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(67) ,ug m1-1, respectively, at the highest dose. Median tmax in plasma was 6.5 h and in erythrocytes 24.5 h, when approximately 60% of the administered dose was in the target tissue. Plasma drug concentrations fell biexponentially with commencement of the apparent terminal elimination phase at approximately 24 h. The terminal elimination half-life from plasma increased with dose (r = 0.77; P < 0.0001) from 133-190 h at 400 mg to a mean (s.d.) of 289 (30) h at 3600 mg. Erythrocyte drug concentrations declined monoexponentially with a half-life that was always shorter than the apparent terminal halflife in plasma: overall mean (95% CI) of t1/2 erythrocyte/t1/2 plasma ratio was 0.57 (0.53, 0.61). The erythrocyte AUC/plasma AUC ratio increased with dose (r = 0.67; P < 0.001). 4 The proportion of haemoglobin modified to a form with high oxygen affinity (% MOD) increased in a dose-related manner above doses of 800 mg reaching 19-26% after the 3600 mg dose. The % MOD was directly proportional to erythrocyte drug concentrations and declined in parallel during the elimination phase. 5 The drug was well tolerated, with no clear effects on resting or exercise heart rates or blood pressures. Small increases in reticulocyte counts were seen following doses of 2800 and 3600 mg suggesting stimulation of erythropoiesis.

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Faecal samples from 110 horses, 115 pigs, 111 sheep and 123 cows were examined for the presence of Aeromonas hydrophila, which was also sought in the available drinking water. The overall faecal rate was 11.8%, but significantly more bovine than other samples were found to be positive. There was significant association between the isolation of A. hydrophila from all animal faeces and its presence in drinking water, but this was not found when individual animal groups were analysed separately. An enrichment technique increased the total number of isolates by 77.1%. Strains of differing origins could not be differentiated by biotyping, although fermentation of sorbitol was associated with bovine isolates. There was a strong positive correlation between positive reactions for V--P, gluconate oxidase and haemolysis of rabbit erythrocytes, tests which had previously been shown to correlate with production of enterotoxin and cytotoxin. Biotypes giving positive reactions for these tests were most frequently isolated from cows, sheep and untreated water, and less frequently from pigs and horses. Most strains of A. hydrophila were resistant to amoxycillin, carbenicillin and cephradine, and sensitive to gentamicin, chloramphenicol and neomycin.

ABSTRACT. Bacteria isolated from cultures of 4 different strains of the diatom Pseudo-nitzschia multiseries following numerous transfers in a defined medium were identified as mainly Moraxella and Alteromonas sp. These bacteria apparently form a characteristic suite of microorganisms living in a symbiotic relationship with the diatom. The bacterial isolates from each of the P. multiseries strains divided metabolically into 2 groups; those that produced significant amounts of acid from carbohydrates and those that grew readily at the expense of amino acids. The specific acid forming bacteria isolated from each diatom species grown in the presence of glucose produced gluconic acid/gluconolactone in quantity and released it to the surrounding medium. For growth of the diatom a salinity of 33 ppt was more favorable than 26 or 38 ppt; sorbitol varied with the salinity and thus might be an osmolyte. Glucose was present in s~gnificant quantities In the diatom grown at all 3 salinities Nonaxenic growth of the diatom was stimulated considerably by the presence of proline alone and to approximately the same level when it was combined with glucose or sodium acetate, but not when glycine was substituted for the proline. Stimulation of the growth of the diatom by the presence of proline was considered to be a function of the associated bacteria. Glycine combined with sodium acetate was slightly inhibitory to the growth of the diatom but both glycine plus sodium acetate and glycine plus glucose combinations were markedly inhibitory to the growth of the associated bacteria. The possible role of all of these features in the initiation of a bloom of Pseudo-nitzschia rnultiseries, espec.idlly in an inshore environment enriched by organic nitrogen, and the consequent production of domolc acid is discussed.