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Biomedical subjects

J M Andrews

Publications and source records attributed to J M Andrews.

At least 19 recordsLinked to original sources

Squamous cell carcinoma of the larynx in HIV-positive patients: difficulties in diagnosis and management.

Patients who are infected with human immunodeficiency virus (HIV) are at increased risk of developing laryngeal squamous cell carcinoma. This malignancy on average appears in a younger age group at a more advanced stage and has a more aggressive course in HIV patients. These patients have difficult management challenges, diagnostically, in staging, and particularly in determining the optimal treatment for each individual patient because their underlying HIV infection can markedly increase morbidity associated with active treatments. They frequently have problems associated with swallowing both before and after treatment. We present two cases that highlight difficulties in the diagnosis and management of these patients as well as post-treatment complications, with particular emphasis on swallowing problems.

Adult↗

Comparative study of the in vitro activity of a new fluoroquinolone, ABT-492.

OBJECTIVES: The in vitro activity of a new fluoroquinolone, ABT-492, was determined. METHODS: MICs were compared with those of two beta-lactams, telithromycin, ciprofloxacin and four later generation fluoroquinolones. The effects of human serum and of inoculum concentration were also investigated. RESULTS: MIC data indicate that ABT-492 has potent activity against Gram-positive organisms with enhanced anti-staphylococcal activity compared with earlier fluoroquinolones, in addition to activity against beta-haemolytic streptococci, pneumococci including penicillin- and fluoroquinolone-resistant strains and vancomycin-susceptible and -resistant Enterococcus faecalis but not Enterococcus faecium. ABT-492 was the most active agent tested against Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitidis, fluoroquinolone-susceptible Neisseria gonorrhoeae and anaerobes. Good activity was observed for ABT-492 amongst the Enterobacteriaceae and anaerobes tested, but ciprofloxacin showed superior activity for species of Proteus, Morganella and Providencia, as well as for Pseudomonas spp. In common with the other fluoroquinolones tested, organisms with reduced susceptibility to ciprofloxacin had raised MIC(90)s to ABT-492. The one isolate of H. influenzae tested with reduced fluoroquinolone susceptibility had an ABT-492 MIC close to that of the population lacking a mechanism of quinolone resistance. ABT-492 was more active than ciprofloxacin against Chlamydia spp. An inoculum effect was observed with a number of isolates of Staphylococcus aureus, Streptococcus pneumoniae, E. faecium, Klebsiella spp. and Escherichia coli, in addition to moderately raised MICs in the presence of 70% serum protein. The clinical significance of these findings is yet to be determined. CONCLUSIONS: ABT-492 is a new fluoroquinolone with excellent activity against both Gram-positive and Gram-negative organisms, with many potential clinical uses.

Anti-Bacterial Agents↗

Use of fluorescently labeled phage in the detection and identification of bacterial species.

Phages are viruses whose hosts are bacterial cells. They identify their hosts by specific receptor molecules on the outside of the host cell. Once the phages find their specific receptors, they bind to the bacterial cell and inject their nucleic acid inside the cell. The binding between phage and host can be so specific that only certain strains of a single species can be infected. In this communication, the specificity of phage P22 for Salmonella typhimurium LT2 is exploited to allow the detection of Salmonella in the presence of other bacterial species. In particular, the dsDNA of P22 is bound to SYBR gold, a highly sensitive, fluorescent nucleic acid stain. When multiple phages infect the same cell, the fluorescence emissions of the phage DNA inside the cell allow it to be imaged using an epifluorescence microscope. The advantages of using phages as the bacterial recognition element in a sensor over antibodies are discussed.

Bacteriophage P22↗

Human duodenal phase III migrating motor complex activity is predominantly antegrade, as revealed by high-resolution manometry and colour pressure plots.

Abstract Late phase III migrating motor complex activity has been said to be primarily retroperistaltic but has not been assessed with high resolution manometry or three-dimensional colour pressure plots (pressure/time/distance). Duodenal phase III was examined in healthy young volunteers (seven male, two female) with a 20-lumen assembly. With the most proximal sidehole in the distal antrum, after a 4.5-cm interval 18 sideholes at 1.5-cm intervals spanned the duodenum with a final sidehole 3 cm beyond. Fasting pressures were recorded until phase III occurred. Comparisons were made between proximal (P) and distal (D) duodenum during early (E) (first 0.5-1 min) and late (L) (last 0.5-1 min) phase III. With colour pressure analysis, 121 of 180 pressure wave (PW) sequences were purely antegrade, two purely retrograde and 57 bidirectional. Ten of fifty-seven bidirectional PW sequences were complex, branching to become two separate sequences. Bidirectional sequences occurred more frequently in late than early phase III (L 43 vs. E 14 of 57), but their occurrence did not differ between proximal and distal duodenum (P31 vs. D 24 of 57). Antegrade propagation velocity was faster in late compared with early phase III (L 28.50 vs. E 17.05 mm s(-1); P = 0.006), but did not differ between proximal and distal duodenum. Colour pressure analysis also indicated an intermittent segmental pattern to phase III, with each subject exhibiting a change in velocity or direction, or a relative failure of peristalsis somewhere along the duodenum during part of phase III. Duodenal phase III is not homogenous and, in contrast with previous studies, does not primarily constitute a retroperistaltic pump. Colour pressure analysis is useful in interpreting intraluminal pressure profiles and may improve the sensitivity and specificity of clinical studies.

Adult↗

The in vitro activity of BMS-284756, a new des-fluorinated quinolone.

The in vitro activity of BMS-284756 (previously T-3811ME), a des-fluoro(6) quinolone, was investigated and compared with those of six other antimicrobial agents. Susceptibility tests were performed on 919 Gram-positive, Gram-negative (including nine quinolone-resistant Escherichia coli) and anaerobic bacteria, three Chlamydia isolates and four Mycobacteria spp. BMS-284756 was marginally less active against the Enterobacteriaceae, but was the most active quinolone against staphylococci, enterococci and peptostreptococci. Against Streptococcus pneumoniae, BMS-284756 and gemifloxacin were more active than other quinolones. The MIC(90) of BMS-284756 was > or = 2 mg/L for the following bacteria: E. coli (MIC(90) 16 mg/L), Acinetobacter spp. (8 mg/L), Pseudomonas aeruginosa (64 mg/L) and Enterococcus faecium (4 mg/L). The MIC of BMS-284756 for Mycobacterium spp. was within one dilution of the MIC of ciprofloxacin. BMS-284756 was markedly more active than ciprofloxacin against the Chlamydia isolates tested.

Anti-Bacterial Agents↗

Comparison of the in vitro activities of several new fluoroquinolones against respiratory pathogens and their abilities to select fluoroquinolone resistance.

In this study the in vitro activities and pharmacodynamic properties of moxifloxacin, levofloxacin, gatifloxacin and gemifloxacin were compared on recently isolated respiratory pathogens and strains of Streptococcus pneumoniae with known mechanisms of fluoroquinolone resistance. In addition, the resistance selection frequencies of moxifloxacin and levofloxacin on three recently isolated respiratory pathogens and four strains of S. pneumoniae with known mechanisms of fluoroquinolone resistance were investigated. The four fluoroquinolones had similar activities against both Moraxella catarrhalis (MIC(90)s 0.015-0.06 mg/L) and Haemophilus influenzae (MIC(90)s 0.008-0.03 mg/L). More marked differences in activity were noted with S. pneumoniae, with MIC(90)s of 0.25, 1, 0.5 and 0.03 mg/L for moxifloxacin, levofloxacin, gatifloxacin and gemifloxacin, respectively. With the S. pneumoniae strains, the four fluoroquinolones exhibited similar concentration-dependent time-kill kinetics. The resistance selection frequencies of levofloxacin were higher than those of moxifloxacin at concentrations equivalent to those at the end of the dosing interval. Therefore moxifloxacin may have less of an impact on the development of resistance than levofloxacin.

Anti-Infective Agents↗

Effect of protein binding on the in vitro activity and pharmacodynamics of faropenem.

The influence of protein binding upon different aspects of the in vitro activity of faropenem on recently isolated Staphylococcus aureus and respiratory pathogens was determined. The protein binding of faropenem was investigated in inactivated human serum and albumin by ultrafiltration. The effect of the presence of inactivated human serum and albumin on the in vitro activity of faropenem and amoxicillin was established and the influence of protein binding on the pharmacodynamic properties of faropenem and amoxicillin was compared. The protein binding of faropenem was 96% and 95% in pooled inactivated human serum and 99% and 98% in 45 mg/L human albumin, at 8 and 25 mg/L, respectively. The presence of inactivated human serum (20% and 70%) increased the mean faropenem MICs by two dilution steps and albumin increased the mean faropenem MICs by three dilution steps. The mean amoxicillin MICs were less affected than faropenem by the presence of either inactivated human serum or albumin. Faropenem and amoxicillin exhibited similar time-dependent kinetics. Faropenem was bacteriostatic on Moraxella catarrhalis, Haemophilus influenzae and group A streptococci, and bactericidal for Streptococcus pneumoniae (after 4 h with concentrations equivalent to 5 x and 10 x MIC) in Iso-Sensitest broth. In 70% inactivated human serum faropenem was slowly bactericidal against M. catarrhalis, H. influenzae (one strain) and S. pneumoniae (one strain) but not group A streptococci and the other S. pneumoniae strain. A significant inoculum effect was observed with all strains except S. pneumoniae. Both faropenem and amoxicillin appeared more active in 70% inactivated human serum than in Iso-Sensitest broth.

Amoxicillin↗

Single-dose pharmacokinetics and penetration of BMS 284756 into an inflammatory exudate.

The pharmacokinetics of a single dose of BMS 284756 were determined following oral administration of a 600-mg dose to eight healthy male volunteers. Concentrations of the drug were measured in plasma and a cantharidine-induced inflammatory exudate by a microbiological assay. The mean peak concentration in plasma of 10.4 microg/ml (standard deviation [SD], 1.3 microg/ml) was attained at a mean time of 1.2 h (SD, 0.5 h) after the dose. The penetration into the inflammatory exudate was 82% (SD, 15.7%). A mean peak concentration of 7.2 microg/ml (SD, 2.4 microg/ml) was attained in the inflammatory exudate at 5.3 h (SD, 1.5 h). The elimination half-lives from plasma and inflammatory fluid were 9.8 h (SD, 1.1 h) and 8.5 h (SD, 1.9 h), respectively. The areas under the concentration-time curves for plasma and inflammatory fluid were 96.7 microg x h/ml (SD, 10.3 microg x h/ml) and 77.9 microg x h/ml (SD, 19.2 microg x h/ml), respectively.

Adult↗

Pharmacokinetics and inflammatory fluid penetration of intravenous daptomycin in volunteers.

The lipopeptide antimicrobial daptomycin was administered intravenously at a dose of 4 mg/kg of body weight to seven healthy male volunteers. The concentrations of daptomycin in plasma, cantharidin-induced inflammatory fluid, and urine were measured by a microbiological assay. The mean +/- standard deviation peak concentrations in plasma and inflammatory fluid were 77.5 +/- 8.3 and 27.6 +/- 9.5 microg/ml, respectively; the mean terminal elimination half-lives were 7.74 and 13.2 h, respectively. The overall penetration of total drug into the inflammatory fluid (measured by ratio of the area under the concentration-time curve from 0 to 24 h for inflammatory fluid compared with that for plasma) was 68.4%. The mean urinary recovery over 24 h was 59.7%.

Adult↗