[Drug therapy of stroke in the stroke unit. A race against time]. / Medikamentöse Schlaganfalltherapie in der Stroke-Unit. Ein Wettlauf gegen die Zeit.

Ischemic stroke is usually a manifestation of arteriosclerosis in the elderly patient. The major risk factors are age and high blood pressure; prevention is particularly successful in hypertensives. All known antihypertensive agents can be applied, and ACE inhibitors and the lipid-lowering agents, in particular the statins are now well established. That said, under certain circumstances it might be of importance to pay greater attention to the other lipid fractions. It is currently estimated that only one-third of patients with a disturbance of lipid metabolism actually receives treatment. Results of treatment in the acute phase of apoplexy have been improved by the establishment of stroke units that provide the facilities for intensive and comprehensive management of stroke victims. Inhibitors of platelet aggregation, in particular aspirin, now have a permanent role in the acute and follow-up phase. For specific risk factors such as stenosis of the carotid artery or atrial flutter, special therapeutic guidelines apply.

[Carotid angioplasty]. / Carotisangioplastie.

The first angioplasty of a carotid artery stenosis was performed 20 years ago. However, only in recent years has the method been improved, mainly by cardiologists (guiding catheters, stents), and is performed today as primary stent implantation (PTCS). This procedure is achieving an increase not only of the immediate success rate (nearly 100%) but also of the long-term success rate. Additionally neurologic complications (< 6%) and rate of restenosis (< 10%) have been reduced. Further technological improvement is expected (cerebral protection). Some indications are now accepted by vascular surgeons. Patients with high risk for carotid thrombendarterectomy (TEA) are mainly treated interventionally since TEA is still accepted as the gold standard. A definitive validation of PTCS compared to TEA is still outstanding, but reguired in the near future.

[Use of coronary angiography after acute myocardial infarction in Germany: a comparison of daily clinical practice with international guidelines. MITRA Study]. / Indikationsstellung zur Herzkatheteruntersuchung nach akutem Myokardinfarkt in Deutschland: Klinische Praxis vs. Richtlinien. MITRA-Studie.

OBJECTIVES: Two third of patients with acute myocardial infarction are admitted to hospitals without cardiac catheterization facilities. Whether a postinfarction patient will undergo cardiac catheterization or not is more often decided by general physicians than by cardiologists. The purpose of this presentation is to investigate the determinants for decision making to use cardiac catheterization in patients after myocardial infarction. METHODS: MITRA is a prospective, multicenter registry, which enrolls all consecutive patients with acute Q wave infarction admitted to 54 hospitals in Southwestern Germany. During the pilot phase 949 consecutive survivors of acute myocardial infarction were included, and inhospital outcome as well as therapeutic strategies were registered. RESULTS: Only half of the patients underwent cardiac catheterization regardless of whether a catheterization facility was available or not. In 63% of the patients under 65 years of age coronary angiography was performed; however, every fourth patient with age above 70 years was transferred to an invasive therapeutic strategy. The percentage of male patients was twice a high in the invasive group, whereas patients with prior infarction, clinical signs of congestive heart failure, patients with moderately or severely impaired left ventricular function, and finally patients with a prehospital delay of more than 4 hours were more frequent in the conservative group. The following three parameters were calculated to be independent determinants of an invasive strategy: pathological stress ECG (OR: 2.8; CI: 1.80-4.60), patients < 70 years without stress ECG (OR: 2.18; CI: 1.5-3.18), and male gender (OR: 1.45: CI: 1.10-2.00). Independent factors of a conservative strategy were primary PTCA (OR: 0.2; CI: 0.09-0.46), prehospital delay > 4 hours (OR: 0.71; CI: 0.51-0.97), and the combination of age > 70 years and the absence of a stress ECG (OR: 0.78; CI: 0.55-1.11). CONCLUSIONS: In Germany, patients with acute myocardial infarction are less likely to undergo cardiac catheterization compared to patients in other Western countries (e.g. , the United States). Despite recommended guidelines, invasive strategies are more frequent in low risk groups (younger patients, male gender) than in postinfarction patients at high risk (severely impaired left ventricular function, clinical signs of congestive heart failure, the elderly).

Daytime and nighttime differences in patterns of performance of primary angioplasty in the treatment of patients with acute myocardial infarction. Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) Study Group.

BACKGROUND: Concern exists regarding the results of primary angioplasty for acute myocardial infarction when the procedure is performed during night hours. METHODS AND RESULTS: Between June 1994 and January 1997, 491 patients with acute myocardial infarction who underwent primary angioplasty procedures were consecutive registered in the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) study. Three hundred seventy-eight patients (77%) were treated during the day and 113 (23%) at night. Baseline characteristics showed no major differences between the 2 groups. Prehospital delay time was 60 minutes shorter during the night (median value 180 minutes for day, 120 minutes for night, P =.005), and in-hospital time to treatment was 9 minutes longer (median value 85 minutes day, 94 minutes night, P =.037). Patients treated during the night more often received angiotensin-converting enzyme blockers (61.4% day, 76.1% night, P =.004) and the so-called optimal adjunctive therapy (54% day, 64.6% night, P =.045). There were no differences concerning clinical events between the 2 groups. Hospital mortality was 8.7% during the day and 5.3% during the night (univariate analysis P =.238; logistic regression P =.653). CONCLUSIONS: In a clinical setting, primary angioplasty for acute myocardial infarction can be performed safely during the night with a clinically insignificant prolongation of in-hospital time to reperfusion compared with practice during the day.

Impact of early risk stratification on the length of hospitalization in patients with acute Q-wave myocardial infarction. 'The 60-minutes myocardial infarction project'.

UNLABELLED: An assessment of individual risk factors may identify a subgroup of postinfarction patients at low risk, i.e. patients appropriate for early discharge. Using a large unselected population of the national registry, 'The 60-Minutes Myocardial Infarction Project', we (1) attempted to provide a retrospective analysis of clinical factors and in-hospital mortality in a population living on the 6th hospital day following admission to define a low-risk patient group with a residual in-hospital mortality of less than 1% eligible for early discharge, and (2) to analyze the current impact of risk stratification based on these clinical factors on the length of hospitalization. The study group consisted of 12,045 survivors on the 6th day after admission out of 14,980 patients of the registry with proven Q-wave myocardial infarction. Risk modeling was performed with multiple logistic regression. RESULTS: A total of 873 patients (7.3%) died after day 6 in hospital. The most important prognostic factors were cardiopulmonary resuscitation prior to admission (odds ratio, OR: 7.2, confidence interval, CI: 5.11-10.22), thrombolysis complicated by severe bleedings (OR: 6.2, CI: 1.2-31. 2) and age >70 years (OR 4.7, CI 3.51-6.39). The other more significant independent predictors of increased mortality were end-stage renal disease, age between 56 and 70 years, systolic blood pressure <95 mm Hg on admission, history of trauma

[Ultra-high dosage streptokinase lysis in dysfunction of a St. Jude aortic prosthesis]. / Ultrahochdosierte Streptokinase-Lyse bei Dysfunktion einer St.-Jude-Aortenprothese.

HISTORY AND CLINICAL FINDINGS: A 64-year-old man was hospitalised because of progressively worsening dyspnoea over the preceding few months. Three years previously he had undergone aortic valve replacement (St. Jude Medical bileaflet valve) for severe aortic stenosis and some regurgitation. He was much improved postoperatively and one year after the operation echocardiography demonstrated a well functioning prosthetic valve and a transvalvar pressure gradient (by Doppler echocardiography) of 28 mm Hg. On admission the patient reported to have stopped phenprocoumon 9 months before admission. The patient was in cardiac failure, grade III (NYHA classification). On auscultation there was a 4/6 crescendo-decrescendo systolic murmur and a 2/6 early diastolic decrescendo murmur maximal over the second right ICS. INVESTIGATIONS: Echocardiography confirmed the suspected diagnosis of dysfunction of the prosthetic valve, one leaflet being immobile, with severe outflow obstruction (peak transvalvar pressure gradient 101 mm Hg) combined with severe regurgitation. At fluoroscopy one leaflet moved normally, the other one being fixed between opening and closing positions. TREATMENT AND COURSE: As thrombosis was the most likely cause of the prosthetic valve dysfunction, thrombolysis treatment was started. After administration of 9 mill. IU streptokinase both leaflets showed normal movement. The peak transvalvar gradient (by echocardiography) was now 40 mm Hg and there was only slight regurgitation. No complications were noted. After oral anticoagulation for 6 months the prosthetic valve was functioning normally with unchanged movement pattern of both leaflets. CONCLUSION: Thrombolysis may be successful in thrombotic dysfunction of a prosthetic valve. If there are no contraindications, this form of treatment should be tried before reoperation is undertaken.

More rapid, complete, and stable coronary thrombolysis with bolus administration of reteplase compared with alteplase infusion in acute myocardial infarction. RAPID Investigators.

BACKGROUND: Early restoration and maintenance of normal (TIMI 3) blood flow during acute myocardial infarction is critical for optimal preservation of left ventricular function and survival. Recombinant plasminogen activator (r-PA, reteplase) is a nonglycosylated deletion mutant of wild-type tissue-type plasminogen activator (TPA) that has been shown to achieve more rapid and complete thrombolysis compared with other plasminogen activators in animal models. METHODS AND RESULTS: The RAPID Trial was designed to test the hypothesis that bolus administration of one or more dosage regimens of r-PA was superior to standard-dose alteplase (TPA) in achieving infarct-related artery patency 90 minutes after initiation of treatment. Six hundred six patients with acute myocardial infarction were randomized to one of four treatment arms: (1) TPA 100 mg i.v. over 3 hours, (2) r-PA as a 15-MU single bolus, (3) r-PA as a 10-MU bolus followed by 5 MU 30 minutes later, or (4) r-PA as a 10-MU bolus followed by 10 MU 30 minutes later. Coronary arteriography was performed at 30, 60, and 90 minutes after initiation of treatment and at hospital discharge. The 10 + 10-MU r-PA group achieved better 90-minute and 5- to 14-day TIMI 3 flow (63% [CI, 55% to 71%] versus 49% [41% to 57%], P = .019, and 88% [82% to 94%] versus 71% [63% to 79%], P < .001, respectively) than the TPA group. The TIMI 3 flow in the 10 + 10-MU r-PA group at 60 minutes was equivalent to that in the TPA group at 90 minutes (51 versus 49%). Global ejection fraction and regional wall motion in the 10 + 10-MU r-PA group were superior to those of the TPA group at hospital discharge (53 +/- 1.3% versus 49 +/- 1.3%, P = .034; -2.19 +/- 0.12 versus -2.61 +/- 0.13 SD per chord, P = .02, respectively). The 15-MU and 10 + 5-MU r-PA patency and left ventricular function results were similar to those of the TPA and inferior to those of the 10 + 10-MU r-PA group. Bleeding complications were similar between the groups. CONCLUSIONS: r-PA given as a double bolus of 10 + 10 MU achieves more rapid, complete, and sustained thrombolysis of the infarct-related artery than standard-dose TPA, without an apparent increased risk of complications. This was associated with improved global and regional left ventricular function at hospital discharge.

Open, noncontrolled dose-finding study with a novel recombinant plasminogen activator (BM 06.022) given as a double bolus in patients with acute myocardial infarction.

The novel recombinant plasminogen activator (r-PA) (BM 06.022) is a mutant of tissue-type plasminogen activator expressed in escherichia coli which can be given as a bolus because of a prolonged half-life. The primary objective of this trial was to determine the efficacy of an intravenous r-PA double bolus (first bolus of 10 MU followed by 5 MU after 30 minutes) in patients with acute myocardial infarction. All patients received heparin intravenously and acetylsalicylic acid orally. Efficacy was assessed from infarct artery patency by coronary angiography (Thrombolysis in Myocardial Infarction trial perfusion grades 2 or 3) in 50 patients. Ninety minutes after administration of the first r-PA bolus, the infarct-related coronary artery was patent in 39 of 50 patients (78%; 95% confidence interval 64 to 88%). An angiographically confirmed reocclusion occurred in 1 patient between 90 minutes and 24 to 48 hours. The reocclusion rate was influenced by 8 interventions and 1 angiogram missing at 24 to 48 hours. Measurements of hemostatic parameters showed a decrease in fibrinogen to 37% of baseline value. There were 3 clinical reinfarctions before discharge and 2 major puncture site hemorrhages. No further serious bleeding and no serious adverse event with lethal outcome occurred. The 10 + 5 MU r-PA double bolus regimen appears to be effective with regard to patency and the success of thrombolysis. The incidence of reocclusion is very low. From the limited number of patients treated in this study, one need not be concerned about the safety profile of r-PA.

Coronary reperfusion studies with pro-urokinase in acute myocardial infarction: evidence for synergism of low dose urokinase.

Pro-urokinase is a single chain precursor of two chain urokinase, which has been shown to induce fibrin-selective plasminogen activation. In the present study, thrombolytic efficacy of 9 million U of glycosylated pro-urokinase administered intravenously was compared with that of a combined regimen utilizing 4.5 million U of pro-urokinase and 0.2 million U of urokinase. Seventy-five patients with a first myocardial infarction were randomized to receive high dose pro-urokinase (n = 40, group A) or the combination therapy (n = 35, group B). Reperfusion of the infarct-related artery was assessed by repeat coronary angiography. Thrombolysis in Myocardial Infarction trial (TIMI) grade II or III reperfusion was achieved in 73% of group A patients compared with 66% of group B patients (p = NS). A trend toward faster reopening of the infarct-related artery was observed in patients in group B. Coronary artery reocclusion occurred in 5 (10%) of 49 patients in whom angiography was repeated within 36 h after the start of therapy. Clot-selective thrombolysis was indicated by a minimal fibrinogen decline (15% and 13%, respectively, in groups A and B). Alpha 2-antiplasmin levels, however, decreased more rapidly in patients in group B (p less than 0.05). This finding and the equivalent reperfusion rate in the combined treatment group strongly suggest synergistic interaction between these two thrombolytic agents. In summary, the high incidence of reperfusion, the low rate of early reocclusion and the paucity of side effects, particularly with regard to bleeding complications, indicate that pro-urokinase possesses the characteristics of an ideal thrombolytic agent.

[Estimation of the quantity of herbage ingested by dairy cows on pasture land. Comparison of methods of estimating digestibility and the mode of fecal sampling]. / Prévision de la quantité d'herbe ingérée par la vache laitière au pâturage. Comparaison de méthodes d'estimation de la digestibilité et du mode d'échantillonnage des fécès.

Herbage intake of grazing dairy cows was estimated with several techniques. Grab sampling introduced an upward bias in the estimate of faecal output in comparison with field sampling. Estimates of OM digestibility by NIR and faecal index methods were similar except with high level of concentrates.

[Results of embolectomy in massive pulmonary embolism (author's transl)]. / Ergebnisse der Embolektomie bei massiver Lungenembolie

In ten patients successful embolectomy after acute massive pulmonary embolism was performed. Clinical symptoms included circulatory arrest and shock as well as collaps, syncope and dyspnoe. Pulmonary angiography regularly showed massive, bilateral emboli. In 9 patients more than one half of the pulmonary artery system was involved (perfusion defect more than 50%). Right heart catheterization demonstrated pulmonary hypertension in all cases. In 8 patients the pulmonary artery mean pressure (PAm) exceeded 30 mm Hg. In 9 patients there were signs of right heart failure (RVEDP more than 11 mm Hg). At recatheterization 6 to 30 (mean 19) days after operation using cardiopulmonary bypass there was a marked improvement of pulmonary angiograms, which were normal in 3 cases. PAm decreased from 34.3 mm Hg to 14.6 mm Hg postoperatively and RVEDP from 14.4 to 5.1 mm Hg (p less than 0.001). These results confirm, that pulmonary embolectomy leads to a good functional results.

[Calcification of the mitral valve ring, a cardiac manifestation of Marfan's syndrome (author's transl)]. / Verkalkung des Mitralklappenringes als kardiale Manifestation des Marfan-Syndroms

A 29-year-old patient with calcification of the mitral valve annulus with Marfan's syndrome and severe malformation of the chest is reported. There are 8 other cases with calcification of the mitral annulus in this syndrome in the literature. It seems to be a specific but rare cardiac manifestation of Marfan's syndrome with calcification occurring also in the younger age group. These patients, in contrast to other patients with Marfan's syndrome who mostly have mitral insufficiency of minor degree mainly in late systole, present with hemodynamically severe mitral regurgitation. Our patient died 7 weeks after implantation of a prosthetic valve in low output syndrome, probably caused by a paraprosthetic leak and newly developed aortic insufficiency. It therefore seems that indication for prosthetic replacement of the mitral valve in these patients should be made with caution, particularly in regard to the technical difficulties at operation.