ST-segment analysis: a useful marker for reperfusion after thrombolysis with APSAC? The Belgian EMS Study Group.

The European Multicentre Study (EMS) assessed coronary reperfusion, functional outcome and safety of anistreplase (anisoylated plasminogen streptokinase activator complex = APSAC) compared to a control group treated with heparin alone in patients with a clinical diagnosis of acute myocardial infarction (AMI). In the Belgian subset of data (n = 103) the reperfusion results, based on non-invasive clinical parameters, were significantly better in the APSAC group: 66% versus 18% in the heparin group (P less than 0.0001). No significant difference was found between the two treatment groups with respect to left ventricular function and adverse events. The purpose of the present study was to analyse the indicative value of ST-segment changes as a possible predictor of reperfusion in threatened myocardial tissue. Two scoring systems were used: the first was based on the combined evaluation of three clinical non-invasive parameters (course of chest pain, ECG evaluation of ST segment changes, reperfusion arrhythmias); the second was based on the changes of the sum of the ST-segment (sigma-ST) evaluations on consecutive 12-lead ECGs. There was a good correlation between the combined clinical scoring system and the residual stenosis on coronary angiography (P less than 0.05) and early CK peak (P less than 0.0001). Analysis of the ECG data revealed that a decrease of greater than or equal to 50% of the sum of ST-elevations (sigma-ST) at 2 h post-treatment in both limb and precordial leads is a fairly useful predictor of reperfusion (sensitivity = 73%, specificity = 63%, predictive value = 88%).

Prehospital thrombolytic treatment of acute myocardial infarction with anisoylated plasminogen streptokinase activator complex.

In cooperation with a group of general practitioners (GP), we investigated the possible risk and benefit of prehospital initiation of thrombolytic therapy in acute myocardial infarction (AMI) with anisoylated plasminogen streptokinase activator complex (APSAC) at the patient's home. During a 14-month period, 58 patients with suspected AMI were evaluated by their GP using a protocol with strict inclusion and exclusion criteria. The GP alerted a special mobile intervention team which administered APSAC at home in 13 of the 19 patients. Coronary reperfusion was achieved in ten of these 13 patients. Apart from short and easily treated episodes of bradycardia and/or hypotension after the injection of the thrombolytic drug in four of 13 patients, no major adverse events were noted in the early treatment period. The estimated time gain by treating the patient at home instead of starting the treatment in the coronary care unit was 46 +/- 14 min. Therefore, at-home initiation of thrombolytic treatment seems feasible, fast, and safe.

Thrombolytic treatment of pulmonary embolism with APSAC.

BRL 26921 (Eminase registered trade mark in Belgium, Germany and The Netherlands) is the p-anisoyl derivative of the primary (human) lys plasminogen-streptokinase activator complex (APSAC). The acyl-enzyme has the theoretical advantage of causing fibrinolysis in situ in the presence of fibrin clotbound plasminogen. It was administered to 34 patients with severe pulmonary embolism (PE) in an open multicentre study. PE was suspected on clinical, blood gas, ECG, and radiographic data. Pulmonary angiograms performed pre- and post-treatment confirmed the diagnosis and were assessed using the Miller Index (MI). Fibrinogen, plasminogen, alpha-2-antiplasmin, fibrinogen degradation products (FDP), activated partial thromboplastin time (APTT), partial thromboplastin time (PTT) were closely monitored before and after each administration of APSAC. Median angiographic improvement was 50% (range 0-94%). The following adverse events were reported: bleeding at puncture sites (n = 12), haematuria (n = 1), epistaxis (n = 3), fever (n = 2). A blood transfusion was given in one patient with an inguinal haematoma. Systemic fibrinogenolysis occurred in 20/28 patients.

Paroxetine in the treatment of depression. A double-blind multicenter study versus mianserin.

Paroxetine is a new antidepressant drug. It is a potent and selective 5-HT re-uptake inhibitor with only weak anticholinergic properties and less effect on the cardiovascular system than the classical tricyclics. In this double-blind multicenter study the antidepressant effect of paroxetine was compared with mianserin in 70 patients with unipolar or bipolar depression. Each drug was administered for 6 weeks after a 1 week run-in period at a daily dosage of 30 mg for paroxetine or 60 mg for mianserin. The 21-item Hamilton Depression Rating Scale (HAM-D) and the physician's global assessment were used to assess efficacy. Both treatment groups showed statistically significant improvement of the HAM-D at Weeks 1 (base-line values: paroxetine mean 28.5; mianserin mean 30.8) through to Week 6 (paroxetine mean 11.5; mianserin mean 17.8) (P less than 0.06). The endpoint differences between treatments however were not statistically different (P = 0.11). The Cleary and Guy factor analysis showed a significant difference (P less than 0.03) at Weeks 2 and 4 for cognitive disturbance and at Weeks 4 and 6 for retardation in favour of paroxetine compared with mianserin. Both drugs were well tolerated with nausea and headache in four patients and somnolence in six patients being reported as the most common side-effect for paroxetine and mianserin respectively.

Analysis of coagulation and fibrinolysis after intravenous anisoylated plasminogen streptokinase activator complex or heparin in patients with acute myocardial infarction. A Belgian multicentre study.

A multicentre randomised trial including 87 patients admitted for acute myocardial infarction compared the effects of a single intravenous bolus of an anisoylated plasminogen streptokinase activator complex (APSAC) 30 units with those of heparin treatment on haemostasis during the first 4 days after treatment. In the APSAC group, a rapid and significant reduction in fibrinogen, plasminogen and alpha 2-antiplasmin was observed, associated with an increase of fibrin(ogen) degradation products, reflecting a strong systemic lytic activity. None of these parameters were significantly modified by heparin, but the anticoagulant effect was apparent as assessed by the activated partial thromboplastin time. The systemic fibrinolysis induced after different regimens of streptokinase infusion demonstrated that an intravenous bolus of APSAC 30U was as potent as streptokinase 500,000 or 1,500,000IU administered intravenously over 45 minutes and definitely more fibrinolytic than intracoronary infusion of streptokinase 250,000IU. Despite the demonstrated fibrin specificity of the drug at a low dose, a high dose of APSAC (30U intravenously) induced an important systemic lytic state for at least 12 hours.

Temocillin in the treatment of pyelonephritis in children.

Temocillin is a beta-lactamase-stable penicillin with a selective. Gram-negative spectrum of activity and a long half-life. Previous studies in adult patients have demonstrated its efficacy and safety in the treatment of Gram-negative infections. The aim of the study was to evaluate the clinical and bacteriological efficacy and safety of temocillin in children with complicated urinary tract infections. Twenty-two children, aged 3 months to 13 years (mean 5.8 years) were treated with temocillin i.v. at a dose of 25 mg/kg 12 hourly for a mean period of 5.9 days (range 3-12 days). Acute pyelonephritis was diagnosed in 21 patients (one case associated with septicaemia); one patient presented recurrent bacteriuria due to a multiresistant pathogen. Some 20/22 children presented an underlying condition complicating the urinary tract infection (UTl). The causative pathogens, isolated from the urine, were: E. coli (17), Proteus mirabilis (3), Enterobacter cloacae (1), enterococcus (1). The enterococcus and one Proteus mirabilis were found to be resistant to temocillin. Clinical improvement was obtained after 24-36 h in all children with temocillin-sensitive organisms. Bacteriological cure was obtained in all patients with temocillin-sensitive organisms. The two patients with temocillin-resistant pathogens were treated with another antibiotic. Follow-up treatment was given per os during +/- 2 weeks. No adverse reactions or abnormal laboratory values were noted. In the authors' limited experience temocillin proved to be effective and safe in the treatment of pyelonephritis often due to ampicillin-resistant strains in children.

Efficacy and safety of nabumetone in long-term treatment of osteoarthritis.

Nabumetone, belonging to a new class of anti-inflammatory drugs, was administered to 9 patients suffering from radiologically-confirmed osteoarthritis of one or more of the following articulations: knees, hips, cervical and lumbar spine. A single nightly dose of 1 g was given for at least one year, and up to three years. The drug was found to be generally effective on such criteria as articular mobility, night pain, and pain during activity. No significant alterations which could be attributed to the treatment were seen in haematological parameters, blood creatinine and urea levels, protein, transaminases, alkaline phosphatase, gamma-glutamyl transferase and other blood and urine tests. The side-effects claimed by the patients included gastric upset, pyrosis, epigastric pain, constipation, malleolar oedema and drowsiness. These complaints did not lead to termination of the treatment. The efficacy and safety of nabumetone found in this and other studies warrant its further investigation in the treatment of rheumatic diseases.

Cellular and humoral responses following one year of hyposensitization with aqueous and tyrosine adsorbed Dermatophagoides pteronyssinus extracts.

The present study compared the influence of hyposensitization treatment with a tyrosine adsorbed house dust mite solution (Migen) and an aqueous house dust mite (HDM) solution on the immunological parameters in 41 adult asthma and rhinitis patients. The immunological parameters included total IgE, spec. IgE and spec. IgG antibody determination, circulating immune complexes (CIC), lymphocyte response to Dermatophagoides pteronyssinus and to candidin and streptokinase-streptodornase (SKD). The two groups were compared to a control group of 123 non-allergic subjects. An increase in spec. IgG antibodies was found, with no change in the total and spec. IgE antibodies. The one year hyposensitization treatments had no influence on the appearance and level of CIC. A positive lymphocyte test to HDM antigen was found in 62% of the controls and in 70% of the treated patients. The response was significantly greater in the allergic patients than in the controls. Under the influence of hyposensitization, an early increase of the lymphocyte response to HDM, followed by a decrease, was noticed, whereas the response to candidin and to SKD remained unchanged. The present study demonstrated that the tyrosine adsorbed HDM extract had the same immunological consequences as the aqueous solution.

Double-blind crossover study of nabumetone versus naproxen in the treatment of osteoarthritis.

Twenty-one patients entered a double-blind crossover study to compare nabumetone with naproxen. After a 1-week run-in period using a coated acetylsalicylic acid preparation, ten patients received nabumetone (1 g at night) over a period of 2 weeks, followed by 2 weeks on naproxen (250 mg b.i.d), while eleven patients received the same treatments in the reverse order. Morning stiffness, overall pain and night pain showed no significant difference after either treatment. A wide range of objective measurements were made relating to the hips, knees, and cervical and lumbar spine. No statistically significant differences were observed in the relatively small number of patients involved. Both treatments, however, appeared to produce a similar improvement in the patients. The physician's assessment showed that improvement occurred in a majority of the patients over the total trial period. Both drugs were considered to be equally effective and were both well tolerated. There was no special patient preference for either the first or second treatment. A total of eight patients reported side-effects, three during naproxen alone, three during both treatments, and two during the run-in period. In terms of tolerance, fifteen patients had no drug preference, six preferred nabumetone, none preferred naproxen. No evidence was found of changes in renal, hepatic or haematopoietic function with the two drugs tested.