Polymer-based or polymer-free stents in patients at high bleeding risk

BACKGROUND Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited. METHODS In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus­coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority. RESULTS A total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drugcoated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P=0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P=0.007 for noninferiority). CONCLUSIONS Among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.). (AU)

Elective coronary stent implantation in cardiogenic shock complicating acute myocardial infarction: in-hospital and six-month clinical and angiographic results.

Effective treatment of patients with acute myocardial infarction and cardiogenic shock depends on restoring persistent patency of the infarct-related artery. Coronary stenting, reducing abrupt or delayed closure related to dissection and suboptimal result, may improve PTCA results in cardiogenic shock. Eighteen patients (14 males and 4 females, mean age 59 +/- 7 years), referred to catheterization laboratory for acute myocardial infarction and shock, had elective stent implantation during 14 primary and 4 rescue PTCA. Time delay between shock onset and PTCA was 4.1 +/- 3 hr (range, 30 min to 12 hr). The IRA was LAD in seven patients (38%), LCx in two (11%), and RCA in eight (45%). One patient (5.%) had distal LMCA occlusion. Stent deployment was successful in 100% of patients and resulted in TIMI 3 flow in 13 (72%) patients. In 13 (72%) cases, cardiogenic shock gradually resolved and the patients were discharged alive. Five patients (28%) died because of irreversible hemodynamic deterioration without evidence of reinfarction. At 6-month follow-up, all the discharged patients were alive and no patient had reinfarction or recurrent angina. Heart transplant was required in one patient 5 months after stenting because of refractory congestive heart failure. Angiography demonstrated patency of all the coronary arteries treated, with TIMI 3 flow in all patients. Stent restenosis rate was 30%, and target lesion revascularization with CABG or re-PTCA was not required in any case. LV function improved from 39% +/- 15% to 51% +/- 15% (P < 0.01). Elective coronary stenting is an effective treatment for acute myocardial infarction complicated by cardiogenic shock and may improve acute and long-term survival.

Use of a new diagnostic catheter for transradial internal mammary artery angiography early after minimally invasive coronary bypass.

We describe a new diagnostic catheter specifically designed for selective catheterization of the left internal mammary artery via the ipsilateral radial approach. We used this catheter to assess the patency of the distal mammary-left anterior descending coronary artery anastomosis in 30 consecutive patients early after minimally invasive direct coronary artery bypass grafting. The new catheter design allowed easy and fast engagement of the left internal mammary artery leading to optimal vessel opacification in all cases. Angiography revealed graft problems in seven (23.3%) patients, two of whom required anastomosis revision, surgical in one case and with PTCA in the other. No LIMA injury occurred as a result of selective catheterization. Patients with functionally normal anastomosis were discharged on the same day of the diagnostic procedure.

Clinical and angiographic outcome after coronary arterial stenting with the carbostent.

The Carbostent is a new balloon-expandable, stainless steel, tubular stent with innovative multicellular design and unique turbastratic carbon coating (Carbofilm). This open nonrandomized 2-center study assesses the immediate and long-term clinical and angiographic outcomes after Carbostent implantation in patients with native coronary artery disease. The Carbostent was implanted in 112 patients with 132 de novo lesions. Most patients (55%) had unstable angina, and 38% of lesions were type B2-C. The mean lesion length was 12.5 +/- 7.0 mm, and 29% of lesions were > 15 mm in length. No stent deployment failure occurred, as well as acute or sub-acute stent thrombosis. The 6-month event-free survival was 84 +/- 4%. One patient with a stented right coronary artery and no restenosis at the angiographic follow-up died after 6 months of fatal infarction due to abrupt closure of a nontarget vessel. In-hospital non-Q-wave myocardial infarction occurred in 1 patient, and 11 patients had repeat target lesion revascularization (target lesion revascularization rate 10%). The 6-month angiographic follow-up was obtained in 108 patients (96%) (127 lesions). Angiographic restenosis rate was 11%. The loss index was 0.29 +/- 0.28. The results of this study indicate a potential benefit of Carbostent for the prevention of stent thrombosis and restenosis in these relatively high-risk patients. A larger trial is being planned to confirm these promising results.

Successful stent delivery with deep seating of 6 French guiding catheters in difficult coronary anatomy.

Despite improvements in coronary stent design, delivery difficulties may still be encountered. Between April 1996 and September 1998, 945 patients underwent coronary stenting in our Institute. New 6 Fr Long Brite Tip (LBT) guiding catheters, allowing deep coronary artery intubation and increased backup support, were used in 25 (2.6%) of these patients presenting complex coronary anatomy and poor stent accessibility, electively in 3 (12%) and after stent delivery failure with multiple (2.1 +/- 1.2) standard guiding catheters in 22 (88%). Deep coronary artery intubation (>/= 20 mm) was successfully performed in 22 (88%) patients and was associated with adequate pressure recording and contrast opacification without blood flow compromise. Ten (22.7%) Palmaz-Schatz stents and 34 (77.3%) second-generation stents of various lengths were successfully delivered to different coronary vessels (RCA = 15, LAD = 9, LCx = 1) in all patients in whom deep coronary intubation was obtained. These data demonstrate that deep coronary artery cannulation with LBT catheters is feasible and safe and may markedly increase the rate of stent delivery success in very complex coronary anatomy and when standard guiding catheters have failed.

Emergency stenting of totally occluded left main coronary artery in acute myocardial infarction.

We report a case of emergency stenting for acute occlusion of the left main coronary artery in the setting of acute myocardial infarction. Although stent implantation allowed prompt revascularization and successful immediate management of this life-threatening condition, subacute stent thrombosis occurred, requiring re-PTCA followed by surgical revascularization. This case suggests that stenting of an acutely occluded left main coronary artery may be a life-saving procedure but should only be used as a bridge to surgery rather than a definitive treatment modality.

[Implantation of the Palmaz-Schatz stent in coronary vessels irrigating and non-irrigating necrotic myocardial areas: comparison of acute results and at mid-term]. / Impianto di stent di Palmaz-Schatz in vasi coronarici tributari e non tributari di aree miocardiche necrotiche: confronto dei risultati acuti e a medio termine.

Recent evidence suggests that higher restenosis rate is observed after coronary angioplasty of an infarct-related artery. Furthermore, angiographic restenosis seems associated with a deterioration of left ventricular function at follow-up. The aim of this study was to assess the acute results and angiographic restenosis following coronary artery stenting of infarct-related (Group 1) and non infarct-related coronary arteries (Group 2). We retrospectively analyzed the results of 381 consecutive patients treated with Palmaz-Schatz coronary stent implantation between May 1992 and January 1996. Stenting of the infarct-related artery was performed in 154 patients (Group 1), while 227 patients (Group 2) received stenting of the non infarct-related artery. Both groups had similar age, gender, clinical conditions and coronary angiographic pattern. There were no significant differences between groups, concerning type of stented coronary vessel (left anterior descending-LAD 52.4% vs non-LAD 47.6%, Group 1, LAD 59.5% vs non-LAD 40.5%, Group 2) and number of stents per patient (1.31 +/- 0.48 in Group 1, 1.18 +/- 0.56 in Group 2) and per coronary vessel (1.17 +/- 0.54 in Group 1, 1.09 +/- 0.46 in Group 2). The procedure was performed using similar maximal inflation pressures in both groups (13.3 +/- 2.9 atm in Group 1, 13.40 +/- 3.17 atm in Group 2). Technical success was achieved in 96.8% of Group 1 and in 96% of Group 2 patients. Acute coronary stenting success and major adverse events (acute myocardial infarction, emergency bypass, death) were similar in both groups of patients. No difference was found in restenosis rate at 6-month angiographic follow-up (Group 1 = 29.8%, Group 2 = 27%). In conclusion, this study indicates that stenting of infarct and non infarct-related coronary arteries has similar success and 6-month restenosis rates.

Local heparin delivery prior to coronary stent implantation: acute and six-month clinical and angiographic results.

Stents increase smooth muscle cell proliferation, which may also lead to in-stent restenosis. A local delivery strategy provides higher drug concentration at the angioplasty site and may limit the proliferative response following stenting. Local heparin delivery was attempted in 35 patients following balloon angioplasty using an "over-the-balloon" style catheter (infusion sleeve). The infusion sleeve was successfully tracked and heparin was delivered in 33 (94%) patients. Heparin (1,000 IU/ml) was delivered under low (45 psi, 2 ml, n = 4), intermediate (75 psi, 4 ml, n = 11), and high (100 psi, 4 ml, n = 18) proximal infusion pressures. Stent placement was successful in all cases. Acute and in-hospital complications were a severe arterial spasm after heparin delivery, a non Q-wave myocardial infarction, and two vascular complications. Ten dissections were observed after PTCA and prior to heparin delivery. Of these dissections, 7 remained unchanged, 2 worsened, and 1 improved with local delivery. When heparin was delivered in the absence of dissection, no new dissections were observed. Of the 33 patients who received heparin, 30 (91%) had no symptoms and a negative exercise test at clinical follow-up. QCA analysis of 6-month follow-up angiograms, performed in 32 of 33 (97%) patients, demonstrated an acute gain of 1.98 +/- 0.67 mm, a late loss of 0.94 +/- 0.78 mm, a net gain of 1.04 +/- 0.78 mm, and a loss index of 0.48 +/- 0.32. Restenosis (> or = 50% stenosis) was observed in 4 of 32 (12%) patients. Local delivery of heparin via the infusion sleeve following PTCA and prior to stent deployment is feasible with an acceptable safety profile and a low clinical and angiographic restenosis rate at 6 months.

Changes in right ventricular filling dynamics during left anterior descending, left circumflex and right coronary artery balloon occlusion.

AIM: Transient coronary artery occlusion during percutaneous transluminal coronary angioplasty may cause left ventricular diastolic dysfunction. The aim of this study was to evaluate the effect of left anterior descending, left circumflex and right coronary artery balloon occlusion on right ventricular diastolic function. METHODS: Thirty-five patients with single-vessel coronary artery disease and no previous myocardial infarction were selected. Left and right ventricular filling pressures were monitored by Doppler echocardiography and haemodynamic monitoring. This was performed during and immediately after 60 s of coronary balloon occlusion of the left anterior descending artery in 21 cases (Group 1), the left circumflex artery in eight cases (Group 2) and the right coronary artery in six cases (Group 3). Doppler analysis of left and right ventricular filling included peak velocity of early (PFVE) and late ventricular filling (PFVA) and PFVE to PFVA ratio (PFVE/PFVA). RESULTS: In all three groups, balloon inflation induced a significant increase in left and right filling pressures (P < 0.05). No qualitative difference in haemodynamic changes was found between groups during inflation. Significant impairment in the Doppler pattern of left and right ventricular filling occurred after 20 s of coronary occlusion: PFVE values in mitral and tricuspid valves decreased by 14% and 25% in Group 1, 13% and 25% in Group 2, and 10% and 21% in Group 3, respectively, as PFVA remained unchanged in all groups, the PFVE/PFVA ratio of mitral and tricuspid valve flows significantly decreased (Group 1: -12% and -20%, Group 2: -10% and -21%, Group 3: -14% and -21%, respectively). All parameters returned to baseline within 30 s after each balloon deflation. CONCLUSION: Our data suggest that brief episodes of acute myocardial ischaemia, such as those induced by 60 s of coronary artery occlusion during percutaneous transluminal coronary angioplasty, elicit simultaneous diastolic dysfunction of both ventricles, independent of the coronary artery involved.

Treatment of ostial lesions of the left anterior descending coronary artery with Palmaz-Schatz coronary stent.

We evaluated acute and long-term clinical and angiographic results of elective Palmaz-Schatz coronary stent implantation for left anterior descending coronary artery (LAD) ostial stenosis in 23 consecutive patients. Eight patients had stable angina, 14 had unstable angina, and 1 had recent myocardial infarction. Sixteen patients had single-vessel, 5 had double-vessel, and 2 had triple-vessel disease. Clinical success without major complications (death, acute myocardial infarction, emergency coronary artery bypass grafting) was obtained in all cases and technical success in 20 cases (86.9%). After stenting, minimal lumen diameter increased from 1.05 +/- 0.45 mm to 2.89 +/- 0.52 mm (p < 0.001), and percent diameter stenosis decreased from 65.49% +/- 13.36% to 2.94% +/- 19.93% (p < 0.001). One case of subacute thrombosis and no major bleeding occurred. Twenty patients were followed-up for 6 months, during which no acute cardiac event (death, acute myocardial infarction) was observed. Eighteen patients were eligible for follow-up coronary angiography; restenosis (> or = 50% diameter stenosis) was observed in 4 (22.2%). Minimal lumen diameter was 1.77 +/- 0.55 mm, percent diameter stenosis was 39.66% +/- 17.62%, late loss was 1.01 +/- 0.69 mm, net gain was 0.79 +/- 0.55 mm, and loss index (late loss/acute gain) was 0.53 +/- 0.37. This study suggests that elective Palmaz-Schatz stent implantation may be a safe and successful treatment of LAD ostial lesions and provides a large increase in lumen diameter.

Prompt and safe femoral hemostasis with a collagen device after intracoronary implantation of Palmaz-Schatz stents.

We report the safety and efficacy of sealing the femoral puncture site with percutaneously applied collagen after Palmaz-Schatz stent implantation in 100 consecutive patients. Patients were anticoagulated with continuous heparin infusion, overlapping oral anticoagulants, and antiplatelet therapy by dextran, aspirin, and dipyridamole. At the time of sheath removal and collagen application, the mean activated partial thromboplastin time and prothrombin time values expressed as international normalized ratio were 3.2 +/- 2.1 and 1.6 +/- 0.7, respectively. The hemostasis time ranged from 1 to 8 minutes (mean 2.18 +/- 2.08 minutes). Only two (2%) patients had major puncture-site bleeding (not seal related in one case) that required surgery and blood transfusions. Small (< 6 cm) and medium (6 to 10 cm) hematomas observed in 12 (12%) and 2 (2%) patients, respectively, resolved spontaneously without sequelae. Local infection developed in 2 (2%) patients, who were successfully treated with antibiotics without clinical consequences. Subacute stent thrombosis was observed in only 1 (1%) patient. Repeat catheterization through the same femoral artery was performed at 6-month follow-up in 55 patients without difficulty or vascular complications. These findings suggest that percutaneous collagen application after coronary stenting is a secure method of achieving prompt and effective femoral hemostasis with a low incidence of major vascular bleeding complications despite intense anticoagulation. Stable hemostasis may allow continued full-dose anticoagulation, reducing the risk of stent subacute thrombosis.

Successful transcatheter management of Palmaz Stent embolization after superior vena cava stenting.

A 34-year-old patient with benign superior vena cava syndrome (SVCS) was treated with thrombolytic therapy, balloon angioplasty, and placement of two peripheral Palmaz stents. Embolization of one stent to the right atrium occurred 10 min after successful implantation. This serious complication was successfully managed by percutaneous transcatheter technique with retrieval from the right atrium and subsequent deployment into the right external iliac vein of the lost stent. Complete resolution of SVCS symptoms occurred within 24 hr and moderate superior vena cava restenosis was successfully dilated 8 months later. At 12-month follow-up the patient continues to be asymptomatic.

[Percutaneous administration of collagen (VasoSeal): an efficacious system of hemostasis after catheterization or interventional procedures using arterial approach]. / Applicazione percutanea di collagene (vasoseal): un'efficace sistema di emostasi dopo cateterismo o procedure interventistiche per via arteriosa.

INTRODUCTION: The widespread use of PTCA and complex percutaneous interventional techniques has significantly increased peripheral vascular complications prompting the development of innovative hemostatic closure devices. METHODS: To evaluate the efficacy and safety of a bovine collagen plug (VasoSeal), we sealed 362 consecutive femoral artery puncture sites in 324 patients (240 males) (mean age 57.9 +/- 11.3 years), who underwent interventional procedures or diagnostic catheterization during acute or chronic anticoagulant treatment. RESULTS: Complete hemostasis was achieved in 2.31 +/- 1.97 minutes in 342 cases (94.4%), with a mean activated clotting time at collagen deployment of 197 +/- 56". In 20 cases, mechanical arterial compression was needed in order to obtain vascular hemostasis (mean time: 44 +/- 13 min). We observed 1 arteriovenous fistula and 1 acute arterial thrombosis (collagen related at surgical inspection) which underwent successful surgical treatment. Minor complications without clinical sequelae were: small hematomas in 13 cases (3.8%), 4 groin abscesses (1.1%) and 4 cases of lymphangitis (1.1%). CONCLUSIONS: Percutaneous collagen application at the femoral artery puncture site allows quick and effective hemostasis with low incidence of peripheral vascular complications following interventional percutaneous procedures or catheterization during anticoagulant treatment.

[Intravenous ultrasonography as a method for imaging the morphoanatomical effects of coronary angioplasty]. / L'ultrasonografia intravascolare quale metodica di indagine degli effetti morfoanatomici dell'angioplastica coronarica.

Despite the therapeutic success of percutaneous transluminal coronary angioplasty (PTCA), the mechanisms by which PTCA increase vessel luminal size remain uncertain. To better understand the transmural morphologic changes associated with PTCA of stenosed coronary arteries, we studied with a high-frequency intravascular ultrasound catheter 18 coronary artery segments in 18 patients following balloon angioplasty. High-quality cross-sectional images were obtained from 15 coronary sites without complications in all patients. Two distinctive morphologic features following balloon angioplasty were appreciated by intravascular ultrasound imaging. The first pattern, observed in 10 cases (67%), consisted of a stretched plaque without any evidence of dissection. The second pattern, found in 5 cases (33%), demonstrated a dissection of the plaque ranging from a radial tear with separation of the 2 ends of the plaque to an extensive dissection which, in 1 case, encompassed the entire circumference of the artery. Although angiography showed a good post-angioplasty result in all cases, intravascular ultrasound evidenced a large amount of residual atheroma occupying the artery cross-sectional area. In addition, this imaging modality revealed more often than angiography the presence of calcification and dissection. These data demonstrate that PTCA creates different morphologic patterns which are related to the mechanisms of lumen enlargement and that the coronary artery anatomy after dilatation is much more complex than that observed with angiography. This study confirms that intravascular ultrasound is a feasible and safe imaging modality which provides new valuable insight into the mechanisms by which angioplasty improves vessel patency.

Coronary adrenergic hyperreactivity in patients with syndrome X and abnormal electrocardiogram at rest.

Syndrome X is characterized by an abnormal vasomotility of coronary microvessels. It is unknown whether the presence of an ischemic-like pattern in the electrocardiogram at rest (T-wave inversion) reflects a more severe vasomotion disturbance. Changes in coronary sinus flow (thermodilution) and epicardial vessel diameter (quantitative angiography) during adrenergic activation were measured with a standard cold pressor test in patients with syndrome X whose electrocardiogram at rest was normal (group 1: 17 patients) or showed stable, symmetrically inverted T waves (group 2: 22 patients). Cold pressor test increased mean blood pressure and rate-pressure product to a similar extent in both groups, increased coronary sinus flow in group 1 (88 +/- 29 to 119 +/- 36 ml/min; p less than 0.05) and not in group 2 (109 +/- 37 vs 104 +/- 36 ml/min; p = not significant), and decreased coronary resistance in group 1 (1.38 +/- 0.42 to 1.19 +/- 0.38 mm Hg/ml/min; p less than 0.05) and augmented it in group 2 (1.06 +/- 0.32 to 1.28 +/- 0.43 mm Hg/ml/min; p less than 0.02). During cold stimulus, the proximal and middle segments of epicardial arteries showed negligible changes in their lumen, whereas the distal segment dilated in group 1 (1.81 +/- 0.27 to 2.01 +/- 0.32 mm; p less than 0.05) and constricted in group 2 (1.82 +/- 0.12 to 1.62 +/- 0.20 mm; p less than 0.05). Differences in coronary hemodynamic and angiographic responses between the groups were statistically significant (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiographic evolution of coronary atherosclerosis in patients receiving propranolol. A two-year follow-up.

STUDY OBJECTIVE: To test whether propranolol may influence the progression of coronary atherosclerosis. DESIGN: Repeat coronary angiography after two year treatment and evaluation of changes in coronary narrowings. SETTING: Subjects with effort angina of recent onset requiring coronary angiography and medical treatment. PATIENTS: 80 untreated patients, with a greater than or equal to 50 percent focal narrowing on a major coronary branch associated or not with a less than 50 percent stenosis of other major branches. They were randomized to isosorbide dinitrate (40 mg bid) (group 1, control group) or to propranolol (80 mg qid) (group 2, treatment group). RESULTS: At restudy, there were more diseased vessels and These narrowings per patient in both groups. Multivessel involvement and greater than or equal to 50 percent obstructions were also augmented. These changes were not statistically significant. Patients with progression of the stenotic tracts (both greater than or equal to 50 percent and less than 50 percent were 19 (48 percent) in group 1 and 28 (70 percent) in group 2 (p less than 0.05). Narrowings with progression were 25 in group 1 and 48 in group 2. Thirteen narrowings in group 1 and 15 in group 2 were newly detected at restudy. Eighteen patients (45 percent) in group 1 and nine (23 percent) in group 2 had a steady disease. Smoking, high blood pressure, family history of coronary disease, blood glucose values and lipid levels were considered; the only significant group differences were 31 percent rise of total triglyceride and 23 percent decrease of HDL cholesterol in patients who were treated with propranolol. CONCLUSIONS: Propranolol showed an adverse influence on coronary atherosclerosis, regarding the evolution of both greater than or equal to 50 percent and less than 50 percent narrowings and not the formation of new stenoses. Changes in serum lipid values might have a role.

Coronary angiographic patterns in hypertensive compared with normotensive patients.

Patients in this study were assessed by coronary angiography because of classic effort angina and a positive exercise test. Of these patients, 320 had untreated primary hypertension and 320, similar in age and gender distribution, were normotensive. In all patients coronary angiography documented that at least one major epicardial branch was restricted by 50% or more. Prevalence of single- and double-vessel disease in the fourth and fifth decades of life was similar in the two populations and in both tended to decline with age. Prevalence of triple-vessel disease was also similar in the two populations in the fourth and fifth decades; in either population it rose with age and reached a peak at the seventh decade of life. The percentages of hypertensive patients in the sixth and seventh decades with triple-vessel disease was significantly (p less than 0.01) greater (40% and 50%, respectively) than the corresponding values in normotensive individuals (25% and 31%, respectively). The left main coronary artery was not significantly more involved in the high blood pressure group. Pressure was moderately and similarly raised at any age in hypertension; serum cholesterol and triglyceride levels, blood glucose, and smoking habits were comparable in the two populations. These results suggest that hypertension does not accelerate the appearance of significant coronary narrowing or multiple vessel involvement. Starting from the sixth decade, the natural age-related evolution of coronary disease seems to be aggravated in hypertensive subjects, as reflected by an augmented number of diseased vessels. This process is probably related to high blood pressure in itself; whether the severity of hypertension might also exert an influence is not deducible from this study.(ABSTRACT TRUNCATED AT 250 WORDS)