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Biomedical subjects

R Wise

Publications and source records attributed to R Wise.

At least 19 recordsLinked to original sources
PubMed2006

Lower limb amputation with CPR in progress: recovery following prolonged cardiac arrest.

Intravenous drug users (IVDUs) often present to the emergency services with the medical complications of drug use. We report a case in which an acutely ischaemic lower limb of one such patient was thought to be the cause of cardiac arrest occurring during treatment in the emergency department (ED). Amputation of the limb was performed with cardiopulmonary resuscitation (CPR) in progress, spontaneous cardiac output was restored, and the patient made an excellent neurological recovery despite a total arrest time of 85 minutes. Possible causes of cardiac arrest, in relation to the release of potassium and metabolic toxins are discussed, as well as the decision making processes of the involved clinicians and other possible management strategies.

Adult↗
PubMed2005

A study of the prevalence of significant increases in serum creatinine following angiotension-converting enzyme inhibitor administration.

Angiontension-converting enzyme inhibitors (ACEIs) are beneficial in the treatment of diabetic and nondiabetic kidney disease, coronary artery disease and congestive heart failure. One adverse effect of ACEIs use is a rise in serum creatinine and potential renal failure. This paper attempts to quantify this risk and assess the need for pre- and post-ACEI serum creatinine measurements. A computerized search of Kaiser Permanente Northwest's electronic medical record was conducted to find patients over the age of 40 years taking lisinopril between July 1, 2000 and June 30, 2002. Patient demographic information and presence in diabetes and coronary artery disease registries was collected. A subsequent search for pre- and postlisinopril serum creatinine levels within 6 months of initial lisinopril prescription was conducted. Patients with prelisinopril creatinine < or = 1.2 mg/dl and postlisinopril creatinine > 2.5 mg/dl underwent chart review to discern adverse events associated with the rise in serum creatinine. A total of 18,977 patients were prescribed lisinopril between July 1, 2000 and June 30, 2002. In all 13 166 patients had a pre- and postlisinopril creatinine checked. In all, 31 patients had a rise in creatinine from < or = 1.2 mg/dl to > 2.5 mg/dl (0.2%). Possible contributors to rise in creatinine included congestive heart failure, dehydration and infection. No patients developed end-stage renal disease, although three died. In conclusion, end-stage renal disease is an unlikely outcome among patients prescribed lisinopril and is most likely associated with other events.

Adult↗
PubMed2004

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↗
PubMed2004

An assessment of the risks associated with the use of antibiotic resistance genes in genetically modified plants: report of the Working Party of the British Society for Antimicrobial Chemotherapy.

Development of genetically modified (GM) plants is contentious, in part because bacterial antibiotic resistance (AR) genes are used in their construction and often become part of the plant genome. This arouses concern that cultivation of GM plants might provide a reservoir of AR genes that could power the evolution of new drug-resistant bacteria. We have considered bacterial DNA transfer systems (conjugation, transduction and transformation) and mechanisms of recombination (homologous recombination, transposition, site-specific recombination and DNA repair) that together might productively transfer AR genes from GM plants to bacterial cells, but are unable to identify a credible scenario whereby new drug-resistant bacteria would be created. However, we cannot entirely rule out the possibility of rare transfer events that involve novel mechanisms. Hence, we also considered if occasional transfers of AR genes (bla(TEM), aph(3'), aadA) from GM plants into bacteria would pose a threat to public health. These AR genes are common in many bacteria and each is found on mobile genetic elements that have moved extensively between DNA molecules and bacterial cells. This gene mobility has already severely compromised clinical use of antibiotics to which resistance is conferred. Accordingly, the argument that occasional transfer of these particular resistance genes from GM plants to bacteria would pose an unacceptable risk to human or animal health has little substance. We conclude that the risk of transfer of AR genes from GM plants to bacteria is remote, and that the hazard arising from any such gene transfer is, at worst, slight.

Bacteria↗
PubMed2003

Nissen fundoplication has a vagolytic effect on the lower esophageal sphincter.

BACKGROUND: Laparoscopic Nissen fundoplication is an increasingly utilized option for the treatment of gastroesophageal reflux disease (GERD). However, many questions remain as to the mechanism by which this operation prevents GERD in those without hiatal hernias or incompetent lower esophageal sphincters (LES). It is known that these patients experience reflux due to excess transient lower esophageal sphincter relaxations (TLESR), inappropriate and short-lived relaxation of the LES and crural diaphragm. The purpose of this study was to determine if Nissen fundoplication affects the neural pathways involved in the TLESR reflex. METHODS: Five dogs were anesthetized and intubated. Both vagal nerves and the right phrenic nerve were isolated. A continuous water perfusion manometric catheter was situated at the LES. The nerves were then electrically stimulated and the resultant pressure at the LES measured at baseline, and during and after an open Nissen fundoplication. RESULTS: The mean LES pressures before dissection, after esophago-gastric mobilization, and after fundoplication were 47 +/- 13 mmHg, 21 +/- 9 mmHg, and 14 +/- 4 mmHg, respectively. All differences were significant. There was no change noted in LES pressure with stimulation of either or both of the phrenic nerves without concomitant vagal stimulation. CONCLUSION: Nissen fundoplication may prevent GERD in those without a hiatal hernia or incompetent LES by disrupting the efferent vagal fibers to the LES. Such fibers mediate TLESR which are responsible for GERD in these patients.

Animals↗
PubMed2003

Concentrations of garenoxacin in plasma, bronchial mucosa, alveolar macrophages and epithelial lining fluid following a single oral 600 mg dose in healthy adult subjects.

A microbiological assay was used to measure concentrations of garenoxacin (BMS-284756) in plasma, bronchial mucosa (BM), alveolar macrophages (AM) and epithelial lining fluid (ELF), following a single 600 mg oral dose. Twenty-four healthy subjects were allocated into four nominal time intervals after the dose, 2.5-3.5, 4.5-5.5, 10.5-11.5 and 23.5-24.5 h. Mean concentrations in plasma, BM, AM and ELF, respectively, for the four nominal time windows were for 2.5-3.5 h 10.0 mg/L (S.D. 2.8), 7.0 mg/kg (S.D. 1.3), 106.1 mg/L (S.D. 60.3) and 9.2 mg/L (S.D. 3.6); 4.5-5.5 h 8.7 mg/L (S.D. 2.2), 6.0 mg/kg (S.D. 1.9), 158.6 mg/L (S.D. 137.4) and 14.3 mg/L (S.D. 8.2); 10.5-11.5 h 6.1 mg/L (S.D. 1.9), 4.0 mg/kg (S.D. 1.4), 76.0 mg/L (S.D. 47.7) and 7.9 mg/L (S.D. 4.6); and 23.5-24.5 h 2.1 mg/L (S.D. 0.5), 1.7 mg/kg (S.D. 0.7), 30.7 mg/L (S.D. 12.9) and 3.3 mg/L (S.D. 2.3). Concentrations at all sites exceeded MIC(90)s for the common respiratory pathogens Haemophilus influenzae (0.03 mg/L), Moraxella catarrhalis (0.015 mg/L) and Streptococcus pneumoniae (0.06 mg/L). These data suggest that garenoxacin should be effective in the treatment of community-acquired pneumonia and chronic obstructive pulmonary disease.

Administration, Oral↗
PubMed2002

Antibiotic resistance--an evolving problem.

In 1998, an influential report on antimicrobial resistance from the House of Lords Select Committee on Science and Technology highlighted the threat posed to public health by resistance, and called for products to be used more prudently in both human and veterinary medicine. Here, Lord Soulsby, who chaired the Lords' committee on antimicrobials, and Richard Wise, who advised the committee and is now chairman of the Government's Specialist Advisory Committee on Antimicrobial Resistance, consider what has been achieved since then, along with the challenges that remain.

Animals↗
PubMed2002

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↗
PubMed2002

Antibiotic therapy of community respiratory tract infections: strategies for optimal outcomes and minimized resistance emergence.

Widespread, increasing antibiotic resistance amongst the major respiratory pathogens has compromised traditional therapy of the major infective respiratory syndromes, including bacterial pneumonia and acute exacerbations of chronic bronchitis. Guidelines for antibiotic prescribing dating from the 1980s to 1990s, which attempted to address such problems, were commonly too prescriptive and difficult to apply, and took little account of end-user practice or locally prevalent resistance levels. Further confusion was caused by conflicting recommendations emanating from differing specialty groups. The evidence that such guidelines benefited either clinical outcomes or treatment costs has been disputed. They have probably had little effect on resistance emergence. We report the recommendations of an independent, multi-national, inter-disciplinary group, which met to identify principles underlying prescribing and guideline formulation in an age of increasing bacterial resistance. Unnecessary prescribing was recognized as the major factor in influencing resistance and costs. Antibiotic therapy must be limited to syndromes in which bacterial infection is the predominant cause and should attempt maximal reduction in bacterial load, with the ultimate aim of bacterial eradication. It should be appropriate in type and context of local resistance prevalence, and optimal in dosage for the pathogen(s) involved. Prescribing should be based on pharmacodynamic principles that predict efficacy, bacterial eradication and prevention of resistance emergence. Pharmacoeconomic analyses confirm that bacteriologically more effective antibiotics can reduce overall management costs, particularly with respect to consequential morbidity and hospital admission. Application of these principles should positively benefit therapeutic outcomes, resistance avoidance and management costs and will more accurately guide antibiotic choices by both individuals and formulary/guideline committees.

Community-Acquired Infections↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

Nasopharyngeal carriage of Streptococcus pneumoniae: a review of the potential role of pharmacokinetics and pharmacodynamics.

Much antibiotic prescribing is based upon irrational practice rather than scientific principles. The advent and the better understanding of the pharmacokinetics and pharmacodynamics of antimicrobials are slowly leading to a change whereby antibiotics are prescribed with a better rationale. The fundamental understanding of the pharmacokinetics of the antimicrobial, for example how well it is absorbed, metabolized, distributed and eliminated from the body, should lead to an appreciation of the correct dosing interval. Pharmacodynamic factors, in particular, appreciation of the MIC of an antimicrobial for an infecting pathogen and whether time-independent or -dependent killing occurs, will also have a profound influence upon how an antimicrobial is used. This review attempts to consider these features as they apply to nasopharyngeal carriage of Streptococcus pneumoniae. The reason for the dosing and dosing frequency of a number of agents is discussed and an attempt is made to point the way to more judicious antibiotic prescribing so as to maximize clinical efficacy yet minimize the possibility of resistance emerging during therapy.

Animals↗