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M L Simoons

Publications and source records attributed to M L Simoons.

At least 181 records · Page 10Linked to original sources
PubMed1993

Tailored thrombolytic therapy. A perspective.

BACKGROUND: In contrast with current standard regimens, it seems more appropriate to tailor thrombolytic therapy to individual patient characteristics. A proposed model for such tailored therapy is based on individual assessment of benefits and risks of thrombolytic therapy, taking into account the response of individual patients to the therapy given. METHODS AND RESULTS: Potential benefits of thrombolysis in individual patients can be predicted by use of demographic patient characteristics (age, sex, history of previous infarction) together with indicators of the ischemic area at risk (total ST segment deviation) and treatment delay. Using these parameters, the number of "lives saved" by thrombolytic therapy for specific patient characteristics can be estimated. Similarly, the risk of intracranial hemorrhage during thrombolytic therapy can be estimated from the patient's age, blood pressure at admission, and body weight. Depending on benefit/risk estimates, a choice can be made between regimens with high, medium, or modest thrombolytic efficacy. Continuous multilead ECG ischemia monitoring and rapid assays of myocardial proteins in serum can be used to assess the occurrence or absence of reperfusion and to detect signs of reocclusion. Such data help to decide whether thrombolytic therapy should be continued or intensified or might be discontinued in individual patients before the total standard dose has been administered. Such tailored reduction of the total thrombolytic dose will reduce the risk for bleeding complications in some of the patients. CONCLUSIONS: The concept of tailoring thrombolytic therapy and the models presented for benefit/risk assessment should be tested in clinical studies and may subsequently help the physician to select the optimal approach in individual patients.

Adult↗
PubMed1993

Intracranial hemorrhage after thrombolytic therapy. A perspective.

The most feared complication of thrombolytic therapy is intracranial hemorrhage. Nevertheless, the benefits of thrombolysis far outweight the potential hazards of a cerebral bleed. In individual patients the expected benefit of thrombolytic therapy can be estimated by subtraction of the risk for intracranial hemorrhage from the predicted gain in survival. Accordingly, the net effect of thrombolysis will be beneficial in most patients who can be treated within the first 12 hours after symptom onset, even if one or two risk factors for intracranial hemorrhage can be identified. On the other hand, thrombolytic therapy is not warranted in elderly patients with a relatively small predicted infarct size and multiple risk factors for intracranial hemorrhage.

Cerebral Hemorrhage↗
PubMed1992

Well shaped ST segment and risk of cardiovascular mortality.

OBJECTIVE: To investigate the prognostic value of frequently occurring slight variations in the ST segment for cardiovascular mortality in healthy subjects. DESIGN: Follow up study of mortality in relation to variations in ST segment level in a cohort over the 28 years from 1953 to 1981. A case-cohort sampling design was applied to limit the number of electrocardiograms that had to be coded by hand. SETTING: General health examination carried out in 1953 of civil servants in Amsterdam and assessment of subsequent mortality. SUBJECTS: Apparently healthy civil servants aged 40 to 65 years: 1583 men and 1508 women. MAIN OUTCOME MEASURES: Relative risk of variations in ST segment level for mortality from all causes, cardiovascular disease, and coronary heart disease. RESULTS: In men the multivariate relative risks of 15 year mortality from cardiovascular disease and coronary heart disease of slight ST elevation at 80 ms past the J point (compared with isoelectric ST segment) were 0.5 (95% confidence interval 0.3 to 0.9) and 0.4 (0.2 to 0.8), respectively. As expected, ST segment depression (greater than 0.25 mm) was associated with increased risk: 1.9 (1.1 to 3.0) and 2.2 (1.2 to 3.9), respectively. In women associations were weaker. The full 28 year period showed a similar pattern of somewhat weaker associations for men; among women, however, no predictive value was apparent. CONCLUSION: These results are empirical evidence for the intuitive opinion among doctors that a curved, upward sloping ST segment, resulting in slight ST elevation at 80 ms, indicates low risk compared with the isoelectric flat, stretched ST segment.

Adult↗
PubMed1992

Polyclonal versus monoclonal rejection prophylaxis after heart transplantation: a randomised study.

Recent studies comparing the effects of induction therapy with polyclonal antilymphocyte globulins (ALG) or with monoclonal T-cell-specific antibodies are not unanimous. Therefore, 55 heart recipients were allocated to either 7-day courses of polyclonal ALG (n = 28) or of monoclonal OKT3 (n = 27). Additionally, azathioprine and low dose steroids were given. There were no severe side effects after OKT3; the course of ALG, however, had to be discontinued in 20 patients because of extensive flares. No differences between the two groups were found in freedom from rejection or in the incidence of infection. The 1- and 2-year survival was 96% in both groups. Although monoclonal and polyclonal induction therapies are equally effective for rejection prophylaxis, OKT3 may be preferred because of a lack of important side effects. However, the fact that a shorter course of ALG is equally effective may be in favour of ALG.

Adolescent↗
PubMed1992

5-Hydroxytryptamine-induced contractions of the human isolated saphenous vein: involvement of 5-HT2 and 5-HT1D-like receptors, and a comparison with grafted veins.

The receptors mediating the contractile effect of 5-hydroxytryptamine (5-HT) on the human isolated saphenous vein, obtained from 42 patients undergoing coronary bypass surgery, have been further characterized using a number of 5-HT-related drugs. The rank order of agonist potency was 5-carboxamidotryptamine (5-CT) approximately 5-HT greater than methysergide approximately sumatriptan approximately alpha-methyl-5-HT approximately 5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indolesuccinate (RU 24969) approximately 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) greater than 2-methyl-5-HT greater than 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT). Flesinoxan was inactive as an agonist. Ketanserin (1 mumol/l) hardly affected sumatriptan-induced contractions but it caused a rightward shift of the upper part of the concentration-response curve of 5-HT and 5-CT. The same concentration of ketanserin caused a parallel rightward shift of the concentration-response curves of alpha-methyl-5-HT and DOI with pKB values of 7.1 and 7.1, respectively. The responses to sumatriptan were antagonized by methiothepin (0.1 mumol/l), metergoline (0.1 and 1 mumol/l), rauwolscine (1 mumol/l) and cyanopindolol (1 mumol/l); the calculated pKB values were 7.3, 6.9, 7.3, 6.7 and 6.5, respectively. Contractions to 5-HT were antagonized by methysergide (1 mumol/l), methiothepin (0.1 mumol/l; pKB = 7.1), ICS 205-930 (1 mumol/l; pKB = 5.9) and flesinoxan (30 mumol/l; pKB = 5.3). Remarkably, the contractions elicited by 2-methyl-5-HT were not attenuated by ICS 205-930, but were antagonized by methiothepin (0.1 mumol/l) and, more markedly, by ketanserin (1 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Artery Bypass↗
PubMed1992

Intracranial hemorrhage in association with thrombolytic therapy: incidence and clinical predictive factors.

In a period of 18 months, 2,469 patients with acute myocardial infarction treated with a thrombolytic agent were prospectively registered in 61 hospitals. Most patients (73%) were treated with streptokinase. Intracranial hemorrhage was observed in 24 patients, corresponding to an incidence rate of 1% (95% confidence interval 0.6% to 1.3%). The median time interval between the start of thrombolytic therapy and the first clinical signs of intracranial bleeding was 16 h (range 3 to 36). In total, 16 (66%) of the 24 patients died as a result of cerebral hematoma. To determine clinical predictive factors, a case-control study was conducted. For every patient with intracranial hemorrhage, two control patients who received thrombolytic therapy because of acute infarction in the same hospital and in the same period were selected. Detailed clinical characteristics of 22 of the 24 patients as well as of 7 other patients with documented intracerebral bleeding from the European Cooperative Study Group and of 2 patients who sustained intracranial hemorrhage outside the registry period were compared with 62 control patients. The results of multivariate logistic regression analysis indicate that patients taking an oral anticoagulant before admission, patients with a body weight less than 70 kg and those greater than 65 years old are at higher risk for intracranial hemorrhage during thrombolytic therapy.

Aged↗
PubMed1992

Too early for cardiac transplantation--the right decision?

In 109 out of 479 patients who were referred for cardiac transplantation it was considered to be too early to put them on the waiting list for a donor heart. The clinical course of these 109 patients was analysed in order to verify whether this decision had been right. The mean age of the patients was 43 years, half of them suffered from ischaemic heart disease. The systolic left ventricular function of the patients was severely depressed (mean left ventricular ejection fraction 21%) and the left ventricular cavity was markedly dilated (mean echocardiographic end diastolic dimension 73 mm). Functional capacity, measured by bicycle ergometry, was low: mean maximal workload 62% of the expected load for gender, height and age. The median follow-up duration was 31 months. The survival rate of the patients was better than that of 175 patients who were accepted for transplantation after referral, 92%, 87%, 81%, 71% and 73%, 73%, 71%, 68% after 1, 2, 3 and 4 years respectively. Re-assessment was necessary in 29% of the patients within 1 year and in 52% within 3 years. Twenty patients died: 12 patients died before re-assessment had been initiated (eight sudden deaths), six patients because of progressive heart failure before heart transplantation could be performed and two patients died after heart transplantation. Left ventricular ejection fraction, pulmonary capillary wedge pressure and transpulmonary gradient were not reliable predictors of the course of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Prehospital thrombolysis with alteplase (rt-PA) in acute myocardial infarction.

The improvement in survival in patients undergoing thrombolytic therapy in myocardial infarction is determined by the delay between coronary occlusion and reperfusion. The REPerfusion in Acute Infarction Rotterdam (REPAIR) study was designed to examine the feasibility and safety of prehospital thrombolysis with alteplase (rt-PA, 'Actilyse'). A small portable ECG computer system is used to confirm the presence of a large myocardial infarction (at least 1.0 mV ST-deviation) 'on the spot'. Between 22 June 1988 and 1 January 1991, 226 patients were treated by the ambulance service after the evaluation of 9052 patients complaining of chest pain. Therapy could be initiated within an average of 100 +/- 56 min (SD) after the onset of symptoms, and within 22 +/- 9 min after ambulance arrival. Three patients were defibrillated during transportation. Six patients (3%) died after arrival in the hospital. The time gained by prehospital treatment was 47 min (95% confidence limits 44-51 min) in comparison with 220 patients who did not meet the criteria for prehospital thrombolysis, but received thrombolytic therapy as soon as possible after hospital admission. The developed procedure allows rapid and safe initiation of thrombolytic therapy in selected patients, even in the absence of a physician. The observed low mortality supports the concept that prehospital thrombolytic therapy is indeed beneficial to the patient.

Adult↗
PubMed1992

Effect of early intravenous heparin on coronary patency, infarct size, and bleeding complications after alteplase thrombolysis: results of a randomised double blind European Cooperative Study Group trial.

OBJECTIVE: To determine whether concomitant treatment with intravenous heparin affects coronary patency and outcome in patients treated with alteplase thrombolysis for acute myocardial infarction. DESIGN: Double blind randomised trial. TREATMENT REGIMENS: Alteplase 100 mg (not weight adjusted) plus aspirin (250 mg intravenously followed by 75-125 mg on alternate days) plus heparin (5000 units intravenously followed by 1000 units hourly without dose adjustment) was compared with alteplase plus aspirin plus placebo for heparin. SETTING: 19 cardiac centres in six European countries. SUBJECTS: 652 patients aged 21-70 years with clinical and electrocardiographic features of infarcting myocardium in whom thrombolytic therapy could be started within six hours of the onset of major symptoms. MAIN OUTCOME MEASURE: Angiographic coronary patency 48-120 hours after randomisation. RESULTS: Coronary patency (TIMI grades 2 or 3) was 83.4% in the heparin group and 74.7% in the group given placebo for heparin. The relative risk of an occluded vessel in the heparin treated group was 0.66 (95% confidence interval 0.47 to 0.93). Mortality was the same in both groups. There were non-significant trends towards a smaller enzymatic infarct size and a higher incidence of bleeding complications in the group treated with heparin. CONCLUSIONS: Concomitant intravenous heparin improves coronary patency in patients with alteplase. Whether this can be translated into improved clinical benefit needs to be to be tested in a larger trial.

Adult↗
PubMed1992

Changes in left ventricular function and wall thickness in heart transplant recipients and their relation to acute rejection: an assessment by digitised M mode echocardiography.

OBJECTIVE: Assessment of changes in left ventricular diastolic function and wall thickness after heart transplantation to verify whether these changes predicted acute rejection assessed by endomyocardial biopsy. DESIGN: Follow up according to a predefined protocol of consecutive patients from the first week after transplantation. SETTING: Heart transplantation unit of the Thoraxcentre, University Hospital Rotterdam Dijkzigt, The Netherlands. PATIENTS: All 32 patients undergoing orthotopic heart transplantation from 1 January 1989 to 31 March 1990 were examined. Two were excluded from the analysis. Patients were treated with cyclosporin and low dose steroids. MAIN OUTCOME MEASURES: Data obtained by digitised M mode echocardiography were compared with the results of endomyocardial biopsy (Billingham classification). Mean values for left ventricular wall thickness, internal dimension, and their standardised rates of change and fractional shortening were determined from 4-6 consecutive expiratory beats. Mean values and individual trends during follow up were also investigated for each ultrasound variable. The results of these average values were compared with values in a group of 10 healthy volunteers. RESULTS: Median follow-up was 177 days (range 10-399). Two hundred and sixty three consecutive M mode studies were examined in relation to concurrent biopsy results. No significant differences were observed between the ultrasound variables at the time of moderate acute rejection (Billingham class 2, n = 37) and other biopsy classes (n = 226). Nor did changes in individual patients predict (moderate) acute rejection episodes. Twenty six of the 30 patients had an abnormal (slow) left ventricular relaxation pattern throughout follow up. CONCLUSIONS: Digitised left ventricular M mode echocardiography did not predict the presence of acute rejection. In most patients there was a persistent slow left ventricular relaxation pattern.

Acute Disease↗
PubMed1992

Recombinant tissue-type plasminogen activator and immediate angioplasty in acute myocardial infarction. One-year follow-up. The European Cooperative Study Group.

BACKGROUND: The European Cooperative Study Group conducted two randomized trials in patients with suspected myocardial infarction to assess the effect of 100 mg single-chain recombinant tissue-type plasminogen activator (rt-PA, alteplase) on enzymatic infarct size, left ventricular function, morbidity and mortality relative to placebo (alteplase/placebo trial) and to assess the effect of immediate percutaneous transluminal coronary angioplasty (PTCA) in addition to alteplase (alteplase/PTCA trial). One-year follow-up results are reported. METHODS AND RESULTS: In the alteplase/placebo trial, 721 patients with chest pain of less than 5 hours and extensive ST-segment elevation were allocated at random to 100 mg alteplase or placebo (double-blind) over 3 hours. In the alteplase/PTCA trial, 367 similar patients received alteplase and subsequently were allocated at random to immediate coronary angiography and angioplasty of the infarct-related vessel or control. All patients received aspirin and intravenous heparin. In the alteplase/placebo trial, mortality during the first year was reduced by 36% with alteplase (from 9.3% to 5.6%; difference, -3.7%; 95% confidence interval, -7.5% to 0.2%). Revascularization was performed more frequently after alteplase, and more patients in the alteplase group were in New York Heart Association functional class I or II. Reinfarction tended to occur more frequently after alteplase than after placebo. In the alteplase/PTCA trial, reinfarction was less common after immediate PTCA, and revascularization procedures were less frequent. However, this benefit was offset by a high rate of immediate reocclusion and early recurrent ischemia and by higher mortality at 1 year (9.3% versus 5.4%; difference, 3.9%; 95% confidence interval, -1.5% to 9.2%) in the invasive group. In a multivariate analysis of 1,043 hospital survivors, mortality after discharge was related to coronary anatomy, left ventricular function, age, and previous infarction but not to initial treatment allocation. Reinfarction after hospital discharge tended to be more common after alteplase and related to coronary anatomy. CONCLUSIONS: Benefit from treatment with alteplase, heparin, and aspirin is not diminished at 1 year. Routine immediate PTCA does not confer additional benefit. Prognosis after hospital discharge mainly is determined by coronary anatomy and residual left ventricular function and is unrelated to initial treatment assignment.

Angioplasty, Balloon, Coronary↗
PubMed1991

[Long-term survival following successful resuscitation outside the hospital].

Between 1983 and 1989, 962 patients in Rotterdam were resuscitated outside hospital, of whom 240 (25%) could be discharged alive. A follow-up study was performed to determine prognosis in these patients. Data were collected through the Municipal Health Service, Population Registries, the hospitals where the patients were admitted, and the general practitioners. Of these 240 survivors of out-of-hospital resuscitation 80% survived after 1 year and 61% after 5 years. During the first year, 9% suffered from myocardial (re)infarction and 13% underwent coronary bypass surgery or angioplasty. Within the first three years after resuscitation 60% of the patients were readmitted to a hospital. Permanent or temporary neurological deficits were observed in 30 patients (14%). Patients with a primary arrhythmia without myocardial infarction had a poorer prognosis than patients with cardiac arrest in the context of an infarct. Survival was better in patients in whom resuscitation was initiated by physicians or ambulance-nurses, than in patients resuscitated by lay-people. Multivariate analysis revealed that this difference was caused by a larger proportion of patients with a primary arrhythmia in the latter group. Since long-term prognosis after out-of-hospital resuscitation is satisfactory, programmes for resuscitation courses should be stimulated. Such courses should be aimed predominantly at relatives of patients with known heart disease, police officers and children.

Adolescent↗
PubMed1991

Reasons for the lack of benefit of immediate angioplasty during recombinant tissue plasminogen activator therapy for acute myocardial infarction: a regional wall motion analysis. European Cooperative Study Group.

Regional ventricular wall motion analysis utilizing three different methods was performed on predischarge left ventriculograms from 291 of 367 patients enrolled in a randomized trial of single chain recombinant tissue-type plasminogen activator (rt-PA), aspirin and heparin with and without immediate angioplasty in patients with acute myocardial infarction. With univariate analysis, no difference in regional wall motion variables between the two treatment groups was observed. However, with individual baseline risk assessment by multivariate linear regression analysis using baseline characteristics known to be related to left ventricular function after thrombolytic therapy or outcome of coronary angioplasty, or both, an excess of high risk patients in the invasive treatment group was detected. To adjust for this unequal distribution of baseline risk, multivariate linear regression analysis was performed. No benefit of immediate coronary angioplasty was observed after adjustment. Reocclusion or reinfarction, or both, occurred more frequently in the invasive than in the noninvasive treatment group (18% versus 13%, respectively). Among patients with a patent infarct-related vessel on angiography between days 10 and 22 and without reinfarction before angiography, there was a trend toward benefit from the invasive strategy, indicating that reocclusion and reinfarction might be responsible for the lack of benefit of the invasive strategy. This implies that immediate coronary angioplasty may be beneficial in selected patients, provided that these complications can be prevented.

Angioplasty, Balloon, Coronary↗
PubMed1991

Tissue plasminogen activator in refractory unstable angina. A randomized double-blind placebo-controlled trial in patients with refractory unstable angina and subsequent angioplasty.

To evaluate the effect of recombinant tissue plasminogen activator (alteplase) on the clinical course, angiographic changes and the outcome of subsequent coronary angioplasty, 36 patients with angina at rest, despite bedrest and medical treatment including heparin, and with concomitant ECG changes, were studied. After diagnostic angiography, patients were randomized to receive either alteplase 100 mg in 3 h (19 patients), or placebo (17 patients). The mean interval between qualifying anginal episode and initial angiography was 10 and 9 h for the alteplase and placebo group, respectively. Angiography was repeated and angioplasty was performed within 24 hours. Between the first and the second angiogram, five patients in the alteplase and seven in the placebo group had recurrent ischaemic episodes, while four alteplase and three placebo patients showed signs of myocardial necrosis (creatine kinase (CK) rise greater than or equal to twice the upper limit for normal). Intracoronary clots were recognized in three alteplase patients and one placebo patient at the first angiogram, while two alteplase patients and one placebo patient showed total occlusion of the ischaemic-related vessel. After infusion, thrombi were present in four alteplase patients and one placebo patient, and total occlusion in three alteplase patients and one placebo patient. Quantitative coronary angiography showed no change in the percentage diameter stenosis of the ischaemia-related segment after drug infusion, (alteplase 67 +/- 16 to 69 +/- 16%; placebo 65 +/- 11 to 63 +/- 12%). Angioplasty was successful in 14 of 19 alteplase and 14 of 16 placebo patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Cost-utility analysis of thrombolytic therapy.

An analysis of the cost-effectiveness of thrombolytic therapy was performed, based on 3- to 5-year follow-up data, from 533 patients randomized to receive conventional therapy or intracoronary streptokinase. At the 3-year follow-up, mortality was 22% in the former group and 14% after thrombolysis. The estimated average gain in life years by thrombolytic therapy was 3.4, whereas this figure was only 1.6 years in patients with inferior wall infarction, and 5.1 years in patients with anterior wall infarction. The lifetime costs for conventional therapy, estimated as ECU 15,110, were increased by ECU 5530 when thrombolytic therapy was applied, including direct treatment costs and the additional costs of extra coronary bypass surgery and PTCA. After correction for quality of life, and discounting future costs and future events at 5% year-1, the additional costs for each life year were ECU 2940 for all patients treated. This was broken down into ECU 7030 and ECU 2000 for patients with inferior and anterior wall infarction respectively. These figures compare favourably with other modes of cardiovascular therapy. Thrombolytic therapy does not substantially increase the need for bypass surgery or PTCA. It is very cost-effective, and its application should not be limited by economic resources.

Angioplasty, Balloon, Coronary↗