An evaluation of the safety of cefuroxime axetil during six months oral administration to beagle dogs.

The effects of repeated oral administration of cefuroxime axetil were assessed in Beagles. The test material, an ester, is hydrolysed following absorption from the intestine to yield the therapeutically active moiety, cefuroxime, together with acetic acid and acetaldehyde; in this study cefuroxime and unhydrolyzed cefuroxime axetil were detected in the blood. Cefuroxime axetil was administered twice daily during 27 weeks by gavage of aqueous, suspensions, total daily doses were equivalent to 100, 400 or 1600 mg cefuroxime/kg/day. Apart from three cases of intercurrent illness, unrelated to treatment, the dogs remained in good health. Effects observed in the 1600 mg/kg group included vomiting and slight suppression of body weight gain. Minor variations in haematological measurements included rather low haemoglobin levels, packed cell volumes and erythrocyte counts. Slightly smaller numbers of neutrophils were thought to reflect reduced demand on normal defensive mechanisms due to continued antibiotic treatment. Prolongation of prothrombin time and activated partial thromboplastin time is attributed to disturbance of the intestinal microbial flora and reduced synthesis of vitamin K, on which the dog is highly dependent. Cefuroxime does not have the N-methylthiotetrazole side chain thought to be responsible for inhibition by other cephalosporins of the vitamin K-dependent step in the synthesis of clotting factors. Variations in plasma chemistry included rather low levels of plasma protein. Electrophoresis showed this to be a generalised reduction; only gamma globulins were proportionally decreased and this finding, like the low neutrophil counts, is attributed to the protective action of the antibiotic. Minor metabolic adjustments to the compound are reflected in plasma levels of cholesterol and triglycerides. This spectrum of findings was seen only to a very limited extent in the 400 mg/kg group; the 100 mg/kg group was, with very few exceptions, unaffected by the treatment. Macroscopic post mortem examination and microscopic examination of tissues revealed no treatment-related features indicative of toxicity. Cefuroxime axetil was thus shown to possess very little toxicity when administered repeatedly in large doses to Beagles. The lowest dose level in this study was ten times the proposed daily clinical dose in man.

Association of long lasting unsurmountable histamine H2 blockade and gastric carcinoid tumours in the rat.

The oral administration of loxtidine, a potent histamine H2-antagonist, to a total of 378 rats at doses of 50, 185, or 685 mg/kg/day for 116 weeks resulted in the late formation of carcinoid tumours of the gastric fundus. The first such tumour was detected after 712 days of treatment. There was no dose related response; 11 rats at the low level of treatment were affected, 12 at the intermediate and 11 at the high. Twenty seven females but only seven males were affected. No gastric tumours were found in the 228 controls. There is no evidence that loxtidine acts as a direct carcinogen and it is suggested that the tumours were the result of prolonged achlorhydria produced by a potent unsurmountable histamine H2 receptor antagonist.

Polyarteritis in a colony of beagles.

The clinical and pathological features of polyarteritis occurring in a colony of beagles are described. Meningeal and cardiac arteries were most commonly involved. Amyloidosis and lymphocytic thyroiditis were also present in some of the affected dogs. The polyarteritis is probably of autoimmune origin.

The hospital consultant's secretary.

Analysis of work done by the secretaries attached to one medical unit in a general hospital showed that much was discretionary in character and entailed making decisions. Work in the unit was made easier and more efficient by this intelligent use of initiative by the secretaries. At present the pay given to medical secretaries in hospital is below a level that would be commensurate with their responsibility.