Biomedical subjects
Publications and source records attributed to C B Jackson.
Prophylactic intramedullary nailing of the tibia for stress fracture was performed successfully in a professional football player, enabling him to resume his career. No similar case has been reported previously.
In ferrets, the oral emetic activity of zacopride was compared with its R- and S-enantiomers. Increasing doses of 0.01, 0.1, 1.0, 10.0 and 31.6 mg/kg of zacopride or its 2 enantiomers were each administered at hourly intervals to separate groups of animals until emesis occurred. The emetic (100%) dose for zacopride and its S-enantiomer was 0.11 mg/kg p.o. (cumulative dose). The R-enantiomer at a cumulative dose of 42.71 mg/kg p.o. produced emesis in 25% of the animals. By the i.p. route zacopride and its S-enantiomer were more potent than the R-enantiomer in blocking the emetic activity of 0.1 mg/kg p.o. of zacopride. The involvement of 5-HT3 mechanisms is indicated by a correlation between zacopride and its enantiomers to cause and prevent emesis and their affinity at 5-HT3 binding sites. Further, the putative 5-HT3 agonists, 2-methyserotonin and phenylbiguanide, at 10 mg/kg p.o., produced emesis that was blocked by zacopride (0.1 mg/kg i.p.) or ICS 205-930 (1 mg/kg i.p.). The results suggest that in the ferret the S-enantiomer is predominantly responsible for both the emetic and antiemetic properties of zacopride and that 5-HT3 agonism and antagonism are involved in these actions.
Zacopride administered orally was more emetic in fed than in fasted ferrets. The emetic activity of zacopride (0.1 mg/kg p.o.) was inhibited (100%) by 0.1 mg/kg i.p. of zacopride and 1 mg/kg i.p. of ICS 205-930. Haloperidol (3.16 mg/kg i.p.) and prochlorperazine (3.16 mg/kg i.p.) were weakly effective. N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide, a 5-HT1P antagonist, was inactive. Thus, the emetic activity of zacopride, like that of cisplatin, is blocked by 5-HT3 receptor antagonists.
The antiemetic activity of zacopride against a variety of emetogenic agents has been determined in dogs. Zacopride was highly effective in inhibiting emesis due to a wide range of cancer chemotherapeutic agents, particularly cisplatin. It was well absorbed orally since the dose of zacopride required to inhibit cisplatin-induced emesis in dogs by 90% was 28 micrograms kg-1 both by i.v. and p.o. routes. Further, zacopride (1 mg kg-1 p.o.), administered after the onset of cisplatin-induced emesis, reduced the number of subsequent emetic episodes by 91%. Zacopride at 0.1, 1, or 3.16 mg kg-1 p.o. or i.v., reduced the number of emetic episodes due to dacarbazine, mechlorethamine, adriamycin, actinomycin D, or peptide YY by 100, 100, 86, 96 and 79%, respectively. However, zacopride was not effective in inhibiting emesis due to either apomorphine, copper sulphate, protoveratrine A, histamine, or pilocarpine. No adverse effects attributed to zacopride were observed. Zacopride is thus a unique and potent antiemetic agent as it selectively inhibits the emetic response to cancer chemotherapy agents and peptide YY.
A technique for acquiring dynamic geometric mean studies utilizing a single-headed rotating gamma camera has been developed. The camera head is repeatedly rotated between opposed views under computer control. A single data set results, from which a dynamic sequence of geometric mean images can be produced. Software has been developed to accomplish data acquisition and the reformatting required. The accuracy of the geometric mean data formed using this technique has been studied experimentally, and compared with results obtained from anterior and posterior sequences. In a simple clearance experiment of a 1-I volume with a known clearance of 20 ml.min-1, the geometric mean data resulted in estimates of volume remaining in the container with a mean error or +2.0 ml (s.d. = 5.7 ml, range -4.5 +/- 15.3 ml), while the anterior and posterior images yielded volume estimates with mean errors of -10.1 ml (s.d. = 16.6 ml, range -47.4 +/- 10.5 ml) and +35.5 ml (s.d. = 22.6 ml, range -3.2 +/- 51.6, ml), respectively. The technique is easy to implement and does not require modification of existing hardware. An application of the technique to a clinical study of gastric emptying is also included.
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