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L Degli Esposti,1 M Andretta,2 G Di Pasquale,3 M Gambera,4 S Saragoni,1 V Perrone,1 S Buda1 1CliCon S.r.l. Health, Economics & Outcomes Research, Ravenna, Italy; 2Local Pharmaceutical Service, Verona Local Health Authority, Verona, Italy; 3Department of Cardiology, Maggiore Hospital, Bologna, Italy; 4Local Pharmaceutical Service, Bergamo Local Health Authority, Bergamo, ItalyCorrespondence: V PerroneCliCon S.r.l, Health, Economics and Outcomes Research, Via Salara, 36, Ravenna 48100, ItalyTel +39 054438393Fax +39 0544212699Email valentina.perrone@clicon.itObjectives: 1) To evaluate anticoagulation treatment patterns and health care resource use in adult patients with a discharge diagnosis of non-valvular atrial fibrillation (NVAF) in an Italian real-world setting and 2) to describe the characteristics of NVAF patients in relation to treatment.Design: A retrospective cohort study in a “real-world” setting.Setting: Data were analysed by integrating administrative databases that included approximately 2,000,000 individuals assisted by the National Health System from two Italian Local Health Units.Participants: All adult patients with at least one hospital discharge or ≥2 outpatient visits with a diagnosis code for NVAF from 1/01/2011 to 31/12/2015 were included.Main outcome measures: Anticoagulation treatment patterns, health care resource use and major bleeding events that occurred during the follow-up period were evaluated.Results: 32,863 NVAF patients were included, of whom 7,831 had at least one prescription of oral anticoagulants. Among them, 6,876 patients were vitamin K antagonists (VKA) users and 955 were non-vitamin K antagonist oral anticoagulant (NOAC) users at index date (ID). During the follow-up period, the use of antiplatelet drugs was higher among VKA-naïve users than the NOAC-naïve users. Among NOAC users, 76.1% showed an adherence level ≥80% during follow-up. The rate of bleeding events resulted higher for VKA patients compared to NOAC patients. The unadjusted incidence rate was 10.46 per 1000 person-year for VKA patients and 4.55 per 1,000 person-years for NOAC patients. The overall annual cost (in term of drugs, hospitalisations and outpatient specialist services) was € 5,156.13 for VKA and € 4,630.57 for NOAC.Conclusion: This unselected cohort study, on NVAF patients being prescribed oral anticoagulants, highlights that VKA was largely prescribed and the great majority of patients on NOACs were adherent to treatment. Most of the OAC patients still received antiplatelet agents in combination, and in NOAC patients, we registered a lower number of bleeding events compared with VKA.Keywords: non-valvular atrial fibrillation, vitamin K antagonists, non-vitamin K antagonist oral anticoagulants, anticoagulation treatment patterns, real-world setting

Branching morphogenesis is essential for the formation of salivary glands, kidneys, lungs, and many other organs during development, but the mechanisms underlying this process are not adequately understood. Microarray and other gene expression methods have been powerful approaches for identifying candidate genes that potentially regulate branching morphogenesis. However, functional validation of the proposed roles for these genes has been severely hampered by the absence of efficient techniques to genetically manipulate cells within embryonic organs. Using ex vivo cultured embryonic mouse submandibular glands (SMGs) as models to study branching morphogenesis, we have identified new vectors for viral gene transfer with high efficiency and cell-type specificity to developing SMGs. We screened adenovirus, lentivirus, and 11 types of adeno-associated viruses (AAV) for their ability to transduce embryonic day 12 or 13 SMGs. We identified two AAV types, AAV2 and bovine AAV (BAAV), that are selective in targeting expression differentially to SMG epithelial and mesenchymal cell populations, respectively. Transduction of SMG epithelia with self-complementary (sc) AAV2 expressing fibroblast growth factor 7 (Fgf7) supported gland survival and enhanced SMG branching morphogenesis. Our findings represent, to our knowledge, the first successful selective gene targeting to epithelial vs. mesenchymal cells in an organ undergoing branching morphogenesis.

All fats, including saturated fatty acids, have important roles in the body. However, the most important fats are those that the body cannot make and thus must come from the food we eat. These essential fatty acids (EFAs) are based on linoleic acid (omega-6 group) and alpha-linolenic acid (omega-3 group). We need both groups of essential fatty acids to survive. For various reasons EFA deficiency is common in the general population, as is a disproportionate intake of omega-6 fatty acids over omega-3 fatty acids. As such, it is important to eat the right foods to make sure that you're taking in enough and the right kinds of the essential fatty acids. However, there is much more to the story. Studies have shown that increasing the intake of certain essential fatty acids, either alone or in combination with other fats and compounds, can increase health, help in treating certain diseases, and even improve body composition, mental and physical performance.

The aim of this paper was to compare the in-hospital management and outcome of patients on oral anticoagulation (OAC) undergoing coronary artery stenting (PCI-S) for ST-elevation myocardial infarction (STEMI) vs. other indications.One hundred and sixteen patients on OAC at the time of PCI-S who were prospectively enrolled in a multi-center, observational registry, were evaluated. Patients were segregated according to whether PCI-S was performed for STEMI (group 1) or other indications, such as non ST-elevation acute coronary syndromes, stable angina, silent ischemia, etc. (group 2), and the pharmacological and procedural management, as well as the in-hospital outcome, were compared.No significant differences were observed in vascular access site, sheath size and type of stent implanted, nor was significantly different the use of glycoprotein IIb/IIIa inhibitors, and the use and dose of intravenous unfractionated heparin. Although not statistically different, the in-hospital occurrence of death (3.7% vs. 1.1%; OR 3.3; 95% confidence intervals [CI] 0.2-56.0), stent thrombosis (3.7% vs. 1.1%; OR 3.3; 95% CI 0.2-56.0) and major bleeding (7.4% vs. 2.2%; OR 3.4; 95% CI 0.4-25.9) was consistently about 3-fold higher in group 1.The in-hospital pharmacological and procedural management of OAC patients undergoing PCI-S for STEMI vs. other indications appears not different. Although not significantly different however, the in-hospital occurrence of major bleeding, as well as of death and stent thrombosis, appears substantially higher in patients treated for STEMI, warranting therefore further larger, prospective studies.

Published studies of gene transfer to mouse salivary glands have not employed the parotid glands. Parotid glands are the likely target tissue for most clinical applications of salivary gene transfer. The purpose of the present study was to develop a convenient and reproducible method of retroductal gene transfer to mouse parotid glands.The volume for vector delivery was assessed by infusion of Toluidine Blue into Stensen's ducts of Balb/c mice after direct intraoral cannulation. Recombinant, serotype 5 adenoviral vectors, encoding either firefly luciferase or human erythropoietin (hEpo), were constructed and then administered to parotid glands (10(7) vector particles/gland). Transgene expression in vivo was measured by enzyme activity (luciferase) or an enzyme-linked immunosorbent assay (hEpo). Vector biodistribution was measured by real-time quantitative (Q) PCR.The chosen volume for mouse parotid vector delivery was 20μL. Little vector was detected outside of the targeted glands, with both QPCR and luciferase assays. Transgene expression was readily detected in glands (luciferase, hEpo), and serum and saliva (hEpo). Most secreted hEpo was detected in saliva.These studies show that mouse parotid glands can be conveniently and reproducibly targeted for gene transfer, and should be useful for pre-clinical studies with many murine disease models.

The cardiologic evaluation of patients with cerebral ischaemia should be aimed at: (1) identifying potential cardiac sources for cerebral emboli, (2) detecting a coexisting ischaemic heart disease, even asymptomatic. The present data concerns a ten-year experience of a systematic cardiologic evaluation of patients admitted to the 1st Division of Neurosurgery, Bellaria Hospital, Bologna, Italy, for cerebral ischaemia. A two-dimensional echocardiography was carried out in 344 consecutive patients (mean age 53 years), cardiac abnormalities were observed in 92 (28%) out of the 328 cases with technically adequate examination, embologenic lesions in 57 (17%). In 18 cases the cardiac lesion was unknown before the cerebral event. An exercise ECG testing was carried out in 322 patients (mean age 56 years), resulting in abnormal in 69 out of the 258 with adequate examination (17%). A subsequent exercise 201Tl myocardial scintigraphy confirmed the presence of ischaemic heart disease in 58 cases. Among patients unable to perform an adequate exercise, a dipyridamole 201Tl myocardial scintigraphy was performed in 38 cases showing perfusional defects in 23 (60%), while a dipyridamole echocardiography was performed in 25 cases showing wall motion abnormalities in 9 (36%). A 24-h Holter monitoring was performed in 65 cases: arrhythmias were detected in 27 patients (41%), but a correlation with the cerebral event was suggested only in 3 cases with atrial fibrillation. According to our experience patients with recent ischaemia should be submitted to the following non-invasive cardiologic screening: (1) exercise ECG testing followed, if abnormal or indeterminant, by 201Tl myocardial scintigraphy in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To assess the clinical impact of a regional network for the treatment of ST-segment elevation myocardial infarction (STEMI). Methods: All patients with STEMI (n = 1823) admitted to any of the hospitals of an area with one million inhabitants during the year 2002 (n = 858) - that is, before the network was implemented, and in 2004 (n = 965), the year of full implementation of the network, were enrolled in this study. The primary evaluation was inhospital mortality. Secondary outcomes included the incidence of major adverse cardiac and cerebrovascular events (MACCE), defined as death, myocardial infarction, stroke and coronary revascularisation procedures over 1-year follow-up. Results: Between 2002 and 2004, there was a major change in reperfusion strategy: primary angioplasty increased from 20.2% to 65.6% (p

To investigate the antianginal efficacy and tolerability of felodipine, a new dihydropyridine calcium antagonist, 20 patients with stable exertional angina, not completely controlled by beta-blocker monotherapy, entered a randomized, double-blind, placebo-controlled, crossover study. Patients on standard beta-blocker therapy, who had at least 3 weekly anginal episodes and a reproducible exercise test (stopped for angina and ECG signs of ischaemia) at the end of 2 weeks placebo treatment, were eligible for the study. They were randomized to one sequence of treatment: felodipine 5 mg twice daily for 2 weeks followed by placebo for a further 2 weeks, or vice versa. Beta-blocker treatment was unchanged throughout the study. A treadmill test was carried out at the end of each crossover period, 2-4 h after drug administration. The number of anginal attacks and nitroglycerin consumption was recorded on a diary card. At rest, felodipine significantly (P less than 0.05) reduced standing systolic but not diastolic blood pressure. Heart rate was not modified by the active treatment. At ischaemic threshold and at peak exercise, heart rate, systolic blood pressure and rate-pressure product remained unchanged. Exercise duration was increased by felodipine (P less than 0.01) and maximal ST change was reduced (P less than 0.01). Time to 1 mm ST depression was prolonged non-significantly by felodipine (basal 5.7 +/- 1.5, felodipine 7.4 +/- 2.0, placebo 6.6 +/- 1.5 min). The number of patients who stopped exercise due to angina and ST change was 20/20 at baseline, 16/20 with placebo and 10/20 with felodipine. Felodipine significantly reduced weekly anginal episodes (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial fibrillation (AF) is the most common cardiac arrhythmia seen by physicians and its prevalence is projected to rise dramatically as the population ages [1]. This will undoubtedly place an increasing strain on healthcare resources needed to treat this disease. While a variety of serious long-term complications are associated with AF, including congestive heart failure, the most serious risk is from ischemic stroke. AF accounts for almost half of all cardioembolic strokes and the association between AF and stroke is particularly strong in the elderly [2]. Several randomized clinical trials suggest that the yearly incidence of stroke for patients with non-valvular AF is almost 4.5%, half of them being disabling [2]. At present, a great deal of data clearly suggest which patient could be recognized as being at risk for stroke and well-defined factors separate a subset of subjects with a yearly incidence of stroke >10% from a moderateto low-risk group [3] (Table 1).

Since the large multicenter DIG trial has shown no effects of digitalis on the all-cause mortality of patients with chronic heart failure (HF), the broad prescription of this drug in patients with HF appears to be at the very least, questionable. The aims of this study were: to analyze prescription patterns of digitalis, from 1995 to 2000, in a large group of outpatients with HF; to analyze the independent predictors of digitalis prescription and to evaluate the impact of the results of the DIG trial on the prescription rate of this drug.From 1995 to 2000, 11 070 HF outpatients (mean age 64 +/- 12 years, ejection fraction 35 +/- 12%) were enrolled in a large Italian database.Out of 11 070 patients, 7198 (65%) were treated with digitalis. At multivariate analysis, the following variables were independently associated with digitalis prescription; atrial fibrillation (odds ratio [OR] 3.3, 95% confidence interval [CI] 2.9-3.8), ejection fraction30% (OR 1.7, 95% CI 1.5-1.9), NYHA class III-IV vs II-III (OR 1.3, 95% CI 1.2-1.5), admission for HF during the previous year (OR 1.4, 95% CI 1.2-1.5). After the publication of the DIG trial, there was a significant reduction in the rate of digitalis prescription: the percentage of patients taking digitalis fell from 68% in 1996-1997 to 61% in 1998-1999 (p0.001).Over 60% of Italian outpatients with HF were treated with digitalis; as expected, patients with a low ejection fraction, atrial fibrillation and in a more advanced stage of HF are more likely to receive this drug. Finally, after the publication of the DIG trial, the rate of digitalis prescription significantly decreased.

The pathogenic mechanisms underlying the increase in peripheral resistance and the contraction of smooth muscular fibre cells in essential hypertension are not yet clearly understood. However, it is now known that immune system activation plays a role in the pathogenesis of some forms of arterial hypertension, and recent data show that the Ca2+ influx in some cells (i.e. red blood cells, leukocytes, platelets, smooth muscular fibre cells) is increased in subjects with essential hypertension, thus revealing a possible alteration in cellular membrane. The end-points of this study were therefore to ascertain whether red blood cells used as a cellular membrane model have a greater Ca2+ dependent K+ flow (Gardos effect) in hypertensive patients than in normotensive controls, to point out a different regulation of ionic channels, and whether IL-8 and the adhesion molecule ICAM-1 influence the membranous outflow.The study was conducted on 87 Caucasian subjects. Of these, 50 (25 men, 25 women; mean age 43 +/- 3 years, mean body mass index (BMI) 27 +/- 0.5 and 22.3 +/- 0.3 kg/m(2), respectively) had mild-to-moderate hypertension (mean arterial blood pressure 120 +/- 8 mmHg ). The other 37 (18 men, 19 women; mean age 39 +/- 3 years; BMI 23.8 +/- 0.5 kg/m(2) and 22.8 +/- 0.5 kg/m(2), respectively were normotensive healthy volunteers (mean arterial blood pressure 89 +/- 2 mmHg). All the patients and subjects were untreated for at least 4 weeks before blood sampling.Ca2+-dependent K+ outflow was found to be greater in samples from patients with essential hypertension than in those from normotensive controls. lL-8 and ICAM-1 significantly enhanced the Ca2+-dependent K+ outflow in red blood cells from hypertensive subjects but had an inhibitory effect on cells from controls. In the experimental model, the presence of TMB-8, a membrane calcium antagonist, significantly reduced the Ca2+-dependent K+ efflux.Vasoconstriction in subjects with essential hypertension may therefore depend on a different regulation of ionic flow that probably supports an increased Ca2+ inflow in smooth muscle fibre cells. Under certain pathological conditions, some immune system components (i.e. interleukins, adhesion molecules) may directly enhance membrane permeability to Ca2+, thus inducing vasoconstriction in the smooth muscle cells.

Hemodialysis influences the transport of water through the erythrocytic membrane, and induces morphologic and functional modifications. Recently water channels, called aquaporins (AQP), have been identified on the membrane of red blood cells. The aim of the present study was, therefore, to evaluate any relationships between volumetric changes in erythrocytes (MCV), plasma osmolarity and membrane expression of AQP1 in 22 uremic patients during a hemodialysis session, and compare value with those in a control group of 22 healthy volunteers. Membranal AQP1 expression was evaluated using three methods: indirect immunofluorescence under confocal microscopy, immunoenzymatic method after membrane extraction, and immunoblotting. In uremic subjects, at baseline membrane AQP1 expression was significantly lower, whereas plasma osmolality was higher than in controls. At 1 and 2 h of replacement therapy, a progressive increase was observed in erythrocytic AQP1, values similar to those in controls being attained after 3.5 h. During the session osmolality values reduced progressively, becoming significantly lower than basal values. The mean erythrocytic corpuscular volume in patients with ESRD was significantly lower than in cntrols at baseline. This value increased during hemodialysis, attaining statistical significance with respect to the basal value at 3.5 h of dialysis. Close correlations were found between plasma osmolality and AQP1 values (r = –0.930; p < 0.05), and also between MCV and plasma osmolality trend (r = –0.909; p < 0.05). There was a linear correlation (r = 0.63, p < 0.05) between plasma AVP concentrations and plasma osmolality. The variations found in plasma osmolarity during hemodialysis, may induce AQP1 expression on the membrane of intact red blood cells.

Thrombosis is responsible for the acute manifestations of coronary artery disease. Intravenous heparin has been shown to be effective in reducing the risk of death or myocardial infarction in patients with acute coronary syndromes. Compared to standard heparin, low-molecular weight heparins (LMWHs) have improved pharmacological and pharmacokinetic properties. A number of LMWHs, such as nadroparin, dalteparin and enoxaparin, have been evaluated in patients with acute coronary syndromes. FRISC (Fragmin during Instability in Coronary Artery Disease) and FRIC (Fragmin in Unstable Coronary Artery Disease), evaluated dalteparin and found the LMWH to be more effective than aspirin alone (FRISC) and as effective as heparin in a direct comparison (FRIC). In a small trial, nadroparin was shown to significantly reduce the risk of ischemic outcomes compared with a combination of aspirin and heparin, but this effect was no longer significant in the large FRAX.I.S. trial (FRAXiparine in Ischaemic Syndrome). Enoxaparin resulted in a statistically significant reduction in the combined outcome of death, myocardial infarction and recurrent angina or of urgent revascularization when compared with heparin in the ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events) and TIMI 11B trials. Meta-analyzing of the data of these two trials revealed that even the combination of death and myocardial infarction was significantly reduced by the use of enoxaparin. There is accumulating evidence that LMWHs are safe and effective alternatives to standard heparin for the treatment of acute coronary syndromes and that they offer practical and therapeutic advantages.

Functional mitral regurgitation is a hemodynamic adverse consequence of right ventricular apical pacing that profoundly modifies the contraction and relaxation of the left ventricle by inverting and delaying its activation sequence. The aim of this study was to analyze by Doppler echocardiography in the acute setting the true incidence and the mechanism responsible for the right ventricular apical pacing-induced mitral regurgitation.We studied 27 consecutive patients submitted to pacemaker implantation (VVI n = 9; DDD n = 18) because of bradyarrhythmias. The exclusion criteria were structural cardiac disease and permanent atrioventricular block. Patients underwent Doppler echocardiographic examination during both spontaneous rhythm (pacemaker off) as well as during programmed pacing at a rate of 70 b/min. In case of a double chamber pacemaker, a non-optimized atrioventricular delay of 150 ms was chosen.Two groups were identified: 11 patients with (Group 1, mean age 71 +/- 7 years) and 16 patients without (Group 2, mean age 71 +/- 4 years) new-onset pacing-induced mitral regurgitation. The incidence of mitral regurgitation was found to be higher during DDD (33%) than during VVI (24%) pacing mode. The relationship between gender and the occurrence of pacing-induced mitral regurgitation was striking: 10/13 women (77%) presented with mitral regurgitation during acute right ventricular apical pacing while this complication occurred in only 1/14 men (7%). Moreover, analysis of variance (ANOVA) and post-hoc pairwise multiple comparison showed an increased size of the mitral apparatus, as defined by the enlargement of the annulus (long axis 28 +/- 3 vs 23 +/- 2 mm; short axis 25 +/- 3 vs 20 +/- 3 mm, p = 0.05) and the lengthening of the anterior mitral leaflet (23 +/- 4 vs 18 +/- 2 mm, p = 0.05) and chordae tendineae (16 +/- 3 vs 13 +/- 2 mm, p = 0.05). This was probably related to the high female prevalence (91%) in Group 1 as compared to the control group (50 healthy subjects; 17 men, 33 women; mean age 71 +/- 8 years). No significant differences were observed between Group 2 and controls.Our study confirmed that functional mitral regurgitation is a frequent consequence of right ventricular apical pacing. Despite the maintenance of normal atrioventricular synchrony, we found that the pathway for ventricular depolarization was the critical determinant of normal mitral valve function. Such data show the importance of the preservation of a normal ventricular activation sequence during permanent cardiac pacing where it is technically feasible. Female patients seemed to be exposed to a higher risk of pacing-induced mitral regurgitation due to an anatomic predisposing condition of the mitral apparatus and to the left ventricular dyssynchronous contraction secondary to right ventricular apical pacing.

The congenital absence of pericardium is a rare condition which may determine electrocardiographic ST-T abnormalities. The case of a 16-year-old athlete who presented T-wave abnormalities at standard electrocardiogram performed during a physical checkup is reported. Ventricular repolarization tended to normalize during exercise and in right lateral decubitus. Chest x-ray and echocardiography showed typical signs of complete absence of the left pericardium. The definite diagnosis was made by computer tomography (CT) scan. The importance of a complete investigation of athletes with T-wave abnormalities is emphasized. Diagnostic and therapeutic features of the congenital absence of pericardium are discussed.

Helicobacter pylori infection elicits a local and systemic immune response against bacterial antigens, including a heat-shock protein of 60 kDa (HSP60). The homology between microbial and human HSP suggests that the immune response to bacterial HSP may play a role in the pathogenesis of autoimmune disorders. Since gastric involvement and H. pylori have been reported in Sjögren's syndrome (SS), we investigated the prevalence of antibodies against H. pylori and its specific HSP60 in sera from patients with SS.Four groups of patients were studied. Group 1, 34 patients with primary SS (pSS); Group 2.19 patients with secondary SS; Group 3, 22 patients with various autoimmune diseases and Group 4, 43 healthy controls. Serum IgG levels against HSP60 were determined by an ELISA using recombinant full length HSP60 expressed in Escherichia coli, as the antigen. To confirm the H. pylori infection, a commercial ELISA was used.Out of 34 patients in Group 1, 27 (79.4%) and 30 (88.2%) had antibodies against H. pylori and its HSP60, respectively. The prevalence was significantly higher than that found in Group 3 (18.2%, p0.0001 and 27.3%, p0.0001) and in Group 4 (48.8%, p0.005 and 37.2%, p0.0001) but not than that of Group 2 (48.8% and 37.2%). If the prevalence of patients either positive or negative for both antibodies was considered, a statistically significant difference was found between Group I and respectively Groups 3 and 4.The hypothetical role of HSP60 in the development of the immune response both in pSS and secondary SS seems strictly linked to the prevalence rate of H. pylori infection.

The concentrations of bcl-2 protein that can block programmed cellular death in various cell lines were evaluated in blood samples from 10 uremic patients on hemodialysis, 10 uremics not yet on hemodialysis, and in 10 healthy controls. The bcl-2 protein variations (in uremics on dialysis) were ascertained in patients during the dialysis session. Oxidative stress was evaluated in all groups by assaying the products of intraerythrocytic lipoperoxidation. Dialyzed and nondialyzed uremic patients had higher bcl-2 protein concentrations than healthy subjects. Dialysis causes a significant reduction in the concentrations of bcl-2 protein which becomes statistically significant during the 3rd hour. In both groups of uremic patients a positive correlation was found between bcl-2 protein and products of lipoperoxidation.

Recent Italian legislative directives have focused on lowering health-service costs and improving the quality of health care. The AI-CARE study on unstable angina represents the initial observational step in a survey on health-care quality in the Italian region Emilia-Romagna.This study was performed to identify the processes usually involved in the management of patients with unstable angina admitted to a regional cardiology department. The consumption of health service resources and the clinical events related to angina were evaluated.AI-CARE is an observational, descriptive and prospective study. Between 15/3/95 and 15/6/95, the patients admitted consecutively to 25 cardiology units for unstable angina, as diagnosed on a clinical basis, were enrolled in the study. A six-week follow-up was provided. The data regarding demographics, history, entry electrocardiogram, symptoms, examinations, treatment and outcome were recorded on a detailed personal questionnaire. The participating centers have been divided according to complexity of organization: 18 with intensive care unit as level I, five with hemodynamic laboratory as level II and two with cardiosurgery as level III. Mortality, myocardial infarction, revascularization procedures and readmissions for angina were considered clinical events.We recruited 463 patients. At discharge, 411 patients were affected with unstable angina while other 40 developed non-Q wave infarctions. The final study population comprised 451 patients. The mean age was 68 years (range 61-76). There were 316 men (69%, mean age 68) and 135 women (mean age 72). All 451 patients were stratified according to the Braunwald classification: IIIB in 66.9%, IIIC in 9.9%, IB in 9.9%. Mean hospital stay was 10 +/- 6 days, while mean stay in intensive care units was 4.3 +/- 2.9 days. Medical treatment included antiplatelet agents (89%), nitrates i.v. (81%), nitrates per os (86%), heparin (55%) and beta-blockers (47%). The most common non-invasive test performed was echocardiogram (70% of patients), Holter ECG and exercise stress testing (19%). Selective coronary arteriography was performed in 50% of patients (23% during the first 10 days). Additionally, 32% of patients underwent revascularization. During follow-up, ten patients (2.21%) had a myocardial infarction, nine patients (1.99%) died and 49 patients (10.8%) were readmitted for angina.This study indicates that in spite of the poor use of diagnostic procedures (especially coronary arteriography) and myocardial revascularization, mortality and morbidity were relatively low. Our data are similar to the results of the recent Italian EARISA study but differ greatly from the results of foreign studies. Consequently, further observation of our study population is needed.

Cardiac complications are frequent in patients with subarachnoid hemorrhage (SAH). They include ECG abnormalities, cardiac arrhythmias, myocardial damage, and neurogenic pulmonary edema. The pathophysiology of these abnormalities is related to an imbalance of the autonomic cardiovascular control and to increased circulating and local myocardial tissue catecholamines. Cardiac involvement is more common in patients with severe neurological deficits and it may increase the morbidity associated with SAH because of the occurrence of life-threatening arrhythmias or pulmonary edema. Monitoring of cardiac events in patients with SAH might result in a better understanding of their clinical outcome, as well as providing a basis for specific treatment capable of preventing myocardial necrosis and cardiac arrhythmias.

Focal myocardial necrosis reported in patients who died of brain lesions and in donor hearts soon after insertion has been attributed to catecholamine-related injury induced before operation, or in the perioperative period. Interpretation of the morphofunctional type of myocardial injury observed and its quantification may help understand both its pathophysiology and clinical relevance.In 27 patients without heart disease who died of intracranial brain hemorrhage after berry aneurysm rupture, terminal clinical signs were correlated with the presence of absence of myocardial injury. All hearts were systematically examined, and the total histologic area was measured in square millimeters, with both the number of foci and myocardial cells showing necrosis, normalized to 100 mm2. Forty-five cases of fatal head trauma (26 "instantaneous" and 19 "rapid" deaths) in normal subjects and 38 cases of acquired immunodeficiency syndrome with (14 cases) or without (24 cases) severe brain damage were used as control subjects.Contraction band necrosis was the only form of myocardial necrosis found in 89% of patients with acute brain hemorrhage. Its extent was 26 +/- 34 foci and 67 +/- 104 necrotic myocardial cells x 100 mm2. In patients with acquired immunodeficiency syndrome, its frequency was 58% in those without and 78.5% with severe brain lesions, with foci and myocardial cell values of 1 +/- 1.5 and 10 +/- 22 and 7 +/- 16 and 17 +/- 32, respectively. In head trauma cases with instantaneous death, the frequency was 4% (one case only with foci 0.5 and myocardial cells 35), whereas with a rapid death it was 40% (foci 12 +/- 18 and myocardial cells 21 +/- 33).The observed myocardial injury was present in all groups examined, being maximal in patients with intracranial brain hemorrhage with longer survival and minimal in patients with head trauma who died instantaneously. In this setting, this lesion is typical of catecholamine myotoxicity and may express a sympathetic overstimulation either in the agonal period and independent of therapy or be caused by brain injury, especially intracranial brain hemorrhage. However, the extent of myocardial injury observed was minimal and should not jeopardize cardiac function if hearts from such subjects are transplanted.

ST-segment depression on exercise stress test (EST) is an independent predictor of future cardiac events. Nevertheless, in apparently healthy subjects without angina the occurrence of false positive results is frequent. Thallium myocardial imaging (TMI) may improve diagnostic and prognostic accuracy of EST. The aim of the present study was to assess the role of a normal exercise TMI for excluding a coronary artery disease in subjects with asymptomatic abnormal EST.Subjects referred for TMI from 1/1980 to 5/1991 with an abnormal EST and without history of ischemic, congenital, or valvular heart disease or abnormal resting ECG were included into the study. 137 subjects (98 men, 39 women), mean age 53 +/- 8 yrs (range 37-74 yrs) were enrolled and followed-up for 6.4 yrs (range 3-13 yrs). Clinical indications for EST were: atypical chest pain in 56 (41%) cases, check-up in 52 (38%) cases, sport activity in 29 (19%) cases. All subjects had a maximal symptom-limited EST. Abnormal EST was defined by a horizontal or downslopingor = 1 mm or upslopingor = 1.5 mm ST-segment depression at 0.08 sec. from J-point, in at least 2 leads. EST was discontinued for fatigue in 129 (94%) cases, for ST-segment depressionor = 3 mm in 8 (6%) cases. None had chest pain during EST. All subjects selected for the study had normal TMI. Criteria for normal TMI were homogeneous Thallium uptake on postexercise images and a normal washout in the delayed images by qualitative analysis. Planar images were obtained in 118 (86%) cases, and tomographic SPECT images in 19 (14%).During the follow-up period no subject died for cardiac causes and only 9 subjects (1%/yr) had non fatal cardiac events: 4 (0.45%/yr) had a non fatal myocardial infarction (one subject had coronary angiography for postinfarction angina and subsequent 3 coronary bypass graft for multivessels disease), 2 subjects (0.2%/yr) became symptomatic for unstable angina (both had coronary angiography and subsequent PTCA for critical left main coronary artery stenosis) and 3 (0.34%/yr) developed stable angina (one had coronary angiography and subsequent bypass graft for a critical stenosis of left main coronary artery). Four further subjects died for non cardiac events. Comparing clinical data and TE results of subjects with and without coronary events, we found that some parameters were related to a higher incidence of cardiac events: hypertension (78% vs 31% respectively in subjects with and without cardiac events, p0.01), hypercholesterolemia (33% vs 4.7%, p0.01);or = 2 conventional coronary risk factors (56% vs 17%, p0.02); and a slow regression of abnormal ST-segment depression during recovery (2.8 +/- 2 vs 1.5 +/- 1 min, p0.01).In conclusion, in subjects without typical chest pain and with abnormal asymptomatic EST, a normal exercise TMI identifies subjects with very low risk of future cardiac events (1%/yr). Our data suggest that subjects with abnormal asymptomatic EST should be routinely submitted to exercise TMI.

We refer a case of a 57-year-old woman with an acute myocardial infarction of the anterior wall, treated with rt-PA, aspirin and heparin. In the following days, in spite of the therapy, occurred a second acute myocardial infarction of the inferior wall complicated with ventricular fibrillation. Coronary angiography showed multiple coronary dissection involving the left anterior descending and the circumflex coronary arteries. The characteristic feature of this case consists of the multiple coronary dissection responsible for myocardial infarctions, an event seldom reported in the literature.

Patients with symptomatic carotid stenosis who are candidates for carotid endarterectomy are at high short- and long-term risk of coronary events. To stratify patients at different risk of coronary events we investigated the usefulness of a noninvasive preoperative cardiological workup. We studied 172 consecutive patients admitted to the Neurosurgical Department for symptomatic high-grade (70% to 99%) carotid stenosis (age, 42 to 74 years; mean, 57.8 years). Patients without history of coronary artery disease (CAD) and able to exercise were submitted to exercise electrocardiographic testing (EET) and, if abnormal, to exercise thallium myocardial imaging (TMI). Patients were classified into four groups: group 1, patients without CAD: no history of CAD, normal EET, or normal TMI in the presence of indeterminant EET (n = 93, 54%); group 2, patients with silent CAD: no history of CAD and concordant abnormal EET and TMI (n = 28, 16%); group 3, patients unable to exercise: no history of CAD and inability to perform adequate EET because of previous stroke or claudication (n = 29, 17%); and group 4, patients with known CAD: history of angina or myocardial infarction (MI) (n = 22; 13%). The four groups were comparable in regard to age, sex, and computed tomographic scan of the brain. The prevalence of stroke was higher in patients unable to exercise; hypercholesterolemia was more frequent in patients with known CAD. During the perioperative period (< or = 30 days after carotid endarterectomy), coronary events occurred in 3 patients (2%): fatal MI in 2 patients in group 4 and 1 patient in group 3. One hundred percent of patients were followed up for 6.2 years. Coronary events occurred in 23 of the 168 patients discharged from the hospital (13.7%); these were fatal in 11 (6.5%): 3 patients of group 1 (3%; sudden death in 2, fatal MI in 1), 8 patients of group 2 (29%; fatal MI in 5, unstable angina in 3), 8 patients of group 3 (28%; fatal MI in 4, nonfatal MI in 4), and 4 patients of group 4 (18%; fatal MI in 2, sudden death in 1, unstable angina in 1). Kaplan-Meier estimated curves of survival free from fatal and nonfatal coronary events were 97%, 51%, 49%, and 59%, respectively (P < .001, group 1 versus groups 2 and 3; P < .01, group 1 versus group 4). Among patients undergoing carotid endarterectomy, coronary events occurred twice as often as cerebral recurrences. A preoperative noninvasive cardiac investigation, including EET, can adequately identify groups of patients with diverse short- and long-term prognoses. In addition to patients with known CAD, those with silent CAD or who are unable to exercise represent, without the need of further investigation, groups at high risk of coronary events in long-term follow-up.

Atrial fibrillation (AF) carries a high risk of systemic embolism, in particular stroke. This is true not only when AF is associated with rheumatic valvular heart disease, but also in the so-called nonvalvular AF (NVAF). The recent randomized clinical trials assessing antithrombotic therapy as primary prevention in NVAF have shown that, untreated, disabling stroke occurs in 2.5%/year, ischemic stroke in 5%/year, stroke and transient ischemic attack in 7%/year, and stroke, transient ischemic attack and silent stroke in7%/year. All AF does not carry identical stroke risk. A risk stratification is important in order to decide long-term antithrombotic prophylaxis. A number of important clinical predictors of stroke have been identified. They include age, hypertension, congestive heart failure, previous arterial thromboembolism and previous myocardial infarction. Idiopathic or "lone" AF in patients60 years old, without hypertension and diabetes mellitus, carries an extremely low risk of stroke. Also in paroxysmal AF, when patients are60 years old and without organic heart disease, the embolic risk is low. The recent onset of AF does not seem to be associated with an excess of embolic risk, in comparison with long-standing AF. In conclusion, the underlying heart disease represents the main determinant of embolic risk. Within the broad spectrum of patients with NVAF a satisfactory risk stratification for thromboembolism can be accomplished by the analysis of clinical risk factors, possibly in association with echocardiographic variables.

We evaluated the performance and analytical parameters of a one-step magnetic IRMA kit for the measurement of myosin in serum. The method uses two monoclonal antibodies selected for their high affinity to the heavy chains of human ventricular myosin. The first antibody is coupled to a magnetic solid phase and the second one is labeled with 125I. The working range of the IRMA (range of myosin concentrations measured with an imprecision10% CV) was 250-3600 microU/L and the sensitivity 20.8 +/- 7.2 microU/L. The between-assay variability, evaluated from replicate measurements in different runs of two serum pools was 14.6 CV% for the first pool (259.1 +/- 37.8 microU/L) and 14.3 CV% for the second pool (442.0 +/- 63.1 microU/L), respectively. To evaluate the clinical usefulness of myosin as a marker of myocardial cell damage, serum myosin was measured in patients with acute myocardial infarction (AMI) (n = 9) or subarachnoid hemorrhage (n = 20). The results obtained with the myosin assay were compared with those of two other markers considered specific for myocardial necrosis (CK-MB and myoglobin). In eight patients with AMI, serum myosin was elevated 24-36 hours after the onset of chest pain and reached a maximum at 4-7 days, returning to control levels at 8-11 days. The one remaining AMI patient showed two subsequent peaks in serum CK-MB and myoglobin concentrations (thus suggesting an extension of myocardial necrosis), the myosin concentrations reaching their peak only after 9 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Human proteoglycan was aggregated to an immobilized hyaluronan solid phase on a 96-well ELISA plate. This complex was then degraded by recombinant human stromelysin. The remaining proteoglycan fragments were detected using a monoclonal antibody probe directed against the chondroitin sulfate (CS) region of the core protein. Stromelysin degraded the aggregate in a time and dose dependent manner as reflected by the loss of the CS epitope. Assay sensitivity was 0.125 U/well with total loss of the CS epitope occurring at 4 U/well. o-phenanthroline (IC50 = 52 microM) and U24522 (IC50 = 9 microM) inhibited degradation, while phosphoramidon did not. Serine and cysteine protease inhibitors had no effect. A comparative analysis of this assay with a reference method, substance P assay, gave similar inhibitor profiles. The use of aggregated human proteoglycan (native conformation) as a substrate, may better reflect how stromelysin inhibitors behave in the presence of complex substrates such as cartilage matrix.

The authors applied a widely used radiographic system of classifying acetabular fractures to axial computed tomographic (CT) scans and three-dimensional reconstructions in over 100 cases. In the classification system, fractures are analyzed according to the extent of involvement of two acetabular columns--the posterior and the anterior. To provide a better understanding of the CT anatomy of the acetabulum, the authors defined the boundaries of the columns on axial CT scans. They illustrated the most common fractures (posterior wall, transverse, transverse with posterior wall, and both columns) with radiographs, axial CT scans, and three-dimensional reconstructions. Axial CT scans readily demonstrated the fractures and presence of intraarticular fragments. Three-dimensional images helped in understanding the precise plane of the fracture, the degree of disruption of the articular surface, and spatial relationships of fragments. Although present three-dimensional CT is not without limitations, the authors believe that the technique is valuable and that, in their experience, it has facilitated preoperative planning.

Etiology and long-term prognosis were prospectively investigated in 155 consecutive patients (96 men and 59 women), aged 16 to 45 years, referred to our Neurosurgical Unit with cerebral transient ischemic attacks or infarction during the period 1978-1988. All patients underwent neurological and medical-cardiological evaluation, cerebral computerized tomography scanning, electrocardiogram, and laboratory tests. Two-dimensional echocardiography was performed in 123 cases (79%), cerebral angiography in 147 (95%). Atherosclerosis was the leading etiology occurring in 48 patients (31%). A cardioembolic disorder was considered the probable cause of ischemia in 8 cases (5.1%). Further possible etiologies were contraceptive pill assumption (5.8% of the total, but 15.3% within the female group), spontaneous arterial dissection (4.5%), migraine (4%), puerperium (2.6%), cervical trauma (2.6%), and other, more uncommon conditions. Despite extensive evaluation, the cause of cerebral ischemia remained unknown in 40% of cases. All patients received antiplatelet medication and 16 underwent surgery. The long-term outcome at a mean follow-up of 5.8 years was favorable: 91% of subjects resumed their work on a full or part-time basis.Etiology and longterm prognosis were prospectively investigated in 155 consecutive patients (96 men, 50 women) ages 16-45 years who were referred to the Neurosurgical Unit with cerebral transient ischemic attacks or infarction during the period 1978-88. All patients underwent neurological and medical-cardiological evaluation, cerebral computerized tomography scanning, electrocardiogram, and laboratory tests. 2-dimensional echocardiography was performed in 123 cases (79%), cerebral angiography in 147 (95%). Atherosclerosis was the leading etiology, occurring in 48 patients (31%). A cardioembolic disorder was considered the probable cause of ischemia in 8 cases (5.1%). Further possible etiologies were though to be: oral contraceptives (5.8% of the total, but 15.3% within the females), spontaneous arterial dissection (4.5%), migraine (4%), puerperium (2.6%), cervical trauma (2.6%), and other, more uncommon conditions. Despite extensive evaluation, the cause of cerebral ischemia remained unknown in 40% of the cases. All patients received antiplatelet medication and 16 underwent surgery. The longterm outcome at a mean followup of 5.8 years was favorable in that 91% of the subjects resumed their workload on a full or parttime basis.

In 25 full-term infants at birth and in their mothers, we determined plasma and mononuclear blood cell (MBC) Mg levels in order to investigate the relationship between maternal and fetal Mg status. MBC isolation for Mg analysis was carried out with a Ficoll-Isopaque gradient which is commercially available in disposable tubes. There was no difference in the plasma and MBC Mg levels between infants and their mothers. Neonatal MBC Mg content was significantly correlated with maternal plasma Mg concentration. The data demonstrate that MBC Mg content does not present any difference on the basis of age and emphasize that the constitution of fetal Mg reserve depends on maternal plasma Mg concentration.

Mediastinal haematoma as a complication of anticoagulant therapy has rarely been described in the literature. A case is reported of an anterior mediastinal haematoma which developed in a patient with mitral valve disease while on oral anticoagulant therapy. This occurred in spite of well-controlled anticoagulation therapy and the clinico-radiological features did not directly recall the hemorrhagic complication. Computerized tomographic scan of the chest, even if not conclusive, was essential for the clinical strategy. A definite diagnosis was obtained by percutaneous needle aspiration followed by iodinate contrast medium injection. This procedure also led to the resolution of the haematoma, thus avoiding hazardous surgical therapy.

Serial electrocardiograms (ECGs) were studied prospectively in 80 apparently healthy newborn infants; 30 infants exposed in utero to prolonged tocolytic therapy (21 to ritodrine and 9 to isoxsuprine) and 50 infants non-exposed in utero to drugs (control group) matched for gestational age, Apgar score, and birth weight. Duration of exposure to tocolysis was at least 30 days (30–180 days) with an oral dosage of 10 mg 3 times daily. ECGs were graded for changes suggestive of ischaemia using the arbitrary grading system described by Jedeikin et al. [12]. In all infants with ECG features of myocardial ischaemia, serum creatine-phosphokinase iso-enzyme (CK-MB) activity was measured. Six out of 21 infants to ritodrine and six out of nine infants exposed to isoxsuprine showed a degree of ECG ischaemia which persisted for several weeks. No control infant presented grade 2 or 3 ECG changes after the 5th day of life. The results of this study seem to show that prolonged tocolytic therapy with β-sympathomimetics has side-effects on the fetal myocardium and suggest that this treatment be reserved only for selective cases and/or for short periods of time.

A prospective cardiologic evaluation was performed in 83 consecutive patients with transient cerebral ischemia or mild stroke and without symptoms or electrocardiographic signs of ischemic heart disease. Patients were studied with an electrocardiographic exercise test; a positive test was followed by exercise Thallium-201 myocardial scintigraphy. Results were compared to those obtained in a group of 83 age and sex-matched healthy subjects submitted to the same study protocol. Asymptomatic coronary artery disease was detected in 28% of cerebrovascular patients with adequate electrocardiographic exercise test. A scintigraphic perfusion defect of variable extension was found in 19 of them. In the control group the electrocardiographic exercise test was positive in only 6% (p less than 0.01). Our results support the concept that: asymptomatic ischemic heart disease is often associated with cerebrovascular disease; therefore cerebral ischemic attacks may be a marker of coronary artery disease, an active investigation of the heart should be considered in cerebrovascular patients in order to plan optimal, comprehensive management.

Serum concentrations of T4, T3, reverse T3 (rT3), TSH, Thyroxine binding globulin (TBG) and Thyroxine binding prealbumin (TBPA) were measured and a TRH-stimulation test was performed in 10 iodide untreated children affected by cystic fibrosis (CF) and in 84 controls. As compared to the controls, CF patients had lower T4 and rT3, similar T3 and TBG and increased T3:T4 ratios. They also had lower TBPA, but this could not account for the low T4. Finally they had higher basal and TRH-stimulated TSH. Our results indicate subclinical hypothyroidism in CF. The mechanisms responsible for this situation are not elucidated by our data.

Primary oxalosis is a rare disorder of oxalate metabolism, characterized by nephrocalcinosis, nephrolithiasis, and extrarenal deposition of calcium oxalate in several tissues, including the heart. We report the case of a 34-year-old man with sudden right hemiparesis and aphasia from the occlusion of the left middle cerebral artery. Clinical features and the results of laboratory investigations led to the diagnosis of primary oxalosis. Two-dimensional echocardiography disclosed the presence of massive intracardiac calcifications compatible with deposition of calcium oxalate. The absence of other causes of stroke strengthened a cause-and-effect relation between cardiac oxalosis and cerebral infarction. Consequently, cardiac oxalosis should be considered among possible occult cardiac sources of cerebral embolism.

Many cardiac disorders can cause acute cerebrovascular insufficiency. The spectrum of potentially embolic cardiac conditions is wide; early recognition may determine a definite change in the management and prognosis of patients. In recent years the relevance of echocardiography in the screening of patients with cerebral ischemia has been emphasized. In order to identify potentially embolic cardiac conditions, 180 consecutive non selected patients with cerebrovascular insufficiency, underwent a clinical cardiological evaluation and an echocardiogram. The study population included 132 men and 48 women; the mean age was 51.7 years (range 19 to 72 years). A technically adequate echocardiogram was obtained in 153 patients. In 131 patients echocardiography was negative; cardiac lesions were detected in 22 patients (14.4%): mitral stenosis in 2, calcified aortic stenosis in 1, valvular endocarditis vegetations in 3, dilatative cardiomyopathy in 2, hypertrophic cardiomyopathy in 4, mitral valve prolapse in 4, regional left ventricular diskynesia in 5, mitral anulus calcification in 1. Patients were divided into 3 groups according to the results of cerebral angiography: 68 patients with normal angiography (Group I), 54 patients with atheromasic lesions on cerebral angiography (Group II), 31 patients in whom cerebral angiography was not performed (Group III). A higher incidence of cardiac diseases was found in the patients of Group I. The lack of lesions on cerebral angiography and the presence of embolic high-risk cardiac conditions strengthened a causal relationship of the cardiac disorder with cerebrovascular insufficiency in 10 of the 23 patients. In the mean follow-up period of 18 months of these 10 patients who underwent cardiac surgery or anticoagulation, no further attacks of cerebrovascular insufficiency were observed.(ABSTRACT TRUNCATED AT 250 WORDS)