Transcriptional regulation of arylalkylamine-N-acetyltransferase-2 gene in the pineal gland of the gilthead seabream.

Pineal serotonin-N-acetyltransferase (arylalkylamine-N-acetyltransferase; AANAT) is considered the key enzyme in the generation of circulating melatonin rhythms; the rate of melatonin production is determined by AANAT activity. In all the examined species, AANAT activity is regulated at the post-translational level and, to a variable degree, also at the transcriptional level. Here, the transcriptional regulation of pineal aanat (aanat2) of the gilthead seabream (Sparus aurata) was investigated. Real-time polymerase chain reaction quantification of aanat2 mRNA levels in the pineal gland collected throughout the 24-h cycle revealed a rhythmic expression pattern. In cultured pineal glands, the amplitude was reduced, but the daily rhythmic expression pattern was maintained under constant illumination, indicating a circadian clock-controlled regulation of seabream aanat2. DNA constructs were prepared in which green fluorescent protein was driven by the aanat2 promoters of seabream and Northern pike. In vivo transient expression analyses in zebrafish embryos indicated that these promoters contain the necessary elements to drive enhanced expression in the pineal gland. In the light-entrainable clock-containing PAC-2 zebrafish cell line, a stably transfected seabream aanat2 promoter-luciferase DNA construct exhibited a clock-controlled circadian rhythm of luciferase activity, characteristic for an E-box-driven expression. In NIH-3T3 cells, the seabream aanat2 promoter was activated by a synergistic action of BMAL/CLOCK and orthodenticle homeobox 5 (OTX5). Promoter sequence analyses revealed the presence of the photoreceptor conserved element and an extended E-box (i.e. the binding sites for BMAL/CLOCK and OTX5 that have been previously associated with pineal-specific and rhythmic gene expression). These results suggest that seabream aanat2 is a clock-controlled gene that is regulated by conserved mechanisms.

One-year clinical follow-up with the serpentine balloon expandable stent: report of the first 100 patients.

BACKGROUND: We recently reported a high technical and 30-day clinical success rate among the first 100 patients treated with the tubular, serpentine design, stainless steel, balloon-expandable stent (beStent) in Israel. The present study examined the clinical results in these patients after the first year. METHODS: Seventy-eight men and 22 women were included in the study. Previous myocardial infarction, bypass surgery and percutaneous transluminal coronary angioplasty had occurred in 52%, 12% and 26% of the patients, respectively. Diabetes mellitus was present in 30 patients and hypertension in 34 patients. One hundred and forty-eight stents of 15, 25, and 35 mm lengths were used. The indications for stenting were suboptimal results (n = 85), bailout conditions (n = 10) or for the prevention of restenosis (n = 8), and lesion types were A (n = 10), B1 (n = 29), B2 (n = 20), and C (n = 44). All patients were clinically monitored with regular visits at 1, 3, 6, 9 and 12 months. RESULTS: Overall, the 12-month event-free survival rate was 82%. Subacute thrombosis occurred in two patients. There were two non-cardiac deaths, one O-wave myocardial infarction, six elective bypass surgeries and 12 target lesion revascularizations. Event-free survival was significantly higher for those with lesions shorter than 15 mm than for those with lesions longer than 15 mm (90% versus 67%, P = 0.003), and for women compared with men (96% versus 78%, P = 0.02). CONCLUSIONS: The initial experience with the beStent shows favorable long-term results with an overall event rate of 18% for this subset of relatively complex lesions; higher event rates were observed for longer lesions.

First clinical experience with the premounted balloon-expandable serpentine stent: acute angiographic and intermediate-term clinical results.

The beStent-Artist coronary stent is a newly developed, stainless steel coronary stent with a serpentine tubular design and terminal stent markers, premounted on a semicompliant balloon. During this pilot evaluation we aimed to test the acute clinical and angiographic results, short-term (30 days) and 6-month clinical results. A total of 57 stents were used to treat 43 lesions in 40 patients. Deployment strategy included predilatation, stent deployment, balloon repositioning to match the distal end of the balloon to the distal stent marker, and subsequent 12-14 atm postdilatation. There were two cases of stent dislodgment, but no procedural complications. In four cases, stent recrossing with another balloon was necessary. In two of these cases, distal dissections were observed and treated with another stent. The minimal lumen diameter (MLD) increased from 0.84+/0.52 mm at baseline to 2.7+/-0.62 mm at the end of the procedure (a corresponding decrease in diameter stenosis from 78.6 > 16.4 to 18.2+/-10.7%). The acute gain was 1.89+/-0.61mm. No adverse events occurred by 30 days. During six months, 7/40 (18.5%) of patients required target vessel revascularization due to in-stent restenosis. In summary, the premounted beStent-Artist can be delivered and deployed with favorable immediate results and high success rate with favorable long-term recurrent event rates.

Initial and long-term results with the CrossFlex stent--data from a national registry.

The Cordis CrossFlex trade mark stent is a balloon expandable helical coil made of stainless steel. OBJECTIVE: To assess the short- and long-term safety and efficacy of this stent by conducting a multi-center national registry. METHODS: One hundred and sixteen stents were implanted in 109 patients (mean age 59 3 10 years, 95 males). The lesions were classified as type B2 or C in 56 patients (51%). Successful deployment was achieved in 103 patients (94.5%). Failure was due to damage to the stent (two patients) or inability to reach the lesion (four patients). High-pressure deployment (>14 atm) was used in 68% of cases. RESULTS: Edge dissections occurred in nine patients after high-pressure deployment and necessitated implantation of a second stent. One patient with a large acute myocardial infarction died during hospitalization. Side branch occlusion occurred in five patients (4.6%). Subacute thrombosis occurred in two patients (1.8%) during the first four weeks. During a six-month follow-up period, 18 patients (16.5%) were rehospitalized with recurrent angina. Fifteen patients had coronary angiography and 13 (12.1%) needed additional target lesion revascularization (TLR). Twelve patients required a second PTCA for in-stent restenosis, and one needed a coronary artery bypass graft operation. CONCLUSIONS: The CrossFlex coronary stent can successfully be used in complex coronary lesions, with few short-term complications and a low TLR rate. Operators should be aware of the possibility of edge dissection during high-pressure implantation.

Treatment and outcome of patients with acute myocardial infarction and prior cerebrovascular events in the thrombolytic era: the Israeli Thrombolytic National Survey.

BACKGROUND: Patients with a history of stroke presenting with acute myocardial infarction (MI) are often excluded from thrombolytic therapy owing to fear of intracranial hemorrhage. Few data, however, are available on the risks vs the benefits of thrombolysis in patients with an acute MI and a prior cerebrovascular event (PCE). METHODS: Data were derived from 2 nationwide surveys of 2012 consecutive patients with acute MI admitted to all 25 coronary care units in Israel during 1992 and 1994. Thrombolytic therapy was given to patients with a PCE at the discretion of the treating physicians. Outcomes were compared between patients with an acute MI with and without a PCE and between patients with a PCE treated with or excluded from thrombolysis. RESULTS: Patients with a PCE (n = 115 [6%]) were older, with higher rates of atherosclerotic risk factors and in-hospital complications than their counterparts without a prior event (n = 1897). They were treated less often with thrombolysis or mechanical reperfusion. The 1-year mortality rates were higher among patients with a PCE (28% vs 19%, P<.01), but not after multivariate adjustments for clinical characteristics (adjusted hazard ratio, 1.08; 95% confidence interval, 0.75-1.55). Patients with an acute MI and a PCE who were treated with thrombolysis (n = 29 [25%]) were compared with 46 patients found ineligible for thrombolysis primarily because of their PCE. The timing of the PCE was comparable in both groups (one fifth in the preceding year), while prior transient ischemic attacks were more prevalent among patients who had undergone thrombolysis. The patients who were treated with thrombolysis (n = 29) were older, had a higher rate of anterior infarction, and, while in the hospital, received aspirin, anticoagulants, and beta-blockers more often than their counterparts (n= 46). In-hospital intracranial hemorrhage did not occur in either group. The 1-year mortality rates were 2-fold higher among patients who had not undergone thrombolysis compared with those who had (33% vs 18%; adjusted hazard ratio, 2.44; 95% confidence interval, 0.78-7.64). CONCLUSIONS: These findings, derived from 2 nationwide surveys of consecutive patients with acute MI, suggest that patients with PCEs have an adverse outcome attributed to their older age and less favorable risk profile. Thrombolytic therapy, however, based on our preliminary data, may be beneficial in selected patients with an acute MI with a nonrecent PCE.

Acute and 30-day results of the serpentine balloon expandable stent implantation in simple and complex coronary arterial narrowings.

We report the acute and 30-day results with a new serpentine-design, tubular, stainless steel, balloon-expandable stent (beStent) in the first 100 patients. One hundred forty-eight stents were used to treat 103 narrowings in the left anterior descending (n = 46), left circumflex (n = 20), and right coronary (n = 37) arteries. There were 85 de novo and 18 restenotic lesions (lesion length: < 10 mm [31], 10 to 20 mm [43] > 20 mm [29]; lesion type: A [10] B1 [29], B2 [20], C [44]; total occlusions, 23. More than 1 stent was used in 31 patients for treatment of long lesions that could not be covered by 1 stent. The stents used were 15-mm (n = 106), 25-mm (n = 38), or 35-mm (n = 4) long. Stent implantation strategy involved predilatation, deployment, and high-pressure dilatation, using the same balloon if possible. Clinical in-hospital success was 97% (2 patients had stent thrombosis that was recanalyzed, with myocardial infarction developing in 1, and 1 patient died on day 14 from retroperitoneal bleeding treated with surgery and complicated by sepsis). One-month event-free survival was 96%, with 1 death on day 21 due to hypertensive crisis. There were no other major adverse cardiac events in this first complex cohort of patients. In conclusion, the initial experience with this stent demonstrates its safety and efficiency for treating simple and complex coronary disease, with a relatively low rate of complications. Long-term clinical follow-up awaits further investigation.

The contribution of task-related factors to ERP repetition effects at short and long lags.

Event-related potentials (ERPs) were used to assess the relative contribution of task-related decision-making processes to the repetition effect at Lags 0 and 15. Electrophysiological activity was recorded from 16 subjects in two tasks. Task A required a lexical decision: subjects were instructed to silently count infrequently occurring nonwords in a list of words and nonwords. Task B, a recognition memory task presented in four blocks, required subjects to distinguish between old and new probes in each block. Significant ERP repetition effects, equivalent in both tasks, were found at Lag 0. In contrast, at Lag 15, the repetition effect was significant only in Task A. These results suggest that ERPs are sensitive primarily to poststimulus-identification sources of the repetition effect, such as the recovery of episodic traces related to stimulus-categorization and decision-making processes.

Recurrent preexcited reciprocating tachycardia, concealed ventricular preexcitation and conduction disturbances in the normal atrioventricular pathway in a newborn.

We describe a newborn infant with concealed ventricular preexcitation in sinus rhythm on the early ECGs, and who developed recurrent episodes of preexcited reciprocating tachycardia. Manifestation of the ventricular preexcitation and initiation of the tachycardias were dependent on the presence of severe conduction disturbances in the normal atrioventricular pathway, probably in the atrioventricular node.

Sublingual isosorbide dinitrate in severe congestive heart failure.

Sublingual isosorbide dinitrate was administered to 17 patients with severe congestive heart failure to characterize the hemodynamic action of the drug. Isosorbide dinitrate effect was maximal 30-60 min after administration. The most striking effect was a marked fall of the mean pulmonary capillary wedge pressure which dropped from 28 to 20 mm Hg (p less than 0.01). Pulmonary artery systolic pressure dropped from 55 to 43 mm Hg (p less than 0.01) and right atrial pressure from 11 to 8 mm Hg (p less than 0.01). Arterial blood pressure fell slightly whereas no significant change in heart rate or cardiac index was noted. 8 of the 17 patients showed a marked and sustained reduction of their pulmonary capillary wedge pressure. The hemodynamic response was moderate in 2 patients whereas 6 patients showed no appreciable improvement. A symptomatic but transient reduction in arterial blood pressure occurred in the last patient. Patients responding favorably to the drug had significantly higher initial systolic blood pressure that nonresponders (133 vs. 102 mm Hg, p less than 0.01). However, there was no reliable clinical parameter to predict which of the subjects will respond favorably to the administration of isosorbide dinitrate.

Early detection of doxorubicin cardiotoxicity by M-mode echocardiography.

The influence of increasing doses of doxorubicin on the heart was examined in 30 patients with solid tumors, M-mode echocardiography being used to evaluate left ventricular contractility. The function of the left ventricle remained normal in 26 subjects, whereas four patients had evidence of cardiotoxicity after cumulative doses of 220, 380, 420, and 450 mg/m2. Transient overt heart failure was noted in one subject only. Doxorubicin cardiotoxicity can be detected by M-mode echocardiography, a simple and non-invasive technique, prior to the appearance of overt congestive heart failure. Patients demonstrating left ventricular dysfunction are probably not candidates for receiving further therapy with anthracycline antibiotics. Limitation of M-mode echocardiography include a 28% incidence of inadequate studies in this group of patients, and a relative inaccuracy of the technique in evaluating patients with prior myocardial infarction.

Echocardiography in infective endocarditis. Lack of specificity in patients with valvular pathology.

59 patients with suspected infective endocarditis on a natural valve were studied by M-Mode echocardiography to determine the specificity of the ultrasonic technique in detecting valvular vegetations. All echocardiograms were read independently by two observers who were unaware of the final diagnosis. Among 40 patients who later proved not to have infective endocarditis, two (5%) were diagnosed by echocardiography as having either possible or probably vegetation by at least one observer. Both patients with a false positive diagnosis of vegetation had pre-existing valvular pathology, the presence of which greatly complicated the interpretation of the echocardiogram. Inter-observer disagreement occurred in 5 of the 59 studies (8.5%). The results of this study suggest that caution should be exerted in the echocardiographic diagnosis of vegetation in patients with pre-existing valvular pathology.

Contribuiton of M-mode echocardiography to cardiac diagnosis. An assessment in 1,000 successive patients.

The contribution of M-mode echocardiography to cardiac diagnosis was evaluated in a series of 1,000 successive patients. Among subjects in whom a presumptive clinical diagnosis had been made, echocardiography demonstrated totally unexpected findings in 10 per cent, supported the clinical diagnosis in 50 per cent and was entirely within normal limits in 19 per cent. Among patients with evidence of heart disease but no firm clinical diagnosis, echocardiography established the diagnosis in 23 per cent, including 20 per cent of all patients referred for evaluation of chest pain or arrhythmia of unclear etiology. "Missed" clinical diagnosis frequently involved patients with mitral valve prolapse, congestive cardiomyopathy, pericardial disease or asymmetrical septal hypertrophy of the heart. This study quantifies the amount of independent information contributed by echocardiography to cardiac diagnosis and demonstrates that this technic provides data of important clinical relevance in a surprisingly large number of cardiac patients.