[Effect of ciprofibrate on the endothelial dysfunction of patients with combined dyslipidemia]. / Ciprofibrát hatása kombinált dyslipidaemiás egyének kóros endothelfunkciójára.

Endothelial dysfunction can be detected in the early phase of atherosclerosis. Two unresolved questions have been raised the wether, (1) the dyslipidemic state alone without any other risk factors can be harmful for the endothelial function measured by ultrasound, and (2) the use of the antilipidemic fibrate is sufficient to influence the endothelial functions. From 38 subjects with solitary combined dyslipidaemia 32 (84%) showed endothelial dysfunction measured by flow mediated vasodilatation (FMD) on the forearm and this group of patients was featured only by higher fibrinogen levels (no differences on BMI, serum lipid and glucose level). The patients with endothelial dysfunction were treated with 100 mg of ciprofibrate per day (12 women, 20 men, average age: 44.6 +/- 9 years, BMI 24.6 +/- 3.4 kg/m2). The pretreatment serum lipid levels were: total cholesterol 6.9 +/- 0.4, triglyceride 4.2 +/- 0.3, HDL cholesterol 1.13 +/- 0.21 mmol/l. After the 4 weeks treatment period the cholesterol and triglyceride level decreased, the concentration of HDL cholesterol increased significantly, which changes were in correspondence with significant improvement of FMD (3.9 +/- 0.7% vs. 7.0 +/- 1.6%). The level of fibrinogen also declined significantly. At the 8th week there were no significant further changes compared to the data received at the 4th week. Using the lineal regressive analysis the improved vasodilatator respond at both check points was correlated only with the fall of total cholesterol level. The ciprofibrate was suspended after the 8th week for a 4 weeks period and the triglyceride and the fibrinogen levels increased whereas the HDL cholesterol level decreased significantly. The FMD impaired significantly (to 5.8 +/- 1.2%). There were no correlations among the changes. The results demonstrated the lipid and probably non-lipid-factors are important in these early damages of endothelial functions.

A method for detection of doxorubicin-induced cardiotoxicity: Flow-mediated vasodilation of the brachial artery.

BACKGROUND: The cardiotoxicity of anthracyclin antibiotics such as doxorubicin (DOX) is a serious side effect in cancer therapy. Reduced antioxidant capacity may be a factor responsible for DOX-induced oxidative damage to the heart. The endothelial dysfunction that results from excessive free radicals can be easily detected by flow-mediated vasodilation (FMD) of the brachial artery. OBJECTIVES: To determine the change in endothelial function after intravenous DOX bolus; to determine the change in biochemical parameters, reflecting increased activity of free radicals or decreased endogenous antioxidant capacity, after intravenous DOX bolus; and to determine the relation between alteration of en-dothelial function after the first DOX bolus and the change in left ventricular function during follow-up. PATIENTS AND METHODS: Twenty-two patients, with either non-Hodgkin's lymphoma (18 patients) or Hodgkin's disease (four patients) were enrolled for the study (seven women and 15 men), with a mean age of 37.3+/-13.7 years. Each patient was treated with a DOX-containing regimen. The actual mean dose of DOX was 33+/-12 mg/m(2). FMD was evaluated before and after DOX administration. In nine patients more frequent measures were taken to determine the time course of change in FMD after DOX administration. FMD was measured 6, 12, 24 and 48 h after DOX. On average each patient was followed up for 18.6+/-8.1 months following the first DOX administration. The mean cumulative DOX dose was 229+/-112 mg/m(2) by the end of the follow-up period. Left ventricular ejection fraction was determined regularly during and at the end of the study. RESULTS: FMD was normal (more than 5%) at baseline in each patient but decreased significantly after DOX bolus (9.9+/-4.4% versus 6.1+/-4.6%, P<0.02). Marked individual differences were found in FMD changes after DOX. Patients who had a more than 5% decrease in FMD after DOX bolus were pretreated with 1000 mg of vitamin C intravenously, just before the next intravenous bolus of DOX was given. The decrease in FMD was prevented. Stepwise multiple regression analysis showed that the decrease in left ventricular ejection fraction during follow-up significantly and independently correlated with the cumulative DOX dose and the value of FMD alteration after the first DOX bolus administration. CONCLUSIONS: FMD in the brachial artery was significantly impaired after the first DOX bolus. The marked individual differences suggest different antioxidant capacities in these patients. The results suggest that alterations in FMD after DOX allows for detection of patients with insufficient antioxidant capacity and patients at a higher risk of DOX-induced cardiotoxicity.

[The rate of acetylsalicylic acid non-respondents among patients hospitalized for acute coronary disease, previously undergoing secondary salicylic acid prophylaxis]. / Az acetilszalicilsav nonreszponderek gyakorisága akut coronaria-szindróma miatt kórházba felvett, megelözöen acetilszalicilsav szekunder preventív kezelésben részesült betegek körében.

The authors determined the rate of acetylsalicylic acid (ASA) non-responders among patients receiving secondary prevention due to cardiovascular diseases at the appearance of acute coronary events. The non-responders were defined as: patients who have been treated with ASA because of acute coronary syndrome, but the subsequently performed platelet aggregation study did not confirmed an appropriate platelet inhibition. Among the 75 patients being investigated (44 male, 31 female, average age: 61.3 ys) 21 were hospitalized due to acute myocardial infarction and 54 for unstable angina, respectively. The daily doses of ASA were 200-325 mg. The aggregation of platelets was measured within 24 h after the admission. The investigations were performed with different amounts of 4 different inducers (ADP, arachidonic acid, epinephrine and collagen) taking dose-response curves. The antiaggregatory treatment with ASA was considered to be ineffective if the typical aggregation curves were obtained above the following final concentrations of the inducers: ADP: > 5 microM, epinephrine: > 5 microM, arachidonic acid: > 250 microM, collagen: > 2 micrograms/ml. These upper-threshold concentrations of the inducers were determined with the help of the data of healthy drug free volunteers. Twenty-six of the 75 patients (34%) were found to be non-responder to ASA, whereas the antiaggregatory effect of ASA was proven in 49 cases. No differences were found in gender. The compliance was proven with the HPLC-determination of urinary metabolites of ASA performed immediately after the upon admission. Seven patients (10.9%) showed a non-compliance, not showing any traces of ASA-metabolites in their urine. The authors emphasizing the importance of the laboratory control even of the prophylactic ASA treatment in order to continue the effective antiaggregatory therapy with other effective drugs.

Effect of transfusion on the endothelium dependent dilatation of brachial artery in patients with chronic anemia.

The effect of changes in the main determinants of whole blood viscosity after red blood cell transfusion on endothelium dependent dilatation of brachial artery was studied in patients treated with symptoms of chronic anemia. 10 patients were involved in the study, 8 males, 2 females, mean age 52.7+/-18.7 years. Following blood tests performed at hospital admission: hemoglobin (Hgb), red blood cell count (RBC), hematocrit (Hct), white blood cell count, platelet count, plasma total protein, fibrinogen, plasma viscosity, BUN, creatinine, cholesterol, triglycerides. Flow mediated dilatation of brachial artery (FMD) was determined by Doppler method. Blood tests and FMD study were repeated after transfusion. The main determinants of whole blood viscosity increased after transfusion. The increases of Hgb, RBC, Htc were highly significant. The central flow velocity in brachial artery decreased at rest and during hyperemia as well. FMD of brachial artery was not changed significantly after transfusion. The change in factors determining whole blood viscosity did not cause a significant change in FMD. The probable explanation for this is that the increase of whole blood viscosity is associated with a decrease of central flow velocity. These two counteracting changes can equal each other.

[Incidence of familial defective apolipoprotein B-100 in cases of patients diagnosed with familial hypercholesterolemia]. / A familiáris defektív apolipoprotein B-100 elöfordulási gyakorisága klinikailag familiáris hypercholesterinaemiásnak tartott betegek között.

Familial Hypercholesterolemia (FH) and Familial Defective Apolipoprotein B-100 (FDB) are monogenic, autosome, dominantly inherited diseases appearing as type II/a primary hypercholesterolemia. The frequency of the heterozygositic forms is 1:700-1:500 in European population. Both forms of hypercholesterolemia causes early onset coronary heart diseases (CHD). According to the recommendations of the international MED-PED program (Make Early Diagnoses--Prevent Early Death), we found 73 FH cases and their 377 first relatives (parents, siblings, children) were also assessed. 156 patients were diagnosed clinically FH (131 alive and 25 deceased), and 31.8% of the males and 32.4% of females suffered from early onset CHD. One family with FH consists of 5.46 members on the average and there are 2.39 FH patients in one family. In our FH cohort four patients with FDB (R3500Q mutation) were diagnosed with allelspecific PCR, and the mutation was detectable also in 9 cases out of 11 living family members. The plasma total cholesterol level of the FDB patients--especially at younger age--was very close to the normal values, which is in contrast to the findings in FH patients. Nevertheless, FDB can be one of the independent causes of the early onset CHD. Therefore, in families with high frequency of cardiovascular diseases the R3500Q mutation has to be considered.

Effect of benazepril on endothelial function in previously untreated hypertensive patients. The Working Group of Cardiology of the Academic Committee of Veszprém, Hungary.

The aim of this study was to determine whether angiotensin-converting enzyme inhibitor administration improves the endothelial function of patients with previously untreated essential hypertension. Using high-resolution ultrasonography, we measured the arteria brachialis diameter at rest, during reactive hyperemia (endothelium-dependent flow-mediated dilatation [FMD]), and after sublingual nitroglycerin (endothelium-independent dilatator). Twenty-one previously untreated hypertensive patients participated in the study (13 men, 8 women; mean age, 39.1 +/- 15 years). In the 21 patients, the basal FMD was 5.02% +/- 4.1%. Two hours after the first 10-mg benazepril dose, the FMD was 6.67% +/- 3.9%, and after 1 month of daily 10-mg benazepril administration, the FMD was 5.59% +/- 2.9%. These changes were not significant compared with the baseline value. Nine patients had relatively normal FMD (>5%), whereas the other 12 patients had abnormal FMD (<5%) at baseline. In the latter group, the first 10 mg benazepril produced significant improvement in FMD, from 2.4% +/- 2.5% to 5.08% +/- 2.4% (P < 0.05), but 10 mg benazepril daily for 1 month resulted in no further improvement (4.78% +/- 2.7%) compared with the acute effect. No difference was found between groups with regard to age, gender, blood pressure, blood lipids, and basal arteria brachialis diameter. The previously untreated patients with essential hypertension have endothelial dysfunction, but individual differences were found. The angiotensin-converting enzyme inhibitor treatment improves endothelial function only in those patients who had endothelial dysfunction before the treatment.

Arrhythmic effects of intermittent dobutamine therapy in chronic heart disease failure. The Working Group of Cardiology of the Academic Committee of Veszprém, Hungary.

It is known that intermittent dobutamine therapy improves the symptoms and physical condition of patients with chronic heart failure, but its arrhythmogenic effect is insufficiently described. The aim of this study was to assess ventricular arrhythmias and the condition of patients before, during, and after intermittent dobutamine therapy. The 23 patients participating in the study were in New York Heart Association functional classes III and IV despite therapy with digitalis, diuretics, and angiotensin-converting enzyme inhibitors. Starting dosage of dobutamine was 2 microg/kg/min, which was raised gradually up to 12 microg/kg/min, or until the appearance of complaints or symptoms. In group I (7 patients), for 24 hours before dobutamine infusion, Holter monitoring had been performed. In the subsequent 24 hours, during the infusion, patients were monitored in the critical care unit, but the second Holter test was performed only after the infusion, i.e., in the third 24 hours. In group II (16 patients), the Holter monitoring was started 4 hours before dobutamine infusion and was continued for an additional 20 hours, during the drug administration. In the 24 hours after dobutamine treatment, another Holter monitoring was performed. There was no increase in frequency of ventricular arrhythmias after the dobutamine infusion compared with the preinfusion period, but during dobutamine administration, ventricular arrhythmias occurred more frequently than in the preinfusion and postinfusion periods. No ventricular fibrillation was observed in the 23 patients. In conclusion, ventricular arrhythmias are frequent in congestive heart failure, and dobutamine infusion increases their incidence. The arrhythmogenic effect of dobutamine subsides on the day after the dobutamine infusion. Because of the arrhythmogenic effect of dobutamine, admission to the critical care unit is suggested during the infusion, but monitoring is not necessary after the end of the infusion.

[Effect of chronic anemia on the endothelium-dependent dilatation of the brachial artery]. / Krónikus anaemia hatása az arteria brachialis áramlásfügg"o dilatációjára.

UNLABELLED: The effect of changes in main determinants of whole blood viscosity after red blood cell transfusion on endethel dependent dilatation of brachial artery was studied in patients treated with transfusion because of symptoms of chronic anaemia. PATIENTS AND METHODS: 10 patients were involved, 8 females 2 males, mean age 50.9 +/- 16.6 years. Following blood tests were performed at hospital admission: hemoglobin, red blood cell count, heamatocrit, white blood cell count, platelet count, plasma total protein, fibrinogen, plasma viscosity, blood urea nitrogen, creatinine, cholesterol, triglicerides. Flow mediated dilatation of brachial artery was determined, too. Blood tests and flow mediated dilatation study were repeated after transfusion. RESULTS: The main determinants of whole blood viscosity increased after transfusion. The increase of hemoglobin, red blood cell count, hematocrit were highly significant. The central flow velocity in brachial artery decreased at rest and during hyperemia as well. The flow mediated dilatation of brachial artery wasn't significantly changed by transfusion. CONCLUSIONS: Change of determinants of whole blood viscosity caused by transfusion didn't change the flow mediated dilatation of brachial artery. The probable reason for this that the increase of whole blood viscosity in associated with the decrease of central flow velocity. These two counteracting changes probably equal each other.

[Adverse effects of combined use of acenocoumarol and acetylsalicylic acid after myocardial infarct and unstable angina]. / Acenocoumarol és acetylsalicylsav együttes alkalmazásának szövödményei szívinfarktus után és instabil anginában.

The authors examined the bleeding complications in 75 patients who received acenocoumarol and acetylsalicylic acid combined therapy. The studied population suffered from either acute myocardial infarction or unstable angina. Among the 75 patients in two cases (2.7%) appeared serious bleeding and in another 25 cases (33.3%) mild bleeding complications. There were no fatal cases. Comparing these data with literary data, the authors stated that in the study group the proportion of serious complications didn't increase in comparison with patients who received either acenocoumarol, warfarin or acetylsalicylic acid but mild bleeding appeared more frequently. This finding suggests that in high risk patients the combined acenocoumarol-acetylsalicylic acid therapy can be considered under strict control.

[Effect of lovastatin on serum lipids and lipoproteins. Hungarian multicenter, open-label study]. / Lovastatin kezelés hatása a serum lipidekre és lipoproteinekre. Hazai, nyitott, többcentrumos vizsgálat.

The authors studied the effects of lovastatin on the parameters of serum and lipoprotein lipids in an open multicenter trial. 160 patients with hypercholesterolemia participated in the study, 151 of whom completed the trial. After a 4 week period of dietary measures, the patients were treated with lovastatin for 12 weeks while combining standard lipid lowering diet. The initial dose of the drug was 20 mg, this was increased until serum cholesterol level decreased under 5.2 mmol/l, or to a maximal daily dose of 80 mg. By the end of the 12th week, serum cholesterol level was reduced by an average of 33% (p < 0.001), LDL-cholesterol by an average of 45% (p < 0.001), serum triglyceride concentration by an average of 22% (p < 0.001) and HDL-cholesterol increased by an average of 13% (p < 0.001). Lovastatin showed a very good safety profile, therapy had to be cancelled due to the occurrence of adverse events only in 4 cases.

Consequence and therapy of primary tooth intrusion.

The consequences of primary tooth intrusion to the permanent successors are as follows: internal white enamel hypoplasy, external white or yellow-brown enamel hypoplasy, crown dilaceration and root angulation. Questions of therapy have also been discussed.

Telemetric evaluation of the atrioventricular conduction system.

A telemetric method was developed to record His-bundle ECG. With this technique the His-potential of ambulatory patients could be continuously monitored. The heart rate, AH intervals and HV intervals were recorded at rest, during exercise and during atrial pacing in ten patients with various arrhythmias. It was found that atrial pacing increased, and exercise, at comparable rates, decreased the AH intervals. The HV intervals did not change. The telemetric method is useful in dynamic evaluation of the atrioventricular conduction system in the clinical practice.

[Prognosis for patients with myocardial infarct treated with a transitory pacemaker during the 1st year]. / Zur Prognose der mit transitorischem Schrittmacher behandelten Herzinfarktpatienten im ersten Jahr.

The authors investigated the occurrence of mortality during hospitalisation (first 4 weeks) and in the following period (from the 5th week till the end of the first year) on 70 patients with acute myocardial infarction subject to temporary pacemaker therapy due to bradyarrhythmia and/or conduction disorders. Progression of conduction disorder has been commonly observed during hospitalisation, mortality amounted to 43 per cent. Almost each of the conduction disorders has been discontinued by means of prophylactic pacemaker therapy. Despite the successful pacemaker therapy during the acute phase one third of the patients died within one year. It was found by the authors that the mortality in both periods showed close relationship not with the character of the block, but with the localisation and the severity of the infarction.