Approach to the patient with drug allergy

Drug allergies are adverse drug reactions mediated by the specific immune system. Despite characteristic signs (eg, skin rash) that raise awareness for possible drug allergies, they are great imitators of disease and may hide behind unexpected symptoms. No single standardized diagnostic test can confirm the immune-mediated mechanism or identify the causative drug; therefore, immune-mediated drug hypersensitivity reactions and their causative drugs must be recognized by the constellation of exposure, timing, and clinical features including the pattern of organ manifestation. Additional allergologic investigations (skin tests, in vitro tests, provocation tests) may provide help in identifying the possible eliciting drug.

Maternal transfer of IgE and subsequent development of IgE responses in the horse (Equus callabus)

Immunoglobulin E (IgE) mediates the immune response to parasites, but can also cause allergies. In humans maternal IgE is not transferred to cord blood and high levels of cord blood IgE are associated with subsequent allergy. In horses, both maternal IgG and IgE are transferred via colostrum; the IgE levels in the mare's serum, the colostrum and the foal's serum are correlated but the consequences of IgE transfer to foals are not known. By about 6 weeks of age the levels of IgE in foal serum have dropped to a nadir, at 6 months of age the level of IgE has risen only very slightly and is no longer correlated with the levels seen at birth, IgE(+) B-cells could be detected in lymphoid follicles of some foals at this age. Surprisingly, the levels of total IgE detected in a foals serum at 6 months of age are significantly correlated with the level in its serum at 1, 2 and even 3 years of age suggesting that by 6 months of age the foals are synthesizing IgE and that a pattern of relatively higher or lower total serum IgE has been established. The neonatal intestinal mucosa contained connective tissue mast cells which stained for bound IgE in foals up to 9 weeks of age but not mucosal mast cells, thereafter, the intestinal mast cells were IgE negative until 6 months of age. IgE antibodies to Culicoides nubeculosus salivary antigens were detected in Swiss born foals from imported Icelandic mares allergic to Culicoides spp. yet the foals showed no signs of skin sensitization and such second generation foals are known not to have an increased risk of developing allergy to Culicoides. Overall this evidence suggests there is a minimal effector role of maternal IgE also that maternal IgE has waned prior to the onset of IgE synthesis in foals and does not support maternal priming of IgE responses in foals. Furthermore the total levels of IgE in any given foal are seen to be relatively high or low from soon after the onset of IgE synthesis, and most likely they are determined by genetic factors.

Politikgeschichte in der Schweiz – eine historiographische Skizze

Die traverse lancierte im Jahr 2010 eine Reihe von vier historiographischen Sonderheften. Nach der Wirtschaftsgeschichte (1/2010), der Sozialgeschichte (1/2011) und der Kulturgeschichte (1/2012) wird die Reihe mit einem Heft zur Politikgeschichte (1/2013) abgeschlossen. In 14 Artikeln werden Themen aus dem Mittelalter, der Neuzeit, der Sattelzeit und der Zeitgeschichte aufgenommen. Die Beiträge bieten Forschungsüberblicke zur Geschichte der Parteien und der politischen Bewegungen, der Militärgeschichte, der Rechtsgeschichte, der staatsbürgerlichen Rechte und der Staatsbürgerschaft, den auswärtigen Beziehungen, der Neutralität, der schweizerischen Mitarbeit in internationalen Organisationen, des Service Publics, des Parlamentes und der Verfassung, der Religionsgeschichte und des Säkularismus, der Umwelt und zur Konstruktion von Geschichte und nationaler Indentität. Zusätzlich werden die beiden Arbeitsinstrumente Diplomatische Dokumente der Schweiz und das Jahrbuch Schweizerische Politik (L'Année politique suisse) vorgestellt und am Beispiel des Bergier-Berichts wird die politische Instrumentalisierung der Geschichte diskutiert.

Relationship between threshold and suprathreshold perception of position and stereoscopic depth.

We seek to determine the relationship between threshold and suprathreshold perception for position offset and stereoscopic depth perception under conditions that elevate their respective thresholds. Two threshold-elevating conditions were used: (1) increasing the interline gap and (2) dioptric blur. Although increasing the interline gap increases position (Vernier) offset and stereoscopic disparity thresholds substantially, the perception of suprathreshold position offset and stereoscopic depth remains unchanged. Perception of suprathreshold position offset also remains unchanged when the Vernier threshold is elevated by dioptric blur. We show that such normalization of suprathreshold position offset can be attributed to the topographical-map-based encoding of position. On the other hand, dioptric blur increases the stereoscopic disparity thresholds and reduces the perceived suprathreshold stereoscopic depth, which can be accounted for by a disparity-computation model in which the activities of absolute disparity encoders are multiplied by a Gaussian weighting function that is centered on the horopter. Overall, the statement "equal suprathreshold perception occurs in threshold-elevated and unelevated conditions when the stimuli are equally above their corresponding thresholds" describes the results better than the statement "suprathreshold stimuli are perceived as equal when they are equal multiples of their respective threshold values."

Späte Scheidungen: Fakten, Gründe und Auswirkungen. Ein interdisziplinärer Blick auf Ergebnisse einer Schweizer Studie

Scheidungen im Alter sind eine zunehmende gesellschaftliche Realität, allerdings wurde dieses Phänomen bislang kaum wissenschaftlich untersucht. In diesem Beitrag werden neueste Forschungsergebnisse einer Schweizer Studie vorgestellt, welche zeigen, dass späte Scheidungen ein einschneidendes kritisches Lebensereignis mit multiplen Gründen und mannigfachen negativen Auswirkungen auf persönlicher, familialer und sozialer Ebene ist. Allerdings gibt es grosse individuelle Unterschiede, insbesondere Geschlechterunterschiede, hinsichtlich der Gründe und auch bezüglich der psychosozialen Adaptation. Das Ausleuchten der Forschungsresultate trägt nicht nur zu einem besseren Verständnis des Phänomens bei, sondern liefert auch Grundlagen für die familienrechtliche Praxis.

Therapie und Prävention von opportunistischen Infektionen

Incidence as well as morbidity and mortality of opportunistic infections (OI) have declined remarkably since the availability of antiretroviral treatment (ART). Nearly half of all persons infected with HIV however do not know their HIV-status, and the diagnosis of an OI may be the first manifestation of their HIV infection. Therefore, knowledge of the presentation of OIs as well as their management should remain an essential part of clinicians' expertise. After starting ART the immune system will improve; in this context OI may be unmasked or the clinical presentation of known OI may worsen. Before starting ART therefore, it is essential to rule out any asymptomatic or latent OI. For the same reason, in the case of a known OI, the start of ART must often be deferred for some weeks after the start of OI treatment. Treatment of OIs is complex and often results in a large pill-burden for the patient with the potential for multiple drug-drug-interactions, particularly once ART has to be started. Many of the OI treatments are also associated with frequent drug side-effects and allergies. OIs can be prevented with specific antimicrobial agents once the CD4 have decreased below a defined threshold. However, the main prevention of OI is the timely recognition of HIV infection and an early start of ART before complications of OI appear.

Multiple Hypersensitivities Including Recurrent Airway Obstruction, Insect Bite Hypersensitivity, and Urticaria in 2 Warmblood Horse Populations.

BACKGROUND Multiple hypersensitivities (MHS) have been described in humans, cats, and dogs, but not horses. HYPOTHESES Horses suffering from recurrent airway obstruction (RAO), insect bite hypersensitivity (IBH), or urticaria (URT) will have an increased risk of also being affected by another one of these hypersensitivities. This predisposition for MHS also will be associated with decreased shedding of strongylid eggs in feces and with a single nucleotide polymorphism (SNP BIEC2-224511), previously shown to be associated with RAO. ANIMALS The first population (P1) included 119 randomly sampled horses representative of the Swiss sporthorse population; the replication population (P2) included 210 RAO-affected Warmblood horses and 264 RAO-unaffected controls. All horses were Warmbloods, 14 years or older. METHODS Associations between disease phenotypes (RAO, IBH, URT, MHS) fecal egg counts, the SNP BIEC2-224511 as well as management and environmental factors were investigated. RESULTS In P1, RAO-affected horses had a 13.1 times higher odds ratio (OR) of also suffering from IBH (P = .004). In P2, the respective OR was 7.4 (P = .002) and IBH-affected horses also showed a 7.1 times increased OR of concomitantly suffering from URT (P < .001). IBH, URT, and MHS phenotypes were significantly associated with the absence of nematode eggs in the feces. CONCLUSIONS AND CLINICAL IMPORTANCE This is the first report of MHS in horses. Specifically, an increased risk for IBH should be expected in RAO-affected horses.

A relation between screening masses and real-time rates

Thermal screening masses related to the conserved vector current are determined for the case that the current carries a non-zero Matsubara frequency, both in a weak-coupling approach and through lattice QCD. We point out that such screening masses are sensitive to the same infrared physics as light-cone real-time rates. In particular, on the perturbative side, the inhomogeneous Schrödinger equation determining screening correlators is shown to have the same general form as the equation implementing LPM resummation for the soft-dilepton and photon production rates from a hot QCD plasma. The static potential appearing in the equation is identical to that whose soft part has been determined up to NLO and on the lattice in the context of jet quenching. Numerical results based on this potential suggest that screening masses overshoot the free results (multiples of 2πT) more strongly than at zero Matsubara frequency. Four-dimensional lattice simulations in two-flavour QCD at temperatures of 250 and 340 MeV confirm the non-static screening masses at the 10% level. Overall our results lend support to studies of jet quenching based on the same potential at T ≳ 250 MeV.

Hyperammonemic encephalopathy in multiple myeloma

HISTORY AND CLINICAL FINDINGS A 54-year old man had suffered from advanced multiple myeloma for two years. After initially good response the myeloma was refractrory to treatment with dexamethasone, cyclophosphamide, bortezomibe, zoledronate and additionally doxorubicine. The patient then complained of dyspnea without clinical signs of cardiopulmonary disease. INVESTIGATIONS Arterial blood gas analysis showed hyperventilation with respiratory alkalosis and normal alveolo-arterial gradient as the reason for the dyspnea. With a normal MRI of the brain and lumbal puncture, a neurological disease could be excluded. Serum calcium, creatinine and serum viscosity were normal. Eventually, serum ammonia levels were found to be substantially elevated (144 µmol/l) and hyperammonemic encephalopathy was diagnosed. TREATMENT AND COURSE Therapy with bortezomib and high dose dexamethason was repeated, and the patient also received bendamustin. Despite this treatment, he lost consciousness and died after two weeks because of aspiration pneumonia. CONCLUSION The existence of respiratory alkalosis and multiple myeloma should prompt a search for hyperammonemia.

How Do Gastroenterologists Assess Overall Activity of Eosinophilic Esophagitis in Adult Patients?

OBJECTIVES:There is no "gold standard" for assessing disease activity in patients with eosinophilic esophagitis (EoE). We aimed to compare physicians' judgment of EoE activity with patients' judgment of symptom severity. We also aimed to examine the relative contribution of symptoms as well as endoscopic and histologic findings in shaping physicians' judgment of EoE activity.METHODS:Six gastroenterologists (all EoE experts) assessed EoE-associated symptoms in adult patients. Patients completed a symptom instrument and provided global assessment of EoE symptom severity (PatGA) (Likert scale: 0 (inactive) to 10 (most active)). Following esophagogastroduodenoscopy with biopsy sampling, gastroenterologists provided a global assessment of EoE activity (PhysGA) (Likert scale from 0 to 10) based on patient history and endoscopic and histologic findings. Linear regression and analysis of variance was used to quantify the extent to which variations in severity of EoE symptoms and endoscopic and histologic findings explain variations in PhysGA.RESULTS:A total of 149 EoE patients were prospectively included (71.8% male, median age at inclusion 38 years, 71.8% with concomitant allergies). A moderate positive correlation between PhysGA and PatGA (rho=0.442, P<0.001) was observed and the mean difference in the Bland-Altman plot was 1.77. Variations in severity of endoscopic findings, symptoms, and histologic findings alone explained 53%, 49%, and 30%, of the variability in PhysGA, respectively. Together, these findings explained 75% of variability in PhysGA.CONCLUSIONS:Gastroenterologists rate EoE activity mainly on the basis of endoscopic findings and symptoms and, to a lesser extent, on histologic findings.Am J Gastroenterol advance online publication, 3 March 2015; doi:10.1038/ajg.2015.32.

Should we perform a screening ECG among asymptomatic adults?

The resting ECG is a safe, low cost and widely available in the clinical investigation of several cardiac symptoms. However, there is controversy regarding the use as a screening tool or routine cardiovascular (CV) risk assessment test among healthy asymptomatic adults. Two recent studies reported that ECG adds supplemental information in the estimation of coronary artery disease (CAD) risk in asymptomatic patients, especially in those with intermediate risk. However, we currently need more data on the impact of ECG on the prevention of clinical CV outcomes, especially in a randomized clinical trial, and on additional costs of testing and treatment. For the time being, routine ECG testing is not recommended for the prevention of CV events among healthy asymptomatic adults.

The Hypereosinophilic Syndromes in Childhood.

The hypereosinophilic syndromes are rare disorders in childhood and require extensive differential diagnostic considerations. In the last years the earlier "idiopathic HES" called syndromes could be differentiated into molecular biologically, immunophenotypically and clinically more characterized heterogeneous diseases with high therapeutic and prognostic relevance. Nowadays the term HES summarizes diseases, which go hand in hand with a local or systemic hypereosinophilia (HE) connected with an organ damage. Depending on the cause of the HE one differentiates primary/neoplastic HES (HESN) from secondary/reactive HES (HESR). The latter develops reactively in connection with allergies, parasitosis, medications, neoplasia or a clonal increase of T-lymphocytes among others. With HESN the HE results from a clonal increase of eosinophilic granulocytes. While for some subgroups of the HESN (among others FIP1L1-PDGFRA fusion gene) the administration of a tyrosine kinase inhibitor is a new and effective therapy option, glucocorticoids still represent the medication of first choice for many not PDGFRA associated variants. Different immunomodulatory drugs or cytostatic agents are necessary to allow dose reduction of glucocorticoids. The promising therapy with anti-IL-5 antibodies is still not approved in infancy, could however become a treatment option in the future. Due to the present lack of knowledge about the HES in infancy the establishment of a register should be aimed for the treatment of HES in infancy.

La lutte contre les abus dans le domaine de l’asile: émergence et développement d’un discours structurant le droit d’asile suisse

La « lutte contre les abus » en matière d'asile s'est imposée comme le discours dominant à l'origine des multiples révisions de la loi sur l'asile depuis son entrée en vigueur en 1981. Cette contribution, issue d'un workshop tenu lors des journées des doctorant-e-s du Centre de droit des migrations en novembre 2013, se propose de porter un regard interdisciplinaire sur l'émergence et le développement de cette notion, ainsi que sur le type de mesures adoptées dans le cadre de ce discours.

Einfluss von relativer Luftfeuchtigkeit und Applikationszeit auf die Dentinhaftkraft von sechs verschiedenen Adhäsivsystemen

Einleitung und Ziel: Das Arbeiten mit Adhäsivsystemen und Kompositmaterialien ist techniksensitiv und oft auch zeitaufwändig. Adhäsivsysteme und Kompositmaterialien sind feuchtigkeitsanfällig, weswegen die Verwendung eines Kofferdams von den Herstellern empfohlen wird - nicht nur, um während des Arbeitens mit Adhäsivsystemen und Kompositmaterialien die Gefahr einer Blut- oder Speichelkontamination zu minimieren sondern auch, um die hohe relative Luftfeuchtigkeit in der Mundhöhle auf die Luftfeuchtigkeit der Umgebung zu reduzieren. Abgesehen davon bestehen viele Adhäsivsysteme aus mehreren Applikationsschritten und diese Applikationsschritte weisen jeweils von den Herstellern genau angegebene Applikationszeiten auf. Je nach Adhäsivsystem erscheinen diese Applikationszeiten relativ lang und im klinischen Alltag kann die Gefahr bestehen, dass es zu einer Reduktion der vom Hersteller angegeben Applikationszeiten kommt. Es ist sehr wahrscheinlich, dass sowohl erhöhte relative Luftfeuchtigkeit als auch reduzierte Applikationszeiten die Dentinhaftkraft von Adhäsivsystemen negativ beeinflussen. Das Ziel dieser Studie war folglich, den Einfluss von relativer Luftfeuchtigkeit und Applikationszeit auf die Dentinhaftkraft von sechs verschiedenen Adhäsivsystemen zu untersuchen. Material und Methoden: Insgesamt 360 extrahierte menschliche Molaren ohne Füllungen und/oder Karies wurden verwendet (n=15 pro Gruppe; 24 Gruppen). Die Molaren wurden gereinigt und von okklusal bis ins mittlere Zahnkronendentin plangeschliffen. Die plangeschliffenen Molaren wurden anschliessend in selbsthärtendem Kunststoff eingebettet. Danach wurden die Oberflächen des Zahnkronendentins mit einem von sechs Adhäsivsystemen behandelt und Komposit (Filtek Z250; 3M ESPE) in Form eines Zylinders appliziert. Die sechs Adhäsivsysteme umfassten: 1) Syntac Classic (Ivoclar Vivadent), 2) OptiBond FL (Kerr), 3) Clearfil SE Bond (Kuraray), 4) AdheSE (Ivoclar Vivadent), 5) Xeno Select (DENTSPLY DeTrey) sowie 6) Scotchbond Universal (3M ESPE). Die Applikation des Adhäsivsystems und des Kompositzylinders wurde unter vier experimentellen Bedingungen durchgeführt. Die vier experimentellen Bedingungen wurden in einer modifizierten Handschuhbox erstellt (Abb. 1; CSL-GB24, Cleaver Scientific, Rugby, Grossbritannien) und umfassten: a) relative Luftfeuchtigkeit der Umgebung (~45%) und Applikationszeit gemäss Herstellerangaben, b) relative Luftfeuchtigkeit der Umgebung (~45%) und reduzierte Applikationszeit, c) erhöhte relative Luftfeuchtigkeit (≥85%) und Applikationszeit gemäss Herstellerangaben sowie d) erhöhte relative Luftfeuchtigkeit (≥85%) und reduzierte Applikationszeit. Nach 24 Stunden Lagerung wurden die auf Dentin applizierten Kompositzylinder in einer Universalprüfmaschine (Abb. 2; zwicki Z1.0 TN, Zwick, Ulm, Deutschland) mittels Scherkrafttest belastet (Traversengeschwindigkeit: 1 mm/min) und so die Haftkraftwerte bestimmt. Die Haftkraftwerte wurden anschliessend mit einer nichtparametrischen Varianzanalyse statistisch analysiert, gefolgt von Kruskal-Wallis- und Mann Whitney U-Tests sowie einer Bonferroni-Holm Korrektur für multiples Testen. Das Signifikanzniveau wurde auf α = 0.05 festgelegt. Resultate: Erhöhte relative Luftfeuchtigkeit sowie reduzierte Applikationszeit hatten keinen signifikanten Einfluss auf die Haftkraft von zwei der sechs untersuchten Adhäsivsysteme (Clearfil SE Bond und Scotchbond Universal; p = 1.00). Die Haftkraft der anderen vier Adhäsivsysteme (Syntac Classic, OptiBond FL, AdheSE und Xeno Select) wurde durch eine reduzierte Applikationszeit nicht signifikant beeinflusst (p ≥ 0.403). Allerdings reduzierte eine erhöhte relative Luftfeuchtigkeit (ungeachtet der Applikationszeit) die Haftkraft von Syntac Classic, OptiBond FL und Xeno Select signifikant (p ≤ 0.003). Eine erhöhte relative Luftfeuchtigkeit reduzierte die Haftkraft von AdheSE nur dann signifikant, wenn das Adhäsivsystem mit Applikationszeit gemäss Herstellerangaben verwendet wurde (p = 0.002). Hinsichtlich Unterschiede in der Haftkraft zwischen den sechs Adhäsivsystemen zeigte sich, dass OptiBond FL und Scotchbond Universal generell (sprich ungeachtet der vier experimentellen Bedingungen) die höchste Haftkraft erzielten. Von den anderen vier Adhäsivsystemen wurde Clearfil SE Bond am wenigsten durch erhöhte relative Luftfeuchtigkeit oder reduzierte Applikationszeit beeinflusst und zeigte zwar niedrigere Haftkraftwerte im Vergleich zu OptiBond FL und Scotchbond Universal dafür aber die konstanteste Haftkraft unter allen vier experimentellen Bedingungen. Schlussfolgerung: Die Dentinhaftkraft von zwei der sechs untersuchten Adhäsivsysteme (Clearfil SE Bond und Scotchbond Universal) wurde weder durch erhöhte relative Luftfeuchtigkeit noch durch reduzierte Applikationszeiten beeinflusst. Die Haftkraft der anderen vier Adhäsivsysteme wurde vor allem durch eine erhöhte relative Luftfeuchtigkeit negativ beeinflusst, grossmehrheitlich aber nicht durch eine reduzierte Applikationszeit. Klinisch ist daher die Kontrolle und Reduktion der relativen Luftfeuchtigkeit durch die Verwendung eines Kofferdams sehr zu empfehlen. Obwohl diese Studie gezeigt hat, dass reduzierte Applikationszeiten einen weniger starken, negativen Einfluss auf die Haftkraft haben, ist es trotzdem angezeigt, die Gebrauchsanleitungen der Adhäsivsysteme zu befolgen und sich an die Herstellerangaben zu halten.