Controlled Ordering of Topological Charges in an Exciton-Polariton Chain.

We demonstrate, experimentally and theoretically, controlled loading of an exciton-polariton vortex chain into a 1D array of trapping potentials. Switching between two types of vortex chains, with topological charges of the same or alternating signs, is achieved by appropriately shaping an off-resonant pump beam that drives the system to the regime of bosonic condensation. In analogy to spin chains, these vortex sequences realize either a "ferromagnetic" or an "antiferromagnetic" order, whereby the role of spin is played by the orbital angular momentum. The ferromagnetic ordering of vortices is associated with the formation of a persistent chiral current. Our results pave the way for the controlled creation of nontrivial distributions of orbital angular momentum and topological order in a periodic exciton-polariton system.

Exciton-polariton topological insulator.

Topological insulators-materials that are insulating in the bulk but allow electrons to flow on their surface-are striking examples of materials in which topological invariants are manifested in robustness against perturbations such as defects and disorder1. Their most prominent feature is the emergence of edge states at the boundary between areas with different topological properties. The observable physical effect is unidirectional robust transport of these edge states. Topological insulators were originally observed in the integer quantum Hall effect2 (in which conductance is quantized in a strong magnetic field) and subsequently suggested3-5 and observed6 to exist without a magnetic field, by virtue of other effects such as strong spin-orbit interaction. These were systems of correlated electrons. During the past decade, the concepts of topological physics have been introduced into other fields, including microwaves7,8, photonic systems9,10, cold atoms11,12, acoustics13,14 and even mechanics15. Recently, topological insulators were suggested to be possible in exciton-polariton systems16-18 organized as honeycomb (graphene-like) lattices, under the influence of a magnetic field. Exciton-polaritons are part-light, part-matter quasiparticles that emerge from strong coupling of quantum-well excitons and cavity photons19. Accordingly, the predicted topological effects differ from all those demonstrated thus far. Here we demonstrate experimentally an exciton-polariton topological insulator. Our lattice of coupled semiconductor microcavities is excited non-resonantly by a laser, and an applied magnetic field leads to the unidirectional flow of a polariton wavepacket around the edge of the array. This chiral edge mode is populated by a polariton condensation mechanism. We use scanning imaging techniques in real space and Fourier space to measure photoluminescence and thus visualize the mode as it propagates. We demonstrate that the topological edge mode goes around defects, and that its propagation direction can be reversed by inverting the applied magnetic field. Our exciton-polariton topological insulator paves the way for topological phenomena that involve light-matter interaction, amplification and the interaction of exciton-polaritons as a nonlinear many-body system.

Treatment of very preterm preeclampsia via heparin-mediated extracorporeal LDL-precipitation (H.E.L.P.) apheresis: The Freiburg preeclampsia H.E.L.P.-Apheresis study.

OBJECTIVE: Soluble Fms-like tyrosine kinase-1 (sFlt-1) is thought to be causative in the pathogenesis of preeclampsia (PE) and specific removal of sFlt-1 via dextran sulfate cellulose (DSC)-apheresis was suggested as cure to allow prolongation of pregnancy in preterm PE. However, in addition a deranged lipoprotein metabolism may impact endothelial and placental function in PE. Lipoprotein-apheresis by heparin-mediated extracorporeal LDL-precipitation (H.E.L.P.) was previously applied and has been shown to alleviate symptoms in PE. This clinical trial reevaluates the clinical efficacy of H.E.L.P.-apheresis in PE considering sFlt-1. STUDY DESIGN: Open pilot study assessing the prolongation by H.E.L.P.-apheresis in 6 women (30-41 years) with very preterm PE (24+4 to 27+0 gestational weeks (GW)) (NCT01967355) compared to a historic control-group matched for GW at admission (<28 GW; n = 6). Clinical outcome of mothers and babies, and pre- and post H.E.L.P.-apheresis levels of sFlt-1 and PlGF were monitored. MAIN OUTCOME MEASURES: In apheresis patients (2-6 treatments), average time from admission to birth was 15.0 days (6.3 days in controls; p = 0.027). Lung maturation was induced in all treated cases, and all children were released in healthy condition. Apheresis reduced triglycerides and LDL-cholesterol by more than 40%. Although H.E.L.P.-apheresis induced a transient peak baseline levels did not change and rather stabilized sFlt-1 levels at pre-apheresis levels throughout treatments, with sFlt-1/PLGF ratio remaining unaffected. CONCLUSIONS: H.E.L.P.-apheresis proved again to be safe and prolongs pregnancies in PE. However, without changing sFlt-1 levels below baseline lowering lipids or other yet undefined factors appear to be of more relevance than reducing sFlt-1.

Exciton-polariton trapping and potential landscape engineering.

Exciton-polaritons in semiconductor microcavities have become a model system for the studies of dynamical Bose-Einstein condensation, macroscopic coherence, many-body effects, nonclassical states of light and matter, and possibly quantum phase transitions in a solid state. These low-mass bosonic quasiparticles can condense at comparatively high temperatures up to 300 K, and preserve the fundamental properties of the condensate, such as coherence in space and time domain, even when they are out of equilibrium with the environment. Although the presence of a confining potential is not strictly necessary in order to observe Bose-Einstein condensation, engineering of the polariton confinement is a key to controlling, shaping, and directing the flow of polaritons. Prototype polariton-based optoelectronic devices rely on ultrafast photon-like velocities and strong nonlinearities exhibited by polaritons, as well as on their tailored confinement. Nanotechnology provides several pathways to achieving polariton confinement, and the specific features and advantages of different methods are discussed in this review. Being hybrid exciton-photon quasiparticles, polaritons can be trapped via their excitonic as well as photonic component, which leads to a wide choice of highly complementary trapping techniques. Here, we highlight the almost free choice of the confinement strengths and trapping geometries that provide powerful means for control and manipulation of the polariton systems both in the semi-classical and quantum regimes. Furthermore, the possibilities to observe effects of the polariton blockade, Mott insulator physics, and population of higher-order energy bands in sophisticated lattice potentials are discussed. Observation of such effects could lead to realization of novel polaritonic non-classical light sources and quantum simulators.

Talbot Effect for Exciton Polaritons.

We demonstrate, experimentally and theoretically, a Talbot effect for hybrid light-matter waves-an exciton-polariton condensate formed in a semiconductor microcavity with embedded quantum wells. The characteristic "Talbot carpet" is produced by loading the exciton-polariton condensate into a microstructured one-dimensional periodic array of mesa traps, which creates an array of phase-locked sources for coherent polariton flow in the plane of the quantum wells. The spatial distribution of the Talbot fringes outside the mesas mimics the near-field diffraction of a monochromatic wave on a periodic amplitude and phase grating with the grating period comparable to the wavelength. Despite the lossy nature of the polariton system, the Talbot pattern persists for distances exceeding the size of the mesas by an order of magnitude. Thus, our experiment demonstrates efficient shaping of the two-dimensional flow of coherent exciton polaritons by a one-dimensional "flat lens."

Lipoprotein binding to anionic biopolyelectrolytes and the effect of glucose on nanoplaque formation in arteriosclerosis and Alzheimer's disease.

Arteriosclerosis with its clinical sequelae (cardiac infarction, stroke, peripheral arterial occlusive disease) and vascular/Alzheimer dementia not only result in far more than half of all deaths but also represent dramatic economic problems. The reason is, among others, that diabetes mellitus is an independent risk factor for both disorders, and the number of diabetics strongly increases worldwide. More than one-half of infants in the first 6months of life have already small collections of macrophages and macrophages filled with lipid droplets in susceptible segments of the coronary arteries. On the other hand, the authors of the Bogalusa Heart Study found a strong increase in the prevalence of obesity in childhood that is paralleled by an increase in blood pressure, blood lipid concentration, and type 2 diabetes mellitus. Thus, there is a clear linkage between arteriosclerosis/Alzheimer's disease on the one hand and diabetes mellitus on the other hand. Furthermore, it has been demonstrated that distinct apoE isoforms on the blood lipids further both arteriosclerotic and Alzheimer nanoplaque formation and therefore impair flow-mediated vascular reactivity as well. Nanoplaque build-up seems to be the starting point for arteriosclerosis and Alzheimer's disease in their later full clinical manifestation. In earlier work, we could portray the anionic biopolyelectrolytes syndecan/perlecan as blood flow sensors and lipoprotein receptors in cell membrane and vascular matrix. We described extensively molecular composition, conformation, form and function of the macromolecule heparan sulfate proteoglycan (HS-PG). In two supplementary experimental settings (ellipsometry, myography), we utilized isolated HS-PG for in vitro nanoplaque investigations and isolated human coronary artery segments for in vivo tension measurements. With the ellipsometry-based approach, we were successful in establishing a direct connection on a molecular level between diabetes mellitus on the one side and arteriosclerosis/Alzheimer's disease on the other side. Application of glucose at a concentration representative for diabetics and leading to glycation of proteins and lipids, entailed a significant increase in arteriosclerotic and Alzheimer nanoplaque formation. IDLapoE4/E4 was by far superior to IDLapoE3/E3 in plaque build-up, both in diabetic and non-diabetic patients. Recording vascular tension of flow-dependent reactivity in blood substitute solution and under application of different IDLapoE isoforms showed an impaired vasorelaxation for pooled IDL and IDLapoE4/E4, thus confirming the ellipsometric investigations. Incubation in IDLapoE0/E0 (apoE "knockout man"), however, resulted in a massive flow-mediated contraction, also complemented by strongly aggregated nanoplaques. In contrast, HDL was shown to present a powerful protection against nanoplaque formation on principle, both in the in vitro model and the in vivo scenario on the endothelial cell membrane. The competitive interplay with LDL is highlighted through the flow experiment, where flow-mediated, HDL-induced vasodilatation remains untouched by additional incubation with LDL. This is due to the four times higher affinity for the proteoglycan receptor of HDL as compared to LDL. Taken together, the studies demonstrate that while simplistic, the ellipsometry approach and the endothelial-mimicking proteoglycan-modified surfaces provide information on the initial steps of lipoprotein-related plaque formation, which correlates with findings on endothelial cells and blood vessels, and afford insight into the role of lipoprotein deposition and exchange phenomena at the onset of these pathophysiologies.

High complication rate after septic orthopaedic implant removal of the lower leg.

INTRODUCTION: The aim of the study was to determine predictive risk factors for revision surgery in patients with septic orthopaedic implant removal of the lower leg. MATERIALS AND METHODS: A total of 196 patients with septic removal of orthopaedic implants after primary trauma of the lower leg between 2008 and 2012 were evaluated. Patients with endoprosthesis infection were excluded from this study. RESULTS: Thirteen patients (22.4 %) had infectious complications with revision surgery. We found 14 patients with soft tissue infections, 10 patients with osteomyelitis, 19 patients with wound-healing problems, 10 patients with pin track infections and two patients with fistulas. High complication rates were associated with severity of the initial trauma, localisation, and the state of union or non-union. Patients with peripheral arterial disease, anaemia and smoking showed a significantly higher risk for revision surgery; whereas patients with diabetes and arterial hypertension did not. A total of 22.6 % had open fractures as an initial trauma. In 76 %, bacteria could be detected. The complication rate was 41.2 % after initial open fractures and 19.6 % after initial closed fractures. A higher grade of soft tissue damage showed no increasing complication rate (p > 0.05). CONCLUSIONS: In this study, complications after septic implant removal of the lower leg were evaluated and risk factors were determined. The awareness of the risks for complications after septic orthopaedic implant removal can lead to a better treatment for patients. Decision-making can be based on scientific results to prevent patients suffering from further severe disease progression.

Therapeutic hypothermia reduces middle cerebral artery flow velocity in patients with severe aneurysmal subarachnoid hemorrhage.

BACKGROUND: Transcranial Doppler (TCD) is widely used to detect and follow up cerebral vasospasm after subarachnoid hemorrhage (SAH). Therapeutic hypothermia might influence blood flow velocities assessed by TCD. The aim of the study was to evaluate the effect of hypothermia on Doppler blood flow velocity after SAH. METHODS: In 20 patients treated with hypothermia (33°) due to refractory intracranial hypertension or delayed cerebral ischemia (DCI), mean flow velocity of the middle cerebral artery (MFV(MCA)) was assessed by TCD. Thirteen patients were treated with combined hypothermia and barbiturate coma and seven with hypothermia alone. MFV(MCA) was obtained within 24 h before and after induction of hypothermia as well as before and after rewarming. RESULTS: Hypothermia was induced on average 5 days after SAH (range 1-12) and maintained for 144 h (range 29-270). After hypothermia induction, MFV(MCA) decreased from 113.7 ± 49.0 to 93.8 ± 44.7 cm/s (p = 0.001). The decrease was independent of SAH-related complications and barbiturate coma. MFV(MCA) further decreased by 28.2 cm/s between early and late hypothermia (p < 0.001). This second decrease was observed in patients with DCI (p < 0.001), but not in patients with intracranial hypertension (p = 0.715). Compared to late hypothermia, MFV(MCA) remained unchanged after rewarming (65.6 ± 32.1 vs 70.3 ± 36.8 cm/s; p = 0.219). However, patients treated with hypothermia alone showed an increase in MFV(MCA) after rewarming (p = 0.016). CONCLUSION: Therapeutic hypothermia after SAH decreases Doppler blood flow velocity in both intracranial hypertension and DCI cases. The results can be the effect of hypothermia-related mechanisms or resolving cerebral vasospasm during prolonged hypothermia.

Laboratory-based real and reciprocal space imaging of the electronic structure of few layer graphene on SiC(0001¯) using photoelectron emission microscopy.

We present real and reciprocal space photoelectron emission microscopy (PEEM) results on few layer graphene using laboratory based He I and II radiation. The combination of a focused high-intensity source and high transmission PEEM electron optics provides good signal to noise ratios for the different modes of acquisition. We demonstrate work function mapping and secondary electron analysis, related to the graphene layer thickness, band structure imaging from micron scale regions by wave vector resolved PEEM (k-PEEM) and local secondary electron spectroscopy, giving information on the valence and conduction band states and the dispersion relations of the π bands. Dark field PEEM is done by selecting the Dirac cone corresponding to the specific rotation of each graphene layer and allows spatial mapping of the commensurate rotation angles. The use of He II radiation increases the volume of reciprocal space accessible to k-PEEM and improves signal to background. The preferential linear polarization of the light source is used to investigate aspects of the electronic chirality near the Dirac cone. Recent developments in sample manipulation and cooling are presented.

Antibiotic-impregnated versus silver-bearing external ventricular drainage catheters: preliminary results in a randomized controlled trial.

BACKGROUND: Evaluation of antibiotic-impregnated (AI) and ionized silver particle coated external ventricular drainage catheters (EVD) in patients with subarachnoid (SAH) or intracranial hemorrhage (ICH). METHODS: Between February 2011 and June 2012, 40 patients with acute hydrocephalus due to SAH, ICH or intraventricular hemorrhage were enrolled in a prospective, randomized, mono-center pilot study. Primary endpoints were defined as: number of events of cerebrospinal fluid (CSF) infections. Secondary endpoints were defined as: neurosurgical complications following the placement of the EVD, number of revisions of EVD catheters, and cost effectiveness. RESULTS: Sixty-one EVD placements in 40 patients, 32 antibiotic-coated (Bactiseal(®)), 29 silver-bearing catheters (VentriGuard(®)), have been performed. Confirmed or high suspicion of CSF infections occurred in 11 out of 61 events (confirmed infection: p = 0.71, probable infection: p = 0.90). Revisions of EVD were needed in 13 cases (22 %) due to CSF infection, dysfunction, impaired healing, or malplacement (p = 0.37). CONCLUSION: Regarding CSF infection rate and dysfunction, no statistical significant differences between the two EVD catheters Bactiseal(®) versus VentriGuard(®) were found. The silver-bearing catheter might offer a safe and cost-conscious alternative to the AI catheter.

Female fertility loss and preservation: threats and opportunities.

BACKGROUND: Ovarian aging and cytotoxic treatments are the most common causes for fertility loss in women. With increasing numbers of young female survivors following cytotoxic cancer treatments, the issue of fertility preservation has assumed greater importance. METHODS: We review the literature on the causes of female fertility loss as well as the recent advances in fertility preservation options and strategies that might be of interest to oncologists. Currently, several methods and techniques exist for fertility preservation of female patients with cancer including embryo freezing, ovarian protection techniques, oocyte cryopreservation, ovarian tissue cryopreservation followed by autotransplantation, and recently in vitro culture of ovarian tissue, follicles, and oocytes. Each method or technique has advantages and disadvantages related to current success rate, required delay in cancer treatment, sperm requirement, and risk of reintroducing cancer cells. RESULTS: To date, embryo freezing is the only established method successfully and widely used for fertility preservation of female patients with cancer. The other methods are promising but still considered experimental. CONCLUSION: Patient awareness, physician knowledge, early counseling, costs management, international registry, interdisciplinary networks, and research development are necessary to improve the current care in the field of female fertility preservation.

Dark field photoelectron emission microscopy of micron scale few layer graphene.

We demonstrate dark field imaging in photoelectron emission microscopy (PEEM) of heterogeneous few layer graphene (FLG) furnace grown on SiC(000-1). Energy-filtered, threshold PEEM is used to locate distinct zones of FLG graphene. In each region, selected by a field aperture, the k-space information is imaged using appropriate transfer optics. By selecting the photoelectron intensity at a given wave vector and using the inverse transfer optics, dark field PEEM gives a spatial distribution of the angular photoelectron emission. In the results presented here, the wave vector coordinates of the Dirac cones characteristic of commensurate rotations of FLG on SiC(000-1) are selected providing a map of the commensurate rotations across the surface. This special type of contrast is therefore a method to map the spatial distribution of the local band structure and offers a new laboratory tool for the characterisation of technically relevant, microscopically structured matter.

Serum glucose and electrolyte levels in alcohol-intoxicated adolescents on admission to the emergency department: an unmatched case-control study.

Aimed at examining serum glucose and electrolytes concentrations in adolescents with acute alcohol intoxication (AAI) on admission to the pediatric Emergency Department (ED), a retrospective unmatched, case-control study was conducted. Two cohorts of adolescents were compared, patients presenting with AAI and patients presenting with non-alcohol intoxication. The study group included ED patients aged 12-18 years with AAI. The control group included ED patients aged 12-18 years who had poisoning from a non-illicit drug. Demographic characteristics and glucose and electrolyte blood levels were extracted from the medical files. The records of patients who were admitted between January 2007 and December 2009 were analyzed. The study group and the control group included 106 subjects and 27 subjects, respectively. The study subjects had serum ethanol levels in the range of 55.6-297 mg/dL. No case of hypoglycemia was recorded. The study subjects had higher glucose levels and lower potassium levels compared to the controls (p < 0.005 and p < 0.0001, respectively). No such difference was found when the levels of sodium and bicarbonate were compared (p = 0.3 and p = 0.14, respectively). In conclusion, the findings of this study suggest that at presentation to the ED adolescents with AAI are at low risk for hypoglycemia.

Elevated serum thymidine kinase activity in canine splenic hemangiosarcoma*.

Thymidine kinase 1 (TK1) is a soluble biomarker associated with DNA synthesis. This prospective study evaluated serum TK1 activity in dogs presenting with hemoabdomen and a splenic mass. An ELISA using azidothymidine as a substrate was used to evaluate TK1 activity. Sixty-two dogs with hemoabdomen and 15 normal controls were studied. Serum TK1 activity was significantly higher in dogs with hemangiosarcoma (HSA) than in normal dogs (mean ± SEM = 17.0 ± 5.0 and 2.01 ± 0.6, respectively), but not dogs with benign disease (mean ± SEM = 10.0 ± 3.3). Using a cut-off of 6.55 U/L, TK activity demonstrated a sensitivity of 0.52, specificity of 0.93, positive predictive value of 0.94 and negative predictive value of 0.48 for distinguishing HSA versus normal. When interval thresholds of <1.55 and >7.95 U/L were used together, diagnostic utility was increased. Serum TK1 evaluation may help to discriminate between benign disease and HSA in dogs with hemoabdomen and a splenic mass.

Genotypic and phenotypic evaluation of Rutilus spp. from Skadar, Ohrid and Prespa Lakes supports revision of endemic as well as taxonomic status of several taxa.

One mtDNA gene (cytochrome b), one nuclear DNA fragment, five microsatellites and a suite of morphological characters were evaluated in samples of Rutilus spp. from Skadar, Ohrid and Prespa Lakes. Both genetic and phenotypic data supported two sympatric taxa in Lake Skadar, whereby Prespa and Ohrid Lakes revealed only a single taxon each. One of the taxa from Lake Skadar was similar to samples from Lake Prespa, whereas the second taxon was the most divergent in the data set. The estimated time to the most recent common ancestor of these two sympatric taxa in Lake Skadar was between 125 000 and 500 000 years. The data did not support existing taxonomic schemes for Rutilus in these lakes. This study poses the following working hypothesis: (1) Rutilus prespensis lives both in Lake Prespa and Lake Skadar and therefore is not endemic to Lake Prespa, (2) Rutilus ohridanus lives in Lake Ohrid only and therefore could be considered an endemic if its species status is retained and (3) a third recently described taxon (Rutilus albus) sympatric to R. prespensis lives in Lake Skadar.

Nocturnal blood pressure but not insulin resistance influences endothelial function in treated hypertensive patients.

The impact of insulin sensitivity, casual blood pressure and 24-h ambulatory blood pressure on endothelial function was studied in treated hypertensive subjects. Flow-mediated dilatation of the brachial artery after reperfusion was used to determine endothelial function. Insulin sensitivity indices were obtained by using the homeostasis model assessment, after 75 g Dextrose oral glucose tolerance tests (Matsuda index) and the euglycemic hyperinsulinemic clamp (M-value) in 49 patients with arterial hypertension. The insulin sensitivity indices were compared with healthy controls matched for body weight, age and sex (n=23). Hypertensive patients under therapy were insulin resistant, had higher LDL-cholesterol levels, higher blood pressure and lower endothelial function than healthy controls. Flow-mediated dilatation showed, in the study population being treated for arterial hypertension, no relationships of all insulin sensitivity indices with flow-mediated dilatation, casual blood pressure in the morning before the tests and 24-h ambulatory blood pressure. Flow-mediated dilatation was strongly influenced by nocturnal systolic and diastolic 24-h ambulatory blood pressure (systolic: R²=0.0943, P<0.05; diastolic: R²=0.0947, P<0.05). Therefore, endothelial function in these patients is predominantly influenced by nocturnal systolic and diastolic blood pressure and not by insulin sensitivity.

Plasma PCSK9 is increased by fenofibrate and atorvastatin in a non-additive fashion in diabetic patients.

OBJECTIVE: Proprotein convertase subtilisin kexin/type 9 (PCSK9) is an inhibitor of the low density (LDL) lipoprotein receptor. Plasma PCSK9 is increased by fenofibrate and statins. Here, we determined how standard dose of statin and combined therapy with fenofibrate modulate PCSK9. METHODS: Randomized, open-label cross-over study investigating the effect of fenofibrate (160 mg), atorvastatin (10 mg), and combination of both in patients with type 2 diabetes mellitus and atherogenic dyslipidemia. After the single administration of atorvastatin and fenofibrate for 6 weeks, patients received both for another 6 weeks. PCSK9, lipids and lipoproteins levels were determined at day 1, weeks 6, 9 and 12. RESULTS: Upon 6 weeks of treatment, atorvastatin decreased LDL-cholesterol by 30% (p<0.001) and fenofibrate decreased triglyceride level by 31% (p<0.01) and increased HDL-cholesterol by 13% (p<0.05). Combination did not show further benefit. Atorvastatin increased PCSK9 by 24% at day 1 and by 14% at week 6 (p < or = 0.01). Fenofibrate increased PCSK9 by 26% at week 6 (p < or = 0.01), but had no effect at day 1. Three weeks of combination therapy increased PCSK9 by 42%, 6 weeks by 19% (p < or = 0.01). PCSK9 changes were not different between treatments over 6-week periods. CONCLUSION: Fenofibrate and atorvastatin increased circulating PCSK9 in diabetic patients, with no additive effect after 6 weeks of combined therapy.

[Metabolic surgery and remission of type 2 diabetes]. / Metabolische Chirurgie und Remission des Diabetes mellitus Typ 2.

A new therapeutic field is developing from bariatric surgery. Gastrointestinal surgery does not only seem to be a very efficacious method for weight reduction but may also have the potential to reduce obesity-related metabolic disorders. Even if there is still a lack of prospective randomized trials evaluating the correct indications for metabolic surgery in patients with type 2 diabetes mellitus, there is the legitimate expectation that the surgical approach can be successful. This article provides an overview of the current state of bariatric surgery and gives a surgical perspective on the treatment of type 2 diabetes mellitus.

Fluvastatin/fenofibrate vs. simvastatin/ezetimibe in patients with metabolic syndrome: different effects on LDL-profiles.

BACKGROUND: Patients with metabolic syndrome (MS) and type 2 diabetes (T2DM) show increased risk for coronary artery disease. Lipoprotein metabolism is characterized by elevated triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C) and predominance of atherogenic small, dense low-density lipoprotein (sdLDL), while low-density lipoprotein (LDL) cholesterol is only slightly elevated. METHODS: Multicentre, randomized, open-label cross-over study investigating the effect of combination of fluvastatin/fenofibrate (80/200 mg) (F&F) on LDL-subfractions compared with combination of simvastatin/ezetimibe (20/10 mg) (S&E) in patients with MS/T2DM. RESULTS: Seventy-five patients were randomized, 69 completed the study and LDL-subfractions of 56 patients were analysed. Thirty-eight out of 56 patients (68%) showed a profile dominated by sdLDL. In these, TG and total cholesterol (TC) were elevated compared with non-sdLDL patients. In all patients, reduction of TC and LDL cholesterol (LDL-C) by S&E was stronger than by F&F. The increase of HDL-C was stronger with S&E in the non-sdLDL group, whereas in the sdLDL group, there was no difference between treatments. In non-sdLDL patients, there was no effect on TG or LDL-radius. However, in the sdLDL group, F&F was more effective in reducing TG and increased LDL radius, whereas S&E reduced LDL radius even further. CONCLUSIONS: S&E is more efficient in reducing TC and LDL-C. This is also true for HDL-C increase in non-sdLDL patients. However, in patients with sdLDL, F&F was more efficient in reducing TG and increasing LDL radius.

Genetic variants and haplotypes of lipoprotein associated phospholipase A2 and their influence on cardiovascular disease (The Ludwigshafen Risk and Cardiovascular Health Study).

BACKGROUND: There is increasing evidence that lipoprotein-associated phospholipase A2 (LpPLA2) is associated with cardiovascular disease. However, it is still unclear whether LpPLA2 is simply a marker or has a causal role as either a pro- or anti-atherogenic factor. METHODS: We analyzed the association of five polymorphisms (-1357G>A, -403T>C, Arg92His, Ile198Thr, Ala379Val) and related haplotypes at the PLA2G7 locus with angiographic coronary artery disease (CAD), plasma LpPLA2 activity, and long-term survival in 3234 patients scheduled for coronary angiography. RESULTS: The promoter variant -403C and His(92) were associated with a decrease and Val(379) with an increase in plasma LpPLA2 activity. Both coding variants revealed a clear gene-dose effect. Interestingly, the rare Thr(198) allele, which was not associated with any change in plasma LpPLA2 activity, was more frequent in subjects without CAD (P = 0.009), with an adjusted odds ratio for CAD of 0.69 (95% CI: 0.49-0.96; P = 0.029). None of the analyzed variants showed any robust association with all-cause or cardiovascular mortality. CONCLUSION: Irrespective of the significant association between some variants with plasma LpPLA2 activity, it is still unclear whether these polymorphisms or haplotypes are associated with the risk and outcome of cardiovascular disease in Caucasians.