and epilepsy ' (prevalence: 3.4%, 95% CI 3.1% to 3.7%; n=455), ' diseases of the urinary system ' (prevalence: 1.4%; 95% CI 1.2% to 1.6%; n=191) or ' atrial fibrillation and flutter ' (prevalence: 1.0%, 95% CI 0.8% to 1.2%, n=134) are not included in all of the current ACSC definitions. The results highlight the need for an optimised, ED-specific ACSC definition. Particular ACSC diagnoses (such as ' convulsion and epilepsy ' or ' diseases of the urinary system ' and others) seem to be of special relevance in an ED population but are not included in all available ACSC definitions. Further research towards the development of a suitable and specific ACSC definition for research in the ED setting seems warranted. German Clinical Trials Register Deutsches Register für Klinische Studien: DRKS-ID: DRKS00000261. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

visCOS: An R-package to evaluate model performance of hydrological models

NASA Astrophysics Data System (ADS)

Klotz, Daniel; Herrnegger, Mathew; Wesemann, Johannes; Schulz, Karsten

2016-04-01

The evaluation of model performance is a central part of (hydrological) modelling. Much attention has been given to the development of evaluation criteria and diagnostic frameworks. (Klemeš, 1986; Gupta et al., 2008; among many others). Nevertheless, many applications exist for which objective functions do not yet provide satisfying summaries. Thus, the necessity to visualize results arises in order to explore a wider range of model capacities, be it strengths or deficiencies. Visualizations are usually devised for specific projects and these efforts are often not distributed to a broader community (e.g. via open source software packages). Hence, the opportunity to explicitly discuss a state-of-the-art presentation technique is often missed. We therefore present a comprehensive R-package for evaluating model performance by visualizing and exploring different aspects of hydrological time-series. The presented package comprises a set of useful plots and visualization methods, which complement existing packages, such as hydroGOF (Zambrano-Bigiarini et al., 2012). It is derived from practical applications of the hydrological models COSERO and COSEROreg (Kling et al., 2014). visCOS, providing an interface in R, represents an easy-to-use software package for visualizing and assessing model performance and can be implemented in the process of model calibration or model development. The package provides functions to load hydrological data into R, clean the data, process, visualize, explore and finally save the results in a consistent way. Together with an interactive zoom function of the time series, an online calculation of the objective functions for variable time-windows is included. Common hydrological objective functions, such as the Nash-Sutcliffe Efficiency and the Kling-Gupta Efficiency, can also be evaluated and visualized in different ways for defined sub-periods like hydrological years or seasonal sections. Many hydrologists use long-term water-balances as a pivotal tool in model evaluation. They allow inferences about different systematic model-shortcomings and are an efficient way for communicating these in practice (Schulz et al., 2015). The evaluation and construction of such water balances is implemented with the presented package. During the (manual) calibration of a model or in the scope of model development, many model runs and iterations are necessary. Thus, users are often interested in comparing different model results in a visual way in order to learn about the model and to analyse parameter-changes on the output. A method to illuminate these differences and the evolution of changes is also included. References: • Gupta, H.V.; Wagener, T.; Liu, Y. (2008): Reconciling theory with observations: elements of a diagnostic approach to model evaluation, Hydrol. Process. 22, doi: 10.1002/hyp.6989. • Klemeš, V. (1986): Operational testing of hydrological simulation models, Hydrolog. Sci. J., doi: 10.1080/02626668609491024. • Kling, H.; Stanzel, P.; Fuchs, M.; and Nachtnebel, H. P. (2014): Performance of the COSERO precipitation-runoff model under non-stationary conditions in basins with different climates, Hydrolog. Sci. J., doi: 10.1080/02626667.2014.959956. • Schulz, K., Herrnegger, M., Wesemann, J., Klotz, D. Senoner, T. (2015): Kalibrierung COSERO - Mur für Pro Vis, Verbund Trading GmbH (Abteilung STG), final report, Institute of Water Management, Hydrology and Hydraulic Engineering, University of Natural Resources and Applied Life Sciences, Vienna, Austria, 217pp. • Zambrano-Bigiarini, M; Bellin, A. (2010): Comparing Goodness-of-fit Measures for Calibration of Models Focused on Extreme Events. European Geosciences Union (EGU), Geophysical Research Abstracts 14, EGU2012-11549-1.

Online Measurement of Microembolic Signal Burden by Transcranial Doppler during Catheter Ablation for Atrial Fibrillation-Results of a Multicenter Trial.

PubMed

von Bary, Christian; Deneke, Thomas; Arentz, Thomas; Schade, Anja; Lehrmann, Heiko; Fredersdorf, Sabine; Baldaranov, Dobri; Maier, Lars; Schlachetzki, Felix

2017-01-01

Left atrial pulmonary vein isolation (PVI) is an accepted treatment option for patients with symptomatic atrial fibrillation (AF). This procedure can be complicated by stroke or silent cerebral embolism. Online measurement of microembolic signals (MESs) by transcranial Doppler (TCD) may be useful for characterizing thromboembolic burden during PVI. In this prospective multicenter trial, we investigated the burden, characteristics, and composition of MES during left atrial catheter ablation using a variety of catheter technologies. PVI was performed in a total of 42 patients using the circular-shaped multielectrode pulmonary vein ablation catheter (PVAC) technology in 23, an irrigated radiofrequency (IRF) in 14, and the cryoballoon (CB) technology in 5 patients. TCD was used to detect the total MES burden and sustained thromboembolic showers (TESs) of >30 s. During TES, the site of ablation within the left atrium was registered. MES composition was classified manually into "solid," "gaseous," or "equivocal" by off-line expert assessment. The total MES burden was higher when using IRF compared to CB (2,336 ± 1,654 vs. 593 ± 231; p  = 0.007) and showed a tendency toward a higher burden when using IRF compared to PVAC (2,336 ± 1,654 vs. 1,685 ± 2,255; p  = 0.08). TES occurred more often when using PVAC compared to IRF (1.5 ± 2 vs. 0.4 ± 1.3; p  = 0.04) and most frequently when ablation was performed close to the left superior pulmonary vein (LSPV). Of the MES, 17.004 (23%) were characterized as definitely solid, 13.204 (18%) as clearly gaseous, and 44.366 (59%) as equivocal. We investigated the burden and characteristics of MES during left atrial catheter ablation for AF. All ablation techniques applied in this study generated a relevant number of MES. There was a significant difference in total MES burden using IRF compared to CB and a tendency toward a higher burden using IRF compared to PVAC. The highest TES burden was found in the PVAC group, particularly during ablation close to the LSPV. The composition of thromboembolic particles was balanced. The impact of MES, TES, and composition of thromboembolic particles on neurological outcome needs to be evaluated further. (Clinical Trial Registration: Deutsches Register Klinischer Studien, https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00003465. DRKS00003465.).

Study protocol of the Diabetes and Depression Study (DAD): a multi-center randomized controlled trial to compare the efficacy of a diabetes-specific cognitive behavioral group therapy versus sertraline in patients with major depression and poorly controlled diabetes mellitus

PubMed Central

2013-01-01

Background Depression is common in diabetes and associated with hyperglycemia, diabetes related complications and mortality. No single intervention has been identified that consistently leads to simultaneous improvement of depression and glycemic control. Our aim is to analyze the efficacy of a diabetes-specific cognitive behavioral group therapy (CBT) compared to sertraline (SER) in adults with depression and poorly controlled diabetes. Methods/Design This study is a multi-center parallel arm randomized controlled trial currently in its data analysis phase. We included 251 patients in 70 secondary care centers across Germany. Key inclusion criteria were: type 1 or 2 diabetes, major depression (diagnosed with the Structured Clinical Interview for DSM-IV, SCID) and hemoglobin A1C >7.5% despite current insulin therapy. During the initial phase, patients received either 50–200 mg/d sertraline or 10 CBT sessions aiming at the remission of depression and enhanced adherence to diabetes treatment and coping with diabetes. Both groups received diabetes treatment as usual. After 12 weeks of this initial open-label therapy, only the treatment-responders (50% depression symptoms reduction, Hamilton Depression Rating Scale, 17-item version [HAMD]) were included in the subsequent one year study phase and represented the primary analysis population. CBT-responders received no further treatment, while SER-responders obtained a continuous, flexible-dose SER regimen as relapse prevention. Adherence to treatment was analyzed using therapeutic drug monitoring (measurement of sertraline and N-desmethylsertraline concentrations in blood serum) and by counting the numbers of CBT sessions received. Outcome assessments were conducted by trained psychologists blinded to group assignment. Group differences in HbA1c (primary outcome) and depression (HAMD, secondary outcome) between 1-year follow-up and baseline will be analyzed by ANCOVA controlling for baseline values. As primary hypothesis we expect that CBT leads to significantly greater improvement of glycemic control in the one year follow-up in treatment responders of the short term phase. Discussion The DAD study is the first randomized controlled trial comparing antidepressants to a psychological treatment in diabetes patients with depression. The study is investigator initiated and was supported by the ‘Förderprogramm Klinische Studien (Clinical Trials)’ and the ‘Competence Network for Diabetes mellitus’ funded by the Federal Ministry of Education and Research (FKZ 01KG0505). Trial registration Current controlled trials ISRCTN89333241. PMID:23915015

Lignes directrices canadiennes sur la rhinosinusite bactérienne aiguë

PubMed Central

Kaplan, Alan

2014-01-01

Résumé Objectif Faire un résumé clinique des lignes directrices canadiennes sur la rhinosinusite bactérienne aiguë (RSBA) qui présente des éléments d’intérêt pour les médecins de famille. Source des données Les auteurs des lignes directrices ont effectué une recherche documentaire systématique et ont rédigé des recommandations. Une cote a été donnée à la fois en fonction de la fiabilité des données probantes et de la solidité des recommandations. On a sollicité les commentaires d’experts en la matière venant de l’extérieur, ainsi que l’aval de sociétés médicales canadiennes (Association pour la microbiologie médicale et l’infectiologie Canada, Société canadienne d’allergie et d’immunologie clinique, Société canadienne d’otorhinolaryngologie et de chirurgie cervicofaciale, Association canadienne des médecins d’urgence et Regroupement canadien des médecins de famille en santé respiratoire). Message principal Le diagnostic de la RSBA repose sur la présence de symptômes particuliers et leur durée; l’imagerie ou une culture n’est pas nécessaire dans les cas peu compliqués. Le traitement dépend de la gravité des symptômes, notamment avec des corticostéroïdes intranasaux (CSIN) recommandés comme monothérapie pour les cas de légers à modérés, quoique leurs bienfaits soient modestes. Le recours à des CSIN accompagnés d’antibiotiques est réservé aux patients qui ne répondent pas aux CSIN après 72 heures et comme traitement initial des patients dont les symptômes sont graves. Le choix de l’antibiotique doit tenir compte du pathogène soupçonné, du risque de résistance, des problèmes concomitants et des tendances locales de la résistance aux antimicrobiens. Des thérapies d’appoint comme l’irrigation nasale avec une solution saline sont recommandées. En présence de cas réfractaires au traitement, d’épisodes récurrents et de signes de complications, on devrait demander une consultation en otorhinolaryngologie. Les lignes directrices portent sur les situations particulières à l’environnement canadien des soins de santé, y compris les actions à prendre durant les périodes d’attente prolongées pour avoir une consultation avec un spécialiste ou une imagerie. Conclusion Les lignes directrices canadiennes offrent des recommandations à jour pour le diagnostic et le traitement de la RSBA qui tiennent compte de la compréhension en évolution de la maladie. De plus, les lignes directrices présentent des outils utiles pour aider les cliniciens à cerner les épisodes viraux par opposition à ceux d’origine bactérienne, ainsi qu’à prendre en charge de manière optimale leurs patients atteints de RSBA.

Fluorescence optical imaging and musculoskeletal ultrasonography in juvenile idiopathic polyarticular disease before and during antirheumatic treatment - a multicenter non-interventional diagnostic evaluation.

PubMed

Klein, Ariane; Just, Georg Werner; Werner, Stephanie Gabriele; Oommen, Prasad T; Minden, Kirsten; Becker, Ingrid; Langer, Hans-Eckhard; Klee, Dirk; Horneff, Gerd

2017-06-30

Valid detection of inflamed joints is essential for correct classification, therapeutic decisions, prognosis and assessment of treatment efficacy in juvenile idiopathic arthritis (JIA). Fluorescence optical imaging (FOI) enables visualization of inflammation in arthritis of finger and hand joints and might be used for monitoring. A 24-week observational study in polyarticular JIA patients newly starting treatment with methotrexate or an approved biologic was performed in three centers. Patients were evaluated clinically, by gray-scale ultrasonography (GSUS), power-Doppler ultrasonography (PDUS) and FOI at baseline, week 12 and week 24. Of 37 patients enrolled, 24 patients started methotrexate and 13 patients a biologic for the first time (etanercept n = 11, adalimumab and tocilizumab n = 1 each). Mean JADAS 10 decreased significantly from 17.7 at baseline to 12.2 and 7.2 at week 12 and 24 respectively. PedACR 30/50/70/100 response rates at week 24 were 85%/73%/50%/27%. The total number of clinically active joints in hand and fingers at baseline/week 12/week 24 was 262 (23.6%)/162 (16.4%)/162 (9.0%). By GSUS, at baseline/week 12/week 24, 192 (19.4%)/135 (16.1%)/83 (11.5%) joints showed effusions and 186 (18.8%)/107 (12.7%)/69 (9.6%) showed synovial thickening, and by PDUS 68 (6.9%)/15 (1.8%)/36 (5%) joints showed hyperperfusion. Any sign of arthritis was detected by US in a total of 243 joints (24.5%) at baseline, 161 joints (19.2%) at week 12 and 123 joints (17%) at week 24. By FOI at baseline/week 12/week 24, 430 (38.7%)/280 (29.2%)/215 (27.6%) showed a signal enhancement in at least one phase. Summarizing all three points of time, the highest numbers of signals were detected by FOI with 32% of joints, especially in phase 2, while by US 20.7% and by clinical examination 17.5% of joints were active. A high number of joints (21.1%) had FOI signals but were inactive by clinical examination. A total 20.1% of joints with signals in FOI did not show effusion, synovial thickening or hyperperfusion by US. Because of the high number of negative results, specificity of FOI compared with clinical examination/US/PD was high (84-95%), and sensitivity was only moderate. FOI and US could detect clinical but also subclinical inflammation. FOI detected subclinical inflammation to a higher extent than US. Improvement upon treatment with either methotrexate or a biologic can be visualized by FOI and US. Deutsches Register Klinischer Studien DRKS00011579 . Registered 10 January 2017.

Vogt-Koyanagi-Harada disease: inquiry into the genesis of a disease name in the historical context of Switzerland and Japan.

PubMed

Herbort, Carl P; Mochizuki, Manabu

2007-01-01

To delineate the historical steps associated with the genesis of the name and the definition of Vogt-Koyanagi-Harada (VKH) disease. A bibliographical review of the major publications that were relevant to the original development of the name of the clinical entity known today as Vogt-Koyanagi-Harada disease, in the historical context of the early 20th century. Three distinct time periods can be considered to be important in terms of providing a historical perspective on VKH disease. Given that the cutaneous manifestations of VKH disease are so characteristic, these could not have been missed even before the actual clinical entity of VKH was recognized in the early 20th century. Indeed, several authors, including the Arabic doctor Mohammad-al-Ghâfiqî in the 12th century as well as Jacobi, Nettelship and Tay in the 19th century, described poliosis, neuralgias and hearing disorders. Many of these cases were probably due to sympathetic ophthalmia, but some were clearly VKH cases. The second phase is characterized by the surge of articles that appeared early in the 20th century that defined the disease more precisely. A number of these authors subsequently became associated with the disease name, the first being Alfred Vogt from Switzerland, followed by Japanese researchers. Yoshizo Koyanagi was in fact not the first Japanese author to describe the disease; this honor goes to the first Japanese Professor of Ophthalmology at the University of Tokyo, Dr. Jujiro Komoto, who published in a German language journal, Klinische Monatsblätter für Augenheilkunde in 1911. Yoshizo Koyanagi published his first report in the Nippon Ganka Gakkai Zasshi 3 years later, in 1914, but it was a much later article, one published in 1929, that definitively associated his name with the disease. In this review article, Koyanagi reported 16 cases, of which six were his own cases, that beautifully illustrate the natural course of the disease. In this same time period, Einosuke Harada, in an article published in Nippon Ganka Gakkai Zasshi in 1926 that was based on several case studies, comprehensively described a syndrome that included (1) a prodromal phase of malaise and meningeal irritation; (2) bilateral uveitis of diverse intensity; (3) bilateral retinal detachments spontaneously resolving; (4) integumentary changes; (5) lymphocytosis of the spinal fluid; (6) dysacousia. It is now accepted that Vogt-Koyanagi disease and the syndrome described by Harada are one entity with a diverse clinical spectrum bearing the universally accepted name of Vogt-Koyanagi-Harada disease. The third phase and most recent phase is characterized by the rapid progress made in terms of knowledge of the physiopathology of the disease, primarily due to the development of immunological methods. The evidence accumulated to date clearly points towards an autoimmune Th1 disease directed against proteins associated with choroidal melanin. Other analytical techniques, such as indocyanine green angiography, have enabled researchers to monitor more closely the primary lesional process at the level of the choroid, and standardized diagnostic criteria have been generated in the recent past. Those who earn scientific merit in clinical medicine are the ones who are able to visualize an overview based on the synthesis of 'new' medical facts that have been made available, usually reported singly by several, unassociated authors concomitantly. This is certainly the case for Yoshizo Koyanagi and Einosuke Harada. Conversely, Alfred Vogt was primarily lucky in that he encountered and subsequently precisely described the first case in the literature.

A lecithin phosphatidylserine and phosphatidic acid complex (PAS) reduces symptoms of the premenstrual syndrome (PMS): Results of a randomized, placebo-controlled, double-blind clinical trial.

PubMed

Schmidt, Katja; Weber, Nicole; Steiner, Meir; Meyer, Nadin; Dubberke, Anne; Rutenberg, David; Hellhammer, Juliane

2018-04-01

Many women experience emotional and physical symptoms around the time of ovulation and more so before menstruation interfering with their daily normal life also known as premenstrual syndrome (PMS). Recent observational data suggest that supplementation with Lipogen's phosphatidylserine (PS) and phosphatidic acid (PA) complex (PAS) alleviates these PMS symptoms. The aim of this study was to confirm these observations on the effects of PAS on PMS symptom severity within a controlled clinical trial setting. Forty women aged 18-45 years with a diagnosis of PMS were assigned to either take PAS (containing 400 mg PS & 400 mg PA per day) or a matching placebo. The study comprised 5 on-site visits including 1 baseline menstrual cycle followed by 3 treatment cycles. Treatment intake was controlled for by using an electronic device, the Medication Event Monitoring System (MEMS ® ). Primary outcome of the study was the PMS symptoms severity as assessed by using the Daily Record of Severity of Problems (DRSP). Further, SIPS questionnaire (a German version of the Premenstrual Symptoms Screening Tool (PSST)), salivary hormone levels (cortisol awakening response (CAR) and evening cortisol levels) as well as serum levels (cortisol, estradiol, progesterone and corticosteroid binding globulin (CBG)) were assessed. PMS symptoms as assessed by the DRSP Total score showed a significantly better improvement (p = 0.001) over a 3 cycles PAS intake as compared to placebo. In addition, PAS treated women reported a greater improvement in physical (p = 0.002) and depressive symptoms (p = 0.068). They also reported a lower reduction of productivity (p = 0.052) and a stronger decrease in interference with relationships with others (p = 0.099) compared to the placebo group. No other DRSP scale or item showed significant results. Likewise, the reduction in the number of subjects fulfilling PMS or premenstrual dysphoric disorder (PMDD) criteria as classified by the SIPS did not differ between the PAS and the placebo group. For the biomarkers, the salivary cortisol percentage increase of the CAR was significantly less pronounced in the follicular phase of cycle 4 than in the follicular phase of cycle 1 for subjects taking PAS when compared to subjects taking placebo (p = 0.018). Furthermore, the change of serum cortisol levels between visit 1 and visit 5 differed significantly between groups (p = 0.043). While serum cortisol levels of PAS treated females slightly decreased between visit 1 and visit 5, cortisol levels of females treated with placebo increased. For all other biomarkers, no treatment effects were observed over the 4 cycles study period. Overall, this study confirms that a daily intake of PAS, containing 400 mg PS and 400 mg PA, can be considered as safe. Results substantiate the efficacy of PAS in reducing symptoms of PMS. In view of the recent inclusion of severe PMS symptoms (PMDD) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the positive results of this clinical study merits consideration of developing the PAS complex as a botanical drug for treatment of PMDD. The study is registered at Deutsches Register Klinischer Studien with the registration number DRKS00009005. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

A new hydrogeological model of charging shallow and deep aquifers in the Lake Neusiedl - Seewinkel region (Northern Burgenland, Austria)

NASA Astrophysics Data System (ADS)

Häusler, Hermann; Müllegger, Christian; Körner, Wilfried; Ottner, Franz; Prohaska, Thomas; Irrgeher, Johanna; Tchaikovsky, Anastassiya; Dober, Gregor; Gritzmann, Romana; Mykhaylyuk, Ivanna

2014-05-01

The hypothesis of ascending thermal groundwater in the Seewinkel was introduced by Tauber (1965), favoured by Schmid (1970), and followed up by Wurm (2000). The main idea of this hypothesis was up welling of saline waters from a deep aquifer along faults, which in the 1950s have been identified as such in seismic sections. An aquifer of marine deposits of Badenian to Sarmatian age was postulated as source, and hydrochemical composition of water should have changed during migration due to high contents of sodium carbonate and sulphate instead of potassium chloride in the shallow groundwater bodies of the Seewinkel. Häusler (2010) argued, however, that fault aquifers discharging saline waters nowhere have been identified in this region. Supposed that according to the ascendance hypothesis ion composition of up welling formation water could have undergone a change, the primary isotope signal of marine water should have not. In order to get a better insight to the groundwater cycle we compare results from geochemical analyses, clay mineralogical analyses, and leachates of source rocks of potential recharge areas with respective analyses of shallow and deep aquifers, and apply the method of stable hydroisotopes such as oxygen, deuterium, strontium and chloride for distinguishing origin of groundwaters. We evaluate the hypothesis of up welling connate waters, and eventually come up with a new conceptual hydrogeological model for the Neusiedl-Seewinkel region regarding composition, origin, flow direction and residence time of groundwater in shallow and deeper aquifers. The very low value of -12.26‰ for oxygen isotope ratio of thermal groundwater from the deepest aquifer drilled to a depth of about 1000 metres at Frauenkirchen in northern Seewinkel, which is not highly mineralised, excludes connate water as major source, which basically is characterized by high oxygen isotope ratio values. Taking into account that oxygen isotope ratio-values ranging from -12.0‰ to -10.5‰ in the catchment of Lake Neusiedl are characteristic for waters derived from the cooler period of the Pleistocene (Rank et al., 1982), we conclude that groundwater of the deepest aquifer of the Seewinkel is not of Badenian to Sarmatian age but only several tens of thousands of years old. The artesian wells of the Seewinkel region drilled down to several hundreds of metres yielded groundwater with oxygen isotope ratio-values ranging between -11.90‰ and -10.83‰, values fitting well to waters of Pleistocene age of that region. Since wells discharging the Leitha Mountains also revealed oxygen isotope ratio-values varying from -11.10‰ to -10.22‰, we conclude that the mountain chains surrounding Lake Neusiedl basically charged both shallow and deeper aquifers of the Seewinkel. From oxygen isotope ratios of these groundwater bodies we therefore conclude that first the majority of aquifers of the Lake Neusiedl region was charged from the surrounding mountain chains, and second that salinity of soils in the Seewinkel region cannot be derived from up welling connate water, as has been proofed for Lake Kelemenszék area south of Budapest (Simon et al., 2011). There is no doubt on the fact, however, that differing amounts of free carbon dioxide in several aquifers of the Seewinkel region originate from deep-seated post volcanic activity in this region. Häusler, H. (2010)(ed.): Geologische Karte der Republik Österreich 1:50.000, Erläuterungen zur Geologischen Karte 78 Rust.- 191 S., 65 Abb., 5 Tab., 2 Taf., (Geologische Bundesanstalt), Wien. Rank, D., Rajner, V., Staudner, F. and Papesch, W. (1982): Zur Altersdatierung der Grundwässer am Ostufer des Neusiedlersees.- BFB-Bericht, 43, 197-204, 2 Abb., (Biologisches Forschungsinstitut für Burgenland), Illmitz. Simon, S., Mádl-Szőnyi, J., Müller, I. and Pogácsás, G. (2011): Conceptual model for surface salinization in an overpressured and a superimposed gravity-flow field, Lake Kelemenszék area, Hungary.- Hydrogeology Journal, 19, 701-717. Tauber, A. F. (1965): Geologische Typologie und Genese der Mineralquellen und Mineralwässer im Neusiedlerseegebiet.- Wissenschaftliche Arbeiten aus dem Burgenland, 34, 259-304, 6 Tab., Eisenstadt. Wurm, M. (2000): Hydrogeochemische Methodik zur Klärung von Interaktionsprozessen von Formations-, Mineral-, Tiefengrund- und oberflächennahen Grundwässern im Einzugsgebiet des Neusiedlersees.- Unveröffentlichte Diplomarbeit, Institut für Geowissenschaften, Abteilung für Geologie und Lagerstättenlehre, Montanuniversität Leoben, 125 S., zahlr. Abb., Anhang (71 hydrochemische Analysen), Leoben.

An open, self-controlled study on the efficacy of topical indoxacarb for eliminating fleas and clinical signs of flea-allergy dermatitis in client-owned dogs in Queensland, Australia

PubMed Central

Fisara, Petr; Sargent, Roger M; Shipstone, Michael; von Berky, Andrew; von Berky, Janet

2014-01-01

Background Canine flea-allergy dermatitis (FAD), a hypersensitivity response to antigenic material in the saliva of feeding fleas, occurs worldwide and remains a common presentation in companion animal veterinary practice despite widespread availability of effective systemic and topical flea-control products. Hypothesis/Objectives To evaluate the clinical response in dogs with FAD treated topically with indoxacarb, a novel oxadiazine insecticide. Animals Twenty-five client-owned dogs in Queensland, Australia diagnosed with pre-existing FAD on the basis of clinical signs, flea-antigen intradermal and serological tests. Methods An open-label, noncontrolled study, in which all dogs were treated with topical indoxacarb at 4 week intervals, three times over 12 weeks. Results Twenty-four dogs completed the study. Complete resolution of clinical signs of FAD was observed in 21 cases (87.5%), with nearly complete resolution or marked improvement in the remaining three cases. Mean clinical scores (Canine Atopic Dermatitis Extent and Severity Index-03) were reduced by 93.3% at week 12. Mean owner-assessed pruritus scores were reduced by 88% by week 12. Mean flea counts reduced by 98.7 and 100% in weeks 8 and 12, respectively. Conclusions and clinical importance Topical indoxacarb treatment applied every 4 weeks for 12 weeks, without concomitant antipruritic or ectoparasiticide therapy, completely alleviated flea infestations in all dogs and associated clinical signs of FAD in a high proportion of this population of dogs in a challenging flea-infestation environment. Résumé Contexte La dermatite par allergie aux piqures de puces (FAD), une hypersensibilité aux antigènes salivaires des puces, est décrite dans le monde entier et reste une présentation fréquente en médicine vétérinaire des animaux de compagnie malgré une large gamme d'antiparasitaires topiques et systémiques efficaces disponibles. Hypothèses/Objectifs Estimer la réponse clinique des chiens atteints de FAD recevant de l'indoxacarb topique, un nouvel insecticide de la classe des oxadiazines. Sujets Vingt cinq chiens de propriétaires du Queensland, Australie, précédemment diagnostiqués allergiques aux puces à partir des signes cliniques, des tests intradermiques et des tests sérologiques. Méthodes Une étude ouverte, non contrôlée, dans laquelle tous les chiens ont été traités avec de l'indoxacarb topique à 4 semaines d'intervalles, trois fois sur 12 semaines. Résultats Vingt quatre chiens ont été inclus dans l'étude. Une résolution complète des signes cliniques de FAD a été observée pour 21 cas (87.5%), ave une résolution presque complète ou une amélioration marquée pour les trois autres cas. Les scores cliniques moyens (Canine Atopic Dermatitis Extent and Severity Index-03) ont été réduits de 93.3% à la semaine 12. Les scores de prurit moyens ont été réduits de 88% à la semaine 12. Les comptages moyens de puce ont été réduits de 98.7% et 100% respectivement aux semaines 8 et 12. Conclusions et importance clinique Le traitement topique d'indoxacarb appliqué toutes les 4 semaines pendant 12 semaines, sans antiprurigineux ou ectoparasitaire concomitant, a complètement supprimé l'infestation de puces pour tous les chiens et les signes cliniques associés à la FAD pour une large proportion de cette population de chiens dans un environnement contenant des puces. Resumen Introducción la dermatitis alérgica a las pulgas en perros (FAD), es una respuesta de hipersensibilidad a material antigénico en la saliva de las pulgas que se alimentan en los perros. Ocurre a nivel mundial y aún permanece como una presentación común en los animales de compañía en las prácticas veterinarias, a pesar de la disponibilidad de efectivos tratamientos sistémicos y tópicos para el control de las pulgas. Hipótesis/Objetivos evaluar la respuesta clínica en perros con FAD tratados tópicamente con inoxacarb, novedoso insecticida de tipo oxadiacina. Animales 25 animales de propietarios particulares en Queensland, Australia, diagnosticados con FAD en base a los signos clínicos, y pruebas serológicas intradérmicas para el antígeno de las pulgas. Métodos se realizó un estudio abierto no controlado en el cual los perros fueron tratados con indoxacarb por vía tópica a intervalos de cuatro semanas, tres veces en el curso de 12 semanas. Resultados 24 perros completaron el estudio. La resolución completa de los signos clínicos de FAD fue observada en 21 casos (87,5%), con casi completa resolución o una marcada mejora en los restantes tres casos. El valor medio de evaluación clínica (índice de extensión y severidad de la dermatitis atópica canina-03) se redujo un 93,3% en la semana 12. Los valores medios de prurito evaluados por los propietarios se redujeron en un 88% en la semana 12 los recuentos medios de pulgas se redujeron un 98,7 y un 100% en las semanas 8 y 12, respectivamente. Conclusiones e importancia clínica el tratamiento tópico con indoxacarb aplicado cada cuatro semanas durante 12 semanas, sin tratamientos complementarios antipruriticos o terapia ectoparásiticida, alivian completamente la infestación por pulgas en todos los perros y los signos clínicos asociados con FAD en una alta proporción de esta población de perros en un ambiente con contacto con pulgas. Zusammenfassung Hintergrund Die Flohspeichelallergie des Hundes (FAD), bei der es sich um eine Hypersensibilitätsreaktion auf das Antigenmaterial im Speichel von saugenden Flöhen handelt, kommt weltweit vor und stellt einen häufigen Vorstellungsgrund in der Kleintierpraxis dar, obwohl weltweit wirksame systemische und topische Flohkontrollprodukte verfügbar sind. Hypothese/Ziele Eine Evaluierung der klinischen Antwort von Hunden mit FAD, die topisch mit Indoxacarb, einem neuen Oxadiazin Insektizid, behandelt worden waren. Tiere Fünfundzwanzig private Hunde in Queensland, Australien, die mit bereits existierender FAD basierend auf klinischer Symptomatik, positiven Intradermaltests und positiver Serologie auf Flohallergen diagnostiziert worden waren. Methoden Eine offene, nicht kontrollierte Studie, in der alle Hunde mit topischem Indoxacarb in 4 wöchigen Intervallen, drei Mal über einen Zeitraum von 12 Wochen behandelt wurden. Ergebnisse Vierundzwanzig Hunde beendeten die Studie. Eine gänzliche Abheilung der klinischen Anzeichen von FAD wurde in 21 Fällen beobachtet (87,5%), bei nahezu völligem Verschwinden oder einer deutlichen Verbesserung in den restlichen drei Fällen. Die durchschnittlichen klinischen Werte (Canine Atopic Dermatitis Extent and Severity Index-03) waren in der zwölften Woche um 93,3% reduziert. Die durchschnittlichen, von den BesitzerInnen beurteilten, Juckreizwerte waren in der zwölften Woche um 88% reduziert. Die durchschnittliche Anzahl an Flöhen war in den Wochen 8 und 12 um 97,7 bzw 100% reduziert. Schlussfolgerungen und klinische Bedeutung Indoxacarb, welches topisch alle 4 Wochen 12 Wochen lang ohne begleitende juckreizstillende Behandlung oder einer Behandlung von Ektoparasiten verabreicht wurde, milderte die Flohinfestationen bei allen Hunden und die mit FAD auftretenden klinischen Symptome in einer großen Proportion dieser Hundepopulation, die in einer schwierigen Umgebung mit hohem Flohvorkommen, lebten. PMID:24797425

Guideline on allergen-specific immunotherapy in IgE-mediated allergic diseases: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Society for Pediatric Allergy and Environmental Medicine (GPA), the Medical Association of German Allergologists (AeDA), the Austrian Society for Allergy and Immunology (ÖGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Dermatology (DDG), the German Society of Oto- Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), the German Society of Pediatrics and Adolescent Medicine (DGKJ), the Society for Pediatric Pneumology (GPP), the German Respiratory Society (DGP), the German Association of ENT Surgeons (BV-HNO), the Professional Federation of Paediatricians and Youth Doctors (BVKJ), the Federal Association of Pulmonologists (BDP) and the German Dermatologists Association (BVDD).

PubMed

Pfaar, Oliver; Bachert, Claus; Bufe, Albrecht; Buhl, Roland; Ebner, Christof; Eng, Peter; Friedrichs, Frank; Fuchs, Thomas; Hamelmann, Eckard; Hartwig-Bade, Doris; Hering, Thomas; Huttegger, Isidor; Jung, Kirsten; Klimek, Ludger; Kopp, Matthias Volkmar; Merk, Hans; Rabe, Uta; Saloga, Joachim; Schmid-Grendelmeier, Peter; Schuster, Antje; Schwerk, Nicolaus; Sitter, Helmut; Umpfenbach, Ulrich; Wedi, Bettina; Wöhrl, Stefan; Worm, Margitta; Kleine-Tebbe, Jörg; Kaul, Susanne; Schwalfenberg, Anja

The present guideline (S2k) on allergen-specific immunotherapy (AIT) was established by the German, Austrian and Swiss professional associations for allergy in consensus with the scientific specialist societies and professional associations in the fields of otolaryngology, dermatology and venereology, pediatric and adolescent medicine, pneumology as well as a German patient organization (German Allergy and Asthma Association; Deutscher Allergie- und Asthmabund, DAAB) according to the criteria of the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). AIT is a therapy with disease-modifying effects. By administering allergen extracts, specific blocking antibodies, toler-ance-inducing cells and mediators are activated. These prevent further exacerbation of the allergen-triggered immune response, block the specific immune response and attenuate the inflammatory response in tissue. Products for SCIT or SLIT cannot be compared at present due to their heterogeneous composition, nor can allergen concentrations given by different manufacturers be compared meaningfully due to the varying methods used to measure their active ingredients. Non-modified allergens are used for SCIT in the form of aqueous or physically adsorbed (depot) extracts, as well as chemically modified allergens (allergoids) as depot extracts. Allergen extracts for SLIT are used in the form of aqueous solutions or tablets. The clinical efficacy of AIT is measured using various scores as primary and secondary study endpoints. The EMA stipulates combined symptom and medication scores as primary endpoint. A harmonization of clinical endpoints, e. g., by using the combined symptom and medication scores (CSMS) recommended by the EAACI, is desirable in the future in order to permit the comparison of results from different studies. The current CONSORT recommendations from the ARIA/GA2LEN group specify standards for the evaluation, presentation and publication of study results. According to the Therapy allergen ordinance (TAV), preparations containing common allergen sources (pollen from grasses, birch, alder, hazel, house dust mites, as well as bee and wasp venom) need a marketing authorization in Germany. During the marketing authorization process, these preparations are examined regarding quality, safety and efficacy. In the opinion of the authors, authorized allergen preparations with documented efficacy and safety, or preparations tradeable under the TAV for which efficacy and safety have already been documented in clinical trials meeting WAO or EMA standards, should be preferentially used. Individual formulations (NPP) enable the prescription of rare allergen sources (e.g., pollen from ash, mugwort or ambrosia, mold Alternaria, animal allergens) for specific immunotherapy. Mixing these allergens with TAV allergens is not permitted. Allergic rhinitis and its associated co-morbidities (e. g., bronchial asthma) generate substantial direct and indirect costs. Treatment options, in particular AIT, are therefore evaluated using cost-benefit and cost-effectiveness analyses. From a long-term perspective, AIT is considered to be significantly more cost effective in allergic rhinitis and allergic asthma than pharmacotherapy, but is heavily dependent on patient compliance. Meta-analyses provide unequivocal evidence of the efficacy of SCIT and SLIT for certain allergen sources and age groups. Data from controlled studies differ in terms of scope, quality and dosing regimens and require product-specific evaluation. Therefore, evaluating individual preparations according to clearly defined criteria is recommended. A broad transfer of the efficacy of certain preparations to all preparations administered in the same way is not endorsed. The website of the German Society for Allergology and Clinical Immunology (www.dgaki.de/leitlinien/s2k-leitlinie-sit; DGAKI: Deutsche Gesellschaft für Allergologie und klinische Immunologie) provides tables with specific information on available products for AIT in Germany, Switzerland and Austria. The tables contain the number of clinical studies per product in adults and children, the year of market authorization, underlying scoring systems, number of randomized and analyzed subjects and the method of evaluation (ITT, FAS, PP), separately given for grass pollen, birch pollen and house dust mite allergens, and the status of approval for the conduct of clinical studies with these products. Strong evidence of the efficacy of SCIT in pollen allergy-induced allergic rhinoconjunctivitis in adulthood is well-documented in numerous trials and, in childhood and adolescence, in a few trials. Efficacy in house dust mite allergy is documented by a number of controlled trials in adults and few controlled trials in children. Only a few controlled trials, independent of age, are available for mold allergy (in particular Alternaria). With regard to animal dander allergies (primarily to cat allergens), only small studies, some with methodological deficiencies are available. Only a moderate and inconsistent therapeutic effect in atopic dermatitis has been observed in the quite heterogeneous studies conducted to date. SCIT has been well investigated for individual preparations in controlled bronchial asthma as defined by the Global Initiative for Asthma (GINA) 2007 and intermittent and mild persistent asthma (GINA 2005) and it is recommended as a treatment option, in addition to allergen avoidance and pharmacotherapy, provided there is a clear causal link between respiratory symptoms and the relevant allergen. The efficacy of SLIT in grass pollen-induced allergic rhinoconjunctivitis is extensively documented in adults and children, whilst its efficacy in tree pollen allergy has only been shown in adults. New controlled trials (some with high patient numbers) on house dust mite allergy provide evidence of efficacy of SLIT in adults. Compared with allergic rhinoconjunctivitis, there are only few studies on the efficacy of SLIT in allergic asthma. In this context, newer studies show an efficacy for SLIT on asthma symptoms in the subgroup of grass pollen allergic children, adolescents and adults with asthma and efficacy in primary house dust mite allergy-induced asthma in adolescents aged from 14 years and in adults. Aspects of secondary prevention, in particular the reduction of new sensitizations and reduced asthma risk, are important rationales for choosing to initiate treatment early in childhood and adolescence. In this context, those products for which the appropriate effects have been demonstrated should be considered. SCIT or SLIT with pollen or mite allergens can be performed in patients with allergic rhinoconjunctivitis using allergen extracts that have been proven to be effective in at least one double-blind placebo-controlled (DBPC) study. At present, clinical trials are underway for the indication in asthma due to house dust mite allergy, some of the results of which have already been published, whilst others are still awaited (see the DGAKI table "Approved/potentially completed studies" via www.dgaki.de/Leitlinien/s2k-Leitlinie-sit (according to www.clinicaltrialsregister.eu)). When establishing the indication for AIT, factors that favour clinical efficacy should be taken into consideration. Differences between SCIT and SLIT are to be considered primarily in terms of contraindications. In individual cases, AIT may be justifiably indicated despite the presence of contraindications. SCIT injections and the initiation of SLIT are performed by a physician experienced in this type of treatment and who is able to administer emergency treatment in the case of an allergic reaction. Patients must be fully informed about the procedure and risks of possible adverse events, and the details of this process must be documented (see "Treatment information sheet"; available as a handout via www.dgaki.de/Leitlinien/s2k-Leitlinie-sit). Treatment should be performed according to the manufacturer's product information leaflet. In cases where AIT is to be performed or continued by a different physician to the one who established the indication, close cooperation is required in order to ensure that treatment is implemented consistently and at low risk. In general, it is recommended that SCIT and SLIT should only be performed using preparations for which adequate proof of efficacy is available from clinical trials. Treatment adherence among AIT patients is lower than assumed by physicians, irrespective of the form of administration. Clearly, adherence is of vital importance for treatment success. Improving AIT adherence is one of the most important future goals, in order to ensure efficacy of the therapy. Severe, potentially life-threatening systemic reactions during SCIT are possible, but - providing all safety measures are adhered to - these events are very rare. Most adverse events are mild to moderate and can be treated well. Dose-dependent adverse local reactions occur frequently in the mouth and throat in SLIT. Systemic reactions have been described in SLIT, but are seen far less often than with SCIT. In terms of anaphylaxis and other severe systemic reactions, SLIT has a better safety profile than SCIT. The risk and effects of adverse systemic reactions in the setting of AIT can be effectively reduced by training of personnel, adhering to safety standards and prompt use of emergency measures, including early administration of i. m. epinephrine. Details on the acute management of anaphylactic reactions can be found in the current S2 guideline on anaphylaxis issued by the AWMF (S2-AWMF-LL Registry Number 061-025). AIT is undergoing some innovative developments in many areas (e. g., allergen characterization, new administration routes, adjuvants, faster and safer dose escalation protocols), some of which are already being investigated in clinical trials. Cite this as Pfaar O, Bachert C, Bufe A, Buhl R, Ebner C, Eng P, Friedrichs F, Fuchs T, Hamelmann E, Hartwig-Bade D, Hering T, Huttegger I, Jung K, Klimek L, Kopp MV, Merk H, Rabe U, Saloga J, Schmid-Grendelmeier P, Schuster A, Schwerk N, Sitter H, Umpfenbach U, Wedi B, Wöhrl S, Worm M, Kleine-Tebbe J. Guideline on allergen-specific immunotherapy in IgE-mediated allergic diseases - S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Society for Pediatric Allergy and Environmental Medicine (GPA), the Medical Association of German Allergologists (AeDA), the Austrian Society for Allergy and Immunology (ÖGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Dermatology (DDG), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), the German Society of Pediatrics and Adolescent Medicine (DGKJ), the Society for Pediatric Pneumology (GPP), the German Respiratory Society (DGP), the German Association of ENT Surgeons (BV-HNO), the Professional Federation of Paediatricians and Youth Doctors (BVKJ), the Federal Association of Pulmonologists (BDP) and the German Dermatologists Association (BVDD). Allergo J Int 2014;23:282-319.

IMP3 can predict aggressive behaviour of lung adenocarcinoma

PubMed Central

2012-01-01

Background Lung cancer most often presents as an inoperable tumour and the diagnosis is usually performed on a small biopsy/cytology specimen. In the group of non small cell lung cancer - not otherwise specified, adenocarcinoma phenotype can be determined immunohistochemically using TTF-1 and Napsin A. Expression of oncofetal protein IMP3 in human cancer is associated with poor differentiation and aggressive behaviour. In the present study expression of IMP3 was correlated with expression of TTF-1 and Napsin A, histological subtype and clinical stage of lung adenocarcinoma. We were interested whether distant metastases are associated with IMP3 overexpression, regardless of the histologic subtype of adenocarcinoma. Methods In retrospective study, consecutive series of 105 patients with advanced lung adenocarcinoma diagnosed from 2006 to 2009 in Clinical Hospital Center Split, Croatia, were analysed. Clinical data were collected from the Pulmology Department and time of death from the Mortality Registry. Paraffin blocks of bronchoscopic biopsies were collected from the Institute of Pathology and 15 cases excluded from the analysis due to insufficient material. Expression of IMP3, Napsin A and TTF-1 were analysed by indirect enzyme immunohistochemistry. Statistical analysis was performed and P values less than 0.05 considered significant. Results Of 90 patients, 71 (78%) were males and 19 (22%) females. Median age for males was 61.5 years (min-max 43–83) and for females 61 years (min-max 44–86). Pleural effusion was found in 15 (16.6%) and distant metastases in 45 (50%) cases. According to histological subtypes, there were 34 acinar, 2 lepidic, 2 papillary and 52 solid subtypes. IMP3 overexpression was found in 63 cases (70%) and was correlated with solid subtype (P = 0.002) and negative/weak Napsin A expression (P = 0.004). Strong Napsin A expression correlated with TTF-1 expression (P = 0.003) and lower histological grades (P = 0.031). Patients with IMP3 overexpression more often had distant metastases than patients with negative IMP3, 55.5% versus 33.3% (P = 0.033). Non solid subtypes with IMP3 overexpression developed distant metastasis more common than non solid subtypes with negative IMP3, 72% versus 35% (P = 0.028). Conclusions Expression of IMP3 correlates with solid subtype and with distant metastases regardless of histological subtype of lung adenocarcinoma. Virtual slides http://www.diagnosticpathology.diagnomx.eu/vs/1966211581795258 Zusammenfassung Hintergrund Das Lungenkarzinom kommt meistens als nicht resektabler Tumor vor und die Diagnose kann nur in kleinen Biopsaten oder zytologisch gestellt werden. In der Gruppe der nicht kleinzelligen Lungenkarzinome kann der nicht anders spezifizierte Adenokarzinom Phänotyp mit Hilfe der Antikörper TTF-1 und Napsin A diagnostiziert werden. Die Expression des onkoföetalen Proteins IMP3 ist bei humanen Karzinomen mit agressivem Verhalten und metastatischem Potential verbunden. In dieser Studie korreliert die Expression von IMP3 mit TTF-1, Napsin A, histologischem Typ und klinischem Staging des Lungenkarzinoms. Wir waren daran interessiert, ob Fernmetastasen mit IMP3 Überexpression assoziiert sind, unabhängig von der histologischen Subtyp von Adenokarzinom. Methode In der retrospektiven Studie wurden die von 2006 bis 2009 im Klinischem Krankenhaus Split, Kroatien diagnostizerte Adenokarzinome der Lunge von 105 Patienten analysiert. Die klinischen Daten stammten aus der Abteilung für Pulmologie und im Falle des Todes vom Todesregister. Die Paraffinblöcke der primären Lungenbiopsate dieser Patienten wurden im Institut für Pathologie mit der indirekter Enzym - Immunohistochemie mittels Kombination der Antikörper gegen IMP3, Napsin A und TTF1 untersucht. 15 Fälle aus der Analyse aufgrund unzureichender Material ausgeschlossen. Es wurde eine statistische Untersuchung durchgeführt und Werte weniger als 0.05 P wurden als statistisch signifikant bezeichnet. Ergebnisse Von 90 Patienten mit Lungencarcinom waren 71 (78%) mänlich, durchschnittliches Alter war für Männer 61.5 Jahre (min-max 43–83) und 61 Jahre für Frauen (min-max 44–86). Pleurale Effusionen fand man in 15 Fällen (16.6%) und Fernmetastasen in 45 (50%) Fällen. Histologische Sybtypen waren: 2 lepidic Karzinome, 34 azinäre Karzinome, 2 papilläre und 52 solide Karzinome. IMP3 war exprimiert in 63 Fälle (70%). Positive IMP3 Expression war mit solidem Typ (P = 0.002) und negativer Napsin A Expression (P = 0.004) assoziert. Napsin A Expression war mit niedrigem Gradus (P = 0.031) und positiver TTF-1 Expression (P = 0.003) assoziert. Patienten mit IMP3 Überexpression öfter hatten Fernmetastasen als Patienten mit negativen IMP3, 55.5% versus 33.3% (P = 0.033). Non solide Subtyp mit IMP3 Überexpression entwickelten Fernmetastasen Meer häufiger als nicht festem Subtyp mit negativen IMP3, 72% versus 35% (P = 0.028). Schlussworte Die Expression von IMP3 ist mit negaativer Expression von Napsin A, solidem Subtyp und Metastasen verbunden und hat praktische predictive Werte in der pathologischen Diagnose des Adenokarzinoms der Lunge. Die Expression von IMP3 korreliert mit soliden Subtyp und mit Fernmetastasen unabhängig von histologische Subtyp Lungenadenokarzinom. PMID:23190601

A new approach to the study of therapeutic work in the transference.

PubMed

Pessier, J; Stuart, J

2000-02-01

This article proposes a new method for evaluating the effects of therapist and patient work in the transference. Work in the transference is often difficult for the patient, and may show a characteristic pattern of lag between a transference interpretation and its therapeutic effect. To account for this lag, we assessed patient responses to interpretations over the course of entire sessions. The narratives patients told about others, or Relationship Episodes (REs), were used as units of study. In a sample of three consecutive sessions taken from each of three psychodynamic cases, we identified several instances when transference work appeared to have an initial inhibitory effect, but facilitated progress over the course of the entire session. We recommend that to examine the effects of interpretations future studies use longer, more clinically meaningful segments of patient speech than have been used in the past. Dieser Beitrag propagiert eine neue Methode zur Evaluierung der Effekte von Übertragungsarbeit durch Therapeut und Patient. Arbeit in der Übertragung ist für den Patienten oftmals schwierig und zeigt häufig eine charakteristisches Muster von zeitlichen Verzögerungen bzgl. Übertragungsdeutungen und deren therapeutischen Effekten. Um diese zeitliche Verzögerung zu erklären, untersuchten wir die Reaktionen von Patienten auf derartige Deutungen im Verlauf ganzer Sitzungen. Narrative, in denen die Patienten über andere berichteten, also Beziehungsepisoden, dienten in dieser Studie als Einheit. In einter Stichprobe dreier aufeinanderfolgender Sitzugnen, die sich auf drei Fälle bezogen, identifizierten wir verschiedene Umstände, unter denen Übertragungsarbeit anfänglich einen hemmenden Affekt zu haben schien, letztlich aber den Gesamtverlauf der Sitzung günstig beeinflussten. Wir empfehlen, in Zukunft die Effekte von Übertragungsdeutungen auf der Basis längerer, klinische sinnvoller Segmente von Patientenäußerungen zu untersuchen als dies in der Vergangenheit der Fall war. Cet article propose une nouvelle méthode pour évaluer les effets du travail sur le transfert entre thérapeute et patient. Ce travail est souvent difficile pour le patient, et il peut y avoir un pattern caractéristique de délai entre une înterprétation de transfert et son effet thérapeutique. Pour expliquer ce délai, nous avons évalué les réponses des patients à des interprétatios au cours de séances entières. C'est les narrations des patients sur d'autres, ou Episodes Relationnels (ERs), qui ont constitué les unités de base de cette étude. Dans un échantillon de 3 séances consécutives venant de 3 cas psychodynamiques, nous avons identifié plusieurs moments où le traail sur le transfert semblait avoir un effet inhibitoire initial, mais favorisait le progrès en regardant la séance entière. Nous recommandons pour de futures études sur l'effet des interprétations de prendre des segments plus longs et cliniquement significatifs du récit du patient que ceux utilisés dans le passé. Este artículo propone un nuevo método para evaluar los efectos del trabajo de terapeuta y paciente en la transferencia. El trabajo en la transferencia es, con frecuencia, dificil para el paciente y puede mostrar un lapso característico entre una interpretación transferencial y sus efectos terapéuticos. Para explicar este lapso, hemos evaluado las respuestas del paciente a las interpretaciones a lo largo de sesiones enteras. Como unidad de estudio se usaron las narrativas de los pacientes acerca de otros, o sea, los episodios relacionales (REs). En una muestra de tres sesiones consecutivas tomadas de tres casos psicodinámicos, identificamos varioss casos en los que la trasferencia parecía tener un efecto inicial inhibitorio, aunque se vio que a lo largo de la sesión facilitaba el progreso. Recomendamos que, para examinar los efectos de las interpretaciones, los futuros estudios usen segmentos más largos y clínicamente más significativos del habia del paciente que los que se usaron en el pasado.

The effects of training in time-limited dynamic psychotherapy: changes in therapeutic outcome.

PubMed

Bein, E; Anderson, T; Strupp, H; Henry, W; Schacht, T; Binder, J; Butler, S

2000-02-01

The present study explored the effects on therapeutic outcomes of training therapists in brief manualized therapy. As part of the Vanderbilt II project, each of 16 therapists (8 psychiatrists and 8 clinical psychologists) treated 2 moderately disturbed adult patients using his or her customary short-term treatment methods; they then received a year of training in a manualized form of brief dynamic therapy, Time-Limited Dynamic Psychotherapy (TLDP); finally, they administered TLDP to 2 additional patients. It was hypothesized that training would result in improved outcomes generally and that differentially greater improvement would be seen in patients commonly considered less suitable for brief dynamic therapy. Outcome data obtained at termination failed to support either hypothesis. Measurements of interpersonal dependency obtained at a one-year follow-up were consistent with the first hypothesis, but the follow-up data were inconsistent with the second. A systematic review of the 32 posttraining cases suggested that the majority of the therapists had not achieved basic competence at TLDP. Die hier beschriebene Studie untersucht die Wirkungen eines Trainings in manualisierter Kurzzeitherapie auf das Therapierergebnis. Als Teil des Vanderbilt II Projektes behandelten jeweils 16 Therapeuten (8 Psychiater und 8 klinische Psychologen) zwei mittelgradig beeinrächtigte erwachsene Patienten mit den ihnen vertrauten Kurzzeitbehandlungsmethoden. Danach wurden sie über ein Jahr in einer manualisierten Form psychodynamischer Kurzzeittherapie ausgebildet und wandten diese Therapie auf zwei weitere Patienten an. Es wurde angenommen, dass die Ausbildung in besseren Ergebnisdaten, die bei Ende der Therapie erhoben wurden, konnten diese Hypothese nicht bestätigen. Maße für die interpersonale Abhängigkeit zu einem Einjahreskatamnesezeitpunkt waren mit der ersten Hypothese konform, aber inkonsistent mit der zweiten. Eine systematische Untersuchung der 32 nach der Ausbildung behandelten Fälle legt nahe, dass die Mehrzahl der Therapeuten keine grundlegende Kompetenz in zeitlich limitierter dynamischer Psychotherapie erworben hatte. Cette éude explore les effets sur les résultats thérapeutiques de la formation des thérapeutes dans une thérapie brève, manualissée. Dans le cadre du projet Vanderbilt II, chacun des 16 thérapeutes (8 psychiatrs et 8 psychologues cliniciens) a traité deux patients adultes modérément perturbés, chacun par sa méthode habituelle de thérapie brève; ensuite ils ont reçu une formation d'une année dans une méthode manualisée de thérapie brève, la Psychothérapie Dynamique Limitée dans le Temps (TLDP); pour finir, ils ont appliqué la TLDP à de meilleurs résultats en général, et qu'une amélioration comparativement plus importante sera observée chez des patients habituellement considérés comme moins adaptés à une thérapie dynamique brè. Les résultats obtenus à la terminaison n'ont pu confirmer aucune de ces hypothèses. Des mesures de la dépendance interpersonnelle une année après étaient consistantes avec la première hypothèse, mais les données catamnestiques étaient inconsistantes avec la deuxième. Une revue systématique des 32 cas après formation a suggéré que la majorité des thérapeutes n'avait pas acquis une compétence de base en TLDP. Este estudio exploró la efectividad del entrenamiento de terapeutas en una terapia breve manualizada. Como parte del proyecto Vanderbilt II, dieciséis terapeutas (ocho psiquiatras y ocho psicólogos clínicos) trataron dos pacientes adultos mooderadamente perturbados con sus métodos habituales de tratamiento a corto plazo. Estos terapeutas recibieron luego un año de entrenamiento en terapia dinámica breve manualizada que se Ilamó Psicoterapia Dinámica de Tiempo limitado (TLDP). Finalmente, administraron esta TLDP a dos pacientes más. La hipótesis fue que el entrenamiento ilevaría, en general, a resultados mejores y que habría mayor mejoramiento en pacientes menos aptos para una terapia dinámica breve. Los resultados a la terminación no apoyaron ninguna de las dos hipótesis. Las mediciones de dependencia interpersonal al año de seguimiento resultaron consistentes con la primera hipótesis, mientras que los resultados de seguimiento fueron inconsistentes con la segunda. Una revisión sistemática de los treinta y dos casos luego del entrenamiento sugiere que la mayoría de los terapeutas no había l.

The effects of topical mesenchymal stem cell transplantation in canine experimental cutaneous wounds

PubMed Central

Kim, Ju-Won; Lee, Jong-Hwan; Lyoo, Young S; Jung, Dong-In; Park, Hee-Myung

2013-01-01

Background Adult stem cells have been widely investigated in bioengineering approaches for tissue repair therapy. We evaluated the clinical value and safety of the application of cultured bone marrow-derived allogenic mesenchymal stem cells (MSCs) for treating skin wounds in a canine model. Hypothesis Topical allogenic MSC transplantation can accelerate the closure of experimental full-thickness cutaneous wounds and attenuate local inflammation. Animals Adult healthy beagle dogs (n = 10; 3–6 years old; 7.2–13.1 kg) were studied. Methods Full-thickness skin wounds were created on the dorsum of healthy beagles, and allogenic MSCs were injected intradermally. The rate of wound closure and the degree of collagen production were analysed histologically using haematoxylin and eosin staining and trichrome staining. The degree of cellular proliferation and angiogenesis was evaluated by immunocytochemistry using proliferating cell nuclear antigen-, vimentin- and α-smooth muscle actin-specific antibodies. Local mRNA expression levels of interleukin-2, interferon-γ, basic fibroblast growth factor and matrix metalloproteinase-2 were evaluated by RT-PCR. Results Compared with the vehicle-treated wounds, MSC-treated wounds showed more rapid wound closure and increased collagen synthesis, cellular proliferation and angiogenesis. Moreover, MSC-treated wounds showed decreased expression of pro-inflammatory cytokines (interleukin-2 and interferon-γ) and wound healing-related factors (basic fibroblast growth factor and matrix metalloproteinase-2). Conclusion and clinical importance Topical transplantation of MSCs results in paracrine effects on cellular proliferation and angiogenesis, as well as modulation of local mRNA expression of several factors related to cutaneous wound healing. Résumé Contexte Les cellules souches adultes ont été largement étudiées dans les approches de bio-ingénierie pour la thérapie de réparation tissulaire. Nous évaluons l'efficacité clinique et la sécurité de l'application de cellules souches mésenchymateuses allogéniques en culture dérivées de moelle osseuse (MSCs) pour le traitement de plaies cutanées dans un modèle canin. Hypothèse La transplantation de MSC allogénique topique peut accélérer la fermeture en toute épaisseur de plaies cutanées expérimentales et atténuer l'inflammation locale. Sujets Des chiens beagles adultes sains (n = 10; 3–6 ans; 7.2–13.1 kg) ont été étudiés. Méthodes Des plaies cutanées en pleine épaisseur ont été crées sur la face dorsale des beagles sains et des MSCs allogènes ont été injectées par voie intradermique. Le taux de cicatrisation et le degré de production de collagène ont été analysés sur le plan histologique par colorations à l'hématoxyline et éosine et par trichrome. Le degré de prolifération cellulaire et d'angiogénèse ont été évalués par immunohistochimie à l'aide d'anticorps spécifiques d'antigène nucléaire de prolifération cellulaire, de vimentine et d'actine de muscle lisse α. Les taux d'expression local d'ARNm d'interleukine-2, d'interféron-γ, du facteur de croissance basique de fibroblaste et de métalloprotéinase-2 de matrice, ont été évalués par RT-PCR. Résultats Comparé avec les plaies traitées par excipient, les plaies traitées par les MSCs ont montré une plus rapide cicatrisation et une augmentation de synthèse de collagène, de prolifération cellulaire er d'angiogénèse. En outre, Les plaies traitées au MSC ont montré une expression diminuée de cytokines pro-inflammatoires (interleukine-2 et interféron-γ) et des facteurs liés à la cicatrisation (facteur de croissance basique de fibroblaste et métalloprotéinase-2 de matrice). Conclusion et importance clinique La transplantation topique de MSCs résulte en des effets paracrines de prolifération cellulaire et d'angiogénèse ainsi qu'en une modulation de l'expression locale d'ARNm de plusieurs facteurs liés à la cicatrisation cutanée. Resumen Introducción Las células madre de adultos se han estudiado extensivamente en estrategias de bioingeniería para la reparación de tejidos. Hemos evaluado el valor clínico y la seguridad de la aplicación de células madre mesenquimales (MSCs) alogenéicas derivadas de la medula ósea para tratar las heridas de la piel en un modelo canino. Hipótesis El transplante tópico alogenéico de MSCs puede acelerar la cicatrización de heridas cutáneas experimentales de todo el grosor de la piel y disminuir la inflamación local. Animales Se estudiaron perros de raza Beagle sanos adultos (n=10; de 3-6 años de edad; 7,2-13,1 kg de peso). Métodos Se crearon heridas de todo el grosor de la piel en el dorso de perros Beagle sanos, y se inyectaron MSCs alogenéicas intradérmicamente. El ritmo de reparación de la herida y el grado de producción de colágeno se analizaron histológicamente utilizando tinciones de hematoxilina-eosina y tricrómico. El grado de proliferación celular y la angiogenesis se evaluaron mediante inmunohistoquímica utilizando anticuerpos específicos para el antígeno de proliferación celular nuclear (PCNA), vimentina y α-actina de músculo liso. La expresión local de mRNA para interleuquina-2 (IL-2), interferón- γ (IFN- γ), factor básico de crecimiento de fibroblastos (BFGF) y metaloproteinasa de matriz-2 se evaluaron mediante RT-PCR. Resultados comparado con las heridas tratadas solo con el vehículo, las heridas tratadas con MSCs mostraron una reparación más rápida y un aumento en la producción de colágeno, proliferación celular y angiogenesis. Además, las heridas tratadas con MSCs mostraron una expresión aumentada de citoquinas proinflamatorias (IL-2 e IFN- γ) y factores relacionados con la reparación de la herida (BFGF y metaloproteinasa de matriz-2). Conclusión e importancia clínica El transplante tópico de MSCs resulta en efectos paracrinos en la proliferación celular y angiogenesis, así como en la modulación de la expresión de mRNA de diversos factores relacionados con la cicatrización de heridas. Zusammenfassung Hintergrund Adulte Stammzellen sind für ihre biotechnologische Verwendung bei der Wiederherstellung von Geweben bereits weit reichend erforscht. Wir haben die klinische Bedeutung und Sicherheit der Applikation von kultivierten allogenen mesenchymalen Stammzellen (MSCs) aus dem Knochenmark zur Behandlung von Hautwunden in einem caninen Modell evaluiert. Hypothese Die topische allogene MSC Transplantation kann den Wundverschluss experimenteller Hautwunden (Brandwunden Grad III) beschleunigen und die lokale Entzündung mildern. Tiere Erwachsene gesunde Beagles (n=10; 3-6 Jahre alt; 7,2-13,1kg) wurden in der Studie verwendet. Methoden Es wurden Hautwunden 3. Grades am Rücken der gesunden Beagles verursacht und allogene MSCs intradermal injiziert. Die Schnelligkeit des Wundverschlusses und das Ausmaß der Kollagenproduktion wurden histologisch mittels Hämatoxylin und Eosin Färbung und Trichromfärbung untersucht. Das Ausmaß der zellulären Proliferation und der Angiogenese wurde mittels Immunzytochemie unter Verwendung von Proliferating-Cell-Nuclear-Antigen, Vimentin und Alpha Smooth Muscle Actin-spezifischen Antikörpern evaluiert. Die lokale Exprimierung von mRNA von Interleukin-2, Interferon-γ, Basic Fibroblasten Wachstumsfaktor und Matrix Metalloproteinase-2 wurde mittels RT PCR evaluiert. Ergebnisse Im Vergleich zu den Wunden, die nur mit dem Trägermedium behandelt worden waren, zeigten die mit MSC-behandelten Wunden einen rascheren Verschluss und eine erhöhte Kollagensynthese, zelluläre Proliferation und Angiogenese. Darüber hinaus zeigten MSC-behandelte Wunden eine verminderte Exprimierung pro-entzündlicher Zytokine (Interleukin-2 und Interferon-γ) und Wundheilungsfaktoren (Basic Fibroblasten Wachstumsfaktor und Matrix Metalloproteinase-2). Schlussfolgerung und klinische Bedeutung Die topische Transplantation von MSCs resultiert in parakrinen Effekten auf die zelluläre Proliferation und Angiogenese sowie die Modulierung lokaler mRNA Exprimierung verschiedener Faktoren, die mit der Wundheilung der Haut im Zusammenhang stehen. 摘要 背景 以成体干细胞的生物工程法用于组织修复治疗已被广泛研究。将骨髓培养得到的外源性间充质干细胞(MSCs)用于犬模型上治疗皮肤创伤,我们来评估其临床价值和安全性。 假设 局部外源性MSC移植能使试验的皮肤创口全层愈合加快,并使局部炎症减轻。 动物 研究成年健康比格犬(n = 10;3–6 岁;7.2–13.1 kg)。 方法 在健康的比格犬背部创造全层皮肤创口,皮内注射外源性MSCs。使用苏木精和伊红染色法和三色染色法,从组织结构上分析伤口愈合率和胶原产生的程度。通过免疫细胞化学使用增殖细胞核抗原、维生素和α-平滑肌肌动蛋白-特定抗体,评估细胞增殖和血管生成程度。通过RT PCR评估白介素-2、γ-干扰素、基纤维母细胞生长因子和基质金属蛋白酶-2局部mRNA表达等级。 结果 与媒介物治疗创口相比,MSC治疗创口显示出更快的创口愈合,以及胶原合成、细胞增殖和血管生成增加。 此外,MSC治疗创口显示出炎性细胞因子(白介素-2和γ-干扰素)和与创口愈合相关因子(碱性成纤维细胞生长因子和基质金属蛋白酶-2)表达减少。 结论和临床价值 局部移植MSCs造成了对细胞增殖和血管生成的旁分泌作用,也同样引起几个与皮肤创伤愈合相关因子局部mRNA表达的调节。 要約 背景 成熟した幹細胞は組織修復療法に対して生物工学的なアプローチで広く研究されている。著者らは培養した骨髄由来の同種異系の間葉系肝細胞(MSCs)を犬の皮膚創傷の治療に応用し、臨床的な価値と安全性を評価した。 仮説 同種異系MSCの局所への移植は実験的な皮膚全層創傷の閉鎖と炎症の軽減を加速する可能性がある。 供与動物 成熟した健常ビーグル犬(n = 10; 3–6 歳齢; 7.2–13.1 kg)を用いた。 方法 健常ビーグルの背部に皮膚全層潰瘍を作成し、同種異系MSCを皮内に注射した。創傷閉鎖率とコラーゲン産生度をヘマトキシリン染色トリクローム染色を用いて組織学的に解析した。細胞増殖度と血管新生は核内増殖抗原−、ビメンチン−、α−平滑筋アクチン−特異的抗体を用いて免疫組織化学染色で評価した。局所のインターロイキン−2、インターフェロンγ、塩基性線維芽細胞増殖因子とマトリックスメタロプロテアーゼ2のmRNA発現レベルをRT-PCRで評価した。 結果 賦形剤のみで治療した創傷と比較し、MSCで治療した創傷はより早期に閉鎖し、コラーゲン合成の増加、細胞増殖や血管新生を示した。さらに、MSCで治療した創傷は炎症後サイトカイン(インターロイキン−2とインターフェロン−γ)と創傷治癒関連因子(塩基性線維芽細胞増殖因子とマトリックスメタロプロテアーゼ−2)の発現が減少していた。 結論と臨床的な重要性 MSCの局所への移植により細胞増殖と血管新生に対してはパラクライン効果を示すのと同時に,皮膚創傷治癒に関連する様々な因子の局所mRNA発現を調節した。 PMID:23432413

A pilot study of the efficacy of wipes containing chlorhexidine 0.3%, climbazole 0.5% and Tris-EDTA to reduce Malassezia pachydermatis populations on canine skin

PubMed Central

Cavana, Paola; Peano, Andrea; Petit, Jean-Yanique; Tizzani, Paolo; Perrot, Sébastien; Bensignor, Emmanuel; Guillot, Jacques

2015-01-01

Background Wipes containing chlorhexidine and azole derivates have been recommended for veterinary use. No study has been published about their activity against Malassezia pachydermatis. Hypothesis/Objectives To evaluate the in vivo and in vitro activity of wipes soaked in a chlorhexidine, climbazole and Tris-EDTA solution against Malassezia pachydermatis. Animals Five research colony shar-pei dogs. Methods Wipes were applied once daily onto the left axilla, left groin and perianal area (protocol A), and twice daily on the right axilla, right groin and umbilical region (protocol B) for 3 days. In vivo activity was evaluated by quantifying Malassezia colonies through contact plates on the selected body areas before and after wipe application. The activity of the solution in which the wipes were soaked was assessed in vitro by contact tests following the European Standard UNI EN 1275 guidelines. Results Samples collected after wipe application showed a significant and rapid reduction of Malassezia yeast CFU. No significant difference in the Malassezia reduction was found between protocols A and B. In vitro assay showed 100% activity against Malassezia yeasts after a 15 min contact time with the wipe solution. Conclusions and clinical importance Wipes containing chlorhexidine, climbazole and Tris-EDTA substantially reduced the M. pachydermatis population on the skin of dogs. The results, although this was an uncontrolled study performed on a small number of dogs, suggest that these wipes may be useful for topical therapy of Malassezia dermatitis involving the lips, paws, perianal area and skin folds. Résumé Contexte Des lingettes contenant de la chlorhexidine et des dérivésazolés ont été recommandés en médicine vétérinaire. Aucune étude n'a été publiée sur leur activité contre Malassezia pachydermatis. Hypothèses/Objectifs Evaluer l'activité in vivo et in vitro de lingettes imprégnées d'une solution de chlorhexidine, climbazole et Tris-EDTA contre Malassezia pachydermatis. Sujets Cinq colonies de shar-pei de recherche. Méthodes Les lingettes ont été appliquées une fois par jour au niveau du pli axillaire gauche, le pli inguinal droit et de la zone périanale(protocole A) et deux fois par joursur le pli axillaire droit, le inguinal droit et l'ombilic (protocole B) pendant 3 jours. L'activité in vivo a été évaluée par quantification des colonies de Malassezia par disques de contact sur les zones corporelles choisies avant et après application des lingettes. L'activité de la solution d'imprégnation des lingettes a été testée in vitro par tests de contact suivant les recommandations de l'European Standard UNI EN 1275. Résultats Les échantillons prélevés après application ont montré une diminution importante et rapide des CFU des levures Malassezia. Aucune différence significative dans la diminution des Malassezia n'a été mise en évidence entre les protocoles A et B. Des tests in vitro ont montré 100% d'activité contre les Malassezia après un temps de contact de 15 minutes avec la solution des lingettes. Conclusions et importance Clinique Les lingettes contenant la chlorhexidine, le climbazole et le Tris-EDTA réduisent substantiellement la population de M. pachydermatis sur la peau des chiens. Les résultats, bien qu'il s'agisse d'une étude non contrôlée réalisée sur un faible nombre de chiens, suggère que ces lingettes peuvent être utiles en traitement local de la dermatite à Malassezia des lèvres, des pattes, du périnée et des plis cutanés. Resumen Introducción las gasas que contienen clorhexidina y derivados de azol son recomendadas para uso veterinario. No se ha publicado ningún estudio acerca su actividad contra Malassezia paquidermatis. Hipótesis/Objetivos evaluar la actividad in vivo e in vitro de las gasas con clorhexidina, climbazol y soluciónb Tris-EDTA frente a Malassezia pachydermatis Animales cinco colonias de investigación de perros Sharpei. Métodos las gasas se aplicaron una vez al día en la axila izquierda, zona inguinal izquierda, y zona perianal (protocolo A), y dos veces al día en la axila derecha, zona inguinal derecha, y región umbilical (protocolo B) durante tres días. La actividad in vivo se evaluó mediante cuantificación de las colonias de Malassezia en placas de contacto de zonas seleccionadas del cuerpo antes y después de la aplicación de las gasas. La actividad de la solución en las que las gasas se empaparon se evaluó in vitro mediante pruebas de contacto siguiendo los estándares europeos UNI EN 1275. Resultados las muestras recogidas tras la aplicación de las gasas mostraron una reacción rápida y significativa de las colonias de Malassezia. No hubo significativas en la reducción de Malassezia en los dos protocolos. El ensayo in vitro demostró una actividad del 100% frente a Malassezia tras 15 minutos de contacto con la solución de las gasas. Conclusiones e importancia clínica las gasas que contienen clorhexidina, climbazol y Tris-EDTA reducen sustancialmente la población de Malassezia paquidermatis en la piel de perros. Aunque este era un estudio no controlado y desarrollado en un pequeño número de perros, los resultados sugieren que estas gasas pueden ser útiles para la terapia tópica de dermatitis producida por Malassezia en zonas de los labios, almohadillas plantares, y zonas perianales y pliegues de la piel. Zusammenfassung Hintergrund Feuchttücher, die Chlorhexidinund Azolderivate beinhalten, werden für den veterinärmedizinischen Gebrauch empfohlen. Es gibt keine Studie über ihre Wirkung im Einsatz gegen Malasseziapachydermatis. Hypothese/Ziele Eine Evaluierung der in vivo und der in vitro Aktivität dieser Feuchttücher in einer Chlorhexidin, Climbazol und Tris-EDTA Lösung gegen Malasseziapachydermatis. Tiere Fünf Shar-Peis aus einer Versuchstierkolonie. Methoden Die Feuchttücher wurden einmal täglich in der linken Achsel, in der linken Inguinalgegend und perianal (Protokol A) angewendet, und zweimal täglich in der rechten Achsel, in der rechten Inguinalgegend und umbilikal (Protokol B); beide Protokolle wurden 3 Tage lang durchgeführt. Die in vivo Aktivität wurde durch die Quantifizierung von Malassezienkolonien durch Kontaktplatten an den ausgewählten Körperstellen vor und nach Verwendung der Feuchttücher beurteilt. Die Aktivität der Lösung, in der die Feuchttücher getaucht waren, wurde in vitro mittels Kontakttest, den European Standard UNI EN 1275 Richtlinienfolgend, beurteilt. Ergebnisse Die Proben, die nach Anwendung der Feuchttücher genommen wurden, zeigten eine signifikante und rasche Abnahme der Malassezienhefen CFU. Zwischen den Protokollen A und B wurden keine signifikanten Unterschiede bei der Reduktion der Malassezien gefunden. Der in vitro Test zeigte nach einer 15 minütigen Kontaktzeit mit der Feuchtlösung eine 100%ige Wirkung gegen Malassezien. Schlussfolgerungen und klinische Bedeutung Feuchttücher, die Chlorhexidin, Climbazol und Tris-EDTA enthalten, reduzierten die M. pachydermatisPopulation auf der Haut der Hunde signifikant. Obwohl es sich um eine unkontrollierte Studie handelte, die an einer kleinen Zahl von Hunden durchgeführt wurde, weisen die Ergebnisse darauf hin, dass diese Feuchttücher für eine topische Behandlung der Malasseziendermatitis der Lippen, der Pfoten, der Perianalgegend und der Hautfaltennützlich sein könnten. PMID:26083147

The joint in vitro action of polymyxin B and miconazole against pathogens associated with canine otitis externa from three European countries

PubMed Central

Pietschmann, Silvia; Meyer, Michael; Voget, Michael; Cieslicki, Michael

2013-01-01

Background Canine otitis externa, an inflammation of the external ear canal, can be maintained and worsened by bacterial or fungal infections. For topical treatment, combinations of anti-inflammatory and antimicrobial ingredients are mainly used. Hypothesis/Objectives This study was conducted to elucidate the in vitro activity of polymyxin B and miconazole against clinical bacterial isolates from three European countries, to investigate possible differences in sensitivity and to assess drug interactions. Animals Seventeen strains of Escherichia coli, 24 strains of Pseudomonas aeruginosa, 24 strains of Proteus mirabilis and 25 strains of Staphylococcus pseudintermedius from dogs with diagnosed otitis externa had been isolated in Germany, France and Italy. Methods Drug activities were evaluated by minimal inhibitory concentration (MIC) and minimal bactericidal concentration. The potentiation of polymyxin B plus miconazole was calculated using the fractional inhibitory concentration index (FICI). An FICI ≤0.5 defined synergy. Furthermore, geographical variations in the FICI and MIC were assessed by statistical analysis. Results Bacterial susceptibilities were comparable in different European countries, because there were no significant MIC and FICI variations (P > 0.05). As a single agent, polymyxin B had bactericidal activity against most E. coli and P. aeruginosa strains and, in higher concentrations, against S. pseudintermedius strains. Miconazole was bactericidal against all Staphylococcus strains. Synergy was demonstrated against strains of E. coli and P. aeruginosa (FICI = 0.25 and 0.50, respectively), whereas overall there was no interaction against S. pseudintermedius strains (FICI = 1.25). Proteus mirabilis strains were not inhibited by each of the drugs individually or by their combination. Conclusions and clinical importance In vitro synergy of polymyxin B and miconazole against E. coli and P. aeruginosa isolates indicates a rationale for applying both agents in combination to treat otitis externa when infected with these types of bacteria. Résumé Contexte L'otite externe canine, une inflammation du conduit auriculaire externe, peut être entretenue et aggravée par les infections bactériennes ou fongiques. Pour le traitement topique, les associations d'anti-inflammatoires et d'antimicrobiens sont principalement utilisées. Hypothèses/Objectifs Cette étude a été menée pour déterminer l'activité in vitro de la polymyxine B et du miconazole contre les souches bactériennes cliniques isolées dans trois pays européens, d'étudier les différences possibles de sensibilité et de déterminer les interactions médicamenteuses. Sujets Dix-sept souches d'Escherichia coli, 24 souches de Pseudomonas aeruginosa, 24 souches de Proteus mirabilis et 25 souches de Staphylococcus pseudintermedius ont été isolées de chiens atteints d'otite externe en Allemagne, France et Italie. Résultats L'activité des molécules a été évaluée par la concentration minimale inhibitrice (CMI) et la concentration minimale bactéricide. La potentialisation de la polymyxine B et du miconazole a été calculée par l'indice de concentration inhibitrice fractionnaire (FICI). Un FICI ≤ 0.5 définissait la synergie. En outre, les variations géographiques dans le FICI et la CMI étaient évaluées par analyses statistiques. Résultats Les sensibilités bactériennes étaient comparables dans les différents pays européens parce qu'aucune différence significative n'a été mise en évidence entre les variations de CMI et de FICI (P > 0.05). La polymyxine B en tant que seul agent avait une activité bactéricide contre la plupart des souches de E. coli et P. aeruginosa, et, à plus forte concentration, contre les souches de S. pseudintermedius. Le miconazole était bactéricide contre toutes les souches de S. pseudintermedius. Une synergie a été mise en évidence contre les souches de E. coli et P. aeruginosa (FICI = 0.25 et 0.50, respectivement), alors qu'aucune interaction n'a été mise en évidence contre les souches de S. pseudintermedius (FICI = 1.25). Les souches de Proteus mirabilis n'ont été inhibées par aucune des molécules, individuellement ou en association. Conclusions et importance clinique La synergie in vitro de la polymyxine B et du miconazole contre les souches d'E. coli et de P. aeruginosa justifie l'application de la combinaison des deux agents dans le traitement de l'otite externe lors d'infection par ces bactéries. Resumen Introducción la otitis externa canina, inflamación del canal auditivo externo, puede perpetuarse y empeorar debido a la presencia de infecciones bacterianas o fúngicas. Para el tratamiento tópico se utilizan fundamentalmente combinaciones de ingredientes antiinflamatorios y antimicrobianos. Hipótesis/objetivos este estudio se condujo para elucidar la actividad in vitro de polimixina B y miconazol frente a aislados clínicos bacterianos de tres países europeos, investigar posibles diferencias en sensibilidad y analizar interacciones de fármacos. Animales diecisiete cepas de Escherichia coli, 24 cepas de Pseudomonas aeruginosa, 24 cepas de Proteus mirabilis y 25 cepas de Staphylococcus pseudintermedius de perros diagnosticados con otitis externa asilados de Alemania, Francia e Italia. Métodos se evaluó la actividad de los fármacos mediante la concentración inhibitoria minima (MIC) y la concentración bactericida minima. La potenciación de polimixina B y miconazol se calculó usando el índice de concentración fraccional inhibitoria (FICI). Un FICI≤ 0,5 definía sinergismo. Además se analizaron estadísticamente las variaciones en la FICI y MIC dependiendo de la región de origen. Resultados la susceptibilidad bacteriana fue comparable en los diferentes países europeos ya que no hubo diferencias significativas en MIC y FICI (P > 0,05). Como agente único la polimixina B tuvo actividad antimicrobiana frente a la mayoría de cepas de E. coli y P. aeruginosa, y a mayores concentraciones frente a cepas de S. pseudintermedius. El miconazol fue bactericida frente a todas las cepas de Staphylococcus. Se observó sinergismo frente a cepas de E. coli y P. aeruginosa (FICI = 0.25 y 0,50, respectivamente), mientras en general no hubo sinergismo frente a las cepas de S. pseudintermedius (FICI = 1.25). Cepas de Proteus mirabilis no fueron inhibidas por los fármacos individualmente ni en combinación. Conclusiones e importancia clínica el sinergismo in vitro de la polimixina B y el miconazol frente a aislados de E. coli y P. aeruginosa indica un motivo para utilizar ambos agentes en combinación para tratar casos de otitis externa producidos por infecciones con estas bacterias. Zusammenfassung Hintergrund Die canine Otitis externa, eine Entzündung des äußeren Ohrkanals, kann durch eine bakterielle Infektion oder durch eine Infektion mit Hefepilzen aufrechterhalten bzw. verschlimmert werden. Zur topischen Behandlung werden hauptsächlich Kombinationen aus entzündungshemmenden und antimikrobiellen Wirkstoffen verwendet. Hypothese/Ziele Diese Studie wurde durchgeführt, um die in vitro Aktivität von Polymyxin B und Mikonazol gegenüber klinischen Bakterienisolaten aus drei europäischen Ländern zu beleuchten und um mögliche Unterschiede in der Sensibilität zu untersuchen und um Interaktionen von Medikamenten zu beurteilen. Tiere Siebzehn Stämme von Escherichia coli, 24 Stämme von Pseudomonas aeruginosa, 24 Stämme von Proteus mirabilis und 25 Stämme von Staphylokokkus pseudintermedius von Hunden mit einer diagnostizierten Otitis externa waren in Deutschland, Frankreich und Italien isoliert worden. Methoden Die Wirkstoffaktivitäten wurden mittels minimaler inhibitorischer Konzentration (MIC) und minimaler bakterizider Konzentration evaluiert. Die Potenzierung von Polymyxin B plus Mikonazol wurde mittels „Fractional Inhibitory Concentration Index” (FICI) kalkuliert. Ein FICI ≤ 0,5 definierte eine Synergie. Weiters wurden geographische Variationen des FICI und der MIC mittels statistischer Analyse beurteilt. Ergebnisse Die bakteriellen Empfindlichkeiten waren in den verschiedenen europäischen Ländern vergleichbar, da keine signifikanten Unterschiede bei MIC und FICI bestanden (P > 0,05). Als alleiniger Wirkstoff zeigte Polymyxin B eine bakterizide Wirkung gegenüber den meisten E. coli und P. aeruginosa Stämmen und, in höheren Konzentrationen, gegenüber S. pseudintermedius Stämmen. Eine Synergie wurde gegen E. coli und P. aeruginosa Stämme (FICI = 0.25 bzw. 0,50) demonstriert, während insgesamt keine Interaktion gegen S. pseudintermedius Stämme (FICI = 1.25) bestand. Proteus mirabilis Stämme wurden von keinem dieser Wirkstoffe, weder individuell noch in Kombination, inhibiert. Schlussfolgerungen und klinische Bedeutung Eine in vitro Synergie von Polymyxin B und Mikonazol gegenüber E. coli und P. aeruginosa Isolaten bekräftigt die Argumentation dafür, beide Wirkstoffe in Kombination zu verwenden, um eine Otitis externa, bei der diese Bakterien vorkommen, zu behandeln. PMID:23721182

Editorial . Quantum fluctuations and coherence in optical and atomic structures

NASA Astrophysics Data System (ADS)

Eschner, Jürgen; Gatti, Alessandra; Maître, Agnès; Morigi, Giovanna

2003-03-01

From simple interference fringes, over molecular wave packets, to nonlinear optical patterns - the fundamental interaction between light and matter leads to the formation of structures in many areas of atomic and optical physics. Sophisticated technology in experimental quantum optics, as well as modern computational tools available to theorists, have led to spectacular achievements in the investigation of quantum structures. This special issue is dedicated to recent developments in this area. It presents a selection of examples where quantum dynamics, fluctuations, and coherence generate structures in time or in space or where such structures are observed experimentally. The examples range from coherence phenomena in condensed matter, over atoms in optical structures, entanglement in light and matter, to quantum patterns in nonlinear optics and quantum imaging. The combination of such seemingly diverse subjects formed the basis of a successful European TMR network, "Quantum Structures" (visit http://cnqo.phys.strath.ac.uk/~gianluca/QSTRUCT/). This special issue partly re.ects the results and collaborations of the network, going however well beyond its scope by including contributions from a global community and from many related topics which were not addressed directly in the network. The aim of this issue is to present side by side these di.erent topics, all of which are loosely summarized under quantum structures, to highlight their common aspects, their di.erences, and the progress which resulted from the mutual exchange of results, methods, and knowledge. To guide the reader, we have organized the articles into subsections which follow a rough division into structures in material systems and structures in optical .elds. Nevertheless, in the following introduction we point out connections between the contributions which go beyond these usual criteria, thus highlighting the truly interdisciplinary nature of quantum structures. Much of the progress in atom optics has been generated by the application of concepts from wave optics to matter waves. An example is the contribution by Franke-Arnold et al. The authors investigate the coherence properties of two trapped cold atoms using concepts developed in wave optics. Nevertheless, novel features appear in this system due to the quantum statistics - as atoms may be bosons or fermions - and due to interactions. Matter waves find a spectacular manifestation in Bose-Einstein condensates (BECs) of cold dilute atomic gases. Several concepts of wave optics, like the laser, have been discussed in relation to BECs, and the .eld of atom optics with BECs is rapidly developing. The similarity between the theoretical description of a weakly interacting BEC with that of a non-linear optical system has motivated a series of experiments that led to the observation of, e.g., solitons, vortices and vortex crystallization in matter waves. In this context, the paper by Josopait et al. describes the dynamics of a Bose-Einstein condensate containing a vortex. The vortex stability is discussed as a function of the interparticle interaction, which can be tuned using Feshbach resonances, and the dynamics of the BEC reflected by an atomic mirror is investigated. Non-linear optics merges with atomic physics also in a relatively new research area which aims at quantum non-linear optics with cold atomic gases. Labeyrie et al. use a dense, laser-cooled atomic gas as a non-linear medium for light propagation, and discuss the conditions for observing optical patterns in the transmitted beam. Pattern formation in non-linear optical media is one of the numerous forms of self-organization that these systems display, including also turbulence and optical solitons. With respects to other physical systems, where these phenomena are commonly observed, optical systems are however special: at optical frequencies thermal .uctuations are negligible and do not hide the presence of quantum .uctuations, even at room temperature. Remarkably, the interplay between non-linearity and quantum noise leads to novel phenomena, including optical patterns driven by quantum noise, quantum images, non-classical spatio-temporal correlations, and spatial quantum entanglement. Quantum images are an example of spatial structures dominated by quantum noise, where the structure is absent at a classical level and only proper correlation functions of quantum fluctuations reveal the presence of a regular spatial order. Hoyuelos et al. describe an example of such an image, which is formed in the cross section of the light emitted by an optical parametric oscillator, close to but below the threshold for a square pattern formation. The optical parametric oscillator is also studied in the paper by Rabbiosi et al. which describes the onset of a spatial structure consisting of arrays of localized peaks (cavity solitons) in the transverse cross section of the signal beam. This represents an example of a "disorder to order" transition mediated by quantum noise, where the ordered arrays of solitons are selected among the many possible stable states, only thanks to the presence of quantum noise. As the study of the dynamics of quantum .uctuations in spatially extended systems is a nontraditional subject in quantum optics, alternative techniques of theoretical analysis are needed. The paper by Zambrini et al. proposes an approach based on the use of phase-space representations, in particular of the Q-function with its associated nonlinear Langevin equations. This method provides a full description of the transition from a quantum image to a classical structure through a modulation instability. The Q-representation is also used in a different physical system, the dynamics of the electrons in a driven Helium atom, in the paper by Schlagheck and Buchleitner. Here the authors investigate the quantum manifestations of order and disorder in the motion of the electrons, identifying correspondences between features of the classical phase space and the quantum dynamics. In optical patterns the structure and stability are critically determined by the type of non-linearity of the medium where light propagates, and by the cavity geometry. In atom optics, spatial atomic patterns can be created by light potentials, in particular by arrangements of suitably polarized laser beams which form an optical lattice. The atoms experience mechanical forces arising from the gradient of the light potential. Depending on the tuning of the lasers with respect to the driven atomic transition, these light forces can have a strong or negligible dissipative component, leading to incoherent or coherent motional dynamics. Atomic motion in optical lattices is experimentally investigated in the contributions by Carminati et al. and Jersblad et al. The first article investigates motion-induced resonances in a three-dimensional optical lattice which are observed through pumpprobe laser spectroscopy. The latter contribution studies the effect of the lattice geometry on the atomic steady-state by measuring velocity distributions. The creation of more complex light structures is the subject of the paper by Ellmann et al., where the realization of a double optical lattice is discussed. Such lattices may open up the possibility of coherent manipulation of the atoms in the individual potential wells. An alternative way to structure atoms spatially is discussed by Grabowski and Pfau: here, a regular arrangement of magnetic and magneto-optical traps for ultracold atoms above a surface is described and experimentally observed, where the lattice con.guration is determined by the direction of currents in wire segments beneath the surface. In a different physical systems, semiconductor quantum dots, Jacak et al. study the coupling of arti.cial atoms with the collective excitations of the bulk material in which they are embedded, and investigate coherent and incoherent effects due to this interaction. The presence of correlations at the quantum level leads naturally to the issue of entanglement. This is an exclusive feature of the quantum world, which represents a valuable resource for quantum information processing and for high-precision measurements. The de.nition and criteria for measuring entanglement have been traditionally formulated within the Hilbert-space formalism (the quantum state formalism). However, quantum structures are intrinsically multi-mode systems, for which the Hilbert-space approach is often unpractical and cumbersome. More appealing are the "classical looking" phase space descriptions, where it is hence of great importance to reformulate concepts such as entanglement or Bell inequalities. The paper by Santos addresses the general problem of characterizing the entanglement properties of an electromagnetic field in the language of Q-representation. Entanglement involving the spatial modes of the electromagnetic field carrying orbital angular momentum provides new degrees of freedom and could play an important role in the field of quantum information, since such non-classical states enable the possibility of multichannel communications. The paper by Barbosa discusses quantum states of twin photons produced by parametric down-conversion and entangled in polarization and orbital angular momentum. The issue of entanglement is intrinsically connected to decoherence, and to the transition from the quantum to the classical world. In particular, massive systems are characterized by strong interactions with the environment, and at room temperature they usually exhibit classical behaviour. In this context, the paper by Karlsson discusses the decay of quantum correlations of protons and positive muons in condensed matter, a system characterized by strong coupling to the environment, and proposes experiments where such quantum correlations could be measured. Mancini et al. investigate macroscopic manifestations of quantum features, presenting a proposal for entangling the macroscopic oscillation modes of two cavity mirrors by coupling them to an optical cavity mode. This kind of continuous-variable quantum entanglement may find applications in highprecision measurements, like in atomic force microscopy or gravity wave detection. The question of entanglement for high-precision measurements is also addressed by the paper of Yurtsever et al. which discusses entanglement between matter waves, and proposes the use of entangled atom pairs for a highly sensitive quantum gravity gradiometer. Besides their fundamental interest as a manifestation of quantum .uctuations, spatial quantum correlations in optical beams find their most natural and promising applications in the field of image processing and, more in general, of parallel processing of information. This has opened a new chapter of quantum optics that has been given the name "quantum imaging". In this context, one of the .rst achievements have been the so-called entangled two-photon imaging experiments. This is a technique that exploits the quantum entanglement of a two-photon state to retrieve information about a remote object. In the typical set-up, one photon out of a pair produced by spontaneous parametric down-conversion is used to probe an object, while the other provides a reference. The image of the object emerges in the coincidence counting rate registered as a function of the second photon position. The paper by Shih offers an extensive review of fundamental aspects linked to the entangled two-photon imaging phenomena. It illustrates how quantum imaging techniques may improve classical spatial resolution and presents some of their potential applications for lithography and other microsystem fabrication technologies. A different view on the problem is offered by the paper of Tan et al., which reformulates the two-photon quantum imaging theory from the point of view of retrodictive quantum theory. Since long, quantum noise has been known to represent a limit in high-precision optical measurements. In this context, the contribution by Eschner discusses a single trapped atom probing an optical field and shows that the quantum noise in the atomic motion poses the ultimate limit to the achievable resolution. Recently, it was recognized that quantum noise affects also our ability to resolve an optical image or to detect a small displacement of an optical beam. Properly synthesized multi-mode quantum states are able to circumvent the quantum noise limit and to improve our resolution capabilities in measuring beam displacements. The paper by Barnett et al. shows the similarities between longitudinal phase shifts and transverse beam displacements measurements. Like in interferometry, the sensitivity in the transverse displacement measurement is ultimately limited by the quantum nature of light and can be improved by the use of specific non classical states. The problem of realizing a multi-mode squeezed state is addressed by the paper of Petsas et al. It discusses a realistic implementation of parametric down-conversion in a confocal cavity, able to produce a significant amount of squeezing in small portions of the signal beam cross section. Quantum imaging with macroscopic light beams is a rather new subject of investigation, which represents a non-trivial challenge from the point of view of experimental implementations. One of the main problems is posed by detectors, which should be able to resolve the spatial features of the detected beam with a sensitivity in the photon number measurement beyond the shot noise level. The calibrated CCD camera developed by Jiang et al. makes it possible to get rid of electronic noise or spatial inhomogeneities, a.ecting most of the spatially resolved detectors, and allows the retrieval of spatial shot noise in its full dynamic range. We hope that this special issue helps stimulating further collaborations and fruitful scientific exchange between and beyond the presented fields. We would like to thank the authors for their contributions and the referees for their time and their thoroughness. Our sincerest thanks go to Solange Guéhot in the EPJ D editorial office for very efficiently taking care of all administrative matters. Jürgen Eschner, Institut für Experimentalphysik, Universität Innsbruck, Technikerstr. 25, 6020 Innsbruck, Austria Alessandra Gatti, Istituto Nazionale per la Fisica della Materia, Unitá di Como, Via Valleggio 11, 22100 Como, Italy Agnàs Maītre, Laboratoire Kastler-Brossel, Université Pierre et Marie Curie, 4 place Jussieu, 75252 Paris Cedex 05, France Giovanna Morigi, Abteilung Quantenphysik, Universitát Ulm, Albert-Einstein Allee 11, 89069 Ulm, Germany