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With increasing clinical emergence of multidrug-resistant Gram-negative pathogens and the paucity of new agents to combat these infections, colistin (administered as its inactive prodrug colistin methanesulfonate [CMS]) has reemerged as a treatment option, especially for critically ill patients. There has been a dearth of pharmacokinetic (PK) data available(More)
Despite its recent evolutionary origin, the sex chromosome system of the plant Silene latifolia shows signs of progressive suppression of recombination having created evolutionary strata of different X-Y divergence on sex chromosomes. However, even after 8 years of effort, this result is based on analyses of five sex-linked gene sequences, and the maximum(More)
We attempted to find a relationship between the microbiological properties of bloodstream isolates of methicillin-resistant Staphylococcus aureus (MRSA) and the efficacy of vancomycin in the treatment of bacteremia. Vancomycin susceptibility testing was performed, and bactericidal activity was determined for 30 isolates from 30 different patients with MRSA(More)
BACKGROUND Vancomycin is commonly used to treat staphylococcal infections, but there has not been a definitive analysis of the pharmacokinetics of this antibacterial in relation to minimum inhibitory concentration (MIC) that could be used to determine a target pharmacodynamic index for treatment optimisation. OBJECTIVE To clarify relationships between(More)
Since the advent of the modern era of antimicrobial chemotherapy in the 1930s, animal infection models have allowed for the in vivo evaluation of antimicrobial agents for the treatment of experimentally induced infection. Today, animal pharmacokinetic-pharmacodynamic (PK-PD) infection models serve as a cornerstone of the preclinical assessment process for(More)
We studied methicillin-resistant Staphylococcus aureus (MRSA) isolates to determine if the group II polymorphism at the accessory gene regulator (agr) locus demonstrated any relationship with the clinical efficacy of vancomycin. One hundred twenty-two MRSA isolates from 87 patients treated with vancomycin were evaluated. Forty-five of 87 patients had no(More)
Seventy-four acutely ill patients were treated with intravenous ciprofloxacin at dosages ranging between 200 mg every 12 h and 400 mg every 8 h. A population pharmacokinetic-pharmacodynamic analysis relating drug exposure (and other factors) to infectious outcome was performed. Plasma samples were obtained and assayed for ciprofloxacin by high-performance(More)
OBJECTIVE To determine whether there are gender-specific differences in the pharmacokinetics and pharmacodynamics of metoprolol enantiomers. METHODS Twenty normal volunteers (10 men and 10 women) received 100 mg oral metoprolol tartrate twice daily for a total of nine doses. Pharmacokinetics and pharmacodynamics were studied after the last dose. Subjects(More)
OBJECTIVE To determine any cardiac or vascular morbidity associated with long term treatment with tamoxifen given after mastectomy for primary breast cancer. DESIGN Cohort study using linkage between database of a randomised trial and statistics of Scottish hospital inpatients to identify episodes of cardiac and vascular morbidity. SETTING NHS hospitals(More)
BACKGROUND To determine whether, when primary breast cancer is treated by local excision supported by systemic therapy appropriate to the oestrogen receptor status (ER) of the tumour, local radiotherapy can be avoided. METHODS We carried out a randomised controlled trial in 585 patients aged less than 70 years with primary breast cancers of 4 cm or less(More)