The first coronary angioplasties in Germany.
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Biomedical subjects
Publications and source records attributed to M Kaltenbach.
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Earlier studies have reported on the potentiated muscarinic vasoconstriction of intracoronary acetylcholine after metoprolol application in patients with coronary artery disease. The present study investigated the effect of celiprolol, atenolol, and placebo on acetylcholine-induced vasomotion in patients with coronary artery disease. Furthermore, direct effects on coronary vasomotion and on hemodynamics were evaluated. Acetylcholine (intracoronary concentrations of 6.3x10(-7), 2.0x10(-6), and 6.3x10(-6) M) was given before and after double-blind celiprolol (0.30 mg/kg IV), atenolol (0.15 mg/kg IV), or placebo in 3x12 patients. Vasomotion was investigated by quantitative coronary angiography in proximal and distal segments of epicardial coronary arteries, and by the determination of the coronary resistance index based on Doppler-flow measurements. The investigated drugs had no direct affect on the diameter of the epicardial coronary arteries. However, celiprolol, in contrast to atenolol, significantly reduced systemic vascular resistance (change after atenolol: from 1,855+/-308 to 2,161+/-550 dyne s cm(-5); celiprolol: 1,691+/-435 to 1,411+/-343 dyne s cm(-5); and placebo: 1,722+/-215 to 1,710+/-213 dyne s cm(-5), p<0.001) and the coronary resistance index (change after atenolol: 2.52+/-3.58 to 2.86+/-4.24; celiprolol: 2.70+/-1.55 to 2.49+/-2.26; and placebo: 1.97+/-1.35 to 1.92+/-1.25, p<0.01). Celiprolol, atenolol, and placebo did not have different effects on acetylcholine-induced coronary vasomotion of epicardial conductance vessels (diminution of proximal lumen diameter before/after atenolol: 0.42+/-0.39/0.44+/-0.39 mm; celiprolol: 0.32+/-0.26/0.30+/-0.24 mm; and placebo: 0.36+/-0.29/0.43+/-0.40 mm) and of coronary resistance vessels (reduction of coronary resistance index before/after atenolol: 1.95 +/-4.74/ 1.92+/-3.74; celiprolol: 0.98+/-0.73/1.41+/-1.50; and placebo: 1.16+/-1.29/1.16+/-1.04). In contrast to atenolol, celiprolol possesses vasodilative properties in systemic and coronary resistance vessels. There was no direct effect on the diameter of conductance vessels. Acetylcholine-induced coronary vasomotion both in conductance and resistance vessels was not influenced by the beta blockers that were studied. This suggests that atenolol and celiprolol do not influence endothelium-dependent, nitric oxide related vasomotion.
1956 7th grade students of high schools and secondary modern schools in three cities with 110,000 to 180,000 inhabitants were asked about cigarette, alcohol and drug consumption using questionnaires. Subsequently 1080 of the students took part in a newly invented non-smoking curriculum which was held during 8 lessons within 4 weeks (intervention group (I)). The lessons were performed by non-smoking physicians who had passed a training programme before. 876 students served as control (C) group. 2 years later the questioning was repeated. The number of students who started smoking within the two years was significantly lower in the intervention group. In the high schools a significant effect was seen in boys (I: 13.0%, K: 22.4%; p < 0.01) and girls (I: 21.4%, K: 28.4%; p < 0.05) whereas in secondary modern schools a significant effect was seen only in boys (I: 17.4%, K: 25.2%; p < 0.05) not in girls (I: 18.0%, K: 22.0%; n.s.). First-time consumers of drugs like cannabis, marihuana and organic solvents were found less often in the intervention group among boys in high schools than in the control group (I: 14.9%; K: 23.6%; p < 0.05). No effects of the intervention were seen in girls of high schools and in students of secondary modern schools. No effects of the intervention were seen on alcohol consumption. Students who drank beer, wine or liquor several times a week were found at the same rate in the intervention and control groups. We conclude that a non-smoking intervention of 8 lessons in the 7th grade of high schools and secondary modern schools may lower the rate of first-time consumers of cigarettes but not of alcohol and drugs.
Since 1995, the German Society for Cardiac Angiography and Interventions in Private Practice (BNK) has been intensely involved in quality assurance; since 1996, it has registered relevant data for diagnostic left heart catheterization (DIAG) and coronary interventions (PTCA). The following data are based on a total of 72,777 cardiac catheters, of which 54,513 were DIAG and 18,264 were PTCA (DIAG in 1996: 10,316; in 1997: 15,692 and in 1998: 28,505. PTCA in 1996: 2,597; in 1997: 5,600 and in 1998: 10,067). The mean patient age was 61.9 years for males and 65.3 years for females (31%). DIAG was performed on an out-patient basis in 60% of the cases. The proportion of self-referrals is circa one-third and has not increased over time. A s/p PTCA was present in 21% of the DIAG patients; those after coronary bypass surgery showed a steadily increasing trend towards a follow-up DIAG (8% of the patients). There was a distinctive decrease in the use of contrast medium from an average of 164 ml (1996) to 138 ml (1998). The symptoms leading to DIAG did not substantially change in the years from 1996 to 1998; the angiographic range of the coronary disease and the degree of an impaired myocardial function have remained virtually unchanged. The treatment recommendations appear to tend towards medical therapy with decreasing indications for PTCA (20%) and open heart surgery (16%). The mean duration of a PTCA procedure decreased from 57 +/- 8 (1996) to 44.6 +/- 25 (1998) minutes. The success rates remained unchanged for coronary stenoses as well as for recanalization of chronic total occlusions. PTCA complications: the incidence of abrupt coronary occlusions was 2% and of emergency bypass surgery 0.4%; mortality was 0.1%.
Vinblastine and vincristine are two medically important bisindole alkaloids from Catharanthus roseus (Madagascar periwinkle). Attempts at production in cell cultures failed because a part of the complex pathway was not active, i.e. from tabersonine to vindoline. It starts with tabersonine 16-hydroxylase (T16H), a cytochrome P450-dependent enzyme. We now show that T16H is induced in the suspension culture by light and we report the cloning of the cDNA. The enzyme was expressed in Escherichia coli as translational fusion with the P450 reductase from C. roseus, and the reaction product was identified by mass spectrometry. The protein (CYP71D12) shares 47-52% identity with other members of the CYP71D subfamily with unknown function. The induction by light was strongly enhanced by a nutritional downshift (transfer into 8% aqueous sucrose). We discuss the possibility that the entire pathway to bisindoles can be expressed in suspension cultures.
We investigated the P450 dependent flavonoid hydroxylase from the ornamental plant Catharanthus roseus. cDNAs were obtained by heterologous screening with the CYP75 Hf1 cDNA from Petunia hybrida. The C. roseus protein shared 68-78% identity with other CYP75s, and genomic blots suggested one or two genes. The protein was expressed in Escherichia coli as translational fusion with the P450 reductase from C. roseus. Enzyme assays showed that it was a flavonoid 3', 5'-hydroxylase, but 3'-hydroxylated products were also detected. The substrate specificity was investigated with the C. roseus enzyme and a fusion protein of the Petunia hybrida CYP75 with the C. roseus P450 reductase. Both enzymes accepted flavanones as well as flavones, dihydroflavonols and flavonols, and both performed 3'- as well as 3'5'-hydroxylation. Kinetics with C. roseus cultures on the level of enzyme activity, protein and RNA showed that the F3'5'H was present in dark-grown cells and was induced by irradiation. The same results were obtained for cinnamic acid 4-hydroxylase and flavanone 3beta-hydroxylase. In contrast, CHS expression was strictly dependent on light, although CHS is necessary in the synthesis of the F3'5'H substrates. Immunohistochemical localization of F3'5'H had not been performed before. A comparison of CHS and F3'5'H in cotyledons and flower buds from C. roseus identified CHS expression preferentially in the epidermis, while F3'5'H was only detected in the phloem. The cell-type specific expression suggests that intercellular transport may play an important role in the compartmentation of the pathways to the different flavonoids.
UNLABELLED: One-hundred patients undergoing routine diagnostic or interventional catheterization were randomly assigned to receive either percutaneously applied collagen (group A; n = 50) or conventional pressure dressing (group B; n = 50) for sealing of the femoral artery. Clinical variables were comparable in both groups. The heparin dose was 100 IU/kg in 30 patients and 200 IU/kg in 20 patients of either group. The average compression time was 4.3 minutes in group A and 42.3 minutes in group B (p < 0.001). Bleeding was not observed in group A but was observed in 6/50 patients in group B. The time to ambulation was 6.4 hours (range: 4-12 hours) in group A and 21.6 hours (range: 10-48 hours) in group B (p < 0.001). Hematomas with a diameter of > 6 cm developed in 4/50 patients in group A and in 11/50 patients in group B (p < 0.05). Blood transfusion or surgical interventions were not required and there was no loss of ankle pulses in either group. CONCLUSION: Percutaneously applied collagen reduced compression time and duration of bedrest after diagnostic catheterization and PTCA. Despite earlier ambulation, the incidence of bleeding was lower with collagen than with conventional pressure dressing.
The German Society for Cardiac Angiography and Interventions in Private Practice has started a registry of cardiac procedures since 1996 in order to establish a standard for performance. Although quality management for the cath lab makes sense and is also legally required, there is no generally recommended infrastructure for quality assurance existing in Germany at this time. Therefore, the German Society of Cardiologists in Private Practice (BNK) initiated a project in 1994 to develop a computer program for paperless documentation of diagnostic cardiac catheterizations and coronary interventions (PTCA) using a minimal data set. In 1996, 8 private associated groups participated in this project. The (anonymous) analysis of 10,316 diagnostic cardiac catheterizations and 2597 PTCA yielded the following results: In 95% of the patients, diagnostic cardiac catheterization was performed using the femoral and in 5% the brachial/radial approach. The mean volume of administered contrast medium was 164 +/- 138 ml/patient. The mean LV-EF was greater than 50% in 58.4% of the patients and between 30% and 50% in 10.1%. Coronary artery disease was diagnosed in 69.6% of the patients and valvular/congenital heart disease in 8.5%. In 18.4% of the patients undergoing diagnostic cardiac catheterizations no significant heart disease was identified. Mortality in the cath lab as well as the rate of cerebral insults was 0.05%. In 22.9% and 19% of the patients PTCA and cardiac surgery respectively was recommended. In patients undergoing PTCA, stable angina was present in 74.4% and unstable angina in 13.1%. Of the total number of PTCA procedures, 5.8% were performed in the setting of acute myocardial infarction. The PTCA lesion success rate was 96%, the mean diameter stenosis was 81% pre and 6% post-intervention. The mortality rate at 1 month post-PTCA was 0.4%, and myocardial infarction 1.0%. An acute occlusion occurred in 1.3% of the PTCA patients; 0.6% had to be transferred for emergency bypass surgery. None of the cath labs had on-site surgery. In comparison to other registries, our data show some similarities but also some different trends. Thus, our newly developed software proved to be reliable, fast and easy to use. Participating centers receive immediate feedback regarding their position within the whole group.
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Phylogenetic relationships among Phlebotominae were inferred through a pilot study using parsimony analysis of the D2 domain of ribosomal DNA sequences: 455 pairs of bases were sequenced in nine species of Phlebotomine sandflies which belong to the genera Lutzomyia, Phlebotomus and Sergentomyia. Two taxa are used as outgroups: Psychoda sp. and Nemapalpus flavus which is the sister group of the Phlebotominae. The South American genus Lutzomyia appears to be monophyletic. The Mediterranean species Sergentomyia dentata is its sister group and is not clustered with the Old World genus Phlebotomus. The latter is a paraphyletic genus with an early individualization of the branch including the closely related subgenera Phlebotomus and Paraphlebotomus, and a late individualization of the subgenus Larroussius. These results have some consequences on the biogeography of the leishmaniasis in the Old World.
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BACKGROUND: Unfractionated heparin and its low molecular fragments possess antiproliferative effects and have been shown to reduce neointimal smooth muscle cell migration and proliferation in response to vascular injury in experimental studies. OBJECTIVES: The specific objective of the REDUCE trial was to evaluate the effect of a low molecular weight heparin on the incidence and occurrence of restenosis in patients undergoing percutaneous transluminal coronary angioplasty. METHODS: The REDUCE trial is an international prospective, randomized, double-blind, multicenter study. Twenty-six centers in Europe and Canada enrolled 625 patients with single lesion coronary artery obstructions suitable for PTCA. Three hundred and six patients received reviparin as a 7000 U bolus before PTCA followed by 10,500 U as an infusion over 24 hours and then twice a day 3500 U s.c. application for 28 days. The 306 patients in the control group received a bolus of 10,000 U unfractionated heparin followed by an infusion of 24,000 U over 24 hours. These patients then received 28 days of s.c. placebo injections. The primary endpoints were efficacy (defined as a reduction in the incidence of major adverse events, i.e., death, myocardial infarction, need for reintervention or bypass surgery), absolute loss of minimal luminal diameter, and incidence of restenosis during the observation period of 30 weeks after PTCA. RESULTS: Using the intention-to-treat analysis for all patients, 102 patients (33.3%) of the reviparin group and 98 patients (32%) of the control group have reached a primary clinical endpoint (relative risk = 0.98; 95% confidence limit, 0.88-1.09; p = 0.707). Likewise, no difference in late loss of minimal luminal diameter was evident for either group. Acute events within 24 hrs occurred in 3.9% of the reviparin group and in 8.2% of the control group (relative risk = 0.49; 95% confidence limit, 0.26-0.92; p = 0.027) during or immediately after the initial procedure. In the control group, 8 major bleedings occurred, and in the reviparin group, 7 major bleeding complications were observed within 35 days after PTCA. CONCLUSIONS: Reviparin use during and after coronary angioplasty did not reduce the occurrence of major clinical events or the incidence of angiographic restenosis over 30 weeks.
In chronic coronary occlusions the chance of successful reopening by angioplasty can be judged from the age of the occlusion. Often, however, time since occlusion cannot be accurately assessed. Therefore we determined whether the chance of reopening can be predicted from angiographic morphology. In cineangiograms from 60 consecutive patients with chronic coronary occlusions morphological details in at least two projections were evaluated in relation to the rate of success and the estimated age of occlusion. Morphological features associated with a higher rate of success (type A) were a clearcut proximal stump, absence of side branches at the site of occlusion, absence of bridging collaterals, and only slight filling of the distal part of the vessel. Features associated with a low success rate (type B) were absence of proximal stump, side branches at the site of occlusion, bridging collaterals, and rapid high-contrast filling of the distal part of the vessel. 48/60 (80%) of occlusions could be classified as type A or type B. The success rate was 17/21 (81%) in type A versus 5/27 (18.5%) in type B (P < 0.0002). The estimated age of type B occlusions was higher than that of type A medians 8 and 4 months (P < 0.002). Thus in chronic coronary occlusions the likelihood of successful reopening can be judged in many patients from morphological features.
OBJECTIVES: The specific objective of the REDUCE trial was to evaluate the effect of low molecular weight heparin on the incidence and occurrence of restenosis in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Unfractionated heparin and its low molecular weight fragments possess antiproliferative effects and have been shown to reduce neointimal smooth muscle cell migration and proliferation in response to vascular injury in experimental studies. METHODS: The REDUCE trial is an international prospective, randomized, double-blind, multicenter study. Twenty-six centers in Europe and Canada enrolled 625 patients with single-lesion coronary artery obstructions suitable for PTCA. Three hundred six patients received reviparin as a 7,000-U bolus before PTCA, followed by 10,500 U as an infusion over 24 h and then twice-daily 3,500-U subcutaneous application for 28 days. The 306 patients in the control group received a bolus of 10,000 U of unfractionated heparin followed by an infusion of 24,000 U over 24 h. These patients then underwent 28 days of subcutaneous placebo injections. The primary end points were efficacy (defined as a reduction in the incidence of major adverse events [i.e., death, myocardial infarction, need for reintervention or bypass surgery]), absolute loss of minimal lumen diameter and incidence of restenosis during the observation period of 30 weeks after PTCA. RESULTS: Using the intention to treat analysis for all patients, 102 (33.3%) in the reviparin group and 98 (32%) in the control group have reached a primary clinical end point (relative risk [RR] 1.04, 95% confidence interval [CI] 0.83 to 1.31, p = 0.707). Likewise, no difference in late loss of minimal lumen diameter was evident for both groups. Acute events within 24 h occurred in 12 patients (3.9%) in the reviparin group and 25 (8.2%) in the control group (RR 0.49, 95% CI 0.26 to 0.92, p = 0.027) during or immediately after the initial procedure. In the control group, eight major bleeding complications occurred, and in the reviparin group, seven were observed within 35 days after PTCA. CONCLUSIONS: Reviparin use during and after coronary angioplasty did not reduce the occurrence of major clinical events or the incidence of angiographic restenosis over 30 weeks.
In post mortem studies the alterations produced by arteriosclerosis present a panorama of structural changes that defies the determination of an orderly sequence of events (Netter). Proliferation of fibromuscular vascular wall cell elements and over-production of extracellular matrix is quantitatively predominant. Lipid dispositions comprise less than 5% of the average plaque volume. Arteriosclerosis induced experimentally by cholesterol feeding and vessel wall traumatisation shows dependency in plaque composition from cholesterol feeding. The resulting vessel lumen narrowing is predominantly caused by overproliferation and equal with and without cholesterol feeding. The vision of arteriosclerosis as a "Proliferation disease" therefore appears more adequate than that as a "cholesterol storage disease". When patient groups are separated from coronary arteriography into those with normal coronary arteries and into those with coronary arteriosclerosis differences in cholesterol values are found below the age of 50 years, while above the age of 60 years no difference exists. In all groups the overlap is large and the individual risk can not be determined on the base of cholesterol levels. Between extend of angiographic changes and plasma lipid levels no correlation exists. Angiographic progression of disease which is closely correlated with clinical progression is independent of plasma cholesterol levels determined at the beginning of the observation period. The rate of restenosis after PTCA has been found to be independent of plasma cholesterol levels and can not be influenced by cholesterol lowering. In the report from the NHLBI on more than 600 000 individuals total mortality was independent from plasma cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)
Cyclosporine-associated hypertension (CAH) may be mediated in part by sodium and volume retention. To investigate this issue, we studied the effects of a calcium antagonist, nitrendipine (NIT, 10-20 mg b.i.d.), and a converting enzyme inhibitor, lisinopril (LIS, 10-20 mg o.d.), on blood pressure (office BP, 24 hr ambulatory BP), excretion of an acute sodium load (200 mmol/2 hr i.v.), glomerular filtration rate (insulin clearance), cumulative dopamine excretion, plasma atrial natriuretic peptide (ANP), and endothelin excretion in 8 patients with CAH after cardiac transplantation in a double-blind, randomized, crossover trial for 6 weeks. Five patients received a diuretic during the trial at a constant dose. Office diastolic BP (DBP) decreased significantly with LIS from 97 +/- 6 to 87 +/- 9 mmHg and with NIT from 96 +/- 7 to 92 +/- 12 mmHg. Ambulatory 24 hr DBP decreased significantly from 96 +/- 7 mmHg to 86 +/- 10 mmHg (LIS) and to 84 +/- 11 mmHg (NIT). Ambulatory DBP during the day was lowered significantly from 98 +/- 11 mmHg to 87 +/- 10 mmHg (LIS) and to 88 +/- 9 mmHg (NIT) and during the night from 95 +/- 9 mmHg to 86 +/- 8 mmHg (LIS) and to 79 +/- 7 mmHg (NIT). Cumulative sodium excretion 6 hr after an acute sodium load increased to 52 +/- 39 mmol (placebo), 96 +/- 44 mmol (LIS, P < 0.05 vs. placebo), and 71 +/- 34 mmol (NIT). Glomerular filtration rate, cumulative dopamine excretion, ANP, and endothelin excretion did not differ between either treatment group. We conclude, that: (1) both drugs were similar in lowering office BP and during the day, but NIT tended to be more effective during the night; and (2) cumulative sodium excretion during LIS was significantly increased compared with placebo. There was a similar trend during NIT also. Therefore, it is possible that chronic angiotensin-converting enzyme inhibition and possibly calcium antagonists might improve the sodium-retaining state in CAH independent of differences in blood pressure, ANP, dopamine, or renal function.
STUDY OBJECTIVE: To analyze the extent of pericardial constraint on right ventricular function in humans. PATIENTS AND METHODS: Twenty patients, 59 +/- 2 (mean +/- SEM) years old, undergoing coronary bypass surgery. Right ventricular volumes and pressures were evaluated using a rapid response Swan-Ganz thermodilution catheter. INTERVENTIONS: Parameters were determined before and after pericardiotomy, both before and during increased right ventricular systolic pressure by partial compression of the pulmonary artery (before pulmonary compression: 25 +/- 1 mm Hg; during: 39 +/- 1 mm Hg). RESULTS: Pericardiotomy alone did not significantly affect right ventricular end-diastolic volume (before: 79 +/- 4 mL m-2; after: 78 +/- 3 mL m-2), right ventricular ejection fraction (before: 48 +/- 1%; after: 48 +/- 2%), and right atrial pressure (before: 4.3 +/- 0.8 mm Hg; after: 4.3 +/- 0.7 mm Hg). Before pericardiotomy, the increase in right ventricular afterload significantly increased right atrial pressure (to 5.5 +/- 0.7 mm Hg, p < 0.05) and reduced right ventricular ejection fraction (to 43 +/- 2%, p < 0.01). Right ventricular end-diastolic volume remained unchanged. After pericardiotomy, the increase in right ventricular afterload significantly increased right ventricular end-diastolic volume (to 85 +/- 3 mL m-2, p < 0.01) and also reduced right ventricular ejection fraction (to 42 +/- 2%, p < 0.01), while right atrial pressure was not significantly changed. During increased right ventricular afterload, the right ventricular diastolic pressure-volume relation was shifted rightward. CONCLUSIONS: At normal levels of right ventricular diastolic filling, the pericardium does not exert constraining effects on right ventricular function. However, with increasing levels of right ventricular preload, pericardial constraint significantly influences right ventricular function in humans.
A total of 2,979 schoolboys and schoolgirls attending different types of German schools during their seventh year of school attendance (which begins at the age of six) were investigated by means of an anonymous questionnaire in two medium-sized German cities and their suburbs, in respect of smoking behaviour and consumption of drugs and alcoholic beverages. The proportion of schoolboys and schoolgirls smoking at least once or twice a week depended on the type of school: pupils of high schools (linguistic branch, known as "Gymnasium" in Germany) had a quota of 2.7%, whereas there were 14.3% smokers among those attending a category of public school termed "Hauptschule" (a kind of school with elementary and continuing education and a total of nine years' school attendance) and 5.6% smokers among the so-called "Realschüler" (a kind of grammar school stressing practical subjects with a total of 10 years of school attendance) and 8.2% among pupils attending a kind of integrated grammar-cum-"Hauptschule" with an alternative-choice 9-year or 10-year schedule (so-called "Gesamtschule"). A similar distribution was seen in respect of alcohol and drug consumption. Schoolboys and schoolgirls smoking at least once or twice a week will also be drinking a glass of beer per week six times as often as non-smoking pupils. In respect of wine the ratio is 4:1 and in respect of brandy 7:1. Smokers among the pupils have been trying out drugs at least once, six times as often as non-smokers. Results are statistically highly significant (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)