[Vascular complications at the femoral access: impact of the percutaneous closure device Perclose]. / Complications vasculaires de l'abord artériel fémoral: impact du système de fermeture percutanée Perclose.

INTRODUCTION: Vascular complications at the femoral access site is an important factor of morbidity. The aims of this study were to evaluate the efficacy and safety of the percutaneous closure device (Perclose) during interventional cardiology procedures. PATIENTS AND METHODS: All patients with percutaneous closure of the femoral access site by the Perclose system in 2010 were included. We evaluated the indications of the procedures, the success rate of implantation and the bleeding complications according to antithrombotic therapy used. RESULTS: Three hundred and seventy five patients underwent a percutaneous closure by the Perclose system. Acute coronary syndromes with or without elevation of ST segment were the main indications of procedures (74.9%). The success rate of percutaneous closure of the femoral access site was 97.3%. The rate of minor, moderate, and severe bleeding of the entire cohort according to the GUSTO classification was respectively 4.2%, 0.5% and 1%. Bleeding complications were similar in both groups of patients (2.1% vs 7% P=0.122). In case of unsuccessful deployment of femoral closure devices, the risk of bleeding complications range from 4.3% to 60% (P=0.0000036). CONCLUSION: The use of the Perclose system is associated with a low rate of severe bleeding at the femoral access site. However, the failures of percutaneous closure increase the risk of bleeding complications.

[Very late bare-metal stent thrombosis 10 years after the implantation: a case report]. / Thrombose très tardive d'un stent nu dix ans après son implantation : à propos d'une observation.

Very late thrombosis occurring after bare-metal stent (BMS) implantation is a rare complication. It differs from very late thrombosis of drug-eluting stents in terms of both frequency and pathophysiological mechanism. We report a case of very late stent thrombosis of a bare-metal stent 10 years after his implantation for treatment of a myocardial infarction. The patient had a new acute coronary syndrome without persistent ST-segment elevation related to bare-metal stent thrombosis. He was treated by thrombo-aspiration and implantation of a new bare-metal stent.

[Use of drug-eluting stents: impact of French recommendations on the rate of clinical restenosis at 2 years]. / Utilisation des stents actifs : impact des recommandations françaises sur le taux de resténose clinique à deux ans.

AIMS: The drug-eluting stents (DES) reduce restenosis rate compared to bare metal stents. The clinical efficacy is greater in some subgroups of patients at high risk of restenosis. The aim of this study is to evaluate the use of drug-eluting stent based on the recommendations of the French Society of Cardiology and its impact on the restenosis rate at 2 years. METHODS: We included all patients who had coronary angioplasty with stenting in 2008. We evaluated the percentage of drug-eluting stent, the proportion of patients for which the French recommendations have been followed, and the rate of clinical restenosis at 2 years. RESULTS: Four hundred and seventy-nine angioplasties were performed in 2008. The percentage of drug-eluting stents was 21.8%. Acute coronary syndrome with or without elevation of the ST segment were the main indications of angioplasty (67.9%). For the 115 drug-eluting stents implanted in 2008, French recommendations were followed in 93% of cases (107 stents). For 89 patients who received DES, these recommendations were followed in 91% of cases (81 patients). The clinical restenosis rate at 2 years evaluated in 89% of patients was 5.6%. The rate of in-stent restenosis in bare metal and drug-eluting stents were 5.9 and 3.7%. CONCLUSION: The use of DES in our center is characterized by a small rate and a good compliance of the recommendations of the French Society of Cardiology. This strategy is associated with a low rate of restenosis at 2 years of follow-up.

Randomised comparison of coronary stenting with and without balloon predilatation in selected patients.

BACKGROUND: The SWIBAP (stent without balloon predilatation) prospective randomised trial was designed to compare direct coronary stenting with stenting preceded by lesion predilatation with an angioplasty balloon. OBJECTIVE: To determine the feasibility and safety of direct stenting in non-complex coronary lesions in a prospective study. PATIENTS AND DESIGN: All patients < 76 years of age scheduled to undergo angioplasty of a non-complex, non-calcified lesion in a coronary artery of > 3.0 mm, who granted their informed consent, were randomised into the trial. In group I, the stent was placed without balloon predilatation, while in group II stent implantation was preceded by balloon predilatation. The primary end point was the angiographic result according to procedure assigned by randomisation. An intravascular ultrasound substudy was performed in 60 patients. RESULTS: Stent implantation was successful without predilatation in 192 of the 197 group I patients (97.5%), and with predilatation in 197 of the 199 group II patients (99%) (NS). No in-hospital stent thrombosis or death occurred. Overall procedural times, fluoroscopy times, and volumes of contrast agent given (mean (SD)) in group I v group II were 23.50 (13.54) min v 27.96 (15.23) min (p = 0.002), 6.04 (4.13) min v 6.67 (3.65) min (NS), and 135 (65) ml v 157 (62) ml (p < 0.001), respectively. No major adverse cardiovascular events had occurred by 30 days. CONCLUSIONS: The feasibility and safety of direct stenting of selected and non-complex coronary lesions is confirmed. This technique was as successful as the conventional approach and was associated with a minor reduction in fluoroscopic exposure and procedure time and the administration of less contrast agent.

Emergency coronary artery bypass surgery following coronary angioplasty and stenting: results of a French multicenter registry.

This study investigates the influence of coronary stenting on the risk of emergency bypass surgery performed within 24 hr of percutaneous transluminal coronary angioplasty (PTCA) with particular concern for incidence and indication. Since 1995, coronary stenting has been increasingly performed in France during angioplasty procedures, altering significantly the role of emergency bypass surgery. The outcome of elective stenting and widespread use of coronary stenting and its influence on emergency surgery have not been evaluated so far. Through a retrospective (1995) and prospective (1996) registry, we analyzed the incidence, indication and results of emergency bypass surgery performed within 24 hr of PTCA in 68 and 57 centers, respectively, accounting for nearly half of all angioplasty procedures in France. Data were collected through questionnaires consisting of separate forms for every case report that were sent to every center. Over the two years, 26,885 and 27,497 procedures were investigated with a stenting rate of 46% and 64%, respectively. The observed need for emergency surgery was constantly low throughout this period (0.38% and 0.32%, respectively). Indications for surgery included complications directly due to stent in 37% of cases in the 2-year period. Outcome remained poor, with in-hospital mortality in 10% and 17% and myocardial infarction in 27% and 25% of cases, respectively. A comparison of the results in centers with and without surgical facilities showed no differences in outcome, despite a longer time to surgery (359 min +/- 406 min vs. 170 min +/- 205 min, P = 0.0001) and a lower incidence of emergency surgery (0.25% vs. 0.44%, P = 0.0001) in centers without on-site surgery backup. The French multicenter registry reveals an increase in the use of stents together with a dramatic decrease in the incidence of emergency bypass surgery (below 0.5%) following PTCA. There has been a significant evolution in the indication, and stent implantation now accounts for a third of the indications for emergency bypass surgery.

Experience with a lead fixation/suture sleeve.

Current anchoring systems on pacemaker leads are crude in comparison to the lead technology. Poor anchoring technique may cause damage to the lead or early displacement from incorrect suture tension. We describe experience with a locking anchoring sleeve that applies a constant gripping force to the lead body. This can be locked and unlocked to allow optimal positioning after fixation of the sleeve to underlying tissues. The sleeve was fitted to a 55D polyurethane lead (Medtronic 4024, 7 Fr, bipolar, steroid eluting) implanted in the ventricular position in 22 patients at four European centers. All implants were uncomplicated; data were collected on handling and ease of use. Assessments were made using a scale of 1-10 (10 = excellent, 5 = equivalent to conventional sleeve). Overall ease of use compared to conventional sleeve was 7.79 +/- 0.62 (mean +/- SD). Mean scoring of flexibility of the lead at the transition points was 7.92 +/- 0.72; ability to lock/unlock the sleeve scored 6.28 +/- 1.78. Ease of suturing around the sleeve scored 8.07 +/- 0.77, and ability to slide the sleeve along the lead body scored 6.48 +/- 1.99. Chest X rays at 6 weeks showed no change in lead position with respect to postimplant films, and all leads showed a straight path on either side of the sleeve with no evidence of conductor distortion. Follow-up to 3 years has been without problem. All leads remain intact and in place, with stable thresholds and no evidence of erosion. There have been no complaints of patient discomfort. We conclude that this device is safe and effective and offers a significant advance in lead fixation.

[Primary angioplasty in acute myocardial infarction. A one-year experience in a small urban community]. / Angioplastie primaire à la phase aiguë de l'infarctus du myocarde. Expérience d'une année d'activité dans une ville de moyenne importance.

The aim of this study was to assess the feasibility, safety and efficacy of primary angioplasty in acute myocardial infarction in a cardiology centre of a small urban community without on-site cardiac surgery. During 1995, 50 patients underwent angioplasty for MI in the first 12 hours. The average age was 66.7 +/- 12.6 years. Eighty six per cent of patients had at least one poor prognostic criteria (32% over 75 years of age, 70% anterior wall infarcts, 30% with heart rates > 100 min on admission). The angiographic result was successful in 45 patients (90%). The time between onset of pain and reopening the vessel was 240 +/- 116 min and between admission to the catheter laboratory and reopening 31 +/- 8 min. A coronary stent was implanted in 24 cases (48%) and intra-aortic balloon pumping was necessary in 14 cases (28%). Ischaemia recurred during the hospital phase in 7 cases (14%), 4 of which (8%) were caused by rethrombosis of the dilated artery: in 3 cases, the ischaemia was in another zone. No emergency coronary bypass surgery was required. The hospital mortality was 10%, always in patients over 80 years of age. The average duration of the hospital stay was 5.8 +/- 2.6 days with 15.7 +/- 7.3 days of convalescence. The average global cost was 61850 +/- 20686 F. These results were comparable to previously reported figures and confirm that primary angioplasty in acute infarction is possible and effective with an acceptable risk in a small urban community without on-site cardiac surgery.

[Estimation of the long-term efficacy of anti-arrhythmia treatment with flecainide in ventricular tachycardia]. / Prévision de l'efficacité à long terme du traitement antiarythmique par flécaïnide dans les tachycardies ventriculaires.

Flecainide, a Class IC antiarrhythmic agent, was used in 12 patients with an average age of 57 years to treat spontaneous monomorphic sustained ventricular tachycardia (S-VT, n = 9), with a ventricular rhythm of 203 +/- 41 bpm (5 right bundle branch and 4 left bundle branch block pattern) and non-sustained ventricular tachycardia (NS-VT, n = 3). The patients had ischaemic heart disease (n = 5, including 2 cases of aneurysm), idiopathic dilated cardiomyopathy (n = 1), ventricular dysplasia (right, n = 1; left n = 2; biventricular, n = 1). The remaining 2 patients had no overt cardiac disease on coronary angiography. None of the patients had signs of cardiac failure; the left ventricular ejection fraction was 0.49 +/- 0.7. Before treatment, programmed ventricular stimulation (PVS) induced 12 S-VT (214 +/- 41 bpm) which reproduced the clinical VT in 8 out of 10 cases. A second series of electrophysiological studies was performed after an average of 5 weeks treatment with Flecainide 300 mg/day (200-400 mg). It was not possible to induce VT in 2 patients (17% total prevention); NS-VT replaced S-VT in 4 patients (33%); S-VT was less rapid in 5 patients (at least 50 bpm slower) (41%); one patient had S-VT as rapid as before treatment (9%). The 12 patients were prescribed long-term Flecainide therapy. During follow-up there were 4 early (7, 10 and 15 days) and one late recurrence (16 months) (42% failure rate) whilst the other 7 patients had no further attacks of VT (follow-up of 19.1 +/- 5 months) (58% success rate).(ABSTRACT TRUNCATED AT 250 WORDS)

[Value of the esophageal approach in the diagnosis, treatment and therapeutic surveillance of arrhythmia in children]. / Intérêt de la voie oesophagienne dans le diagnostic, le traitement et la surveillance thérapeutique des troubles du rythme de l'enfant.

For the past few years, a new method for the investigation and treatment of arrhythmias has been used: transoesophageal atrial pacing and recording (TAPR). In the light of 6 cases observed recently, we review the technical aspects and the indications for TAPR. A bipolar stimulation catheter is inserted in the oesophagus and positioned in the area where the atrial wave of greater amplitude is recorded. Atrial stimulation is done with impulses of long duration obtained with a special stimulator. Two cases validated this technique which was effective to correct atrial flutter in a neonate with heart failure resistant to medical treatment as well as in a 5 year-old child. The value of TAPR as a diagnostic tool in cases of tachycardia is discussed in the context of 2 cases: a 5 week-old with wide QRS and a 14 month-old with narrow QRS. Finally, the value of TAPR for monitoring the efficacy of anti-arrhythmia medications is illustrated by 4 cases of supraventricular tachycardia, in whom the optimal dosage of the anti-arrhythmic drug used was determined with the help of TAPR-induced tachycardia. The current literature concerning the technique, indications and results of TAPR are reviewed. This method is likely to take a great importance for the study and treatment of supraventricular arrhythmias in children.

Late ventricular potentials and spontaneous and induced ventricular arrhythmias in dilated or hypertrophic cardiomyopathies. A prospective study about 83 patients.

In a series of 83 patients with dilated (DCM) (n = 56) or hypertrophic cardiomyopathies (HCM) (n = 27), were performed 24-hour-Holter monitorings, exercise stress testings, noninvasive recordings of late ventricular potentials (LVP), and programmed ventricular stimulations (PVS) (sinus rhythm and three cycles of stimulation, two extrastimuli, two right ventricle sites) (n = 53), in order to appreciate the frequency of ventricular premature depolarisations (VPDs), to correlate these results with myocardial vulnerability to TV induction, and to compare electrophysiologic and hemodynamic results. Holter monitoring showed that 80% of group A patients had VPDs (75% Lown's grade 3 or over) and 63% in group B (37% greater than or equal to grade 3). LVP were found in 15/56 DCM, and 2/27 HCM; in comparison with a control group of 32 normal subjects, the prevalence of LVP was only significant for DCM group. LVP were more frequent in cases of VPD's greater than or equal to Lown's grade 3 at Holter monitoring in DCM group, (33% versus 7% if VPDs less than or equal to Lown's grade 3) and HCM group (20% versus 0) but the correlation was not significant. Exercise stress testing, conducted only in group B, revealed about 20% of VPDs. PVS provoked ventricular arrhythmia (greater than 5 QRS) in 13 out of 33 cases in group A and in 2 out of 20 cases in group B. There was no significant correlation between the results of these methods of study and those of hemodynamic or echocardiographic explorations except for cardiac index in group A (lower when LVP were present, and VPDs greater than or equal to grade 3 during Holter) and end diastolic diameter (larger when PVS provoked fewer ventricular arrhythmias). In group B, PVS induced monomorphic VT in 2/3 patients with syncopes. Thus: (1) ventricular arrhythmias are frequent in cardiomyopathies but LVP had a significant prevalence only in dilated forms; (2) in DCM monomorphic induced VT reproduce spontaneous crisis, whereas in HCM it is possible to provoke VT in patients with syncopes but without this clinical arrhythmia; (3) in DCM as in HCM, ventricular arrhythmia can be independent from hemodynamic disorders.

[Pre- and postoperative study of arrhythmia in atrial septal defects (ostium secundum and sinus venosus)]. / Etude pré et postopératoire des troubles du rythme et de la conduction au cours de la communication interauriculaire (ostium secundum et sinus venosus).

An electrophysiological study was carried out pre- and postoperatively in 25 patients (children and adults) presenting with an atrial septal defect of the ostium secundum type (OSASD). The purposes of the study were to find out whether early electrophysiological abnormalities were present in children, to compare the results obtained in children and in adults and to evaluate the impact of surgery by comparing preoperative and late postoperative electrophysiological data. Patients were divided into two groups. Group I was composed of 11 children (mean age 8.18 +/- 1.03 years) with a mean pulmonary/systemic blood flow ratio of 2.33 +/- 0.24. Group II comprised 14 adults (mean age 36.79 +/- 4.89 years) with a mean pulmonary/systemic blood flow ratio of 3.42 +/- 0.24. Preoperatively, in group I 55 p. 100 of the patients (6/11) had sinus node dysfunction, 18 p. 100 (2/11) had disturbances of atrioventricular conduction, and none had atrial dysrhythmia. Preoperatively, in group II 43 p. 100 of the patients (6/14) had sinus node dysfunction, 36 p. 100 (5/14) had disturbances of atrioventricular conduction, and 36 p. 100 (5/14) had sustained atrial dysrhythmia (flutter or paroxysmal atrial fibrillation). The frequency of sustained atrial dysrhythmia correlated positively with the patient's age and with the presence of sinus node dysfunction. Following surgical closure of the atrial septal defect, the electrophysiological parameters were not significantly modified in both groups. This study confirmed the presence of early electrophysiological abnormalities of sinus node function and atrioventricular conduction in children with OSASD. The most significant finding in adults was the occurrence of atrial dysrhythmias in the oldest patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Isotope angiocardiographic study of 30 cases of ventricular tachycardia with Fourier phase analysis]. / Etude de 30 tachycardies ventriculaires par angiocardiographie isotopique avec analyse de phase de Fourier.

Twenty-seven patients (15 men, 12 women; mean age 48.9 years) suffering from ventricular tachycardia (VT) (n = 30) were studied by radionuclide angiocardiography with Fourier phase analysis, both in sinus rhythm and during tachycardia. VT was spontaneous, electrically inducible, sustained, haemodynamically stable and monomorphous, with a mean rate of 174 beats/min (range: 115-260 beats). Heart diseases responsible for VT were: non-obstructive cardiomyopathy (n = 7), hypertrophic cardiomyopathy (n = 1), ischaemic heart disease (n = 5), probable right ventricular arrhythmogenic dysplasia (n = 4), congenital left ventricular aneurysm (n = 2), sequela of myocarditis (n = 2) and aortic valve regurgitation (n = 1); no heart disease was detectable in 5 patients. On surface electrocardiogram there was good concordance between the initial radionuclide site of VT activation and the configuration and electrical axis of QRS. At Fourier phase analysis all 17 VT of the right lag type originated in the left ventricle, arising from the apical septum (n = 7) or lateral segment (n = 2) in case of left axis, from the basal segment (n = 6) or the lateral segment (n = 1) in case of vertical or right axis, and from the middle left septum (n = 1) in case of normal axis. Nine VT of the left lag type originated in the right ventricle, arising from the basal septum or the latero-basal region in case of vertical or right axis (n = 6), from the apical septum or the inferior-apical region in case of left axis (n = 2) and from the middle septum in case of normal axis (n = 1). Four of our patients (3 with coronary disease and 1 with congenital left ventricular aneurysm) had VT of the left lag type and an initial radionuclide site of activation in the middle part of the left septum in case of left axis (n = 2) and in the basal part of that septum in case of right axis (n = 2). Seven patients were operated upon for recurrent VT: 4 had intra-operative mapping which in every case confirmed the results of radionuclide angiocardiography, a method which in the other 3 patients was the only surgeon's guide. Correlations between the site of origin of VT at radionuclide mapping and kinetic abnormalities visualized at radiological angiography and gamma-ray angiocardiography were common in our study. In one of our patients the same lesion gave birth to 2 VT of different morphologies.(ABSTRACT TRUNCATED AT 400 WORDS)

[Limitations of scintigraphy using metaiodobenzylguanidine for locating pheochromocytomas. Apropos of 2 cases]. / Limites de la scintigraphie à la MIBG pour localiser les phéochromocytomes. A propos de deux cas.

Two cases of MIBG (metaiodobenzylguanidine) scintigraphy are reported: the first case concerns a female patient hospitalized for high blood pressure (HBP) with symptoms evocative of pheochromocytoma. Urinary titration of catecholamines metabolites, which are usually abnormally high, and tomodensitometry permit the visualization of a left adrenal tumor. On the contrary, the MIBG scintigraphy does not show any abnormal fixation. After resection, the pathological examination confirms the diagnosis of pheochromocytoma. The second case concerns a female patient hospitalized for HBP with, on the chest X-Ray, a left postero-inferior density. Serum and urinary catecholamine levels are normal. Tomodensitometry confirms the tumor of the posterior mediastinum and the MIBG scintigraphy demonstrates a focus of thoracic opposite the tumor. After resection, the pathological examination shows an ectopic supernumerary bronchial bud. These two cases illustrate the limitations of MIBG scintigraphy to locate pheochromocytomas. There are false negative (10%) which may be explained by an insufficient uptake of the tracer by the tumor, by an insufficient image formation or by medication interferences. On the contrary, there may be false positives because of histochemical similarities between the chromaffin tissues and certain glandular or neural tumors. Nevertheless, in spite of serious limitations, which we must be aware of, MIBG scintigraphy remains the best primary examination for the location of pheochromocytomas.

[Value of esophageal stimulation for decreasing auricular flutter]. / Intérêt de la stimulation cesophagienne pour la réduction du flutter auriculaire.

The purpose of this study was to evaluate the effectiveness of trans-esophageal atrial stimulation in decreasing atrial flutters. 31 patients, aged between 26 and 86 years, underwent 38 esophageal stimulations between August 1986 and April 1987. Esophageal stimulation was carried out with a device delivering major stimuli (10 to 20 ms) as well as high voltages (10 to 20 volts). A bipolar probe of permanent intracardiac stimulation was placed behind the left atrium, via a trans-esophageal approach under ECG guidance. Stimulations were carried out at a slightly faster rhythm than that of the atrial flutter, for 1 to 30 seconds with a progressive increase of the stimulation frequency (280 to 960 impulses/min) until either a sinus rhythm or an atrial fibrillation was obtained. A sinus rhythm was obtained immediately (21 times out of 38; 55.3%) and at the 24th hour after temporary atrial fibrillation in 8 additional patients (21%). The reduction percentage at 24 hours was therefore 76.3 p. cent. In 6 patients (15.8%), esophageal stimulation failed and in 3 additional patients, after atrial fibrillation, there was either relapse into flutter, or persistence of atrial fibrillation at the 24th hour. Esophageal stimulation was well tolerated in all cases. There were no local or rhythm complications. In conclusion, trans-esophageal atrial stimulation appears to be effective, easy to implement, economical and well tolerated. Its primary use to decrease atrial flutter seems justified, permitting to avoid in 75 p. cent of the time, recourse to intracardiac atrial stimulation or external shock.

[Cardiovascular involvement in acromegaly. Apropos of 3 cases]. / Atteinte cardiovasculaire au cours de l'acromégalie. A propos de trois cas.

The authors report 3 cases of acromegaly diagnosed while the patients were in hospital for cardiovascular disease: arterial hypertension in two and hypertrophic myocardiopathy in all three. Coronary arteriography was normal in the 3 patients. The exercise-induced dyspnoea observed in these 3 cases was unexplained by right and left cardiac catheterization results (normal pressures, normal or increased cardiac index). It was most probably related to the myocardial hypertrophy and to abnormalities in diastolic function demonstrated by radioisotopic methods in patients 2 and 3. The degree of myocardial hypertrophy present in these 3 patients seemed to correlate with the size of the pituitary adenoma and the plasma level of growth hormone rather than with the duration or degree of arterial hypertension. After excision of the pituitary adenoma hypertension persisted in 1 case, due to associated adrenal gland hyperplasia, and subsided in the other cases. Abnormalities of diastolic function and dyspnoea are gradually regressing but left ventricular hypertrophy has not significantly decreased after 6 post-operative months.

[Treatment of ventricular tachycardia with propafenone. Parallel study of ventricular provocation tests]. / Traitement des tachycardies ventriculaires par la propafénone. Etude "en parallèle " des tests de provocation ventriculaire.

Propafenone (P), a class IC antiarrhythmic drug, was tested intravenously and orally in the curative and preventive treatment of sustained (VTS) and non-sustained (VTNS) ventricular tachycardia. The 16 patients involved included 11 men and 5 women of mean age 49 years. They all had heart disease: ischaemia in 3, right ventricular arrhythmogenic dysplasia in 6, dilated myocardiopathy in 5 and left ventricular aneurysm in 2. Intravenous P in doses of 1.5 mg/kg controlled VT within 2 or 3 minutes on average in 9 out of 12 patients. Following the injection VT could not be reinduced in 2 out of 10 patients; other inductions were harder to obtain or resulted in VTNS instead of VTS (n = 3), or remained unchanged (n = 5). When P was administered orally (mean dose 900 mg) to 14 patients reinduction of VT was no longer possible in 2 cases, more difficult in 1 case, remained unchanged in 7 cases and was easier in 4 cases. Long-term oral therapy at the same dosage level prevented recurrences of VT in 7 out of 14 patients; the drug was discontinued in 2 patients owing to its arrhythmogenic effect on induced VT. The patients were followed up for 5 to 36 months (mean: 16.4 +/- 11.7 months). In this trial the results of long-term treatment could not be predicted from Holter recordings or measurements of plasma levels.(ABSTRACT TRUNCATED AT 250 WORDS)