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Biomedical subjects

A MacGowan

Publications and source records attributed to A MacGowan.

18 recordsLinked to original sources
PubMed2001

In vitro models, in vivo models, and pharmacokinetics: what can we learn from in vitro models?

In vitro pharmacokinetic models of infection can make an important contribution to the study of the pharmacodynamic properties of an antibacterial agent. In conjunction with animal and human pharmacodynamic evaluations, they provide data to allow for the optimization of drug dosing regimens. In vitro models can be used simply to describe the effect of a drug on a bacterial population as well as to provide data for more-analytical studies, including hypothesis testing. Analytical study designs provide information on the pharmacodynamic parameter best related to the chosen outcome, as well as its magnitude. Factors such as the characteristics of the model (method of drug removal, inoculum density, and growth phase), doses simulated, species and susceptibility range of bacteria, and methods and analytical tools used to measure antibacterial effect will have an effect on the conclusions drawn. In vitro models have an important future role in ensuring antibiotic efficacy and in reducing the risks of resistance.

Animals↗
PubMed2001

Genomic organization of the mouse plunc gene and expression in the developing airways and thymus.

Few genes have been isolated which display specific expression in the proximal airways. A recently identified mouse cDNA, plunc, appears to be confined to the upper airways and nasopharyngeal epithelium, and may prove a useful marker for these regions. We now report the genomic cloning and characterization of the mouse plunc gene as well as its developmental expression in the nasal and airway epithelium. We also report the novel finding that plunc is also expressed in the medullary compartment of the murine thymus. The mouse gene contains nine exons and the intron-exon boundaries are conserved with those in the human homologue. At e14.5 plunc is expressed in the nasal epithelium and several days later is seen in the thymic lobes, but not in the lining of the tracheobronchial tree. Expression in the trachea and main-stem bronchi first appears at 1--2 days after birth. Tracheobronchial expression persists at high levels throughout adulthood, as do regional areas of nasal and thymic expression. Finally, we show that the human homologue is expressed in bronchial epithelium, suggesting a transcript that is evolutionarily conserved in the mammalian airway.

Animals↗
PubMed2000

Assessment of different antibacterial effect measures used in in vitro models of infection and subsequent use in pharmacodynamic correlations for moxifloxacin.

A dilutional culture in vitro pharmacodynamic model of infection was used to assess the best measure of antibacterial effect for moxifloxacin at simulated human doses of 400 mg 24 hourly for 48 h. This was then related to two pharmacodynamic parameters, the drug area under curve: MIC ratio (AUC/MIC) and the length of time that the drug concentration remained above the MIC of the bacterium (T > MIC). Twenty-one bacterial strains (Streptococcus pneumoniae n = 6; Haemophilus influenzae n = 6; Moraxella catarrhalis n = 3; beta-haemolytic streptococci n = 3; Staphylococcus aureus n = 3; MIC range 0.06-3.6 mg/L) were tested in 69 individual simulations. The measures or parameters of antibacterial effect considered were log change in viable count in the initial inoculum at 12 h (triangle up12), 24 h (triangle up24), 36 h (triangle up36), 48 h (triangle up48), maximum reduction in count (triangle up(max)); time for bacterial counts to reduce by 100-fold from the initial density (T99) or 1,000-fold (T99.9); and area under the bacterial kill curve from 0 to 24 h (AUBKC(24)) or from 0 to 48 h (AUBKC(48)). triangle up12, triangle up24, triangle up36, triangle up48, triangle up(max), T99, T99.9 did not vary over the complete range of MICs; at high MICs, especially with Gram-positive bacteria the T99 and T99.9 values were >48 h while at low MICs, especially with Gram-negative bacteria, bacterial counts were reduced below the limit of detection with triangle up12, triangle up24, triangle up36, triangle up48 and triangle up(max) exceeding >6.5 log reduction. AUBKC(24) and AUBKC(48) varied more completely over the range of MICs and more importantly had the best within-strain reproducibility (median percentage coefficient of variation <15%). The relationship between the transformed AUBKC(24) and AUC/MIC could be described by a sigmoid Emax model but the relationship with T > MIC could not. Use of weighted least squares regression to examine the combined effect of AUC/MIC and T > MIC on AUBKC(24) indicated that AUC/MIC provided a good fit to the data (r(2) = 0.94) and adding T > MIC did not improve the model fit. Cox proportional hazards regression indicated that AUC/MIC was predictive of T99 and in a multivariate model although AUC/MIC predicted outcome after fitting AUC/MIC, T > MIC was not significant. AUBKC was thus shown to be the optimum measure of antibacterial effect to use in pharmacodynamic studies of moxifloxacin and AUC/MIC the best predictor of antibacterial effect as measured by AUBKC(24) or T99. These results are in good agreement with animal data on moxifloxacin pharmacodynamics and human data for some other fluoroquinolones.

Animals↗
PubMed2000

The passage of bacteria through surgical drapes.

The passage of bacteria through surgical drapes is a potential cause of wound infection. Previous studies have shown that liquids and human albumin penetrate certain types of drapes. We studied the passage of bacteria through seven different types of surgical drape and an operating tray. Bacteria easily penetrated all the woven re-usable fabrics within 30 min. The disposable non-woven drapes proved to be impermeable, as did the operating tray. We recommend the use of non-woven disposable drapes or woven drapes with an impermeable operating tray in all surgical cases.

Bacteria↗
PubMed1999

Ultrastructural studies demonstrate that epithelial polarity is established in cultured mouse pre-Sertoli cells by extracellular matrix components.

The effect of three different substrates, laminin, fibronectin and reconstituted basement membrane, on isolated mouse pre-Sertoli cells maintained in vitro has been investigated. Cultures were monitored on a daily basis by phase contrast microscopy, and processed for light and electron microscopy at the end of the culture period. Extra-cellular matrix components have been found to influence Sertoli cell differentiation: both fibronectin and laminin promoted cell adhesion and differentiation, though laminin cultures showed poor viability. Pre-Sertoli cells cultured on reconstituted basement membrane showed the highest degree of differentiation, developing a polarized epithelial phenotype and forming cord-like aggregates; such cultures provide a model system for the investigation of factors involved with gonadal differentiation.

Animals↗
PubMed1998

Venous allografts prepared from stripped long saphenous vein. Is there a need for antibiotic sterilisation?

AIM: Can useful lengths of vein be retrieved from varicose vein stripping procedures; is it necessary to sterilise this tissue prior to use as vein allografts? METHOD: Stripped long saphenous vein was retrieved at operation. Vein samples were cultured using direct plate inoculation and enrichment culture. Further samples were immersed in two low concentration antibiotic solutions and recultured. Smooth muscle viability was assessed after antibiotic immersion and storage by cryopreservation. RESULTS: High quality vein could be retrieved by vein stripping. Vein segments grew skin commensals on enrichment culture despite negative cultures with standard media plate inoculation (Chi-squared = 53.34 1 d.f. p < 0.001). Low concentration antibiotic solutions sterilised processed vein. Smooth muscle cell viability was reduced by cryopreservation, Mann-Whitney p = 0.008 (control 98% S.E. 0.93 vs. cryopreserved 64% S.E. 6.58), but prior exposure to antibiotics did not compound this effect. CONCLUSION: Useful lengths of vein grafts can be retrieved from varicose vein stripping procedures. Venous segments are frequently contaminated by skin commensals. Enrichment culture is required to detect contamination. Low concentration antibiotics sterilise venous-tissue without affecting smooth muscle cell viability.

Anti-Bacterial Agents↗
PubMed1997

External quality assessment of the serum bactericidal test: results of a methodology/interpretation questionnaire.

Two hundred microbiology laboratories in the UK took part in two separate experimental external quality assessment distributions related to the serum bactericidal test (SBT). In the first, Staphylococcus aureus NCTC 6571 (vancomycin MIC 1 mg/L), was tested against a human serum containing vancomycin 38 mg/L plus gentamicin 0.5 mg/L. In the second, Streptococcus oralis PAJ 112/4183 (penicillin MBC < or = 0.03 mg/L) and Streptococcus sanguis PAJ 107/4184 (penicillin MBC = 128 mg/L) were tested against human serum containing penicillin 15 mg/L. Respondents returned their laboratory results and a questionnaire on clinical interpretation and technical aspects. Most laboratories (194/199, 97.5%) recommend the use of the SBT in the management of infective endocarditis but only 48 (25.2%) often or always change therapy on the basis of the result. A wide range of interpretative criteria, definitions of bactericidal endpoints and methodologies are used. Performance in the first distribution was acceptable for 75% of laboratories but in the second only 34% could identify penicillin tolerance; 34 respondents reported an SBT result of < or = 2 for the tolerant strain, 81 laboratories reported one of > or = 16. Technical factors related to acceptable performance were: sonication of broth before counting the inoculum; knowing the inoculum size in cfu/mL; use of a 4-8 h broth culture to make the inoculum; incubation of recovery plates for > 36 h; use of a calibrated pipette to sample for surviving bacteria; use of measured volumes to add the inoculum. Use of uncalibrated pipettes or standard loops to recover survivors was related to poor performance. Microbiology departments in the UK should review the clinical need to perform the SBT in the light of their local circumstances and if they elect to continue to offer this test, revise their methodologies which could be producing misleading results when testing alpha-haemolytic streptococci.

Bacteriological Techniques↗
PubMed1992

Genetic basis of tetracycline resistance in clinical isolates of Listeria monocytogenes.

The genetic basis of tetracycline resistance was studied in 25 clinical isolates of Listeria monocytogenes. Resistance to tetracycline was associated with resistance to minocycline and due to the presence of the tet(M) gene in 24 strains. Association of tet(M) with int-Tn, the gene encoding the protein required for the movements of Tn1545-like conjugative transposons, was found in all strains. Cotransfer of tet(M) and int-Tn among L. monocytogenes cells and from L. monocytogenes to Enterococcus faecalis was detected in 7 of the 12 strains studied at frequencies similar to those obtained with the prototype element Tn1545. tet(L), the second most prevalent tetracycline resistance gene in enterococci and streptococci, was detected in the remaining strain, where it was borne by a 5-kb plasmid. These observations indicate that two types of movable genetic elements, transposons and plasmids, in enterococci and streptococci are responsible for emergence of drug resistance in L. monocytogenes.

Culture Media↗