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  • 1
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Interleukin-18 (IL-18) plays an important role in the regulation of TH1 as well as TH2 immunologic responses and thus in the development of chronic inflammatory diseases. Positive association studies of polymorphisms in IL-18 with different diseases have underlined the involvement of IL-18 in the pathogenetics processes. Our interest was to test polymorphisms of IL-18 for association with a typical TH1-mediated disease – juvenile idiopathic arthritis – and the TH2-mediated disease bronchial asthma in Caucasian children.Methods:  We genotyped five polymorphisms that were in association with chronic inflammatory diseases (−607C, −137C, 113G, 127T, and −133G). This was performed by restriction fragment length polymorphism in populations of asthmatic children, control individuals, and children with antinuclear antibodies (ANA)-positive juvenile idiopathic arthritis. Statistical analysis was performed by the Armitage trend test; haplotypes were calculated by the Arlequine program.Results:  No significant association was found between any single nucleotide polymorphism or any haplotype and bronchial asthma or ANA-positive juvenile idiopathic arthritis.Conclusion:  We conclude that the effect of IL-18 in the immunologic context of diseases like bronchial asthma or juvenile arthritis might be too complex to be reflected in a simple one-way association study. Furthermore, the polymorphisms under investigation might be nonfunctional.
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  • 2
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Dissecting complex diseases in underlying distinct traits and studying these for their genetic basis might enhance the power as well as the specificity, of detection of disease genes. These phenoypes are known as intermediate phenotypes.Objective:  We were interested in the atopic basis of asthma, and used the sensitization to mite (Dermatophagoides pteronyssinus) allergens as a pathophysiologically important intermediate phenotype.Methods:  This time we performed a genome-wide scan based on the same already used multiethnic European population consisting of 82 nuclear families with at least two affected siblings. We carried out nonparametric as well as parametric MOD-score analyses based on the genotypes of 603 microsatellite markers.Results:  In comparison with our first genome-wide candidate region search three novel regions additionally appeared to be significant. We obtained significant results for the region 2p12 with a MOD score of 3.35 and for the region 16q21 with a MOD score of 4.18. The most significant result was found for the region 3q21.3 with the same microsatellite marker, which showed significant linkage to atopic dermatitis (AD) in another study with a MOD score of 4.51 and an nonparametric linkage analysis (NPL) of 4.00.Conclusion:  Our findings indicate that atopy, allergic asthma, allergic rhinitis and AD on the one hand are distinct traits on both the clinical and genetic basis, but on the other hand, our results also underline that these traits are closely related diseases concerning the atopic basis of the traits.
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  • 3
    ISSN: 1435-1285
    Keywords: Schlüsselwörter Instabile Angina – Myokardinfarkt – Prädiktoren – Quantitative Koronarangiographie – Restenose ; Key words Myocardial infarction – predictors – quantitative coronary¶angiography – restenosis –¶unstable angina
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Angioplasty in acute coronary syndromes is complicated by a high rate of early vessel reocclusion and restenosis. Therefore, it is recommended to achieve a „stent-like” result by percutaneous transluminal coronary angioplasty (PTCA) or otherwise use coronary stenting (provisional stenting).¶   This study sought to determine angiographic and patient-related factors that are associated with early target vessel reocclusion or luminal renarrowing after coronary intervention in acute coronary syndromes (ACS).¶   In an observational prospective study we investigated 161 patients with ACS (acute myocardial infarction and unstable angina) submitted to PTCA. In 140 patients a follow-up angiography after 10 days was obtained. All angiograms were quantitatively evaluated by computerized measurements.¶   Target vessel reocclusion and early luminal renarrowing was observed in 10 patients (7.1%) and 19 patients (13.6%), respectively. Using univariate analysis, significant risk factors (P 〈0.05) for early reocclusion and renarrowing were diabetes mellitus (relative risk [RR] 6.1 and 5.0), arterial hypertension (RR 7.7 and 3.3), postprocedural lesion length ≥2.5mm (RR 6.8 and 7.1), postprocedural minimal lumen diameter ≤2.5 mm (RR9.0 and 5.8), residual stenosis ≥25% (RR 4.8 and 3.5) and absence of stents (RR 4.1 and 3.2). Moreover, in multivariate analysis hypertension and postprocedural lesion length could be identified as independent risk factors for reocclusion and renarrowing. Diabetes mellitus was found to be an independent risk factor for renarrowing.¶   Conclusions: In a consecutive series of patients with ACS undergoing PTCA with provisional stenting the occurrence of early target vessel reocclusion and luminal renarrowing is lower than previously reported for this subset of patients treated by PTCA alone. Adverse outcome is related to absence of stents, angiographic factors (residual stenosis, lesion length, minimal lumen diameter after procedure) and patient-related factors such as diabetes and hypertension.
    Notes: Zusammenfassung Die Angioplastie beim akuten Koronarsyndrom wird durch eine hohe Rate früher Gefäß-Reokklusionen und Restenosen kompliziert. Daher wird bei der perkutanen transluminalen Koronarangioplastie (PTCA) im klinischen Alltag oft ein „stent-gleiches“ Ergebnis angestrebt und andernfalls eine intrakoronare Stentimplantation durchgeführt (provisional stenting).¶   Diese Studie sollte angiographische und patientenbezogene Risikofaktoren aufzeigen, die für Frühverschluss oder Lumeneinengung des Zielgefäßes nach Koronarintervention bei akutem Koronarsyndrom (AKS) prädisponieren.¶   In einer prospektiven Verlaufsbeobachtung untersuchten wir 161 Patienten mit AKS (akuter Myokardinfarkt und instabile Angina pectoris), die mittels PTCA behandelt wurden. Bei 140 Patienten konnte eine Verlaufsangiographie nach 10 Tagen durchgeführt werden. Alle Angiogramme wurden quantitativ durch computerunterstützte Auswertung analysiert.¶   Reokklusion und Lumeneinengung des Zielgefäßes traten bei 10 Patienten (7,1%) bzw. 19 Patienten auf (13,6%). Als signifikante Risikofaktoren (p 〈0,05) für Frühverschluss und Lumeneinengung zeigten sich in der univariaten Analyse Diabetes mellitus (relatives Risiko [RR] 6,1 und 5,0), arterieller Hypertonus (RR 7,7 und 3,3), postinterventionelle Läsionslänge ≥2,5 mm (RR 6,8 und 7,1), postinterventioneller minimaler Lumendiameter ≤2,5 mm (RR 9,0 und 5,8), Reststenose ≥25% (RR 4,8 und 3,5) und das Fehlen eines Stents (RR 4,1 und 3,2). Außerdem konnten in der multivariaten Analyse Hypertonus und postinterventionelle Läsionslänge als unabhängige Risikofaktoren für Reokklusion und Lumeneinengung identifiziert werden. Zusätzlich fand sich Diabetes mellitus als unabhängiger Risikofaktor für eine Lumeneinengung.¶   Schlussfolgerungen: In einer Verlaufsserie von Patienten mit AKS, die mittels PTCA und provisional stenting behandelt wurden, ist die Inzidenz für Frühverschluss und Lumeneinengung des Zielgefäßes niedriger als bisher für dieses Patientenkollektiv bei alleiniger PTCA beschrieben. Die genannten Komplikationen sind verknüpft mit dem Fehlen eines Stents, angiographischen Faktoren (Reststenose, postinterventionelle Läsionslänge und minimaler Lumendiameter) und patientenbezogenen Faktoren wie Diabetes oder Hypertonus.
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  • 4
    ISSN: 1435-1285
    Keywords: Key words Angioplasty – centerline method – PTCA – quantitative angiography – wall motion reduction ; Schlüsselwörter Angioplastie – Centerline-Methode – PTCA – quantitative Angiographie – Wandbewegungsstörung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Im akuten Myokardinfarkt führt die intrakoronare Stentimplantation zu einem höheren Interventionserfolg und einer geringeren Anzahl kardialer Ereignisse als die alleinige PTCA. Unklar ist jedoch, ob auch die linksventrikuläre (LV) Funktion durch Stentimplantation verbessert werden kann. Hierzu wurden angiographische Parameter der Myokardfunktion bei Infarktpatienten bestimmt, die mit primärer PTCA behandelt wurden und bei unbefriedigendem koronarangiographischem Ergebnis eine zusätzliche Stentimplantation erhielten (provisional stenting). Neunzehn Infarktpatienten, die nach alleiniger PTCA ein angiographisch zufriedenstellendes (“stentgleiches”) Ergebnis zeigten, wurden 19mit Stent behandelten Patienten in einer Paarbildung gegenübergestellt. Es wurden nur Patienten eingeschlossen, bei denen die Koronarangiographie 10 Tage nach Intervention ein offenes Infarktgefäß zeigte und bei denen zwischenzeitlich keine kardialen Ereignisse aufgetreten waren. Die Gruppen glichen sich in der Schwere der koronaren Gefäßerkrankung, dem Segment des Koronarverschlusses, der Killip-Klasse und dem postinterventionellen TIMI-Fluß. Auch hinsichtlich Alter, Geschlecht, enzymatischer Infarktgröße, Ischämiezeit (max. bis 12 h) und kardiovaskulärer Risikofaktoren zeigten sich keine signifikanten Unterschiede zwischen beiden Gruppen. Die Myokardfunktion wurde angiographisch ermittelt und anhand computergestützter, quantitativer LV-Antiographie nach der Centerline-Methode analysiert. Die mit Stent behandelte Patientengruppe zeigte eine signifikant höhere Ejektionsfraktion (60,3 ± 2,1% vs. 52,6 ± 2,9%). Ebenso ergab sich bei den mit Stent behandelten Patienten für alle Parameter der regionalen Wandbewegung eine signifikant geringere Funktionsstörung gegenüber alleiniger PTCA (hypokinetische Wandanteile: 7,4 ± 2,4% vs. 16,1 ± 3,4%, maximale Hypokinesie in der zentralen Infarktregion: −0,98 ± 0,20 vs. −1,52 ± 0,15 SD, Schweregrad der regionalen Hypokinesie: 7,3 ± 2,6 vs. 21,9 ± 5,4 Flächenmaß). Die Ergebnisse dieser Untersuchung bei primärer PTCA im akuten Myokardinfarkt weisen darauf hin, daß die Stentimplantation auch im Blick auf die Erholung der LV-Funktion einer alleinigen PTCA überlegen ist. Dies galt selbst wenn mit PTCA angiographisch ein “stentgleiches” Ergebnis erzielt werden konnte und deutet auf eine effizientere Reperfusion durch Stentimplantation hin.
    Notes: Summary In acute myocardial infarction intracoronary stenting is superior to PTCA regarding interventional success and occurrence of cardiac events. It is, however, uncertain whether myocardial function also improves with stenting. We, therefore, assessed angiographic parameters of myocardial function in patients with acute myocardial infarction who were treated with primary PTCA and received additional stenting in case of an unsatisfactory angiographic result (provisional stenting). Nineteen patients with acute myocardial infarction, in whom a “stent-like” angiographic result was achieved by PTCA alone, were compared with an equal number of patients receiving provisional stenting. The groups were exactly matched with respect to severity of coronary heart disease, segment of coronary occlusion, Killip class, and TIMI flow after intervention. We only included patients without inhospital cardiac events, in whom repeat angiography after ten days revealed a patent target vessel. There were no differences between both groups regarding age, gender, enzymatic infarction size, duration of ischemia (≤ 12 h), and cardiac risk factors. Myocardial function was assessed by ventriculography and was analyzed quantitatively by the centerline method. The group treated by intracoronary stenting showed a significantly improved ejection fraction (60.3 ± 2.1% vs. 52.6 ± 2.9%). All parameters of regional wall motion also indicated significantly less functional disturbance in the stented group compared to PTCA alone (circumferential extend of hypokinesia: 7.4 ± 2.4% vs. 16.1 ± 3.4% chords, maximum hypokinesia in the central infarct region: −0.98 ± 0.20 vs –1.52 ± 0.15 SD, severity of regional hypokinesia: 7.3 ± 2.6 vs 21.9 ± 5.4 area). In summary, these results in patients undergoing primary PTCA in acute myocardial infarction indicate that intracoronary stenting is superior to PTCA alone with respect to myocardial recovery, even if an angiographically “stent-like” result can be achieved. Probably, stenting results in a more efficient reperfusion.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 352 (1995), S. 491-496 
    ISSN: 1432-1912
    Keywords: Key words Arrhythmias ; Catecholamines ; Desipramine ; Uptake1 ; Myocardial ischemia ; Rat heart
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In myocardial ischemia, nonexocytotic noradrenaline release has been identified as underlying mechanism of ischemia-evoked noradrenaline release. Nonexocytotic noradrenaline release can be suppressed by inhibitors of the neuronal noradrenaline carrier (uptake), such as desipramine. Utilizing this pharmacological intervention the role of local noradrenaline release in the genesis of ischemia-induced ventricular arrhythmias was studied. Regional ischemia was induced in rat isolated perfused hearts by ligature of the left anterior descending coronary artery, and the venous effluent obtained during the first 2 min of reperfusion was used to measure the release of endogenous noradrenaline by high-performance liquid chromatography methods. Coronary occlusion caused ventricular fibrilation in a well reproducible manner with an incidence of 70 to 80% during a 30 min observation period. Blockade of uptake1 by desipramine decreased the occurrence of ischemia-induced ventricular fibrillation to 60% (0.01 μmol/l) or 20% (0.1 μmol/l), and ventricular fibrillation was completely suppressed by 1 μmol/l desipramine. Likewise, desipramine (0.01–1 μmol/l) concentration-dependently reduced endogenous noradrenaline release during 30 min of regional myocardial ischemia. Nisoxetine, a structurally unrelated inhibitor of uptake1, also suppressed ischemia-evoked ventricular fibrillation. In contrast to its antifibrillatory effect during regional myocardial ischemia, desipramine precipitated arrhythmias when ventricular fibrillation was induced by perfusing normoxic hearts with exogenous noradrenaline. Combination of desipramine (0.1 μmol/l) with exogenous noradrenaline (0.01 to 1 μmol/l) increased the incidence of ventricular fibrillation compared to noradrenaline perfusion alone. Under these conditions, uptake1-blockade is known to increase the extracellular concentration of the perfused noradrenaline. Finally, in the isolated, spontaneously beating papillary muscle of the left rat heart, desipramine (0.1 and 1.0 μmol/l) had no effect on the upstroke velocity of action potentials, the action potential duration and the effective refractory period. In conclusion, the findings demonstrate that nonexocytotic noradrenaline release is an important mediator of ischemia-induced ventricular fibrillation in isolated hearts of the rat. It is also documented that uptake1 inhibitors such as desipramine reveal their effects on ventricular fibrillation secondary to their action on transmembrane noradrenaline transport.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Monatshefte für Chemie 71 (1937), S. 1-5 
    ISSN: 1434-4475
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Zusammenfassung 1. Das Raman-Spektrum der Hexabromozinnsäure zeigt an, daß dem Ion SnBr6” in wässeriger Lösung keine oktaedrische, sondern eine niedrigere Symmetrie, offenbar D4h , zukommt. 2. Das Streuspektrum einer salzsauren Lösung von SeCl4 läßt auf die Existenz des Ions SeCl6” schließen. 3. Die Streuspektren von Antimonpentachlorid und Arsentribromid wurden ergänzt. 4. In den Streuspektren von Natriumhypophosphit und phosphoriger Säure wurden die erwarteten Wasserstofffrequenzen aufgefunden. Natriumhypophosphit gibt sechs gut vermeßbare Linien.
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  • 7
    ISSN: 1435-1803
    Keywords: Angioplasty ; catecholamines ; epinephrine ; norepinephrine ; myocardial ischemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study investigated arterial and coronary venous catecholamine concentrations in patients undergoing either elective coronary angioplasty (PTCA) or direct PTCA for acute myocardial infarction. We included 17 patients with stenoses of the left anterior descending coronary artery (LAD) and 10 patients with acute anterior myocardial infarction (AMI) undergoing PTCA. During the initial balloon dilatation arterial and coronary venous plasma concentrations of norepinephrine and epinephrine were determined. In elective PTCA, coronary occlusion (2 min) resulted in a transient increase of arterial concentrations of norepinephrine (2.04±0.30 vs. 1.26±0.13 nmol/L before dilatation) and epinephrine (0.52±0.08 vs. 0.34±0.04 nmol/L) in the first minute of reperfusion, whereas coronary venous concentrations of catecholamines were not changed after dilation. Among the 10 patients with AMI, immediate reperfusion of the LAD (TIMI grade 3) was achieved in 6 patients. In these patients, baseline arterial concentrations for norepinephrine (3.91±1.16 nmol/L) and epinephrine (4.68±2.07 nmol/L) were elevated and no transcardiac gradient for catecholamines was found. In the first minute after successful reopening of the LAD we detected a distinct rise of the transcardiac norepinephrine gradient from −0.10±0.53 to 85.02±24.64 nmol/L, which declined in the fifth minute of reperfusion to 4.36±2.30 nmol/L. Conversely, venous epinephrine and arterial concentrations for both catecholamines remained unchanged within the observation period. In the four patients with incomplete (TIMI 0–2) reopening of the LAD, we found no cardiac washout of norepine phrine. In summary, a transient rise of systemic catecholamines, but no cardiac release of norepinephrine was observed in patients after brief coronary occlusion. Conversely, a massive washout of norepinephrine from the infarcted myocardium occurred during AMI.
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  • 8
    ISSN: 1435-1803
    Keywords: Key words Angioplasty – catecholamines – epinephrine – norepinephrine – myocardial ischemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study investigated arterial and coronary venous catecholamine concentrations in patients undergoing either elective coronary angioplasty (PTCA) or direct PTCA for acute myocardial infarction. We included 17 patients with stenoses of the left anterior descending coronary artery (LAD) and 10 patients with acute anterior myocardial infarction (AMI) undergoing PTCA. During the initial balloon dilatation arterial and coronary venous plasma concentrations of norepinephrine and epinephrine were determined. In elective PTCA, coronary occlusion (2 min) resulted in a transient increase of arterial concentrations of norepinephrine (2.04 ± 0.30 vs. 1.26 ± 0.13 nmol/L before dilatation) and epinephrine (0.52 ± 0.08 vs. 0.34 ± 0.04 nmol/L) in the first minute of reperfusion, whereas coronary venous concentrations of catecholamines were not changed after dilatation. Among the 10 patients with AMI, immediate reperfusion of the LAD (TIMI grade 3) was achieved in 6 patients. In these patients, baseline arterial concentrations for norepinephrine (3.91 ± 1.16 nmol/L) and epinephrine (4.68 ± 2.07 nmol/L) were elevated and no transcardiac gradient for catecholamines was found. In the first minute after successful reopening of the LAD we detect a distinct rise of the transcardiac norepinephrine gradient from –0.10 ± 0.53 to 85.02 ± 24.64 nmol/L, which declined in the fifth minute of reperfusion to 4.36 ± 2.30 nmol/L. Conversely, venous epinephrine and arterial concentrations for both catecholamines remained unchanged within the observation period. In the four patients with incomplete (TIMI 0–2) reopening of the LAD, we found no cardiac washout of norepinephrine. In summary, a transient rise of systemic catecholamines, but no cardiac release of norepinephrine was observed in patients after brief coronary occlusion. Conversely, a massive washout of norepinephrine from the infarcted myocardium occurred during AMI.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Basic research in cardiology 93 (1998), S. 264-268 
    ISSN: 1435-1803
    Keywords: Key words Adenosine – catecholamines – norepinephrine – rat heart – ventricular tachyarrhythmias
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Adenosine is an antiarrhythmic substance particularly effective in catecholamine-dependent tachycardias. Although endogenous adenosine substantially accumulates in catecholamine-stimulated hearts, little is known about the antiarrhythmic potency of endogenous adenosine in this condition. Therefore, we sought to demonstrate a potential antifibrillatory effect of endogenous adenosine either by blockade of adenosine receptors with 8-phenyltheophylline (8-PT) or by suppression of endogenous adenosine release with nitrobenzyl-6-thioinosine (NBTI). The study was performed in spontaneously beating Langendorff-perfused rat hearts. Adenosine release into the effluent was determined by HPLC methods. Catecholamine stimulation was induced by perfusing the hearts with norepinephrine (1 μmol/l) for 30 min, which caused ventricular tachycardia (VT) in 31% and ventricular fibrillation (VF) in 25% of control hearts (n=35). When 8-PT (10 μmol/l) was added to the perfusion buffer prior to norepinephrine, the incidence of VT and VF increased to 79 and 68%, respectively. The addition of 8-PT did not affect the catecholamine-dependent formation of adenosine. Perfusion of the hearts with NBTI (10 μmol/l) prior to norepinephrine reduced adenosine release and increased the occurrence of both VT (65%) and VF (40%). In summary, the results indicate that adenosine is an endogenous antiarrhythmic substance, which accumulates in catecholamine-stimulated myocardium to a level, which effectively suppresses the occurrence of ventricular arrhythmias.
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