Cerebrospinal fluid biomarkers of neurodegeneration in patients with juvenile and classic myotonic dystrophy type 1.

BACKGROUND AND PURPOSE: The aim of the present study was to analyze cerebrospinal fluid (CSF) levels of total tau (T-tau), phosphorylated tau (P-tau) and the 42-amino-acid form of ß-amyloid (Aß42 ) in patients with myotonic dystrophy type 1 (DM1), and their possible correlations with cognitive and behavioral manifestations in these patients. METHODS: Lumbar puncture was performed in 74 patients with DM1 [27 with the childhood/juvenile form (jDM1) and 47 with the adult form (aDM1) of the disease] and 26 control subjects who were subjected to orthopedic surgery. Sandwich ELISA was used for measuring the levels of T-tau, P-tau and Aß42. RESULTS: The CSF level of Aß42 was at its lowest in patients with jDM1 and at its highest in controls (P < 0.05). A tendency of T-tau and P-tau to increase was greater in aDM1 patients than in jDM1 patients and controls (P > 0.05). In both jDM1 and aDM1 patients, significant correlations were found between Aß42 and T-tau (rho = 0.81 and rho = 0.67, respectively, P < 0.01), as well as between Aß42 and P-tau (rho = 0.87 and rho = 0.67, respectively, P < 0.01). The Aß42/P-tau ratio decreased with age in aDM1 patients (rho = -0.30, P < 0.05). Only the level of Aß42 in the CSF of jDM1 patients was correlated with the size of the CTG expansion (rho = -0.53, P < 0.05). Only a few correlations were observed between levels of biomarkers and neuropsychological testing. CONCLUSION: The CSF level of Aß42 was decreased in patients with jDM1, whilst the Aß42/P-tau ratio was decreased in aDM1 patients. Positive correlations between Aß42 , T-tau and P-tau were observed in both forms of disease. Further studies with larger cohorts of DM1 patients are necessary.

Clopidogrel cessation triggers aspirin rebound in patients with coronary stent.

WHAT IS KNOWN AND OBJECTIVE: Premature discontinuation of clopidogrel in patients undergoing percutaneous coronary intervention is a significant risk factor for thrombotic adverse outcomes. However, recent studies indicate that even discontinuation of long-term use of clopidogrel may be associated with multiple adverse outcomes, that is, rebound phenomenon whose mechanism is not definitely clear. The aim of the study was to examine the effect of clopidogrel withdrawal in those on combined aspirin and clopidogrel therapy. METHODS: This prospective, multicenter study enrolled 200 patients who underwent coronary stent implantation and were on dual antiplatelet therapy (100 mg aspirin + 75 mg clopidogrel) 1 year after the stent placement. In all patients, we measured the platelet aggregation, by multiplate electrode aggregometry, using two agonists [adenosine diphosphate with PGE1 (ADPHS) and arachidonic acid (ASPI)] two times: on the day of cessation of clopidogrel and 90 days after clopidogrel was stopped. RESULTS AND DISCUSSION: Following clopidogrel discontinuation, we registered an increase in ASPI values (P < 0·001), linear correlation between changes in ASPI and ADPHS values (P = 0·009) and significant difference in the values of ASPI first quartile of ADPHS compared with the other three (P < 0·001, P = 0·016, P < 0·001, I vs. II, I vs. III and I vs. IV quartile of ADPHS, respectively). WHAT IS NEW AND CONCLUSION: Our findings show that cessation of clopidogrel causes loss of antiplatelet synergism with aspirin, leading to a weakening of the response to aspirin, which may be one explanation for the rebound after the clopidogrel cessation.

[Current opinion in epidural analgesia influence on incidence of complications after major abdominal surgery].

Review article summarizes current knowledge of general and epidural anaesthesia combination for major abdominal surgery and incidence of postoperative complications. Continuous epidural local anaesthetics especially through thoracic placed epidural catheter decrease opioids use and as part of "acute rehabilitation" plays important role in postoperative recovery. Most of the studies showed tion is not dependent on kind of anaesthesia and analgesia. Successfully treated postoperative pain prevents chronic postoperative pain, which is best achieved in abdominal surgery with thoracic epidural use.

[Total intravenous anesthesia using remifentanil and propofol with midazolam co-induction in laparoscopic surgery of the gallbladder]. / TIVA remifentanilom i propofolom uz koindukciju midazolamom za laparoskopske operacije zucne kese.

We investigated effects of total intravenous anesthesia (TIVA) with propofol and remifentanil (in two parallel continuous infusions), on 28 ASA I-II patients undergoing laparoscopic cholecystectomy. All patients received midazolame (0.05 mg/kg b.w.), and 90 sec thereafter, remifentanil (0.5 g/kg b.w.). Computer controlled intravenous infusion of propofol started at dose of 6 mg/kg/h (by Graseby 3400 Syringe Pump). Muscle relaxation was achieved by rocuronium (0.6 mg/kg b.w.). After endotracheal intubation, rate of propofol was decreased on 3 mg/kg/h and started with another infusion of remifentanil (0.5 ug/kg/min). Before (T0) and after induction (T1), after start of surgery (T2), and at the end of surgery (T3), we evaluated: systolic, diastolic, and medial arterial blood pressure (SAP, DAP, MAP), heart rate (HR), peripheral saturation of O2 (O2Sat), and capnometry (ETCO2), by Datex-Engstrome AS/3 Monitore. It was followed side effects of anaesthesia, early and complete recovery rate, and frequency of nausea and vomiting in postoperative period. Results showed haemodynamic stability of patients after induction in anaesthesia (defined as decreasing of MAP 20%, compared with preinduction values). During investigation (T0-T3), results of 0.2Sat and ETCO2 were excellent (0.60 +/- 2 and 5.1 +/- 2.4 min). There wasonly one case of postoperative nausea and vomiting, and no significant side effects of anaesthesia. TIVA remifentanil-propofol and co-induction with midazolame makes possible haemodynamic stability of patients after induction in anaesthesia, good oxygenation during surgery, fast early and complete recovery, and avoiding of side effects of anaesthesia and postoperative nausea and vomiting. We concluded that it is a good choice of anaesthesia for laparoscopic cholecystectomy.

Dipyridamole-atropine-induced myocardial infarction in a patient with patent epicardial coronary arteries.

BACKGROUND: The diagnostic accuracy of the physical and pharmacological stress echocardiography tests is higher than routine exercise electrocardiography. They have an acceptable safety profile and have been rarely associated with severe adverse effects. CASE REPORT: We present a case of acute anterior myocardial reinfarction immediately after exercise and pharmacological (dipyridamole-atropine) stress echocardiography testing 1 month after successful stent implantation in LAD. Our patient was a 43-year-old man with a history of heavy smoking and hypertension. Remarkably, the stress echocardiogram was non-diagnostic few hours before the infarction occurred. Angiography performed 4 months after the reinfarction revealed neither a culprit lesion nor stent thrombosis. CONCLUSION: Aggressive "last generation" pharmacological stress testing may provide optimal diagnostic accuracy, but as in our case, complications may occur, even after negative stress testing. To our knowledge, this is the first reported case of an acute myocardial infarction as a severe complication of stress testing, which developed in a patient after stent implantation.

[The yentl syndrome in women with arterial hypertension and positive findings on the echocardiography dipyridamole stress test]. / Sindrom jentl kod zena s arterijskom hipertenzijom i positivnim nalazom ehokardiografskog testa stres-dipiridamol.

UNLABELLED: The aim of this study was to assess the possible gender differences between positive (new wall motion abnormality) combined dipyridamole stress echocardiography and coronary angiography or myocardial revascularization procedures. We evaluated 127 consecutive patients (82 males, 53.5 years old and 45 females, 56.1 years old) with systemic hypertension and chest pain (angina or atypical chest pain) who underwent pharmacological stress echocardiography (dipyridamole-atropine or dipyridamole-dobutamine) for detection of myocardial ischaemia. Coronary angiography was carried out in 84 patients (58 males and 26 females). Diagnostic accuracy of the test was the same in women as in men (92.3 vs 89.1%, females vs males, respectively). Coronary angiography was done in 73.6% of male and 66.7% of female patients with positive test; the difference was not significant. Over a two-year follow-up there were 31 myocardial revascularization procedures (20 coronary surgery and 11 angioplasty), 25 in men and 6 in women (p = 0.028). There was a trend in women with positive test to have less surgery or angioplasty (28.6%) than in men (45.3%), but the difference was not significant. Cox multivariate regression analysis revealed that women were less likely to receive revascularization (relative risk for females RR = 0.1457, 95% CI 0.0416-0.5101). CONCLUSION: Although diagnostic accuracy of third generation dipyridamole stress echocardiography was not different between men and women, in patients with positive test there was a trend in women to undergo coronary angiography and coronary surgery or angioplasty in lesser degree than in men. Cox multivariate model showed low relative risk of females for revascularization procedures and possible Yentl's syndrome in studied population.

Arrhythmias in acute pericarditis. An endomyocardial biopsy study.

It is still controversial whether the arrhythmias in acute pericarditis are of myocardial or pericardial origin. The aim of the present study was to investigate the occurrence of arrhythmias and conduction disorders in patients with acute pericarditis with no endomyocardial biopsy evidence of myocarditis (group 1: 40 patients, 65% males, mean age 45.6 +/- 15.7 years, mean heart rate [HR] 98.7 +/- 22.2 beats per minute) in comparison to endomyocardial biopsy proven acute myocarditis/perimyocarditis (group 2: 10 patients, 3/10 with perimyocarditis, 70% males, mean age 46.1 +/- 15.8 years, mean heart rate 76.7 +/- 33.1 beats per minute). At the initial assessment all patients underwent comprehensive clinical work-up including echocardiography, cardiac catheterization, and endomyocardial biopsy. In all patients biventricular endomyocardial biopsy was performed using standard femoral approach and Schikumed 7 F or 8 F bioptomes. Tissue samples were stained by H & E, v. Gieson and independently reviewed by two cardiac pathologists. In addition immunohistochemistry and immunocytochemistry were performed, and only patients fulfilling Dallas and World Heart Federation criteria were selected for group 2. Comparative analysis of electrocardiograms and 24-hour Holter recordings at initial presentation revealed in group 1 vs group 2 significantly less frequent paroxysmal supraventricular tachyarrhythmias (5% vs 40%), and ventricular fibrillation (0 vs 20%), in contrast to atrial fibrillation that occurred more often (20% vs 0) (all p < 0.05). Furthermore, in the group 2 one patient died due to VF and two patients underwent ICD implantation. Low voltage (40% vs 30%) and ST/T wave changes (47.5% vs 30%), as well as the incidence of the II degree AV block (5% vs 0) and complete AV block (2.5% vs 10%) were not significantly different between the groups. In conclusion, patients with pericarditis and no endomyocardial biopsy indications of myocarditis had significantly less often life threatening rhythm disorders in contrast to patients with endomyocardial biopsy proven acute myocarditis/perimyocarditis. On the contrary, incidence of transitory atrial fibrillation was higher in acute pericarditis, than in myocarditis.

Flexible percutaneous pericardioscopy: inherent drawbacks and recent advances.

Pericardioscopy enables endoscopic inspection and aimed biopsy of the parietal and visceral pericardium. To elucidate possible technical modifications contributing to the feasibility, diagnostic value and safety of the procedure, pericardioscopy with an Olympus HYF-1T flexible endoscope was performed in 32 patients (53.1% males, mean age 46.2 +/- 13.1 years) with pericardial effusions. In all patients, the initial step of the procedure was subxiphoid fluoroscopically controlled pericardiocentesis and drainage of the pericardial effusion. An Olympus FB-41ST biopsy forceps was applied for endoscopically guided pericardial biopsies. Standard sampling was used in 22/32 patients (3 to 6 samples/patient) and extensive sampling in 10/32 patients (18 to 20 samples/patient). In additional 12 patients pericardial biopsy was performed without pericardioscopy, under fluoroscopic control. Endoscopic visualization was clearly superior when pericardial effusion was partially replaced with 100 to 300 ml of air (29/32 procedures) in comparison to 3/32 procedures in which the pericardial effusion was replaced with warm normal saline (37 degrees C). In patients with hemorrhagic effusion (12/32), we either repeatedly injected and removed 100 to 150 ml volumes of normal saline (37 degrees C), or postponed pericardioscopy for 2 to 3 days of active drainage. The specificity of endoscopic findings is low and not decisive for the diagnosis. However, pericardioscopy is significantly contributing to the diagnostic value of pericardial biopsy, especially regarding establishing the new diagnosis and etiology of the pericardial disease. Sampling efficiency was also significantly higher for procedures using aimed pericardial biopsy with standard and extensive sampling compared to procedures performed under fluoroscopy: 86.2%, 87.3%, and 43.7%, respectively. No major complications directly related to the procedure were encountered. Minor complications included: short-run ventricular tachycardia (6.3%), pain at the sheath entry site (75%) and transient fever (37.5%). In conclusion, pericardioscopy with Olympus HYF-1T, after air instillation, is a technically complex, but safe procedure that enables excellent visualization and extensive pericardial sampling with improved diagnostic value of pericardial biopsies.

Initial clinical experience with PerDUCER device: promising new tool in the diagnosis and treatment of pericardial disease.

BACKGROUND: The idea to enter the normal pericardial sac safely was unrealistic until recently. The development of a novel instrument (PerDUCER pericardial access device) for percutaneous access to the pericardium could potentially have a significant impact, not only on patients with pericardial diseases but even more, or primarily, on diagnosis and treatment of myocardial and coronary disease and arrhythmias. HYPOTHESIS: The overall objective of the present study was to evaluate the feasibility and safety of the percutaneous pericardial access with PerDUCER in patients with pericardial disease, and to analyze our initial experience with this new technique, with particular emphasis on sequential procedural steps. METHODS: The device was studied in five patients with pericardial disease (two men, mean age 50.4 years, range 30-68, four with normal body mass index). The procedure consists of two distinct techniques: (1) access to the mediastinal space, and (2) pericardial capture, puncture, and insertion of the guidewire. Access to the mediastinal space includes the introduction of a blunt cannula, a 0.038 guidewire, a dilator-introducer sheath set, and insertion of the PerDUCER device. Key points of the PerDUCER procedure are as follows: introduction of the blunt cannula without resistance, placement of the dilator-introducer sheath at the upper third of the heart, systolic movements of the PerDUCER device, successful vacuum and capture of pericardium, puncture and introduction of the intrapericardial guidewire. RESULTS: Access to the mediastinal space was accomplished in four of five patients, as were pericardial capture and probably puncture. However, despite numerous successful captures and probably punctures of pericardium, we were not able to confirm introduction of the intrapericardial guidewire into the pericardial cavity in any of our patients (0/5). The procedure was very well tolerated in all patients (5/5). No major complications developed during the procedure, bearing in mind that the intrapericardial placement of the guidewire was not achieved. Minor complications included pain at the dilator-introducer sheath entry site (5/5) and mild transient fever (2/5). CONCLUSIONS: According to the present experience, we believe that, with minor modifications, the PerDUCER device could be successfully implemented for pericardial entry in patients with pericardial disease. Further studies are needed to evaluate the feasibility and safety of this new instrument in patients with a normal pericardium. This could open a most exciting spectrum of possible implementations of the device in the future.

Coronary vasodilation without myocardial erection. Simultaneous haemodynamic, echocardiographic and arteriographic findings during adenosine and dipyridamole infusion.

AIM: The aim of this study was to evaluate simultaneously echocardiographic, haemodynamic and angiographic changes that occur during adenosine and dipyridamole infusion, in patients with one-vessel coronary artery stenosis. This would assess whether deterioration in left ventricular haemodynamics during vasodilator agent infusion is influenced by vasodilation per se, or the development of myocardial ischaemia. METHODS AND RESULTS: We performed adenosine (140 micrograms.kg-1.min-1 over 4 min) and dipyridamole (up to 0.84 mg.kg-1 over 10 min) stress echocardiography tests, together with angiographic and haemodynamic assessment, in 26 patients undergoing elective coronary angioplasty. In 12 of 26 patients, adenosine and dipyridamole tests were repeated 24 h after angioplasty. The criterion for echocardiography test positivity was the appearance of a new transient regional wall motion abnormality. Coronary angiograms were analysed with quantitative coronary arteriography. Adenosine and dipyridamole induced regional dysfunction in 18/26 (69%) and 14/26 (54%) patients before angioplasty, respectively (P = ns). In the echocardiography-positive patients, the percent diameter stenosis was significantly (P < 0.05) tighter stenosis than in the echocardiography-negative patients (adenosine, 66.6 +/- 8.3% vs 58.0 +/- 8.9%; dipyridamole, 69.2 +/- 7.1% vs 57.7 +/- 7.6%). During both tests, left ventricular end-diastolic pressure significantly increased (P < 0.05) in echocardiography-positive patients (adenosine, 9.8 +/- 2.7 mmHg to 13.5 +/- 4.1 mmHg; dipyridamole, 10.1 +/- 2.8 mmHg to 14.1 +/- 4.3 mmHg), but not in echocardiography-negative patients. In the patients who had undergone successful angioplasty (reduction to < 50% diameter stenosis), both adenosine and dipyridamole confirmed the arteriographic success of the procedure (echocardiography negative in all patients). In this group of patients, no significant change was observed in left ventricular end-diastolic pressure during adenosine or dipyridamole infusion. CONCLUSIONS: Intravenous infusion of either adenosine or dipyridamole was accompanied by an obvious increase in left ventricular end-diastolic pressure only in patients with induced wall motion abnormalities. Coronary vasodilation per se has no significant effect on left ventricular end-diastolic pressure when no ischaemia is induced, disproving any clinically significant 'erectile' and adverse effects of coronary vasodilation per se.

High dose adenosine stress echocardiography for noninvasive detection of coronary artery disease.

OBJECTIVES: The aim of this study was to assess the tolerability and incremental diagnostic value of high adenosine doses in stress echocardiography testing in patients with coronary artery disease (CAD). BACKGROUND: In comparison with other pharmacologic stress echocardiography tests, standard dose adenosine stress has sub-optimal sensitivity for detecting milder forms of CAD. METHODS: Adenosine stress echocardiography was performed in 58 patients using a starting dose of 100 micrograms/kg body weight per min over 3 min followed by 140 micrograms/kg per min over 4 min (standard dose). If no new wall motion abnormality appeared, the dose was increased to 200 micrograms/kg per min over 4 min (high dose). All patients underwent coronary angiography. Significant CAD was defined as > or = 50% diameter stenosis in at least one major coronary artery. Thirty-three patients had one-vessel and seven had multivessel CAD. Coronary angiographic findings were normal in 18 patients. RESULTS: The high adenosine dose caused a slight but significant increase over baseline values in rate-pressure product. Limiting side effects occurred in two patients during the standard dose protocol and in one patient receiving the high dose regimen. The test was stopped in 30 patients after the standard adenosine dose regimen because of a provoked new wall motion abnormality. The sensitivity of adenosine echocardiography with the standard dose was 75% (95% confidence interval [CI] 63% to 87%). After completion of the standard dose protocol, 28 patients continued testing with the high dose adenosine protocol. The overall sensitivity of adenosine echocardiography, calculated as cumulative, increased to 92% (95% CI 84% to 100%) with the high dose (p < 0.05). The specificity of adenosine testing was 100% and 88%, respectively, with the standard and high dose regimen (p = 0.617). CONCLUSIONS: We believe that use of a higher than usual adenosine dose protocol for stress testing may improve the diagnostic value of adenosine echocardiography, mainly by increasing sensitivity in patients with single-vessel disease without deterioration of the safety profile and with only a mild reduction in specificity.

Infra-low dose dipyridamole test. A novel dose regimen for selective assessment of myocardial viability by vasodilator stress echocardiography.

Low (0.56 mg.kg-1 over 4 min) and high (0.84 mg.kg-1 over 10 min) doses of dipyridamole can identify viable myocardium through the contractile recovery of basally dyssynergic regions; however, it also induces ischaemia in susceptible patients. The aim of this study was to assess the potential of an "infra-low' dose of dipyridamole to selectively identify myocardial viability, independently evaluated by low dose dobutamine. Forty patients with resting dyssynergy and angiographically assessed coronary artery disease (1-vessel in 18, 2-vessel in 12, and 3-vessel in 10 patients) separately underwent a low dose dobutamine (5-10 micrograms.kg-1.min-1 for 3 min) echo test and an infralow dose (0.28 mg.kg-1 over 4 min) dipyridamole echo test. Systolic blood pressure (rest: 131 +/- 19 mmHg) changed slightly after dobutamine (137 +/- 21, P < 0.05 vs rest) and remained stable after dipyridamole (130 +/- 17, P = ns vs rest). Heart rate (rest: 68 +/- 13 beats.min-1) was also unchanged after dipyridamole (69 +/- 12, P = ns vs rest) and increased slightly after dobutamine (71 +/- 15, P < 0.05 vs rest and vs dipyridamole). No patient developed echocardiographic or electrocardiographic signs of ischaemia after either dipyridamole or dobutamine. Of the 243 segments with baseline dyssynergy, 70 were responders (i.e. they showed an improvement of 1 grade or more, from 1 = normal/hyperkinetic to 4 = dyskinetic in a 16-segment model of the left ventricle) by both dipyridamole and dobutamine, 157 were non-responders (i.e. they showed no change) by both dipyridamole and dobutamine, and 16 showed discordant results (five responders by dipyridamole only; 11 by dobutamine only). The overall concordance of dipyridamole and dobutamine was 93%. An echocardiographic follow-up could be obtained > 6 weeks after successful revascularization (achieved with angioplasty in 17, with by pass surgery in 3) in 19 patients and showed an improvement of one grade or more in 50 segments (viable) and no improvement in 50 segments (necrotic). The sensitivity of dobutamine and dipyridamole for predicting recovery was 76 and 78% respectively (P = ns); the specificity of both tests was 94%. In conclusion, infra-low dose dipyridamole is a haemodynamically neutral stress test which does not affect either heart rate or systolic blood pressure; it allows myocardial viability to be explored selectively, without eliciting ischaemia; it shows excellent overall concordance with low dose dobutamine and has good sensitivity and excellent specificity for predicting functional recovery following successful revascularization.

Unruptured congenital aneurysm of the right sinus of Valsalva. Dissecting into the interventricular septum.

We report the case of a congenital aneurysm of the right sinus of Valsalva dissecting into the interventricular septum in a 21-year-old man. This condition was diagnosed by echocardiography and magnetic resonance imaging. In particular, transthoracic and transesophageal color-coded Doppler echocardiography showed that there was no communication between the aneurysm and the surrounding heart chambers. The findings were confirmed by angiography. Heart enlargement and other symptoms and signs of heart failure indicated surgical repair of the lesion. Early postoperative dehiscence of the sutured orifice was accurately diagnosed with Doppler echocardiography and angiography. Reintervention was successful in filling and sealing the septal cavity. This case confirms the reported difficulties in the surgical correction of aneurysms of sinus of Valsalva lying within the interventricular septum.

Myocardial catecholamines in primary heart muscle disease: fact or fancy?

The pathophysiological role of myocardial catecholamines in cardiomyopathies is still not completely understood. We there-fore assessed myocardial catecholamine concentrations (MCC) in 34 patients with hypertrophic cardiomyopathy (HCM) (76.5% males; mean age 46.7 +/- 11.6 years; left ventricular ejection fraction [LVEF] 75.3 +/- 9.8%) and in 32 patients with dilated cardiomyopathy (DCM) (87.5% males, mean age 43.1 +/- 12.5 years, LVEF 34.9 +/- 8.3%). Initial assessment included clinical work up, cardiac catheterization and endomyocardial biopsy. Myocardial norepinephrine (MNEC), epinephrine (MEC), and dopamine (MDC) concentrations in endomyocardial biopsy samples were measured using the catechol-O- methyl transferase radioenzymatic method. Significantly higher MNEC and MEC were demonstrated in HCM than in DCM patients (MNEC: 781.9 +/- 125.8 ng.g-1 fresh myocardial tissue (ft) HCM vs 262.6 +/- 68.9 ng.g-1 ft DCM, p < 0.01; and MEC: 91.6 +/- 13.9 ng.g-1 ft HCM vs 35.8 +/- 6.2 ng.g-1 ft DCM, P < 0.01). The difference in MDC did not reach statistical significance (76.1 +/- 8.3 ng.g-1 ft HCM vs 70.1 +/- 11.8 ng.g ft DCM; P > 0.05). In addition, we compared the MCC levels in 24 patients, clinically presented as dilated cardiomyopathy categorized according to the various aetiologies: 12/24 with primary DCM (75.0% males, mean age 49.6 +/- 9.5 years; LVEF 25.8 +/- 63%), 7/24 with alcohol-induced heart disease (85.7% males, mean age 46.8 +/- 7.1 years; LVEF 26.4 +/- 4.6%), and 5/24 with hypertensive heart disease (100% males, 45.1 +/- 10.6 years; LVEF 25.6 +/- 9.1%), but no significant difference was found among them (P > 0.05). There was no significant difference in tissue dopamine concentrations.

Coffee consumption, alcohol use, and cigarette smoking as determinants of serum total and HDL cholesterol in two Serbian cohorts of the Seven Countries Study.

The associations between serum total and HDL cholesterol and three lifestyle factors--consumption of Turkish coffee, consumption of alcohol, and cigarette smoking--were examined in two Serbian cohorts of the Seven Countries Study. In 1988 and 1989, 319 men from Zrenjanin and Belgrade, 65 to 84 years old and free of myocardial infraction, participated. The men from Zrenjanin were originally working in a large cooperative, and the men from Belgrade were faculty members of the university. HDL cholesterol, alcohol consumption, and cigarette smoking were significantly higher in Zrenjanin than in Belgrade. Serum total cholesterol levels and coffee consumption were not different. ANCOVA showed that serum total cholesterol levels were 8.2% higher (P < .05) in men consuming two small cups of coffee per day compared with abstainers, and this was also seen after adjustment for cigarette smoking, age, body mass index, cohort, and alcohol consumption. In men consuming one or more alcoholic drinks per day (more than 10 g/d alcohol), HDL cholesterol levels were increased by 0.19 mmol/L (15.4%) compared with men consuming no alcohol (P < .001). This association was stronger in the Zrenjanin cohort than in the Belgrade cohort (P < .05). Smoking was not associated with total cholesterol or with HDL cholesterol levels. In Serbian men, boiled Turkish coffee and alcohol consumption are independently associated with serum total and HDL cholesterol levels, respectively.

Changes in major risk factors for cardiovascular diseases over 25 years in the Serbian cohorts of the Seven Countries Study.

The Serbian cohorts of the Seven Countries Study were examined four times during a 25-year period. Large changes were observed in average serum cholesterol, blood pressure and the prevalence of smoking in these ageing cohorts. Comparison of men of the same age strata e.g. men aged 50-59 examined at baseline and after 10 years of follow-up and of men aged 65-69 examined after 10 and 25 years of follow-up showed that serum cholesterol increased by about 45% in Zrenjanin, 35% in Velika Krsna and 15% in Belgrade over the last 25 years. Systolic blood pressure increased by 9% in Zrenjanin and 7% in Velika Krsna. No significant increase in systolic blood pressure was observed in Belgrade. There was no major secular trend in smoking and the changes observed during 25 years were mainly due to ageing. No major change was observed in body mass index. The increases in serum cholesterol and blood pressure observed in the Serbian cohorts during the last 25 years are compatible with the increase in cardiovascular disease mortality observed in Yugoslavian men aged 30-69 during the period 1970-1984.

Endomyocardial biopsy: a meta-analysis of diagnostic value.

To clarify the controversy of endomyocardial biopsy (EMB) in terms of its diagnostic value, we performed a meta-analysis of EMB studies published between 1982 and 1993, including our own experience. A total of 255 articles was retrieved using both a computer search of the Medline database and a manual bibliographic search, but only 30 studies with 4,313 patients met the predefined inclusion/exclusion criteria. The diagnostic value of EMB was classified into four categories, according to the effect of EMB findings on the discharge diagnosis: aetiology uncovered, new diagnosis of heart muscle disease (HMD) revealed, clinical diagnosis confirmed, and no useful information obtained. Clarification of aetiology of HMD was reported in 28 out of 30 studies with a total of 4,195 patients and it was achieved by EMB in 17.9% of these patients (95% confidence interval (CI) was 16.8-19.1%). A new unexpected diagnosis of HMD was arrived at in 25 of 30 studies (3,947 patients) and this occurred in 19.3% of patients (95% CI = 18.1-20.6%). Confirmed clinical diagnosis of HMD by EMB was covered by 12 studies (1,231 patients) and was proven in 40.1% of patients (95% CI = 37.3-42.7%). EMB not providing any useful clinical information was mentioned in seven of 30 studies (857 patients); this happened in 5.9% of patients (95% CI = 4.5-7.4%). Therefore, these results confirmed the remarkable diagnostic value of EMB. It was equally helpful in all diagnostic categories and had considerable overall diagnostic utility.

Coronary heart disease deaths in 25 years. The experience in the three Serbian cohorts of the Seven Countries Study.

Three cohorts of men aged 40-59 at entry examination were enrolled between 1962 and 1964 in the Serbian section of the Seven Countries Study of Cardiovascular Diseases. They were a sample in the rural village of Velika Krsna (n = 511), the workers in an agro-industrial cooperative in the city of Zrenjanin (n = 516), and the University professors of Belgrade (n = 536). At entry examination and then after 5 and 10 years, some cardiovascular risk factors were measured while the follow-up for mortality and causes of death was continued for 25 years. The 25 year standardized death rates from coronary heart disease (CHD) were higher in Zrenjanin (177 per 1000) and lower in Belgrade (118) and Velika Krsna (122). The multivariate prediction of CHD mortality by the Cox model in the lumped samples showed significant coefficients for age, body mass index, systolic blood pressure and cigarette consumption. The coefficient of serum cholesterol did not reach a statistically significant level. An unknown but significantly protective factor was identified for the Belgrade sample, likely bound to the higher social class of this group. Changes of systolic blood pressure in the first 10 years of follow-up were positively and highly related to the deaths occurred in the subsequent 15 years. The three population groups showed, between year 0 and year 10 follow-up, large increases in mean levels of blood pressure and mainly of serum cholesterol (+30 mg/dl in Velika Krsna; +36 mg/dl in Belgrade and +61 mg/dl in Zrenjanin). The sample in Zrenjanin started from intermediate levels (168.7 mg/dl) but attained the greatest increase and reached the highest CHD death rate in 25 years.

Mitral valve replacement and septal myomectomy in hypertrophic cardiomyopathy. Ten-year follow-up in 80 patients.

Between 1970 and 1980, 80 patients with hypertrophic cardiomyopathy were treated with mitral valve replacement (MVR) at our institution; 54 of these (Group 1) underwent MVR alone, and the remaining 26 (Group 2) underwent MVR plus septal myomectomy. The 1-month mortality was 7.4% for Group 1 and 7.6% for Group 2. After 10 years of follow-up, the annual mortality was 1.5% for Group 1 and 1.6% for Group 2 (this difference was not significant). Sixty-nine percent of the patients in both groups continued to experience marked symptomatic improvement. In Group 1, 96% of the patients had been assigned to New York Heart Association (NYHA) functional class III or IV before surgery; only 17% remained in these two classes postoperatively (p less than 0.01). In Group 2, 98% had been assigned to NYHA functional class III or IV before surgery, whereas only 20% remained in these two classes postoperatively (p less than 0.01). A comparison of preoperative and postoperative hemodynamic findings revealed that the left ventricular end-diastolic pressure was significantly reduced from 20 to 14 mm Hg in Group 1 and from 20 to 15 mm Hg in Group II (p less than 0.05). There was also a significant postoperative reduction in left ventricular outflow gradient at rest (from 79 to 6 mm Hg in Group 1 and from 75 to 7 mm Hg in Group 2) (p less than 0.01). These findings indicate that, in patients with hypertrophic cardiomyopathy who require surgical treatment, MVR alone or in conjunction with septal myomectomy offers significant improvement of symptoms and hemodynamic values.(ABSTRACT TRUNCATED AT 250 WORDS)