Animal models as predictors of therapeutic efficacy in bacterial infections in humans.
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Biomedical subjects
Publications and source records attributed to D F Brown.
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Thirty-one Kanagawa-positive and -negative Vibrio parahaemolyticus isolates from patient stools and seafood were examined for plasmid deoxyribonucleic acid content, culture characteristics, and indices of pathogenicity. No significant correlation was found between plasmid deoxyribonucleic acid contents and indices of pathogenicity for the strains tested.
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Insulin is apparently not required for VMH glucose oxidation in vitro. Ouabain, an inhibitor of the Na-K pump ATPase, does not prevent VMH glucose oxidation in vitro. These data suggest (a) the VMH does not exhibit a cotransport phenomenon of glucose with the Na-K pump mechanism, and (b) glucose oxidation in the VMH is not insulin dependent. Alloxan-diabetes was induced to increase tissue insulin sensitivity. A comparison of glucose oxidation rates in alloxan-diabetic VMH tissue and normal VMH tissue, supplemented only with saline, indicated a highly significant (p < 0.001) depression of glucose oxidation in the alloxan-treated tissue. Cell membranes in the VMH are perhaps altered by alloxan.
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New qualitative and quantitative methods are described for the investigation of the antibacterial activity of lipids on solid media by the application of lipid-impregnated filter paper over a lawn of the organisms. The methods have been used to investigate the antibacterial activity of unsaturated fatty acids that are important in skin defence. Oleic and linoleic acids inhibited Streptococcus pyogenes markedly, Staphylococcus aureus and Staph epidermidis to a lesser extent and had no effect on Escherichia coli and Pseudomonas aeruginosa. The inhibition of growth of a strain of Str. pyogenes from a sore throat was greater than that of a strain from an outbreak of impetigo. Linoleic acid was a more potent inhibitor of bacterial growth than oleic acid, and with both acids inhibition was more pronounced under aerobic than under anaerobic conditions of incubation. The methods described could be applied in other fields such as pharmacology, horticulture and industry.
Gold thioglucose (800-1000 mg/kg ip) failed to cause lesions in the hypothalamus of Rana pipiens within 48 h of injection. Since this dose is a pharmacological one in mammals it is likely that the frog hypothalamus differs significantly in its sensitivity.
Life-threatening episodes of ventricular tachycardia were documented in a patient with an implanted Omni-Stanicor pacemaker due to episodic pacemaker runaway. The unit generated impulses at rates varying from 73 to 500 per minute. Ventricular capture at high rates was variable, but frequently resulted in heart rates in excess of 200 per minute. These episodes were associated with loss of consciousness secondary to inadequate cardiac output. Although the pacemaker could be inactivated by reprogramming its output to 2 mA, and suppressed by chest wall stimulation with an external pulse generator, no spontaneous rhythm resulted during these maneuvers. Urgent removal of the battery at the bedside and immediate resumption of pacing with an external generator was required to resolve the problem. Although runaway is infrequent with current generation pacemakers, it should be considered in addition to the more common causes of pacemaker malfunction in the patient with appropriate symptoms.
The effects of epinephrine on cyclic AMP content and protein kinase activity were examined in an in situ rat heart preparation. Bolus injection of epinephrine into the superior vena cava caused an increase in the activity ratio (-cyclic AMP/"cyclic AMP) of 12 000 X g supernatant protein kinase. The increase was significant within 5 s and maximal in 10 s. Epinephrine produced a dose-dependent increase in both protein kinase activity ratio and cyclic AMP content. The increases in both parameters exhibited a high degree of correlation. The increase in protein kinase activity ratio observed with low doses of epinephrine (less than or equal to 1 microgram/kg) resulted from an increase in independent protein kinase activity (-cyclic AMP) without a change in total protein kinase activity (+cyclic AMP). However, the increase in the activity ratio observed with higher doses of epinephrine (greater than 1 microgram/kg) was due mainly to a decrease in total protein kinase activity rather than a further increase in independent protein kinase activity. The loss of supernatant total protein kinase activity could be accounted for by an increase in activity associated with particulate fractions obtained from the homogenates. A similar redistribution of protein kinase could be demonstrated by the addition of cyclic AMP to homogenates prepared from hearts not stimulated with epinephrine. These results demonstrate that epinephrine over a wide dose range produces a parallel increase in the content of cyclic AMP and the activation of soluble protein kinase. The findings also suggest that protein kinase translocation to particulate material may depend on the degree of epinephrine-induced enzyme activation.
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The aetiological agent of contagious equine metritis (CEM) has been investigated bacteriologically in a wide range of cultural and conventional biochemical tests, in the eletron microscope, for DNA base composition (36.1 per cent GC), for susceptibility to various antimicrobial agents and antigenically by means of tube and slide agglutination tests. The organism is a fastidious, Gramnegative, non acid-fast coccobacillus which in biochemical tests is very unreactive. In conventional tests, only the oxidase, catalase and phosphatase tests were positive. Dependance on neither X nor V factors could be demonstrated, but some stimulation of growth by X factor was observed. The organism could not be identified with any known species and even allocation to an appropriate characters, we propose the organism as a new species of the genus Haemophilus: H. equigenitalis, type strain NCTC 11184 (61717/77).
A strain of Vibrio parahaemolyticus, serotype O4/K4, that was Kanagawa positive and reactive in the rabbit ileal loop test, was isolated in low numbers from raw oysters implicated in a case of acute gastroenteritis. To our knowledge, this is the first report of the isolation of a Kanagawa-positive strain from suspect food in the United States.
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