bluuebunny/crossref_metadata_2025 huggingface dataset:
Prophylactic Administration of Surfactant in Extremely Premature Infants
Authors: Koch Lutz , Frommhold David , Beedgen Bernd , Ruef Peter , Poeschl Johannes
Published: June 2010

Objective. To investigate whether prophylactic surfactant administration is superior over selective treatment in preterm infants with respiratory distress syndrome (RDS).Methods. In our retrospective analysis, we compared premature infants (23 + 0 to 26 + 6 weeks) receiving 200 mg/kg surfactant (curosurf) within five minutes after birth (prophylactic group, ) with those infants who received surfactant therapy for established RDS (selective group, ).Results. Prophylactic therapy significantly decreased the need for mechanical ventilation (74 hours per patient versus 171 hours per patient, resp.). We observed a reduced incidence of interstitial emphysema (0% versus 9%, resp.), pneumothoraces (3% versus 9%, resp.), chronic lung disease (26% versus 38%, resp.), and surfactant doses per patient (1.3 versus 1.8, resp.), although those variables did not reach significance.Conclusion. We conclude that infants under 27 weeks' gestation profit from prophylactic surfactant administration by reducing the time of mechanical ventilation. This in turn could contribute to reduce the risk for mechanical ventilation associated complications, without any detrimental short-term side effects.
Comparison Study of Three Common Technologies for Freezing-Thawing Measurement
Authors: Yu Xinbao , Zhang Bin , Liu Nina , Yu Xiong (Bill)
Published: June 2010

This paper describes a comparison study on three different technologies (i.e., thermocouple, electrical resistivity probe and Time Domain Reflectometry (TDR)) that are commonly used for frost measurement. Specially, the paper developed an analyses procedure to estimate the freezing-thawing status based on the dielectric properties of freezing soil. Experiments were conducted where the data of temperature, electrical resistivity, and dielectric constant were simultaneously monitored during the freezing/thawing process. The comparison uncovered the advantages and limitations of these technologies for frost measurement. The experimental results indicated that TDR measured soil dielectric constant clearly indicates the different stages of the freezing/thawing process. Analyses method was developed to determine not only the onset of freezing or thawing, but also the extent of their development. This is a major advantage of TDR over other technologies.
On Potentials and Limitations of a Hybrid WLAN-RFID Indoor Positioning Technique
Authors: Spinella Silverio C. , Iera Antonio , Molinaro Antonella
Published: June 2010

This paper addresses the important issue of position estimation in indoor environments. Starting point of the research is positioning techniques that exploit the knowledge of power levels of RF signals from multiple 802.11 WLAN APs (Access Points). In particular, the key idea in this paper is to enhance the performance of a WLAN fingerprinting approach by coupling it to a RFID-based procedure. WLAN and RFID technologies are synergistically used to provide a platform for a more performing positioning process, in which the very strong identification capabilities of the RFID technology allow to increase the accuracy of positioning systems via WLAN fingerprinting. The algorithm performance is assessed through general and repeatable experimental campaigns, during which the main algorithm parameters are dimensioned. The results testify both to the feasibility of the solution and to its higher accuracy (attainable at very reduced costs) compared to traditional positioning techniques.
Interactions among Ecological Factors That Explain the Psychosocial Quality of Life of Children with Complex Needs
Authors: Thurston Sandy , Paul Louise , Ye Chenglin , Loney Patricia , Browne Gina , Thabane Lehana , Rosenbaum Peter
Published: June 2010

Purpose. To explore the associations and interactions among ecological factors and explain the psychosocial quality of life of children with complex needs.Methods. In this cross-sectional survey consenting parents were identified by the Children's Treatment Network. Families were eligible if the child from 0 to 19 years, resided in Simcoe/York, and there were multiple family needs. Regression analysis was used to explore associations and interactions.n=429.Results. Younger children, without conduct disorder, without hostile and punitive parenting and with low adverse family impact demonstrated the highest levels of psychosocial quality of life. Statistically significant interactions between processes of care and parent variables highlight the complexity of real life situations.Conclusions. It is not possible to fully understand the child's psychosocial quality of life in complex needs families by considering only simple associations between ecological factors. A multitude of factors and interactions between these factors are simultaneously present and the care of these families requires a holistic approach.
A New Method Solving Contact/Detach Problem in Fluid and Structure Interaction Simulation with Application in Modeling of a Safety Valve
Authors: Guo Zheng
Published: June 2010

A new virtual baffle methodology is implemented to solve contact/detach problem which is often encountered in fluid and structure interaction simulations while using dynamic grids technique. The algorithm is based on tetrahedral unstructured grid, and a zero thickness baffle face is generated between actually contacted two objects. In computation process, this baffle face is divided into two parts representing convective and blocked area, respectively; the area of each part is calculated according to the actual displacement between the two objects. Convective part in a baffle face is treated as inner interface between cells, and on blocked part wall boundary condition is applied; so convective and blocking effect can be achieved on a single baffle face. This methodology can simulate real detaching process starting from contact, that is, zero displacement, while it has no restriction to minimum grid cell size. The methodology is then applied in modeling of a complicated safety valve opening process, involving multidisciplinary fluid and structure interaction and dynamic grids. The results agree well with experimental data, which proves that the virtual baffle method is successful.
Development of Th1 Imprints to rBCG Expressing a Foreign Protein: Implications for Vaccination against HIV-1 and Diverse Influenza Strains
Authors: Power Carl , Marfleet Travis W. , Qualtiere Louis , Xiao Wei , Bretscher Peter
Published: June 2010

We demonstrate here that immunizing naïve mice with low numbers of recombinant Bacille Calmette-Guérin (rBCG) expressingβ-galactosidase (β-gal) generates predominant Th1 responses to both BCG andβ-gal whereas infection with high numbers generates a mixed Th1/Th2 response to both BCG andβ-gal. Furthermore, the Th1 response to both BCG andβ-gal is stable when mice, pre-exposed to low numbers of rBCG, are challenged four months later with high numbers of rBCG. Thus the Th1/Th2 phenotypes of the immune responses toβ-gal and to BCG are “coherently” regulated. Such rBCG vectors, encoding antigens of pathogens preferentially susceptible to cell-mediated attack, may be useful in vaccinating against such pathogens. We discuss vaccination strategies employing rBCG vectors that are designed to provide protection against diverse influenza strains or numerous variants of HIV-1 and consider what further experiments are essential to explore the possibility of realizing such strategies.
Novel Insights for Systemic Inflammation in Sepsis and Hemorrhage
Authors: Cai Bolin , Deitch Edwin A. , Ulloa Luis
Published: June 2010

The inflammatory responses in sepsis and hemorrhage remain a major cause of death. Clinically, it is generally accepted that shock in sepsis or hemorrhage differs in its mechanisms. However, the recognition of inflammatory cytokines as a common lethal pathway has become consent. Proinflammatory cytokines such as tumor necrosis factor (TNF) or high-mobility group box1 (HMGB1) are fanatically released and cause lethal multiorgan dysfunction. Inhibition of these cytokines can prevent the inflammatory responses and organ damage. In seeking potential anti-inflammatory strategies, we reported that ethyl pyruvate and alpha7 nicotinic acetylcholine receptor (alpha7nAChR) agonists effectively restrained cytokine production to provide therapeutic benefits in both experimental sepsis and hemorrhage. Here, we review the inflammatory responses and the anti-inflammatory strategies in experimental models of sepsis and hemorrhage, as they may have a consistent inflammatory pathway in spite of their different pathophysiological processes.
Kung Fu Training Improves Physical Fitness Measures in Overweight/Obese Adolescents: The “Martial Fitness” Study
Authors: Tsang Tracey W. , Kohn Michael R. , Chow Chin Moi , Fiatarone Singh Maria Antoinette
Published: June 2010

Aim. To examine the efficacy of a six-month Kung Fu (KF) program on physical fitness in overweight/obese adolescents.Methods. Subjects were randomly assigned to the KF or sham exercise (Tai Chi, TC) control group. Physical measurements in cardiovascular fitness and muscle fitness occurred at baseline and after 6 months of training thrice weekly.Results. Twenty subjects were recruited. One subject was lost to follow-up, although overall compliance to the training sessions was46.7±27.8%. At follow-up, the cohort improved in absolute upper (P=.002) and lower (P=.04) body strength, and upper body muscle endurance (P=.02), without group differences. KF training resulted in significantly greater improvements in submaximal cardiovascular fitness (P=.03), lower body muscle endurance (P=.28; significant 95% CI: 0.37–2.49), and upper body muscle velocity (P=.03) relative to TC training.Conclusions. This short-term KF program improved submaximal cardiovascular fitness, lower body muscle endurance, and muscle velocity, in overweight/obese adolescents with very low baseline fitness.
Synthesis and Characterization of LiNiO2 Nanopowder with Various Chelating Agents
Authors: Balandeh Mehrdad , Asgari Sirous
Published: June 2010

LiNiO2 powders were synthesized with acrylic acid, citric acid, oxalic acid, and triethanolamine (TEA) as a chelating agent. Crystallized LiNiO2 was synthesized in air at a calcinations temperature of 500 ∘C for 12 hours, when the molar ratio of chelating agents to total metal ion (RPM) was 1.0. The TEA‐assisted method had the highest intensity ratio of (003)/(104) peaks of X‐ray diffraction (XRD) spectrum. The transmission electron microscopy (TEM) analysis indicates that the sample prepared with triethanolamine obtained the smallest particle size with average particle size of only 12 nm. The results indicate that chelating agents have an important role in the intensity ratio of (003)/(104) peaks of XRD spectrum, size and shape of powders.
Large Mesenteric Cyst Mimicking Tuberculous Ascites
Authors: Dulger Cumhur , Adali Ertan , Avcu Serhat , Kurdoglu Zehra
Published: June 2010

Background. Intraabdominal lesions such as mesenteric cysts are uncommon disorders. Most are discovered incidentally during routine abdominal examinations.Methods. We report a patient with a mesenteric cyst masquerading as tuberculous peritonitis and ascites.Conclusion. Mesenteric cysts generally do not show typical clinical findings. They may also present with peritoneal tuberculosis findings such as low albumin gradient ascites with high ascitic adenosine deaminase levels. Surgery is used to remove a wide variety of mesenteric cysts. A correct diagnosis can be made by the combined use of radiographic and sonographic examinations in conjunction with the clinical signs.
Comparative Evaluation of Whole Body and Hepatic Insulin Resistance Using Indices from Oral Glucose Tolerance Test in Morbidly Obese Subjects with Nonalcoholic Fatty Liver Disease
Authors: Qureshi Kamran , Clements Ronald H. , Saeed Fahad , Abrams Gary A.
Published: June 2010

Nonalcoholic Fatty Liver Disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is a marker of Insulin Resistance (IR). Euglycemic-hyperinsulinemic clamp is the gold standard for measuring whole body IR (hepatic + peripheral IR). However, it is an invasive and expensive procedure. Homeostasis Model Assessment Index for Insulin Sensitivity (HOMA-IS), Quantitative Insulin Sensitivity Check Index (QUICKI) for hepatic IR and Insulin Sensitivity Index (), and Whole Body Insulin Sensitivity Index (WBISI) for whole body IR are the indices calculated after Oral Glucose Tolerance Test (OGTT). We used these indices as noninvasive methods of IR (inverse of insulin sensitivity) estimation and compared hepatic/peripheral components of whole body IR in NAFLD.Methods. 113 morbidly obese, nondiabetic subjects who underwent gastric bypass surgery and intraoperative liver biopsy were included in the study. OGTT was performed preoperatively and the indices were calculated. Subjects were divided into closely matched groups as normal, fatty liver (FL) and Non-Alcoholic Steatohepatitis (NASH) based on histology.Results. Whole body IR was significantly higher in both FL and NASH groups (NAFLD) as compared to Normal, while hepatic IR was higher only in NASH from Normal.Conclusions. FL is a manifestation of peripheral IR but not hepatic IR.
Effects of Sizes and Conformations of Fish-Scale Collagen Peptides on Facial Skin Qualities and Transdermal Penetration Efficiency
Authors: Chai Huey-Jine , Li Jing-Hua , Huang Han-Ning , Li Tsung-Lin , Chan Yi-Lin , Shiau Chyuan-Yuan , Wu Chang-Jer
Published: June 2010

Fish-scale collagen peptides (FSCPs) were prepared using a given combination of proteases to hydrolyze tilapia (Oreochromissp.) scales. FSCPs were determined to stimulate fibroblast cells proliferation and procollagen synthesis in a time- and dose-dependent manner. The transdermal penetration capabilities of the fractionationed FSCPs were evaluated using the Franz-type diffusion cell model. The heavier FSCPs, 3500 and 4500 Da, showed higher cumulative penetration capability as opposed to the lighter FSCPs, 2000 and 1300 Da. In addition, the heavier seemed to preserve favorable coiled structures comparing to the lighter that presents mainly as linear under confocal scanning laser microscopy. FSCPs, particularly the heavier, were concluded to efficiently penetrate stratum corneum to epidermis and dermis, activate fibroblasts, and accelerate collagen synthesis. The heavier outweighs the lighter in transdermal penetration likely as a result of preserving the given desired structure feature.
Nasopharyngeal Chondrolipoma
Authors: Kinshuck A. J. , Agrawal S. , Patel V. M. , Bishop P. W. , Jones P. H.
Published: June 2010

In this case report, we describe the presentation and treatment of a patient with nasopharyngeal chondrolipoma. Lipomas are common soft tissue tumours, although their incidence in the nasopharynx is very low. A rarer variant of lipoma, chondrolipomas are benign mesenchymal tumours. They are formed by the proliferation of mature adipocytes and contain different amounts of mature cartilaginous tissue; Weiss “Enzinger and Weiss's soft tissue tumours”, 4th ed: Mosby, St Louis; 2001 This represents the second reported case of a nasopharyngeal chondrolipoma. An endonasal approach to excision has not been previously described.
UGT2B10 Genotype Influences Nicotine Glucuronidation, Oxidation, and Consumption
Authors: Berg Jeannette Zinggeler , von Weymarn Linda B. , Thompson Elizabeth A. , Wickham Katherine M. , Weisensel Natalie A. , Hatsukami Dorothy K. , Murphy Sharon E.
Published: June 2010

Background: Tobacco exposure is routinely assessed by quantifying nicotine metabolites in plasma or urine. On average, 80% of nicotine undergoes C-oxidation to cotinine. However, interindividual variation in nicotine glucuronidation is substantial, and glucuronidation accounts for from 0% to 40% of total nicotine metabolism. We report here the effect of a polymorphism in a UDP-glucuronsyltransferase, UGT2B10, on nicotine metabolism and consumption.

Methods: Nicotine, cotinine, their N-glucuronide conjugates, and total trans-3′-hydroxycotinine were quantified in the urine (n = 327) and plasma (n = 115) of smokers. Urinary nicotine N-oxide was quantified in 105 smokers. Nicotine equivalents, the sum of nicotine and all major metabolites, were calculated for each smoker. The relationship of the UGT2B10 Asp67Tyr allele to nicotine equivalents, N-glucuronidation, and C-oxidation was determined.

Results: Individuals heterozygous for the Asp67Tyr allele excreted less nicotine or cotinine as their glucuronide conjugates than did wild-type, resulting in a 60% lower ratio of cotinine glucuronide to cotinine, a 50% lower ratio of nicotine glucuronide to nicotine, and increased cotinine and trans-3′-hydroxycotinine. Nicotine equivalents, a robust biomarker of nicotine intake, were lower among Asp67Tyr heterozygotes compared with individuals without this allele: 58.2 (95% confidence interval, 48.9-68.2) versus 69.2 nmol/mL (95% confidence interval, 64.3-74.5).

Conclusions: Individuals heterozygous for UGT2B10 Asp67Tyr consume less nicotine than do wild-type smokers. This striking observation suggests that variations in nicotine N-glucuronidation, as reported for nicotine C-oxidation, may influence smoking behavior.

Impact: UGT2B10 genotype influences nicotine metabolism and should be taken into account when characterizing the role of nicotine metabolism on smoking. Cancer Epidemiol Biomarkers Prev; 19(6); 1423–31. ©2010 AACR.
Association of Body Size Measurements and Mammographic Density in Korean Women: The Healthy Twin Study
Authors: Sung Joohon , Song Yun-Mi , Stone Jennifer , Lee Kayoung , Kim Sun-Young
Published: June 2010

Background: Both greater body size and higher mammographic density seem to be associated with a risk of breast cancer. To understand a mechanism through which body size confers a higher risk of breast cancer, associations between mammographic measures and various measures of body size were examined.

Method: Study subjects were 730 Korean women selected from the Healthy Twin study. Body size measurements were completed according to standard protocol. Mammographic density was measured from digital mammograms using a computer-assisted method from which the total area and the dense area of the breast were calculated, and nondense area and percent of dense area were straightforwardly derived. Linear mixed models considering familial correlations were used for analyses.

Results: Total and nondense areas were positively associated with current body mass index (BMI), BMI at 35 years, total fat percent, waist circumference, and waist-hip ratio, whereas percent dense area was inversely associated with these characteristics in both premenopausal and postmenopausal women. Height was not associated with any mammographic measure. Total and nondense areas had strong positive genetic correlations with current BMI, total fat percent, waist circumference, and waist-hip ratio, whereas percent dense area had strong inverse genetic correlations with these body size measurements.

Conclusion: Mammographic density and obesity are inversely associated with each other possibly from common genetic influences that have opposite effects on mammographic density and obesity in Korean women.

Impact: The association between obesity and breast cancer does not seem to be mediated through mammographic density. Cancer Epidemiol Biomarkers Prev; 19(6); 1523–31. ©2010 AACR.
Synergistic Effects ofNAT2slow andGSTM1null Genotypes on Carcinogen DNA Damage in the Lung
Authors: Lee Mi-Sun , Su Li , Christiani David C.
Published: June 2010

Background: Polymorphisms in carcinogen detoxification enzymes, NAT2 and GSTM1, have been suggested as susceptibility factors for DNA damage and lung cancer. However, little information is available on DNA adduct burden in the lung tissue and polymorphisms in NAT2 and GST genes. We investigated the independent and combined effects of the metabolic gene polymorphisms of NAT2 and GSTs on DNA adduct formation in different tissues (lung and blood) in lung cancer patients.

Methods: DNA adducts were measured in lung and blood by the 32P-postlabeling assay. Multiple regression models were used to assess adjusted percent change in DNA adduct levels associated with GST and NAT2 genotypes.

Results: After adjusting for potential confounders, as well as for other GST gene variants, lung adduct levels significantly increased by 150.3% [95% confidence interval (95% CI), 35.4-362.6%] for the GSTM1 null and by 73.9% (95% CI, −3.2% to 212.4%) for the NAT2 slow acetylator genotype, respectively. No association was seen with polymorphisms of other GST genes such as GSTT1 and GSTP1. The high-risk group, the combined GSTM1 null plus NAT2 slow, had significantly enhanced levels of lung adducts by 295% (95% CI, 72.7-803.5%) over those associated with single genes, suggesting a synergistic effect on DNA damage in the target lung tissue.

Conclusions: The increase in DNA adduct levels in lung is associated with the GSTM1 null and NAT2 slow genotypes alone or in combination.

Impact: These results suggest that GSTM1 and NAT2 genotypes play an independent and interactive role in the formation of carcinogen DNA adduct in the lung. Cancer Epidemiol Biomarkers Prev; 19(6); 1492–7. ©2010 AACR.
Incidence, Duration, and Reappearance of Type-Specific Cervical Human Papillomavirus Infections in Young Women
Authors: Insinga Ralph P. , Perez Gonzalo , Wheeler Cosette M. , Koutsky Laura A. , Garland Suzanne M. , Leodolter Sepp , Joura Elmar A. , Ferris Daron G. , Steben Marc , Brown Darron R. , Elbasha Elamin H. , Paavonen Jorma , Haupt Richard M.
Published: June 2010

Background: We describe the incidence and duration of cervical human papillomavirus (HPV) infection episodes along with the risk of infection reappearance following a period of nondetection.

Methods: Women (1,788) ages 16 to 23 years underwent cytologic testing and PCR-based testing of cervical swab samples for HPV DNA (HPV-16/18/31/33/35/45/52/58/59) at ∼6-month intervals for up to 4 years in the context of a phase 3 clinical trial (placebo arm). HPV type–specific incidence rates were estimated per 100 person-years. Duration of type-specific cervical infection episodes and risk of reappearance following a period of nondetection were estimated using Kaplan-Meier methods.

Results: HPV-16 exhibited the highest (5.9), and HPV-35 and HPV-33 exhibited the lowest (1.0) incidence rates per 100 person-years. Mean cervical infection durations ranged from 13 months for HPV-59 to 20 months for HPV-16 and 58 (with ongoing infections censored at the time of treatment, if done). The risk of cervical infection reappearance within ∼3 years following a period of nondetection ranged from 0% to 16% across HPV types, with a mean of 8%. Limited evidence was found for a role of false-positive HPV tests, missed infections that were above the threshold for detection, or new acquisition of infection in accounting for patterns of infection reappearance.

Conclusions: Incidence of high-risk cervical infection was observed to vary considerably more across HPV types than infection duration. A nontrivial proportion of women exhibited infection reappearance following a period of nondetection, with a potential explanation for many such events observed within this analysis being a return to detectable levels of a previously acquired infection.

Impact: The risk of HPV infection reappearance following a period of nondetection has not been previously reported for individual HPV types, and this study finds that a nontrivial proportion of infected women exhibit reappearances. Future studies could ascertain subject-level factors that potentially modify the risk of infection reappearance. Cancer Epidemiol Biomarkers Prev; 19(6); 1585–94. ©2010 AACR.
Indoor Tanning and Risk of Melanoma: A Case-Control Study in a Highly Exposed Population
Authors: Lazovich DeAnn , Vogel Rachel Isaksson , Berwick Marianne , Weinstock Martin A. , Anderson Kristin E. , Warshaw Erin M.
Published: June 2010

Background: Indoor tanning has been only weakly associated with melanoma risk; most reports were unable to adjust for sun exposure, confirm a dose-response, or examine specific tanning devices. A population-based case-control study was conducted to address these limitations.

Methods: Cases of invasive cutaneous melanoma, diagnosed in Minnesota between 2004 and 2007 at ages 25 to 59, were ascertained from a statewide cancer registry; age-matched and gender-matched controls were randomly selected from state driver's license lists. Self-administered questionnaires and telephone interviews included information on ever use of indoor tanning, types of device used, initiation age, period of use, dose, duration, and indoor tanning–related burns. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for known melanoma risk factors.

Results: Among 1,167 cases and 1,101 controls, 62.9% of cases and 51.1% of controls had tanned indoors (adjusted OR 1.74; 95% CI, 1.42-2.14). Melanoma risk was pronounced among users of UVB-enhanced (adjusted OR, 2.86; 95% CI, 2.03-4.03) and primarily UVA-emitting devices (adjusted OR, 4.44; 95% CI, 2.45-8.02). Risk increased with use: years (P < 0.006), hours (P < 0.0001), or sessions (P = 0.0002). ORs were elevated within each initiation age category; among indoor tanners, years used was more relevant for melanoma development.

Conclusions: In a highly exposed population, frequent indoor tanning increased melanoma risk, regardless of age when indoor tanning began. Elevated risks were observed across devices.

Impact: This study overcomes some of the limitations of earlier reports and provides strong support for the recent declaration by the IARC that tanning devices are carcinogenic in humans. Cancer Epidemiol Biomarkers Prev; 19(6); 1557–68. ©2010 AACR.
Pigmentary Characteristics, UV Radiation Exposure, and Risk of Non–Hodgkin Lymphoma: a Prospective Study among Scandinavian Women
Authors: Veierød Marit Bragelien , Smedby Karin Ekström , Lund Eiliv , Adami Hans-Olov , Weiderpass Elisabete
Published: June 2010

Background: UV radiation and pigmentary characteristics may be associated with non–Hodgkin lymphoma (NHL) risk, but few prospective studies exist. We investigated these associations in a Norwegian-Swedish cohort.

Methods: The cohort included women ages 30 to 50 years at enrolment in 1991 to 1992. Host factors, and exposure to sun and artificial tanning devices in life-decades 0 to 50 years were collected by questionnaire. Relative risks (RR) with 95% confidence intervals (CI) were estimated by Poisson regression.

Results: Among 104,953 women with complete follow-up through 2006 (Sweden) and 2007 (Norway), 158 were diagnosed with NHL. Women with brown hair had an increased risk of NHL compared with dark brown–haired/black-haired women (RR, 1.72; 95% CI, 1.08-2.74); decreased risks were found among women with gray, green or mixed (RR, 0.50; 95% CI, 0.32-0.77), or blue (RR, 0.54; 95% CI, 0.35-0.81) eyes compared with those with brown eyes, and among those with high propensity to burn compared with those with low propensity (RR, 0.57; 95% CI, 0.36-0.91). Annual number of sunburns and bathing vacations in any age decade, or ever use of artificial tanning devices were not significantly associated with NHL risk. After exposure at ages 10 to 39 years, RRs for ever versus never exposed were 0.99 (95% CI, 0.65-1.50) for sunburn, 1.00 (95% CI, 0.64-1.54) for bathing vacations, and 0.99 (95% CI, 0.67-1.46) for artificial tanning device use.

Conclusion: Whereas several pigmentary characteristics were associated with NHL risk, our results do not support an association between UV radiation and NHL.

Impact: Studies of UV radiation and NHL are warranted for etiologic understanding and public health recommendations. Cancer Epidemiol Biomarkers Prev; 19(6); 1569–76. ©2010 AACR.
Active and Passive Smoking and the Risk of Pancreatic Cancer in the Netherlands Cohort Study
Authors: Heinen Mirjam M. , Verhage Bas A.J. , Goldbohm R. Alexandra , van den Brandt Piet A.
Published: June 2010

Background: To date, cigarette smoking is the most consistent risk factor for pancreatic cancer. We prospectively examined the role of active cigarette smoking, smoking cessation, and passive smoking as determinants for pancreatic cancer.

Methods: The Netherlands Cohort Study consisted of 120,852 men and women who completed a baseline questionnaire in 1986. After 16.3 years of follow-up, 520 incident pancreatic cancer cases were available for analysis. A case-cohort approach was employed using the person-years of follow-up of a random subcohort (n = 5,000), which was chosen immediately after baseline.

Results: Compared with never cigarette smokers, both former and current cigarette smokers had an increased pancreatic cancer risk [multivariable-adjusted hazard rate ratio (HR), 1.34; 95% confidence interval (CI), 1.02-1.75 and HR, 1.82; 95% CI, 1.40-2.38, respectively]. We observed an increased pancreatic cancer risk per increment of 10 years of smoking (HR, 1.15; 95% CI, 1.08-1.22) and an HR of 1.08 per increment of 10 cigarettes/d (95% CI, 0.98-1.19). Quitting smoking gradually reduced pancreatic cancer risk and approached unity after ≥20 years of quitting. No association was observed for passive smoking exposure and pancreatic cancer risk in women; in men, this association was not investigated because >90% of the men were ever smokers.

Conclusions: Overall, our findings confirmed that cigarette smoking is an important risk factor for pancreatic cancer, whereas quitting smoking reduced risk. No association was observed between passive smoking exposure and pancreatic cancer risk in women.

Impact: Quitting smoking would benefit the burden on pancreatic cancer incidence. Cancer Epidemiol Biomarkers Prev; 19(6); 1612–22. ©2010 AACR.
Associations of Plasma C-Peptide and IGFBP-1 Levels with Risk of Colorectal Adenoma in a Multiethnic Population
Authors: Le Marchand Loïc , Wang Hansong , Rinaldi Sabina , Kaaks Rudolf , Vogt Thomas M. , Yokochi Lance , Decker Robert
Published: June 2010

Background: Circulating levels of insulin and insulin-like growth factor (IGF) hormones have been associated with colorectal cancer risk, but few studies have examined their associations with colorectal adenoma.

Methods: We measured plasma C-peptide, a marker of insulin secretion, and IGF hormones in a case-control study of 554 pathologically confirmed, first-time adenoma cases and 786 controls with normal endoscopy among Caucasians, Japanese, and Native Hawaiians in Hawaii.

Results: High plasma levels of C-peptide were statistically significantly associated with risk of colorectal adenoma [multivariate odds ratio (95% confidence interval) for increasing quartiles: 1.0, 0.91 (0.65-1.27), 1.21 (0.86-1.71), and 1.79 (1.23-2.60); Ptrend = 0.0002]. We also observed a statistically significant inverse association between levels of plasma IGF binding protein-1 (IGFBP-1) and adenoma risk [1.0, 0.97 (0.70-1.34), 0.82 (0.58-1.15), and 0.47 (0.32-0.70); Ptrend <0.0001]. These associations remain significant after adjusting for each other and were not confounded by known risk factors. IGF-I, IGFBP-3, body mass index, and waist or hip circumference were not independently associated with adenoma risk.

Conclusion: These results provide evidence for an association of insulin and IGFBP-1 levels with colorectal adenoma.

Impact: This study suggests that hyperinsulinemia and IGF hormones may act as etiologic factors in colorectal carcinogenesis, as early as during adenoma formation. Cancer Epidemiol Biomarkers Prev; 19(6); 1471–7. ©2010 AACR.
Efficacy and Safety of Pimecrolimus Cream 1% in Mild-to-Moderate Chronic Hand Dermatitis: A Randomized, Double-Blind Trial
Authors: Hordinsky Maria , Fleischer Alan , Rivers Jason K. , Poulin Yves , Belsito Donald , Hultsch Thomas
Published: June 2010

Background: Chronic hand dermatitis is common and difficult to treat. Objective: Our aim was to assess the efficacy of pimecrolimus cream 1% in mild-to-moderate chronic hand dermatitis. Methods: Adult patients (n = 652) were randomized to pimecrolimus 1% or vehicle cream twice daily with overnight occlusion for 6 weeks, followed by a 6-week open-label pimecrolimus treatment. Primary efficacy was 5-point Investigators’ Global Assessment of prospectively selected ‘target hand’ as treatment success (Investigators’ Global Assessment 0 or 1) and treatment failure. Pruritus relief was also assessed. Results: Following double-blind phase treatment, target hand treatment success was achieved in 29.8 and 23.2% of the patients in the pimecrolimus and vehicle groups, respectively (p = 0.057). The proportion of patients experiencing pruritus relief was significantly higher in the pimecrolimus group compared to the vehicle group at all time points throughout the double-blind phase. Conclusion: The groups were comparable with respect to treating disease signs. Pruritus relief, however, was significantly greater in the pimecrolimus group.
Cobb Syndrome: Case Report and Review of the Literature
Authors: Dilmé-Carreras Elisabet , Iglesias-Sancho Maribel , Márquez-Balbás Gemma , Sola-Ortigosa Joaquin , Umbert-Millet Pablo
Published: June 2010

Cobb syndrome is a rare non-inherited neurocutaneous disease, in which there are metameric cutaneous and spinal vascular malformations of the trunk. In cases of segmentally distributed multiple cutaneous vascular lesions, early diagnostic imaging of the spinal cord allows prompt intervention in order to reduce permanent neurological sequelae. We report case of Cobb syndrome in a 12-year-old boy and present a systematic review of the literature.
Image Registration Strategy of T1-Weighted and FIESTA MRI Sequences in Trigeminal Neuralgia Gamma Knife Radiosurgery
Authors: Wang Tony J.C. , Brisman Ronald , Lu Zheng Feng , Li Xiang , Isaacson Steven R. , Shah Jinesh N. , Yoshida Emi J. , Liu Tian
Published: June 2010

Background/Aims: In Gamma Knife radiosurgery, T1 MRI is most commonly used and is generally sufficient for targeting the trigeminal nerve. For patients whose trigeminal nerves are unclear on T1 MRI, FIESTA MRI supplements anatomical structure visualization and may improve trigeminal nerve delineation. The purpose of this study was to develop a registration strategy for T1 and FIESTA MRIs. Methods: We conducted a retrospective study on 54 trigeminal neuralgia patients. All patients were scanned with T1 and FIESTA MRIs. We evaluated 4 methods of registration: automatic image definition, superior-slice definition, middle-slice definition and inferior-slice definition. Target discrepancies were measured by deviations from an intracranial landmark on T1 and FIESTA MR images. Results: The overall range in registration error was 0.10–5.19 mm using superior-, 0.10–1.56 mm using middle- and 0.14–2.89 mm using inferior-slice definition. Registration error >2 mm was observed in 11% of the patients using superior-, 4% using middle- and 7% using inferior-slice FIESTA MRI definition. Conclusions: Among patients for whom FIESTA and T1 MRI are used, registration based on middle-slice definition reduces registration error and improves targeting of the trigeminal nerve.
Multimodal Localization of Electrodes in Deep Brain Stimulation: Comparison of Stereotactic CT and MRI with Teleradiography
Authors: Sauner Dieter , Runge Matthias , Poggenborg Jörg , Maarouf Mohammad , Sturm Volker , Treuer Harald , Hunsche Stefan
Published: June 2010

Objective: In cross-sectional imaging, like CT or MRI, electrodes for deep brain stimulation are visualized by an artifact, which can differ from the real physical size of the electrode and even have an asymmetric appearance on MRI. The accuracy of such artifact-based estimation of the real position of the electrode using CT or MRI is investigated here. Stereotactic teleradiography was used as the gold standard. Methods: Twenty-three patients with implanted electrodes in the subthalamic nucleus (DBS type 3389; Medtronic, Minneapolis, Minn., USA) were included in a retrospective study on multimodal estimation of electrode position by 2 raters. Short spoiled gradient echo MRI (n = 10) and multi-row CT (n = 13) data were compared with teleradiography. Results: Mean radial differences between CT and X-ray for both raters were 0.6 ± 0.2 and 0.7 ± 0.3 mm, with maximum values of 1.0 and 1.2 mm, respectively. Both raters showed quite similar assessments in their ratings. Mean radial differences between MRI and X-ray were 1.2 ± 0.4 and 1.1 ± 0.4 mm, with maximum values of 1.7 and 2.2 mm. Concordance of the assessment was lower compared to CT. Conclusion: Spoiled gradient echo MR imaging cannot be recommended for visual localization of the quadripolar macroelectrode type 3389 from Medtronic. In contrast, CT imaging in absolute terms and with quite similar assessments by both raters is intra- and postoperatively a satisfactory alternative to teleradiography.
Epirubicin Followed by Cyclophosphamide, Methotrexate and 5-Fluorouracil versus Paclitaxel Followed by Epirubicin and Vinorelbine in Patients with High-Risk Operable Breast Cancer
Authors: Boccardo Francesco , Amadori Dino , Guglielmini Pamela , Sismondi Piero , Farris Antonio , Agostara Biagio , Gambi Angelo , Catalano Giuseppina , Faedi Marina , Rubagotti Alessandra
Published: June 2010

Objective: Breast cancer patients with >3 involved nodes (N+) have a poor outcome. Chemotherapy (CT), alone or combined with endocrine therapy (ET) in hormone receptor (HOR)-positive patients, is the standard for these women. However, there are still questions surrounding the optimal adjuvant CT regimen. Methods: 244 patients with >3 N+ were randomized to receive either four 3-weekly courses of epirubicin (E: 100 mg/m2, day 1) followed by four 4-weekly cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF: 600, 40, 600 mg/m2, days 1, 8: n = 122) or four 3-weekly courses of paclitaxel (T: 175 mg/m2, day 1) followed by four 3-weekly cycles of epirubicin and vinorelbine (E: 75 mg/m2, day 1; V: 25 mg/m2, days 1, 8: n = 122). After CT, tamoxifen (plus an LH-RH analog in menstruating women) was given to all HOR-positive patients over a period of 5 years. Overall survival (OS) was the primary end point. Relapse-free survival (RFS) and toxicity were secondary end points. Results: At a median follow-up time of 102 months (range 3–146), OS and RFS did not differ significantly between groups (E-CMF vs. T-EV: OS, HR 0.94, 95% CI 0.59–1.48, p = 0.8; RFS, HR 0.86, 95% CI 0.57–1.29, p = 0.45). The lack of any difference between assigned treatments was confirmed by multivariate analysis (E-CMF vs. T-EV: RFS, HR 0.98, 95% CI 0.64–1.48, p = 0.9). The 2 regimens showed different toxicity profiles. In fact, significantly more women assigned to E-CMF were affected by stomatitis (p = 0.001) while significantly more women in the T-EV group developed peripheral neuropathy (p < 0.0001) and musculoskeletal disorders (p < 0.0001). However, side effects were moderate and manageable and no toxic death occurred in either arm of the study. Conclusions: T-EV was safe and moderately toxic but was not superior to E-CMF.
FDA Review Summary: Mozobil in Combination with Granulocyte Colony-Stimulating Factor to Mobilize Hematopoietic Stem Cells to the Peripheral Blood for Collection and Subsequent Autologous Transplantation
Authors: Brave Michael , Farrell Ann , Ching Lin Sue , Ocheltree Terrance , Pope Miksinski Sarah , Lee Shwu-Luan , Saber Haleh , Fourie Jeanne , Tornoe Christoffer , Booth Brian , Yuan Weishi , He Kun , Justice Robert , Pazdur Richard
Published: June 2010

Purpose: On December 15, 2008, the US Food and Drug Administration approved plerixafor (Mozobil®; Genzyme Corp.), a new small-molecule inhibitor of the CXCR4 chemokine receptor, for use in combination with granulocyte colony-stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSC) to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM). This summary reviews the database supporting this approval. Experimental Design: The safety and efficacy of plerixafor were demonstrated by 2 multicenter, randomized, placebo-controlled studies in patients with NHL and MM who were eligible for autologous HSC transplantation. The primary efficacy end points were the collection of ≧5 × 106 CD34+ cells/kg from the peripheral blood in 4 or fewer apheresis sessions in patients with NHL or ≧6 × 106 CD34+ cells/kg from the peripheral blood in 2 or fewer apheresis sessions in patients with MM. Results: The 2 randomized studies combined enrolled 600 patients (298 with NHL and 302 with MM). Fifty-nine percent of patients with NHL who were mobilized with G-CSF and plerixafor had peripheral blood HSC collections of ≧5 × 106 CD34+ cells/kg in 4 or fewer apheresis sessions, compared with 20% of patients with NHL who were mobilized with G-CSF and placebo (p < 0.001). Seventy-two percent of patients with MM who were mobilized with Mozobil and G-CSF had peripheral blood HSC collections of ≧6 × 106 CD34+ cells/kg in 2 or fewer apheresis sessions, compared with 34% of patients with MM who were mobilized with placebo and G-CSF (p < 0.001). Common adverse reactions included diarrhea, nausea, vomiting, flatulence, injection site reactions, fatigue, arthralgia, headache, dizziness, and insomnia. Conclusions: This report describes the Food and Drug Administration review supporting the approval of plerixafor.
Cellular and Biochemical Characterization of the Anti-Inflammatory Effects of DuP 654 in the Arachidonic Acid Murine Skin Inflammation Model (Part 2 of 2)
Authors: Harris Richard R. , Mackin William M. , Bait Douglas G. , Rakich Suzanne M. , Collins Robert J. , Bruin Elaine M. , Ackerman Neil R.
Published: June 2010

The possible utility of DuP 654, a potent 5-lipoxygenase inhibitor, for treating human inflammatory skin disease was investigated in murine skin treated with 1.0 mg arachidonic acid (AA). When DuP 654 was applied to murine skin treated with AA, it inhibited the resulting inflammation and influx of cells. High performance liquid chromatography and radioimmunoassay analysis of lipid extracts from AA-treated ears indicated that the influx of polymorphonuclear leukocytes (PMN) was temporally preceded by an appearance of significant amounts of 5-HETE (6.7 ± 1.4 ng/ear) and Leukotriene B4 LTB4 0.92 ± 0.2 ng/ear) when compared with extracts of untreated ears (5-HETE, 02 ± 0.3 ng/ear; LTB4, < 0.1 ng/ear). The levels of the 5-lipoxygenase products were reduced by treatment with 10 µg/ear DuP 654. Lipid extracts from AA-treated ears contain chemotactic activity for human PMN and this chemotactic activity in the AA-treated ears could be reduced but not eliminated by immunosorption with anti-LTB4 antibodies coupled to protein A-agarose. The appearance of the chemotactic activity was inhibited by DuP 654. Taken together, these data suggest that DuP 654 may have utility in human inflammatory skin disease.
Genetic Regulation of Serum Phytosterol Levels and Risk of Coronary Artery Disease
Authors: Teupser Daniel , Baber Ronny , Ceglarek Uta , Scholz Markus , Illig Thomas , Gieger Christian , Holdt Lesca M. , Leichtle Alexander , Greiser Karin H. , Huster Dominik , Linsel-Nitschke Patrick , Schäfer Arne , Braund Peter S. , Tiret Laurence , Stark Klaus , Raaz-Schrauder Dorette , Fiedler Georg M. , Wilfert Wolfgang , Beutner Frank , Gielen Stephan , Großhennig Anika , König Inke R. , Lichtner Peter , Heid Iris M. , Kluttig Alexander , El Mokhtari Nour E. , Rubin Diana , Ekici Arif B. , Reis André , Garlichs Christoph D. , Hall Alistair S. , Matthes Gert , Wittekind Christian , Hengstenberg Christian , Cambien Francois , Schreiber Stefan , Werdan Karl , Meitinger Thomas , Loeffler Markus , Samani Nilesh J. , Erdmann Jeanette , Wichmann H.-Erich , Schunkert Heribert , Thiery Joachim
Published: June 2010

Background—

Phytosterols are plant-derived sterols that are taken up from food and can serve as biomarkers of cholesterol uptake. Serum levels are under tight genetic control. We used a genomic approach to study the molecular regulation of serum phytosterol levels and potential links to coronary artery disease (CAD).

Methods and Results—

A genome-wide association study for serum phytosterols (campesterol, sitosterol, brassicasterol) was conducted in a population-based sample from KORA (Cooperative Research in the Region of Augsburg) (n=1495) with subsequent replication in 2 additional samples (n=1157 and n=1760). Replicated single-nucleotide polymorphisms (SNPs) were tested for association with premature CAD in a metaanalysis of 11 different samples comprising 13 764 CAD cases and 13 630 healthy controls. Genetic variants in the ATP-binding hemitransporter
ABCG8
and at the blood group
ABO
locus were significantly associated with serum phytosterols. Effects in
ABCG8
were independently related to SNPs rs4245791 and rs41360247 (combined
P
=1.6×10
−50
and 6.2×10
−25
, respectively; n=4412). Serum campesterol was elevated 12% for each rs4245791 T-allele. The same allele was associated with 40% decreased hepatic
ABCG8
mRNA expression (
P
=0.009). Effects at the
ABO
locus were related to SNP rs657152 (combined
P
=9.4×10
−13
). Alleles of
ABCG8
and
ABO
associated with elevated phytosterol levels displayed significant associations with increased CAD risk (rs4245791 odds ratio, 1.10; 95% CI, 1.06 to 1.14;
P
=2.2×10
−6
; rs657152 odds ratio, 1.13; 95% CI, 1.07 to 1.19;
P
=9.4×10
−6
), whereas alleles at
ABCG8
associated with reduced phytosterol levels were associated with reduced CAD risk (rs41360247 odds ratio, 0.84; 95% CI, 0.78 to 0.91;
P
=1.3×10
−5
).

Conclusion—

Common variants in
ABCG8
and
ABO
are strongly associated with serum phytosterol levels and show concordant and previously unknown associations with CAD.
Free Fatty Acid Causes Leukocyte Activation and Resultant Endothelial Dysfunction Through Enhanced Angiotensin II Production in Mononuclear and Polymorphonuclear Cells
Authors: Azekoshi Yoko , Yasu Takanori , Watanabe Saiko , Tagawa Tatsuya , Abe Satomi , Yamakawa Ken , Uehara Yoshinari , Momomura Shinichi , Urata Hidenori , Ueda Shinichiro
Published: June 2010

Release of free fatty acid (FFA) from adipose tissue is implicated in insulin resistance and endothelial dysfunction in patients with visceral fat obesity. We demonstrated previously that increased FFA levels cause endothelial dysfunction that is prevented by inhibition of the renin-angiotensin system (RAS) in humans. However, the mechanisms for FFA-mediated activation of RAS and the resultant endothelial dysfunction were not elucidated. We investigated effects of elevated FFA on activity of circulating and vascular RAS, angiotensin II–forming activity of leukocytes, and leukocyte activation of normotensive subjects. We showed that increased FFA levels significantly enhanced angiotensin II–forming activity in human mononuclear (mean fold increase: 3.5 at 180 minutes;
P
=0.0016) and polymorphonuclear (2.0;
P
=0.0012) cells, whereas parameters of the circulating and vascular RAS were not affected. We also showed that FFA caused angiotensin II– dependent leukocyte activation, which impaired endothelial function partly via increased myeloperoxidase release and presumably enhanced adhesion of leukocytes. We propose that the enhanced production of angiotensin II by FFA in mononuclear and polymorphonuclear cells causes activation of leukocytes that consequently impairs endothelial function. RAS in leukocytes may regulate the leukocyte-vasculature interaction as the mobile RAS in humans.