Antidepressant-associated maniform states in acute treatment of patients with bipolar-I depression

Medical records of 158 patients with bipolar depression were analysed for the incidence of a switch from depression to maniform states (mania and hypomania). Relation to psychopharmacological treatment was investigated. Thirty-nine (25%) patients of the total sample had switched to a maniform state during the treatment period in the hospital. Among that group the phenomenon occurred in 23 patients (15%) as a hypomania and in 16 patients (10%) as a mania. Patients with a switch were significantly more often treated with tricyclic antidepressants (TCA) than patients without switch (79.5% vs 51.3%). Mood stabilising medication might reduce the risk for switching, especially in patients treated with TCA; however, it seems not totally sufficient, since 59% of the switched patients received mood stabilisers. The switch phenomenon was not associated with sociodemographic or clinical data. Received: 23 September 1998 / Accepted: 28 September 1998     

Evidence for a human IgG1 class switch program

In activated murine B lymphocytes, immunoglobulin class switch recombination occurs as a highly regulated process which is targeted to distinct switch regions. Here we present first evidence that in human B lymphocytes, switch recombination is targeted to distinct switch regions as well. In a panel of clonally unrelated IgG1-expressing human B cells, immortalized by Epstein-Barr virus (EBV) transformation, seven out of nine cells show switch recombination between Sμ and Sγ1 on both alleles, the active and inactive one. The remaining cells show no switch recombination on the inactive IgH locus. The very strong correlation of switch recombination on both alleles of IgG1-expressing cells proves that class switch recombination to IgG1 is not random but directed in human B lymphocytes.     

In vivo and in vitro IgE isotype switching in human B lymphocytes: Evidence for a predominantly direct IgM to IgE class switch program

Molecular analysis of circular excision products and composite genomic switch regions has demonstrated that in mice, immunoglobulin (Ig) isotype switching from IgM to IgE often proceeds sequentially via IgG1. Based on analysis of Ig production in cell cultures, it has been suggested that human B cells may switch to IgE via IgG4, whereas limited molecular data from in vitro switched B cells suggest a direct IgM to IgE switch program. To obtain a quantitative assessment of direct versus sequential IgE switching in humans, we have analyzed the nucleotide sequences of 29 composite Sμ/S? switch regions from freshly isolated human B lymphocytes from patients with atopic dermatitis and from B lymphocytes induced to switch to IgE synthesis in vitro. The data show that in these B cells IgE isotype switching progressed directly from IgM to IgE. We conclude that, in contrast to the murine IgM/IgE switch program, the IgM to IgE switch in B lymphocytes from patients with atopic dermatitis as well as in vitro stimulated B cells from healthy donors preferentially proceeds via direct Sμ to S? switch recombination.     

Switching from intravenous to oral antibiotics in hospitalized patients with community-acquired pneumonia: A real-world analysis 2010–2018

The Japanese Respiratory Society 2017 guidelines strongly recommend switching from intravenous (IV) to oral antibiotics in patients with community-acquired pneumonia (CAP), following improvement in clinical symptoms and laboratory findings. Here, we retrospectively investigated the real-world, nationwide treatment and switching patterns for hospitalized patients with CAP in Japan using administrative data from 372 Japanese Diagnosis Procedure Combination hospitals from April 2010 to December 2018. Hospitalizations for CAP (patient age ≥20 years) with an A-DROP classification for CAP severity and IV antibiotics initiated on the admission date were included. Overall, 210,314 hospitalizations (moderate CAP: 61.7%) in 183,607 patients were analyzed. The median (interquartile range [IQR]) age at admission was 79 (70–86) years. Penicillin (51.9%) and cephalosporin (38.9%) were the most common IV antibiotic classes used and the median (IQR) duration of IV use was 8 (6–11) days. Switching to oral antibiotics during a hospitalization occurred in 30.1% (n = 63,311) of patients after a median (IQR) of 7 (5–10) days of IV treatment. The most frequently used oral antibiotic classes after a switch were fluoroquinolone (45.9%) and penicillin (24.8%). The switch rate was higher among hospitalizations with milder CAP, in respiratory medicine ward and in larger hospitals. The overall switch rates did not change over the study period. The findings from this analysis suggest that early switch from IV to oral antibiotics was not widely implemented during the 8 years of the study period. Further observation will be needed to see the potential impact of the guidelines update in 2017 in Japan.     

Interchangeability of biosimilar and biological reference product: updated regulatory positions and pre- and post-marketing evidence

Introduction: Since 2006, biosimilars have been available in several countries worldwide, thus allowing for potential savings in pharmaceutical expenditure. However, there have been numerous debates about the interchangeability of biosimilars and reference products based on concerns of immunogenicity by switching between biological products, which may cause lack of effect and toxicity.

Areas covered: The authors provide the reader with an overview of the different positions of regulatory authorities on the interchangeability and automatic substitution of biosimilars and reference products. Presently, the FDA allows automatic substitution without prescriber intervention if the biosimilar is interchangeable with reference products, while the European Medicines Agency delegate to each single EU member state.

Expert opinion: Different approaches in defining interchangeability and automatic substitution call for harmonization to increase confidence of healthcare professionals and patients about the clinical impact of switching. Networks of electronic healthcare records and administrative databases, potentially linkable to clinical charts and registries may rapidly assess frequency and benefit-risk profile of different switching patterns in routine care at different levels, thus integrating and strengthening pre-marketing evidence.     

Activation-induced cytidine deaminase induces DNA break repair events more frequently in the Ig switch region than other sites in the mammalian genome

Activation-induced cytidine deaminase (AID) produces DNA breaks in immunoglobulin genes during antibody diversification. Double-stranded breaks (DSB) in the switch region mediate class switch recombination, and contribute to gene conversion and somatic hypermutation in the variable regions. However, the relative extent to which AID induces DSB in these regions or between these and other actively expressed sequences is unknown. Here, we exploited an enhancer-trap plasmid that identifies DSB in actively expressed loci to investigate the frequency and position of AID-induced vector integration events in mouse hybridoma cells. Compared to control cells, wild-type AID stimulates plasmid integration into the genome by as much as 29-fold. Southern and digestion-circularization PCR analysis revealed non-uniformity in the integration sites, with biases of 30- and 116-fold for the immunoglobulin kappa light chain and mu heavy chain genes, respectively. Further, within the immunoglobulin mu gene, 73% of vector integrations map to the mu switch region, an enhancement of five- and 12-fold compared to the adjacent heavy chain variable and mu gene constant regions, respectively. Thus, among potential highly transcribed genes in mouse hybridoma cells, the immunoglobulin heavy and light chain genes are important AID targets, with the immunoglobulin mu switch region being preferred compared to other genomic sites.     

转换疗法及其在医院合理应用抗菌药物中的作用

目的:明确转换疗法在医院合理应用抗菌药物、降低医疗费用方面的作用。方法:介绍转换疗法的概念、源由及优点,查阅近年国内、外应用抗菌药物转换疗法的相关文献,论证其优点及可靠性。结果:抗菌药物转换疗法不仅疗效可靠,而且经济,能有效降低医疗费用。结论:转换疗法是促进合理应用抗菌药物、降低医疗费用的有力措施之一,值得推广。     

深低温体外循环在婴幼儿大动脉转位矫治术中的应用

目的分析深低温体外循环在婴幼儿大动脉转位矫治(Switch)术中的运用和技术关键进行探讨和总结。方法回顾本院2004年1月至2006年7月期间,共对131例婴幼儿Switch术采用的深低温体外循环技术。占同期体外循环手术的3.2%。女16例,男115例。年龄从出生7个小时至12个月(3.6±2.2)个月,体重从1.79~8(4.2±1.4)kg。采用深低温低流量(DHLF)14例,深低温停循环(DHCA)5例,深低温停循环结合低流量(DH-CA DHLF)112例。所有病例采用pH稳态结合α稳态的血气管理方法。术毕131例均采用改良超滤法(MUF),其中57例采用传统超滤(CUF)结合改良超滤的方法。结果体外循环时间45~215(126.5±45.2)min;主动脉阻断时间44~160(80.9±26.4)min;停循环时间4~53(18.5±12.6)min;低流量时间8~150(65.4±34.3)min。MUF时间10~15min,滤出液体(229.9±121.3)ml;在体外循环期间CUF时间5~30min,滤出液体(237.8±107.5)ml。体外循环中Hb(86±8.7)g/L,MUF后Hb可达到(118±17)g/L。本组死亡率10.7%,自动复跳率100%。结论新生儿和低体重的婴儿选择在深低温体外循环下进行Switch术更为有利。     

Ultrasonic identification and examination of fetal heart structures

Ultrasonic studies were performed on normal fetuses ranging from 36 to 40 weeks gestational age in an attempt to visualize anatomical details of the fetal heart. We were able to visualize cardiac structures hitherto thought to be unidentifiable. Two-dimensional B-scan exposures of sections showed transverse and longitudinal sections of the fetal heart, including the cardiac septa and inlet and outlet sites of the large vessels. To attempt to elucidate the dynamics of the fetal heart, the motility patterns of the cardiac structures were examined by time-motion mode scanning and the patterns obtained were compared to those observed in the postnatal heart. The reliability of the theories advanced and the further prospects are discussed.