The use of 3.15% chlorhexidine gluconate/70% alcohol hub disinfection to prevent central line-associated bloodstream infections in dialysis patients.

PURPOSE: Preventing CLABSI events in the dialysis inpatient population represents significant challenges. Bacteremia associated with lines or grafts are common health-associated infections that lead to adverse patient outcomes. Dialysis patients represent a much higher infection risk due to health frequency needs, more frequent hospitalizations, multiple comorbidity issues, fistula functionality, and multiple attempts for line access leading to additional complications, costs, morbidity, and mortality. METHODS: An observational study was conducted including central line device days, CLABSI events, and possible confounding variables in admitted dialysis patients. All CLABSI data were identified according to the Centers for Disease Control and Prevention's National Healthcare Safety Network's definitions for CLABSIs. The intervention involved the removal of 70% alcohol swabs and alcohol hub disinfecting caps, then replacing with swabs containing 3.15% chlorhexidine gluconate/70% alcohol for central line hub disinfection and vascular graft access skin disinfection. RESULTS: The 5-year preintervention period (2008-2012) involved 7568 central line days, 11 CLABSI events, and a 1.45 per 1000 device day rate. The 6-month trial period involved 1559 central line days and no CLABSI events. The 5-year postimplementation period (2013-2017) involved 9787 central line days, 5 CLABSI events, and a 0.51 per 1000 device day rate. The postimplementation period represented a statistically significant (P value=0.0493) reduction with 65% fewer CLABSI events compared with the preimplementation period. LIMITATIONS: A limitation was variations in scrub time and dry time during central venous catheter hub access. While we were comparing 2 products, behavioral practices using these 2 products were possible influencers and represent a possible confounding variable. CONCLUSIONS: This study found that using alcohol with chlorhexidine gluconate prior to accessing central line hubs and vascular grafts allows for reduction in CLABSI events and sustains statistically significant lower CLABSI rates in the inpatient dialysis population. HIGHLIGHTS Using alcohol with chlorhexidine gluconate (CHG) before accessing central line hubs helps reduce central line-associated bloodstream infection (CLABSI) events Using alcohol with CHG before accessing vascular grafts helps reduce CLABSI events A statistically significant reduction (65%) in CLABSI events occurred after use. Statistically significant lower CLABSI rates are sustainable with use of alcohol with CHG.

The impact of ileal pouch-anal anastomosis on graft survival following liver transplantation for primary sclerosing cholangitis.

BACKGROUND: Liver transplantation is the only life-extending intervention for primary sclerosing cholangitis (PSC). Given the co-existence with colitis, patients may also require colectomy; a factor potentially conferring improved post-transplant outcomes. AIM: To determine the impact of restorative surgery via ileal pouch-anal anastomosis (IPAA) vs retaining an end ileostomy on liver-related outcomes post-transplantation. METHODS: Graft survival was evaluated across a prospectively accrued transplant database, stratified according to colectomy status and type. RESULTS: Between 1990 and 2016, 240 individuals with PSC/colitis underwent transplantation (cumulative 1870 patient-years until first graft loss or last follow-up date), of whom 75 also required colectomy. A heightened incidence of graft loss was observed for the IPAA group vs those retaining an end ileostomy (2.8 vs 0.4 per 100 patient-years, log-rank P = 0.005), whereas rates between IPAA vs no colectomy groups were not significantly different (2.8 vs 1.7, P = 0.1). In addition, the ileostomy group experienced significantly lower graft loss rates vs. patients retaining an intact colon (P = 0.044). The risks conferred by IPAA persisted when taking into account timing of colectomy as related to liver transplantation via time-dependent Cox regression analysis. Hepatic artery thrombosis and biliary strictures were the principal aetiologies of graft loss overall. Incidence rates for both were not significantly different between IPAA and no colectomy groups (P = 0.092 and P = 0.358); however, end ileostomy appeared protective (P = 0.007 and 0.031, respectively). CONCLUSION: In PSC, liver transplantation, colectomy + IPAA is associated with similar incidence rates of hepatic artery thrombosis, recurrent biliary strictures and re-transplantation compared with no colectomy. Colectomy + end ileostomy confers more favourable graft outcomes.

Implementation Lessons Learned From the Benefits of Enhanced Terminal Room (BETR) Disinfection Study: Process and Perceptions of Enhanced Disinfection with Ultraviolet Disinfection Devices.

OBJECTIVE To summarize and discuss logistic and administrative challenges we encountered during the Benefits of Enhanced Terminal Room (BETR) Disinfection Study and lessons learned that are pertinent to future utilization of ultraviolet (UV) disinfection devices in other hospitals DESIGN Multicenter cluster randomized trial SETTING AND PARTICIPANTS Nine hospitals in the southeastern United States METHODS All participating hospitals developed systems to implement 4 different strategies for terminal room disinfection. We measured compliance with disinfection strategy, barriers to implementation, and perceptions from nurse managers and environmental services (EVS) supervisors throughout the 28-month trial. RESULTS Implementation of enhanced terminal disinfection with UV disinfection devices provides unique challenges, including time pressures from bed control personnel, efficient room identification, negative perceptions from nurse managers, and discharge volume. In the course of the BETR Disinfection Study, we utilized several strategies to overcome these barriers: (1) establishing safety as the priority; (2) improving communication between EVS, bed control, and hospital administration; (3) ensuring availability of necessary resources; and (4) tracking and providing feedback on compliance. Using these strategies, we deployed ultraviolet (UV) disinfection devices in 16,220 (88%) of 18,411 eligible rooms during our trial (median per hospital, 89%; IQR, 86%-92%). CONCLUSIONS Implementation of enhanced terminal room disinfection strategies using UV devices requires recognition and mitigation of 2 key barriers: (1) timely and accurate identification of rooms that would benefit from enhanced terminal disinfection and (2) overcoming time constraints to allow EVS cleaning staff sufficient time to properly employ enhanced terminal disinfection methods. TRIAL REGISTRATION Clinical trials identifier: NCT01579370 Infect Control Hosp Epidemiol 2018;39:157-163.

Endothelial nitric oxide synthase induces heat shock protein HSPA6 (HSP70B') in human arterial smooth muscle cells.

Endothelial nitric oxide synthase (eNOS) is the major source of nitric oxide (NO) production in blood vessels. One of the pleitropic functions of eNOS derived NO is to inhibit vascular smooth muscle cell proliferation in the blood vessel wall, and whose dysfunction is a primary cause of atherosclerosis and restenosis. In this study there was an interest in examining the gene profile of eNOS adenoviral (Ad-eNOS) transduced human coronary artery smooth muscle cells (HCASMC) to further understand the eNOS inhibitory effect on smooth muscle cell proliferation. To this aim a whole genome wide analysis of eNOS transduced HCASMCs was performed. A total of 19 genes were up regulated, and 31 genes down regulated in Ad-eNOS transduced HCASMCs compared to cells treated with an empty adenovirus. Noticeably, a cluster of HSP70 gene family members was amongst the genes up regulated. Quantitative PCR confirmed that transcripts for HSPA1A (HSP70A), HSPA1B (HSP70B) and HSPA6 (HSP70B') were elevated 2, 1.7 and 14-fold respectively in Ad-eNOS treated cells. The novel gene HSPA6 was further explored as a potential mediator of eNOS signaling in HCASMC. Immunoblotting showed that HSPA6 protein was induced by Ade-NOS. To functionally examine the effect of HSPA6 on SMCs, an adenovirus harboring the HSPA6 gene under the control of a constitutive promoter was generated. Transduction of HCASMCs with Ad-HSPA6 inhibited SMC proliferation at 3 and 6 days post serum growth stimulation, and paralleled the Ad-eNOS inhibition of SMC growth. The identification in this study that HSPA6 overexpression inhibits SMC proliferation coupled with the recent finding that inhibition of HSP90 has a similar effect, progresses the field of targeting HSPs for vascular repair.

Ethnic differences in serum adipokine and C-reactive protein levels: the multiethnic cohort.

BACKGROUND: Ethnic disparities in metabolic disease risk may be the result of differences in circulating adipokines and inflammatory markers related to ethnic variations in obesity and body fat distribution. SUBJECTS/METHODS: In a cross-sectional design, we compared serum levels of leptin, adiponectin, C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in control subjects (321 men and 930 women) from two nested case-control studies conducted within the Multiethnic Cohort Study consisting of whites, Japanese Americans (JA), Latinos, African Americans (AA) and Native Hawaiians (NH). General linear models were applied to evaluate ethnic differences in log-transformed serum biomarker levels before and after adjusting for body mass index (BMI) at cohort entry. RESULTS: In comparison to whites, significant ethnic differences were observed for all biomarkers except TNF-α. JA men and women had significantly lower leptin and CRP levels than whites, and JA women also had lower adiponectin levels. Leptin was significantly higher in AA women (P < 0.01), adiponectin was significantly lower in AA men and women (P = 0.02 and P < 0.001), and CRP and IL-6 were significantly higher in AA men and women. Lower adiponectin (P < 0.0001) and CRP (P = 0.03) levels were the only biomarkers in NH women that differed from whites; no statistically significant differences were seen for NH men and for Latino men and women. When adjusted for BMI at cohort entry, the differences between the lowest and the highest values across ethnic groups decreased for all biomarkers except adiponectin in men indicating that ethnic differences were partially due to weight status. CONCLUSIONS: These findings demonstrate the ethnic variations in circulating adipokine and CRP levels before and after adjustment for BMI. Given the limitation of BMI as a general measure of obesity, further investigation with visceral and subcutaneous adiposity measures are warranted to elucidate ethnicity-related differences in adiposity in relation to disparities in obesity-related disease risk.

Pubertal stage and brain anatomy in girls.

Studies of puberty have focused primarily on changes in hormones and on observable physical bodily characteristics. Little is known, however, about the nature of the relation between pubertal status and brain physiology. This is particularly important given findings that have linked the onset of puberty with both changes in cognitive functioning and increases in the incidence of depression and anxiety. The present study examined relations between pubertal stage, as assessed by Tanner staging, and brain anatomy in a sample of 54 girls aged 9-15 years. Brain morphometric analysis was conducted using high-resolution magnetic resonance imaging (MRI). The hippocampus and amygdala were manually traced on MRI scans in all participants. Stepwise regression analyses were conducted with total intracranial volume (ICV), age, and pubertal status as the predictor variables and hippocampus and amygdala volumes as outcome variables. Pubertal status was significantly associated with left amygdala volume, after controlling for both age and ICV. In addition, puberty was related to right hippocampus and amygdala volumes, after controlling for ICV. In contrast, no significant associations were found between age and hippocampal and amygdala volumes after controlling for pubertal status and ICV. These findings highlight the importance of the relation between pubertal status and morphometry of the hippocampus and amygdala, and of limbic and subcortical structures that have been implicated in emotional and social behaviors.

Association of caspase-9 and RUNX3 with inflammatory bowel disease.

Previous linkage studies have identified a region at 1p36 as the susceptibility locus (IBD7) of inflammatory bowel disease (IBD). The objective of this study was to investigate whether polymorphisms of caspase-9 (CASP9) gene and RUNX3 are associated with IBD susceptibility and clinical phenotypes. We studied 555 Crohn's disease (CD) and 651 ulcerative colitis (UC) patients recruited from a single UK center. A total of 964 healthy Caucasian subjects were recruited as controls from general practitioner well person clinics in Oxfordshire. Fourteen single nucleotide polymorphisms (SNPs) of CASP9 and 11 SNPs of RUNX3 were genotyped using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) (homogenous MassEXTEND, hME, Sequenom™, Sequenom Inc., San Diego, CA). Linkage disequilibrium (LD) and haplotype association analysis were performed using 2ld and phase v2.0 software. No association of individual SNPs of CASP9 or RUNX3 with UC or CD was identified. The rs1052571 of CASP9 was associated with severe UC [P = 0.0034, odds ratio (OR) = 1.957, 95% confidence interval (CI) = 1.240-3.088]. Significant haplotype associations between CASP9 and IBD were identified, while no association of RUNX3 haplotypes with either UC or CD was found. Our findings suggested that CASP9 gene might be another IBD susceptibility gene.

The genetics of NOD-like receptors in Crohn's disease.

The first Crohn's disease (CD) susceptibility gene identified was CARD15, which is a member of the emerging NOD-like receptor (NLR) family. These function as intracellular cystosolic pattern recognition receptors (PRRs) and play a central role in the innate immune response. We studied other members of the NLR family using a gene-wide haplotype tagging approach in a well-characterised collection of 547 CD patients and 465 controls. Four single nucleotide polymorphisms (SNPs) in NLRP3 had P values < 0.05 and are in high linkage disequilibrium (LD) with each other (r(2) > 0.90 for all four SNPs). rs4925648 and rs10925019 were the most strongly associated with CD susceptibility (P = 0.001, odds ratio (OR) 1.62, 95% CI 1.2-2.18; and P = 6.5 x 10(-4), OR 1.65, 95% CI 1.23-2.19, respectively). rs1363758 located in NLRP11 was associated with CD susceptibility [P = 0.002 (1.64, 1.19-2.25)], which was weakly confirmed in an independent case-cohort collection on joint analysis [P = 0.05, (1.28, 1-1.64)]. On sub-phenotype analysis, an interesting association between NLRP1 and skin extra-intestinal manifestations and colonic, inflammatory CD was identified. None of these results was replicated in the Wellcome Trust Case Control Consortium study and therefore need replication in a further large cohort.

Serum 25-hydroxyvitamin D levels and mammographic density among premenopausal women in a multiethnic population.

Although some evidence suggests a protective role of vitamin D against breast cancer, epidemiological findings are inconsistent. The current study investigated the relation of serum 25-hydroxyvitamin D (25(OH)D) levels with mammographic density. Baseline serum samples from 182 premenopausal women including 67 Caucasians and 74 Asians from a nutritional trial were analyzed for 25(OH)D. Mammographic density was assessed using a computer-assisted method. Serum 25(OH)D was not associated with mammographic density after adjustment for confounders (body mass index (BMI), age at mammogram, Asian ethnicity, age at first birth, parity and age at menarche). 25(OH)D levels were significantly lower in Asians than in Caucasians, but no significant ethnic differences in mammographic density were observed after adjusting for BMI. Although the current results indicate that serum 25(OH)D levels were not associated with mammographic density among premenopausal women, a possible protective effect of vitamin D against breast cancer may be mediated through other pathways.

Confirmation of the novel association at the BTNL2 locus with ulcerative colitis.

Linkage in families and association in population case-control investigations have clearly shown that genes within the major histocompatibility complex region on chromosome 6p are relevant to the susceptibility and pathogenesis of ulcerative colitis (UC) and Crohn's disease. However, identifying the causative variants by fine mapping has not been conclusive. In this study using 58 single nucleotide polymorphisms (SNPs) with 616 UC cases, there was significant association with SNP rs2294881 of the (butyrophilin-like 2) BTNL2 gene with odds ratio (OR) = 2.80, confidence interval (CI) = 1.62-4.84 and P = 5.69 x 10(-4) (P(Bonferroni) = 3.3 x 10(-2)) and replication of SNP rs9268480. The missense SNP rs2076523 (K196E) showed novel association with a subset of UC cases with colectomy (n = 126), OR = 0.25, CI = 0.11-0.58 and P = 4.42 x 10(-4) (P(Bonferroni) = 2.56 x 10(-2)). These three associated variants within the BTNL2 gene were neither in linkage disequilibrium with each other nor correlated with the SNPs tagging the human leukocyte antigen (HLA)-DRB1*1502 and HLA-DRB1*0301 alleles.

Effect of gene delivery of NOS isoforms on intimal hyperplasia and endothelial regeneration after balloon injury.

Endothelial cell loss is a critical event in the pathological repair of the injured blood vessel. Impaired endothelial function results in reduced production of key vascular mediators such as nitric oxide (NO) within the vessel wall leading to enhanced smooth muscle cell proliferation and migration and ultimately intimal hyperplasia. The aim of the present study was to directly compare the effects of adenoviral-mediated gene delivery of two nitric oxide synthase (NOS) isoforms, eNOS and iNOS on endothelial regeneration and intimal hyperplasia following endothelial injury in the rabbit carotid artery. The right carotid arteries of male New Zealand white rabbits were denuded by passing a 3French Fogarty balloon catheter along the artery three times. In all, 1 x 10(9) PFU of adenoviral(Ad)eNOS, AdiNOS or Adbeta-galactosidase (Adbeta-Gal) was then delivered intraluminally and allowed to dwell for 20 min. Transgene expression was sought after 3 days by immunohistochemistry and at 7 days by quantitative reverse transcriptase PCR. The effect on intimal hyperplasia was sought using histological staining after 14 days. Evans blue staining was used to determine the effect on endothelial regeneration. eNOS and iNOS expression was detected in transduced arteries. Neointima/media ratios were significantly reduced in eNOS (0.07+/-0.044) and iNOS (0.087+/-0.086) transduced arteries compared with Adbeta-Gal (0.332+/-0.14) transduced arteries (n=7). In addition, AdeNOS treatment (4.21+/-3.12% de-endothelialized area) enhanced endothelial regeneration compared to Adbeta-Gal treatment (10.05+/-4.98), while treatment with AdiNOS (25.17+/-11.92) inhibited endothelial regeneration in the injured rabbit carotid artery (n=7-8). These results highlight the potential of NOS gene therapy, in particular, eNOS gene therapy as a potential therapeutic strategy for the prevention of restenosis after vascular injury.

Estradiol and testosterone concentrations increase with fasting in weaned pups of the northern elephant seal (Mirounga angustirostris).

Although neonatal development is generally associated with increased levels of circulating testosterone (T) and estradiol (E2), food deprivation may inhibit steroidogenesis. Therefore, these potentially conflicting stimuli were examined in fasting weaned northern elephant seal (Mirounga angustirostris) pups by measuring serum concentrations of T, E2, progesterone (P4), and luteinizing hormone (LH) by either radioimmunoassay (P4, LH) or enzymeimmunoassay (T, E2). Blood samples were obtained from 20 male and 20 female pups at both early (<1 wk postweaning) and late (6-8 wk postweaning) periods during their natural postweaning fast. T in males (early: 2.9 +/- 0.4 ng/mL; late: 16 +/- 2 ng/mL; P < 0.0001) and E2 in females (early: 42 +/- 6 pg/mL; late: 67 +/- 5 pg/mL; P < 0.01) increased between the two measurement periods, while P4 (early: 2.5 +/- 0.3 ng/mL; late: 2.1 +/- 0.3 ng/mL; P > 0.05) did not. LH increased (early: 46 +/- 4 pg/mL; late: 65 +/- 6 pg/mL; P < 0.05) in males but not in females (early: 69 +/- 9 pg/mL; late: 65 +/- 6 pg/mL; P > 0.05). Increases in LH and T suggest that LH may stimulate T secretion. Alternatively, relatively low concentrations of LH in both males and females may reflect negative feedback inhibition imposed by elevated T and E2 concentrations. Despite the inherent postweaning fast, concentrations of T and E2 increased, suggesting that they may be critical for the continued development of pups. Therefore, compensatory mechanisms may exist that alleviate the fasting-induced inhibition of gonadal steroidogenesis during neonatal development in elephant seal pups.

Validation of several established equations for resting metabolic rate in obese and nonobese people.

OBJECTIVE: To evaluate several equations for predicting resting metabolic rate against measured values in obese and nonobese people. DESIGN: Resting metabolic rate was measured with indirect calorimetry. Four calculation standards using various combinations of weight, height, and age were used to predict resting metabolic rate: a) Harris-Benedict equation, b) Harris-Benedict equation using adjusted body weight in obese individuals, c) Owen, and d) Mifflin. Main outcome was percentage of subjects whose calculated metabolic rate was outside a +/-10% limit from measured values. Subjects/Setting 130 nonhospitalized adult volunteers grouped by degree of obesity (range of body mass index, 18.8 to 96.8). Statistical Analysis Performed Analysis of proportions was used to determine differences in the percentage of subjects estimated accurately by each equation; alpha was set at 0.05. RESULTS: Calculated resting metabolic rate was more than 10% different from measured in 22% of subjects using the Mifflin equation, 33% using the Harris-Benedict equation (P=.05 vs Mifflin), and 35% using the Owen equation (P<.05 vs Mifflin). The error rate using Harris-Benedict with adjusted weight in obesity was 74% (vs 36% in obese subjects using actual weight in the standard Harris-Benedict equation). APPLICATIONS/CONCLUSION: Of the calculation standards tested, the Mifflin standard provided an accurate estimate of actual resting metabolic rate in the largest percentage of nonobese and obese individuals and therefore deserves consideration as the standard for calculating resting metabolic rate in obese and nonobese adults. Use of adjusted body weight in the Harris-Benedict equation led to less overestimation by that equation in obese people at the expense of increased incidence of underestimation.

Prokinetic effect of indoramin, an alpha-adrenergic antagonist, on human gall-bladder.

BACKGROUND: The effects of alpha- and beta-adrenergic agents on gall-bladder motility remain undefined. AIM: To determine the effects of alpha- and beta-antagonists on gall-bladder motility in healthy humans. METHODS: In this single, blind, three-way crossover study, a slow-release formulation of propranolol 80 mg (beta-antagonist), indoramin 25 mg (post-synaptic alpha1-antagonist) and placebo were administered to 10 healthy volunteers on three separate days 8 h before the assessment of gall-bladder volumes by ultrasonography. Gall-bladder volumes were assessed in the fasting state and at 5-min intervals for 50 min after a standard proprietary enteral feed (Ensure 186 mL, Abbott). RESULTS: The fasting gall-bladder volumes of subjects who received placebo or indoramin were significantly different (mean +/- S.E.M.: 16.50 +/- 2.78 mL and 13.47 +/- 2.24 mL, respectively; P < 0.001, two-way analysis of variance). The fasting gall-bladder volume after the administration of propranolol was 17.49 +/- 2.37 mL and was not significantly different from placebo (16.50 +/- 2.78 mL). When the mean post-prandial gall-bladder volumes were compared, indoramin significantly enhanced post-prandial gall-bladder emptying compared to placebo (P < 0.001). There was no significant post-prandial volume difference between placebo and propranolol. CONCLUSIONS: Indoramin, an alpha-adrenergic antagonist, acts as a prokinetic agent, enhancing post-prandial gall-bladder emptying in healthy individuals.

Histopathological methods for the investigation of microbial communities associated with disease lesions in reef corals.

AIMS: To determine the spatial structure of microbial communities associated with disease lesions of reef corals (Scleractinia). METHODS AND RESULTS: Agarose pre-embedding preserved the structure of the disease lesion and surrounding tissues prior to demineralization of the carbonate exoskeleton and embedding in resin. Fluorescence in situ hybridization (FISH) was used to localize bacteria in the lesions of various diseases. CONCLUSIONS: The techniques successfully preserved the in situ spatial structure of degenerated coral tissues. In one case (white plague disease), significant bacterial populations were found only in fragmented remnants of degenerated coral tissues at the lesion boundary that would not have been detected using conventional histopathological techniques. SIGNIFICANCE AND IMPACT OF THE STUDY: Determining the composition, spatial structure and dynamics of microbial communities within the disease lesions is necessary to understand the process of disease progression. The methods described may be applicable to a wide range of diseases involving necrotic lesion formation and requiring extensive tissue processing, such as skeleton demineralization.

Effects of dietary sesame seeds on plasma tocopherol levels.

The tocopherols, the major vitamers of vitamin E, are believed to play a role in the prevention of human aging-related diseases such as cancer and heart disease, yet little is known concerning determinants of their plasma concentrations. Evidence from animal studies suggests that the dietary source of gamma-tocopherol can significantly affect plasma levels of this tocopherol as well as its functional vitamin E activity. To determine whether plasma levels of tocopherols in humans are similarly altered, a study was undertaken in which subjects (n = 9) were fed muffins containing equivalent amounts of gamma-tocopherol from sesame seeds, walnuts, or soy oil. We observed that consumption of as little as 5 mg of gamma-tocopherol per day over a three-day period from sesame seeds, but not from walnuts or soy oil, significantly elevated serum gamma-tocopherol levels (19.1% increase, p = 0.03) and depressed plasma beta-tocopherol (34% decrease, p = 0.01). No significant changes in baseline or postintervention plasma levels of cholesterol, triglycerides, or carotenoids were seen for any of the intervention groups. All subjects consuming sesame seed-containing muffins had detectable levels of the sesame lignan sesamolin in their plasma. Consumption of moderate amounts of sesame seeds appears to significantly increase plasma gamma-tocopherol and alter plasma tocopherol ratios in humans and is consistent with the effects of dietary sesame seeds observed in rats leading to elevated plasma gamma-tocopherol and enhanced vitamin E bioactivity.

Association of tocopherols with circulating autoantibody levels against an oxidized DNA nucleoside in humans.

Autoantibodies against oxidized DNA bases are found in vivo and have been used as an indicator of oxidative damage, yet little is known concerning their individual variation and relation to serum micronutrients. Human plasma anti-5-hydroxymethyl-2'-deoxyuridine (HMdU) autoantibody (aAb) levels were repeatedly determined in 41 women and 11 men, and found to have small within-individual variation over time, but large between-individual differences. A positive association in both women (r = .5762, p = .0001) and men (r = .415, p = .2) between plasma total tocopherols and antibody levels was observed. Autoantibody levels were lower in postmenopausal women (8.37 +/- 1.61 vs. 17.18 +/- 2.85 in premenopausal women, p < .01), independently of plasma tocopherol. However, aAb titers in postmenopausal women were still significantly associated with plasma tocopherol levels and adjustment for menopausal status in women yielded a highly significant correlation between HMdU aAb levels and total tocopherol (r = .7342, p = .0001). Plasma malondialdehyde equivalents (MDA), a measure of lipid peroxidation, were also higher in individuals with either high plasma alpha-tocopherol or high beta+gamma-tocopherol levels. The positive association of tocopherols with markers of oxidative damage may reflect a response to the generation of endogenous oxidants associated with enhanced immune function. The decrease in aAb level in postmenopausal women may similarly reflect decreased immune function associated with decreased estrogen levels.

Speciation and identification of organoselenium metabolites in human urine using inductively coupled plasma mass spectrometry and tandem mass spectrometry.

A method for speciation and identification of organoselenium metabolites found in human urine samples using high performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC/ICP-MS) and tandem mass spectrometry (MS/MS) is described. Reversed-phase chromatographic separation was used for sample fractionation with the ICP-MS functioning as an element-selective detector, and six distinct selenium-containing species were detected in a human urine sample. Fractions were then collected and analyzed using a triple quadrupole mass spectrometer with electrospray ionization and collision-induced dissociation to obtain structural information. The first two fractions were identified specifically as selenomethionine and selenocystamine, estimated to be present at approximately 11 and 40 ppb, respectively. To the best of our knowledge, this is the first time these two metabolites have been positively identified in human urine.

Use of a human patient simulator in the development of resident trauma management skills.

BACKGROUND: Computerized human patient simulators (HPSs) have been used to improve diagnostic and therapeutic decision making. The goal of this study was to investigate the impact of HPSs and Advanced Trauma Life Support (ATLS) on the development of trauma management skills and self-confidence in surgical interns. METHODS: Three teams of interns completed two ATLS-like trauma scenarios on the HPS (pre-ATLS). They then took the ATLS provider course. After ATLS, the interns were evaluated on two different HPS trauma scenarios (post-ATLS). Two teams of senior residents, experienced in trauma care, completed the same HPS scenarios and were used as controls. Trauma management skills were scored in three areas--critical treatment decisions, potential for adverse outcomes, and team behavior--by staff trauma surgeons. After participating in the HPS trauma scenarios, the interns completed self-confidence questionnaires and a course evaluation survey. RESULTS: Trauma management skill scores increased 23% in critical treatment decisions, 25% in potential for adverse outcomes, and 47% in team behavior after ATLS/HPS (p < 0.002). Senior residents' performance on HPS trauma scenarios was better than the interns (p < 0.05) in all three areas evaluated. The interns' self-confidence scores rose significantly after the course. (p < 0.01) The HPS course evaluation survey averaged 8.3 out of a maximum 10. CONCLUSION: Use of HPSs in conjunction with ATLS appears to enhance the development of trauma management skills. The surgical interns participating in the study deemed the HPS to be a worthwhile experience and a confidence-building tool. In particular, trauma team behavior improved significantly after ATLS/HPS.

The impact of a clinical pathway for gastric bypass surgery on resource utilization.

BACKGROUND: Clinical pathways are believed to improve patient care and reduce costs. Our hypothesis was that a gastric bypass pathway would decrease hospital resource utilization and cost of care without adversely affecting patient care. METHODS: The prepathway (Pre) group consisted of 16 gastric bypasses (6/98 to 3/99). The postpathway (Post) group includes 12 gastric bypass procedures performed after institution of the clinical pathway (4/99 to 12/99). The impact of the clinical pathway on hospital length of stay (LOS) and resource utilization was investigated. A comparison of costs was performed using cost/charge ratios. Hospital readmissions and postoperative complications were also examined. RESULTS: Despite increased obesity/medical acuity of the Post group, hospital LOS decreased by 3 days (P < 0.0001). Total hospital costs decreased by over $1600/case (>15%). Postpathway savings were greatest for room and board (34%), supplies (41%), and lab/radiology costs (50%). An increase in OR costs (22%) was observed in the Post group. This was due to an increase in anesthesia time (epidural catheter placement) and equipment costs (ultrasonic shears). Despite reductions in hospital LOS and resource utilization, the complication rate (Pre 12%, Post 16%) was similar and two patients in each group required brief readmission. CONCLUSIONS: A pathway for gastric bypass decreased hospital LOS and resource utilization. OR-related expenses account for 34-50% of total costs and must be monitored closely for surgical patients. The reduction in costs observed with this clinical pathway was not associated with an increase in postoperative complications or hospital readmission.