[Hot topics in obstetric anesthesia]. / "Hot topics" aus der geburtshilflichen Anästhesie.

In 2019 the annual conference of the scientific working group on obstetric anesthesiology of the German Society of Anesthesiology and Intensive Care Medicine (DGAI) took place in the usual manner. Emergency situations, such as the challenge of a preclinical birth or the recognition and treatment of an amniotic fluid embolism were discussed. In addition, topics on the correct treatment of a female patient with a known addictive disorder were of great interest as well as the discussion on the question when a transfusion should be performed in postpartum anemia and which risks accompany the increasing prevalence of obesity, especially during pregnancy. A further hot topic was the deliberation on the prevalence and differential diagnostic clarification of neurological complications after epidural anesthesia. In connection with the topic of birth, exciting and practice relevant topics for all anesthetists confronted with this field were presented and discussed. The essential aspects are summarized in this article.

[Relevant aspects of the ESC guidelines for the management of cardiovascular diseases during pregnancy for obstetric anaesthesia (update 2018)]. / Anästhesiologisch relevante Aspekte der ESC-Leitlinien für das Management von kardiovaskulären Erkrankungen während der Schwangerschaft (Update 2018).

The current update of the ESC (European Society of Cardiology) guidelines on managing cardiovascular diseases during pregnancy provides instructions for doctors in daily practice. Heart diseases are the most common reason for maternal death during pregnancy in western countries. Among other things, the following topics are dealt with: congenital heart disease, pulmonary hypertension, aortic and valvular diseases as well as arrhythmias and hypertensive disorders. Compared to the guidelines from 2011 some changes have been made regarding the recommendations to classify maternal risk according to the modified World Health Organization (mWHO) classification or in recommendations on anticoagulation for low-dose and high-dose requirements of vitamin K antagonists. The main focus of this summary of recent recommendations is the impact on the anesthesia management in order to provide responsible anesthesiologists with relevant background knowledge.

Caco-2 cells - expression, regulation and function of drug transporters compared with human jejunal tissue.

BACKGROUND: Induction or inhibition of drug transporting proteins by concomitantly administered drugs can cause serious drug-drug interactions (DDIs). However, in vitro assays currently available are mostly for studying the inhibitory potential of drugs on intestinal transporter proteins, rather than induction. Therefore, this study investigated the suitability of the frequently used intestinal Caco-2 cell line to predict transporter-mediated DDIs as caused by induction via activation of nuclear receptors. METHODS: TaqMan® low density arrays and LC-MS/MS based targeted proteomics were used to evaluate transporter expression in Caco-2 cells in comparison with jejunal tissue, in culture-time dependence studies and after incubation with different known inducers of drug metabolism and transport. Additionally, studies on ABCB1 function were performed using Transwell® assays with [3 H]-digoxin and [3 H]-talinolol as substrates after incubation with the prototypical inducers rifampicin, St John's wort, carbamazepine and efavirenz. RESULTS: The gene and protein expression pattern of drug transporters in Caco-2 cells and jejunal tissue differed considerably. For some transporters culture-time dependent differences in mRNA expression and/or protein abundance could be determined. Finally, none of the studied prototypical inducers showed an effect either on mRNA expression and protein abundance or on the function of ABCB1. CONCLUSION: Differences in transporter expression in Caco-2 cells compared with jejunal tissue, as well as expression dependence on culture time must be considered in in vitro studies to avoid under- or overestimation of certain transporters. The Caco-2 cell model is not suitable for the evaluation of DDIs caused by transporter induction. Copyright © 2016 John Wiley & Sons, Ltd.

Pinned orbital moments - A new contribution to magnetic anisotropy.

Reduced dimensionality and symmetry breaking at interfaces lead to unusual local magnetic configurations, such as glassy behavior, frustration or increased anisotropy. The interface between a ferromagnet and an antiferromagnet is such an example for enhanced symmetry breaking. Here we present detailed X-ray magnetic circular dichroism and X-ray resonant magnetic reflectometry investigations on the spectroscopic nature of uncompensated pinned magnetic moments in the antiferromagnetic layer of a typical exchange bias system. Unexpectedly, the pinned moments exhibit nearly pure orbital moment character. This strong orbital pinning mechanism has not been observed so far and is not discussed in literature regarding any theory for local magnetocrystalline anisotropy energies in magnetic systems. To verify this new phenomenon we investigated the effect at different temperatures. We provide a simple model discussing the observed pure orbital moments, based on rotatable spin magnetic moments and pinned orbital moments on the same atom. This unexpected observation leads to a concept for a new type of anisotropy energy.

Comparison of the C-MAC(®) and GlideScope(®) videolaryngoscopes in patients with cervical spine disorders and immobilisation.

In-line stabilisation of the neck can increase the difficulty of tracheal intubation with direct laryngoscopy. We randomly assigned 56 patients with cervical spine pathology scheduled for elective surgery to tracheal intubation using either the C-MAC(®) (n = 26) or GlideScope(®) (n = 30), when the head and neck were stabilised in-line. There was no significant difference in the median (IQR [range]) intubation times between the C-MAC (19 (14-35 [9-90]) s and the GlideScope (23, (15-32 [8-65]) s. The first-attempt failure rate for the C-MAC was 42% (95% CI 23-63%) compared with 7% (95% CI 1-22%) for the GlideScope, p = 0.002. The laryngeal view was excellent and comparable with both devices, with the C-MAC requiring significantly more attempts and optimising manoeuvers (11 vs 5, respectively, p = 0.04). There were no significant differences in postoperative complaints e.g. sore throat, hoarseness and dysphagia. Both devices provided an excellent glottic view in patients with cervical spine immobilisation, but tracheal intubation was more often successful on the first attempt with the GlideScope.

Structure-property relationship of anilino-squaraines in organic solar cells.

Soluble molecular semiconductors are a promising alternative to semiconducting polymers in the field of organic photovoltaics. Here, three custom-made symmetric 1,3-bis(N,N-alkylated-2,6-dihydroxy-anilino)squaraines containing systematic variations in their molecular structures are compared regarding their applicability as donor materials in bulk-heterojunction solar cells. The terminal substitution pattern of the squaraines is varied from cyclic over linear to branched including a stereogenic center. Single crystal structures are determined, and, in the case of chiral squaraine, unusual formation of stereoisomer co-crystals is revealed. The thin film absorbance spectra show characteristic signatures of H- and J-bands or hint at the formation of tautomers. The general feasibility of these model compounds for photovoltaic applications is studied by light-induced electron spin resonance spectroscopy. The impact of the different molecular substitution patterns on aggregation behavior and, consequently, their optoelectronic solid state properties including charge carrier mobility and finally the solar cell performance are investigated.

LC-MS/MS-based quantification of clinically relevant intestinal uptake and efflux transporter proteins.

Multidrug transporter proteins are crucial determinants in the pharmacokinetics of many drugs. To evaluate their impact on intestinal drug absorption, we developed and validated quantification methods for 10 uptake transporters (OATP1A2, OATP2B1, PEPT1, ASBT, OCT1, OCT3) and efflux transporters (ABCB1, ABCC2, ABCC3, ABCG2) that have been reported to be expressed and to be of clinical relevance in the human intestine. Quantification was performed by targeted liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based quantification of proteospecific peptides after tryptic digestion using stable isotope labeled internal standard peptides. The chromatography of the respective peptides was performed by gradient elution using a reversed phase (C18) column (Kinetex(®), 100 × 3.0 mm, 2.6 µm) and 0.1% formic acid (FA) and acetonitrile with 0.1% FA as mobile phases at a flow rate of 0.5 ml/min. The MS/MS detection was done in the positive multiple reaction monitoring (MRM) mode by monitoring in each case three mass transitions for the transporter-derived peptides and the internal standard peptides. The assays were validated with respect to specificity, linearity (0.1-25 nM), within-day and between-day accuracy and precision as well as stability according to current bioanalytical guidelines. Finally, the developed methods were used to determine the transporter protein content in human intestinal tissue (jejunum and ileum). The methods were shown to possess sufficient specificity, sensitivity, accuracy, precision and stability to measure transporter proteins in the human intestine.

Magnetic proximity effect in YBa2Cu3O7/La(2/3)Ca(1/3)MnO3 and YBa2Cu3O7/LaMnO(3+δ) superlattices.

Using neutron reflectometry and resonant x-ray techniques we studied the magnetic proximity effect (MPE) in superlattices composed of superconducting YBa2Cu3O7 and ferromagnetic-metallic La0.67Ca0.33MnO3 or ferromagnetic-insulating LaMnO(3+δ). We find that the MPE strongly depends on the electronic state of the manganite layers, being pronounced for the ferromagnetic-metallic La0.67Ca0.33MnO3 and almost absent for ferromagnetic-insulating LaMnO(3+δ). We also detail the change of the magnetic depth profile due to the MPE and provide evidence for its intrinsic nature.

[Bicycle ergometer for rehabilitation]. / Fahrradergometer für die Rehabilitation.

In patients that are in rehabilitation the physical ability is measured with stationary cycle ergometers. A new ergometer, that can be mounted easily to a bicycle, allows the mobile measurement independent of the location. The principle is based on the simultaneous measurement of chain force and chain velocity. One component of the chain force is measured, that is generated by the change of the chain's direction by pulleys. The velocity of the chain is measured by the rotational speed of one of the pulleys. The new ergometer is easy to attach and remove. The measured values are digitized, numerically processed and recorded. Through a GSM-Modem these data are transmitted to a remote central host computer and allow the control/evaluation of the patient's performance.

Postprandial insulin lispro. A new therapeutic option for type 1 diabetic patients.

OBJECTIVE: For intensified insulin therapy of type 1 diabetes, bolus injection of regular human insulin 30-15 min before a meal is currently recommended. This randomized study is aimed to determine whether insulin lispro (LIS), a new insulin analog with a rapid onset of action, can provide comparable blood glucose (BG) control by injection after the meal. RESEARCH DESIGN AND METHODS: Eighteen type 1 diabetic subjects injected regular insulin (REG) at 40, 20, or 0 min before or LIS at 20 or 0 min before or 15 min after the start of a standardized test meal. BG excursions and area under the curve of BG excursions (AUC) at the six visits were compared by analysis of variance. Hypoglycemic events (BG < or = 2.78 mmol/l) were evaluated in relation to the achieved postprandial BG control. RESULTS: Mean AUC values were 2.00, 2.55, and 3.33 mmol.h.l-1 for REG given 40, 20, and 0 min before the test meal, respectively, and -2.19, -2.15, and 1.98 mmol.h.l-1 for LIS given 20 and 0 min before and 15 min after the start of the test meal, respectively. LIS injected 20 min (-20) or immediately (0) before the meal was significantly more effective in controlling postprandial BG excursion (P < 0.001) than any REG treatment. Postprandial injection of LIS (15) did not compromise postprandial BG control and resulted in less hypoglycemia. REG -40 and LIS -20 were associated with early hypoglycemia, but other hypoglycemic events were equally distributed among groups. CONCLUSIONS: The optimal time for bolus insulin injection was 20 min before the meal for REG and immediately before the meal for LIS. LIS injected immediately after a standard meal provided postprandial BG control at least as good as REG injected from 40 to 0 min before the meal. Postprandial injection of LIS is an attractive new therapeutic option.

Current and future directions of biomedical materials research.

Biomedical materials and implants are not synonymous. Materials per se are not implanted--after configuring, processing, and finishing operations, they constitute parts of implants and other devices. The U.S. Food and Drug Administration currently does not "approve" biomaterials; rather, it approves medical devices, biologicals, and drugs. There have been important advances during the past 40 years in the clinical uses of medical implants and other devices, especially in ophthalmology, cardiology, orthopaedics, surgery and dialysis. In the 21st Century, there will be increased emphasis on curing and preventing major genetic diseases. There will be many nontraditional clinical applications of biomaterials, such as viral- and nonviral-mediated delivery agents in gene therapy, synthetic biomaterials with pharmacologic effects, and biomaterials that can integrate with the biological system to form a long-term, living, renewable interface with prosthetic implants. Therefore, those working in the field of biomaterials must become familiar with new molecular biological techniques and be able to collaborate effectively with molecular biologists.

Nondipping of nocturnal blood pressure is related to urinary albumin excretion rate in patients with type 2 diabetes mellitus.

Although cardiovascular and cerebrovascular morbidity and mortality in type 2 diabetic patients is closely related to urinary albumin excretion rate (UAER), the causative mechanisms are not yet identified. The aim of our study was to define the circadian variation of blood pressure (BP) in 72 type 2 diabetic patients (mean age 60 years, mean diabetes mellitus duration: 12 years) in comparison with 41 nondiabetic controls with essential hypertension (mean age 58 years) by using ambulatory blood pressure measurement. Thirty diabetic patients had normal UAER (< 30 mg/24 h), 27 had microalbuminuria (30 to 300 mg/24 h), and 15 had persistent proteinuria (> 300 mg/24 h). Systolic blood pressure during both nighttime and daytime was significantly elevated in type 2 diabetic patients with macroalbuminuria compared to controls and patients with normal UAER. During nighttime even type 2 diabetic patients with microalbuminuria had significantly elevated systolic blood pressure compared to controls with essential hypertension. We also observed a correlation of nocturnal blood pressure to UAER (systolic: r = 0.32, P < .007 and diastolic: r = 0.24, P < .04). Nondipping (defined as a reduction of nocturnal BP < 10%) was observed in 80% of the macroalbuminuric, 74% of the microalbuminuric, but only in 43% of the normoalbuminuric type 2 diabetic patients and in 37% of the controls (P < .04). Since a loss of circadian variation of BP is closely related to vascular complications in nondiabetics, our findings may indicate an important relationship between nondipping of BP and the high morbidity and mortality rate in diabetic patients with increased UAER.

Long-term stability of intraocular lenses: literature review, assessment, and testing protocol.

A critical review of the literature confirms the generally excellent, very long-term clinical stability and performance of polymethylmethacrylate (PMMA) in intraocular lenses. In contrast, only short-term, largely nonsystematic data are available on the performance of other, newer materials, such as soft silicones based on polydimethylsiloxane and copolymers of dimethyl- and diphenylsiloxane, hydrogels based on poly(2-hydroxyethylmethacrylate), and various "temporary" and "permanent" hydrophilic coatings. Some conflicting reports have been published on the long-term stability of isotactic polypropylene loop materials. However, the medical consensus seems to be that these are essentially stable to ultraviolet light energy reaching intraocular lenses during the expected service life in excess of 20 years. Uncertainty still surrounds the use of various ultraviolet-absorbing chromophores in the optics and/or haptics of intraocular lenses. Published reports indicate varying transmittance and effectiveness of ultraviolet-absorbing intraocular lenses. Furthermore, there is concern about the fate of the ultraviolet-absorbing chromophores during clinical conditions, especially with regard to degradation and leaching. Although a number of papers has been published on the effect of ultraviolet light energy on intraocular lenses, the experimental approaches differed substantively, so that intercomparative deductions must be made guardedly. A few papers have been published on the long-term biostability (hydrolytic, oxidative, and enzymatic) of intraocular lens materials. However, much of what has appeared in the literature is often illustrative of simplistic assumptions that largely ignore the environment of the eye. Clearly, the eventual success of newer materials must be based on performance characteristics that exceed those of the time-tested polymethylmethacrylate and the refined manufacturing technology designed to transform this polymer into intraocular lenses. The unquestioned clinical success of intraocular lenses rests on long historical data with PMMA that are unavailable with proposed newer materials. Thus, the entry of such new materials into the commercial market, meriting the acceptance of clinicians (and patients), must follow rather than precede thorough in vitro accelerated testing procedures under conditions that permit intercomparative conclusions and recommendations.

Implant retrieval, analysis, and database: a challenge for the medical devices industry.

Despite the widespread use of various medical implant devices since the 1960s, there has not been any systematic effort developed for implant retrieval, analysis, and data banking. Most medical implants fail prematurely because of selection of wrong materials and/or processing conditions, selection of wrong in vitro testing methods, inappropriate extrapolation to in vivo conditions, and/or ignorance of the state of the art. Inasmuch as another federal effort is unlikely to deal effectively with these problems, it is proposed that the medical devices industry establish an independent Institute for Medical Implant Retrieval and Analysis using a small percentage of the profits gained from the sale of implants. In addition to carrying out in-house work, this Institute would support appropriate projects in selected academic institutions, with appropriate feedback to regulatory agencies internationally.

[Decreased plasma carnitine in Type I diabetes mellitus]. / Vermindertes Plasmacarnitin bei Typ-I Diabetes mellitus.

Realizing the importance of carnitine for the lipid and carbohydrate metabolism and the possible role for glucose utilization and myocardial function carnitine concentrations in type I and type II diabetic patients in plasma, erythrocytes and 24 h urine were determined. The plasma levels of carnitine were significantly diminished in type I diabetic patients compared to controls, while carnitine concentrations in erythrocytes and 24 h urine did not differ from controls. Plasma carnitine levels did not change significantly during the diurnial profile. No correlation between HbA1c and carnitine levels was observed in the diabetic patients.

Biostability of materials and implants.

The purpose of this paper is to discuss some important parameters that are involved in the biostability of materials and implants aimed at the eventual development of improved in vitro testing and evaluation procedures. In view of the fact that certain terms have been the subject of misunderstandings, definitions are offered for the terms "biomaterials", "bioerosion", "biostability", and "bioresorption". Following brief descriptions of various classes of materials used in biomedical applications, the in vitro and in vivo degradations of selected materials are discussed. The main conclusions are as follows: (1) most synthetic polymers degrade in vivo by nonenzymatic hydrolysis. Hence, it is recommended that initial, in vitro testing schemes of most synthetic polymers and implants omit the use of enzyme solutions. The use of enzyme solutions is appropriate in the case of natural biopolymers as well as synthetic biodegradable polymers that contain peptidic-, glycosidic-, or phosphatidic bonds. (2) The biostability of materials and implants may be greatly affected by the simultaneous presence of stresses and active components in the physiologic environment that may lead to environmental stress cracking. (3) The biostability of polymeric materials is influenced not only by adsorption but also by the absorption of components in the physiologic environment.