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.

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.

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.

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.

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.

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.

[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.

[Long-term therapy with amiodarone in tachyarrhythmias--report on various experiences with special reference to its side effects]. / Langzeittherapie mit Amiodarone bei Tachyarrhythmien--Erfahrungsbericht unter besonderer Berücksichtigung der Nebenwirkungen.

In 23 patients with symptomatic severe supraventricular and ventricular tachyarrhythmias the effectiveness and the side effects of a long-term therapy with the class III antiarrhythmic drug Amiodarone (Cordarone) in a dosage of 100-800 mg/die in monotherapy and combination therapy were investigated. In these cases it proved to be an excellently effecting antiarrhythmic drug in tachycardiac dysrhythmias at atrial and ventricular level with an altogether good tolerance. In 16 patients side effects appeared and above all concerned corneal micro-deposition without any clinical symptoms (10 patients). In 3 patients nuclear-medically insignificant changes of the function of the thyroid gland were found--also without clinical relevance. Three times a photosensitisation was conspicuous, only in one patient the therapy was finished on account of epigastric trouble after three months. Av-blockings of higher degree, particularly with bundle-branch block and severe sinus bradycardias as well as disturbances of the thyroid function are regarded as contraindications without preceding pacemaker implantation.

[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.

[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)

[Mechanocardiography findings and hypertrophic and dilated cardiomyopathy]. / Mechanokardiographische Befunde bei hypertropher und dilatativer Kardiomyopathie.

On 71 patients with hypertrophic cardiomyopathy with and without measurable left-ventricular outflow tract gradients, with typical and atypical morphology (ascertained by catherisation of the right and the left heart and angiocardiography as well as selective coronarography) as well as also by catheter investigation including the cardiography of ascertained dilatative cardiomyopathy in 19 patients mechanocardiographic (systolic time analysis from the carotid sphygmogram as well as parameters of the diastole from the apex cardiogram) investigations concerning the heart function and the course were performed. The hypertrophic cardiomyopathy is characterized particularly by a restricted diastolic function, when a good or very good pumping function is present. On the basis of the mechanography the dilatative cardiomyography particularly shows a bad pumping function with also restricted diastolic function. The two forms of cardiomyopathy are clearly to be separated by means of the methods used. Prognostic statements are possible only with reservation. Apexcardiographic parameters are here better suitable.

[Pathophysiology of ventricular tachyarrhythmias]. / Untersuchungen zur Pathophysiologic ventrikulärer Tachyarrythmien.

On 11 patients at the age between 11 and 60 years with ventricular tachyarrhythmias (6 times relapsing ventricular tachycardia, twice relapsing ventricular fibrillation, 3 times massive polytopic ventricular extrasystoles) complex intracardiac electrophysiological and haemodynamic examinations, including heart catheterization with angiography (and in 6 patients selective coronarography) were performed. In no case we succeeded in evoking a ventricular tachycardia by stimulation. Also the spontaneous long-lasting ventricular tachycardias could not be interrupted by a single or manifold stimulation. By multiple right- and left-ventricular potential deviations we succeeded in differentiating the ventricular tachycardia and ventricular extrasystoles, respectively, according to the place of origin in all patients. As cause of the ventricular tachycardia and of the ventricular fibrillation, respectively, in 4 patients an ectopic focus with increased impulse formation, in the other patients, apart from an increased ectopic automatism, also reentry tachycardia is assumed.

[Clinical aspects, diagnosis, therapy and course of unstable angina pectoris]. / Klinik, Diagnostik, Therapie und Verlauf bei instabiler Angina pectoris.

It is reported on 27 patients aged 32-77 years with an unstable angina pectoris, including coronary spasm. All patients showed an anamnesis of less than 3 months, nearly the half of less than 24 hours. The resting electrocardiogram during the attack was pathological in 22 patients, 7 patients showed a Prinzmetal reaction and 11 patients showed intermittent ventricular dysrhythmias. The exercise electrocardiogram in the stable phase was pathological in 16 of 17 patients. Of 23 patients who underwent a selective coronary angiography with laevocardiography 9 patients each showed a disease of one vessel and three vessels, respectively, and 5 patients a disease of two vessels. Only nearly 50% of the patients could be stabilized medicamentously (nitrates, calcium antagonists, rarely beta-blockers). In three patients still during the unstable phase a surgical revascularization was carried out, in 11 patients after stabilization. Five patients suffered an early infarction; one of them died. Altogether, the unstable angina pectoris is even nowadays to be regarded as a clinical picture with a relatively bad prognosis, which demands rapid action.

[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.

[Clinical experiences with bretylium tosylate]. / Klinische Erfahrungen mit Bretylium tosylat

Because of its antiarrhythmic and antifibrillatory qualities as well as its positively inotropic effect bretylium tosylate increasingly finds interest. The first results of a clinical and haemodynamical mechanocardiographic investigation with bretylium tosylate are presented. In doses between 1.6 and 6.2 mg/kg body weight intravenously and intramuscularly after an initial increase of blood pressure a clear decrease of the systolic system blood pressure develops. The resistance of the peripheral vessels decreases by 10 to 20%. It is an increase of the heart index and the stroke volume index by 10 to 30% to be proved as an expression of a positively inotropic effect. In orientating investigations the antiarrhythmic effect could be confirmed. The side-effects observed cause us to give a strong indication and to observe the patients carefully. The main area of application of bretylium tosylate might be seen in the possibility to achieve a pharmacological defibrillation of the ventricles.

[Endocardial mapping in the differential diagnosis of supraventricular arrhythmias]. / Endokardiales Mapping in der Differentialdiagnostik supraventrikuläer Dysrhythmien.

The surface ECG only in a restricted number allows evidence on the course off conduction in the atria. By introduction of the intracardial electrography into the clinic as well as various stimulation techniques has become possible better to analyse the formation of stimuli and the conduction system in man. The diagnosis of supraventricular arrhythmias renders particular difficulties. By recording of the intracardial potentials in as many as possible and defined points of the atria in relation to the fixed point possibly near to the sinus node (endocardial mapping) a better analysis of the excitation and conduction is possible. Only own examinations on 9 patients with sinus rhythm and supraventricular dysrhythmias by means of atrial mapping showed that origin and course of the conduction of cardial arrhythmias may be clarified better. The method mentioned according to our experiences hitherto made and reports in literature despite several lacks and difficulties in an enrichment of the diagnostic possibilities in supraventricular dysrhythmias.

[Clinical and paraclinical findings on status following prosthetic heart valve replacement with special reference to the behavior of pulmonary pressure]. / Klinische und paraklinische Befunde bei Zustand nach prothetischem Herzklappenersatz unter besonderer Berücksichtigung des pulmonalen Druckverhaltens.

Retrospectively were evaluated clinical findings of 151 patients with condition after replacement of artificial cardiac valves (Björk-Shiley), who were treated in our department of cardiology in 1986. The patients with mitral valve replacement (MVR) and mitral valve and aortic valve replacement showed the highest rate of individualisation in comparison to aortic valve replacement. 18 patients showed complications and acute deteriorations, respectively, two of which had a fatal course. In 53 patients the bicycle-ergometric exercises were performed with measurement of the pulmonary pressure. Of these patients the majority indeed subjectively improved in their behaviour, however, the objective exercise tolerance was altogether low and the rate of invalidisation increased in comparison to the preoperative rate. The pulmonary pressure at rest in the majority of the patients was reduced mostly in dependence on the initial values. Increases appeared only sporadically. Under exercise, however, particularly the patients with mitral valve replacement showed pathological increases of pressure. Altogether the best results showed patients with aortic valve replacement also with regard to the shrinking of the radiologically established size of the heart.

[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.

[Treatment of severe hypertension and hypertensive crises with nitrates]. / Die Behandlung schwerer arterieller Hypertonien und hypertensiver Krisen mit Nitrokörpern.

Taking into consideration the frequent combination of hypertension, ischaemic heart disease and heart insufficiency the effect of blood pressure as well as the influence of pre- and afterload gain increasing importance, when nitrates are used. It is the question, whether the blood pressure reducing effect may be used with a certain aim or not. In own investigations acute haemodynamic experiments with glycerol trinitrate were carried out on 10 patients with arterial hypertension (catheterization, estimation of HMV and so on) in rest and under ergometric load, clinical therapeutic experiments on 10 patients with crisis of hypertension with cerebral and/or cardiac complications as well as long-term experiments with pentaerythrityl tetranitrate on 6 patients with in most cases severe arterial hypertension. The acute effects on the haemodynamics correspond to those in normal blood pressure, in which case the reduction of blood pressure and resistance is more expressed. The favourable effect of glycerol trinitrate in the crisis of hypertension with cardiovascular complications can be regarded as proved. First own experiences with the long-term application of nitrates do not yet result in a clear estimation of effectivity and indications.