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Biomedical subjects

M Verstraete

Publications and source records attributed to M Verstraete.

At least 91 records · Page 5Linked to original sources
PubMed1989

Effects of thrombolytic agents on coronary recanalization and patency, cardiac enzyme release, left ventricular function, and mortality in patients with acute myocardial infarction.

Morbidity and long-term mortality following acute myocardial infarction are directly related to the extent of left ventricular dysfunction. None of the numerous interventions that have been explored in the prevention of myocardial necrosis appears to surpass the benefit provided by rapid restoration of blood flow in the infarct-related coronary artery and attendant reperfusion of the ischemic zone. Although intracoronary administration of thrombolytic drugs results in rapid recanalization (72% with streptokinase or urokinase, 65% with APSAC), this route of administration is not practical and probably not necessary. Indeed, with intravenous administration of thrombolytics, the recanalization rate determined 90 min after the start of 1.5 million U of streptokinase is 43%, after 30 U of APSAC is 56%, after 1 to 2 million U of urokinase is 53%, and after rt-PA is 69%. Coronary patency can be achieved by intravenous therapy, with rates at 90 min of 56% for SK, 77% for APSAC, 71% for prourokinase, and 75% for rt-PA. There is sufficient evidence at present to conclude that the early administration of a thrombolytic agent will reduce infarct size and promote improved ventricular function. The benefits afforded by early recanalization on ejection fraction are clear and unmistakable. When compared to placebo treatment, the hospital mortality reduction in patients treated within 6 h after onset of symptoms is 47% after intracoronary SK. 43% after intravenous SK, 48% after intravenous APSAC, and 51% after intravenous rt-PA. However, the results of direct comparison of these different thrombolytic agents on the left ventricular function and mortality in a large number of patients are crucially important and eagerly anticipated.

Coronary Disease↗
PubMed1989

Detection of human papillomaviruses 16-18 in cervical cells by molecular hybridization: relationship with morphonuclear cell image analyses.

Forty-one Feulgen-stained cervical imprint smears were analyzed by means of the SAMBA 200 cell image processor in order to quantitatively score human papillomavirus (HPV) 16-18-induced morphonuclear modifications as assessed by morphometric, densitometric, and textural parameters. Molecular hybridization technology using 16 and 18 type specific genetic probes made it possible to divide our series into three groups: Group 1, containing noninfected smears; Group 2, containing "suspicious", i.e., borderline positive, smears; and Group 3, those related to infected patients. Our results show that nuclei from infected smears are much more hyperchromatic and bigger than those arising from noninfected smears. This quantitative description of HPV 16-18-induced chromatin modifications enabled us to create preliminary data banks which could lead to an objective and reproducible grading of unknown cases. This approach is now being prospectively assessed on a large series of cases because the value of the current study is limited until the data bank is tested against unknown specimens with a broader spectrum of HPV infection.

Adult↗
PubMed1989

Thrombosis in particular organ veins.

Renal vein thrombosis in early infancy is a complication of dehydration and prolonged hypotension. The onset is usually acute and the most common clinical signs are uni- or bilateral frank masses, hematuria, proteinuria and thrombocytopenia. In most cases, with conservative management, the late outcome is favorable. In the adult, renal vein thrombosis is often a silent complication of the nephrotic syndrome, the hypercoagulability of which may be an important factor in the pathogenesis of the thrombosis. Clinically, the presentation of a sudden complete occlusion is that of severe abdominal and lumbar pain with hematuria and loss of function of the kidney that suffers hemorrhagic infarction. Physical examination often reveals an enlarged kidney. With gradual occlusion, renal function is preserved. The initial diagnostic approach is with ultrasound studies and computed tomography; definitive diagnosis is established by renal venography or by selective renal arteriography. In general, a conservative approach including the use of anticoagulant treatment is preferred to surgical intervention. Priapism is a persistent painful penile erection due to ischemic or non-ischemic causes; therapeutic intracavernosal injection of papaverine is becoming the most common cause. In early and mild stages, aspiration of blood from the corpora cavernosa supplemented with intracavernosal irrigation with alpha-stimulating agents is the procedure of first choice; in late and severe ischemia, a shunt procedure may become necessary. Hepatic vein thrombosis occurs in association with a number of conditions considered predisposing factors including the use of oral contraceptives. The clinical picture may be that of an acute illness with abdominal pain, hepatomegaly, ascites and hepatic failure as well as early death. More often, the onset is insidious with slowly developing ascites and wasting. For the diagnosis, hepatic scintigraphy may be helpful but, at present, ultrasonography, computed tomography and magnetic resonance scanning are procedures of choice. There is, as yet, no adequate treatment. A fatal outcome may be prevented by surgical decompression of the congested liver and, in recent years, liver transplantation has been employed. Portal vein thrombosis, in children, is usually considered a complication of umbilical sepsis or a result of a congenital abnormality of the portal vein. In adults, the most frequent causes are hepatic cirrhosis and neoplasia. Clinically, there may be a sudden appearance of ascites with resolution in a symptom-free interval until the onset of other features of portal hypertension occur. Currently, ultrasound real-time imaging supplemented with Doppler capability, computed tomography and magnetic resonance scanning provide the necessary diagnostic information. Variceal hemorrhage is often the first major complication requiring treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Budd-Chiari Syndrome↗
PubMed1988

Coronary patency after intravenous infusion of recombinant tissue-type plasminogen activator in acute myocardial infarction.

The relation between coronary patency after infusion of recombinant tissue-type plasminogen activator (rt-PA) and clinical and laboratory findings was assessed in patients with acute myocardial infarction. This study focused primarily on information available early in the hospitalization phase. Data were available for 243 patients who received the full dose of rt-PA and who had assessable coronary angiograms 90 min after the start of the intravenous infusion. The infarct-related vessel was scored by an independent assessment committee as being patent in 65% of patients. The left anterior descending coronary artery was involved in 53% of patients, and proximal localization of the infarct-related vessel occurred in 65%. In the majority of patients (85%), the infusion was started within 4 h of the acute event. Neither the angiographic location of the infarct-related vessel nor electrocardiographic evidence of infarct severity or location appeared to have a bearing on thrombolysis with rt-PA. Multivariate logistic regression analysis identified three independent predictors of coronary patency: hematocrit 43 to 47%, blood plasminogen level greater than or equal to 90% of normal and serum alkaline phosphatase greater than or equal to 82% of the local upper normal limit. In addition, the use of intravenous nitrates suggests a positive association with patency.

Aged↗
PubMed1988

Femoro-popliteal artery thrombolysis with intra-arterial infusion of recombinant tissue-type plasminogen activator--report of a pilot trial.

Recombinant tissue-type plasminogen activator (rt-PA) was infused at a rate of 10 mg/h into 50 thrombosed femoral and popliteal arteries. Patency was restored in 43 but a secondary angioplasty led to 2 reocclusions and in 3 patients early rethrombosis occurred. A favourable clinical result was thus obtained in 38 patients (76%). Thirteen bleeding complications occurred in 10 patients, mainly haematomas at puncture sites. One patient required blood transfusion for gastro-intestinal bleeding from a previously unknown ulcer. The angiographic recanalisation rate in 16 patients who received a slower infusion of rt-PA (5 or 3 mg/h) was 94% and the clinical success rate in this series was 81%. However, the incidence of bleeding complications was not decreased by the slower infusion rate. The data obtained confirm the feasibility of rt-PA thrombolysis in peripheral arterial thrombosis and warrant a comparative study with streptokinase.

Angioplasty, Balloon↗
PubMed1988

Intravenous and intrapulmonary recombinant tissue-type plasminogen activator in the treatment of acute massive pulmonary embolism.

Eight centers participated in a study in which intrapulmonary and intravenous administration of recombinant tissue-type plasminogen activator (rt-PA) were compared in 34 patients with acute massive pulmonary embolism. All patients received intravenous heparin in a bolus of 5,000 IU followed by 1,000 IU/hr. After 50 mg rt-PA given over 2 hr the severity of embolism, determined from pulmonary angiograms, declined by 12% in the intrapulmonary drug group (p less than .005) and 15% in the intravenous drug group (p less than .005); mean pulmonary arterial pressure fell from 31 +/- 7 to 22 +/- 6 mm Hg (p less than .005) and from 31 +/- 12 to 21 +/- 9 mm Hg (p less than .005) in the respective groups. After a further 50 mg given over 5 hr (22 patients), the angiographically determined severity of embolism had decreased by 38% from baseline in the intrapulmonary drug group and by 38% in the intravenous drug group. The mean pulmonary arterial pressure further declined to 18 +/- 7 and 12 +/- 5 mm Hg in the respective groups. Fibrinogen levels dropped to 48% of baseline after 50 mg and to 36% of baseline after 100 mg rt-PA. Some degree of bleeding at puncture and/or operation sites was noted in 16 patients, including four who required a transfusion of two or more units of blood and had been operated on an average of 7.5 days (range 2 to 13) before thrombolytic treatment was started.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1988

[Comparative randomized study of the effectiveness of intravenous recombinant tissue-type plasminogen activator and intravenous streptokinase in patients with acute myocardial infarct. Report of the European Cooperative Study Group for Recombinant Tissue-Type Plasminogen Activator].

In a single-blind randomised trial in patients with acute myocardial infarction of less than 6 h duration, the frequency of coronary patency was found to be higher after intravenous administration of recombinant human tissue-type plasminogen activator (rt-PA) than after intravenous streptokinase. 64 patients were allocated to 0.75 mg rt-PA/kg over 90 min, and the infarct-related coronary artery was patent in 70% of 61 assessable coronary angiograms taken 75-90 min after the start of infusion; 65 patients were allocated to 1,500,000 IU streptokinase over 60 min, and the infarct-related vessel was patent in 55% of 62 assessable angiograms. The 95% confidence interval of the difference ranges from +30 to -2% (p = 0.054). Bleeding episodes and other complications were less common in the rt-PA patients than in the streptokinase group. Hospital mortality was identical in the 2 treatment groups. At the end of the rt-PA infusion the circulating fibrinogen level was 61 +/- 35% of the starting value, as measured by a coagulation-rate assay, and 69 +/- 25% as measured by sodium sulphite precipitation. After streptokinase infusion, corresponding fibrinogen levels were 12 +/- 18% and 20 +/- 11%. In the rt-PA group only 4.5% of the fibrinogen was measured as incoagulable fibrinogen degradation products, compared with 30% in the streptokinase group. Activation of the systemic fibrinolytic system was far less pronounced with rt-PA than with streptokinase.

Adult↗
PubMed1988

[Randomized double-blind study comparing tissue-type plasminogen activator with placebo in acute myocardial infarct].

In a double-blind randomised trial 129 patients with first myocardial infarction of less than 6 h duration were allocated to treatment with human recombinant tissue-type plasminogen activator (rt-PA) given intravenously over 90 min, or to placebo infusion. Coronary angiography at the end of this infusion showed that the infarct-related vessel was patent in 61% of 62 assessable coronary angiograms in the rt-PA-treated group compared with 21% in the control group. Treatment with rt-PA was not accompanied by any major complications. In the rt-PA group the circulating fibrinogen level at the end of the catheterisation was 52 +/- 29% (mean +/- SD) of the starting value.

Adult↗
PubMed1988

[Recent developments in fibrinolysis].

Since streptokinase and urokinase became available for clinical use, numerous attempts have been made to improve these useful thrombolytic agents. In order to decrease its antigenicity, streptokinase has been fragmented or coupled to human plasminogen or polyethylene glycols. With a plasmin B-chain-streptokinase complex a more potent agent was obtained. To prolong their half-life, streptokinase and urokinase were immobilized with water-soluble carriers. Coupling urokinase or tissue-type plasminogen activator with fibrin-specific antibodies increases its thrombolytic efficiency, at least in vitro. The only thrombolytic agents with a relative fibrin-selectivity presently available for clinical purposes are tissue-type plasminogen activator and single chain urokinase-type plasminogen activator. Structural manipulation allows to design and produce mutant proteins with specific deletions, additions or substitutions of non-protease domains. Also chimaeric molecules combining fragments of tissue-type plasminogen activator and single chain urokinase-type plasminogen activator have already been constructed. These modifications of natural molecules may further improve their fibrin-specificity and therapeutic potential.

Animals↗
PubMed1987

Acute coronary thrombolysis with recombinant human tissue-type plasminogen activator: initial patency and influence of maintained infusion on reocclusion rate.

An intravenous infusion of 40 mg of recombinant tissue-type plasminogen activator (rt-PA) was given intravenously over 90 minutes to 123 patients with acute myocardial infarction (AMI) of less than 4 hours' duration. A coronary angiogram was recorded at the end of the infusion in 119 patients. Central assessment of the angiograms revealed a patent infarct-related artery in 78 patients (patency rate 66%, 95% confidence limits 57 to 74%). Patients with a patent infarct-related artery at the first angiogram were randomized in a double-blind manner to receive a subsequent 6-hour infusion of either 30 mg of rt-PA or placebo. All patients had received an initial bolus of 5,000 IU of heparin and then 1,000 IU/hour until a second angiogram was recorded 6 to 24 hours after the start of the second perfusion. At central assessment of the second coronary angiogram the reocclusion rate was 2 of 36 patients who received rt-PA at the second infusion and 3 of 37 patients not receiving this drug (or the 2 groups combined 7%, 95% confidence limits 2 to 15%). Three of 60 patients (5%, 95% confidence limits 1 to 14%) with patent arteries on both previous angiograms had a later occlusion as judged on the angiogram recorded at hospital discharge. No difference in late reocclusion rates between the 2 treatment groups was observed.

Clinical Trials as Topic↗
PubMed1987

Local thrombolysis in femoropopliteal occlusion: early and late results.

The early and late results of local thrombolysis with low-dose streptokinase followed by balloon dilatation in 64 patients with an occluded femoropopliteal artery are reviewed. The primary success rate was 77% for the native arteries; it was higher (80%) for short (less than 10 cm) as compared with long occlusion (40%) and for patients with claudication as compared with those with advanced ischemia (89% versus 48%). Eleven complications were observed in 10 patients, most frequently a local hematoma at the puncture site. Ascending thrombosis and absence of lysis or incomplete lysis were the main reasons for failure. The cumulative patency rate after 1 and 2 years follow-up was 87% and 82%, respectively.

Angioplasty, Balloon↗
PubMed1987

The search for the ideal thrombolytic agent.

Since streptokinase and urokinase became available for clinical use, numerous attempts have been made to improve these useful thrombolytic agents. To decrease its antigenicity, streptokinase has been fragmented or coupled to human plasminogen or polyethylene glycols. With a plasmin B chain-streptokinase complex a more potent agent was obtained. To prolong their half-life, streptokinase and urokinase were immobilized with water-soluble carriers. Coupling urokinase with fibrin-specific antibodies increases its thrombolytic efficacy, at least in vitro. The only thrombolytic agents with a relative fibrin specificity available for clinical purposes are tissue-type plasminogen activator and single chain urokinase-type plasminogen activator. Mutants and hybrids of these molecules are being constructed and may further improve their fibrin specificity and therapeutic potential.

Drug Combinations↗