Recommendations for HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions.

OBJECTIVE To systematically review evidence on genetic risk factors for carbamazepine (CBZ)-induced hypersensitivity reactions (HSRs) and provide practice recommendations addressing the key questions: (1) Should genetic testing for HLA-B*15:02 and HLA-A*31:01 be performed in patients with an indication for CBZ therapy to reduce the occurrence of CBZ-induced HSRs? (2) Are there subgroups of patients who may benefit more from genetic testing for HLA-B*15:02 or HLA-A*31:01 compared to others? (3) How should patients with an indication for CBZ therapy be managed based on their genetic test results? METHODS A systematic literature search was performed for HLA-B*15:02 and HLA-A*31:01 and their association with CBZ-induced HSRs. Evidence was critically appraised and clinical practice recommendations were developed based on expert group consensus. RESULTS Patients carrying HLA-B*15:02 are at strongly increased risk for CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in populations where HLA-B*15:02 is common, but not CBZ-induced hypersensitivity syndrome (HSS) or maculopapular exanthema (MPE). HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported from Asian countries only, including China, Thailand, Malaysia, and India. HLA-B*15:02 is rare among Caucasians or Japanese; no HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported so far in these groups. HLA-A*31:01-positive patients are at increased risk for CBZ-induced HSS and MPE, and possibly SJS/TEN and acute generalized exanthematous pustulosis (AGEP). This association has been shown in Caucasian, Japanese, Korean, Chinese, and patients of mixed origin; however, HLA-A*31:01 is common in most ethnic groups. Not all patients carrying either risk variant develop an HSR, resulting in a relatively low positive predictive value of the genetic tests. SIGNIFICANCE This review provides the latest update on genetic markers for CBZ HSRs, clinical practice recommendations as a basis for informed decision making regarding the use of HLA-B*15:02 and HLA-A*31:01 genetic testing in patients with an indication for CBZ therapy, and identifies knowledge gaps to guide future research. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Heinrich Graetz : Abhandlungen zu seinem 100. Geburtstage (31. Oktober 1917)

hrsg. von M. Brann

Geschichtliche Darstellung der Israelitischen Freischule zu Hamburg bei Gelegenheit der Feier ihres fünfundzwanzigjährigen Bestehens (am 31 October 1841)

mitgetheilt von Eduard Kley

Minority Rights and Humanitarianism: The international campaign for the Ukrainians in Poland, 1930-31

In October 1930, violent action of the Polish security forces against the Ukrainian population in Eastern Galicia resulted in an international campaign for the Ukrainians in Poland. Its central claim was the condemnation of these incidents as a violation of the Minorities Treaty of the League of Nations. The article focuses on the involved British extra-parliamentary groups and their international federations as well as leftist intellectuals, socialist parties and the Labour and Socialist International. In most cases, the commitment of the activists was motivated by the desire to expose a humanitarian scandal while the implementation of minority rights played a minor role. When it turned out that the first reports had presented an exaggerated version of the events, they shifted their focus to the Polish opposition whose persecution started in November 1930.

Di un nuovo cimitero giudaico scoperto sulla Via Labicana : discorso letto all'Accademia pontificia di archeologia il 31 Gennaio 1884

Orazio Marucchi

Comparison of (31)P saturation and inversion magnetization transfer in human liver and skeletal muscle using a clinical MR system and surface coils.

(31)P MRS magnetization transfer ((31)P-MT) experiments allow the estimation of exchange rates of biochemical reactions, such as the creatine kinase equilibrium and adenosine triphosphate (ATP) synthesis. Although various (31)P-MT methods have been successfully used on isolated organs or animals, their application on humans in clinical scanners poses specific challenges. This study compared two major (31)P-MT methods on a clinical MR system using heteronuclear surface coils. Although saturation transfer (ST) is the most commonly used (31)P-MT method, sequences such as inversion transfer (IT) with short pulses might be better suited for the specific hardware and software limitations of a clinical scanner. In addition, small NMR-undetectable metabolite pools can transfer MT to NMR-visible pools during long saturation pulses, which is prevented with short pulses. (31)P-MT sequences were adapted for limited pulse length, for heteronuclear transmit-receive surface coils with inhomogeneous B1 , for the need for volume selection and for the inherently low signal-to-noise ratio (SNR) on a clinical 3-T MR system. The ST and IT sequences were applied to skeletal muscle and liver in 10 healthy volunteers. Monte-Carlo simulations were used to evaluate the behavior of the IT measurements with increasing imperfections. In skeletal muscle of the thigh, ATP synthesis resulted in forward reaction constants (k) of 0.074 ± 0.022 s(-1) (ST) and 0.137 ± 0.042 s(-1) (IT), whereas the creatine kinase reaction yielded 0.459 ± 0.089 s(-1) (IT). In the liver, ATP synthesis resulted in k = 0.267 ± 0.106 s(-1) (ST), whereas the IT experiment yielded no consistent results. ST results were close to literature values; however, the IT results were either much larger than the corresponding ST values and/or were widely scattered. To summarize, ST and IT experiments can both be implemented on a clinical body scanner with heteronuclear transmit-receive surface coils; however, ST results are much more robust against experimental imperfections than the current implementation of IT.

Manuel Joels wissenschaftliches Lebenswerk : Festvortrag anlässl. d. Gedächtnisfeier d. Jüdisch-theologischen Seminars am 31. Okt. 1926

von [Isaak] Heinemann. Hrsg. vom Jüdisch-theologischen Seminar Fraencke'scher Stiftung zu Breslau

Dr. David Rosin, geboren am 27. Mai 1823, gestorben am 31. December 1894 : ein Nachruf

von David Kaufmann

Heinrich Graetz : eine Würdigung d. Historikers u. Juden zu seinem 100. Geburtstage 31. Okt. 1917 (21. Cheschwan)

von Josef Meisl

Gastro-oesophageal reflux is common in oligosymptomatic patients with dental erosion: A pH-impedance and endoscopic study.

Background: Dental erosion is a complication of gastro-oesophageal reflux disease (GORD) according to the Montreal consensus statement. However, GORD has not been comprehensively characterized in patients with dental erosions and pH-impedance measures have not been reported. Objectives: Characterize GORD in patients with dental erosions using 24-h multichannel intraluminal pH-impedance measurements (pH-MII) and endoscopy. Methods: This single-centre study investigated reflux in successive patients presenting to dentists with dental erosion using pH-MII and endoscopy. Results: Of the 374 patients, 298 (80%) reported GORD symptoms <2 per week, 72 (19%) had oesophagitis and 59 (16%) had a hiatal hernia. In the 349 with pH-MII the mean percentage time with a pH <4 (95% CI) was 11.0 (9.3–12.7), and 34.4% (31.9–36.9) for a pH <5.5, a critical threshold for dental tissue. The mean numbers of total, acidic and weakly acidic reflux episodes were 71 (63–79), 43 (38–49) and 31 (26–35), respectively. Of the reflux episodes, 19% (17–21) reached the proximal oesophagus. In 241 (69%) patients reflux was abnormal using published normal values for acid exposure time and reflux episodes. No significant associations between the severity of dental erosions and any reflux variables were found. The presence of GORD symptoms and of oesophagitis or a hiatal hernia was associated with greater reflux, but not with increased dental erosion scores. Conclusions: Significant oligosymptomatic gastro-oesophageal reflux occurs in the majority of patients with dental erosion. The degree of dental erosion did not correlate with any of the accepted quantitative reflux indicators. Definition of clinically relevant reflux parameters by pH-MII for dental erosion and of treatment guidelines are outstanding. Gastroenterologists and dentists need to be aware of the widely prevalent association between dental erosion and atypical GORD.

Measurement of negatively charged pion spectra in inelastic p+p interactions at plab = 20, 31, 40, 80 and 158 GeV/c

We present experimental results on inclusive spectra and mean multiplicities of negatively charged pions produced in inelastic p+p interactions at incident projectile momenta of 20, 31, 40, 80 and 158GeV/c (√s = 6.3, 7.7,8.8, 12.3 and 17.3GeV, respectively). The measurements were performed using the large acceptance NA61/SHINE hadron spectrometer at the CERN super proton synchrotron. Two-dimensional spectra are determined in terms of rapidity and transverse momentum. Their properties such as the width of rapidity distributions and the inverse slope parameter of transverse mass spectra are extracted and their collision energy dependences are presented. The results on inelastic p+p interactions are compared with the corresponding data on central Pb+Pb collisions measured by the NA49 experiment at the CERNSPS. The results presented in this paper are part of the NA61/SHINE ion program devoted to the study of the properties of the onset of deconfinement and search for the critical point of strongly interacting matter. They are required for interpretation of results on nucleus–nucleus and proton–nucleus collisions.

Ms. hebr. qu. 31 - Pinḳas shel ḥavurah Shas (=shishah sedarim) u-mishnayot

Vorbesitzer: Carl Wilhelm von Rothschild