The effects of delta1-cortienic acid on skin blanching, pharmacokinetics and stability of loteprednol etabonate.

The effect of delta1-cortienic acid (delta1-CA) on human skin blanching activity of the soft corticosteroid, loteprednol etabonate (LE), has been studied. Ten volunteers had applied to their forearms a dose of LE ranging from 0.1 to 1 mM, or LE from 0.1 to 1 mM in combination with 2-times the concentration of delta1-CA (0.2 - 2mM). The results indicate that delta1-CA increased LE's effect on human vasoconstriction/skin blanching activity, both in the intensity and duration. This enhancing effect of delta1-CA was also observed in other blanching studies with other corticosteroids, such as hydrocortisone. The enhancement may occur through the displacement of LE bound to transcortin (also known as corticosteroid-binding globulin, or CBG) by delta1-CA as delta1-CA has a higher affinity for CBG than that for glucocorticoid receptor (GR), resulting in more free-LE to act on GR, and increased skin blanching. In rat studies, intravenous injection of delta1-CA (5-50 mg/kg) did not affect the pharmacokinetics of LE (5 mg/kg), indicating that delta1-CA is safe for combined use with LE. In stability studies, the presence of delta1-CA at the same concentrations as LE in aqueous suspension (0.1 and 0.2%) significantly increased the stability of LE. Thus, the combination of delta1-CA with LE serves an enhancing and stabilizing role while not impacting the pharmacokinetic properties of LE.

Nicotinic acid: an old drug with a promising future.

Nicotinic acid has been used for decades to treat dyslipidaemic states. In particular its ability to raise the plasma HDL cholesterol concentration has led to an increased interest in its pharmacological potential. The clinical use of nicotinic acid is somewhat limited due to several harmless but unpleasant side effects, most notably a cutaneous flushing phenomenon. With the recent discovery of a nicotinic acid receptor, it has become possible to better understand the mechanisms underlying the metabolic and vascular effects of nicotinic acid. Based on these new insights into the action of nicotinic acid, novel strategies are currently under development to maximize the pharmacological potential of this drug. The generation of both flush-reducing co-medications of nicotinic acid and novel drugs targeting the nicotinic acid receptor will provide future therapeutic options for the treatment of dyslipidaemic disorders.

Mutations in RAD3, MSH2, and RAD52 affect the rate of gene amplification in the yeast Saccharomyces cerevisiae.

We report here the use of the ADH4:CUP1 amplification detection system to identify five high amplification rate (HAR) strains of Saccharomyces cerevisiae that display 40- to 600-fold higher amplification rates than those of parental strains. We have identified a mutation in RAD3 DNA repair helicase gene in HAR strain B9-40 that results in a 40-fold increase in amplification rate. RAD3 is the functional homolog of the human XPD gene, suggesting that this model system will provide important candidates for genes that affect gene amplification in human cells. Isolation of the HAR strains has allowed us to test whether RAD52, which is essential for recombinational repair of DNA double-strand breaks, is also essential for amplification. Deletion of RAD52 in HAR strains B3-10 and B11-60 decreases amplification approximately 100-fold. In contrast, deletion of MSH2, which increases recombination between sequences with limited similarity, increases the amplification rate about 10-fold. These results suggest that recombination is an important step in amplification.

The effect of isolated perfusion on limb circulation in peripheral arterial occlusion.

The effects of isolated limb perfusion were studied in 12 patients suffering from peripheral arterial occlusion. The hemodynamic investigations show that the vascular resistance decreases considerably during isolated limb perfusion. After administration of a vasodilator cocktail, added to the perfusion, the vascular resistance continues to decrease. Angiographic records, made before, during and after the perfusion, suggest that the calibre of the collateral vessels increases significantly and besides new collaterals can also be observed. The mechanism of the effects of isolated hyperbaric limb perfusion and its clinical value are discussed.

[Incidence of stenosis of the internal carotid artery among patients waiting for coronary surgery]. / Arteria carotis interna szükületek gyakorisága coronaria mütétre váró betegek között.

1273 patients awaiting for coronary surgery were screened towards coexisting internal carotid artery stenoses. Non-significant carotid stenosis was revealed in 7.3% of these patients. In 48 patients (3.8%) the revealed stenoses were found to be hemodynamically significant. The coexistence of significant carotid stenoses with coronary artery disease was especially high at elderly patients. Among male patients over 70 years of age the occurrence of high grade carotid stenosis was as high as 10%. The 75% of significant stenoses was found to be asymptomatic. These would not been revealed without the carotid screening. The goal of this study is drawing attention to the frequent coexistence of coronary artery disease with carotid artery stenoses.

[Anesthesia for heart transplantation]. / A szívátültetés anaesthesiája.

Heart transplantation, as a therapeutic possibility, has been available since 1992 in Hungary. The authors present the anaesthetic aspects and clinical experiences of this worldwide used therapeutic method. The specialties of the narcosis, the importance of the aseptic techniques, and the treatment of the denervated heart are emphasised.

[Acute dissection of the ascending aorta diagnosed by two-dimensional echocardiography]. / Kétdimenziós echokardiográfiával diagnosztizált heveny aorta ascendens dissectio.

The authors present a case of acute dissection of ascending aorta diagnosed by two-dimensional echocardiography. Echocardiographic findings were subsequently confirmed by angiography. The patient was successfully operated and has been asymptomatic since the operation. The authors point out the importance the echocardiographic examination in case of any clinical suspicion. The authors have not found any previous report on the echocardiographic diagnosis of aortic dissection in the Hungarian literature.

[Iatrogenic sinus node disease and iatrogenic AV block]. / Az iatrogén színuszcsomó betegség és az iatrogén AV block.

The appearance of long lasting bradycardia due to damage of the sinus node (iatrogen sick sinus syndrome; or the atrioventricular conduction system, iatrogen AV block) is not a rare event after open heart surgery. In the course of 5093 heart operations the development of iatrogen sick sinus syndrome was observed in 234 patients (4.6%) and iatrogen AV block in 91 cases (1.8%). The incidence rate of iatrogen sick sinus syndrome or iatrogen AV block was quite divergent depending mostly on the type of operation. Comparing the data of our earlier (1977-1982) and later (1983-1991) cardiac surgical interventions, the prevalence of iatrogen sinus node disease and iatrogen AV block seems to decrease, mainly due to the progress in techniques of cardiac surgery. With the appearance of iatrogen sick sinus syndrome or AV block, urgent temporary pacing is indicated to prevent the deleterious hemodynamic effect of bradycardia. In the cases of persistent iatrogen sick sinus syndrome and iatrogen AV block, permanent pacemaker implantation is needed. It is remarkable that although the incidence rate of iatrogen sick sinus syndrome is greater than that of iatrogen AV block, in iatrogen sick sinus syndrome the regression is quite frequent, while in iatrogen AV block the 2nd or 3rd degree AV block is usually permanent. We performed pacemaker implantation in 56 cases of iatrogen sick sinus syndrome (24%) and in 57 patients of iatrogen AV block (63%). With pacemaker therapy the outcome of iatrogen sick sinus syndrome and iatrogen AV block is very favourable.

[Echocardiographic diagnosis of intermittent failure of a mitral valve prosthesis]. / Intermittáló mitralis mübillentyü "beragadás" echocardiographiás diagnózisa.

Three cases are reported who had intermittent diastolic jamming of a mitral tilting disc valve. The clinical presentation of this unfrequent but catastrophic early postoperative complication was different in all cases: the first patient presented with heart failure, the third patient had loss of consciousness with enuresis and the second patient was asymptomatic at the time of the diagnosis. Electromechanical dissociation was first suspected by clinical examination in 2 cases but it was confirmed in all 3 cases by 2 dimensional and Doppler echocardiography. Transesophageal echocardiography did not provide any additional information. Besides opening failure of the valve Doppler echocardiography also demonstrated incomplete or delayed opening in the asymptomatic period. Survival is dependent on correct diagnosis and urgent surgical treatment of this type of prosthetic valve dysfunction.

[Cardiovascular autonomic regulation following orthoptic heart transplantation]. / A cardiovascularis autonóm reguláció vizsgálata orthotopicus szívátültetést követóen.

Numerous recent observations have indicated autonomic reinnervation of transplanted human hearts. In order to assess autonomic regulation 5 patients were studied 1 to 5 years following cardiac transplantation. A series of tests were performed, including blood pressure and ECG recordings on rest, during 15/min patterned breathing, isometric handgrip exercise, and Valsalva manoeuvre. The time domain indices (SDRR, pNN50, rMSSD) and the frequency domain indices of heart rate variability were also studied. Among the five patients under study only one exhibited features compatible with both sympathetic and parasympathetic reinnervation. Traditional autonomic reflex tests and the analysis of time and frequency domain indices of HRV serve as simple tool in primary assessment of cardiac reinnervation.

[Importance of carotid artery studies prior to coronary surgery]. / Carotis vizsgálat jelentösége coronaria mütétek kapcsán.

The incidence of cerebral complications following extracorporal cardiac operations is reported to be approximately 2%. One of the possible reasons behind these complications is the presence of significant carotid stenosis as coexistent disease to the cardiac illness requiring surgery. Because of the common etiology carotid stenosis coexists mainly with a coronary artery disease. The authors make known their own screening methods based on the correct exploration of medical history and on the proper physical examinations. Coexistent significant carotid stenosis was revealed in 3.6% of 1056 patients who underwent coronary surgery within the period of 41 months. In all of these cases prophylactic carotid endarterectomy was performed. In twenty cases within this group the carotid reconstructions were performed simultaneously with myocardium revascularization. Staged endprocedures were performed in the other 18 cases. There was no surgical mortality and only one patient suffered major stroke. The authors emphasize the importance of carotid screening among patients awaiting coronary surgery especially in patients who previously sustained cerebral ischemic attacks, the presence of carotid bruits or any other known localization of obliterate arterial disease and finally in all patients over 60 years of age.

[Traumatic rupture of the descending aorta]. / Az aorta descendens traumás eredetü rupturája.

During a ten-year period 16 patients were seen with aortic rupture and false aneurysm secondary to blunt trauma. One patient underwent an acute operation, 4 patients had operative therapy elective delayed and 11 patients were operated on for chronic traumatic false aneurysm. Operative delay was done in case of simultaneous multisystem injury (e.g. shock caused by abdominal injuries, cerebral contusion or pulmonary contusion on the right side). The shunt bypass method of repair was used in the case of 3 patients, cardiopulmonary bypass in 6 cases and simple aortic cross-clamping in 6 patients. One operation was performed without aortic cross-clamping. Primary repair was achieved in three patient, in 3 more cases a patch was inserted and in 9 cases interposition Dacron grafting was accomplished. One "wrapping" operation was performed. In 2 cases, reoperation was necessary because of postoperative bleeding. One patient died in the perioperative period. Right sided hemiparesis occurred in one patient postoperatively. Rupture does not affect the whole aortic wall, especially in young people because of the natural elasticity of vessel. The appearing shock and hypotension might protect the mediastinal pleura against bursting. This could provide a chance to survive. Our experience indicate: Elective delay of operation in patients with multiple system injuries can be achieved with antihypertensive therapy.

[Biatrial pacing--new possibility in the non-pharmacologic treatment of drug-resistant paroxysmal atrial fibrillation]. / Biatrialis ingerlés--a gyógyszerrezisztens paroxizmális pitvarfibrilláció nonfarmakológiás kezelésének újabb lehetósége.

Biatrial pacing seems to be a possible non-pharmacological therapeutic choice in the prevention of drug-refractory, paroxysmal atrial fibrillation. Biatrial pacing using standard right atrial and coronary sinus left atrial pacing shows an antiarrhythmic effect, which mechanism is not well understood. Biatrial pacemaker was implanted in three patients suffering from drug refractory, symptomatic paroxysmal atrial fibrillation (lone and nonvalvular in 2 and in one case, respectively). Interatrial conduction disturbance (P > 120 ms) was found in three case. Bradycardia dependent arrhythmia development was not observed. Left atrial and right atrial premature beats dominated in 2 and in one case, respectively. P-wave duration was decreased by biatrial pacing in every patients. Atrial fibrillation has not been detected in two patients 1 day and 4 weeks after pacemaker implantation (follow up period: 9 and 5 months), however antiarrhythmic drugs has been withdrawn. In the number of left atrial premature beats a marked decrease was observed. Neither biatrial nor standard right atrial pacing nor combined medical and atrial pacing antiarrhythmic therapy were proven to be effective. In Hungary we were the first to implant and apply effectively biatrial pacemaker in the prevention of paroxysmal drug-refractory atrial fibrillation. However better identification the responding patients subgroup with atrial fibrillation is needed.

[Total proximal reconstruction of chronic aortic dissection in patients with Marfan syndrome]. / Marfan-kóros betegeknél észlelt krónikus aorta dissectio teljes proximalis korrekciója.

Authors present two patients suffering from Marfan syndrome. Asymptomatically developed serious cardiovascular complications being characteristic of the syndrome itself were revealed at both cases. Type "A" aortic dissection was found at the first, and type "B" aortic dissection involving even the arch as well revealed at the other patient. They were operated on an elective base. Total proximal aortic reconstructions (aortic root-ascending aorta-arch) were performed under deep hypothermia using total circulatory arrest (35 and 87 min). Both patients are doing well without complaints 3-4 months following the surgical interventions. Control angiographic imagination has found normal anatomic conditions at one of the patients. Anastomosis stenosis at the borderline of the arch and descending aorta was revealed at the other case which should be necessary to operate at an later occasion.

[Clinical importance of monophasic action potential registration in long QT syndrome]. / Monofázisos akciós potenciál regisztrálás klinikai jelentösége hosszú QT-szindrómában.

For more than 30 years, the monophasic action potential has been used as an experimental tool for the study of myocardial repolarisation. With recent improvements in catheter design, the utility of the tool as a means to identify the bases for ventricular arrhythmias in humans has been greatly improved. Abnormalities of repolarisation leading to ventricular arrhythmia formation can be identified and specific pharmacological therapies may be evaluated. The pathomechanism of major arrhythmias (ventricular tachycardia, ventricular fibrillation) occurring in long QT syndrome (LQTS) is not yet fully elucidated. The authors have recorded the monophasic action potentials (MAP) of the right ventricle in three patients with LQTS and with previous episodes of major ventricular arrhythmias. The changes in MAP duration and after depolarisation in response to spontaneous arrhythmias, programmed electrostimulation, atrial pacing and isoproterenol treatment were studied. In all of the three patients the early afterdepolarisation was present, which in two cases exhibited pause-dependent features. Thus in these patients dual chamber pacemaker implantatious were performed. These were the first permanent recordings of MAP during electrophysiological examination in Hungary and also the first evidences that the early afterdepolarisation does play a pathogenic role in the development of idiopathic LQTS. Further evaluation of the technique by cardiac electro-physiologists may improve both the diagnosis and the treatment of ventricular arrhythmias dependent upon afterdepolarisation formation.

[Experience with the surgical management of constrictive pericarditis]. / Tapasztalataink a constrictiv pericarditis sebészi kezelésében.

61 patients were operated on for constrictive pericarditis at the Cardiovascular Surgical Clinic of Semmelweis Medical University in the last 33 years. The average hospital mortality of the surgical pericardiectomy was 4.9%. The final conclusions of this retrospective and follow up study are as follows: pericardiectomy is the method of choice in the treatment of constrictive pericarditis, since it does not has any therapeutic alternative, its hospital mortality is low and it results excellent early and late postoperative functional effects.

[Experience with a transvenous pacemaker-cardioconverter-defibrillator without subcutaneous patch]. / Transzvénás, subcutan patch nélküli pacemaker-cardioverter-defibrillátorokkal szerzett tapasztalataink.

Sudden cardiac death caused by malignant ventricular arrhythmias is one of the main causes of cardiovascular mortality. Implantation of cardioverter-defibrillators has resulted in the reduction of the incidence of sudden cardiac death caused by malignant ventricular arrhythmias from the yearly 10-30% to 1%. For the very first time in Hungary, the authors applied only transvenous lead configuration for automatic cardioverter defibrillators in three patients. The indications of the implantation were ventricular fibrillation in one case, ventricular tachycardias refractory to drug treatment in two cases. Ventricular arrhythmias were secondary to coronary heart disease in two patients, dilatative cardiomyopathy in one patient. Preoperative, intraoperative and postoperative electrophysiological studies were regularly taken. Using Biotronik Phylax 03 device with a right ventricular electrode and a superior vena cava electrode and without subcutaneous patch the intraoperative defibrillation thresholds were 6, 11 and 12 J respectively. The fractally iridium coating increases the surface of the electrodes that has a very good effect on defibrillation threshold. During a mean follow-up of six months the occurring spontaneous ventricular arrhythmias (1 ventricular fibrillation and 5 ventricular tachycardias) were terminated by Phylax 03 with cardioversion-defibrillation or overdrive stimulation. The authors' results of intraoperative testing and clinical experiences show that the Phylax 03 biphasic system due to low defibrillation thresholds without subcutaneous patch can safely be applied with only transvenous implant technique in patients with major ventricular arrhythmias to prevent sudden cardiac death and to terminate ventricular tachycardia.

[Experience with surgical treatment of prosthetic valve endocarditis]. / Múbillentyú-endocarditis sebészi kezelésével szerzett tapasztalataink.

Prosthetic valve endocarditis (PVE) is a rare but dangerous complication that may occur after the implantation. The authors retrospectively summarize their 11-year experience in treating PVE. 2357 prosthetic valve (PV) implantations were performed over 11 years at the Department of Cardiovascular Surgery, Semmelweis University, Budapest, PVE was found to be the indication for operation in 1.8% of the cases (43/2357). 43 surgical interventions were carried out on 38 patients (mean age: 52.5 yrs, male/female ratio: 25/13). Blood cultures were positive in 86% and negative in 14% of the cases. The infected PV-s were replaced emergently (14%), urgently (79%) or electively (7%). The explanted valves were aortic in 55% and mitral 45% of the cases, 63% were mechanical and 37% biological. PVE followed the primary PV implantation in less than a year in 39.5%. Infected environment during the primary PV implantation was found to be a predisposing factor for the late endocarditis episodes. The mean age of the infected and explanted aortic bioprosthetic valves was significantly higher than that of explanted mechanical valves (p < 0.05). No such difference could be found at the mitral valves. The explanted valves were replaced by mechanical (75.5%) or biological (22.5%) devices. Homograft was implanted once. Early postoperative mortality of the primary PV replacements was 10.5%) devices. Homograft was implanted once. Early postoperative mortality of the primary PV replacements was 10.5%. Endocarditis reoccurred in 20% of the cases. Means follow-up duration was 45.5 months. Two-, five- an 10-year survival were 75%, 64% and 51% respectively. In conclusion in the surgical treatment of PVE, bioprosthetic and mechanical valves are suitable alternatives as opposed to homografts and freestyle stentless valves.

[Atrial fibrillation after open-heart surgery--incidence, prevention and treatment]. / Posztoperatív pitvarfibrillàció okai, gyakorisága, megelözése és kezelése szívsebészeti betegeknél.

Atrial fibrillation is a common problem in the postoperative period following open-heart surgery. The pathogenesis of postoperative atrial fibrillation is likely to be multifactorial, however increased sympathetic activation may play a significant role. The aim of the study was to detect the incidence and possible reasons of atrial fibrillation in the first three postoperative days after open-heart surgery. Atrial fibrillation was detected in a total of 48 patients (mean age 64.8 +/- 8.8 years) of the 302 consecutive patients included in the study. The incidence of atrial fibrillation was 15.9%. In the history of patients with atrial fibrillation paroxysmal or persistent atrial fibrillation occurred in 18 cases. Acute ischaemia, hypopotassemia, high dose catecholamines contributed to the development of arrhythmias in 6, 4 and 4 cases, respectively. Lack of perioperative beta-blocker treatment was seen in 35 cases. Postoperative bleeding and reoperation occurred prior to the onset of atrial fibrillation in 9 instances. The applied antiarrhythmic therapy was metoprolol, amiodarone, propafenon and electrical cardioversion in 33, 21, 4 and 2 cases, respectively. Incidence of atrial fibrillation was found significantly lower in patients receiving beta-blocker premedication (13/181 [7.18%] versus 35/121 [28.9%]). There was no correlation between the incidence of atrial fibrillation and the length of the surgery, aortic-cross clamp time and the number of bypass grafts. Absence of preoperative beta-blocker treatment, previous atrial fibrillation and combined surgery were found to be strong predictors of atrial fibrillation. There was weaker association with increased age. On the basis of the outcome of our study beta-blocker premedication is suggested in most patients undergoing open-heart surgery.

[Coronary surgery at the Cardiovascular Surgical Clinic (1976-1990)]. / Coronariasebészet az Er- és Szívsebészeti Klinikán (1976-1990).

In the Cardiovascular Surgical Clinic of the Semmelweis Medical University of Budapest the first coronary artery bypass grafting (CABG) procedure was performed in 1975. Since that time coronary artery surgery has become a routine everyday practice representing more than half of the total workload of adult cardiac surgery. The analysis of 1347 operations performed between 1976-1990 on patients with coronary heart disease showed the followings: the first few years--so called learning curve of CABG operations is characterised by high mortality. With passing time the number of cases performed each year increased rapidly and the surgical technique has improved too. At the same time the operative mortality figures showed decreasing tendency--it was 2.1% for the last 609 cases. All observed parameters showed some progress: in 1990 the average number of grafts per patient was 3.09, internal mammary artery usage 15 percent and the mean aortic cross clamp time per anastomosis 24.5 minutes. Complete myocardial revascularisation is the key point of coronary artery surgery. In order to achieve this target in all operated cases further technical improvement is necessary.