Glutathione trapping to measure microsomal oxidation of furan to cis-2-butene-1,4-dial.

Furan is a liver carcinogen and toxicant. Furan is oxidized to the reactive dialdehyde, cis-2-butene-1,4-dial, by microsomal enzymes. This reactive metabolite readily reacts with glutathione nonenzymatically to form conjugates. A high-performance liquid chromatography-electrochemical method for the detection of cis-2-butene-1,4-dial-glutathione (GSH) conjugates in microsomal preparations was developed to measure the extent of furan metabolism to cis-2-butene-1,4-dial in vitro. Previously unobserved mono-GSH reaction products of cis-2-butene-1,4-dial were detected in addition to the already characterized bis-GSH conjugates. Chemical characterization of these compounds indicated that the alpha-amino group of glutathione had reacted with cis-2-butene-1,4-dial to form a thiol-substituted pyrrole adduct. The analytical method was used to estimate the extent of furan oxidation in rat liver microsomes from untreated or acetone-pretreated F344 rats as well as in human P450 2E1 Supersomes. Our results confirm that cytochrome P450 2E1 can catalyze the oxidation of furan to cis-2-butene-1,4-dial. However, the data are also consistent with the involvement of other P450 enzymes in the oxidation of furan in untreated animals. This assay will be a valuable tool to explore tissue and species differences in rates of furan oxidation.     

Effect of Managed Care Enrollment on Primary and Repeat Cesarean Rates Among U.S. Department of Defense Health Care Beneficiaries in Military and Civilian Hospitals Worldwide, 1999–2002

Abstract: Background : In response to rising cesarean rates, it is reasonable for health care organizations to look to a managed care model as a means of controlling further rate increases. However, little conclusive evidence exists to support this solution. We undertook a study of the Department of Defense health care beneficiary population to assess the impact of enrollment in TRICARE Prime, the Department's managed care health plan, on cesarean delivery rates. Methods : Pooled hospital discharge records from 1999–2002 for live, singleton births were analyzed to calculate primary and repeat cesarean rates for TRICARE Prime and non‐Prime beneficiaries in the military and civilian hospitals that comprise the Department of Defense health care network. Stepwise logistic regression was used to calculate adjusted odds ratios for clinical indicators for each combination of health plan and hospital setting using theχ²difference(p < 0.05)to eliminate nonsignificant variables from the model. Total primary and repeat cesarean rates were compared with primary and repeat cesarean rates for women with no reported clinical complications to account for differences in case mix across subgroups. Statistical significance of the differences calculated for subgroups was assessed usingχ². Results : Primary cesarean rates were significantly lower for TRICARE Prime enrollees relative to non‐Prime beneficiaries for all race subgroups and three of five age subgroups in military hospitals and four of five age subgroups in civilian hospitals. No significant differences in repeat cesarean rates were observed between Prime and non‐Prime beneficiaries within any race or age subgroup. Breech presentation followed by dystocia, fetal distress, and other complications were significant predictors for primary cesarean. Previous cesarean delivery was the leading predictor for repeat cesarean delivery. Primary and repeat cesarean rates observed for military hospitals were consistently lower than rates observed for civilian hospitals within each health plan type and age group. Conclusions : Enrollment in the managed care health plan was significantly associated with lower risk of primary cesarean delivery relative to membership in other health plans offered to Department of Defense health care beneficiaries. Repeat cesarean rates in this population varied independently of health plan type. Primary cesarean delivery was generally associated with clinical complications, whereas previous cesarean delivery was the strongest indictor for a repeat cesarean delivery. A clear explanation of reduced cesarean rates for Prime enrollees remains elusive, but it is likely that factors beyond individual practitioner decision‐making were at work.     

Measurement of upper extremity orientation by video stereometry system

In the attempt to gain a broader understanding of the causal relationships behind work-related symptoms of pain in the human shoulder, monitoring of arm position is crucial. Different methods have been used with varying accuracy. A video-based stereometry system, using infra-red light and reflecting markers for motion analysis, has been introduced for measurements in the fields of ergonomics, biomechanics and sports medicine. The purpose of this study is to investigate the sources of error in using this system for posture registration of the upper limb. Measurements are performed on a calibration fixture, on a mechanical model of the upper limb and on a subject with an exoskeleton. Particular, attention is given to inconsistencies and relative errors due to the finite geometrical precision with which the markers are positioned in the calibration fixture and on the studied objects, the limited capability to align the objects relative to the coordinate system of the calibration fixture and the errors connected to angular measurements using protractors etc. It is concluded that the system makes a valuable addition to existing instruments for non-contact posture measurement, and produces position data with an adequate accuracy in normal handling.     

Studies of Whole Blood Associated Acetaldehyde as a Marker for Alcohol Intake in Mice

Thirty C57BI mice were randomized into two groups. Group 1 served as controls while Group 2 was given 10% V/V ethanol with the drinking water. Whole blood- associated acetaldehyde (WBAA) was measured on capillary blood samples using a fluorigenic high performance chromatographic assay. WBAA peaked at Day 2. A stable mean plateau of 263 +/- 71 SD with a range of 160-400 nmoles/g hemoglobin WBAA was found in the group consuming ethanol compared with 122 +/- 17 SD and a range of 88-150 nmoles/g hemoglobin for controls (p less than 0.001). When ethanol was discontinued, levels of WBAA declined and became similar to those of controls by 9 days following cessation of ethanol. The quantitative difference between ethanol-consuming and control animals and also the rapid rise of whole blood-associated acetaldehyde and the relatively slow decline following cessation of ethanol intake indicate that such a test might be a useful monitor of drinking behavior.     

Network analytic methods for epidemiological risk assessment

The authors measure the efficacy of three methods for predicting the time to infection for susceptible individuals in a population undergoing an HIV epidemic. The methods differ in whether they require detailed information of the contact network and whether they require knowledge of the initial source of infection. Efficacy is evaluated using simulations for 20 different contact patterns. Only the risk score that uses both kinds of information accounts for more than 15 per cent of individual variability. The efficacy of this score ranges from 10 per cent in very unstructured populations to 60 per cent for spatially localized contact networks. This improved performance may be explained by the larger fraction of the total variability not due to the disease dynamics. When all variables are dichotomized, the two poorer methods produce odds ratios between 1.4 and 2.3. The odds ratio for the risk score with full information ranges from 2.5 to 17. Risk assessment protocols and intervention programmes are encouraged to assess contact patterns and detect sources of infection.