Granisetron, a selective 5-HT3 receptor antagonist, for the prevention of radiation induced emesis during total body irradiation.

The antiemetic efficacy of granisetron was tested in an open trial in patients undergoing highly emetogenic treatment by single fraction total body irradiation. Thirty-two consecutive patients were entered. Results were both patient- and observer-rated. Following a single intravenous dose of granisetron 18 patients (56.3%) experienced total protection and a further 13 (40.6%) had major antiemetic protection with four of these patients experiencing nausea only. One patient experienced an anaphylactic reaction on infusion of monoclonal antibody-treated donor marrow 5 h after administration of the trial drug and vomited on multiple occasions. The reaction was associated with hypotension. A further patient experienced transient hypotension secondary to septicaemia 8 h after receiving granisetron. Three patients required a second dose. Headache was the most frequent side-effect occurring in three patients, but in to of these patients the test drug was not thought to be implicated. In conclusion granisetron is a highly effective agent in controlling radiation induced emesis with a favourable toxicity profile.

A study of platelet fibronectin immunofluorescence in peripheral vascular disease and diabetes mellitus.

Platelets hyperaggregability and hypersecretion fibronectin (Fn) are known to occur in peripheral vascular disease (PVD) and diabetes mellitus (DM) with microangiopathy. To determine whether an increase in platelet membrane bound Fn constitutes to hyperaggregability of platelets, washed platelets from normal subjects and from patients with peripheral vascular disease and patients with diabetes mellitus were examined for the presence of fibronectin (Fn) by means of fluorescein linked antibody to Fn. Platelets from peripheral vascular disease and diabetes mellitus patients tended to aggregate during preparation and apparently exhibited greater fluorescence in platelet "smears" than was observed in smears from controls. In contrast, when washed platelet "smears" were prepared from platelet preparations containing iloprost, an analogue of prostacyclin, platelet aggregates did not form and the 'excess' of fluorescence disappeared from all the three groups. When platelets were stained for Fn fluorescence in suspensions, no fluorescence was observed on the surface of platelets from peripheral vascular disease and diabetes mellitus patients or controls. On stimulation with thrombin washed platelet suspension showed fluorescence for Fn. Platelet activation leads to Fn appearing on platelet surface but this effect cannot be quantified by optical fluorescence microscopy.

Fibronectin concentrations in plasma in peripheral vascular disease.

Fibronectin (Fn) concentrations were measured immunoturbidimetrically in plasma of normal subjects and patients with peripheral vascular disease (PVD) before and after venous compression, which caused Fn concentrations to increase in both normal subjects and PVD patients. Basal Fn concentrations and those after 10-min compression were not significantly different in normal subjects and PVD patients. Five minutes after the release of compression, Fn had consistently declined in normal subjects and reverted to baseline values; in contrast, in PVD patients values either increased further or decreased inconsistently. Thus the Fn concentration at 15 min was significantly (P less than 0.001) greater in PVD patients than in normal subjects. Plasma albumin concentrations, measured in parallel to ensure that changes in Fn concentrations were not nonspecific, increased to a greater extent in normal subjects than in PVD patients and reverted to normal after the removal of compression. The Fn/albumin ratio remained unchanged in normal subjects after venous compression, whereas that in PVD patients increased and remained higher, even after decompression. The sustained increase in plasma Fn concentrations and in the Fn/albumin ratio in PVD patients after venous compression may indicate endothelial injury.

Sodium fluoride stimulates osteocalcin in normal subjects.

To test whether the administration of sodium fluoride in vivo results in an increase in osteocalcin concentration, we administered sodium fluoride to seven healthy male subjects for a period of 3 weeks. Fasting calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D, parathyroid hormone and osteocalcin were measured prior to, during and 6 weeks after fluoride administration. Plasma calcium, phosphate and alkaline phosphatase and serum 25-hydroxyvitamin D and parathyroid hormone concentrations did not alter. Serum osteocalcin concentrations increased following fluoride administration, and the mean osteocalcin concentration at 3 weeks was significantly higher than the pretreatment mean. Plasma urea and creatinine concentrations did not alter. Six weeks after the cessation of fluoride treatment, the mean serum osteocalcin concentration had returned to the pretreatment baseline. We conclude that fluoride administration in normal subjects over a short period increases serum osteocalcin concentration and probably stimulates osteoblastic activity.