Effect of 1-(1-naphthylmethyl)-piperazine, a novel putative efflux pump inhibitor, on antimicrobial drug susceptibility in clinical isolates of Escherichia coli

OBJECTIVES: 1-(1-Naphthylmethyl)-piperazine (NMP) has been shown to reverse multidrug resistance (MDR) in Escherichia coli overexpressing resistance-nodulation-cell division type efflux pumps, but there is no data on its activity in clinical isolates of E. coli. METHODS: The antimicrobial susceptibility of 60 clinical isolates of E. coli to a variety of antimicrobial agents was determined in the absence and presence of NMP and, for comparison, of Phe-Arg-beta-naphthylamide (PAbetaN), another putative efflux pump inhibitor (EPI). The intracellular accumulation of ethidium bromide was measured to confirm efflux pump inhibition as the likely mechanism of action of NMP. RESULTS: Based on a 4-fold or greater reduction of the MIC after the addition of NMP in >50% of the isolates, significant effects of NMP at a concentration of 100 mg/L were seen for levofloxacin, linezolid and ethidium bromide. The ethidium bromide MIC changes after NMP addition correlated with differences in the ethidium bromide intracellular accumulation as measured by fluorometry in whole cell accumulation experiments. The activity of PAbetaN was different from that of NMP, in particular regarding macrolide resistance reversal, suggesting different modes of action of the two putative EPIs. CONCLUSIONS: NMP is moderately active in reversing MDR in clinical isolates of E. coli and can partially restore fluoroquinolone susceptibility through inhibition of efflux pumps.     

The epidemiology of liver disease in Tayside database: a population-based record-linkage study

BACKGROUND: The true incidence and prevalence of liver disease is difficult to ascertain because there are few, if any, population-based registers of liver disease available to ensure proper case and comparator selection. The epidemiology of liver disease in Tayside (ELDIT) is a specially built register of liver disease for a well-defined geographical area of Scotland. AIMS: This paper describes the electronic linkage of multiple data sources to form ELDIT and provides initial results from the database. PATIENTS: All subjects resident in Tayside and registered with a general practitioner in the study period 1980-1999, approximately 400,000 people. METHODS: Electronic record-linkage techniques were employed to include anonymised data from primary and secondary sources. Hospital admissions, dispensed medication, and laboratory results from immunology, virology, and biochemistry were used to identify cases of liver disease. Diagnostic algorithms were used to verify and classify subjects with liver disease. A validation of the algorithms against the clinical diagnosis was used to determine the measure of agreement (true positive rate) of ELDIT. RESULTS: At present approximately 10,000 subjects have been identified with liver disease or abnormal liver function. The data set is nearing completion with cases of rarer liver disease being identified last. Incidence densities for the population were calculated. From the validation study, agreement between electronic and clinical diagnosis was 0.98 and positive predictive value was 0.83 showing electronic diagnostic algorithms are sensitive enough to identify liver disease using para-clinical data. CONCLUSIONS: ELDIT demonstrates how clinical information can be harnessed electronically to provide a better understanding of liver disease in a population.     

Relationship of physical performance to maturation in perimenarchal girls

The relationship of physical performance to maturation, characterized by the onset of menarche, was examined annually from 1989 to 1992 among 61 healthy, active perimenarchal girls from 10 to 14 years. Within each age group, differences in selected physical performance variables between and among three maturity groups, early, average, and late, were compared. Subjects categorized as having early or late maturation were those whose age at menarche was minus or plus, respectively, one standard deviation from the mean age at menarche 12.70 + 0.99 yr (range 10.29–14.65). Subjects demonstrated steady progression with age in breast and pubic hair development. Weight, estimated lean body weight and fat weights, and stature increased significantly with age and maturation. With the exceptions of flexibility, bent arm hang, standing vertical jump, and relative maximum oxygen uptake, the performance measures of running speed, functional strength, explosive strength, static strength, upper body power, and aerobic power improved significantly with age and maturation. Generally more mature subjects tended to perform significantly better than the less mature, but there are fewer significant performance differences between and among maturation groups within specific age groups. Therefore, whereas more mature 10- and 14-year-old females may, within the same age group, have only a very slight advantage in some physical performance abilities over their less mature age mates, more mature females aged 11, 12, and 13 years have a greater physical performance advantage. Am. J. Hum. Biol. 9:163–171, 1997. © 1997 Wiley-Liss, Inc.