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Biomedical subjects

P Hanrath

Publications and source records attributed to P Hanrath.

At least 55 records · Page 3Linked to original sources
PubMed2001

The 4G/5G promotor polymorphism of the plasminogen activator inhibitor-1 gene and late lumen loss after coronary stent placement in smoking and nonsmoking patients.

BACKGROUND: Instent restenosis remains a significant clinical problem. Identification of patients at risk for instent restenosis may allow selection of individualized appropriate therapeutic approaches. Genetic polymorphisms have been suggested to be associated with the risk of instent restenosis. Smoking is known to influence hemostatic parameters. HYPOTHESIS: This study investigated the influence of the 4G/5G promotor polymorphism of the plasminogen activator inhibitor type I (PAI-1) gene on instent restenosis in smoking and nonsmoking patients. METHODS: In all, 300 consecutive patients (133 nonsmoking; 167 smoking) with elective coronary stent placement and 6-month angiographic follow-up were studied. Quantitative coronary angiography and genotyping with polymerase chain reaction analysis were performed in all patients. RESULTS: Nonsmoking PAI-1 4G/4G carriers showed a significantly greater late lumen loss (n = 38; 0.54 +/- 0.53 mm) compared with nonsmoking PAI-1 4G/5G (n = 68; 0.38 +/- 0.45 mm) or 5G/5G (n = 27; 0.19 +/- 0.23 mm) carriers, analysis of variance (ANOVA) p < 0.001. Smoking patients with the genotypes 4G/4G (n = 46; 0.53 +/- 0.54 mm) and 4G/5G (n = 79; 0.37 +/- 0.41 mm) had a late loss similar to that of nonsmoking patients. Smoking 5G/5G carriers had the highest late loss of all smoking patients (n = 42; 0.63 +/- 0.50); ANOVA p < 0.05; nonsmoking 5G/5G vs. smoking 5G/5G p < 0.001. CONCLUSION: The promotor polymorphism of the PAI-1 gene has a significant influence on instent restenosis after coronary stent implantation. The 5G/5G genotype predisposes nonsmoking gene carriers to less late lumen loss, whereas in smoking gene carriers this genotype is associated with the greatest late lumen loss. This might be explained by an altered expression pattern of hemostatic parameters.

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PubMed2001

Fragmentation of massive pulmonary embolism by pigtail rotation catheter: possible complication.

Fragmentation by pigtail rotation catheter may be a therapeutic option in acute massive pulmonary embolism, especially in patients with high risk of right ventricular failure. We report a patient with an occlusion of the right intermediate pulmonary artery by a large embolus, slightly protruding into the perfused right upper lobe artery. After initial catheter fragmentation, part of the embolus dislocated and produced an additional occlusion of the upper lobe artery. Hemodynamic parameters deteriorated. Continuation of catheter fragmentation finally provided for a hemodynamic stabilization and partial recanalization. Inadvertent occlusion of a major pulmonary arterial branch by dislocated embolus material may be considered as a complication of catheter fragmentation, which can be successfully managed by continuation of the fragmentation therapy.

Adult↗
PubMed2001

[Onset, stability and electrogram width criteria: efficacy and safety in the detection of supraventricular tachycardia in implantable cardioverter-defibrillators].

Inadequate therapies for supraventricular tachycardia (SVT) by implanted cardioverter defibrillators (ICD) are potentially arrhythmogenic and impair the patient's quality of life. Inadequate detection (ID) of SVT can be reduced by using detection enhancements like the onset- and stability criteria (O + S) or the electrogram width criterion (EGW). 103 patients (85 male, 18 female, mean age 65 +/- 9 years, mean ejection fraction 40 +/- 16%) were initially randomized to O + S active (Onset 12/89%, Stability 30 ms) or O + S inactive in the lowest detection zone. Cross-over between O + S active and O + S inactive occurred every 3 months. In 40 patients (39%) with ICD capable of EGW, this feature was programmed to passive. The number of ID was referred to 1 year of follow-up. During the follow-up period (485 +/- 226 d), 31 patients (32%) developed SVT in the lowest detection zone, 11 patients (11%) ventricular tachycardia (VT) and 14 patients (14%) both. In total, 387 SVT and 127 VT were observed. The mean number of ID was 10.7 +/- 4.8 ID/year with inactive O + S, and was significantly reduced to 1.1 +/- 0.3 ID/year when O + S were active (p < 0.0001). During the whole study period no delayed or inhibited adequate therapy for VT due to O + S was observed. During follow-up using EGW (n = 40), when O + S were inactivated, resulted in a significant reduction from 19.8 +/- 11.6 to 0.5 +/- 0.2 ID/year (p = 0.007). Even while O + S were active EGW would further reduce ID from 1.2 +/- 0.5 to 0.2 +/- 0.1 ID/year (p = 0.028). However, 2 adequate therapies of VT in 2 patients would have been suppressed if EGW had been activated. This results in a sensitivity of 98% and a specificity of 93% when O + S were inactive and respectively 95 and 79% when O + S were active. The empirical programming of O + S is therefore a safe method for the reduction of ID in patients with ICD. Using EGW leads to further reduction of ID but may lead to underdetection in individual cases.

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PubMed2001

[Treatment of stent restenosis using rotational atherectomy: mechanisms and results].

Restenosis after coronary stent implantation remains one of the major limitations of this treatment modality. At present, redilatation is considered the therapeutic option of choice for focal lesions; however, long restenotic lesions (> 10 mm) do not respond favourably. Despite the emerging concept of intracoronary radiation, encouraging acute procedural results are also reported for different debulking techniques (excimer laser angioplasty, directional coronary atherectomy, and rotational atherectomy, or rotablation). Rotablation has been studied most extensively with acute and long-term results published in a total of 500 patients. Experimental and first clinical data indicate favourable results for the rotablator as compared to balloon angioplasty alone for the treatment of in-stent restenosis. Data from the first two randomised clinical trials (ROSTER and A.R.T.I.S.T. trials) have now been published in abstract form, with conflicting results: whereas the monocenter ROSTER trial suggests a clinical benefit to patients treated by the rotablator, the multicenter A.R.T.I.S.T. trial including nearly 300 patients could not prove a benefit for the rotablator as compared to re-dilatation in patients with diffuse stent restenosis. Currently, rotablation for the treatment of restenosis can not be considered as the first line treatment modality in patients with stent restenosis. As a result of unsatisfying angiographic and clinical long-term results by the use of a variety of treatment modalities in diffuse stent restenosis, prevention of this iatrogenic entity will become mandatory.

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PubMed2001

Myocardial viability assessment by endocardial electroanatomic mapping: comparison with metabolic imaging and functional recovery after coronary revascularization.

OBJECTIVES: The objective of this study was to compare electroanatomic mapping for the assessment of myocardial viability with nuclear metabolic imaging using positron emission computed tomography (PET) and with data on functional recovery after successful myocardial revascularization. BACKGROUND: Animal experiments and first clinical studies suggested that electroanatomic endocardial mapping identifies the presence and absence of myocardial viability. METHODS: Forty-six patients with prior (> or =2 weeks) myocardial infarction underwent fluorine-18 fluorodeoxyglucose (FDG) PET and Tc-99m sestamibi single-photon emission computed tomography (SPECT) before mapping and percutaneous coronary revascularization. The left ventricular endocardium was mapped and divided into 12 regions, which were assigned to corresponding nuclear regions. Functional recovery using the centerline method was assessed in 25 patients with a follow-up angiography. RESULTS: Regional unipolar electrogram amplitude was 11.0 mV +/- 3.6 mV in regions with normal perfusion, 9.0 mV +/- 2.8 mV in regions with reduced perfusion and preserved FDG-uptake and 6.5 mV +/- 2.6 mV in scar regions (p < 0.001 for all comparisons). At a threshold amplitude of 7.5 mV, the sensitivity and specificity for detecting viable (by PET/SPECT) myocardium were 77% and 75%, respectively. In infarct areas with electrogram amplitudes >7.5 mV, improvement of regional wall motion (RWM) from -2.4 SD/chord +/- 1.0 SD/chord to -1.5 SD/chord +/- 1.1 SD/chord (p < 0.01) was observed, whereas, in infarct areas with amplitudes <7.5 mV, RWM remained unchanged at follow-up (-2.3 SD/chord +/- 0.7 SD/chord to -2.4 SD/chord +/- 0.7 SD/chord). CONCLUSIONS: These data suggest that the regional unipolar electrogram amplitude is a marker for myocardial viability and that electroanatomic mapping can be used for viability assessment in the catheterization laboratory.

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PubMed2001

Differential effects of atropine and isoproterenol on inducibility of atrioventricular nodal reentrant tachycardia.

BACKGROUND: Radiofrequency ablation of the "slow pathway" in atrioventricular nodal reentrant tachycardia (AVNRT) relies on tachycardia non-inducibility after ablation as success criterion. However, AVNRT is frequently non-inducible at baseline. Thus, autonomic enhancement using either atropine or isoproterenol is frequently used for arrhythmia induction before ablation. METHODS: 80 patients (57 women, 23 men, age 50+/-14 years) undergoing slow pathway ablation for recurrent AVNRT were randomized to receive either 0.01 mg/kg atropine or 0.5-1.0 microg/kg/min isoproterenol before ablation after baseline assessment of AV conduction. The effects of either drug on ante- and retrograde conduction was assessed by measuring sinus cycle length, PR and AH interval, antegrade and retrograde Wenckebach cycle length (WBCL), antegrade effective refractory period (ERP) of slow and fast pathway and maximal stimulus-to-H interval during slow and fast pathway conduction. RESULTS: Inducibility of AVNRT at baseline was not different between patients randomized to atropine (73%) and isoproterenol (58%) but was reduced after atropine (45%) compared to isoproterenol (93%, P<0.001). Of the 28 patients non-inducible at baseline isoproterenol rendered AVNRT inducible in 21, atropine in 4 patients. Dual AV nodal pathway physiology was present in 88% before and 50% after atropine compared to 83% before and 73% after isoproterenol. Whereas both drugs exerted similar effects on ante- and retrograde fast pathway conduction maximal SH interval during slow pathway conduction was significantly shorter after isoproterenol (300+/-48 ms vs. 374+/-113 ms, P=0.012). CONCLUSION: Isoproterenol yields higher AVNRT inducibility than atropine in patients non-inducible at baseline. This may be caused by a more pronounced effect on antegrade slow pathway conduction.

Adult↗
PubMed2001

The vitamin D receptor gene variant is associated with the prevalence of type 2 diabetes mellitus and coronary artery disease.

AIMS: Vitamin D can influence lipolysis and insulin secretion. A common genetic polymorphism of the vitamin D receptor, which has been found to be associated with bone mineral density, has also been reported to be associated with insulin-dependent diabetes mellitus. To test the influence of the vitamin D receptor polymorphism on the prevalence of Type 2 diabetes mellitus and coronary artery disease we studied a population of high-risk patients, who were referred to our clinic for diagnostic coronary angiography. METHODS: A total of 293 patients considered at high risk for coronary artery disease because of angina pectoris and known hypercholesterolaemia underwent diagnostic coronary angiography. The BsmI vitamin D receptor polymorphism was analysed by polymerase chain reaction. RESULTS: Prevalence of Type 2 diabetes mellitus and coronary artery disease was gradually dependent on the number of B alleles (BB 28%, Bb 13%, bb 8% for Type 2 diabetes mellitus, P = 0.002; BB 88% Bb 72%, bb 66% coronary artery disease, P = 0.01). Patients with the BB genotype had an odds ratio of 3.64 (95% confidence interval 1.53-8.55, P = 0.002) to have Type 2 diabetes mellitus compared with patients with the bb genotype. CONCLUSIONS: The genotype of the vitamin D receptor polymorphism determines the prevalence of Type 2 diabetes mellitus and coronary artery disease in a high-risk cohort population.

Coronary Angiography↗
PubMed2001

Verapamil prevents stretch-induced shortening of atrial effective refractory period in langendorff-perfused rabbit heart.

INTRODUCTION: Atrial dilation and rapid pacing reduce atrial effective refractory periods (AERPs), thereby increasing the susceptibility to sustained atrial fibrillation (AF) in Langendorff-perfused rabbit hearts. It is unclear whether similar pathophysiologic mechanisms are operative in short-term electrophysiologic changes caused by dilation and rapid pacing. Therefore, we analyzed whether both forms of short-term electrophysiologic changes are similarly affected by pharmacologic interventions acting on different potential mechanisms underlying these changes. METHODS AND RESULTS: Thirty Langendorff-perfused rabbit hearts underwent a protocol with stepwise increase of intra-atrial pressure from 0 to 12 cm H2O followed by 10 minutes of rapid pacing at 4 cm H2O. The protocol was repeated after addition of glibenclamide (10 micromol/L, n = 7), cariporide (1 micromol/L, n = 7), or verapamil (1 micromol/L, n = 9). In the basal state, increase of intra-atrial pressure from 0 to 12 cm H2O decreased AERPs from 85 +/- 11 to 55 +/- 9 msec (P < 0.01), rapid pacing at low intra-atrial pressure (4 cmH2O) decreased AERP to a similar extent, from 81 +/- 11 to 60 +/- 10 (P < 0.01). At higher intra-atrial pressure, decrease of AERP was more pronounced (10 cm H2O: 37 +/- 2 msec) (n = 7). Addition of verapamil decreased basal AERP from 86 +/- 10 msec to 68 +/- 11 msec (P < 0.05). Short-term electrophysiologic changes due to atrial dilation were abolished; changes due to rapid pacing were reduced but still present. Glibenclamide and cariporide had no significant effect. CONCLUSION: Langendorff-perfused rabbit heart is a suitable model for studying short-term electrophysiologic changes due to both rapid pacing and atrial dilation. AERPs are shortened to a similar extent by both mechanisms, whereas a combination of the two leads to more pronounced AERP reduction. Calcium overload plays a crucial role in short-term electrophysiologic changes caused by atrial dilation, whereas atrial ischemia or acidosis has no significant impact.

Animals↗
PubMed2001

Evidence of sinoatrial block as a curative mechanism in radiofrequency current ablation of inappropriate sinus tachycardia.

Inappropriate sinus tachycardia is a nonparoxysmal tachycardia characterized by high resting heart rates and a disproportionate response to activity. Sinus node modification with radiofrequency current has been used successfully as treatment for this arrhythmia. However, the electrophysiologic mechanisms leading to successful modification are not yet fully elucidated. We report a case of a patient with drug-resistant inappropriate sinus tachycardia in whom successful treatment of the arrhythmia was achieved by documented sinoatrial exit block induced by radiofrequency current applications.

Adult↗
PubMed2001

Shu 508 A (Levovist)-enhanced Doppler echocardiography improves the assessment of valvular heart disease.

OBJECTIVE: To investigate whether intravenous injection of SHU 508 A improves the diagnostic accuracy of Doppler echocardiography in the assessment of valvular pathologies. METHODS AND RESULTS: One hundred and twenty-five consecutive patients with valvular pathology (aortic stenosis, n = 48; aortic regurgitation, n = 20; mitral stenosis, n = 21; and mitral regurgitation, n = 36) and diagnostically insufficient Doppler signal were enrolled in this multicenter study. The severity of valvular pathology was graded on a four-point scale using unenhanced and contrast-enhanced Doppler echocardiography as well as cardiac catheterization. Agreement with cardiac catheterization findings increased from 63% using the unenhanced examination to 73% using the contrast-enhanced Doppler examination. Grading was possible in all patients using SHU 508 A, whereas the unenhanced Doppler examination remained inconclusive in six patients. The weighted kappa coefficient between contrast-enhanced Doppler and cardiac catheterization for all diagnoses was 0.76 as compared to 0.68 between unenhanced Doppler and cardiac catheterization. Agreement was especially improved in aortic stenosis (kappa 0.69 unenhanced vs 0.81 contrast-enhanced) and in aortic regurgitation (kappa 0.45 unenhanced vs 0.75 contrast-enhanced). Patients with mitral stenosis and mitral regurgitation experienced less improvement. CONCLUSIONS: In case of an inconclusive unenhanced Doppler echo study, the administration of a left heart contrast agent should be considered. SHU 508 A is especially useful in improving the severity grading of aortic stenosis and aortic regurgitation, while grading of mitral stenosis and mitral regurgitation is less improved.

Adult↗
PubMed2001

Pulsed tissue Doppler imaging to assess myocardial viability by quantification of regional myocardial functional reserve.

Dobutamine stress echocardiography (DSE) is used widely to evaluate myocardial viability, but is limited by the subjective nature of test interpretation. Assessment of systolic function by pulsed tissue Doppler imaging (TDI) during dobutamine stimulation may allow a more objective evaluation of myocardial functional reserve and, thus, myocardial viability. In 30 patients (58 +/- 9 years) with prior myocardial infarction, pulsed TDI with low dose dobutamine stress (10 microg/kg/min) was performed to assess myocardial viability. Qualitative assessment of two-dimensional (2-D) DSE and positron emission tomography (PET) were used for comparison. Peak systolic myocardial velocity was measured for each left ventricular segment (16 segments) at baseline and low dose dobutamine stress using pulsed TDI. The absolute and relative increases of peak systolic velocity from rest to low dose dobutamine stress were calculated. Three hundred sixty-four segments with adequate pulsed TDI tracing were divided according to either 2-D DSE or PET findings into normal, viable (mismatch), and nonviable (match) segments. The increase of peak systolic myocardial velocity from baseline to low dose dobutamine was significantly different between segments defined as normal, viable, and nonviable by 2-D DSE (2.71 +/- 1.91 cm/sec, 1.86 +/- 2.15 cm/sec, and 0.99 +/- 1.16 cm/sec, respectively; P < 0.001). The increase of peak systolic myocardial velocity from rest to low dose dobutamine for normal, mismatch, and match segments defined by PET was 2.72 +/- 1.96, 1.01 +/- 0.96 and 0.80 +/- 1.07 cm/sec, respectively (P < 0.001). In conclusion, the increase of peak systolic myocardial velocity during low dose dobutamine stimulation determined by pulsed TDI distinguishes between different myocardial viability states. It complements the standard interpretation of stress echocardiograms.

Aged↗
PubMed2001

Stent design related neointimal tissue proliferation in human coronary arteries; an intravascular ultrasound study.

AIMS: Histological restenosis models in animals have indicated that stent design has a significant impact on vessel trauma during stent implantation and on the amount of subsequent neointimal tissue proliferation. The impact of different stent designs on intimal hyperplasia in human atherosclerotic coronary arteries has not been determined. METHODS AND RESULTS: Angiographic and intravascular ultrasound studies were performed at the 6 month follow-up in 131 consecutive native coronary lesions of 131 patients treated with 50 Multi-Link stents, 40 InFlow stents and 41 Palmaz-Schatz stents. Lumen and stent cross-sectional areas (CSA) were measured at 1 mm axial increments. Mean intimal hyperplasia cross-sectional area (stent CSA-lumen CSA) and mean intimal hyperplasia thickness were calculated. Intravascular ultrasound demonstrated different levels of intimal hyperplasia proliferation for the three stents. Mean intimal hyperplasia thickness was 0.16+/-0.08 mm for Multi-Link stents, 0.26+/-0.19 mm for Palmaz-Schatz stents and 0.39+/-0.14 mm for Inflow stents (P<0.001). Multivariate analysis proved that stent type was the only independent predictor of intimal hyperplasia thickness at follow-up (P<0.001). CONCLUSION: Coronary stent design has a significant impact on subsequent intimal hyperplasia after implantation into atherosclerotic human coronary arteries. The corrugated ring design of the Multi-Link stent proved to result in less tissue proliferation at 6-month follow-up than the tubular slotted design of Palmaz-Schatz and InFlow stents.

Coronary Disease↗
PubMed2001

The impact of high pressure vs low pressure stent implantation on intimal hyperplasia and follow-up lumen dimensions; results of a randomized trial.

AIMS: Histology and retrospective clinical studies have indicated that the amount of neointimal hyperplasia is dependent on the arterial injury induced during stent implantation. This study analysed, prospectively, the impact of high vs low pressure stent implantation techniques using a second generation stent on intimal hyperplasia and follow-up lumen dimensions. METHODS AND RESULTS: Post-intervention and follow-up (mean[+/-SD] 5.5+/-1.3 months) angiographic and intravascular ultrasound studies were performed on 120 Multi-Link HP stents randomized to implantation at either low (8-10 atm) or high (16-20 atm) pressure. Intravascular ultrasound measurements of the external elastic membrane, stent, and lumen cross-sectional area were performed at 1 mm axial increments. Peri-stent plaque+media cross-sectional area (external elastic membrane-stent cross-sectional area, intimal hyperplasia cross-sectional area (stent-lumen cross-sectional area at follow-up), intimal hyperplasia thickness and peri-stent tissue growth cross-sectional area (Deltapersistent plaque+media cross-sectional area) were calculated. Intravascular ultrasound demonstrated a larger minimal lumen cross-sectional area post-intervention in the high pressure group (7.3+/-2.0 vs 6.2+/-1.8 mm(2), P<0.001, high vs low pressure group, respectively). At follow-up, the mean intimal hyperplasia cross-sectional area (1.7+/-0.9 vs 1.5+/-0.8 mm(2), P=0.708), the mean intimal hyperplasia thickness (0.16+/-0.12 vs 0.16+/-0.12 mm, P=0.818) and peri-stent tissue proliferation cross-sectional area were not greater in the high pressure group. Thus, the minimal lumen cross-sectional area at follow-up continued to be greater (5.5+/-2.0 vs 4.7+/-1.7 mm(2), P=0.038) in the high pressure group. CONCLUSIONS: High pressure stent implantation results in greater stent expansion even with the less rigid second generation Multi-Link stent. Larger lumen dimensions persist at follow-up, while intimal hyperplasia is not significantly greater after high pressure implantation compared to the low pressure technique.

Coronary Angiography↗
PubMed2001

Tissue tracking allows rapid and accurate visual evaluation of left ventricular function.

AIMS: To evaluate the ability of tissue tracking for rapid assessment of left ventricular function by determination of the systolic mitral annular displacement. Tissue tracking is a new echocardiographic modality based on Doppler Tissue imaging allowing rapid visual assessment of the systolic baso-apical displacement of each myocardial segment in apical views by a graded colour display. METHODS AND RESULTS: We studied 90 patients (69 male, age 60.4 +/- 10.1 years) with different left ventricular function (25 subjects with normal left ventricular function, 25 patients with homogeneous depression of left ventricular function and 40 patients with prior myocardial infarction). Systolic mitral annular displacement was determined by tissue tracking and M-mode echocardiography. Apical two-, three- and four-chamber views were used to determine the mitral annular displacement of six sites. Left ventricular ejection fraction was determined by two-dimensional echocardiography using Simpson's rule. Tissue tracking was possible in all patients. In the 50 patients with normal left ventricular function or homogeneous depression of left ventricular function, mean mitral annular displacement correlated closely with mitral annular displacement determined by M-mode (r=0.99,P <0.001) and with left ventricular ejection fraction (r=0.97, P<0.001). Left ventricular ejection fraction < or = 30% could be predicted with a sensitivity of 98% and a specificity of 78% using a cut-off value of 4.8mm for the mitral annular displacement determined by tissue tracking. In patients with prior myocardial infarction correlation between the mean mitral annular displacement and left ventricular ejection fraction was lower (r=0.87, P<0.001). CONCLUSION: Systolic mitral annular displacement determined by tissue tracking correlates closely with mitral annular displacement determined by M-mode and with left ventricular ejection fraction. Thus, tissue tracking allows rapid semiquantitative evaluation of global left ventricular function by assessment of systolic mitral annular displacement.

Aged↗
PubMed2001

Lack of association among five genetic polymorphisms of the renin-angiotensin system and cardiac hypertrophy in patients with aortic stenosis.

BACKGROUND: Patients with aortic stenosis (AS) have left ventricular hypertrophy (LVH). It is thought that LVH in these patients is a consequence of chronic left ventricular pressure overload. However, there is only a poor correlation between the degree of AS and the degree of LVH. Genetic polymorphisms of the renin-angiotensin-aldosterone system (RAAS) have been considered to trigger the response of the left ventricle to chronic pressure overload and determine the degree of LVH in patients with AS. METHODS: One hundred five consecutive patients with symptomatic AS were examined by echocardiography and left heart catheterization to determine the severity of AS and LVH. Five genetic polymorphisms of the RAAS (ACE, AGTR1, AGT, CMA, CYP11B2) were analyzed in all patients and the results of genetic analysis were correlated to severity of AS and LVH to determine the importance of the polymorphisms for LVH. RESULTS: All tested genotypes were in Hardy-Weinberg equilibrium and allele frequencies were similar to other study populations. There was no correlation between the severity of AS and the severity of LVH. There was no association between the five tested genotypes of the RAAS and the severity of AS (mean gradient and area of the aortic valve) or LVH (LV muscle mass). CONCLUSION: We conclude that LVH in patients with AS is not determined by the tested genetic polymorphisms of the RAAS.

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