Sequence specificity of adriamycin-DNA adducts in human tumor cells

The anticancer anthracycline compound Adriamycin is a known topoisomerase II inhibitor but is also capable of exerting other cellular consequences. After intercalation, Adriamycin can form covalent adducts with DNA, and the magnitude of these adducts appears to be limited by the cellular availability of formaldehyde. Adducts produced by Adriamycin in the presence of formaldehyde have been well characterized in cell-free systems but not in cells. In this study, we show that when Adriamycin is used in conjunction with the formaldehyde-releasing prodrug AN-9 in IMR-32 tumor cells, this allows the formation of sufficiently high levels of adducts in genomic DNA to enable detection of their DNA sequence specificity for the first time. The 340-bp alpha-satellite EcoRI repeat sequence was isolated from drug-treated cells and digested with lambda-exonuclease to determine adduct sites at which exonuclease digestion was blocked. The Adriamycin adducts were formed predominantly at 5'-GC and GG sequences and unstable with respect to elevated temperatures and extended times at 37 degrees C. The use of three anthracycline derivatives lacking a 3'amino group demonstrated that this amino portion is critical for the formation of anthracycline adducts in cells. The structure of these drug-DNA adducts can therefore be considered to be identical to the Adriamycin adducts, which have been characterized rigorously in cell-free systems by X-ray crystallography, two-dimensional nuclear magnetic resonance, and mass spectrometry.     

The biopsychosocial aspects of unwanted teenage pregnancy

Unwanted teenage pregnancy is a major health problem in Wales and perioperative nurses are frequently involved in caring for teenagers undergoing surgical termination of pregnancy. By providing such adolescents with holistic care--by taking into account both biological and psychological aspects of health--nurses can help reduce an adolescent's anxiety and pain.     

Fortification of orange juice with vitamin D: a novel approach for enhancing vitamin D nutritional health

BACKGROUND: Fortification of milk with vitamin D may not be adequate for satisfying the vitamin D requirement because of variability in vitamin D content after fortification and because many persons have milk allergy or lactose intolerance. Additional foods need to be fortified with vitamin D. OBJECTIVE: We determined whether vitamin D, a fat-soluble vitamin, is bioavailable in orange juice and skim milk, 2 nonfat beverages. DESIGN: On 3 separate occasions, 18 adults ingested 25 000 IU vitamin D(2) in 240 mL whole milk or skim milk or in 0.1 mL corn oil applied to toast. A separate, double-blind, randomized, controlled trial investigated whether the consumption of orange juice fortified with vitamin D(3) would increase serum 25-hydroxyvitamin D [25(OH)D] concentrations: 14 subjects ingested 240 mL orange juice fortified with 1000 IU vitamin D, and 12 subjects ingested a control orange juice daily for 12 wk. RESULTS: Peak serum vitamin D(2) concentrations did not differ significantly after the ingestion of vitamin D(2) in whole milk, skim milk, or corn oil on toast. After subjects consumed orange juice fortified with 1000 IU vitamin D(3) daily for 12 wk, serum 25(OH)D(3) concentrations increased by 150%, and serum parathyroid hormone concentrations decreased by 25% compared with baseline; control subjects had a seasonal increase of 45% in 25(OH)D and no significant change in serum parathyroid hormone. CONCLUSIONS: The fat content of milk does not affect vitamin D bioavailability. Vitamin D fortification at 1000 IU/240 mL orange juice for 12 wk safely increased 25(OH)D(3) concentrations in adults.     

Risk factors for resistance to antimicrobial agents among nursing home residents

The authors prospectively collected data on exposure to antimicrobial agents and susceptibility patterns among all clinical isolates of bacteria taken from 9,156 residents of 50 nursing homes in Canada and the United States in 1998-1999. Exposure to antimicrobial agents was measured during the 10 weeks prior to detection of targeted resistant bacteria in residents and compared with antibiotic exposure during a 10-week interval in individuals with sensitive organisms. These main effects were adjusted for infection-control and staffing covariates using multiple logistic regression modeling. Increased staffing of nursing homes with registered nurses (adjusted odds ratio (OR) = 0.79 (95% confidence interval (CI): 0.72, 0.87) per registered nurse per 100 resident-days) and use of antibacterial soap (adjusted OR = 0.40, 95% CI: 0.18, 0.90) were associated with reduced risk of methicillin-resistant Staphylococcus aureus in nursing home residents. An increase in the number of hand-washing sinks per 100 residents was shown to reduce the risk of trimethoprim-sulfamethoxazole (TMP/SMX)-resistant Enterobacteriaceae (adjusted OR = 0.94, 95% CI: 0.90, 0.98). Exposure to TMP-SMX and exposure to fluoroquinolones were significant risk factors for isolation of TMP-SMX-resistant Enterobacteriaciae (adjusted OR = 1.14, 95% CI: 1.06, 1.22) and fluoroquinolone-resistant Enterobacteriaciae (adjusted OR = 1.08, 95% CI: 1.04, 1.11), respectively. These findings suggest that increased staffing, more hand-washing sinks, and use of antimicrobial soap may reduce resistance to antimicrobial agents in long-term care facilities.     

24-hour indirect calorimetry in mechanically ventilated critically ill patients.

BACKGROUND: Energy imbalance in critically ill, mechanically ventilated patients may lead to medical complications. The nutrition care team needs accurate, noninvasive, rapid methods to estimate energy requirements. We investigated whether brief measurements of indirect calorimetry at any time of the day would give valid estimates of 24-hour energy expenditure (EE). METHODS: EE of 12 mechanically ventilated critically ill patients (6 men, 6 women, mean +/- SD age 67 +/- 18 years, weight 70.2 +/- 8.8 kg) was recorded every minute during 24 hours by indirect calorimetry. All patients were continuously fed enteral nutrition. RESULTS: Mean +/- SD EE was 1658 +/- 279 kcal/d (6941 +/- 1167 kJ/d). Within patients, EE during the day fluctuated by 234 kcal in the most constant patient to 1190 kcal in the least constant patient, with a mean fluctuation of 521 kcal (12 patients). No statistically significant difference (p = .53) in mean EE between morning (6-12 hours, 1676 kcal), afternoon (12-18 hours, 1642 kcal), evening (18-24 hours, 1658 kcal), and night (0-6 hours, 1655 kcal) was found. A 2-hour instead of a 24-hour measurement resulted in a maximal error of 128 kcal (536 kJ), which was <10% of the average EE. The maximal error decreased with longer time intervals. CONCLUSIONS: In mechanically ventilated critically ill patients, 24-hour indirect calorimetry measurements can be replaced by shorter (>/=2 hours) measurements. Time of day did not affect EE.