Surface soil and groundwater in Australia have been found to contain high concentrations of arsenic. The relative importance of long-term human exposure to these sources has not been established. Several studies have investigated long-term exposure to environmental arsenic concentrations using hair and toenails as the measure of exposure. Few have compared the difference in these measures of environmental sources of exposure. In this study we aimed to investigate risk factors for elevated hair and toenail arsenic concentrations in populations exposed to a range of environmental arsenic concentrations in both drinking water and soil as well as in a control population with low arsenic concentrations in both drinking water and soil. In this study, we recruited 153 participants from areas with elevated arsenic concentrations in drinking water and residential soil, as well as a control population with no anticipated arsenic exposures. The median drinking water arsenic concentrations in the exposed population were 43.8 micro g/L (range, 16.0-73 micro g/L) and median soil arsenic concentrations were 92.0 mg/kg (range, 9.1-9,900 mg/kg). In the control group, the median drinking water arsenic concentration was below the limit of detection, and the median soil arsenic concentration was 3.3 mg/kg. Participants were categorized based on household drinking water and residential soil arsenic concentrations. The geometric mean hair arsenic concentrations were 5.52 mg/kg for the drinking water exposure group and 3.31 mg/kg for the soil exposure group. The geometric mean toenail arsenic concentrations were 21.7 mg/kg for the drinking water exposure group and 32.1 mg/kg for the high-soil exposure group. Toenail arsenic concentrations were more strongly correlated with both drinking water and soil arsenic concentrations; however, there is a strong likelihood of significant external contamination. Measures of residential exposure were better predictors of hair and toenail arsenic concentrations than were local environmental concentrations.

The short term human exposure studies conducted on populations exposed to high concentrations of inorganic arsenic in soil have been inconsistent in demonstrating a relationship between environmental concentrations and exposure measures. In Australia there are many areas with very high arsenic concentrations in residential soil most typically associated with gold mining activities in rural areas. This study aimed to investigate the relationship between environmental arsenic and urinary inorganic arsenic concentrations in a population living in a gold mining area (soil arsenic concentrations between 9 and 9900 mg kg(-1)), and a control population with low arsenic levels in soil (between 1 and 80 mg kg(-1)). Risk factors for increased urinary arsenic concentrations were also explored. There was a weak but significant relationship between soil arsenic concentrations and inorganic urinary arsenic concentration with a Spearman correlation coefficient of 0.39. When participants with greater than 100 mg kg(-1) arsenic in residential soil were selected, the coefficient increased to 0.64. The geometric mean urinary inorganic arsenic concentration for the exposed group was 1.64 microg L(-1) (

The relative influence of peak concentration (Cmax) versus the area under the antibiotic concentration-time curve (AUC) on the bactericidal effect of gentamicin against Escherichia coil NCTC 10418 was studied. Bacteria in the lag phase were exposed to an in vitro gentamicin concentration series which mirrored the concentrations determined in patients after 80-mg intravenous bolus (1 min) and 80-mg intravenous infusion (30 min) doses. Bacterial viable cell counts and gentamicin concentrations were measured before and during antibiotic exposure. Both the Cmax and AUC were shown to be factors determining antibacterial activity; however, the Cmax was an independent determinant of effect. These findings indicate that bolus intravenous dosing with gentamicin could maximize bactericidal activity. Increased efficacy could result at any given daily antibiotic dose if delivered via bolus with long intervals (12 to 24 h) between doses if appropriate precautions to avoid toxicity are taken.Antibiotic therapeutic effect depends on administration schedules (6,7,20) and the time course of antibiotic concentration in serum, including the area under the antibiotic concentration in plasma-time curve (AUC), the magnitude of the AUC above the MIC (AUC > MIC), the total time that the antibiotic concentration exceeds the MIC, and the maximum antibiotic concentration attained during a dosing interval (Cm,[) (2, 7-10, 13, 14, 22).The issue of Cmax as opposed to AUC as a major determinant of antibiotic activity is of critical importance for dosage design; however, this issue has not yet been definitely resolved (16,22). We report the results of studies designed to test the independent effects of Cmn and AUC of gentamicin on bactericidal effect.Preliminary data were presented to the Australian Society of Clinical and Experimental Pharmacologists and Toxicologists, December 1991.Pharmacokinetic studies involved 20 patients on chronic 8-h dosing regimens with gentamicin at 80 mg; the regimen consisted of a standard 30-min infusion or a bolus over 1 min. Blood samples were drawn predose and at 1, 20, and 30 min postdose. A 10-min postdose in vivo datum point was estimated from a first-order fit of the 0-to 30-min in vivo data.Escherichia coli NCTC 10418 was used in in vitro bactericidal experiments. Both the MIC and the MBC of gentamicin for this organism are 0.5 mg/liter. This organism was cultured under standard conditions in the presence and absence of gentamicin (Delta West, Bentleigh, Australia) as detailed below. An overnight culture of E. coli in brain heart infusion broth (BHIB) (Oxoid, Basingstoke, England) was diluted to 107 CFU/ml in 0.1% peptone water (Difco Laboratories, Detroit, Mich.). A 1-ml sample of the 107-CFU/ml * Corresponding author. culture was added to the experimental culture broth, resulting in an initial density of 106 CFU/ml.In vitro concentration-time modelling of clinical concentrations of gentamicin assumed linear extrapolation of in vivo data (Fig. 1). Bolus and infusion profiles based on these findings at tw...

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A large number of drinking water supplies worldwide have greater than 50 microg l(- 1) inorganic arsenic in drinking water, and there is increasing pressure to reduce concentrations. Few studies have specifically considered low concentrations of arsenic in water supplies and the significance of other factors which may contribute to increased exposure. This study aimed to investigate risk factors for increased urinary inorganic arsenic concentrations, in a population exposed to 10 - 100 microg l(- 1) of arsenic in drinking water, as well as a control population with lower arsenic concentrations in their drinking water. Inorganic arsenic in urine was used as the measure of exposure. The median drinking water arsenic concentration in the exposed population was 43.8 microg l(- 1) (16.0 - 73 microg l(- 1)) and less than the analytical limit of detection of 1 microg l(- 1) (