Focusing of macromolecules using equilibrium between centrifugal and electric force.

A focusing separation model for macromolecules has been theoretically investigated. The method involves an ultracentrifugation device, which however, deploys an electric field gradient oriented longitudinally along the radial direction. When a macromolecular sample solution is centrifuged, the molecules which have different density to the surrounding solvent and a non-zero electric charge, experience a combination of centrifugal and electric forces. This forces the molecules to move to the equilibrium positions along the radius of the rotor, which are characterised by the charge over mass ratio of the molecules. Therefore a molecular sample will be separated into its constituents and bands will form, akin to electrophoresis. The bands are, however, focused at their equilibrium position. An example configuration has been examined whereby four proteins with masses between 20 and 100 kDa can be separated within a radial distance of 20 cm, for a rotor spinning at approximately 130,000 rpm and with a varying electric field between 0 and 100 V/cm.

An arrhythmia classification system based on the RR-interval signal.

OBJECTIVE: This paper proposes a knowledge-based method for arrhythmic beat classification and arrhythmic episode detection and classification using only the RR-interval signal extracted from ECG recordings. METHODOLOGY: A three RR-interval sliding window is used in arrhythmic beat classification algorithm. Classification is performed for four categories of beats: normal, premature ventricular contractions, ventricular flutter/fibrillation and 2 degrees heart block. The beat classification is used as input of a knowledge-based deterministic automaton to achieve arrhythmic episode detection and classification. Six rhythm types are classified: ventricular bigeminy, ventricular trigeminy, ventricular couplet, ventricular tachycardia, ventricular flutter/fibrillation and 2 degrees heart block. RESULTS: The method is evaluated by using the MIT-BIH arrhythmia database. The achieved scores indicate high performance: 98% accuracy for arrhythmic beat classification and 94% accuracy for arrhythmic episode detection and classification. CONCLUSION: The proposed method is advantageous because it uses only the RR-interval signal for arrhythmia beat and episode classification and the results compare well with more complex methods.

Treatment of acute lower limb ischemia following the use of the Duett sealing device: report of three cases and review of the literature.

Three cases of local thrombolysis in the treatment of acute lower limb ischemia complicating the utilization of the Duett sealing device are presented. Routine usage of several vascular closure devices after cardiac catheterization and percutaneous coronary intervention (PCI) has been adopted in our institution during the last 3 years (September 1999 to April 2003). The Duett closure device has been used in 420 patients (post-coronary angiography, 359; post-PCI, 61). Three patients (0.7%) demonstrated acute leg ischemia used by inadvertent intravascular administration of the sealing material related to this device. All three were treated successfully by catheter-directed local thromolysis (tissue plasminogen activator 5 mg bolus followed initially by 1 mg/hr and consequently by 0.5-1.0 mg/hr depending upon the development of significant hematoma and lasting for 24 hr). In conclusion, interventional treatment using local thrombolysis should be the first-line treatment in acute lower limb ischemia complicating the utilization of the Duett sealing device.

Haemodynamic and catecholamine response to simulated ventricular tachycardia in man: effect of baseline left ventricular function.

OBJECTIVE: To examine the effects of baseline left ventricular function on the haemodynamic and catecholamine responses to ventricular tachycardia. DESIGN: Experimental cohort study. SETTING: Cardiac catheterisation laboratory in tertiary referral centre. SUBJECTS: 24 patients (19 male, 5 female; mean (SD) age, 59 (10) years) without coronary artery disease, divided into two groups with normal or impaired left ventricular function: group A, ejection fraction > 65% (n = 10); group B, ejection fraction < 45% (n = 14). Other medical and demographic factors were similar in the two groups. INTERVENTIONS: Ventricular tachycardia was simulated with rapid pacing at 150 beats/min for 10 minutes. MAIN OUTCOME MEASURES: Arterial blood pressure; venous plasma catecholamine concentrations. RESULTS: During rapid pacing, blood pressure was lower in group B (with impaired left ventricular function) than in group A: systolic blood pressure, 102 (11) v 115 (9) mm Hg (p = 0.005); mean blood pressure, 79 (6) v 85 (6) mm Hg (p = 0.02). The ejection fraction correlated with the lowest systolic blood pressure (r = 0.64, p = 0.0006). Although the rise in adrenaline was comparable between the two groups, the rise in noradrenaline was more pronounced (p < 0.05) in patients in group B. CONCLUSION: At low rates and in selected patients, the underlying state of left ventricular function affects haemodynamic tolerance of ventricular tachycardia. Patients with impaired left ventricular function have a lower blood pressure during ventricular tachycardia, despite an exaggerated noradrenaline release.

Effects of delayed (24 h postintervention) beta-irradiation therapy after coronary angioplasty and stenting in de novo native coronary artery lesions; Results of a randomized clinical and intravascular ultrasound study.

BACKGROUND: The effects of brachytherapy performed 24 h postintervention in de novo native coronary artery lesions. METHODS AND RESULTS: Thirty-nine patients with 39 de novo coronary artery lesions were randomised to prompt (immediately after intervention, n=21) or delayed (24 h later, n=18) beta brachytherapy ((90)Sr/(90)Y) after been successfully revascularized with stenting. Clinical follow-up data up to 21 months (median time) were compared. After irradiation and at 6-month follow-up, paired volumetric analysis of the stented segment and the 5-mm proximal and distal reference segments was performed; this included measurements of the external elastic membrane, lumen, plaque, and media (external elastic membrane minus lumen), stent and intima hyperplasia (stent minus lumen). Baseline clinical and angiographic characteristics were similar in the two groups. Postintervention measurements of stent, lumen, and intima hyperplasia volumes as well as postintervention minimum lumen cross-sectional areas were not different. In the stented segments and in the segments 5 mm proximal and distal to the stent, similar changes of all IVUS measurements were measured in the two patient groups, but in the lumen volume at the proximal stent edge of patients irradiated 24 h postinjury. At 21 months median follow-up time, target lesion revascularization (TLR) was performed in 8 patients (38%) in the prompt irradiation group compared with 3 (17%) in the delayed (P=.17). CONCLUSION: Beta irradiation is similarly effective whether performed immediately after percutaneous coronary intervention or 24 h later.

External beam irradiation in angioplasted arteries of hypercholesterolemic rabbits. The dose and time effect.

PURPOSE: To study the dose and time effect of external beam irradiation on the morphometry of both angioplasted and nonangioplasted arteries in a hypercholesterolemic rabbit model. METHODS AND MATERIALS: Eight groups of rabbit femoral arteries were studied: arteries (a) with no intervention, (b) irradiated with a 12-Gy 6 MV X-ray dose, (c) with a 18-Gy, (d) treated with balloon angioplasty, (e) dosed with 12-Gy half an hour post-angioplasty, (f) dosed with 18-Gy half an hour post-angioplasty, (g) dosed with 12-Gy 48 h post angioplasty, (g) dosed with 18-Gy 48 h post angioplasty. RESULTS: External irradiation at either 12 or 18 Gy was not found to change vessel morphometry in noninjured arteries. The 12-Gy dose given soon after angioplasty further increased percentage stenosis (63% on the average), despite the preservation of the lumen cross-sectional area. Positive remodeling was not observed in arteries given 18-Gy half an hour post angioplasty to counterbalance the increased neointimal formation. Therefore, this treatment resulted in a drastic reduction in lumen area and in enhancement of percentage stenosis (84% on the average). On the contrary, the delayed irradiation of the angioplasted arteries at either 12 or 18 Gy was not found to influence any of the studied morphometric parameters 5 weeks after angioplasty. CONCLUSIONS: Uniform external beam irradiation up to 18 Gy was well tolerated by intact femoral arteries. Prompt 12- or 18-Gy irradiations accentuated percentage stenosis. However the lumen cross-sectional area was preserved only at the lower dose point. Delayed irradiation at any dose did not influence the restenosis process.

Platelet hyperaggregability to platelet activating factor (PAF) in non-ST elevation acute coronary syndromes.

It is known that myocardial ischaemia increases platelet aggregatory response to various agonists, ex vivo. We investigated the platelet aggregatory response to platelet activating factor (PAF), ex vivo, in patients with non-ST elevation acute coronary syndromes and determined the specificity and sensitivity of this response. Thirty-two consecutive patients with non-ST elevation acute coronary syndromes and 20 healthy volunteers were studied. Platelet aggregation in platelet-rich plasma was studied on the day of admission. The maximal aggregation achieved within 2 min after the addition of PAF (100 nM) was expressed as a percentage of 100% light transmission. PAF EC50 values were defined as the concentration that induces 50% of maximal aggregation. The PAF EC50 values of the non-ST elevation acute coronary syndromes patients were significantly lower compared to those of the controls (p < 0.0001). The maximal percentage of aggregation was also significantly higher (p < 0.0005). Ninety-one per cent of the patients were correctly classified using PAF EC50 values (specificity 90.0% and sensitivity 91.2%); the corresponding results using the maximal percentage of aggregation were 80% (specificity 70.0% and sensitivity 87.5%). The estimated values used as thresholds were 22.47 nM and 17.97 for the PAF EC50 and the maximal percentage of aggregation, respectively. The results of the present study suggest that platelet hyperaggregability to PAF, ex vivo, in non-ST elevation acute coronary syndromes is characterised by a high specificity and sensitivity, and thus it may represent a mechanism contributing to the pathophysiology of acute coronary syndromes.

Serum lipoprotein(a) concentrations and apolipoprotein(a) isoforms: association with the severity of clinical presentation in patients with coronary heart disease.

OBJECTIVE: The aim of this study was to investigate the possible associations between lipoprotein(a) [Lp(a)] concentrations or apolipoprotein(a) isoforms and the mode of clinical presentation of coronary heart disease (CHD) (acute thrombotic event or not). METHODS: A total of 131 CHD patients and 71 age- and gender-matched individuals without known CAD (free of symptoms of heart disease) were enrolled in the study. CHD patients were classified into patients with a history of an acute coronary syndrome (ACS, n=94) and patients with stable angina (SA, n=37). Lp(a) levels were measured with an ELISA method, whereas apolipoprotein(a) isoform analysis was performed (in all patients and 33 controls) by electrophoresis in 1.5% SDS-agarose gels followed by immunoblotting. Isoform size was expressed as the number of kringle 4 (K4) repeats. RESULTS: ACS patients had higher Lp(a) plasma levels 121.9 (0.8-84.1) mg/dl] and a greater proportion of elevated (> or = 30 mg/dl) Lp(a) concentrations (25.5%) compared with SA patients [9.2 (0.8-50.5) mg/dl, P < 0.01 and 10.8%, P < 0.05] and controls [8.0 (0.8-55.0) mg/dl, P < 0.01 and 11.2%, P < 0.05], while there were no differences between SA patients and controls. The median apolipoprotein(a)-isoform size was 26 K4. In 17 (10%) patients we could not detect any apolipoprotein(a) isoform bands by immunoblotting. ACS patients had a higher proportion of isoforms < 26 K4 (low molecular weight) than SA patients (56/85 vs. 12/33, P < 0.005) and controls (10/29, P < 0.005). CONCLUSIONS: CAD patients with a history of ACS have higher Lp(a) plasma levels and a significantly higher proportion of low molecular weight apolipoprotein(a) isoforms compared with patients with SA or to controls.

Phylogenetic and antigenic characterization of new fish nodavirus isolates from Europe and Asia.

Nodaviruses are widespread causative agents of viral nervous necrosis in fish. Based on the coat protein sequence, fish nodaviruses are categorized into four different genotypes. In this study, we present data on the phylogenetic and antigenic characterization of 12 new isolates, eight European and four of Asian origin, from farmed and wild species of fish. Phylogenetic analysis based on the nucleotide sequence (688 bases) of the coat protein classified the majority of these new isolates to the RGNNV genotype. Geographic or host-species specificities were not revealed by this study. Neutralizing assay experiments, further confirmed the genotypic classification, supporting the possibility that the different nodavirus genotypes can also be serologically distinguishable.

Platelet-associated and secreted PAF-acetylhydrolase activity in patients with stable angina: sequential changes of the enzyme activity after angioplasty.

BACKGROUND: Platelet-activating factor (PAF), the lipid mediator of inflammation and potent platelet agonist, can be hydrolysed and inactivated by PAF-acetylhydrolase (PAF-AH). We investigated the PAF-AH activity in relation to PAF formation in platelets from patients with stable angina undergoing elective percutaneous transluminal coronary angioplasty (PTCA). DESIGN: Twenty-seven patients with stable angina, undergoing PTCA, and 30 age- and sex-matched controls were studied. The platelet-associated and secreted PAF-AH activity was measured, before PTCA, as well as at 4 h, 48 h and 6 months afterwards. PAF formation by thrombin-stimulated platelets and the platelet aggregation responses to PAF and ADP were also determined. RESULTS: The PAF-AH activity secreted by thrombin-stimulated platelets before PTCA (in pmol/10(9) cells/h) was significantly higher compared to controls (892 +/- 222 vs. 624 +/- 144, P < 0.001). The enzyme activity was not altered at 4 h after PTCA, but was significantly increased at 48 h (1284 +/- 312, P < 0.005) to return to the levels observed in the control group 6 months afterwards. Detectable levels of PAF in thrombin-stimulated platelets were found only at 6 months after PTCA. Furthermore, the cell-associated enzyme activity in resting platelets before PTCA was significantly lower compared with controls. Unlike in controls, the platelet-associated enzyme activity in the patient group was not increased after stimulation with thrombin and it was associated by a platelet hyperaggregability to PAF. Both the intact cell-associated activity and the platelet hyper-reactivity to PAF were restored at 6 months after PTCA. CONCLUSIONS: Alterations in the platelet PAF-AH activity, which affect the PAF formation in thrombin-stimulated platelets and are associated by an increased aggregatory response to PAF, are observed in patients with stable angina and are completely restored after PTCA.

Vibrational angioplasty in the treatment of chronic femoropopliteal arterial occlusions: preliminary experience.

PURPOSE: To evaluate the safety and efficacy of vibrational angioplasty in chronic femoropopliteal arterial occlusions. METHODS: Six patients (5 men; ages 52 to 84 years) with peripheral arterial occlusive disease were treated percutaneously using vibrational angioplasty to recanalize the lesion. Three occlusions ranging from 10 to 15 cm long were in the superficial femoral artery (SFA), while 3 other diffusely diseased popliteal arteries were occluded distally (length from 3.5 to 4.5 cm). Vibrational angioplasty using coronary equipment was applied to assist passage of a coronary guidewire, which was followed by conventional angioplasty. Follow-up surveillance featured periodic physical examination, ankle brachial index measurements, and duplex scanning. RESULTS: In all 6 cases, recanalization of the occlusions was successful and without complications. The time to cross the occlusions with the wire ranged from 20 to 25 minutes for the SFA lesions and from 4 to 10 minutes for the popliteal occlusions. Two SFA occlusions were treated with stent implantation. Over a follow-up of 3 to 9 months, all treated vessels were patent. In 3 patients with skin ulcers, healing of the ulcers was observed. CONCLUSIONS: Vibrational angioplasty using coronary guidewires seems to be a promising ancillary technique in the management of chronic femoropopliteal arterial occlusions.

Relatively low red cell folate levels and acute coronary syndromes.

BACKGROUND: Low folate levels are related to increased risk for coronary artery disease in humans, while experimental work has shown that folate deficiency is thrombogenic. We hypothesized that relatively low folate levels are related to the development of acute coronary syndromes in patients with previously stable coronary artery disease. METHODS: One hundred and forty-one men were studied: 53 consecutive patients with acute coronary syndromes, 41 with stable coronary artery disease and 47 control participants. Known clinical and lipid risk factors were identified in all subjects and in addition plasma B12, plasma and red cell folate levels were measured. RESULTS: Red cell folate levels were significantly lower in patients with acute coronary syndromes (510+/-178 nmol/l) than in both stable coronary artery disease patients (638+/-264 nmol/l, P< 0.005) and controls (615+/-193 nmol/l, P< 0.05 respectively). Plasma folate and B12 levels were similar in all three groups. Multiple logistic regression analysis identified red cell folate levels as the only independent predictor of acute coronary events in the whole population of patients with known coronary artery disease and in the subgroup of non-smokers (P=0.010 and P=0.031). CONCLUSIONS: The present study suggests that relatively low red cell folate levels are associated with acute coronary syndromes and are an independent predictor of acute coronary events.

Outcome of patients with congestive heart failure treated with standard versus high doses of enalapril: a multicenter study. High Enalapril Dose Study Group.

OBJECTIVES: We sought to prospectively and randomly compare survival with clinical and hemodynamic variables in patients with congestive heart failure (CHF) treated with standard versus high doses of enalapril. BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors produce hemodynamic and symptomatic benefits in patients with CHF, but there is still controversy about the optimal dose in this clinical setting. METHODS: Two hundred and forty-eight patients with advanced CHF (age 56.3+/-12 years) were randomized to receive a maximal tolerated dose of enalapril, up to 20 mg/day in group 1 (mean dose achieved 17.9+/-4.3 mg/day, n = 122) and 60 mg/day in group 2 (mean dose achieved 42+/-19.3 mg/day, n = 126). RESULTS: At enrollment, patients in group 1 were in New York Heart Association (NYHA) functional class 2.6+/-0.7 and had a mean systolic blood pressure (SBP) of 117+/-18 mm Hg, a mean heart rate (HR) of 85+/-16 beats/min and a left ventricular ejection fraction (LVEF) of 20.0+/-9.8%. In group 2, patients were in NYHA class 2.6+/-0.7; their SBP was 118+/-17 mm Hg, HR 83+/-15 beats/min and LVEF 18.8+/-8.1%. There were no significant differences in these characteristics between the two groups of patients at enrollment. After 12 months of follow-up, 22 (18%) of 122 patients in group 1 and 23 (18%) of 126 patients in group 2 had died (p = 0.995, with 80% power of the study to detect a delta difference of 13%). The NYHA class was the same (1.9+/-0.7) in both groups; SBP was 111+/-16 and 111+/-17 mm Hg, HR 77+/-12 and 79+/-13 beats/min and LVEF 31+/-19% and 30+/-12% in groups 1 and 2, respectively. These differences were not statistically significant. The study had a power of 80% to detect (p = 0.05) the following changes: 13% in death rate, 0.25 units in NYHA class, 6 mm Hg in SBP, 5 beats/min in HR and 6% in LVEF. CONCLUSIONS: No significant differences were found in survival and clinical and hemodynamic variables between patients receiving standard and those receiving high doses of enalapril.

Treatment of refractory unstable angina in geographically isolated areas without cardiac surgery. Invasive versus conservative strategy (TRUCS study).

AIMS: We compared invasive (on-site coronary angioplasty or emergency air-ambulance transfer for bypass grafting surgery) vs conservative (persistent medical treatment) strategies in the management of refractory unstable angina in geographically isolated hospitals without cardiac surgical facilities. METHODS AND RESULTS: One hundred and forty eight randomized patients with refractory unstable angina were compared on an intention-to-treat basis. Outcomes (invasive vs conservative): (a) in hospital: stabilization (96% vs 43%, P=0.0001), non-fatal myocardial infarction (2.6% vs 4.2%, P=ns), death (1.3% vs 8.3%, P=0.046), combined outcome (3.9% vs 12.5%, P=0.053) and hospitalization (11.4+/-6.3 vs 12.4+/-8.0 days, P=ns). (b) 30-days follow-up: non-fatal myocardial infarction (2.6% vs 4.2%, P=ns), death (2.6% vs 11.1%, P=0.030) and combined outcome (5.3% vs 15.3%, P=0.031). (c) 12 month follow-up: non-fatal myocardial infarction (3. 9% vs 4.2%, P=ns), death (3.9% vs 12.5%, P=0.053), combined outcome (7.9% vs 16.7%, P=ns), re-admissions for unstable angina: (17.1% vs 23.6%, P=ns), late coronary angioplasty: (15.8% vs 11.1%, P=ns) and (d) late coronary bypass grafting: (7.9% vs 12.5%, P=ns). CONCLUSION: Invasive treatment of patients with refractory angina in remote areas without surgical back-up results in significant in-hospital stabilization and a reduction in major events in-hospital and at 30 days. Coronary angioplasty in stand-alone units and air-transfer of these patients seems safe.

Noninvasive indexes of left atrial diastolic function in hypertrophic cardiomyopathy.

OBJECTIVES: Our goal was to noninvasively assess left atrial diastolic function and its relation to the impaired left ventricular filling in patients with hypertrophic cardiomyopathy. METHODS AND RESULTS: We studied 34 patients with hypertrophic cardiomyopathy, 26 patients with secondary forms of left ventricular hypertrophy (aortic stenosis, fixed subaortic stenosis, hypertension), and 21 control subjects. Left atrial diastolic function was assessed by measuring acceleration time (SAT), deceleration time (SDT), and the EF (mean deceleration rate) slope of the pulmonary venous flow systolic wave (SW). Left ventricular diastolic function assessed by transmitral Doppler included peak early left ventricular and peak atrial filling velocities, the ratio of early-to-late peak velocities, isovolumic relaxation time, deceleration time, and EF slope. In patients with hypertrophic cardiomyopathy, acceleration time was significantly reduced (P<.05), deceleration time was significantly prolonged (P<.0001), and EF slope was significantly reduced (P<.01). These indexes were similar among the other two groups. No statistically significant difference existed between the subgroups of hypertrophic cardiomyopathy in the above indexes. Patients with hypertrophic cardiomyopathy and secondary forms of left ventricular hypertrophy had evidence of left ventricular diastolic dysfunction. In patients with hypertrophic cardiomyopathy, no correlation existed between left atrial and left ventricular diastolic function indexes (r = -0.26 to 0.33). CONCLUSIONS: Echocardiographic indexes of left atrial relaxation and filling are abnormal in patients with hypertrophic cardiomyopathy but not in secondary forms of left ventricular hypertrophy. These indexes are abnormal in all forms of hypertrophic cardiomyopathy irrespective of left ventricular outflow tract obstruction and distribution of hypertrophy; they are not solely attributable to left ventricular diastolic dysfunction. The above may imply that hypertrophic cardiomyopathy is a cardiac myopathic disease that involves the heart muscle as a whole, irrespective of distribution of hypertrophy and obstruction.

Vibrational angioplasty and hydrophilic guidewires in the treatment of chronic total coronary occlusions.

PURPOSE: To study the efficacy and safety of vibrational angioplasty versus hydrophilic guidewires for recanalizing chronic total occlusions (CTOs) of the coronary arteries. METHODS: In a retrospective study, 99 patients with old (>3 months) CTOs resistant to conventional techniques were treated either with vibrational angioplasty (group A, n = 72) or 0.014-inch hydrophilic guidewires (group B, n = 27). The selection of the technique (vibrational angioplasty or hydrophylic guidewires) was dependent only upon device availability. A variety of guidewires were employed in conjunction with vibrational angioplasty. RESULTS: The crossing success rates in groups A and B were 86.1% (62/72) and 55.5% (15/27) (p < 0.05), with final procedural success rates of 75% (54/72) and 44.4% (12/27) (p < 0.01), respectively. The main reasons for failure were inability to cross the lesion with a guidewire (10/18 in group A and 12/15 in group B) and large dissections resulting in vessel closure (2/18 in group A and 2/15 in group B). Three major complications were seen, 2 in group A and 1 in group B. Three vessel perforations were reported in group A. Both techniques needed prolonged fluoroscopy times. CONCLUSIONS: Vibrational angioplasty was more successful in treating CTOs compared to hydrophilic guidewires and had similar complication rates (most without clinical sequelae).

Isolation and sequencing of a cDNA encoding for a ribonuclease from the insect Ceratitis capitata.

Two overlapping clones encoding for a ribonuclease from six-day-old larvae of the insect Ceratitis capitata (Cc-RNase) have been isolated by immunoscreening a cDNA library and by 5' RACE. The sequence of the Cc-RNase cDNA contains an open reading frame of 414 nucleotides encoding for a precursor protein of 138 amino acids long with a putative signal peptide consisting of 19 amino acids. The calculated M(r) of the mature protein was found to be 13.7 kDa. Multiple alignments of the deduced amino acid Cc-RNase sequence with other ribonucleases revealed an approximate 25% average identity. Despite the low percentage of identity, histidine and lysine residues which are essential for its catalytic activity, were found to be completely conserved. Furthermore, expression of the clone in E. coli resulted in the production of a recombinant product that showed strong immunoreactivity with anti-RNase specific antibodies. These results support the hypothesis that the identified clone encodes for a protein which is a new member of the RNase superfamily.

Ventricular pre-excitation in the general population: a study on the mode of presentation and clinical course.

OBJECTIVE: To describe the mode of presentation and the clinical course of patients with ventricular pre-excitation (Wolff-Parkinson-White (WPW) syndrome), with special emphasis on asymptomatic cases in the general population. METHODS: Over an eight year period (1990-97) a prospective population based survey of cases with WPW pattern was conducted in a defined population in north west Greece (340 000 inhabitants). ECGs with WPW pattern were obtained from a widespread pool of ECGs within the health system. RESULTS: During the study period, 157 cases with WPW pattern were identified (49 female, 108 male). Ages ranged from infants to 84 years, mean (SD) 49.1 (21.0) years in female and 39.6 (20.6) years in male subjects (p < 0.01); 78 (49%) had no history of syndrome related symptoms. Asymptomatic subjects (n = 77; 24 female, 53 male) were older than symptomatic subjects (mean age 46.7 (21.0) v 38.5 (20.6) years, p < 0.03). Documented supraventricular tachycardia was recorded in 27 patients (17%) and atrial fibrillation in 12 (8%) (mean age at first episode 31.2 (18.3) and 51.6 (20.7) years, respectively, p < 0.01). During follow up (mean 55 months) no case of sudden death occurred. Three asymptomatic subjects reported episodes of brief palpitation. CONCLUSIONS: WPW pattern is more common, and diagnosed at a younger age, in men than in women. About half the patients with WPW pattern on ECG are asymptomatic at diagnosis and tend to remain so thereafter. No sudden cardiac death occurred during the study period.

Platelet aggregatory response to platelet activating factor (PAF), ex vivo, and PAF-acetylhydrolase activity in patients with unstable angina: effect of c7E3 Fab (abciximab) therapy.

OBJECTIVE: Platelet activation and aggregation is a dominant feature in the pathophysiology of unstable angina. The final step of platelet aggregation is mediated through the platelet integrin glycoprotein IIb/IIIa (GP IIb/IIIa), while abciximab (ReoPro) is one of the most potent inhibitors of this receptor. Platelet-activating factor (PAF) is a potent platelet agonist which is degraded and inactivated by PAF-acetylhydrolase (PAF-AH). The plasma form of PAF-AH is associated with lipoproteins. We studied the platelet response to the aggregatory effect of PAF, ex vivo, in relation to the plasma PAF-AH activity in 32 patients with unstable angina, as well as the effect of abciximab therapy on the above parameters. METHODS: Thirty two patients with unstable angina and 25 sex- and age-matched healthy controls participated in the study. On the day of admission (day 1) 17 patients received a bolus of abciximab (0.25 mg/kg) followed by a 12-h infusion (10 micrograms/min). Platelet aggregation to both PAF and ADP, in platelet rich plasma, was successively studied in both patients receiving abciximab or remaining untreated. The plasma and HDL-associated PAF-AH activity was also determined at the same times. RESULTS: In the untreated patients, the PAF EC50 values were significantly lower on the day of admission, whereas the maximal percentage of aggregation was significantly higher compared to controls (p < 0.01 for both comparisons). Similar behaviour of the platelets was observed in the aggregatory effect of ADP. This aggregatory response was not significantly altered 4 days, 7 days or 1 month afterwards. In the 17 patients who received abciximab, platelet aggregation to both PAF and ADP was inhibited by 90 +/- 5 and 96 +/- 3%, respectively, 1 h after bolus. At 2 and 3 days after treatment, platelet aggregation to both agonists was significantly recovered being similar to controls. However, it was fully restored 6 days after bolus, still being significantly higher compared to controls (p < 0.01 for PAF and p < 0.003 for ADP). The total plasma PAF-AH activity in both patient groups was not different from that of controls, whereas the HDL-associated PAF-AH activity was significantly lower. The total plasma or HDL-associated enzyme activity was not altered at any time interval studied, and it was not influenced by abciximab. CONCLUSIONS: The increased aggregatory response of platelets to PAF and the low plasma levels of HDL-cholesterol and HDL-associated PAF-AH activity in patients with unstable angina may contribute to the severe atherosclerosis and to acute thrombosis found in these patients. Abciximab therapy may protect platelets from PAF action in vivo the first days after drug administration, but it fails to permanently restore the enhanced aggregatory response observed.