Preliminary safety and tolerance data obtained in the comparative study of anisoylated plasminogen streptokinase activator complex versus heparin.

The safety/tolerance of anisoylated plasminogen streptokinase activator complex (APSAC) versus heparin therapy in acute myocardial infarction has been studied in the first 65 patients treated in a multicentre study. A transient marked hypotensive effect was observed in 2 patients on APSAC given over 2 minutes. Primary ventricular arrhythmias during the first 4 hours after treatment occurred in 16 APSAC-treated patients and in 7 patients who received heparin; in 88% of the cases on APSAC these arrhythmias were reported by the investigators as being associated with reperfusion. Vomiting, shivering and fever were reported transiently in 2 APSAC-treated patients. Bleeding occurred in 7 patients in the APSAC group; none of these required transfusions, but the heparin dosage was adjusted in 1 patient. A reduction of blood haemoglobin was observed in 4 APSAC- and 2 heparin-treated patients; these were possibly drug-related. Three patients on APSAC died, while in the heparin group 4 deaths were reported.

An evaluation of the safety and tolerance of Timentin.

The safety and tolerance of four intravenous formulations of Timentin (ticarcillin + clavulanic acid) have been evaluated in 1659 patients (1512 adults and 147 paediatric) included in clinical trials conducted in Europe and U.S.A. Timentin 3.2 and 5.2 g were administered respectively to 877 and 635 adults and Timentin 1.6 and 2.6 g to 117 and 30 paediatric patients three, four or six times daily for between 7.7 and 9.0 days in adults and 8.0 and 12.0 days in paediatric cases. Patients with septicaemia were 16%, 14% and 28% respectively of the Timentin 3.2, 5.2 g and paediatric groups, which together with respiratory tract and other serious miscellaneous infections accounted for the majority of cases treated within these three groups. Of the 1659 patients studied, 161 adverse reactions were reported from 151 patients (9.1%), 36 of which (2.2%) resulted in discontinuation of treatment. The reactions were at the injection site in 86 cases (5.2%), hypersensitivity in 35 (2.1%) and miscellaneous systemic symptoms in 40 cases (2.4%). Local reactions, i.e. phlebitis, pain and erythema, were self-limiting and did not necessitate early cessation of treatment. Hypersensitivity reactions occurred equally in all groups and necessitated cessation of treatment in about half of the patients. Gastro-intestinal disturbances were observed in eight, four and one patient within the Timentin 3.2, 5.2 g and paediatric groups. Changes in haemostatic status were reported in nine patients treated with Timentin. In all cases they were associated with contributory pathology and/or concurrent use of anticoagulants. Laboratory monitoring revealed transient variations in haemoglobin, blood cellular or plasma composition and plasma enzymatic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparative study of the effectiveness and safety of two non-steroidal anti-inflammatory agents, nabumetone and naproxen in rheumatoid arthritis.

A single-blind crossover study of two non-steroidal anti-inflammatory drugs, nabumetone (1000 mg/day) and naproxen (500 mg/day) was performed in thirty patients suffering from definite or classical rheumatoid arthritis. Nabumetone significantly improved the various parameters assessed, while this was not observed with naproxen. The superiority of nabumetone over naproxen appeared for the anti-inflammatory activity (e.g. E.S.R., articular index, P.I.P. joint circumference, grip strength) as well as for the analgesic activity (patient's opinion). The clinical tolerance appeared equally good for both drugs.

Amoxycillin: a new semi-synthetic penicillin.

Amoxycillin (alpha-amino-p-hydroxybenzylpenicillin) is a new semi-synthetic penicillin with a broad spectrum of antibacterial activity similar to that of ampicillin. Penicillin-sensitive strains of staphylococci, streptococci, and pneumococci were sensitive to concentrations of 0.1 mug or less of amoxycillin/ml. Strains of Haemophilus influenzae were inhibited by a level of 0.5 mug/ml, and most strains of Escherichia coli, Proteus mirabilis, Shigella sonnei, Salmonella species, and Streptococcus faecalis were sensitive to a concentration of 5 mug or less of amoxycillin/ml. Penicillinase-producing strains of Staphylococcus aureus and strains of Pseudomonas aeruginosa, indole-positive Proteus, Klebsiella, and Enterobacter were insensitive to amoxycillin. The new penicillin was bactericidal in activity, as with other penicillins, and its antibacterial activity was not reduced in the presence of serum. After oral administration to volunteer subjects amoxycillin produced serum concentrations twice as high as those obtained with similar doses of ampicillin, and the penicillin was recovered unchanged in high concentrations in the urine. The absorption of amoxycillin was not greatly influenced by food, and administration of probenecid resulted in increased and more prolonged concentrations of amoxycillin in serum.

Successful treatment of osteomyelitis caused by Pseudomonas aeruginosa.

A case of generalized osteomyelitis due to Ps. aeruginosa is described. The condition had failed to respond to therapy with almost all antibiotics available but responded to long-term therapy with carbenicillin in very large doses, and it is suggested that this is now the treatment of choice for severe infections due to this organism.

Flucloxacillin, a new isoxazolyl penicillin, compared with oxacillin, cloxacillin, and dicloxacillin.

Flucloxacillin, a new isoxazole penicillin, is active against penicillinase-producing strains of Staphylococcus aureus and is well absorbed in man after oral and intramuscular administration. Compared with isoxazole penicillins in current clinical use-namely, oxacillin, cloxacillin, and dicloxacillin-flucloxacillin has proved as active against Gram-positive cocci, including penicillin-resistant staphylococci. The extent of binding of flucloxacillin to the protein of human serum was similar to that of oxacillin and cloxacillin and less than that of dicloxacillin. In man flucloxacillin given orally produced total and free serum levels higher than those obtained with oxacillin and cloxacillin; total serum levels similar to those of dicloxacillin, and free levels greater than those of dicloxacillin. Similarly, after intramuscular injection the free serum levels of flucloxacillin were higher than those of oxacillin, cloxacillin, and dicloxacillin.