Different effects of diets rich in olive oil,rapeseed oil and sunflower-seed oil on postprandial lipid and lipoprotein concentrations and on lipoprotein oxidation susceptibility

Elevated concentrations of fasting and non-fasting triacylglycerol-rich lipoproteins (TRL) as well as oxidative changes of lipoproteins may increase the risk of ischaemic heart disease. To compare the effects of different diets rich in unsaturated fatty acids on the concentrations and in vitro oxidation of fasting and postprandial lipoproteins eighteen males consumed diets enriched with rapeseed oil (RO), olive oil (OO), or sunflower-seed oil (SO) in randomised order for periods of 3 weeks followed by a RO test meal. In the postprandial state the concentrations of cholesterol and triacylglycerol (TAG) in TRL were higher after consumption of OO compared with RO and SO (P<0.04), possibly related to differences in the fasting state. The propagation rates for VLDL and LDL oxidation were higher in the postprandial compared with the fasting state irrespective of diet. In the fasting state, the propagation rates were highest after SO (P<0.001), and in the postprandial state, SO gave rise to a shorter VLDL lag time (P=0.03) and a higher propagation rate than OO consumption (P=0.04). Overall, the SO diet resulted in a higher postprandial propagation rate of LDL (P<0.001) compared with RO and OO, while there was no effect of diet on LDL oxidation lag time. Our results suggest that RO and SO diets lower the postprandial cholesterol and TAG concentrations compared with OO, while RO and OO diets result in similar and lower in vitro susceptibility to oxidation of lipoproteins than SO.     

TNF-alpha, TNF-beta, IL-6, and IL-10 polymorphisms in patients with lung cancer

Apart from cigarette smoking, genetic factors seem to be of importance in the development of lung cancer. The present case-control study investigated frequencies of five inflammatory response gene polymorphisms (TNF-alpha-308, TNF-beta-Intron1-252, IL-6-174, IL-10-819 and IL-10-1082) in patients with lung cancer and controls. The study population consisted of 117 patients with lung cancer (77 patients with NSCLC, including 40 Squamous Cell Carcinoma and 26 Adenocarcinoma, and 40 patients with SCLC), 117 matched controls without pulmonary disease and 243 healthy individuals (population control). Genotype analyses revealed no difference in genotype frequencies using matched-pair analysis. However, in comparison to the population control, the IL-10-1082 genotypes carrying the G allele appeared with higher frequency in the SCLC group (p=0.006) [SCLC: 84.6%, population controls: 64.6%]. This yields an odds ratio of 3.01 for SCLC (95% CI = [1.21, 7.48]). No associations were seen for all other polymorphisms analysed. The study raises the possibility of a correlation between the IL-10-1082_G allele and the presence of SCLC in a German population. The functional IL-10-1082 polymorphism correlates with altered IL-10 levels and might influence lung cancer susceptibility by altered inflammatory responses in the airways.     

Vermeidung von Notfallsituationen bei gerinnungshemmender Therapie mit Vitamin-K-Antagonisten

Zusammenfassung Trotz der langen Erfahrungen mit Vitamin-K-Antagonisten bestehen häufig Unsicherheiten, insbesondere bei der Neueinstellung und Umstellung der Therapie. Der vorliegende Beitrag soll zeigen, wie eine gerinnungshemmende Therapie mit Phenprocoumon oder Warfarin eingeleitet wird, welche Maßnahmen bei Unterbrechungen, Überdosierungen oder bei Blutungskomplikationen zu ergreifen und welche gerinnungshemmenden Substanzen zur Überbrückung geeignet sind, solange keine Vitamin-K-Antagonisten verabreicht werden können. Zur Antagonisierung des Therapieeffekts stehen Vitamin K und Prothrombin-Komplex-Präparate (PPSB) zur Verfügung. Wird eine rasche Antagonisierung gewünscht, so sollte PPSB mit einer i.v.-Gabe von Vitamin K kombiniert werden. Bei schweren, beispielsweise intrakraniellen Blutungen oder Trauma kann auch rekombinanter Faktor VIIa eingesetzt werden. Vor größeren Operationen reicht häufig die alleinige Unterbrechung der Therapie mit Vitamin-K-Antagonisten nicht aus, sodass Vitamin K oral oder intravenös zugeführt werden muss. Bei Unterschreiten des therapeutischen INR-Bereichs werden unfraktioniertes oder niedermolekulares Heparin in geeigneter Dosierung verabreicht. Patienten mit Kontraindikationen für Heparin werden mit alternativen Antikoagulanzien wie Danaparoid, Lepirudin oder Fondaparinux behandelt.     

Pathogenetic role of Chlamydia pneumoniae in calcific aortic stenosis: immunohistochemistry study and review of the literature

BACKGROUND AND AIM OF THE STUDY: Non-rheumatic, calcific aortic stenosis (AS) is the most prevalent heart valve disease in the elderly. It is based on a chronic inflammatory process with infiltration and activation of leukocytes, and a rise in systemic inflammatory markers. An association with Chlamydia pneumoniae infection has been discussed, but previous studies have yielded divergent results. METHODS: Tricuspid aortic valves with calcific AS were obtained from patients undergoing aortic valve replacement. Control valves from patients matched for age and cardiovascular risk factors were obtained at autopsy. Immunohistochemistry was performed using monoclonal antibodies directed against C. pneumoniae and against leukocyte common antigen. Cultured HEp-2 cells infected with C. pneumoniae were used as positive controls. RESULTS: Positive immunostaining for C. pneumoniae was demonstrated in 12 of 14 (86%) stenotic valves and in six of nine (67%) control valves. Immunostained cells were located mainly in cell- and leukocyte-rich areas. Although stenotic valves showed a higher staining intensity as assessed by semiquantitative scoring (1.8 +/- 0.4 versus 0.8 +/- 0.2 units, p < 0.05), there was no statistically significant difference between stenotic and control valves regarding the presence of C. pneumoniae (p = 0.90). CONCLUSION: Positive immunostaining for C. pneumoniae was not associated with the presence of calcific AS. As in previous serologic and molecular biology studies, a high prevalence of C. pneumoniae in the adult population was demonstrated, irrespective of heart valve disease. Thus, C. pneumoniae is most likely not involved in the pathogenesis of calcific aortic stenosis.     

Enhanced coagulation activation by in vitro lipopolysaccharide challenge in patients with ventricular fibrillation complicating acute myocardial infarction

BACKGROUND: Indicators of coagulation and inflammation are elevated in patients with coronary heart disease. A role of coagulation activation in ventricular fibrillation during acute myocardial infarction has not been described. METHODS AND RESULTS: Whole blood samples of 21 patients with a history of acute myocardial infarction complicated by ventricular fibrillation and whole blood samples of 18 patients without ventricular fibrillation were incubated with lipopolysaccharide (LPS). In both groups, the in vitro blood coagulation time was measured with the ReoRox, a viscometric whole blood coagulometer. CD62P expression on platelets, tissue-factor binding on monocytes, and platelet-monocyte aggregates were measured with flow cytometry. Without LPS, no difference in the coagulation times were observed in both patient groups. After incubation with LPS, patients with a history of ventricular fibrillation showed a significantly decreased coagulation time compared to patients without ventricular fibrillation. The decrease of coagulation time after incubation with LPS also differed significantly in both groups. Expression of CD62P on platelets was significantly higher in patients with a history of ventricular fibrillation after incubation with LPS. Although in each patient group incubation with LPS induced a significantly increased amount of tissue factor on monocytes and a significantly increased the number of platelet-monocyte aggregates, the two groups did not differ significantly concerning tissue factor binding on monocytes and the amount of platelet-monocyte aggregates. CONCLUSIONS: After in vitro LPS challenge, patients with a history of ventricular fibrillation during myocardial infarction show an enhanced coagulation activation, which may partly be due to an enhanced platelet activation.     

Interleukin-1 beta promotes matrix metalloproteinase expression and cell proliferation in calcific aortic valve stenosis

Calcific aortic valve stenosis (AS), the main heart valve disease in the elderly, is characterized by extensive remodeling of the extracellular matrix. Matrix metalloproteinases (MMPs) are upregulated in calcific AS and might modulate matrix remodeling. The regulatory mechanisms are unclear. As recent studies have suggested that calcific AS might result from an inflammatory process involving leukocyte invasion and activation, the present study aimed to elucidate the role of the pro-inflammatory cytokine interleukin (IL)-1β on MMP expression and cell proliferation in human aortic valves. Immunohistochemistry for leukocytes, IL-1β and MMP-1 was performed on aortic valves with (n=6) and without (n=6) calcification obtained at valve replacement or autopsy. Stenotic valves showed marked leukocyte infiltration and associated expression of IL-1β and MMP-1. In control valves only scattered leukocytes, low staining for MMP-1 and no staining for IL-1β were present. Double-label immunostaining localized IL-1β expression mainly to leukocytes and MMP-1 expression to myofibroblasts. Stimulation of cultured human aortic valve myofibroblasts with IL-1β lead to a time-dependently increased expression of MMP-1 and MMP-2 by Western blotting and zymography, whereas MMP-9 remained unchanged. Cell proliferation was increased by IL-1β as determined by bromodesoxyuridine incorporation. Thus, IL-1β may regulate remodeling of the extracellular matrix in calcific AS.     

A tetravalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine is immunogenic and well-tolerated when co-administered with Twinrix(®) in subjects aged 11-17 years: an open, randomised, controlled trial

The co-administration of the tetravalent meningococcal conjugate vaccine, MenACWY-TT, with a licensed hepatitis A and B vaccine, HepA/B (Twinrix^®), was compared to their separate administration in this open, randomised, controlled study. Healthy subjects 11-17 years of age (n = 611) were randomised (3:1:1) to receive both vaccines, MenACWY-TT alone or HepA/B alone. The co-administration of both vaccines was shown to be non-inferior to their individual administration. At seven months after the first vaccination, 99.4-100% of the subjects who received both vaccines co-administered showed seroprotection against all meningococcal serogroups and at least 99.1% of them were seropositive for hepatitis A and seroprotected against hepatitis B. This study suggests that MenACWY-TT vaccine could be co-administered with HepA/B without adversely impacting the immunogenicity, safety and reactogenicity of either of the vaccines.     

The TAFI system. The new role of fibrinolysis

The primary focus of the blood coagulation system is the prevention of blood loss. The system is regulated by various inhibitors, and by the fibrinolytic system, which removes the final product of the blood coagulation system, the fibrin clot. The fibrinolytic system is activated in the course of coagulation activation. The thrombin-activated fibrinolysis inhibitor (TAFI) is an important regulator of fibrinolysis. TAFI is activated by thrombin, and activation is enhanced in the presence of thrombomodulin. TAFIa, the product of TAFI activation, removes lysine residues from fibrin, which are essential for the binding of t-PA, plasminogen, and plasmin to fibrin. The fibrin loses its cofactor activity in t-PA-induced plasminogen activation, resulting in less plasmin, and the remaining plasmin finds less binding sites on fibrin, resulting in an increased resistance of the clot towards plasmin proteolysis. High concentrations of thrombin result in high TAFIa-activity and consequently in highly resistant fibrin clots. Patients with hyperprothrombinaemia consequently display elevated TAFIa-levels, which may contribute to the risk for thrombosis. Treatment with recombinant factor VIIa also leads to high concentrations of thrombin, resulting in fibrin clots with enhanced resistance towards fibrinolysis. At low thrombin concentration, as observed in patients with bleeding disorders or patients treated with anticoagulant drugs, less TAFIa is produced in the course of coagulation activation, and the clots are less resistant towards fibrinolysis. TAFIa-inhibitors are currently being developed for the treatment of throboembolic disorders or hypofibrinolytic DIC. Enhancement of TAFIa-activity may be helpful in patients with bleeding.     

Endoscopic treatment of symptomatic fibroids at reproductive age and beyond

Objectives: To evaluate the feasibility of endoscopic treatment of symptomatic uterine fibroids based on patient and fibroid characteristics in reproductive, pre-menopausal and post-menopausal women.

Material and methods: The medical records of women with symptomatic uterine fibroids who underwent surgical procedures from 2010 to 2015 were retrospectively reviewed.

Results: A total of 819 patients, of which 710 (86.6%) underwent endoscopic procedures. The mean age of women who underwent laparoscopic myomectomy (LM) was 36.77?±?6.54 and hysteroscopic myomectomy (HSCM) was 43.10?±?10.26. The mean cumulative diameter of fibroids in the LM was 8.94?±?3.1 and 3.68?±?1.64?cm in the HSCM. Furthermore, LM and HCSM were performed when the mean diameter of the largest fibroid was up to 18.50 and 5.5?cm, respectively. The mean age of women in laparoscopic supracervical hysterectomy (LSH) was 46.02?±?6.13 and total laparoscopic hysterectomy (TLH) was 47.30?±?8.12. The mean cumulative diameter of fibroids in the LSH was greater than in the TLH, at 8.94?±?3.1 and 7.63?±?3.60?cm, respectively.

Conclusions: Uterus-preserving procedures are feasible, even if the largest fibroid diameter is more than 10?cm in LM and equal to 5.5?cm in HSCM. For pre- and post-menopausal women, TLH is the definitive treatment modality for uterine fibroids, and LSH represents an alternative to TLH.     

Avoiding emergency situations under anticoagulant therapy with vitamin K antagonists

Despite 50 years of clinical experience with vitamin K antagonists such as phenprocoumon or warfarin, many clinicians are uncertain how to start treatment, deal with overdose or bleeding complications, and how to bridge anticoagulation when treatment with vitamin K antagonists is interrupted. Patients with overdose of vitamin K antagonists or bleeding complications are treated with vitamin K, prothrombin complex concentrates (PCC), or recombinant factor VIIa. Rapid reversal of anticoagulation is only achieved by using PCC or recombinant factor VIIa. Both should be combined with vitamin K for a sustained effect. For elective surgery, treatment with vitamin K antagonists is paused and vitamin K given either orally or intravenously. Unfractionated or low molecular weight heparin is given when INR levels are below therapeutic range. Patients with contraindications to heparin may be treated with alternative anticoagulants such as danaparoid, lepirudin or fondaparinux.