Pharmacokinetics of sustained serum methotrexate concentrations secondary to gastrointestinal obstruction.

A physiological pharmacokinetic model for methotrexate was refined and used to simulate serum methotrexate concentrations after high dose (5000 mg/m2) intravenous infusions with fixed normal values for all model parameters except the GI transit rate. There was good agreement between simulated and measured values when model simulations with the normal GI transit rate were compared to values measured following 109 doses administered to 27 patients with normal GI function. When model simulations were performed using GI transit rates representing 75, 50 and 10% of normal, there was a marked prolongation of the terminal serum methotrexate half-life, which was directly related to the reduction in the transit rate. When simulations were performed with GI transit reduced by 50%, the maximum amount of methotrexate in the GI lumen was 25% higher and occurred 4 hr later. Model simulations of serum methotrexate concentrations, using a GI transit rate reduced by 50%, were also in good agreement with serum concentrations measured in two patients with partial GI obstruction. These data establish a pharmacokinetic basis for previous clinical observations indicating sustained serum methotrexate concentrations in patients with GI obstructions and exemplify the utility of physiological pharmacokinetic models in assessing the potential effects of clinical variables on drug disposition.

Statistical Analysis of On-Road Particulate Matter Emissions from Diesel Vehicles.

During 1996 and 1997, a number of light-and heavy-duty diesel vehicles were recruited in the Denver metropolitan area and subjected to emissions testing, principally for the purposes of assessing on-road particulate emissions. Little if any comparable data had been collected at altitude, particularly from heavy-duty vehicles. When these data were statistically examined using the technique of analysis of variance, they were shown both to exceed the federal standards, on average, and to be highly variable. These findings suggest that typically reported average values of vehicular PM emissions are not sufficient to be used, by themselves, to estimate contamination levels and associated public health risk. The situation is exacerbated in studies involving small numbers of vehicles, which is typical when diesel vehicles are involved, since not all sources of variation can be simultaneously controlled. Precise knowledge of the amount of particulates emitted by diesel vehicles in actual daily use is important because of present government strategies designed to promote the use of diesel as a transportation fuel.

Prevalence of gastrointestinal parasitism in Oklahoma swine.

The prevalence of swine gastrointestinal parasites was determined from all listed large swine operations (28) and a geographically representative sample (70) of the population of small hog farm operations in Oklahoma. Fecal samples (n = 975) were collected from 98 farms. From the 98 farms, parasites were recovered in pig feces as follows: Ascaris, 53.0%, strongyles, 53.1%, Trichuris, 35.7%, spirurids, 6.1%, Strongyloides, 19.4%, coccidia, 57.1%, and Balantidium, 55.1%. A higher percentage (16.5%) of hogs maintained on cement floors were positive for Ascaris than were those on either dirt lots (11.9%) or slatted floors (9.9%), but pigs on dirt lots were more often positive with a higher percentage of coccidia (21.0%) than those on either cement or slatted floors (8.5% and 6.0%, respectively). Prevalence of Trichuris was essentially the same (6.8% to 11.3%) in hogs from all 3 management practices.

Cost-effectiveness of cervical cytologic examination during pregnancy.

BACKGROUND: We undertook a study to determine the cost-effectiveness of performing routine cervical cytologic examination during pregnancy. METHODS: The costs generated by doing routine prenatal cervical cytologic examination were calculated based on chart review in a family practice setting. A consecutive sample of 523 patients giving birth during 1990 was used. Analysis was done on 423 of those patients with prenatal Papanicolaou smear results recorded. Cost savings from detection of curable disease and utility of the test in terms of well-years saved were calculated from published statistics using a single-step Markov process to model the population at risk. RESULTS: For patients of all ages using a discount rate of 5 percent, the cost generated by prenatal cervical cytologic examination was $146,400 per well-year of life saved. Age stratification showed cost per well-year to range from $321,600 for patients aged 15 to 19 years to $48,800 for those aged 35 to 39 years. CONCLUSIONS: Routine prenatal cervical cytologic examination is significantly less cost-effective than the most commonly done medical procedures. If medical funding is limited, elimination of this test should be considered for women with normal findings on cervical cytologic examinations within the previous 2 to 3 years.