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.     

Effects of sex and age on bone microstructure at the ultradistal radius: a population-based noninvasive in vivo assessment.

In a population-based cross-sectional study, we examined effects of sex and age on bone microstructure at the wrist using high-resolution 3-D pQCT. Compared with women, men had thicker trabeculae in young adulthood and had less microstructural damage with aging. These findings may contribute to the virtual immunity of men to age-related increases in wrist fractures. INTRODUCTION: Although changes in bone microstructure contribute to fracture risk independently of BMD, it has not heretofore been possible to assess this noninvasively in population-based studies. MATERIALS AND METHODS: We used high-resolution 3-D pQCT imaging (voxel size, 89 mum) to define, in a random sample of women (n = 324) and men (n = 278) 21-97 years of age, sex and age effects on bone microstructure at the wrist. RESULTS: Relative to young women (age, 20-29 years), young men had greater trabecular bone volume/tissue volume (BV/TV; by 26%, p = 0.001) and trabecular thickness (TbTh; by 28%, p < 0.001) but similar values for trabecular number (TbN) and trabecular separation (TbSp). Between ages 20 and 90 years, cross-sectional decreases in BV/TV were similar in women (-27%) and in men (-26%), but whereas women had significant decreases in TbN (-13%) and increases in TbSp (+24%), these parameters had little net change over life in men (+7% and -2% for TbN and TbSp, respectively; p < 0.001 versus women). However, TbTh decreased to a greater extent in men (-24%) than in women (-18%; p = 0.010 versus men). CONCLUSIONS: Whereas decreases with age in trabecular BV/TV are similar in men and women, the structural basis for the decrease in trabecular volume is quite different between the sexes. Thus, over life, women undergo loss of trabeculae with an increase in TbSp, whereas men begin young adult life with thicker trabeculae and primarily sustain trabecular thinning with no net change in TbN or TbSp. Because decreases in TbN have been shown to have a much greater impact on bone strength compared with decreases in TbTh, these findings may help explain the lower life-long risk of fractures in men, and specifically, their virtual immunity to age-related increases in distal forearm fractures.     

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.     

Survival rates for four forms of cancer in the United States and Ontario.

OBJECTIVES: In this study, cancer survival rates for patients diagnosed in Ontario and selected areas within the United States were compared. METHODS: Relative survival rates were computed for patients aged 15 through 84 years diagnosed with any of four forms of cancer (breast, colon, lung, and Hodgkin's disease). The cohorts represented those diagnosed over the years 1978 through 1986 in the Canadian province of Ontario and in nine regions covered by the US National Cancer Institute's Surveillance Epidemiology and End Results program. Patients were followed through the end of 1990. RESULTS: The cumulative relative survival rates were similar for American and Canadian patients. The largest difference was observed for breast cancer, where patients in the United States enjoyed a survival advantage throughout the follow-up period. CONCLUSIONS: Patients in the United States and Ontario with the diseases studied, except for breast cancer, experience very similar survival. The greater use of mammographic screening in the United States could account for that country's higher breast cancer survival rate by promoting earlier and therefore more efficacious treatment, by introducing bias, or by a combination of both treatment and bias factors.     

Preventive care: do we practice what we preach?

We used insurance claims from enrollees in the Rand Health Insurance Experiment to determine the amount of selected components of preventive care received by a representative sample of the non-aged population in the United States and to determine whether insurance coverage was an important determinant of that amount. Only 45 percent of infants received timely immunization for DPT and polio; 93 per cent received some well child care by 18 months of age. In the three-year experimental period, only 4 per cent of adults had a tetanus shot, 66 per cent of women aged 17-44 and 57 per cent aged 45-65 received a Pap smear, and 2 per cent of women aged 45-65 had a mammogram. Cost sharing was associated with even less preventive care: 60 per cent of children on the free plan and 49 per cent on cost sharing plans received preventive care of any type. For adults, women on the free plan received more preventive care of several kinds, and those aged 45-65 received more Pap smears than those on cost-sharing plans. Even with free care, most enrollees did not receive adequate preventive care. Thus, free care alone, while significant, is not a sufficient incentive to providing recommended levels of preventive care. The average per person insurance charge for increasing the amount of preventive care to a level consistent with that recommended would be $22 for a complete set of immunizations by age 18 months, $9 for a Pap smear every three years, and $97 for a Pap test and mammogram every three years.