The amyotrophic lateral sclerosis client and the issues surrounding mechanical ventilation.
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Biomedical subjects
Publications and source records attributed to A M Farrell.
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Lipase of Staphylococcus epidermidis 9 was purified from culture supernatant fluid. Two polypeptides (51 and 43 kDa) were detected by SDS-PAGE, of which the 43 kDa polypeptide reacted with anti-lipase serum. The S. epidermidis 9 lipase gene (gehC) was cloned in Escherichia coli and localized to a 2.1 kb sequence by subcloning and transposon mutagenesis. The nucleotide sequence of gehC (2064 nucleotides) was determined and the predicted amino acid sequence of the encoded lipase (77 kDa) identified. A 97 kDa lipase was detected in extracts of E. coli harbouring gehC and in post-exponential-phase culture supernatant fluids of S. epidermidis 9. Data presented indicate that the lipase behaves anomalously during SDS-PAGE and that a pro-lipase is proteolytically processed in cultures of S. epidermidis 9 during growth.
The study of virus-induced airway hyperresponsiveness may provide insight into mechanisms that contribute to respiratory diseases such as asthma. We examined changes induced by parainfluenza virus type 3 (PI-3) in lung lesions, tissue weights, and airway responsiveness to aerosols of histamine, methacholine, or citric acid in conscious guinea pigs, using modified whole body plethysmography. During the first week after inoculation, infected lung tissue had peribronchiolitis and airway hyperresponsiveness to various agents when dyspnea and significant respiratory events were measured; these effects persisted throughout postinoculation weeks 2 and 3. Airway hyperresponsiveness was defined by reductions in the onset of dyspnea or significant respiratory events. Throughout the course of the study, PI-3 infected animals had resting respiratory patterns that reflected labored breathing and may have been related to the edema indicated by increased lung weights. Furthermore, increased numbers of inflammatory cells were observed in lung tissue as well as bronchoalveolar lavage fluid of infected animals at these times. Unlike PI-3 infection, exposure to gram-negative endotoxin resulted primarily in airway hyporesponsiveness to histamine aerosol. Hence, we have shown PI-3 infection in guinea pigs causes time-dependent alterations in airway responsiveness to diverse bronchoactive agents as well as in normal breathing patterns, which may persist up to several weeks after inoculation in animals that may otherwise appear normal.
The effect of zinc and erythromycin on cultures inoculated with mixtures of different ratios of erythromycin sensitive (ES) and resistant (ER) Propionibacterium acnes cells was studied in vitro. Propionibacterium acnes ES outgrew P. acnes ER in the absence of erythromycin and zinc. At low levels of erythromycin ES outgrew ER, whilst the addition of 600 pg/ml zinc further reduced the growth of ER compared to ES. Growth of ER and ES were similar at levels of erythromycin near the minimum inhibitory concentration (MIC) of ES cells. Concentrations above the MIC for ES cells inhibited ES but not ER cells. At the higher concentrations of erythromycin, the addition of 96 ng/ml zinc delayed the growth of ER cells, whilst the addition of 300 micrograms/ml zinc prevented the growth of ER cells. The combination of erythromycin and zinc, at appropriate concentrations, inhibits both ES and ER.
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A series of substituted 3,4-dihydro-2H-1,4-thiazines inhibit 5-lipoxygenase from rat leukocytes and exhibit submicromolar IC50 values. A novel synthesis of these compounds was developed based on the formation of hydroxymethyleneamine 13 and its cyclization to the title compounds. The dihydrothiazines have low oxidation potentials, typically E1/2 is near 0.3 V, and a representative compound reduces Fe(III)(phen)3, with k = 10(5) M-1s-1. We propose that these lipophilic compounds bind to 5-lipoxygenase and reduce the iron in the active site, thus inactivating the enzyme.
A total of 110 staphylococcal isolates from human skin were found to express a novel type of erythromycin resistance. The bacteria were resistant to 14-membered ring macrolides (MIC 32-128 mg/l) but were sensitive to 16-membered ring macrolides and lincosamides. Resistance to type B streptogramins was inducible by erythromycin. A similar phenotype, designated MS resistance, was previously described in clinical isolates of coagulase-negative staphylococci from the USA. In the UK, MS resistance is widely distributed in coagulase-negative staphylococci but was not detected in 100 erythromycin resistant clinical isolates of Staphylococcus aureus. Tests for susceptibility to a further 16 antibiotics failed to reveal any other selectable marker associated with the MS phenotype. Plasmid pattern analysis of 48 MS isolates showed considerable variability between strains and no common locus for the resistance determinant. In one strain of S. epidermidis co-resistance to tetracycline, penicillin and erythromycin (MS) was associated with a 31.5 kb plasmid, pUL5050 which replicated and expressed all three resistances when transformed into S. aureus RN4220. The MS resistance determinant was localised to a 1.9 kb fragment which was cloned on to the high-copy-number vector, pSK265. A constitutive mutant of S. aureus RN4220 containing the 1.9 kb fragment remained sensitive to clindamycin. This observation, together with the concentration-dependent induction (optimum 5 mg/l of erythromycin) of virginiamycin S resistance suggests that the MS phenotype is not due to altered expression of MLS resistance determinants (erm genes) but probably occurs via a different mechanism.
An unusual case is presented of a systemic anaphylactoid reaction to tubocurarine and subsequently to vecuronium. Intradermal testing with vecuronium following the latter response was negative at recommended test dose levels but at a higher concentration it initiated a hazardous systemic response. The laboratory investigations and possible mechanisms involved in this unusual case are discussed in detail since they may relate to other patients who experience anaphylactoid responses to anaesthetic drugs and who then undergo intradermal testing.