Arterielle Verschlusssysteme

Clinical/methodical issue

Access site complications after endovascular catheterization sometimes require open surgery and negatively impair safety, patient comfort and reimbursement. Increasing numbers of procedures and patients with multiple anticoagulants as well as cost pressure explain the demand for an immediate and stable access site closure.

Standard radiological methods

Manual compression followed by compression bandage and bed rest for 4–24 h is still the gold standard but is unable to prevent access site complications in all cases.

Methodical innovations

Arterial vascular closure devices allow immediate and stable closure of the puncture channel either by suture or by implantation of occluding foreign bodies or gluing fluids.

Performance

The safety has been proven in several clinical trials. The main advantage lies in closing large lumen access sites without surgery and in patients treated with multiple anticoagulants as well as in outpatient procedures.

Achievements

They have become a valuable supplement to the interventional arsenal.

Practical recommendations

The physician, however, has to decide between different systems and mechanisms with respect to patient constitution, selected access vessel and level of calcification and diameter. Furthermore, all systems require a defined training prior the first use.     

WNT6/ACC2-induced storage of triacylglycerols in macrophages is exploited by Mycobacterium tuberculosis

In view of emerging drug-resistant tuberculosis (TB), host-directed adjunct therapies are urgently needed to improve treatment outcomes with currently available anti-TB therapies. One approach is to interfere with the formation of lipid-laden “foamy” macrophages in the host, as they provide a nutrient-rich host cell environment for Mycobacterium tuberculosis (Mtb). Here, we provide evidence that Wnt family member 6 (WNT6), a ligand of the evolutionarily conserved Wingless/Integrase 1 (WNT) signaling pathway, promotes foam cell formation by regulating key lipid metabolic genes including acetyl-CoA carboxylase 2 (ACC2) during pulmonary TB. Using genetic and pharmacological approaches, we demonstrated that lack of functional WNT6 or ACC2 significantly reduced intracellular triacylglycerol (TAG) levels and Mtb survival in macrophages. Moreover, treatment of Mtb-infected mice with a combination of a pharmacological ACC2 inhibitor and the anti-TB drug isoniazid (INH) reduced lung TAG and cytokine levels, as well as lung weights, compared with treatment with INH alone. This combination also reduced Mtb bacterial numbers and the size of mononuclear cell infiltrates in livers of infected mice. In summary, our findings demonstrate that Mtb exploits WNT6/ACC2-induced storage of TAGs in macrophages to facilitate its intracellular survival, a finding that opens new perspectives for host-directed adjunctive treatment of pulmonary TB.     

Cognitive aging is linked to social role in honey bees (Apis mellifera)

Aging is associated with cognitive impairment in numerous animal species. Across taxa, decline in learning performance is linked to chronological age. The honey bee (Apis mellifera), in contrast, offers an opportunity to study such aspects of aging largely independent of age per se. This is because foraging onset can be decoupled from chronological age, although workers typically first perform tasks inside the nest and later forage outside the hive. Further, early phases of foraging are characterized by growth of specific brain neuropiles, whereas late phases of the forager life-stage are accompanied by accelerated rates of physiological senescence. Yet, it is unclear if these patterns of senescence include cognitive function. The flexibility of worker ontogeny, however, suggests that the bee can become an attractive model for studies of plasticity in cognitive aging that ultimately may lead to insight into mechanisms that govern age-related cognitive decline. To address this potential, we studied effects of honey bee chronological age and of social role on sensory sensitivity and associative olfactory learning performance. Our results show a decline in olfactory acquisition performance that is linked to social role, but not to chronological age. This decline occurs only in foragers with long foraging duration, but at the same time the foragers show less generalization of odors, which is indicative of more precise learning. Foragers that are reversed from foraging to nest tasks, furthermore, do not show deficits in olfactory acquisition. These results point to complex effects of aging on associative learning in honey bees.     

Standardless 1H NMR determination of pharmacologically active substances in dietary supplements and medicines that have been illegally traded over the Internet

Dietary supplements and medicines are widely marketed over the Internet. Such products may be counterfeited and lack some or all of the labelled ingredients, or, in the case of lifestyle supplements, illegally contain pharmacologically active substances, such as anorectic or androgenic compounds. The market control – especially in the case of customs seizures – is complex, as reference substances necessary for identification and calibration in traditional high performance liquid chromatography (HPLC) or gas chromatography–mass spectrometry (GC‐MS) analysis are often unavailable, or extremely expensive. In this study, we introduce a 400 MHz ¹H NMR methodology, which allows identification and quantitative estimation even without such pure compound standards. The identification can be based on literature spectra, or if these data are unavailable, by applying computational NMR spectra prediction. For standardless NMR determination, simple peak‐area comparison of the target compound with the TSP reference was used. The applicability was demonstrated for a wide range of compounds, such as mesterolone, oxymetholone, sibutramine, monacolin K, vinpocetine, evodiamine, caffeine, kavain, and dehydroepiandrosterone. The average relative standard deviations were 5.0% for peak area comparison, and 3.3% for external calibration with standard substance. The method uncertainty is therefore higher in standardless determination, but acceptable for the purpose of proving the presence or absence of pharmacologically active substances. The limit of detection of 0.5–2 mg/kg is sufficient for the purpose. NMR is ideally suited to controlling dietary supplements or illegal medicines as it provides qualitative and at least semi‐quantitative information more rapidly (measurement time 20 min) than with any other currently available spectroscopic or chromatographic method. Copyright © 2012 John Wiley & Sons, Ltd.     

Infektionen und Immuntherapie

Allogeneic stem cell transplantation (SCT) can expose patients to a transient but marked immunosuppression, during which viral and fungal infections are an important cause of morbidity and mortality. Control of these infections ultimately depends on restoring adequate T-cell immunity. Most viral infections after SCT are caused by the endogenous reactivation of persistent pathogens such as adenovirus (ADV), cytomegalovirus (CMV), and Epstein-Barr-virus (EBV), whereas invasive infections due to Aspergillus spp. are mostly exogenous. Cellular immunotherapy is an attractive approach to enable immune protection of the host. The isolation of pathogen-specific T cells from a healthy donor and their infusion into a recipient is done by a procedure known as adoptive T-cell transfer. The separation of pathogen-specific T cells is necessary to deplete alloreactive T cells and avoid graft-versus-host disease. Adoptive T-cell transfer has been performed after allogeneic SCT in many patients with CMV, EBV, and ADV infections using time- and labour-consuming protocols. Based on basic research, new immunotherapeutic protocols aim at a broader and faster availability of adoptive T-cell transfer. However, the manipulation of antigen-specific T-cell responses as a treatment approach remains an ongoing challenge.     

Central venous pressure monitoring during living right donor hepatectomy.

Low central venous pressure (CVP) has been advocated during liver resection to reduce blood loss and transfusion requirements. As a consequence, CVP catheter placement has been considered essential for hepatic surgery, including living donor hepatectomies. We retrospectively analyzed whether intraoperative management without CVP monitoring influenced fluid administration, blood loss, and patient outcome. Medical charts and hospital data system of 50 adult to adult living liver donors were retrospectively reviewed. Data collection included patient demographics, intraoperative variables such as fluid management, blood loss, urine output, and operating room time. Postoperative variables were collected during the postanesthesia care unit stay and for the first 24 hours after surgery. Patients were then grouped on the basis of the presence or absence of a CVP catheter. Data were reanalyzed and groups compared. Patient groups did not differ in terms of demographics at baseline. When divided into groups with CVP and without CVP, the presence of CVP did not result in decreased intraoperative fluid administration. All patients were hemodynamically stable, and renal function was not different between groups throughout hospitalization. Length of postanesthesia care unit and hospital stay was the same. There was no difference in the frequency of complications during the hospital stay and at 3 months' follow-up. CVP monitoring did not appear to reduce blood loss when compared with patients without CVP monitoring. In centers with extensive experience, CVP monitoring may not be necessary in this highly selective patient population.     

Glutamine does not protect against hepatic warm ischemia/reperfusion injury in rats

The administration of glutamine before experimental ischemia/reperfusion (I/R) has been shown to protect intestinal, pulmonary, and myocardial tissue by inducing heat shock proteins (HSP). However, it is not known whether glutamine is protective for all organs. We therefore tested whether pretreatment with glutamine reduces injury following hepatic I/R in rats. Male lean Zucker rats were pretreated with either glutamine (0.75 g/kg intraperitoneally, n=6) or saline (n=6), 24 and 6 hours before ischemia. Seventy percent of the liver was exposed to 75 minutes of warm ischemia followed by 24 hours reperfusion. Liver enzymes, histology, neutrophil accumulation, survival, and heat shock protein (HSP) 70 induction were examined. Glutamine administration did not reduce liver injury. In both groups, 5 of 6 animals survived 24 hours of reperfusion. There was no difference in serum transaminase levels with AST 15113 ± 4336 U/L (glutamine) vs. 17695 ± 8531 U/L (control, P>0.05), and ALT 7763 6 2524 (glutamine) U/L vs. 5884 ± 2063 U/L (control, P>0.05). The degree of neutrophil accumulation and necrosis was not different between groups at 24 hours of reperfusion. Pretreatment did not result in HSP70 upregulation in any of the groups. Pretreatment with glutamine did not reduce hepatic ischemia/ reperfusion injury. The lack of protection was associated with an absence of HSP70 upregulation prior to ischemia. Presented at the 2005 American Hepato-Pancreato-Biliary Association Congress, Hollywood, Florida, April 14–17, 2005.     

Expression and tissue localization of soluble guanylyl cyclase in the human placenta using novel antibodies directed against the alpha(2) subunit

The cytoplasmic or soluble forms of guanylyl cyclase (sGC) are heme-containing heterodimeric enzymes that are regulated by nitric oxide (NO) and carbon monoxide (CO). These gaseous messenger molecules are produced in the human placenta and are potential regulators of vasodilation and trophoblast invasion. The alpha(2)-subunit of sGC has only recently been shown to naturally occur in placental extracts. In the present study, two novel antibodies directed against different epitopes of the alpha(2) subunit, were generated. Western Blot analysis confirmed the presence of a 82 kDa protein, identical with alpha(2) protein overexpressed in Sf9 cells. According to RNase protection analysis the alternatively spliced alpha(2i) variant was absent from human placenta. Immunohistochemical analysis showed the presence of alpha(2) protein in syncytiotrophoblast and villous and umbilical blood vessels, which are known sites of NO production. Strong expression was observed in the extravillous (intermediate) trophoblast, where the expression of CO-generating hemeoxygenases has recently been documented. Localization of alpha(2) subunit expression suggests a role for sGC in mediating the actions of both NO and CO. The novel antibodies characterized in the present study will be powerful tools to further elucidate the role of the NO/CO/cGMP signaling pathways in pathologic states such as preeclampsia and intrauterine growth retardation.     

Open reduction of proximal humerus fractures in the adolescent population

Purpose  

Proximal humerus fractures in the pediatric population are a relatively uncommon injury, with the majority of injuries treated in a closed fashion due to the tremendous remodeling potential of the proximal humerus in the skeletally immature. Yet, in adolescent patients, open treatment is, at times, necessary due to unsatisfactory alignment following a closed reduction, loss of previously achieved closed reduction, and limited remodeling when close to skeletal maturity. The purpose of our study was to examine the open reduction of adolescent proximal humerus fractures.