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1.
Zentralbl Chir ; 138(2): 141-2, 2013 Apr.
Article in German | MEDLINE | ID: mdl-23564548

ABSTRACT

Currently laparoscopic cholecystectomy is the gold standard of therapy for diseases related with gallstones, namely symptomatic cholecystolithiasis, acute and chronic cholecystitis and also as therapy for gallbladder adenoids. Together with laparoscopic appendectomy, this procedure often is one of the first laparoscopic operations performed by new interns. Therefore a standardised, reproducible approach to ensure the patient safety is necessary. The procedure can be subdivided into 10 substeps--so-called "nodal points"--which must be completed before the next substep can be started. This article and the attached video show the ten "nodal points" of a standardised laparoscopic cholecystectomy.


Subject(s)
Cholecystectomy, Laparoscopic/education , Cholecystectomy, Laparoscopic/standards , Cholecystolithiasis/surgery , Internship and Residency , Video-Assisted Surgery/education , Benchmarking/standards , Cholecystolithiasis/diagnosis , Germany , Humans , Patient Safety
2.
QJM ; 104(9): 747-60, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21816811

ABSTRACT

Atrial fibrillation (AF), the most common clinically relevant arrhythmia, affects 2.2 million individuals in the USA and 4.5 million in Europe, resulting in significant morbidity and mortality. Pharmacotherapy aimed at controlling both heart rate and rhythm is employed to relieve AF symptoms, though debate continues about which approach is preferable. AF prevalence rises with age from 0.4% to 1% in the general population to 11% in those aged >70 years. AF is associated with a pro-thrombotic state and other comorbidities; age, hypertension, heart failure and diabetes mellitus all play a key role in AF pathogenesis. Anti-coagulation is essential for stroke prevention in patients with AF and is recommended for patients with one or more risk factors for stroke. Used within the recommended therapeutic range, warfarin and other vitamin K antagonists decrease the incidence of stroke and mortality in AF patients. Warfarin remains under-used, however, because of the perceived high risk of haemorrhage, narrow therapeutic window and need for regular monitoring. Several novel anti-coagulants show promise in AF-related stroke prevention. In particular, the novel, oral, direct thrombin inhibitor, dabigatran etexilate, recently licensed by the US Food and Drug Administration (FDA) and Health Canada has shown improved efficacy and safety compared with warfarin for stroke prevention in AF, and has the potential to replace warfarin in this indication. The increasing number of new therapeutic options, including improved anti-arrhythmic agents, novel anti-coagulants and more accessible ablation techniques, are likely to deliver better care for AF patients in the near future.


Subject(s)
Anticoagulants/therapeutic use , Atrial Fibrillation/complications , Stroke/prevention & control , Aged , Anti-Arrhythmia Agents/therapeutic use , Antithrombins/therapeutic use , Atrial Fibrillation/diagnosis , Atrial Fibrillation/drug therapy , Benzimidazoles/therapeutic use , Dabigatran , Female , Humans , Male , Pyridines/therapeutic use , Stroke/etiology
3.
Minerva Chir ; 66(6): 573-87, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22233664

ABSTRACT

Despite the introduction of proton pump inhibitors and modern flexible endoscopy techniques, upper gastrointestinal bleeding is still a common and serious condition. Once considered the domain of surgery, it is now uncommon to treat endoscopically controllable bleeding surgically. Therefore, most surgically treated cases are complicated and associated with a high mortality rate. This article presents the current management of upper gastrointestinal bleeding. Besides the description of current endoscopic treatment, medical prophylaxis and treatment, as well as radiological intervention, the article describes the indication and the surgical procedure.


Subject(s)
Esophagoscopy , Gastrointestinal Hemorrhage/therapy , Gastroscopy , Upper Gastrointestinal Tract , Algorithms , Anti-Bacterial Agents/therapeutic use , Balloon Occlusion , Drug Therapy, Combination , Esophageal and Gastric Varices/therapy , Evidence-Based Medicine , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/drug therapy , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/surgery , Humans , Incidence , Minimally Invasive Surgical Procedures , Peptic Ulcer Hemorrhage/therapy , Portasystemic Shunt, Transjugular Intrahepatic , Practice Guidelines as Topic , Sclerotherapy/methods , Stents , Treatment Outcome , Vasoconstrictor Agents/therapeutic use
4.
Curr Med Res Opin ; 24(1): 267-74, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18053318

ABSTRACT

OBJECTIVES: To model the 2-year cost-effectiveness of secondary prevention with clopidogrel versus aspirin (acetylsalicylic acid) (ASS) in German patients with myocardial infarction (MI), ischaemic stroke (IS) or diagnosed with peripheral arterial disease (PAD), based on CAPRIE trial data and from the perspective of German third party payers (TPP). METHODS: An existing Markov model was adapted to Germany by using German cost data. The model was extended by using different datasets for cardiovascular event survival times (Framingham vs. Saskatchewan health databases) and in two separate scenarios. RESULTS: The treatment with clopidogrel leads to a reduction of 13.19 vascular events per 1000 patients, of which 2.21 are vascular deaths. The overall incremental costs for the 2-year management of atherothrombotic patients with clopidogrel instead of ASS are calculated to be about euro1 241 440 per 1000 patients. The number of life-years saved (LYS) has been calculated as the difference in the number of life-years lost due to vascular death or events with ASS versus clopidogrel: it is 86.35 LYS when analysis is based on Framingham data and 66.07 LYS with Saskatchewan-based survival data. The incremental costs per LYS are euro14 380 and euro18 790, respectively. Cost-effectiveness is sensitive to changes in survival data, discounting and daily costs of clopidogrel, but stable against substantial (+/- 25%) changes in all other cost data. CONCLUSION: The findings for Germany are in line with published results for Belgium (euro13 390 per LYS) and also with results for Italy (euro17 500 per LYS), both based on Saskatchewan data, and with a French analysis based on Framingham data (euro15 907 per LYS). Even if no officially accepted cost-effectiveness threshold exists for Germany at present, incremental cost-effectiveness results of less than euro20 000 per LYS for the treatment with clopidogrel can be assumed to be acceptable for German third party payers.


Subject(s)
Aspirin/economics , Aspirin/therapeutic use , Atherosclerosis/drug therapy , Coronary Thrombosis/drug therapy , Ticlopidine/analogs & derivatives , Aged , Aged, 80 and over , Atherosclerosis/complications , Atherosclerosis/economics , Atherosclerosis/mortality , Clopidogrel , Cohort Studies , Coronary Thrombosis/complications , Coronary Thrombosis/economics , Coronary Thrombosis/mortality , Cost-Benefit Analysis , Germany , Humans , Models, Econometric , Myocardial Infarction/epidemiology , Myocardial Infarction/mortality , Platelet Aggregation Inhibitors/economics , Platelet Aggregation Inhibitors/therapeutic use , Survival Analysis , Ticlopidine/economics , Ticlopidine/therapeutic use , Treatment Outcome
5.
Z Kardiol ; 94(5): 336-42, 2005 May.
Article in English | MEDLINE | ID: mdl-15868362

ABSTRACT

UNLABELLED: Some medications have been shown to produce reductions in hs-CRP levels after initiating therapy. Whereas the role of the renin-angiotensin system in the inflammatory process has been documented in more detail during the last few years, the impact of an ACE-inhibitor therapy on this process has not been fully understood so far. The aim of this study was to investigate the effect of a therapy with the angiotensin-converting enzyme (ACE) inhibitor ramipril on hs-CRP plasma concentrations in patients with atherosclerosis. METHODS AND RESULTS: A total of 24 patients were enrolled in this prospective, uncontrolled, open-label multicenter study. Inclusion criteria were documented atherosclerosis, baseline high-sensitivity C-reactive protein between 3 and 12 mg/l, LDL-Cholesterol < or =150 mg/dl and no previous treatment with ACE inhibitors or angiotensin receptor blockers. Ten patients, pretreated with statins, and 10 patients not previously treated with statins were eligible for statistical analysis. Baseline high-sensitivity C-reactive protein was significantly decreased from 3.99+/-1.61 mg/l (mean+/-SD) to 2.72+/-1.19 mg/l (-32%) after 3 months treatment with 10 mg ramipril daily (p=0.0002). The decrease was more pronounced in patients who had not been treated with statins previously (-1.50 mg/l+/-1.44 mg/l) compared to those who were pretreated (-0.90 mg/l+/-0.93 mg/l). CONCLUSIONS: The ACE inhibitor ramipril administered in a daily dose of 10 mg to patients with atherosclerosis reduces the high-sensitivity C-reactive protein concentration. This effect may contribute to cardiovascular risk reduction mediated by ramipril aside from the blood pressure lowering effect.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Arteriosclerosis/drug therapy , Coronary Artery Disease/drug therapy , Ramipril/therapeutic use , Adult , Aged , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Blood Pressure/drug effects , Cholesterol, LDL/blood , Coronary Disease/blood , Coronary Disease/drug therapy , Drug Therapy, Combination , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypolipidemic Agents/therapeutic use , Male , Middle Aged , Premedication , Prospective Studies , Ramipril/adverse effects , Treatment Outcome
6.
Biochem J ; 380(Pt 3): 831-6, 2004 Jun 15.
Article in English | MEDLINE | ID: mdl-15025562

ABSTRACT

Previously, we have shown that the human insulin receptor (IR) interacts with G(i)2, independent of tyrosine kinase activity and stimulates NADPH oxidase via the Galpha subunit of G(i)2. We have now investigated the regulatory role of G(i)2-proteins in IR function. For the experiments, isolated IRs from plasma membranes of human fat cells were used. The activation of IR autophosphorylation by insulin was blocked by G-protein inactivation through GDPbetaS (guanosine 5'-[beta-thio]disphosphate). Consistently, activation of G-proteins by micromolar concentrations of GTPgammaS (guanosine 5'-[gamma-thio]triphosphate) induced receptor autophosphorylation 5-fold over baseline and increased insulin-induced autophosphorylation by 3-fold. In the presence of 10 microM GTPgammaS, insulin was active at picomolar concentrations, indicating that insulin acted via its cognate receptor. Pretreatment of the plasma membranes with pertussis toxin prevented insulin- and GTPgammaS-induced autophosphorylation, but did not disrupt the IR-G(i)2 complex. The functional nature of the IR-G(i)2 complex was made evident by insulin's ability to increase association of G(i)2 with the IR. This leads to an augmentation of maximal receptor autophosphorylation induced by insulin and GTPgammaS. The specificity of this mechanism was further demonstrated by the use of isolated preactivated G-proteins. Addition of G(i)2alpha and Gbetagamma mimicked maximal response of insulin, whereas Galphas or Galphao had no stimulatory effect. These results define a novel mechanism by which insulin signalling mediates tyrosine kinase activity and autophosphorylation of the IR through recruitment of G(i)-proteins.


Subject(s)
GTP-Binding Protein alpha Subunits, Gi-Go/physiology , Receptor, Insulin/metabolism , Adipocytes/chemistry , Adipocytes/enzymology , GTP-Binding Protein alpha Subunits, Gi-Go/metabolism , GTP-Binding Protein beta Subunits/metabolism , GTP-Binding Protein gamma Subunits/metabolism , Guanine Nucleotides/pharmacology , Humans , Ligands , Pertussis Toxin/pharmacology , Phosphorylation/drug effects , Receptor Protein-Tyrosine Kinases/metabolism , Recombinant Proteins/metabolism , Signal Transduction/drug effects , Signal Transduction/physiology
8.
Eur J Epidemiol ; 18(5): 407-11, 2003.
Article in English | MEDLINE | ID: mdl-12889686

ABSTRACT

BACKGROUND: Current studies on secondary prevention of cardiovascular events (CARE, LIPID, 4S) illustrate the necessity of an effective lipid-lowering therapy. An important part of secondary prevention is the prompt measurement of lipids following an infarct, to be able to start therapy as quickly as possible. AIMS: This study should show the general situation in the prescription of lipid-lowering drugs in patients with acute myocardial infarction (MI) and if there are gender differences in therapy and in the lipid parameters. The second aim was to determine the therapeutical conclusions for secondary prevention made in-hospital in patients with heart attacks. METHODS: Post-infarct lipid parameters (total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG) were examined in 5361 patients within 24 hours following an acute MI. Lipid parameters from 576 patients were measured again after 1 week. RESULTS: 80.1% of men under examination and 81.9% of the women had suffered from their first MI. Only 9% of all patients were already under lipid-lowering therapy before the MI. After the MI TC and LDL-C levels decreased significantly in a time-dependent manner. Around 50% of patients received lipid-lowering drug, or the recommendation of one, during their hospital stay. CONCLUSION: The range of TC values of the patients examined was comparable to those in the CARE and the 4S secondary prevention studies. It can therefore be assumed that the results of these studies are also applicable to Germany. Nevertheless, according to existing data, therapy with lipid-lowering drugs is currently unsatisfactory, even in secondary prevention.


Subject(s)
Cholesterol/blood , Hypolipidemic Agents/therapeutic use , Myocardial Infarction/drug therapy , Myocardial Infarction/prevention & control , Triglycerides/blood , Aged , Aged, 80 and over , Cholesterol, HDL/blood , Cholesterol, HDL/drug effects , Cholesterol, LDL/blood , Cholesterol, LDL/drug effects , Female , Germany , Humans , Male , Middle Aged , Random Allocation , Sex Factors , Time Factors , Treatment Outcome
9.
FASEB J ; 17(1): 38-40, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12424219

ABSTRACT

Recent findings indicate that platelet-derived growth factor (PDGF) plays a role in the generation of reactive oxygen species (ROS) as second messengers in smooth muscle cells (SMC). To identify the source and signal transduction pathway of ROS formation in SMC, we investigated PDGF-induced ROS formation. Stimulation of SMC with PDGF resulted in a rapid increase of ROS production. Using an inactivating antibody, we identified the increase to be dependent on p22phox, a NAD(P)H-oxidase subunit. ROS release was completely inhibited by the Gi protein inhibitor PTX as well as an antibody against Galphai1,2, however, not by antibodies against Galphai3/0, Gas, and Gbeta1beta2. The effect of PDGF on ROS production in SMC membranes could likewise be mimicked by the use of a recombinant Galphai2 subunit but not by Galphai3, Galphai0, Gas, and Gbetagamma subunits. Immunoaffinity chromatography demonstrated coupling of Galphai1,2 to the PDGF a-receptor, which, after preincubation of the SMC membranes with PDGF, was increased in the absence of GTPgammaS but decreased in the presence of GTPgammaS and prevented by PTX treatment. These data define a novel G protein-dependent mechanism by which PDGF signaling is transduced through direct coupling of the Gai1,2 subunit of the trimeric G proteins to the PDGF tyrosine kinase receptor.


Subject(s)
GTP-Binding Protein alpha Subunits, Gi-Go/physiology , Membrane Transport Proteins , Muscle, Smooth, Vascular/enzymology , NADH, NADPH Oxidoreductases/metabolism , Platelet-Derived Growth Factor/pharmacology , Proto-Oncogene Proteins/physiology , Reactive Oxygen Species/metabolism , Animals , Enzyme Activation , GTP-Binding Protein alpha Subunit, Gi2 , Models, Biological , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , NADPH Dehydrogenase/physiology , NADPH Oxidases , Phosphoproteins/physiology , Receptor, Platelet-Derived Growth Factor alpha/metabolism , Signal Transduction
10.
Curr Vasc Pharmacol ; 1(2): 123-33, 2003 Jun.
Article in English | MEDLINE | ID: mdl-15320839

ABSTRACT

Before it gets to the development of manifest atherosclerotic lesions, all known risk factors primarily induce functional alterations in the vascular wall, namely in endothelial cells. Being termed endothelial dysfunction or endothelial activation, this condition is characterized by an altered availability of nitric oxide (NO). Under physiological conditions, NO is of unequivocal importance for the regulation of vascular homeostasis. Endothelium-derived NO released abluminally increases soluble guanylat cyclase activity in smooth muscle cells, thereby inducing relaxation and consequently vasodilatation. Intraluminally, NO inhibits the expression of adhesion molecules both on endothielial cells and neutrophils, thus preventing the adherence of cellular elements to the vascular wall. Furthermore, NO has antithrombotic effcts by inhibiting platelet aggregation and directly infuencing the synthesis of different factors involved in the coagulation cascade. Finally, in the long term, NO has been shown to exert antiproliferative properties. NO is generated intracellularly from L-arginine via NO-synthase with the help of several cofactors, including tetrahydobiopterin. Interestingly, it has recently become evident that under certain conditions, when there is a lack of tetrahydrobiopterin, NO-synthase produces reactive oxygen species instead of NO. Reactive oxygen species counteract the effects of NO and also scavenge NO resulting in the formation of peroxynitrite (ONOO). Peroxynitrite has been shown to have deleterious effects with respect to vascular function. The aim of the current review is to elucidate recent progress regarding the pathophysiological understanding of endothelial dysfunction. Furthermore, the significance of this condition for the evaluation and prognosis of patients is discussed. Finally, current therapeutical strategies in the treatment and improvement of endothelial dysfunction are highlighted.


Subject(s)
Endothelium, Vascular/physiopathology , Nitric Oxide/physiology , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , Arginine/therapeutic use , Clinical Trials as Topic , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Homocysteine/antagonists & inhibitors , Homocysteine/blood , Hormone Replacement Therapy , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Nitric Oxide/biosynthesis , Vascular Diseases/drug therapy , Vascular Diseases/physiopathology
11.
Acta Physiol Scand ; 176(2): 109-15, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12354170

ABSTRACT

Chemotaxis of blood monocytes into the vessel wall together with the change of the relative content of the extracellular matrix (ECM) proteins at sites of predilection is an early cellular marker of atherogenesis. To examine the influence of ECM proteins on secretion of chemoattractants by endothelial cells (EC), porcine EC were seeded on gelatin (G), fibronectin (Fn) and fibrinogen (Fg). After 24 h cells seeded on G and Fn showed the histiotypic 'cobblestone'-morphology whereas cells seeded on Fg did not. Chemotactic activity for monocytes in supernatants from cells seeded on Fg was more than two-fold higher compared with G and was independent of soluble Fn or Fg in the supernatant. Quantification of monocyte chemoattracting protein-1, PDGF-AB and IL-8 in EC supernatants showed that Fg led to a significant increase in secretion of all three proteins compared with cells cultured on G. Preincubation of porcine EC with the tripeptide arginine-glycine-aspartic acid, as inhibitor of binding of Fg to integrin receptors, but not with the control tripeptide arginine-glycine-glutamic acid showed a decrease in chemotactic activity for cells cultured on Fg but not on Fn or G. Inhibition of protein kinase C (PKC) activity in EC by GF109203 resulted in a decrease of fibrinogen-induced chemotactic activity. Also the tyrosine-kinase inhibitor herbimycin inhibited fibrinogen mediated secretion of chemokines. The role of the PKC pathway for matrix mediated signal transduction is further corroborated by Fg-dependent induction of the PKC isoform delta. These data indicate an integrin-dependent signal transduction pathway leading to induction of chemotactic activity by the ECM protein fibrinogen. This mechanism may contribute to induction of chemokines in early atherosclerotic lesions.


Subject(s)
Chemotaxis, Leukocyte/physiology , Endothelium, Vascular/physiology , Fibrinogen/physiology , Animals , Arteriosclerosis/blood , Arteriosclerosis/etiology , Cell Adhesion/physiology , Cell Division/physiology , Cells, Cultured , Endothelium, Vascular/cytology , Enzyme-Linked Immunosorbent Assay/methods , Extracellular Matrix Proteins/physiology , Fibronectins/physiology , Gelatin , Humans , Immunoblotting/methods , Monocytes/cytology , Monocytes/physiology , Protein Kinase C/analysis , Signal Transduction/physiology , Swine
12.
Basic Res Cardiol ; 97(1): 9-16, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11998981

ABSTRACT

Restenosis is the major obstacle interfering with a successful long-term outcome of balloon angioplasty. Neointima formation following endothelial injury is the result of phenotype modulation and proliferation of smooth muscle cells (SMC). To characterize these time-dependent changes, a rat balloon injury model of carotid artery restenosis was assessed. We applied monoclonal antibodies recognizing desmin, sm-alpha-actin and smoothelin, a novel marker specific for the differentiated phenotype of SMC. Neointima formation could be seen from day 7 after injury onwards. During early phases, the number of smoothelin-positive cells in the media was decreased compared with uninjured controls. Smoothelin staining was absent in the neointima during formation. Increased levels of smoothelin in both media and neointima were observed at days 28 and 56, correlating with a decrease in proliferation as assessed by Ki-67 antigen staining. No such changes were observed for desmin and sm-alpha-actin. Following balloon injury, SMC in both the media and the neointima underwent an early, reversible dedifferentiation, followed by proliferation. The novel SMC-specific marker protein smoothelin can be used to monitor this SMC (de)differentiation in neointima and media. These findings support the pivotal role of SMC phenotype modulation in neointima formation and restenosis.


Subject(s)
Angioplasty, Balloon/adverse effects , Carotid Artery Injuries/metabolism , Coronary Restenosis/metabolism , Cytoskeletal Proteins/metabolism , Muscle Proteins , Muscle, Smooth/injuries , Muscle, Smooth/metabolism , Actins/analysis , Animals , Antibodies, Monoclonal , Carotid Artery Injuries/pathology , Coronary Restenosis/pathology , Desmin/analysis , Disease Models, Animal , Male , Microscopy, Fluorescence , Muscle, Smooth/pathology , Phenotype , Rats , Rats, Sprague-Dawley , Time Factors , Tunica Intima/metabolism , Tunica Intima/pathology , Wound Healing
13.
Circulation ; 104(25): 3057-62, 2001 Dec 18.
Article in English | MEDLINE | ID: mdl-11748100

ABSTRACT

BACKGROUND: The crucial function of hepatic lipase (HL) in lipid metabolism has been well established, but the relationship between HL activity and coronary artery disease (CAD) is disputed. METHODS AND RESULTS: We measured HL activity in the postheparin plasma of 200 consecutive men undergoing elective coronary angiography and determined the degree of CAD with the extent score, which has been shown to be better correlated with known risk factors than other measures of CAD extent. We found a significant inverse correlation between HL activity and the extent of CAD (r=-0.19, P<0.01). This association was mainly due to patients with HDL levels >0.96 mmol/L (n=94, r=-0.30, P<0.005). HL activity was lower in 173 patients with CAD than in 40 controls with normal angiograms (286+/-106 versus 338+/-108 nmol. mL(-1). min(-1), P<0.01). To correct for potential confounding factors, we performed multivariate analyses that confirmed the independent association of HL activity with CAD extent. In addition, the presence of the T allele at position -514 in the HL promoter, which leads to a reduced HL promoter activity, was associated with lower HL activity (r=0.30, P<0.001) and higher CAD extent (42.2+/-20.8 versus 35.3+/-23.6 [extent score], P<0.05). In patients with heterozygous familial hypercholesterolemia, calcified lesions in ECG-gated spiral computed tomography were higher in patients with low HL activity (6.3+/-6.8 versus 1.5+/-3.1, P=0.01). CONCLUSIONS: Our data show that low HL activity is associated with CAD. Therefore, HL might be useful for CAD risk estimation and might be a target for pharmacological intervention.


Subject(s)
Coronary Artery Disease/pathology , Lipase/blood , Liver/enzymology , Adult , Alleles , Coronary Artery Disease/blood , Coronary Artery Disease/enzymology , Coronary Vessels/enzymology , Coronary Vessels/pathology , Humans , Lipase/genetics , Male , Polymorphism, Genetic , Promoter Regions, Genetic/genetics , Risk Factors , Severity of Illness Index
14.
Brain Res Dev Brain Res ; 129(2): 147-55, 2001 Aug 23.
Article in English | MEDLINE | ID: mdl-11506859

ABSTRACT

This paper examines maturational changes in the spatiotemporal features of central and lateral N1 components of the auditory evoked potentials (AEPs) to tone stimuli presented with a long stimulus onset asyncrony (SOA; 4200 ms) using the scalp current density (SCD) technique. A group of typically developing children ranging from 6 to 12 years of age and a group of adults were studied. Recently studies have begun to explore the topography of these components in children. These studies, however, often used rapidly presented stimuli and did not elicit observable central N1s in the younger children. Our stimuli elicited both central and lateral N1s. Peak latencies of both components decreased with age. Peak amplitude also decreased with age for the lateral N1 but not for the central N1. Consequently, the difference between the lateral N1 and the central N1 amplitudes (or the ratio of lateral N1 amplitude to central N1 amplitude) also decreased with age, dramatically altering the morphology of the elicited AEP waveforms. Topography of the lateral N1 did not change with age. The location of maximal activation for the central N1 appeared to move more medially with age but this 'apparent' movement is probably due to the decreasing impact of the partially overlapping lateral N1 component whose amplitude is significantly smaller in adults than in children.


Subject(s)
Aging/physiology , Evoked Potentials, Auditory/physiology , Acoustic Stimulation , Adult , Brain Mapping , Child , Child Development/physiology , Dominance, Cerebral/physiology , Electroencephalography , Female , Humans , Male , Reaction Time/physiology
15.
Thromb Haemost ; 85(6): 1104-10, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11434692

ABSTRACT

UNLABELLED: Activation of vascular smooth muscle cells (VMSC) by thrombin induces the expression of the chemokine, monocyte chemoattractant protein-1 (MCP-1). We investigated in cultured human and rat VSMC whether reactive oxygen species (ROS) derived from the vascular NADPH oxidase contribute to this effect. Exposure of cultured VSMC to thrombin rapidly increased ROS formation, phosphorylation of p38 MAP kinase as well as the expression of MCP-1. Specific inhibition of the p22phox subunit of the vascular NADPH oxidase using either p22phox neutralizing antibody or p22phox antisense oligonucleotides attenuated thrombin-induced ROS generation. Furthermore, thrombin-induced p38 MAP kinase activation as well as MCP-1 expression were impaired by antioxidants as well as by p22phox antisense oligonucleotides. Inhibition of p38 MAP kinase diminished the thrombin-induced expression of MCP-1. CONCLUSION: Thrombin, by activating a p22phox-containing NADPH oxidase, elicits ROS generation and activation of p38 MAP kinase in VSMC. The subsequent induction of MCP-1 expression highligts the crucial role of the p22phox-containing NADPH oxidase in thrombin-induced signal transduction in VSMC.


Subject(s)
Chemokine CCL2/metabolism , Membrane Transport Proteins , Muscle, Smooth, Vascular/drug effects , NADPH Dehydrogenase , NADPH Oxidases/metabolism , Phosphoproteins , Thrombin/pharmacology , Animals , Aorta/cytology , Cell Culture Techniques , Dose-Response Relationship, Drug , Enzyme Activation/drug effects , Humans , Kinetics , MAP Kinase Signaling System/drug effects , Male , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/enzymology , Muscle, Smooth, Vascular/metabolism , NADPH Oxidases/chemistry , NADPH Oxidases/pharmacology , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , Thrombin/physiology
16.
Circulation ; 104(4): 387-92, 2001 Jul 24.
Article in English | MEDLINE | ID: mdl-11468198

ABSTRACT

BACKGROUND: We studied whether lipid-lowering therapy with atorvastatin (target LDL cholesterol [LDL-C] <100 mg/dL) compared with a moderate treatment regimen that used other lipid-lowering drugs led to a lesser progression of atherosclerosis and to different changes in plaque echogenicity in patients with coronary artery disease. METHODS AND RESULTS: This study was a 12-month, open-label, randomized, multicenter trial, which used serial 3D intracoronary ultrasound to calculate plaque volume and plaque echogenicity. After transcatheter therapy, 131 patients were randomized (atorvastatin n=65, usual care n=66). The target plaque had to be a minor lesion (ie, a diameter stenosis of <50% on angiography). After 12 months, mean LDL-C was reduced from 155 to 86 mg/dL in the atorvastatin group and from 166 to 140 mg/dL in the usual care group. Mean absolute plaque volume showed a larger increase in the usual care group compared with the atorvastatin group (usual care 9.6+/-28.1 mm(3), atorvastatin 1.2+/-30.4 mm(3); P=0.191). The hyperechogenicity index of the plaque increased to a larger extent for the atorvastatin group than for the usual care group, with a significant treatment effect for the percent change (atorvastatin 42.2%, usual care 10.1%; P=0.021). CONCLUSIONS: One year of lipid-lowering therapy to <100 mg/dL LDL-C most likely led to a slowdown of plaque growth of minor lesions. The significantly larger increase in plaque hyperechogenicity is most likely due to a change in plaque composition.


Subject(s)
Anticholesteremic Agents/therapeutic use , Arteriosclerosis/drug therapy , Coronary Disease/drug therapy , Heptanoic Acids/therapeutic use , Pyrroles/therapeutic use , Anticholesteremic Agents/adverse effects , Arteriosclerosis/pathology , Arthralgia/chemically induced , Atorvastatin , Butyrates/therapeutic use , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, HDL/drug effects , Cholestyramine Resin/therapeutic use , Coronary Disease/pathology , Creatinine/blood , Exanthema/chemically induced , Heptanoic Acids/adverse effects , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Patient Dropouts , Pyrroles/adverse effects , Treatment Outcome , Triglycerides/blood , Ultrasonography, Interventional , Venous Thrombosis/chemically induced
18.
Basic Res Cardiol ; 96(1): 50-8, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11215532

ABSTRACT

Expression of cytokeratins (CK) is considered a hallmark of the state of epithelial differentiation. CK also occur in certain vascular smooth muscle cells (VSMC), inferring an association with a less differentiated phenotype. Recently, CK posttranslational modification was shown to occur in epithelial cells in stress, mitosis or apoptosis. The aim of this study was to determine potential CK phosphorylation patterns in human VSMC. Tissue samples of normal peripheral and coronary arteries, atherosclerotic lesions and umbilical cord vessels were evaluated by immunofluorescence microscopy applying antibodies specific for cytokeratins 8 and 18, specific cytokeratin phosphorylation sites, Ki-67-antigen as a proliferation marker and nick end labeling (TUNEL) to detect apoptosis. All samples contained cytokeratin-positive VSMC but diverse phosphorylation patterns. The C-terminal serine 431 of cytokeratin 8 (CK8Ser-431) was phosphorylated in the vast majority of CK-expressing VSMC of coronary artery lesions. Only a subset of these cells demonstrated phosphorylation of CK18Ser-33 or, to an even lesser extent, CK8Ser-73. DNA fragmentation occurred predominantly in samples containing cells with phosphorylated CK8Ser-431 domains. In contrast, occluded peripheral lesions exhibited little or no phosphorylation. Neonatal VSMC in umbilical cord vessels contain abundant phosphorylated CK domains, again predominantly CK8Ser-431, but also CK18Ser-33. Again, only single cells were found to be proliferating or to contain DNA fragmentation. Thus, abundant CK phosphorylation in VSMC of atherosclerotic lesions suggests a specific functional response to cell stress and a possible relation to apoptosis.


Subject(s)
Coronary Artery Disease/metabolism , Keratins/metabolism , Muscle, Smooth, Vascular/metabolism , Umbilical Cord/blood supply , Aorta/metabolism , Aorta/pathology , Blood Vessels/metabolism , Coronary Artery Bypass , Coronary Artery Disease/pathology , Femoral Artery/metabolism , Femoral Artery/pathology , Humans , Muscle, Smooth, Vascular/pathology , Phosphorylation , Saphenous Vein/metabolism , Saphenous Vein/pathology , Saphenous Vein/transplantation
19.
Herzschrittmacherther Elektrophysiol ; 12(4): 178-85, 2001 Dec.
Article in German | MEDLINE | ID: mdl-27432387

ABSTRACT

VDD pacing systems provide a physiologic AV synchronous stimulation with only one lead in patients with high degree AV block and normal sinus node function. They compete with DDD systems. This overview presents actual results of VDD stimulation concerning implantation, atrial sensing and AV synchrony, as well as stability of sinus node function. The results are partly compared with those of DDD systems. Furthermore, ventricular lead performance and cost effectiveness are discussed. New developments towards single-lead DDD stimulation are shown. VDD systems have the advantage of shortening implantation times by up to 40% and fluoroscopy time is reduced by up to 55%. Additionally there is a non-significant trend towards fewer perioperative complications, as compared to DDD implantation. Comparable results for VDD and DDD systems have been shown for the reliability of P-wave sensing, and thereby AV synchrony, with mean values of 99% and above. Sinus node disease requiring atrial stimulation develops in about 1 to 2% of patients. This renders the missing atrial stimulation in VDD systems as not important. Ventricular lead function is similar in both systems. An advantage of VDD systems is their potential to reduce acute costs and during follow-up. The results of actual studies demonstrate that VDD systems are established in the therapy of isolated high degree AV block. They are equal to the competing DDD systems and are, in some aspects, superior to them.

20.
FASEB J ; 14(15): 2370-2, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11024008

ABSTRACT

Activation of the complement system plays an important role in the pathogenesis of atherosclerosis. The proinflammatory cytokine interleukin (IL)-6 is potentially involved in the progression of the disease. We therefore investigated whether the terminal complement complex C5b-9 affects IL-6 production from vascular smooth-muscle cells (VSMC) and set out to determine the underlying signal transduction pathway. Stimulation of human VSMC with C5b-9 resulted in an increase of IL-6 transcript and production of IL-6 protein. Pretreatment with pertussis toxin or pyrrolidine dithiocarbamate inhibited complement-dependent IL-6 mRNA expression and IL-6 release, suggesting the involvement of Gi-proteins and nuclear factor-kB (NF-kB). C5b-9 also induced formation of reactive oxygen species, which, along with IL-6 release, was inhibited by the antioxidant N-acetylcysteine. C5b-9 activated the redox-sensitive transcription factors NF-kB and activator protein-1 (AP-1), which were both involved in the induction of IL-6 by C5b-9, as demonstrated by cis element double-stranded (decoy) oligonucleotides (ODN). The results demonstrate that activation of the complement system induces IL-6 release from human VSMC by a Gi-dependent pathway involving the generation of oxidative stressand the activation of the redox sensitive transcription factors NF-kB and AP-1. Our data support a new mechanism for the proatherogenic effect of the terminal complement complex.


Subject(s)
Complement Membrane Attack Complex/pharmacology , Interleukin-6/biosynthesis , Muscle, Smooth, Vascular/immunology , NF-kappa B/metabolism , Transcription Factor AP-1/metabolism , Acetylcysteine/pharmacology , Antioxidants/pharmacology , Humans , Interleukin-6/genetics , Models, Genetic , Oligonucleotides/pharmacology , RNA, Messenger/biosynthesis , Reactive Oxygen Species/metabolism
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