The illegal administration of phenobarbitone to the racing greyhound.
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Biomedical subjects
Publications and source records attributed to H Smith.
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A number of 2-cyanoindan-1,3-diones and 3-cyano-4-hydroxycoumarins have been prepared and assessed for potential antiallergy activity as measured by their ability to inhibit passive cutaneous anaphylaxis in the rat, mediated by rat serum containing antigen specific IgE. The structural requirements for activity were similar not only for both series of compounds but also for the analogous 2-nitroindan-1,3-diones and 4-hydroxy-3-nitrocoumarins previously reported. The most active compounds were 2-cyano-5,6-diethylindan-1,3-dione (4e) and 3-cyano-6,7-diethyl-4-hydroxycoumarin (11h).
A selection of novel 2-hydroxy-3-nitro-1,4-naphthoquinones are shown to be potent inhibitors of rat passive cutaneous anaphylaxis (PCA) and to have highest potency with alkyl substitution at both C-6 and C-7. The most potent compounds were 7c and 7e which produced a 50% inhibition in the rat PCA test at doses of about 10 micrometerM/kg following subcutaneous administration and showed activity after oral administration. Related 4-hydroxy-3-nitro-2(1H)-naphthalenones had no effect on rat PCA in doses up to 500 micrometerM/kg.
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The absorption of 212Pb ions from bronchial epithelium to blood has been investigated in anaesthetized rabbits. The 212Pb ions were introduced by intubation either into the trachea or into smaller, more distal bronchi. Removal from lung was followed by external gamma-counting. Mucociliary clearance to the GI tract was blocked by tracheostomy. Two distinct phases of clearance from bronchial epithelium to blood were observed. Approximately 20% of deposited 212Pb is rapidly absorbed with a half-time of about 4 min, the remainder with a biological half-time of about 9 h, irrespective of the site of instillation in the bronchial tree. Two hours after deposition, the 212Pb remaining in lung was found to be partitioned between mucus and the bronchial epithelium, with a substantial but minor fraction in the epithelium. Uptake of 212Pb in the skeleton was estimated to be about 20% of the 212Pb entering the blood circulation. Removal by the kidneys, at 25%, was comparable with skeletal uptake. These results are compared with previously published work using rodents, dogs and man which demonstrated either rapid or slow absorption but not both phases occuring together.
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Gonococci from subcutaneously implanted chambers in guinea pigs produced, on agar, more than 95% small colonies showing a "double highlight" (DH) effect in oblique reflected light combined with transmitted light. Laboratory strains of gonococci produced some DH colonies, but other showed a single highlight (SH) or no highlight (NH). Selection of DH colonies and comparison of their organisms with gonococci grown in vivo and with those from SH colonies, showed that the DH character was associated with high infectivity for guinea-pig chambers, resistance to killing by human phagocytes and heavy pilation. Furthermore, DH colonies were found in the first culture of three fresh samples of urethral pus. Thus, the DH colony characteristic may be a more reliable criterion of pathogenicity of gonococcal isolates than systems used previously. There were, however, some differences between the gonococci grown in vivo and the DH colony types. The gonococci grown in vivo and cultured once on solid medium possessed one or two antigens which differed from those of DH (or SH) colonies. They also formed smooth suspensions (which separated slowly) in saline, compared with the rough suspensions (which separated quickly) formed by gonococci from DH (or SH) colonies. Finally, the organisms grown in vivo were resistant to killing by human serum whereas the DH (and SH) colony types were susceptible; the resistance of the organisms grown in vivo was lost during one subculture on agar suggesting that the property is a phenotypic characteristic. Hence, in addition to selecting DH colony types the conditions in vivo produce organisms which differ, probably phenotypically, from cultured organisms.
Infection of subcutaneusly implanted chambers in guinea pigs conferred immunity against homologous infection of other chambers in the same animals. However, attempts to immunize guinea pigs by subcutaneous injection of filtered fluid from infected chambers, or with small doses of formalin-killed, chamber gonococci were not successful. Thus, neither organisms grown in vivo nor their extracellular products appeared to be exceptionally immunogenic. In immunizing tests with different isolates of gonococci adapted to growth in guinea-pig chambers, cross-immunity to chamber infection with low challenge doses was detected only between two of six isolates. The killing of gonococci in chambers of immunized animals, which occurred only after homologous challenge or with the heterologous strain showing cross-immunity, was not due primarily to humoral factors in the chamber fluid but probably to an enhanced effectiveness of phagocytosis. The serum of immunized animals was bactericidal for homologous strains and for the strain showing cross-immunity but not for strains showing no cross-immunity. Hence, serum bactericidal activity might be a useful indicator for investigating the specificity of immunity produced by different gonococcal strains.
Gonococci adapted to growth in chambers implanted subcutaneously into guinea pigs are resistant to killing by human serum. This resistance is lost after a few generations in vitro both in culture medium and in fluid taken from guinea-pig chambers. The rate of loss is too rapid to occur by mutation and selection. Furthermore, the resistance is regained after a few generations when bacteria from the first in vitro culture are inoculated back into guinea-pig chambers in vivo. Hence the loss of serum resistance in vitro and the gain in vivo are probably due to phenotypically controlled events. Such events could be important in the pathogenicity of Neisseria gonorrhoeae.
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Evidence is presented that lymphocytes characterised by being large and having abundant feebly staining, and usually profusely granulated cytoplasm ('pale' cells) are a group which is distinct from the other small basophilic ('dark') cells. In patients with genetic storage disorders characterised by abnormalities of lymphocyte structure, the structural peculiarites were confined to the basophilic cells, and cytochemical differences were found between the 'pale' and 'dark' cells in normal subjects.
Four compounds with H1 anti-histamine activity and four adrenoceptor stimulants, each given to rats prior to passive peritoneal anaphylaxis (PPA), inhibited extravasation of serum proteins into the peritoneal fluid at doses which had no effect on histamine release. In contrast, aminophylline and some non-steroidal anti-inflammatory agents inhibited extravasation only at doses which inhibited histamine releases they showed a similar type of avtivity to that of disodium cromoglycate (DSCG) and a nitroindanedione (BRL 10833), although they were much less potent. Predosing with DSCG reduced the potency of subsequent doses of DSCG, BRL 10833 and indomethacin, but not of aminophylline or phenylbutazone, and therefore DSCG, BRL 10833 and indomethacin may share a common pathway to produce activity. In the rat PPA system, no evidence was found for histamine 'feedback' inhibition of histamine release.
Infusion of indomethacin into anesthetized, salt-depleted dogs cuased an increase in mean arterial blood pressure (MABP), and decreases in heart rate (HR), urine flow rate (V), renal plasma flow (RPF), and renin secretion rate. MABP was 112.1 +/-5.4 mm Hg during control periods and was 147.7 +/- 5.6 mm Hg (P less than 0.005) 80 minutes after the infusion of indomethacin. V was 0.38 +/- 0.06 ml/min during control periods and was 0.08 +/- 0.01 ml/min (P less than 0.005) 80 minutes after the infusion of indomethacin. RPF was 126.3 +/- 13.3 ml/min and 41.5 +/- 7.5 ml/min, respectively (P less than 0.005), before and after 80 minutes of infusion. Renin secretion rate decreased from 1,194.1 +/- 353.9 U/min during control periods to reach 384.0 +/- 125.8 U/min (P less than 0.025) by 80 minutes of infusion of indomethacin. Subsequent infusion of prostaglandin E2 (PGE2) into the renal artery for 80 minutes caused increases of V to 0.53 +/- 0.13 ml/min (P less than 0.01), of RPF to 102.4 +/- 23.1 ml/min (P less than 0.01), and of renin secretion rate to 2,582.6 +/- 786.4 U/min (P less than 0.005). The decrease in renin secretion rate during the infusion of indomethacin persisted when renal perfusion pressure (RPP) was maintained relatively constant before and during the infusion of indomethacin. Furthermore, we found that infusion of prostaglandin E1 (PGE1) into the kidney gave the same pattern of response as PGE2. The data suggest that PGE1 and PGE2 play a role in the control of renin secretion.
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Three hundred sixty-three patients representing two groups of consecutive medical admissions to a large city hospital were evaluated on admission to determine what factors might predict "non-medical" or social stay. Periodic follow-up determined when patients were ready for discharge and when their social stay began. A composite index, the 4-Score, was derived as a simple indicator of risk for subsequent social stay; it is defined as the number of positive answers to the questions: 1) Is the patient 80 years old or more? 2) Will the patient have to live somewhere new at discharge? 3) Is there any disorientation? AND 4) If so, is the disorientation chronic? Eighteen per cent of the total inpatient hospital days of this group of patients could be attributed to social stay. The 56 patients with a 4-Score of two or more on admission had on average a week each of social stay while the 307 patients with a score of less than two averaged only one social day each.
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