[Stent PTA in secondary symptomatic proximal subclavian artery obstruction]. / Stent-PTA bei sekundär symptomatischen proximalen Subclaviaobstruktionen.

Stent-PTA of secondary symptomatic proximal subclavian artery stenosis In comparison with conventional surgical revascularisation, percutaneous transluminal angioplasty (PTA) is an alternative treatment for short stenoses or occlusions involving the origin of the subclavian artery. If there is clinical suspicion of subclavian artery obstruction (e.g. blood pressure difference in both arms), digital subtraction angiography of the aortic arch and upper limb should be performed prior to creating radial haemodialysis shunts or coronary bypass crafting involving the internal mammary artery. PTA and stenting can be successfully carried out in symptomatic secondary proximal subclavian artery stenosis, e.g. in radial haemodialysis fistulas with distal ischaemia.

Role of virulence factors, cell components and adhesion in Helicobacter pylori-mediated iNOS induction in murine macrophages.

To investigate the mechanisms involved in Helicobacter pylori-mediated inducible nitric oxide synthase (iNOS) upregulation in mononuclear cells we cocultivated human THP-1 acute monocytic leukemia cells and murine J774A.1 professional macrophages with different H. pylori wild-type strains and mutants. We have shown that H. pylori-mediated iNOS induction in J774A.1 is independent of established virulence factors but dependent on direct interaction between bacteria and cells. In J774A.1, iNOS was equally upregulated by the wild-type strains J99, 26695, P12, and P1 as well as by mutants lacking the cag pathogenicity island, vacA, katA, alpAB genes and the hp0043 gene taking part in lipopolysaccharide biosynthesis when direct cell contact was allowed but not when bacteria and cells were separated by protein-permeable filter membranes. In contrast, iNOS was not induced in THP-1. This indicates that H. pylori-mediated iNOS induction in J774A.1 is independent of important virulence factors whereas cell contact is crucial which suggests a role of adhesion or phagocytosis.

Antihypertensive efficacy and orthostatic tolerance of bunazosin vs nitrendipine: a multicentre double-blind randomized controlled study.

A multicentre double-blind randomized controlled study was conducted in 358 patients with mild to moderate essential hypertension. The goal was to compare the antihypertensive efficacy, tolerability, and in particular postural hypotension of the alpha 1-adrenoreceptor blocker bunazosin with the calcium channel blocker nitrendipine. Both treatment groups had comparable baseline blood pressure (BP) values, namely diastolic BP (DBP) of 103.8 +/- 5.6 mm Hg in the bunazosin group, and 103.4 +/- 6.0 mm Hg in the nitrendipine group, respectively. Baseline systolic BPs (SBP) were 149.7 +/- 14.4 mm Hg (bunazosin) and 149.2 +/- 14.3 mm Hg (nitrendipine). After 12 weeks of therapy, reduction of DBP (-6.1 +/- 11.7 mm Hg on bunazosin vs -6.9 +/- 9.9 mm Hg on nitrendipine; P = n.s.), and SBP (-4.4 +/- 14.3 mm Hg on bunazosin vs -7.0 +/- 14.4 mm Hg on nitrendipine; P = n.s.) was similar in both groups. During a provocative orthostatic tolerance test after the first dose, the incidence of prae-collapses (ie termination of the test due to orthostatic complaints) was higher on bunazosin (17 vs 2; P < 0.05) but orthostatic dysregulation symptoms (symptom score 1.37 on bunazosin vs 0.95 on nitrendipine; n.s.) and collapses (four on bunazosin vs one on nitrendipine; n.s.) occurred to a similar extent in both treatment groups. Three and 9 weeks after treatment, no increased susceptibility to orthostatic stress compared to baseline could be found in either group. Under daily life conditions, the frequency of orthostatic dysregulation was identical in both groups (0.8%). Bunazosin, however, was far better tolerated with 43.8% of the patients complaining of adverse events as opposed to 63.6% on nitrendipine (P < 0.001). The rate of early discontinuations due to adverse events was only 1.3% on bunazosin compared to 13.6% on nitrendipine (P < 0.001). In conclusion, bunazosin has a similar antihypertensive efficacy as nitrendipine. Despite an initially higher susceptibility to orthostatic stress under a provocative manoeuver, bunazosin evoked the same low incidence of orthostatic dysregulation symptoms as nitrendipine under daily life conditions, but was significantly better tolerated than nitrendipine.

[The effects of treatment with trapidil compared to nifedipine on physical, emotional and cognitive exercise tolerance in patients with coronary heart disease]. / Behandlung der körperlichen, emotionalen und kognitiven Belastbarkeit bei Patienten mit koronarer Herzkrankheit unter Trapidil im Vergleich zu Nifedipin.

The present study was carried out to investigate exercise test results and the outcome of the quality of life after administration of trapidil (CAS 15421-84-8, Rocornal) or nifedipine (CAS 21829-25-4) to patients with coronary heart disease. The characteristics of the life quality in combination with the results of exercise test are considered of great importance for selecting medical treatment in patients with chronic stable angina pectoris. However, little information is available on how this first evaluation may be used to select the best pharmacological approach in individual patients. In this prospective multicentre study, 144 patients with stable angina were enrolled in 6 centres. Due to protocol violations and drop-outs 116 patients were evaluated for tolerability; 101 patients were evaluated for efficacy. After baseline evaluation, consisting of an exercise test and a questioning investigating patients' anginal symptoms and several psychometric testings, the patients were randomly allocated to double-blind treatment for 12 weeks with either trapidil, 200 mg t.i.d. or nifedipine, 10 mg t.i.d. according to a parallel group design. After 6 and 12 weeks exercise tests and psychometric testings were repeated. Both trapidil and nifedipine prolonged exercise tolerance (trapidil 39.2% vs. nifedipine 33.3%) or increased the total exercise over baseline levels (trapidil 57.8% vs. nifedipine 61.2%). Using Mann-Whitney U-test the SB-S-rating scale and the physician's assessment revealed a comparable improvement of life quality (trapidil 69.4% vs. nifedipine 80.0%) under both treatments. In addition patient questioning showed a significant reduction in angina attacks and in nitroglycerin consumption. None of the characteristics of anginal symptoms or exercise test gave evidence for a significant difference between nifedipine and trapidil. Both drugs demonstrated similar safety profiles (adverse events (AEs) 12.7% for trapidil and 11.1% for nifedipine); four patients of the trapidil group and one of the nifedipine group discontinued the clinical trial because of AEs. The results of a baseline exercise test and rating questionnaires may offer useful information for selecting medical treatment in stable angina pectoris.

The actions of talinolol, a beta 1-selective beta blocker, in cardiac arrhythmia and acute myocardial infarction.

It has long been known that beta-receptor blocking agents, including mainly cardioselective compounds, have favourable effects on tachyarrhythmias of various origins. They are the only substances known so far in the post-infarction phase to reduce significantly sudden cardiac deaths and to lower the rate of recurrent infarctions. High-risk patients seem to benefit most from the application of cardioselective beta blockers. In the acute infarction phase as well, beta-receptor blockers display favourable effects in the majority of patients, especially as they reduce the myocardial-infarct size and lower the tendency to arrhythmias by protecting the heart from sympathetic stimulation. The favourable effect on the variability of the heart rate must be stressed. Furthermore, the early application of beta-receptor blockers is recommended today not only in the event of hyperkinetic reactivity, but also and particularly in so-called high-risk patients, although always respecting the contra-indication. In these patients, mortality is reduced markedly in the long-term treatment.

Prognostic significance of cell DNA content in early-stage ovarian cancer (FIGO stages I and II/A) by means of automatic image cytometry.

Paraffin-embedded material from 69 patients with epithelial ovarian cancer FIGO stages I and II/A (including 21 patients with borderline carcinoma) was studied with automatic DNA image cytometry. Univariate analysis indicated a significant difference in survival based on the presence of nuclei with high DNA content (higher than 5 C). A group of patients with less than 0.2% cells with high DNA content had a 6-year survival of 87%, whereas in a group of patients with more than 0.2% of such cells, 6-year survival was 49%. This parameter remained significant when used in a group of stage I/a and I/b patients. Statistical analysis of diploid vs. non-diploid tumors also showed significant difference in survival. Separate analysis of 48 invasive ovarian cancers indicated that ploidy, the percentage of cells with high DNA content and tumor stage (stage I/a + b vs. stages I/c + II/a) reached significance for survival, whereas grading did not. In addition, comparison of clinical stage, grading, ploidy and the percentage of cells exceeding 5 C with a threshold at 0.2% by means of a multivariate analysis (Cox regression model) showed that only the percentage of cells exceeding 5 C remained statistically significant.

Modulation of intercellular adhesion molecule-1 expression on human melanocytes and melanoma cells: evidence for a regulatory role of IL-6, IL-7, TNF beta, and UVB light.

Intercellular adhesion molecule-1 (ICAM-1) is involved in cell-cell interactions of leukocytes and parenchymal cells and thus plays an important role in immunologic and inflammatory reactions. The expression of ICAM-1 that is found on many different cells such as melanocytes and melanoma cells is induced by various cytokines, including interferon-gamma (IFN gamma), interleukin (IL)-1 and tumor necrosis factor alpha (TNF alpha). Because expression of ICAM-1 in melanoma was found to correlate with increased risk of metastasis, the regulation of ICAM-1 expression on human melanocytes and melanoma cells was investigated. Foreskin-derived melanocytes and melanoma cell lines (A375, G361) were incubated with different cytokines and ICAM-1 expression was evaluated by fluorescence-activated cell sorter. IFN gamma, IL-1, IL-7, TNF alpha, and TNF beta significantly upregulated ICAM-1 expression in a dose-dependent manner. Most interestingly, the cytokine IL-6, which does not influence adhesion-molecule expression on other cells, significantly upregulated melanocyte and melanoma cell ICAM-1 expression. This effect was dose dependent and could be blocked by an IL-6 antibody. Irradiation with ultraviolet (UVB) light did not influence constitutive ICAM-1 expression on melanoma cells and melanocytes, but suppressed cytokine-induced ICAM-1 expression when cells were harvested 16 h after irradiation. These findings were further confirmed by Northern blot analysis, showing a marked accumulation of ICAM-1 mRNA after cytokine treatment, which was reduced by irradiation with UVB light. However, when UVB-exposed melanoma cells were cultured for at least 48 h induction of ICAM-1 expression was observed. These data indicate that, similar to other cells, ICAM-1 expression on melanoma cells and melanocytes is regulated by cytokines and that UVB light affects ICAM-1 expression on melanocytic cells in a biphasic manner.

Phenotypic characterization of infiltrating leukocytes in benign prostatic hyperplasia.

This study for the first time elaborates on cells of the immune system present in benign prostatic hyperplasia (BPH). Compared with normal prostate, all BPH-derived specimens revealed a marked increase of CD45+ leukocytes, characterization of which demonstrated three major cell types, i.e., CD3+ T lymphocytes, CD11c+ macrophages and CD20+ B lymphocytes. Frequencies of CD3+ cells/mm2 of cryocut sections were increased at least 10 times in BPH specimens, and the CD8+:CD4+ T suppressor/cytotoxic:T helper cell ratio was reversed. The infiltrating leukocytes predominantly populate the interstitium and accumulate around epithelial ducts which, however, were found to be invaded and/or destroyed only in a number of cases. Phenotypic alterations of surface antigen expression on prostate epithelial cells in BPH that might be due to the presence of lymphocytes were examined by using monoclonal antibodies (mAb) directed against human leukocyte antigens (HLA). Whereas anti-HLA-DR reactivity in normal prostate is restricted to small numbers of macrophages and includes neither prostate epithelial cells nor prostate T cells, it was found to be dramatically increased in BPH, comprising CD45+ cells and prostate epithelial cells as demonstrated by double-staining with anti-cytokeratin or anti-prostate-specific antigen. A mean of 40% of analyzed epithelial glands in BPH reacted with anti-HLA-DR, but not with anti-DQ or -DP monoclonal antibodies. A new method for the enrichment of prostate-derived lymphocytes was established to facilitate phenotypic analysis by flow cytometry, demonstrating 70 to 80% of enriched CD45+ cells to stain for CD3, approximately 60% thereof for CD4, 30% for CD8, and the remaining 10% with anti-CD20, a pan-B-cell marker. Flow cytometry showed that, in contrast to peripheral T cells, both CD4+ and CD8+ prostatic T cells were positive for the T cell activation markers HLA-DR and interleukin-2-receptor.

[Acute and long-term effects of pimobendan (UD-CG 115) in NYHA II and III heart failure. Results of a randomized multicenter double-blind study]. / Akut- und Langzeiteffekte von Pimobendan (UD-CG 115) bei Herzinsuffizienz NYHA II und III. Ergebnisse einer randomisierten multizentrischen Doppelblindstudie.

The effects of pimobendan (UD-CG 115) on hemodynamics and exercise capacity after acute (single dose) and chronic (6 month) oral treatment, as well as acute treatment after 6 months were investigated in 67 patients with chronic heart failure of NYHA classes II or III, which had persisted in spite of treatment with diuretics and digitalis. They were treated with pimobendan (2.5 mg bid or 5 mg) or placebo in a randomized, double-blind multicenter trial. With a single administration before and after 6 months' treatment there was-compared to placebo-a significant fall in pulmonary capillary pressure (PCP) at rest (R) and during exercise (E) of 7% to 24%. Right atrial pressure (R) and pulmonary arterial pressure (PAP) (R, E) decreased after pimobendan on day 1; cardiac index (E) increased significantly. All other parameters were not influenced. After chronic therapy, PCP (E), PAP (E), LV stroke work index (E), and pulmonary resistance (R and E) values were significantly lowered by pimobendan when compared to day 1. Exercise duration was prolonged after 6 months by 83 s and 47 s after 5 and 10 mg/day, resp., compared to the placebo group (group difference not significant). Subjective wellbeing was improved in all three groups (no group difference). Clinical symptoms were not altered; six patients (two in each group) died suddenly. Another nine patients discontinued the trial prematurely because of poor efficacy or adverse events (no group difference). Overall, pimobendan was well-tolerated and had favorable effects on both acute and chronic hemodynamics and on exercise capacity. There was no evidence of any tolerance development.

[Behavior and prognostic value of QTc intervals in surface ECG in acute and chronic cerebral processes]. / Untersuchungen zum Verhalten und zur prognostischen Wertigkeit der QTc-Intervalle im Oberflächen-EKG bei akuten und chronischen zerebralen Prozessen.

Abnormal ECG-patterns in patients with acute and chronic cerebral processes are well known; the prognostic value, however, is still uncertain. Therefore, we examined 12 conventional ECG-leads retrospectively (at the day of admission to hospital) with respect to heart rate, occurrence of heart rhythm disturbances, and repolarization abnormalities in 131 patients (pts) with acute strokes and in 116 pts with cerebral tumors. Patients with atrial fibrillation or bundle branch blocks were excluded. In all pts the longest QTc-intervals (heart rate correction according to Bazett) were found in the precordial leads V2-V6 and Nehb D, A, I. Patients with strokes had the longest QTc-intervals: 418 +/- 43 ms (II) - 445 +/- 55 ms (V5). The differences in healthy persons (n = 25) and pts with cerebral tumors were significant (p less than or equal to 0.01). Between the standard and precordial leads the differences in this group were also significant. The QTc-values in non-survivors were significantly longer (429 +/- 45 ms in lead I, 458 +/- 45 ms in V4) than in survivors (409 +/- 35 ms in lead I, 436 +/- 52 ms in Nehb A). Initially, unconscious pts (n = 22) also revealed significantly longer QTc-intervals (485 +/- 58 ms, Nehb D) than conscious pts (440 +/- 45 ms, lead V5). 78.6% of pts with strokes had QTc-values in at least one lead longer than 420 ms, and in 64%, we registered QTc-intervals greater than 440 ms. Significant differences were found between non-survivors (n = 56) and survivors (n = 75).(ABSTRACT TRUNCATED AT 250 WORDS)

[Hemodynamic and clinical studies with Bonnecor--a new anti-arrhythmia drug]. / Hämodynamische und klinische Untersuchungen mit Bonnecor--einem neuen Antiarrhythmikum.

It is reported on clinical and haemodynamic results with Bonnecor, a new antiarrhythmic drug with class I and IV properties, on 68 test persons in parenteral and oral administration. The haemodynamic acute investigations (dosage 2 x 0.1 to 1 x 0.3 mg/kg body weight) which were performed on 10 test persons with compensated heart diseases did not show any negative haemodynamic effects of Bonnecor at rest and on exercition. The chronic effect on ventricular extrasystoles of the degrees of severity mostly II-IV were investigated in the open experiment on 17 patients as well as on 3 patients with supraventricular dysrhythmias and on 30 patients with ventricular extrasystoles Lown III-IV in the single blind cross-over experiments to verapamil retard. A clinically relevant result with regard to the reduction of the ventricular extrasystole about 75% was found in 23% of the patients (open study) and 33.3% of the patients (cross-over), respectively. The reduction of the ventricular extrasystole was significant compared with the empty value. Under the influence of verapamil a significant reduction of the ventricular extrasystole could not be verified, the differences between Verapamil and Bonnecor were, however, not to be ascertained statistically. The effect of Bonnecor on couplets and volleys was clinically relevant in 52 and 46%, respectively, of the patients (reduction greater than or equal to 93%) and approximately corresponds to the results with other antiarrhythmic drugs. The tolerability is to be estimated as relatively good.(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction between nifedipine and cardioactive drugs.

Nifedipine (N) and dehydronifedipine (DHN) plasma levels were measured by gas chromatography in 37 patients before and 2 h after the intake of 20 mg N. They suffered from cardiovascular diseases and were treated with N in daily doses of 30 or 60 mg in combination with nitrates, beta-receptor blocking agents, digitoxin, saluretics and/or vasodilators for several weeks or months. Simultaneously, blood pressure and heart rate were measured. For comparison, six healthy volunteers between the ages of 25 and 46 years took 20 mg N on an empty stomach. Their mean plasma N level amounted to 47.7 (SD: 13.6) ng.ml-1, the DHN level reached a mean value of 46.7 (SD: 22.8) ng.ml-1 2 h after administration. The mean plasma N level of the patients rose from 14.1 to 34.1 ng.ml-1 and that of DHN, from 5.4 to 16.0 ng.ml-1. In 26 of 37 patients the heart rate increased without correlating with the altitude of the N level. The ratio DHN/N was 0.83 (SD 0.24) in the volunteers, while in the patients it amounted to 0.59 (SD 0.30). If the criterion DHN/N plasma level reached values greater than 1.0 the N degradation was enhanced (n = 4), and if it reached values less than 0.2, N degradation was depressed (n = 9). The results did not indicate inhibition of N degradation under long-term treatment with simultaneously administered cardioactive drugs.

Thymus-independent generation of Thy-1+ epidermal cells from a pool of Thy-1- bone marrow precursors.

Thy-1+ dendritic epidermal cells (Thy-1+ DEC) and immature thymocytes share several phenotypic features: CD45+, Thy-1+, asialo-GM1+, CD3+, CD4-, and CD8-. In view of this similarity, it has been suggested that the epidermis may be a site of either post-thymic or extra-thymic T-cell development. In order to address this issue, we used C3H/He/Han (Thy-1.2)----AKR/Ola (Thy-1.1) radiation bone marrow chimeras. Animals were first either thymectomized or sham-thymectomized, then lethally irradiated (750R) and, finally, reconstituted with allogeneic bone marrow cells previously depleted of Thy-1-bearing cells. Six weeks after bone marrow transplantation, spleens and lymph nodes of sham-treated animals, but not of thymectomized animals, contained large numbers of CD3+ donor-type Thy-1+ cells. The epidermis of both thymectomized and sham-treated animals contained not only many recipient-type CD3+, Thy-1+ DEC, but also small numbers of CD3-, donor-type Thy-1+ cells. After 4 months, the frequency of donor cells had greatly increased, but they still lacked CD3 antigens. Most of the donor cells had a rounded shape, but some exhibited a dendritic configuration. These results demonstrate that Thy-1- bone marrow-derived precursors of Thy-1+ DEC can migrate to the epidermis without thymic influence and yet acquire Thy-1 antigens during their journey. Although donor-type Thy-1+ epidermal cells failed to mature into CD3+ dendritic epidermal cells, the experimental model used in this study may be a versatile tool for studying the influence of thymic and extrathymic epithelia on T-cell maturation.

[The extension of heart failure therapy with vasodilators]. / Die Erweiterung der Herzinsuffizienztherapie mit Vasodilatatoren.

By the introduction of the vasodilators into the therapy of the cardiac insufficiency particularly by the application of angiotensin-converting-enzyme (ACE) inhibitors advance could be obtained with regard the peripheral resistance which is always made evident as a sequel of the vasoconstriction in severe cardiac insufficiency the application of vasodilating substances (venous or arterial) leads to a relief of the heart with increase of the cardiac output, decrease of the congestion symptoms and partly amelioration of the exercise tolerance. Whereas all vasodilating substances show these effects in the acute experiment, in the long-term application due to the tolerance development no significant haemodynamic and clinical amelioration is to be made evident any more, with the exception of the ACE-inhibitors. Only the combination of nitrates and hydralazine showed favourable results with regard to the survival time. The therapy with ACE-inhibitors is, when they is used in an expert way and aimed, the hitherto most conducive one to success which has only slight side-effects. Because of the present knowledge all patients with a cardiac insufficiency of the degrees of severity III and IV, perhaps already beginning with degree of severity II, should, in addition to glycosides and diuretics, be treatment with ACE-inhibitors, so far as no contraindication or intolerability are present. Otherwise an experiment with nitrates plus hydralazine is justified.

Prognostic significance of different QT-intervals in the body surface ECG in patients with acute myocardial infarction and in patients with acute or chronic cerebral processes.

In 73 patients after AMI, 131 patients with cerebral stroke and in 116 patients with cerebral tumours the QTc-intervals in different ECG leads were measured. In about 30% of pts with AMI there were prolonged (greater than or equal to 440 ms) QTc-values. Patients with AMI suffering from VT or non-survivors had the longest QTc-values. Also in patients with cerebral stroke and prolonged QT-values (greater than or equal to 440 ms) the risk of dying was significantly higher than in patients that survived. The prolongation of QTc in patients with cerebral tumours are not correlated with prognosis but with the severity of neurological disturbances.

[Deglutition-induced supraventricular tachycardias]. / Schluckinduzierte supraventrikuläre Tachykardien.

We describe the cases of two patients who exhibited a supraventricular tachycardia induced by swallowing. In both cases we found a systemic hypertension, other cardiac or gastroesophagic abnormalities were absent. The electrophysiologic studies demonstrated in the first case a supraventricular tachycardia with 1 : 1 AV-conduction and an origin in the right atrium, in the second case an atrial tachycardia with AV-block originating in the right atrium too. The pathogenetic mechanism is discussed. In both cases after treatment with amiodarone a complete cessation of the tachycardias was reached.

[Long-term effect of various nitrates in ischemic heart disease and latent heart failure]. / Untersuchungen zum Langzeiteffekt verschiedener Nitrate bei ischämischer Herzkrankheit und latenter Herzinsuffizienz.

In 24 patients (pts) with proven coronary artery disease, stable angina pectoris (AP) and elevated pulmonary artery pressure (PAP) during bicycle exercise, the acute and chronic (4 and 8 months) effects of several long-acting nitrates in different dosages: 50-300 mg pentaerythrityltetranitrate (PETN) or 40-120 mg isosorbide dinitrate (ISDN) were evaluated in comparison to sublingual nitroglycerin. Nitroglycerin was about 30%-40% more effective than PETN and ISDN with regard to pulmonary artery pressure at exercise. Beneficial effects of both long-acting nitrates were shown with regard to the number of anginal attacks, nitroglycerin consumption, and ST-segment depression both during short- and long-term treatment. Both nitrates decreased exercise pulmonary artery pressure by 15%-20%, at acute testing and during chronic therapy. There was no difference with respect to the long-term effects of both long-acting nitrates. However, more side-effects were observed during ISDN treatment. There were no signs of nitrate tolerance development with the therapy schedules under investigation.