Purification, molecular characterization and catalytic properties of a Pseudomonas fluorescens enzyme having cholinesterase-like activity.

An enzyme with a cholinesterase (ChE) activity, produced by Pseudomonas fluorescens, was purified to homogeneity in a three-step procedure. Analysis by non-denaturing and SDS-PAGE, and by isoelectric focusing, indicated that the enzyme was a monomer of 43 kDa, with a pI of 6.1. The N-terminal sequence, AEPLKAVGAGEGQLDIVAWPGYIEA, showed some similarities with proteins of the ChE family and a strong similarity with a protein from Escherichia coli with unknown structure and function. Cholinesterase activity at pH 7.0 and 25 degreesC was maximum with propionylthiocholine as substrate (kcat,app=670 min-1), followed by acetylthiocholine, and significantly lower with butyrylthiocholine. Catalytic specificity (kcat/Km) was the same for propionylthiocholine and acetylthiocholine, but was two orders of magnitude lower for butyrylthiocholine. Kinetics of thiocholine ester hydrolysis showed inhibition by excess substrate which was ascribed to binding of a second substrate molecule, leading to non-productive ternary complex (Km=35 microM, KSS=0.49 mM with propionylthiocholine). There was low or no reactivity with organophosphates and carbamates. The enzyme inhibited by echothiophate (kII=0.44x102 M-1 min-1) was not reactivated by pralidoxime methiodide. However, the P. fluorescens enzyme had affinity for procainamide and decamethonium, two reversible ChE inhibitors used as affinity chromatography ligand and eluant, respectively. Although similarity of the N-terminal amino acid sequence of the enzyme with an internal sequence of ChEs is weak, its catalytic activity towards thiocholine esters, and its affinity for positively charged ligands supports the contention that this enzyme may belong to the ChE family. However, we cannot rule out that the enzyme belongs to another structural family of proteins having cholinesterase-like properties. The reaction of the enzyme with organophosphates suggests that it is a serine esterase, and currently this enzyme may be termed as having a cholinesterase-like activity.

Combined percutaneous balloon mitral valvotomy and coronary angioplasty with stent implantation.

A patient with symptomatic pliable mitral stenosis and a significant lesion in the right coronary artery underwent combined interventional procedures during a single session. After an uneventful transseptal puncture that allowed full anticoagulation with heparin, a percutaneous transluminal coronary angioplasty was performed, yielding an unsatisfactory result and necessitating stent implantation. Thereafter, mitral stenosis was relieved by percutaneous balloon valvotomy. The specific problems arising from the combination of the two procedures are discussed.

Can the long-term outcomes of percutaneous balloon mitral valvotomy and surgical commissurotomy be expected to be similar?

The ultimate role of percutaneous balloon mitral valvotomy will depend on its potential for sustained improvement. Long-term outcome data including survival, reoperation and thromboembolism are available for surgical commissurotomy. However, length of follow up for percutaneous balloon mitral valvotomy is inadequate to acquire similar end-point data. We therefore hypothesized that comparison of changes in mitral valve area following balloon or surgical commissurotomy would serve as a useful surrogate end-point by which the long-term benefit of percutaneous balloon mitral valvotomy could be determined. Mitral valve area was determined by Doppler echocardiography following percutaneous balloon mitral valvotomy (N = 230) and surgical commissurotomy (N = 241, 130 closed and 111 open mitral commissurotomy). Regression lines of mitral valve area versus interval from intervention were constructed for each of the two groups. Nine clinical and echocardiographic variables were also analyzed to determine their predictive value for low mitral valve areas. Both groups showed similar and significant negative correlations for mitral valve area versus time (r = -0.48, r = -0.6, balloon vs. surgical commissurotomy respectively, p = 0.001 for both groups). The slopes of the regression lines for both groups were also similar (y = -0.007 x +1.9, y = -0.005 x +1.8, y = -0.006 x +1.8, p = NS). There were no differences in the prevalence of mitral regurgitation. Independent predictors of mitral restenosis according to multivariate analysis were time interval from surgery (p < 0.03), composite mitral valve morphology score (p < 0.04) and subvalvular disease (p < 0.04). Thus, there is a progressive decrease in mitral valve area following percutaneous mitral balloon valvotomy that, at least for the available duration of follow up, appears to parallel changes in valve area following closed or open mitral commissurotomy. A less pliable valve and more subvalvular disease are independent predictors of smaller valve areas. These data suggest that the long term clinical outcome following percutaneous balloon mitral valvotomy may be expected to be similar to the available data for surgical commissurotomy.

Coronary interventions in Europe 1992. The Working Group on Coronary Circulation of the European Society of Cardiology.

The general practice of coronary interventions is influenced by various aspects, traditional, cultural, socioeconomic and personal. The aim of this survey was to collect the data on coronary intervention in all member countries of the European Society of Cardiology. The data from 12 of the 35 national members were missing or grossly incomplete and were therefore excluded from the analysis. CORONARY ANGIOGRAPHY: The total number of coronary angiograms was reported as 683,888, an incidence of 1009 +/- 1021 per million inhabitants (range 9 (Romania) to 3076 (Germany)). Germany (246,115 cases), France (144,754), the United Kingdom (76,296), Italy (45,517) and Spain (43,495) registered 81% of all the coronary angiograms performed. PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY: (PTCA) The total number of reported PTCAs was 147,729, which on average accounted for 19 +/- 11% (range 2 (Lithuania) to 53% (Netherlands)) of the coronary angiograms. Most of the PTCAs (82%) were confined to a single vessel. The highest incidence of multivessel PTCA was reported from Slovakia (28%). PTCA took place immediately after the diagnostic study in only 18% of cases. Adjusted per capita, Germany ranked first with 703 PTCAs per million inhabitants, followed by Iceland (619), France (614), Belgium (568) and Austria (485). A major in-hospital complication was reported in 2.5% of the patients undergoing PTCA: 0.4% hospital deaths, 1.0% emergency CABGs and 1.1% myocardial infarctions. NEW DEVICES: Stents were implanted in 3211 patients (2.7% of all PTCA patients), equally distributed between emergency situations (53%) and elective procedures. Other interventional devices were applied in 4133 cases (2.8% of all PTCA cases): directional atherectomy, rotablator, transluminal extraction catheter, laser and Rotacs accounted for 1452, 1232, 55, 558 and 222, respectively. Coronary ultrasound (1350 cases) and coronary angioscopy (373 cases) were rarely performed. CORONARY ARTERY BYPASS GRAFTING (CABG): A total of 63,477 patients underwent CABG in the reporting centres resulting in a PTCA/CABG ratio of 2.3. A significant under-reporting of surgery in the participating centres must be assumed. CONCLUSIONS: Although partial reporting might bias conclusions, several findings of this survey are noteworthy: (1) PTCA was a well accepted treatment for coronary artery disease, (2) PTCA was applied more frequently than CABG, (3) there was an extremely wide range of coronary angiography and PTCA performed per million inhabitants, (4) the most common additional procedure was stent implantation, but other new devices were only rarely applied.

[Cardiac interventions in Switzerland 1993]. / Herzeingriffe in der Schweiz 1993.

As in the previous years, a survey of all cardiac invasive, interventional and surgical procedures was carried out 1993 by a detailed questionnaire, which was sent to all Swiss centers. The resulting data are presented here for the whole of Switzerland and per individual center. The outstanding findings are: For the first time, more coronary angioplasties than coronary bypass graft operations were performed. At the same time, angioplasty in two or more vessels during the same session was attempted in 10% only. Overall the coronary stent represents the most frequently used new device in interventional cardiology in Switzerland, but large differences regarding the incidence of stent implantations exist among the centers. Compared with the public or university hospitals, the private centers have increased their interventional and surgical volume dramatically during the past years.

Angioplasty for treatment of Takayasu's arteriopathy: case reports.

Two cases of Takayasu's arteritis with severe renovascular hypertension are described. Both patients underwent successful percutaneous balloon angioplasty with attenuation of the systemic hypertensive response. The role of angioplasty as an alternative to surgery for revascularization of symptomatic ischemia in this disease is reviewed.

Comparison of single-dose nifedipine and captopril for chronic severe aortic regurgitation.

The effects of a single dose of either nifedipine 20 mg (n = 10) or captopril 50 mg (n = 10) were compared in 20 patients with symptomatic, chronic severe aortic regurgitation using angiography and micromanometer left ventricular pressure measurements. At 90 minutes, mean arterial pressure was reduced comparably after both drugs (86 +/- 15 to 76 +/- 18 mm Hg for nifedipine vs 95 +/- 19 to 77 +/- 18 mm Hg for captopril, p = NS between groups by analysis of variance), as was wedge pressure (11 +/- 5 to 9 +/- 4 mm Hg vs 13 +/- 9 to 9 +/- 5 mm Hg for captopril). Systemic vascular resistance was reduced more (p = 0.01) after nifedipine than after captopril (1,549 +/- 468 to 1,067 +/- 291 dynes s cm-5 vs 1,632 +/- 559 to 1,436 +/- 392 dynes s cm-5). Heart rate declined after captopril (84 +/- 14/min to 75 +/- 15/min, p = 0.002) but not after nifedipine (78 +/- 13 min to 80 +/- 14 min). Forward stroke volume increased after nifedipine (58 +/- 14 to 70 +/- 16 ml, p < 0.001) but not after captopril (58 +/- 17 to 59 +/- 16 ml). Thus, cardiac output increased after nifedipine (4.4 +/- 0.9 to 5.5 +/- 1.2 liters/min, p < 0.001) but decreased after captopril (4.8 +/- 1.2 to 4.3 +/- 1.0, p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

Effectiveness of amiodarone and electrical cardioversion for chronic rheumatic atrial fibrillation after mitral valve surgery.

Thirty consecutive patients with chronic rheumatic atrial fibrillation (AF) > or = 3 months after successful mitral valve surgery and left atrial diameter < or = 60 mm were treated with oral amiodarone. Protocol included high loading dosages of amiodarone for 4 weeks, and if conversion to sinus rhythm (SR) was not achieved then electrical cardioversion was performed. Patients converted to SR were maintained on low-dose amiodarone for another 4 weeks when treatment was discontinued. Overall, 23 patients (77%) converted to SR after 4 weeks of therapy: 12 (40%) taking amiodarone alone and 11 (37%) with the addition of electrical cardioversion. The duration of AF > 48 months was an adverse factor in the ability to restore SR. Sixteen patients (70%) remained in SR at a mean follow-up of 17 months. The duration of AF < or = 48 months alone or in combination with left atrial diameter < or = 45 mm were the best predictors for long-term maintenance of SR. Thus, short-term amiodarone with or without electrical cardioversion is effective and safe in the treatment of chronic rheumatic AF after mitral valve surgery. The duration of AF and left atrial size can be used to identify patients with successful outcome.

Results of percutaneous balloon mitral valvotomy in young adults.

The results of percutaneous balloon mitral valvotomy (PBMV) were evaluated in 235 young patients (mean age 29 +/- 11 years) with symptomatic rheumatic mitral stenosis, and the single-balloon Inoue technique was compared with the double-balloon Mansfield technique. PBMV was associated with a significant increase in Gorlin mitral valve area (0.78 +/- 0.23 to 1.61 +/- 0.64 cm2; p < 0.001), and improvement in New York Heart Association functional class (2.78 +/- 0.59 to 1.28 +/- 0.58; p < 0.001). Mitral regurgitation increased significantly (0.4 +/- 0.6 to 1.3 +/- 1.0; p < 0.001), but was significant (> or = 3+) only in 19 patients (8%). Comparison of the Inoue and Mansfield techniques showed a significantly lower Gorlin mitral valve area after PBMV (1.55 +/- 0.56 vs 1.74 +/- 0.74 cm2; p < 0.05), but a lower incidence of mitral regurgitation by color Doppler echocardiography (1.1 +/- 0.7 vs 1.5 +/- 0.8; p < 0.05) in the Inoue group. Patients were divided into those with nonpliable (valve score > 8; group I) and pliable (score < or = 8; group II) valves. Although significant increases in mitral valve area were obtained in both groups, mitral valve area by planimetry was significantly lower in group I (1.49 +/- 0.46 vs 1.86 +/- 0.44 cm2; p < 0.05), whereas there was no difference in the amount of color Doppler mitral regurgitation (1.5 +/- 1.0 vs 1.2 +/- 0.7; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term (3-month) effects of a new beta-blocker (nebivolol) on cardiac performance in dilated cardiomyopathy.

OBJECTIVES: This study examined the long-term (3-month) effects of nebivolol, a new beta-adrenergic blocking agent, on cardiac performance in patients with dilated cardiomyopathy. BACKGROUND: Several beta-blocking drugs have been reported to have a beneficial hemodynamic effect in patients with dilated cardiomyopathy, but few data obtained in a placebo-controlled randomized study have addressed the mechanisms of improvement. METHODS: Twenty-four patients with dilated idiopathic (n = 22) or ischemic (n = 2) cardiomyopathy (ejection fraction 0.15 to 0.40) in stable New York Heart Association functional class II or III were entered into a double-blind randomized trial of nebivolol, a new, potent, selective beta 1-antagonist. Exercise time, invasive hemodynamic data (12- and 24-h monitoring) and variables of left ventricular function were examined at baseline and after 3 months of orally administered nebivolol (1 to 5 mg/day, n = 11) or placebo (n = 13). RESULTS: Heart rate decreased (group mean 85 to 71 beats/min vs. 87 to 87 beats/min with placebo) and stroke volume increased significantly (group mean 43 to 55 ml vs. 42 to 43 ml) with nebivolol; decreases in systemic resistance, systemic arterial pressure, wedge pressure and pulmonary artery pressure were not significantly different from those with placebo. Similar hemodynamic results were obtained in the catheterization laboratory. Analysis of high fidelity measurements of left ventricular pressure showed a decrease in left ventricular end-diastolic pressure in the nebivolol group (group mean 21 to 15 vs. 24 to 20 mm Hg with placebo) but no change in the maximal rate of pressure development or in two variables of left ventricular relaxation (maximal negative rate of change of left ventricular pressure [dP/dtmax] and the time constant tau). Left ventricular mass decreased (p = 0.04). Despite a decrease in heart rate with nebivolol, there was a slight decrease in left ventricular end-diastolic volume (p = NS). End-systolic volume tended to decrease (p = 0.07) despite no reduction in end-systolic stress. The net result was a significant increase in ejection fraction (group mean 0.23 to 0.33 vs. 0.21 to 0.23 with placebo), presumably as a result of an increase in contractile performance. This effect was corroborated by an increase in a relatively load-independent variable of myocardial performance. CONCLUSIONS: Nebivolol improved stroke volume, ejection fraction and left ventricular end-diastolic pressure, not through a measurable reduction in afterload or a lusitropic effect, but by improving systolic contractile performance.

Pulmonary hypertension is a contraindication to beta-blockade in patients with severe mitral stenosis.

Intravenous atenolol was given to 31 patients just before balloon mitral valvotomy to assess the hemodynamic efficacy and safety of beta-blockade in mitral stenosis complicated by pulmonary hypertension. Hemodynamic response in patients with pulmonary resistance > 600 dynes.sec.cm-5 (group 2, n = 17) was compared with those (group 1, n = 14) with a resistance below this value. In addition to a higher pulmonary arterial resistance (by design), patients in group 2 had a higher systemic resistance, lower cardiac index, and smaller mitral valve area compared with those in group 1. After atenolol infusion, transmitral gradient and left atrial pressure improved similarly. In spite of the decline in left atrial pressure, pulmonary vascular resistance increased in both groups, more in group 2 (847 +/- 398 dynes.sec.cm-5 to 135 +/- 648 dynes.sec.cm-5) than in group 1 (291 +/- 149 dynes.sec.cm-5 to 363 +/- 200; p < 0.001 for drug effect and p = 0.027 for group effect by two-way analysis of variance). Cardiac index declined similarly from 2.77 +/- 0.51 L/min/m2 to 2.37 +/- 0.37 L/min/m2 in group 1 and from 2.33 +/- 0.58 L/min/m2 to 1.92 +/- 0.54 L/min/m2 in group 2. Systemic pressure tended to decline only in group 2 (mean aortic pressure, 89 +/- 12 mm Hg to 89 +/- 12 mm Hg in group 1 and 90 +/- 9 mm Hg to 83 +/- 12 mm Hg in group 2; p = 0.06 for group effect).(ABSTRACT TRUNCATED AT 250 WORDS)

[Coping with illness by dialysis and tumor patients]. / Krankheitsverarbeitung bei Dialyse- und Tumorpatienten.

In the present article the coping of cancer-patients and patients with chronic renal failure is analysed and compared with each other. We isolated a pattern of strategies that was rated high by the patients, either in their own appraisal or reported by them freely. We describe the most rejected contents, the strategies of defence (threat-regulation), and also the individually experienced main impairments of the diseases. Although we analysed two different groups of illnesses, we have not been able to differentiate the respective coping patterns. The fact that the patients preferred the same strategies and rejected the same ones was a surprising outcome! The only differences were found in the freely reported impairments of the diseases. Within the group of cancer-patients we found heterogeneous strategies of defence (threat-regulation), a fact that points to the necessity of particular analysis in the research of coping.

[Illness adjustment of adult patients with cystic fibrosis I. 1. Coping, personality and perceived health]. / Krankheitsverarbeitung bei erwachsenen Patienten der Cystischen Fibrose I. 1. Coping, Persönlichkeit und Befindlichkeit.

The data of a coping-study of 46 adult patients suffering from Cystic Fibrosis is given. Due to several instruments of coping, personality and well-being and due to the fact, that coping with Cystic Fibrosis is here investigated for the first time with standardized coping-inventories, we emphasize high stability of coping, average values of personality, and well-being. Furthermore we can suggest several Clusters of an adequate coping with Cystic Fibrosis.

[Illness adjustment of adult patients with cystic fibrosis II. 2. Social support and coping]. / Krankheit Verarbeitung bei erwachsenen Patienten der Cystischen Fibrose II. 2. Soziale Unterstützung und Coping.

As a part of our study of the coping with cystic fibrosis we examined the social network and the social support of adult patients. The results suggests that there is only little difference between women and men in the size of network and perceived support and that the family is of great importance as a source of support. Compared with healthy adults, perceived social support seems to be less but greater than for depressive patients. Only some coping-clusters do correlate positively with social support.

Effects of a single oral dose of captopril on left ventricular performance in severe mitral regurgitation.

For comparable decreases in systemic resistance, angiotensin-converting enzyme inhibitors produce a lesser increase in cardiac output than do previously used vasodilators. Although the reason for this is not yet clear, the possibility of a negative inotropic effect of angiotensin-converting enzyme inhibitors was demonstrated by intracoronary injection. The effects of an oral dose of captopril on systolic performance were assessed by examining left ventricular (LV) pressure-volume loops obtained with simultaneous cineangiography and micromanometer pressure recordings before and 90 minutes after administration of oral captopril (25 to 50 mg) in 18 patients with chronic, severe mitral regurgitation. Group 1 (n = 9) was given captopril alone, and group 2 (n = 9) was given captopril plus atropine (0.04 mg/kg intravenous) to assess the role of parasympathetic activity in mediating the effects of captopril. Captopril reduced heart rate (90 to 81 beats/min; p less than 0.002) and LV end-diastolic pressure (13 to 10 mm Hg; p = 0.03), despite a slight increase in end-diastolic volume (257 to 264 ml; p = not significant) that suggests improved diastolic properties. Despite a decrease in end-systolic pressure (103 to 90 mm Hg; p less than 0.001), ejection fraction did not increase (0.60 to 0.58; p = not significant) owing to an increase in end-systolic volume (107 to 114 ml; p = 0.008). Contractile performance, estimated from the end-systolic pressure/volume quotient, was consistently depressed by captopril, as was the relation of preload-corrected ejection fraction to end-systolic stress.(ABSTRACT TRUNCATED AT 250 WORDS)