Automated solid-phase extraction and two-step derivatisation for simultaneous analysis of basic illicit drugs in serum by GC/MS

A combination of automated solid-phase extraction (SPE) and subsequent two-step derivatisation has been developed for the simultaneous analysis of basic drugs of abuse and cocaine metabolites in serum samples. Substances included in this procedure are morphine, codeine, methadone, cocaine, benzoylecgonine, methylecgonine, amphetamine, methamphetamine, MDMA, MDEA and MDA. SPE with mixed-mode cartridges (RP-C8 and cation-exchange) was fully automated with a Zymark RapidTrace SPE robot. GC/MS analysis was performed after derivatisation with a new two-step reaction by trifluoroacetic anhydride and 2,2,3,3,3-pentafluoropropanol. High recoveries (> 85%) with high reproducibility (CV 1.1-3.8%) were found for all drugs. High correlation coefficients (r > 0.998) were obtained due to the addition of deuterated standards prior to extraction. Experience obtained over 2 years of applying this method to drug analysis in serum is discussed.     

Über histologische Befunde beim Verbrennungstod

Zusammenfassung Es wurden die Organe von 8 Verbrennungsfällen histologisch untersucht. Neben leicht degenerativen Veränderungen (Verfettung der Leber, selten auch des Myokards und hyalintropfiger Degeneration der Nieren in einem Fall) wurden hauptsächlich Veränderungen der Milz und Leber gefunden.In der Milz war zum Teil eine Schädigung der Keimzentren der Knötchen, zum Teil eine hyaline Einlagerung in der Wand der kleinen Arterien vorhanden, die jedoch keinen spezifischen Charakter besitzt. Erythrocytentrümmer und globulifere Zellen wurden nur in geringer Zahl angetroffen.In der Leber besteht die Hauptveränderung in einer starken Vermehrung der Leukocyten in den Blutcapillaren, wobei ein großer Teil dieser Leukocyten die vonStaemmler beschriebenen Degenerationsformen der Kerne aufweist. Es deutet dies auf einen stark vermehrten Zerfall der Leukocyten bei tödlicher Verbrennung hin, wobei freilich diese Veränderung für die Verbrennung nicht spezifisch ist. Der erhöhte Untergang der Leukocyten steht mit dem klinisch beobachteten Leukocytensturz in guter Übereinstimmung.Hämoglobinurie wurde nur in einem Falle beobachtet.Die vonKolisko undNakata beschriebenen schweren Veränderungen der Nebenniere wurden nie beobachtet und können deshalb keine ursächliche Bedeutung für den Verbrennungstod beanspruchen.     

Einzelreferate und Buchbesprechungen

Ohne Zusammenfassung     

Effects of an Amino Acid-Based Formula Supplemented with Two Human Milk Oligosaccharides on Growth,Tolerability, Safety,and Gut Microbiome in Infants with Cow’s Milk Protein Allergy

This open-label, non-randomized, multicenter trial (Registration: {"type":"clinical-trial","attrs":{"text":"NCT 03661736","term_id":"NCT03661736"}}NCT 03661736) aimed to assess if an amino acid-based formula (AAF) supplemented with two human milk oligosaccharides (HMO) supports normal growth and is well tolerated in infants with a cow’s milk protein allergy (CMPA). Term infants aged 1–8 months with moderate-to-severe CMPA were enrolled. The study formula was an AAF supplemented with 2′-fucosyllactose (2′-FL) and lacto-N-neotetraose (LNnT). Infants were fed the study formula for 4 months and were offered to remain on the formula until 12 months of age. Tolerance and safety were assessed throughout the trial. Out of 32 infants (mean age 18.6 weeks; 20 (62.5%) male), 29 completed the trial. During the 4-month principal study period, the mean weight-for-age Z score (WAZ) increased from –0.31 at the baseline to +0.28 at the 4-months’ follow-up. Linear and head growth also progressed along the WHO child growth reference, with a similar small upward trend. The formula was well tolerated and had an excellent safety profile. When comparing the microbiome at the baseline to the subsequent visits, there was a significant on-treatment enrichment in HMO-utilizing bifidobacteria, which was associated with a significant increase in fecal short-chain fatty acids. In addition, we observed a significant reduction in the abundance of fecal Proteobacteria, suggesting that the HMO-supplemented study formula partially corrected the gut microbial dysbiosis in infants with CMPA.     

Prior intake of new oral anticoagulants adversely affects outcome following surgery for acute type A aortic dissection

Open in a separate window OBJECTIVESOral anticoagulation prior to emergency surgery is associated with an increased risk of perioperative bleeding, especially when this therapy cannot be discontinued or reversed in time. The goal of this study was to analyse the impact of different oral anticoagulants on the outcome of patients who underwent emergency surgery for acute type A aortic dissection (ATAAD).METHODSThis was a single-centre retrospective study of patients treated with oral anticoagulation at the time of surgery for ATAAD. Outcomes of patients on new oral anticoagulant (NOAC) therapy were compared to respective outcomes of patients on Coumadin. Additionally, a survival analysis was performed comparing these 2 groups with patients who were operated on with no prior anticoagulation.RESULTSBetween January 2013 and April 2020, a total of 437 patients (63.8 ± 11.8 years, 68.4% male) received emergency surgery for ATAAD; 35 (8%) were taking oral anticoagulation at the time of hospital admission: 20 received phenprocoumon; 14, rivaroxaban; and 1, dabigatran. Compared to Coumadin, NOAC was associated with a greater need for blood-product transfusions and haemodynamic compromise. Operative mortality was 53% in the NOAC group and 30% in the Coumadin group. A 5-year survival analysis showed no significant difference between the NOAC and the Coumadin group (P = 0.059). Compared to 402 patients treated during the study period without anticoagulation, patients taking NOAC had significantly worse survival (P = 0.001), whereas that effect was not observed in patients undergoing surgery who were taking Coumadin (P = 0.99).CONCLUSIONSEmergency surgery for ATAAD in patients taking NOAC is associated with high morbidity and mortality. NOAC are a major risk factor for uncontrollable bleeding and haemodynamic compromise. New treatment strategies must be defined to improve surgical outcomes in these high-risk patients.     

Surgical management of portal hypertension and esophageal varices: 10 year experience

The results of 157 operations performed for portal hypertension and esophageal varices on 148 patients at the Cleveland Clinic in the 10 year period between 1970 and 1980 are reported. One hundred four shunt procedures and 53 ligation procedures were performed. The overall operative mortality rate of 13 percent did not differ significantly from the 11 percent rate reported from this institution in 1971. A comparatively higher rate of recurrent variceal hemorrhage and a lower rate of encephalopathy reflected our increased use of selective shunts and ligation procedures. There was no improvement in overall long-term survival, which was approximately 50 percent.The two most important factors in predicting the results of all operations for esophageal varices continue to be assessment of preoperative liver function and the timing of the operation. The best results were obtained in patients with good liver function who had an elective operation. Our data suggest that the portacaval shunt is associated with a higher incidence of late mortality, largely as a result of liver failure; therefore, our preference now is to perform a distal selective splenorenal shunt procedure whenever possible. If a selective shunt procedure cannot be performed, we advocate either a mesocaval shunt or a ligation procedure, depending on patient risk and the suitability of veins for a shunt procedure.     

The Nonhematopoietic Effects of Erythropoietin in Skin Regeneration and Repair: From Basic Research to Clinical Use

Erythropoietin (EPO) is the main regulator of red blood cell production but there exists also a variety of nonhematopoietic properties. More recent data show that EPO is also associated with the protection of tissues suffering from ischemia and reperfusion injury as well as with improved regeneration in various organ systems, in particular the skin. This review highlights the mechanisms of EPO in the different stages of wound healing and the reparative processes in the skin emphasizing pathophysiological mechanisms and potential clinical applications. There is clear evidence that EPO effectively influences all wound‐healing phases in a dose‐dependent manner. This includes inflammation, tissue, and blood vessel formation as well as the remodeling of the wound. The molecular mechanism is predominantly based on an increased expression of the endothelial and inducible nitric oxide (NO) synthase with a consecutive rapid supply of NO as well as an increased content of vascular endothelial growth factor (VEGF) in the wound. The improved understanding of the functions and regulatory mechanisms of EPO in the context of wound‐healing problems and ischemia/reperfusion injury, especially during flap surgery, may lead to new considerations of this growth hormone for its regular clinical application in patients.