Artificially ambiguous genetic code confers growth yield advantage.

A primitive genetic code is thought to have encoded statistical, ambiguous proteins in which more than one amino acid was inserted at a given codon. The relative vitality of organisms bearing ambiguous proteins and the kinds of pressures that forced development of the highly specific modern genetic code are unknown. Previous work demonstrated that, in the absence of selective pressure, enforced ambiguity in cells leads to death or to sequence reversion to eliminate the ambiguous phenotype. Here, we report the creation of a nonreverting strain of bacteria that produced statistical proteins. Ablating the editing activity of isoleucyl-tRNA synthetase resulted in an ambiguous code in which, through supplementation of a limited supply of isoleucine with an alternative amino acid that was noncoding, the mutant generating statistical proteins was favored over the wild-type isogenic strain. Such organisms harboring statistical proteins could have had an enhanced adaptive capacity and could have played an important role in the early development of living systems.

[Persistent angina pectoris in spite of successful myocardial revascularisation]. / Fortbestehende Angina pectoris trotz erfolgreicher Myokardrevaskularisation.

A 73-year-old obese woman underwent coronary artery-bypass operation in 11/1995 because of a coronary two vessel disease. The left coronary artery was bypassed by the left mammarial internal artery. In 2 and 3/2002, balloon-dilatation of stenoses of the right coronary artery and the circumflex was performed. Angina pectoris relapsed and in 9/2002 the patient was admitted to our hospital with tentative diagnosis of restenosis. Physical investigation showed a blood pressure of the right arm of 160/80 and of the left arm of 120/ 80 mmHg. Coronarography showed the three vessel disease known since 2/2002 with a restenosis of the right coronary artery which was immediately treated by balloon-dilatation and stent-implantation. Colour duplex-sonography of the carotid and subclavian arteries revealed extraordinary plaques and a reduced flow of the left vertebral artery. The left subclavian artery could only be seen distal to the discharge of the vertebral artery and showed a poststenotic flow. The patient had angina pectoris when carrying out personal hygiene already 2 days after balloon-dilatation and stent-implantation. ECG showed new aspects. Coronarography showed no relapse of stenosis, but 70% stenosis of the left subclavian artery with a marked coronary-steal-syndrome. In 10/ 2002, the patient underwent balloon-dilatation and stent-implantation of the subclavian stenosis and became free of complaints. Coronary-steal-syndrome can be the reason for persistent angina pectoris in spite of successful coronary artery-bypass operation with a mammarial internal bypass. It is absolutely necessary to take blood pressure from both arms to recognise a possible stenosis of the subclavian artery which can be the key to all.

[Acute myocardial infarction in premenopausal women]. / Akuter Myokardinfarkt bei prämenopausalen Frauen.

UNLABELLED: Prospective, systematic studies of the pathophysiology and prognosis of premenopausal women vs young men who suffer an acute myocardial infarction (MI) and are treated with direct angioplasty are scarce. METHODS AND RESULTS: A total of 782 consecutive and unselected patients who presented with an acute ST-elevation MI within 12 h of symptom onset underwent immediate angiography to guide direct angioplasty. Using this therapeutic approach clinical characteristics, angiographic observations, and short- and long-term prognosis were analyzed in a sub-group of 31 premenopausal women and compared to 192 young men with acute MI. Premenopausal women account for 4% of individuals with acute MI and for 15% (31/205) of all women. Men of the same age range make up 25% (192/782) of all MI patients (p<0.001). Three or more classic risk factors were present in 20/31 women. Young women presented later than men. Angiography demonstrated a coronary occlusion in 27/31 women (88%) but in 98% of young men (p<0.02). Direct PTCA was successful in all premenopausal women and in 179/185 men (97%, p=ns). Predischarge EF was 57% in women and 54% in men (p=ns). After 4 years of follow-up, all women had survived as compared to a 95% survival in young men. Major cardiac events had occurred in 50% of persons of either gender. CONCLUSION: Premenopausal women account for 4% of individuals and for 1/6 of all female patients who presented with acute MI within 12 h of onset. Hospital admittance is delayed in young women. MI was caused by (atherosclerotic) coronary occlusion in most young women and in virtually all young men. Short- and long-term survival of premenopausal women is favorable after direct PTCA for acute MI and not different than men from the same age group.

[Long-term follow-up after direct PTCA in women with acute myocardial infarction]. / Langzeitbefunde der primären Angioplastie bei Frauen mit akutem Myokardinfarkt.

METHODS: Long-term follow-up of 204 consecutive and unselected women vs 577 men after direct PTCA for acute myocardial infarction. RESULTS: Women were older, had more significant comorbidity, and had a longer prehospital phase. Direct PTCA of the infarct artery was angiographically successful in 95% of women and in 94% of men. Total cumulative mortality during 4 years of follow-up was 12.5%, 14.5% 18%, and 23% in women, respectively, vs 9%, 10.5%, 12%, and 15%, respectively, in men (p=ns through year 3, p<0.05 thereafter). After multivariate analysis, gender was no independent risk factor of increased mortality. Major cardiac events and need for target vessel revascularization were unrelated to gender. CONCLUSIONS: There are no gender-specific differences in mortality after direct PTCA for acute myocardial infarction.

[Prevalence and significance of coronary collateral circulation in patients with acute myocardial infarct]. / Prävalenz und Bedeutung der koronaren Kollateralzirkulation bei Patienten mit akutem Myokardinfarkt.

UNLABELLED: Angiograms from consecutive and unselected patients with acute myocardial infarction were studied with respect to the prevalence as well as the significance of coronary collateral circulation to myocardium distal to the acute coronary occlusion. METHODS: Coronary angiograms were obtained from 700 consecutive and unselected patients with an acute transmural infarction within 3.7 +/- 3 hours (0.5-12) of symptom onset. No patient had undergone i.v. thrombolysis prior to angiography. Complete and acute vessel occlusion was found in 626/700 patients (89%). Coronary collaterals were detected and graded using Rentrop's classification. The grade of collateral circulation was related to the clinical course after 30 days and to the global and regional left ventricular wall motion. RESULTS: Collaterals were found in 334 patients (69%); 242 patients (38%) had collateral flow grade 2 or 3. Collaterals were demonstrated more frequently in women vs men and in patients with multivessel disease. The prevalence of collaterals was unrelated to age and the presence of diabetes mellitus. Patients who had angiography within 3 hours of symptom onset had collaterals detected less frequently than patients who had angiography beyond 6 hours (66% vs 75%, p < 0.05). No collaterals were found in 17/37 patients (47%) in cardiogenic shock and inferior MI but in only 30/164 patients (18%, p < 0.01) without shock. Global and regional left ventricular wall motion after 2 weeks was unrelated to the degree of coronary collateral circulation during acute myocardial infarction. CONCLUSION: Collateral circulation to myocardium distal to an acutely occluded coronary artery is detected in 2/3 patients during the acute infarct phase. The absence of collaterals is related to the early occurrence of cardiogenic shock in patients with inferior MI but not to the presence of diabetes mellitus. After direct angioplasty of the infarct vessel, the protective effects of coronary collaterals on chronic LV function remain uncertain.

Purification of a model substrate for transcription factor phosphorylation by ERK2.

ERK2 belongs to the mitogen-activated protein kinase subfamily, which plays a pivotal role in cell signal transduction, in which it mediates effects on proliferation and differentiation by growth factors and hormones. While its cellular function has been under intense scrutiny since its initial discovery nearly 15 years ago, little progress has been made in understanding its kinetic mechanism. Such an understanding is important for the development of potent and specific inhibitors. A contributory factor has been the lack of a protein substrate suitable for rigorous mechanistic studies. Here we report the expression, purification, and characterization of the N-terminus (residues 1 through 138) of the transcription factor Ets-1, an excellent model substrate for ERK2 mechanistic studies. (His(6)-tagged)Ets-1(1-138) was expressed in Escherichia coli and rapidly purified in two steps by nickel-agarose-affinity chromatography, followed by high-resolution Mono-Q anion-exchange chromatography. A yield of 60 mg of the purified protein per liter of culture was obtained and could be stored conveniently at -80 degrees C in water. Rigorous characterization demonstrated that under the assay conditions, (His(6)-tagged)Ets-1(1-138) is exclusively phosphorylated on residue Thr-38 by ERK2 with the following Michaelis parameters: k(cat) = 17 s(-1), K(ATP)(m) = 140 microM, K(ATP)(i) = 68 microM, K(Ets-1)(m) = 19 microM, and K(Ets-1)(i) = 9.3 microM.

Results and significance of Holter monitoring after direct percutaneous transluminal coronary angioplasty for acute myocardial infarction.

Whether acute and direct percutaneous transluminal coronary angioplasty improves the incidence of nonsustained ventricular tachycardia in patients surviving acute myocardial infarction is not known. In 400 consecutively studied patients, Lown classification IVb on Holter monitoring was only associated with arrhythmia morbidity, whereas reduced ejection fraction was related to total and cardiac mortality and arrhythmia morbidity.

The kinetic mechanism of the dual phosphorylation of the ATF2 transcription factor by p38 mitogen-activated protein (MAP) kinase alpha. Implications for signal/response profiles of MAP kinase pathways.

The mitogen-activated protein kinases (MAPKs) are a family of enzymes conserved among eukaryotes that regulate cellular activities in response to numerous external signals. They are the terminal component of a three-kinase cascade that is evolutionarily conserved and whose arrangement appears to offer considerable flexibility in encompassing the diverse biological situations for which they are employed. Although multistep protein phosphorylation within mitogen-activated protein kinase (MAPK) cascades can dramatically influence the sensitivity of signal propagation, an investigation of the mechanism of multisite phosphorylation by a MAPK has not been reported. Here we report a kinetic examination of the phosphorylation of Thr-69 and Thr-71 of the glutathione S-transferase fusion protein of the trans-activation domain of activating transcription factor-2 (GST-ATF2-(1-115)) by p38 MAPKalpha (p38alpha) as a model system for the phosphorylation of ATF2 by p38alpha. Our experiments demonstrated that GST-ATF2-(1-115) is phosphorylated in a two-step distributive mechanism, where p38alpha dissociates from GST-ATF2-(1-115) after the initial phosphorylation of either Thr-69 or Thr-71. Whereas p38alpha showed similar specificity for Thr-71 and Thr-69 in the unphosphorylated protein, it displayed a marked difference in specificity toward the mono-phosphoisomers. Phosphorylation of Thr-71 had no significant effect on the rate of Thr-69 phosphorylation, but Thr-69 phosphorylation reduced the specificity, k(cat)/K(M), of p38alpha for Thr-71 by approximately 40-fold. Computer simulation of the mechanism suggests that the activation of ATF2 by p38alpha in vivo is essentially Michaelian and provides insight into how the kinetics of a two-step distributive mechanism can be adapted to modulate effectively the sensitivity of a signal transduction pathway. This work also suggests that whereas MAPKs utilize docking interactions to bind substrates, they can be weak and transient in nature, providing just enough binding energy to promote the phosphorylation of a specific substrate.

[Thyroid function after iodine-containing contrast agent administration in coronary angiography: a prospective study of euthyroid patients]. / Schilddrüsenfunktion nach Gabe jodhaltigen Röntgenkontrastmittels bei Koronarangiographie--eine prospektive Untersuchung euthyreoten Patienten.

In a prospective study, thyroid metabolism in 102 patients undergoing diagnostic coronary angiography was investigated, stratified for thyroid morphology. The thyroid function serum parameters "TT3, rT3, TT4, fT4 and TSH" and the urinary iodine excretion were measured before and three weeks after diagnostic intraarterial administration of the iodine-containing contrast agent. Only patients with euthyroid function were included in order to answer the questions whether or not the administration of non-ionic iodine containing contrast medium leads to significant thyroid function changes in euthyroid patients and whether thyroid morphology is a prognostic factor for the risk of developing hyperthroidism. Serum concentrations of thyroid autoantibodies (TPO-Ab, Tg-Ab, TSH-receptor-Ab) were measured and thyroid ultrasound was performed. According to the ultrasound findings, 4 morphologic groups were formed: normal thyroid glands (n = 37), normal sized but nodular glands (n = 16), diffuse goiter (n = 15) and nodular goiter (n = 34). Twenty-five patients were positive for Tg-Ab; TPO-Ab were found in 13 patients. TSH-receptor-Abs were not detected in all patients. TT3 levels did not significantly change after iodine application (p = 0.30). TT4 and fT4 levels showed significantly different alterations in the 4 groups (fT4 p < 0.001). The amount of iodine given did not influence alteration of serum concentrations of TSH (p = 0.67), TT3 (p = 0.68), TT4 (p = 0.37), fT4 (p = 0.92) and rT3 (p = 0.81). Elevated levels of urinary iodine excretion correlated with the amount of contrast medium given (p = 0.087). Albeit there was a high number of nodular transformed glands and goitrous patients included, and our cohort was recruited in an iodine deficient area, we did not observe hyperthyroidism in any patient. However, thyroid function parameters are significantly altered after coronary angiography independent of antibody status and the amount of contrast agent given, but dependent on thyroid morphology.

Type 2 diabetes and acute myocardial infarction. Angiographic findings and results of an invasive therapeutic approach in type 2 diabetic versus nondiabetic patients.

OBJECTIVE: Mortality in diabetic patients with acute myocardial infarction (MI) is high. The significance of the pretreatment coronary status in type 2 diabetic patients with acute MI, as well as the effect of mechanical revascularization using percutaneous transluminal coronary angioplasty (PTCA), has not been established. RESEARCH DESIGN AND METHODS: All patients with type 2 diabetes and acute MI (n = 54) were prospectively enrolled into a study of immediate coronary angiography to guide PTCA of the occluded infarct vessel. Hospital and long-term course were assessed and compared with an unselected control group of nondiabetic patients (n = 358) who were enrolled in the same study. RESULTS: Angiography showed that sites of occlusion and acute coronary flow were similar in both groups. Multivessel disease and shock were more common in type 2 diabetic versus nondiabetic patients: 69 vs. 51% and 21 vs. 10% (P < 0.02), respectively. Direct PTCA was successful in > 90% in both groups. Mortality after 30 days was 13% in type 2 diabetic patients versus 5% in patients without diabetes (P < 0.04). Left ventricular (LV) ejection fraction before discharge was lower in diabetic patients (48 +/- 17 vs. 55 +/- 15%, P < 0.05). Mortality 1 year after discharge was 11 vs. 4% in diabetic versus nondiabetic patients (P < 0.02). Multivariate analysis identified type 2 diabetes as an independent risk factor for acute, but not for late, mortality. CONCLUSIONS: Direct PTCA is safe and effective in type 2 diabetic patients with acute MI. Mortality after 30 days in unselected diabetic patients is < 15% with this approach. Advanced disease and shock contribute to an increased mortality in type 2 diabetic patients with acute MI versus nondiabetic patients.

[Acute myocardial infarction late after coronary artery bypass grafting: angiographic findings and results of an invasive approach]. / Akuter Myokardinfarkt spät nach aortokoronarer Bypassoperation: Angiographische Befunde und klinische Ergebnisse eines invasiven Vorgehens.

Patients who have undergone coronary artery bypass grafting may develop acute myocardial infarction late after surgery. It is not exactly known in these patients whether acute infarction is predominantly caused by occlusion of bypass or native vessels. Also, there is no systematic and prospective data available with respect to an invasive, revascularizing therapeutic approach. Therefore, acute coronary angiograms were obtained in 21 consecutive patients with acute infarctions and remote bypass grafting to elucidate mechanisms causing myocardial infarction in these patients, and to assess results of catheter-based recanalization. Infarction was causes by acute graft occlusion in 12/21 patients. Fibrinolysis and/or PTCA of grafts was successful in 6/8 attempts, direct PTCA of a native vessel was effective in 1/2 patients, 1 patient underwent emergency re-CABG, and another patient was treated noninvasively. Occlusion of native, ungrafted vessel caused infarction in 9 patients. Direct PTCA of native vessels was effective in 6/7 of those patients, 1 patient had re-CABG, and another patients was treated non-invasively. Together, catheter-based recanalization was obtained in 13/17 attempts. Thirty-day and 1 year mortality (after discharge) was 5% (1/21 patients) and 12%, respectively. Predischarge ejection fraction was 46%. In conclusion, acute occlusion of bypass grafts is responsible for about half of all cases of myocardial infarction in patients late after surgery. Direct angiography and individually tailored catheter-based recanalization in patients with acute myocardial infarction late after surgery yield promising results.

Low prevalence of Chlamydia pneumoniae in atherectomy specimens from patients with coronary heart disease.

Coronary atherectomy specimens from 50 patients with coronary heart disease were examined for the presence of Chlamydia pneumoniae by two different methods of polymerase chain reaction (PCR) and by in situ hybridization. C. pneumoniae DNA was detected by PCR in atherosclerotic plaques of four patients (8%). Two patients' coronary atheromas were positive, both by a single-step 16S rRNA-based PCR and by an omp1-based nested PCR. The other two patients' specimens were positive only by the nested PCR. In contrast, C. pneumoniae was not detected by in situ hybridization in any of the cardiovascular tissues tested. Of three patients with evidence of C. pneumoniae in coronary atheromas, two had an antibody titer of 1:32 and the third had no specific antibodies detectable. Results of this study demonstrate a low prevalence of C. pneumoniae DNA in coronary atheromas. These findings do not support the hypothesis that the organism plays a major role in atherogenesis.

[Disorders of microcirculation in coronary heart disease]. / Störungen der Mikrozirkulation bei der koronaren Herzkrankheit.

Disturbances of microcirculation in coronary artery disease can be seen in the presence of critical stenosis of epicardial coronary arteries, as a result of endothelial dysfunction in the absence of significant stenosis or during recovery of ischaemic myocardium after successful angioplasty of stenosed or occluded coronary arteries. Diagnostic methods are morphologic/morphometric analyses, measurement of the global coronary reserve, measurement of the regional coronary microcirculation (scintigraphy, positron emission tomography) and laboratory analysis of haemorheological alterations (plasma, erythrocytes, leucocytes). After successful angioplasty, normalisation of glutamate extraction rate takes three to six months. In patients with unstable angina, changes in plasma viscosity, erythrocyte aggregation and neutrophil activation occur. Neutrophils are activated after successful angioplasty in acute myocardial infarction and even after elective angioplasty (when measured in the coronary sinus). Therapeutic improvements of disturbed microvascular flow can be obtained by increasing perfusion pressure (by revascularisation, nitrates, calcium antagonists, physical training), by improving the fluidity of the blood and by reducing the extravascular component of coronary vascular resistance (by antihypertensive treatment).

Long-term follow-up after direct percutaneous transluminal coronary angioplasty for acute myocardial infarction.

OBJECTIVES: The purpose of this study was to analyze long-term follow-up information over several years from consecutive, unselected patients treated with direct percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction (MI). BACKGROUND: Direct PTCA is often used in patients with acute MI. Short-term results are favorable. However, there is less information available on long-term observations over several years in these patients. METHODS: A total of 416 consecutive and unselected patients with acute MI underwent direct PTCA. Survival of the acute infarct phase was 94.2%; the remaining 392 patients--the study population-were discharged and followed for 3.3+/-1.4 years. Mortality as well as cardiac events and reinterventions are reported. Clinical variables assessed at the time of discharge are submitted to statistical analysis to detect potential risk factors. RESULTS: Total cumulative mortality in the first year was 10% for the entire group and 6% for patients not presenting in cardiogenic shock. Mortality after discharge was 4.6% in the first year and dropped to <4% per year thereafter. Reinterventions after discharge were required in 16% in the first year and in <4% per year in years 2 to 4. Poor left ventricular ejection fraction (<35%), three-vessel disease and advanced age (> or =75 years) were long-term risk factors for total mortality after direct PTCA. CONCLUSIONS: The clinical benefit of direct PTCA for acute MI is maintained during follow-up with respect to mortality. However, reinterventions for restenosis or de novo stenosis are often required (10% to 20%). Although few in number (<10%), patients with severely impaired left ventricular function continue to have a poor prognosis.

Endolaryngeal high-frequency ultrasound.

High-frequency ultrasound can provide high-resolution imaging for diagnosing diseases of the head and neck. Over the last few years, a virtual technical evolution has led to the development of small and flexible ultrasound transducers with even greater anatomic resolution. The aim of the present study was to evaluate the efficacy of this new technique for imaging normal and altered anatomical structures of the endolarynx. Specially developed high-resolution, real-time ultrasound transducers (10 and 20 MHz) placed on the tip of endoluminal catheters were inserted into 20 autopsied larynges and five laryngectomy specimens. In a standardized examination process the endolarynx was analyzed in a real-time mode. Using this technique, exact 360 degrees cross sections of the larynx were obtained, demonstrating that it was possible to image the structures of the endolarynx with ultrasonography. Depending on the frequency used, all anatomical structures could be visualized up to a depth of 2 cm. In laryngeal cancer the depth of tumor as well as its relationship to the laryngeal framework could be clearly recognized. These findings suggest that this new endoluminal sonographic procedure represents a potentially important diagnostic tool in the assessment of laryngeal carcinoma.

Positive association of the beta fibrinogen H1/H2 gene variation to basal fibrinogen levels and to the increase in fibrinogen concentration during acute phase reaction but not to coronary artery disease and myocardial infarction.

BACKGROUND: Fibrinogen has been demonstrated to be an independent risk factor of cardiovascular disease. The absence of the HaeIII cutting site (H2 allele) of an H1/H2 gene variation in the promoter region of the beta fibrinogen gene was associated with increased levels of fibrinogen. METHODS AND RESULTS: In the present study, the effects of the H1/H2 gene variation not only on plasma fibrinogen concentrations but also on coronary artery disease (CAD) and myocardial infarction (MI) were investigated in 923 individuals who underwent coronary angiography for diagnostic purposes. Relation of the H1/H2 genotype to fibrinogen plasma levels: A strong association was observed between the H1/H2 gene variation and fibrinogen levels. The differences in fibrinogen plasma levels between H2H2 and H1H1 homozygotes were almost threefold more pronounced within subjects with clinical chemical signs of an acute phase reaction (CRP > or = 7.5 mg/l) than within a subgroup of subjects without these signs (CRP < 7.5 mg/l) (median of CRP distribution: 7.5 mg/l). In 207 patients who underwent aortocoronary bypass surgery plasma fibrinogen levels were almost identical directly after surgery. Two days after operation fibrinogen increased to clearly higher levels in H2H2 homozygotes than in H1H2 and H1H1 genotypes, whereas almost the same maximal increases in fibrinogen concentrations were reached 3-4 days after surgery in all individuals. Relation of the H1/H2 genotype to CAD and MI. Whereas in the total population the plasma fibrinogen concentrations were strongly associated with smoking, CAD and MI, an association of the H1/H2 gene variation to CAD and MI was not detected. However, mean age at first MI of H2H2 individuals (62.9 years) was clearly higher than of H1H2 genotypes (56.9 years) and of H1H1 subjects (56.4 years). In addition, in a subgroup of individuals with a higher risk of MI by either high apoB and/or low apoA1 plasma levels the portion of MI patients was clearly smaller within H2H2 homozygotes than within H1H2 or H1H1 genotypes, although-also in these high risk groups-mean age at first MI of H2H2 individuals were higher than of the other two genotypes. CONCLUSIONS: Obviously, the H2 allele of the fibrinogen H1/H2 genotype does not only influence basal fibrinogen concentrations, but particularly also the extent of fibrinogen level increase during acute phase reaction. Whereas the fibrinogen plasma level is positively associated with coronary artery disease and myocardial infarction, the H2 allele-although exhibiting an association with elevated fibrinogen levels-was not positively associated with CAD and MI.

[New studies, new trends: directional coronary atherectomy]. / Neue Studien, neue Trends: Direktionale koronare Atherektomie.

Despite theoretical advantages of Directional Coronary Atherectomy (DCA) vs. PTCA, the first two controlled studies comparing both methods, the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT), and the Canadian Coronary Atherectomy Trial (CCAT), showed no clinical benefit of DCA, A second generation of trials, the Optimal Atherectomy Restenosis Study (OARS) and the Balloon versus Optimal Atherectomy Trial (BOAT), designed to optimize DCA with the use of 7F devices and adjunctive PTCA revealed lower angiographic restenosis rates compared to CAVEAT. In addition, the preliminary follow-up results of BOAT, presented by Donald S. Baim in Birmingham in August 1996, showed a 20% reduction of angiographic restenosis after DCA compared to PTCA. There was no association between post-procedure CK-MB elevation in the DCA group and late mortality. These results may further expand the application of DCA to clinical routine, whereas this procedure still has specific indications like treatment of ostial and bifurcation lesions and atherectomy in future may be the treatment of choice for restenosis in coronary stents.

The expression of angiotensin-I converting enzyme in human atherosclerotic plaques is not related to the deletion/insertion polymorphism but to the risk of restenosis after coronary interventions.

Plasma and tissue concentrations of the angiotensin-I converting enzyme (ACE) have been shown to be associated with the ACE insertion/deletion (I/D) polymorphism. The purpose of this study was to examine the relation of ACE levels in atherosclerotic plaques to the ACE I/D polymorphism and to restenosis after balloon angioplasty and directional atherectomy (DCA). The study included 104 patients who underwent DCA and received angiographic follow-up at 12 to 18 months. The amount of ACE protein in various morphologically defined plaque components (fibrous, atheromatous, and complicated lesions) of the atherectomy specimens was determined by qualitative and semiquantitative immunohistochemistry. ACE levels were related to the ACE genotype, to plaque morphology and to the risk of restenosis. Sequential staining revealed that pathologic ACE overexpression of the atherosclerotic lesions occurred in intimal smooth muscle cells, fibrocytes/fibroblasts and macrophage/foam cells. The ACE content of the whole plaques and of the single plaque components was not associated with the I/D polymorphism, but with restenosis after coronary interventions. In addition, ACE levels in the atherosclerotic lesions correlated with the severity of vessel wall damage. The ACE phenotype might serve as an indicator for the risk of restenosis after coronary interventions.

[Early and long-term results of direct PTCA in patients with acute myocardial infarct]. / Früh- und Langzeitergebnisse der direkten PTCA bei Patienten mit akutem Myokardinfarkt.

A review of the literature suggests that direct PTCA for acute myocardial infarction is indicated and feasible in 90-95% of unselected, consecutive patients; direct PTCA is reported to be successful in > 90% of procedures. This results in a hospital mortality of 3-7% for unselected patients and a 4% re-infarction rate. A recent meta-analysis of direct PTCA vs i.v. thrombolysis in patients with acute infarction demonstrates a lower mortality after PTCA (4.4% vs 6.5%, p = 0.02) as well as lower mortality/re-infarction rate (7.2% vs 11.9%, p < 0.001). Mortality in the 1st year after discharge is < 5% with about half of the fatalities being due to cardiac causes. Patients presenting with or developing cardiogenic shock in the acute infarct phase experience a 20-50% acute mortality. Mortality rests at < 10% in these patients in the first year after discharge. In conclusion, (1) direct PTCA is feasible without additional risks in patients with acute myocardial infarction, (2) angiographic and clinical success rates of direct PTCA are favorable and superior to i.v. thrombolysis in the hands of expert operators, and (3) referral to an institution providing the option of immediate, direct PTCA must be considered in the patient with acute infarction but contraindication(s) to i.v. thrombolysis.