bluuebunny/crossref_metadata_2025 huggingface dataset:
Underreporting of Myeloid Malignancies by United States Cancer Registries
Authors: Craig Benjamin M. , Rollison Dana E. , List Alan F. , Cogle Christopher R.
Published: March 2012

Background: The recent decrease in myeloid leukemia incidence may be directly attributed to changes in the population-based cancer registries 2001 guidelines, which required the capture of only one malignancy in the myeloid lineage per person and the simultaneous adoption of myelodysplastic syndrome registration in the United States.

Methods: We constructed four claims-based algorithms to assess myeloid leukemia incidence, applied the algorithms to the 1999–2008 Surveillance Epidemiology and End Results (SEER)-Medicare database, and assessed algorithm validity using SEER-registered cases.

Results: Each had moderate sensitivities (75%–94%) and high specificities (>99.0%), with the 2+BCBM algorithm showing the highest specificity. On the basis of the 2+BCBM algorithm, SEER registered only 50% of the acute myelogenous leukemia cases and a third of the chronic myelogenous leukemia (CML) cases. The annual incidence of myeloid leukemia in 2005 was 26 per 100,000 persons 66 years or older, much higher than the 15 per 100,000 reported by SEER using the same sample.

Conclusion: Our findings suggest underreporting of myeloid leukemias in SEER by a magnitude of 50% to 70% as well as validate and support the use of the 2+BCBM claims algorithm in identifying myeloid leukemia cases. Use of this algorithm identified a high number of uncaptured myeloid leukemia cases, particularly CML cases.

Impact: Our results call for the commitment of more resources for centralized cancer registries so that they may improve myeloid leukemia case ascertainment, which would empower policy makers with ability to properly allocate limited health care resources. Cancer Epidemiol Biomarkers Prev; 21(3); 474–81. ©2012 AACR.
Perceived Risk and Worry For One's Partner and Self Correlate With Desire to Quit in Dual-Smoker Couples
Authors: KW Ranby , MA Lewis , BA Toll , MJ Rohrbaugh , IM Lipkus
Published: March 2012

Among smokers, the desire to quit smoking is often related to one's health concerns. However, much less is known about how perceptions of health concerns are related in couples in which both partners smoke (i.e., dual smoker couples) and their associations with desire to quit for self. We explored these issues using baseline survey data collected from 63 dual smoker couples recruited from the community in central North Carolina. Participants were aged 21 to 67 (M = 43.0, SD = 11.3) and had been smoking for 4 to 51 years (M = 22.9, SD = 11.3) with an average of 17 (SD = 8.8) cigarettes per day. Within couples, partners exhibited similar beliefs about worry about physical harm of smoking for oneself (r = .30, p < .05) and partner (r = .30, p < .05), perceived risk of disease for self (r = .26, p < .05) and partner (r = .24, p < .05), and desire that their partner quit (r = .34, p < .01). Individuals' desire to quit was related to their own perceived risk of disease (r = .34, p < .05) and worry about harm (r = .47, p < .001). Further, own desire to quit was related to worry about partner's health (r = .29, p < .01), perceived risk of partner getting a disease if they continued to smoke (r = .39, p < .001), and belief that their smoking has caused partner physical harm (r = .38, p < .001). Participants had an extremely strong desire (78% = 7 on 1–7 scale) for their partner's help if they were to quit smoking. These data show 1) there is significant concordance in partners' rating of risk of disease and worry; and 2) an individual's desire to quit is related to both one's perceptions of risk and worry of harm for self but also importantly perceptions of risk, and worry of harm for the partner. Interventions that highlight how smoking harms a couple may be a fruitful, yet currently underutilized, method to increase cessation in dual smoker couples, a high risk group with lower cessation rates and higher relapse rates.
Reduction in Breast Cancer Risk Associated with Meeting the WCRF/AICR Cancer Prevention Recommendations
Authors: T Hastert , E White
Published: March 2012

In 2007 the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) published eight recommendations related to body weight, physical activity and dietary behaviors aimed at reducing cancer incidence worldwide. These were based on a comprehensive review of the literature on these topics in relation to each of the common cancers. An expert panel operationalized seven of those recommendations (maintaining normal body weight, participating in moderate physical activity for at least 30 minutes per day, avoiding energy-dense foods, eating 5 or more servings of non-starchy fruits and vegetables per day, limiting consumption of red meat to no more than 18 oz per week, limiting alcohol consumption to one drink per day for women and two drinks per day for men, and limiting sodium consumption to 2400 mg per day), and we examined their association with breast cancer incidence over eight years of follow-up in the VITamins And Lifestyle (VITAL) Study cohort. Participants included 24,916 women aged 50–76 years at baseline in 2000–2002 who had no history of cancer and who had complete data for the recommendations evaluated. Incident cancers (n = 694) were tracked through the Western Washington Surveillance, Epidemiology and End Results (SEER) database. The median number of recommendations followed was 3 (0–7). After adjusting for age, education, race/ethnicity, mammogram in previous two years, history of breast cancer in a first-degree relative, years of combined estrogen plus progestin hormone therapy use, age at menarche, age at first birth, and age at menopause, the hazard ratios and 95% confidence intervals associated with meeting 1, 2, 3, 4, 5, and 6–7 recommendations compared with meeting none of the recommendations were: 0.57 (0.35, 0.95), 0.63 (0.39, 1.02), 0.55 (0.34, 0.88), 0.46 (0.28, 0.74), 0.44 (0.26, 0.75), and 0.31 (0.15, 0.65). These results suggest that meeting the WCRF/AICR recommendations could substantially decrease breast cancer risk.
Lifestyle and Dietary Risk Factors for Colorectal Hyperplastic and Adenomatous Polyps
Authors: S Michal , L Li , Z Chen
Published: March 2012

Background: Increasing evidence suggests that colon hyperplastic polyps (HP) increases predisposition to the development of colon cancer, albeit to a lesser degree than colon adenoma. Data on behavioral and lifestyle risk factors for HP are limited.

Methods: We compared the risk factor profiles for colon adenoma and colon HP in 1,826 patients without known history of colorectal cancer or polyps who are undergoing screening colonoscopy at our institution. Five hundred and eight patients were diagnosed with one or more colon adenomas, 215 with HP, 140 patients with both adenoma and HP, and 963 with negative colonscopic examination. Information on behavioral and lifestyle risk factors and dietary habits were collected by computer-assisted personal interview (CAPI) and Food Frequency Questionnaire prior to colonoscopy. We used multivariate unconditional logistic regressions to assess risk associations.

Results: Positive association were found between adenomatous polyps and male gender (OR 1.702, 95% CI 1.210–2.394, p 0.002), current smoker (OR 1.598, 95% CI 1.091–2.340, p 0.016) and family history (OR 1.409, 95% CI 1.034–1.920, p 0.030). For hyperplastic polyps, positive associations were found between current smoker (OR 2.038, 95% CI 1.207–3.441, p 0.008) and regular alcohol drinker (OR 1.661, 95% CI 1.057–2.610, p 0.028). For both types of polyps positive associations were found between male gender (OR 2.282, 95% CI 1.233–4.222, p 0.009), current smoker (OR 2.692, 95% CI 1.475–4.912, p 0.001) and family history (OR 2.472, 95% CI 1.506–4.057, p 0.00). In a subgroup analysis by gender, regular alcohol consumption (OR 1.780, 95% CI 1.008–3.143, p 0.047) was associated with increased risk and HRT (OR 0.450, 95% CI 0.225–0.903, p 0.025) was associated with a decreased risk of hyperplastic polyps in females. Whereas in males, ever smokers (OR 3.074, 95% CI 1.357–6.965, p 0.007) and current smokers (OR 3.311, 95% CI 1.307–8.389, p 0.012) were associated with an increase risk of hyperplastic polyps.

Conclusion: Our data indicate that there are several lifestyle and dietary risk factors that are associated with both colorectal adenomatous and hyperplastic polyps. These risk factors vary not only by type of polyp but also gender.
Observed Social Support Behaviors and Cancer-Related Cognitive Processing in Couples Coping with Head and Neck Cancer (HNC)
Authors: K Milbury , H Badr
Published: March 2012

Given the disfiguring and debilitating nature of HNC and its treatment, patients and their spouses are at risk of experiencing trauma symptoms including cognitive intrusion and avoidance which may exacerbate psychological distress. Even though the Social Cognitive Processing Model (SCPM) posits that social support facilitates adaptive cognitive processing, recent literature has pointed to harmful effects of received support. Most studies use self-report measures of perceived as opposed to actual received support focusing on the patient as the recipient of support. In reality, the support process is reciprocal and interdependent involving both receiving and providing support in both patients and spouses. Further, self-reports of cognitive processing are susceptible to self-presentation and defensive biases. The purpose of this research was to examine the association between actual observed support behaviors and cognitive intrusion and avoidance in 60 newly diagnosed HNC patients (87% male) and their spouses using a multi-method approach. As part of an ongoing longitudinal study, couples completed baseline questionnaires including an explicit measure of cognitive intrusion and avoidance (IES), completed a problem-solving discussion task in the laboratory immediately followed by an implicit assessment of cognitive intrusion (cancer Stroop task (CST)). We used the Social Support Interaction Coding System (SSICS) to code the video-recorded discussions. Dyadic analyses using multi-level modeling revealed that when patients and spouses received more (compared to less) positive support behaviors, they demonstrated slower reaction times (RT) on the CST (p < .01) indicating greater cognitive intrusion. The results were similar using the self-report method (IES; p < .05). No role differences (patients vs. spouses) were found. The current findings map on to recent literature suggesting that receiving support may be initially distressing in the acute phase of the traumatic event as it may elicit negative emotional responses, which are yet necessary to facilitate successful long-term adjustment. Thus, our next step in this ongoing longitudinal study is to examine long-term consequences of these findings as they will reveal clinical implications.
Epidemiological Risk Factors Associated with Inflammatory Breast Cancer Triple Negative Subtype
Authors: RL Atkinson , K Sexton , NT Ueno , S Krishnamurthy , W Woodward , R El-Zein , AM Brewster
Published: March 2012

Background: Inflammatory breast cancer (IBC) is rare and accounts for ∼1% of all invasive breast cancers. The 5-year survival rates are significantly lower than for other types of breast cancer, highlighting the significance of cancer prevention in IBC. A disproportionately higher percentage of IBC patients have triple-negative breast cancer (TNBC; ER−, PR− and Her2−) than patients with non-IBC. TNBCs are thought to arise from normal breast stem cells. Our preliminary data indicates that normal breast stem cells are enriched in adjacent normal tissues of patients with TN IBC. We hypothesize that parity and breastfeeding, risk factors that influence the normal stem cell compartment in the breast, will differ between TN IBC and non-TN IBC subtypes.

Methods: We identified 144 patients diagnosed with IBC in 1991–2011 at MD Anderson. Breast cancer risk factors including parity and breast-feeding were compared between patients with TN and non-TN IBC with chi square or Wilcoxon rank sum tests.

Results: The average age at diagnosis was 54 years; 83% of patients were non-Hispanic white; and 36% were TN IBC. We found that patients with TN IBC had significantly lower frequency (p = 0.02) and duration of breastfeeding (p = 0.02) compared with non-TN IBC patients. No differences were found in the frequency of other breast cancer risk factors.

Conclusion: The association between breastfeeding and TNBC indicates that stem cells that are retained in the absence of breastfeeding may be the cell of origin for TN IBC. These results highlight the importance of evaluating epidemiologic risk factors of IBC according to receptor subtype, which could lead to the identification of distinct etiologic pathways that could be targeted for prevention.
Benefits and Harms of Screening Mammography Frequency by Age and Comorbidity Score
Authors: D Braithwaite , W Zhu , R Hubbard , ES O'Meara , DL Miglioretti , B Geller , K Dittus , K Wernli , D Moore , K Kerlikowske
Published: March 2012

Background: There is uncertainty about the appropriate use of screening mammography in older women. We compared the benefits and harms of screening mammography frequency according to age and comorbidity scores.

Methods: We conducted analyses within a prospective cohort study of four mammography registries in the Breast Cancer Surveillance Consortium that had mammography data linked to Medicare claims information. Participants included 137,949 women aged 66–89 years without breast cancer and 2,993 women with breast cancer. We estimated odds of advanced (IIb, III, IV) stage, large tumor size (>20 millimeters), and estrogen receptor (ER) negative tumors and cumulative probability of false-positive mammography after 10 years of screening by mammography frequency, age and comorbidity score as determined by the Charlson Comorbidity Index.

Results: Mammography biennially vs. annually for women aged 66–89 years does not increase risk of tumors with unfavorable characteristics regardless of women's comorbidity score. Cumulative probability of a false-positive result for annual and biennial screening of women aged 66–89 years with a comorbidity score of ≥1 was 48 (46.1, 49.9) and 29 (28.1, 29.9) respectively. False-positives were more common among annual screeners than among those screened biennially irrespective of women's comorbidity score.

Conclusion: Mammography annually vs. biennially does not have added benefit for women aged 66–89 years, even among those in good overall health as reflected by the lack of comorbidity. Risk of false-positive mammography is much higher with annual mammography.
Immune Responses Contribute to Depression, Fatigue, and Pain in Hematopoietic Stem Cell Transplant Recipients
Authors: E Costanzo , M Juckett , A Nelson , A Erdmann , P Rathouz , P Hematti , C Coe
Published: March 2012

Depression, fatigue, and pain are prevalent and distressing quality of life concerns for individuals recovering from hematopoietic stem cell transplantation (HSCT). Recent research in other cancer populations suggests inflammatory cytokines can activate central nervous system pathways, evoking adverse behavioral responses including depressed mood, fatigue, and pain. We hypothesized that inflammatory responses also contribute to these symptoms among HSCT recipients. Participants (24 allogeneic and 68 autologous transplant recipients) completed well-validated measures of depressive symptoms, fatigue, and pain prior to transplant and 30, 100, and 200 days post-transplant. Circulating proinflammatory (IL-6, TNFÎ±) and regulatory (IL-10) cytokines were measured by ELISA in peripheral blood plasma at the same time points. Subject-level fixed effects and mixed effects linear regression models were employed to examine relationships between cytokine levels and quality of life assessments. Results indicated that depression and fatigue were most severe 30 days post-transplant, with allogeneic recipients showing markedly slower improvement than autologous recipients at later assessments. Pain did not change significantly over time. Among individual patients, changes in IL-6 levels across the assessment points were associated with corresponding changes in depressive symptoms (t = 2.0, p = .048), fatigue (t = 2.7, p = .008), and pain (t = 2.0, p = .048), after adjusting for the effects of time since transplant. Similarly, participants with elevated IL-6 levels reported more severe depression (z = 2.9, p = .004), fatigue (z = 2.9, p = .004), and pain (z = 3.0 p = .003) compared to participants with low/normal IL-6 levels. All models adjusted for graft type and recipient's age. Similar relationships were seen for IL-10, while TNFÎ± was not significantly associated with symptoms. Results provide evidence for a novel biobehavioral pathway by which inflammatory processes secondary to treatment and/or treatment-related complications may contribute to depression, fatigue, and pain among HSCT recipients. Findings may assist health care providers in identifying patients at risk for this constellation of symptoms.
Race and Risk of Large Bowel Polyps in Younger and Older Patients
Authors: K Wallace , D Ahnen , C Burke , E Barry , R Bresalier , F Saibil , J Baron
Published: March 2012

African Americans (AA) have a higher incidence of colorectal cancer (CRC) compared to European Americans (EA). However, AA are consistently diagnosed with CRC at a younger age suggesting a possible biologic difference in neoplasms by race. Few studies have investigated racial differences in risk of adenomas, precursors to most colorectal cancer and, to our knowledge, none have investigated whether this risk differs by adenoma type or age. To address this gap, we analyzed data pooled from three placebo-controlled adenoma chemoprevention trials to explore racial differences in the risk of large bowel polyps among younger and older subjects. Eligible subjects had at least one documented adenoma and were followed until their next scheduled colonoscopy. Using generalized linear regression, we estimated risk ratios and 95% confidence intervals (CI) as measures of the association between race and risk for one or more adenomas, advanced lesions, or hyperplastic polyps (HP) after randomization adjusting for age, sex, follow-up time, and treatment assignment. We defined advanced lesions as adenomas with at least 25% villous component, high-grade dysplasia, or an estimated size of 1 ≥ centimeter. We also assessed the potential interaction between race and age on the risk of large bowel polyps. Of the 2683 subjects enrolled, 2605 completed one follow-up exam after randomization (193 AA, 2412 EA). Overall, our results suggested a racial difference in risk for adenomas among younger (<50 years) but not among older (≥50 years) subjects (p-for interaction between age and race for any adenoma (p = 0.13) and for advanced adenoma (p = 0.04)). Younger AA, when compared to EA had a significantly higher risk of any adenoma (RR 1.73, 95% CI 1.00–3.00) and advanced lesions (RR 4.40, 95% CI 1.47–13.15) but no difference in risk of HP. Among older patients, using the same comparison, there was no racial difference in risk of adenomas (RR 1.06, 95% CI 0.91–1.25) or advanced lesions (RR 1.06, 95% CI 0.71–1.57)) but there was a significantly lower risk of HP (RR 0.64 (95% CI 0.47–0.88). Our findings suggest that older AA have a lower risk of HP; and AA under the age of 50 years of age are at increased risk of adenomas, especially advanced lesions.
Inhibiting Rotavirus Infection by Membrane-Impermeant Thiol/Disulfide Exchange Blockers and Antibodies against Protein Disulfide Isomerase
Authors: Calderon Martha N. , Guerrero Carlos A. , Acosta Orlando , Lopez Susana , Arias Carlos F.
Published: March 2012

Objectives: Determining the effect of membrane-impermeant thiol/disulfide exchange inhibitors on rhesus rotavirus infectivity in MA104 cells and investigating protein disulfide isomerase (PDI) as a potential target for these inhibitors. Methods: Cells were treated with DTNB [5,5-dithio-bis-(2-nitrobenzoic acid)], bacitracin or anti-PDI antibodies and then infected with virus. Triple-layered particles (TLPs) were also pretreated with inhibitors before inoculation. The effects of these inhibitors on α-sarcin co-entry, virus binding to cells and PDI-TLP interaction were also examined. FACS analysis, cell-surface protein biotin-labeling, lipid-raft isolation and ELISA were performed to determine cell-surface PDI expression. Results: Infectivity became reduced by 50% when cells or TLPs were treated with 1 or 6 mM DTNB, respectively; infectivity became reduced by 50% by 20 mM bacitracin treatment of cells whereas TLPs were insensitive to bacitracin treatment; anti-PDI antibodies decreased viral infectivity by about 45%. The presence of DTNB (2.5 mM) or bacitracin (20 mM) was unable to prevent virus binding to cells and rotavirus-induced α-sarcin co-entry. Conclusions: It was concluded that thiol/disulfide exchange was involved in rotavirus entry process and that cell-surface PDI was at least a potential target for DTNB and bacitracin-induced infectivity inhibition.
Urinary Stone Formers with Hypocitraturia and ‘Normal’ Urinary pH Are at High Risk for Recurrence
Authors: Strohmaier Walter Ludwig , Seilnacht Jürgen , Schubert Gernot
Published: March 2012

Background: Citrate is one of the most important inhibitors in urolithiasis. Hypocitraturia is a common risk factor in stone formers. Citrate excretion is regulated – amongst others – by acidosis and protein intake. A considerable number of stone formers, however, show hypocitraturia in the presence of normal urine pH levels. This is potentially due to defects in the renal tubular citrate carriers (NaDC 1 and 3) which may be genetically determined. Patients and Methods: 350 consecutive stone formers were examined. Exclusion criteria were urinary tract infection, hypokalemia, and steatorrhea. The following parameters were measured: serum: creatinine, calcium, potassium, and uric acid; urine: pH profiles, citrate, calcium, uric acid, ammonia, urea, and creatinine. Results: 83/350 patients were hypocitraturic (48 males, 35 females). 14/83 had low urine pH (≤6), 69/83 showed normal levels (>6). In the latter group there was a significantly higher recurrence rate (23 vs. 9%). The two groups were not different in serum parameters apart from uric acid. In urine, only pH and calcium (males) were significantly lower in the first group. Citrate did not correlate with urine pH and creatinine in the hypocitraturia-normal pH group, only with calcium in both sexes and urea and ammonia in females. In the hypocitraturia-low pH patients, there was no significant correlation between citrate and any other parameter tested. Conclusions: Hypocitraturia with normal urine pH is an entity indicating a high risk for recurrence. Since there was no correlation between citrate and pH, urea and ammonia, respectively, citrate excretion is not regulated in these patients as usual. There may be a link to calcium excretion. Potentially, these patients have defects in the renal tubular citrate carriers which may be genetically determined. Genetic examinations should be performed to elucidate a potential genetic disorder in hypocitraturia-normal pH stone formers.
Stapes Surgery in Osteogenesis Imperfecta: Retrospective Analysis of 34 Operated Ears
Authors: Swinnen Freya K.R. , De Leenheer Els M.R. , Coucke Paul J. , Cremers Cor W.R.J. , Dhooge Ingeborg J.M.
Published: March 2012

Intraoperative findings of stapes surgery in 34 ears from 22 patients with genetically confirmed osteogenesis imperfecta (OI) are reported, as well as the audiometric results after the longest postoperative follow-up published to date. Twenty-nine out of 34 ears underwent primary stapes surgery and 5 ears revision surgery. Postoperative audiometric follow-up ranged from 6 months to 37 years. Stapes footplates were fixed in all ears. Additionally, footplates were thickened or fragile, stapes crura atrophic or fractured, and middle ear mucosae thickened or hypervascularized. Short-term postoperative audiometry revealed improved hearing and reduced air-bone gaps in 28/29 primary operated ears and in all revision cases. In the 22 ears with long-term postoperative follow-up (mean duration: 16 years), hearing gain was still significant at the latest audiometric evaluation. Independently of the patients being diagnosed with OI type I or IV and independently of the underlying OI genotype, beneficial results are obtained in the majority of OI patients undergoing primary or revision stapes surgery for reduction of conductive hearing loss components caused by stapes footplate fixation. Despite the progressive course of the concomitant sensorineural component, hearing gain remains beneficial over several decades.
A Critical Role for the Inducible Proteasomal Subunits LMP7 and MECL1 in Cytokine Production by Activated Murine Splenocytes
Authors: Rockwell Cheryl E. , Monaco John J. , Qureshi Nilofer
Published: March 2012

Background and Purpose: The proteasome is a multi-subunit complex that proteolytically cleaves proteins. The replacement of the constitutive proteasome subunits β1, β2, and/or β5 with the IFNγ-inducible subunits LMP2, MECL1, and/or LMP7 results in the ‘immunoproteasome’. The inducible subunits change the cleavage specificities of the proteasome, but it is unclear whether they have functions in addition to this. The purpose of the present study was to determine the role of the proteasome in general, as well as LMP7 and MECL1 specifically, with regard to cytokine production by activated primary splenocytes. Methods: A LMP7/MECL1-null mouse was engineered to determine the roles of these subunits in cytokine production. Isolated splenocytes from wild-type and LMP7/MECL1–/– mice were treated with lactacystin and activated with PMA and ionomycin and subsequently cytokine mRNA levels were quantified. Results: The present study demonstrates that LMP7/MECL1 regulates the expression of IFNγ, IL4, IL10, IL2Rβ, GATA3, and t-bet. In contrast, the regulation of IL2, IL13, TNFα, and IL2Rα by the proteasome appears to occur independently of LMP7/MECL1. Conclusions: Collectively, the present study demonstrates that LMP7 and MECL1 regulate cytokine expression, suggesting this system represents a novel mechanism for the regulation of cytokines and cytokine signaling.
Can Ephedrine Pretreatment Be Effective in Alleviating Rocuronium Injection Pain?
Authors: Akcaboy Zeynep Nur , Akcaboy Erkan Yavuz , Soyal Ozlem Balkız , Turhan Guldane , Gogus Nermin
Published: March 2012

Objective: The aim of this randomized, double-blind, placebo-controlled study was to evaluate the effect of ephedrine pretreatment on the intensity of rocuronium injection pain when rocuronium was applied by timing principle and also to compare this effect with lidocaine and placebo. Subjects and Methods: 120 American Society of Anesthesiology risk score I–II patients scheduled for elective surgery under general anesthesia were randomized into three groups to receive either 70 µg/kg ephedrine (ephedrine group, n = 40) or 0.5 mg/kg lidocaine (lidocaine group, n = 40) or 5 ml NaCl 0.9% (placebo group, n = 40) as pretreatment. Thirty seconds after pretreatment drugs, rocuronium 0.6 mg/kg was administered by the timing principle and rocuronium injection pain scores were recorded. Twenty seconds after rocuronium administration, anesthesia was induced with thiopental and the patient’s trachea was intubated. Hemodynamic parameters and adverse effects were recorded. Results: The overall frequency of having pain was 82.5, 52.5 and 22.5% in placebo, ephedrine and lidocaine groups, respectively. Although the frequency of mild and moderate pain scores was higher in the ephedrine group than in the lidocaine group, this difference was not statistically significant (p = 0.032 and p = 0.001, respectively). Conclusion: Although not as effective as lidocaine 0.5 mg/kg, 70 µg/kg ephedrine pretreatment was able to alleviate rocuronium injection pain when rocuronium was applied by timing principle.
Methanol Extract of Bauhinia purpurea Leaf Possesses Anti-Ulcer Activity
Authors: Zakaria Z.A. , Abdul Hisam E.E. , Norhafizah M. , Rofiee M.S. , Othman F. , Hasiah A.H. , Vasudevan M.
Published: March 2012

Objective: The aim of the present study was to determine the anti-ulcer activity of a methanol extract of Bauhinia purpurea leaf (MEBP). Materials and Methods: MEBP was administered at doses of 100, 500 and 1,000 mg/kg and its effects on acute toxicity, absolute ethanol- and indomethacin-induced gastric ulceration, and pyloric ligation tests in rats were investigated. Results: At a dose of 5,000 mg/kg, MEBP did not cause any signs of toxicity in rats when given orally. Oral administration of MEBP exerted anti-ulcer activity (p < 0.05) in all models tested. However, a dose-dependent protection was observed only in the indomethacin-induced gastric ulceration model. Histological studies supported the observed anti-ulcer activity of MEBP. In the pyloric ligation assay, MEBP significantly increased gastric wall mucus secretion (p < 0.05), but did not affect the acidity of the gastric contents. Conclusion: MEBP exhibited anti-ulcer activity, which could be due to the presence of flavonoids, saponins or other polyphenols, thereby validating the traditional use of B. purpurea in the treatment of ulcers.
Hepcidin Destabilizes Atherosclerotic Plaque Via Overactivating Macrophages After Erythrophagocytosis
Authors: Li Jing Jing , Meng Xiao , Si Hai Peng , Zhang Cheng , Lv Hui Xia , Zhao Yu Xia , Yang Jian Min , Dong Mei , Zhang Kai , Liu Su Xia , Zhao Xue Qiang , Gao Fei , Liu Xiao Ling , Cui Tai Xing , Zhang Yun
Published: March 2012

Objective—

To explore a direct and causal relationship between vascular hepcidin and atherosclerotic plaque stability.

Methods and Results—

Accelerated atherosclerotic lesions were established by perivascular collar placement in apolipoprotein E–deficient (ApoE
−/−
) mice. Adenoviral overexpression of hepcidin in the carotid artery during plaque formation enhanced intraplaque macrophage infiltration and suppressed the contents of collagen and vascular smooth muscle cells, whereas hepcidin shRNA treatment exerts opposite effects. The overexpression or knockdown of hepcidin did not affect plaque lipid deposition but increased or decreased oxidized low-density lipoprotein (ox-LDL) levels within intraplaque macrophages. In cultured macrophages, ox-LDL not only increased reactive oxygen species formation, inflammatory cytokine production, and apoptosis but also upregulated hepcidin expression. However, hepcidin did not exaggerate the ox-LDL–induced activation of macrophages until an onset of erythrophagocytosis. Whereas hepcidin was critical for the upregulation of L-ferritin and H-ferritin in both ox-LDL–treated erythrophagocytosed macrophages and atherosclerotic plaques, the adding of iron chelators suppressed the intracellular lipid accumulation, reactive oxygen species formation, inflammatory cytokine expression, and apoptosis in erythrophagocytosed macrophages.

Conclusion—

Hepcidin promotes plaque destabilization partly by exaggerating inflammatory cytokine release, intracellular lipid accumulation, oxidative stress, and apoptosis in the macrophages with iron retention.
A Novel mRNA Binding Protein Complex Promotes Localized Plasminogen Activator Inhibitor-1 Accumulation at the Myoendothelial Junction
Authors: Heberlein Katherine R. , Han Jenny , Straub Adam C. , Best Angela K. , Kaun Christoph , Wojta Johann , Isakson Brant E.
Published: March 2012

Objective—

Plasminogen activator inhibitor-1 (PAI-1) has previously been shown to be key to the formation of myoendothelial junctions (MEJs) in normal and pathological states (eg, obesity). We therefore sought to identify the mechanism whereby PAI-1 could be selectively accumulated at the MEJ.

Methods and Results—

We identified PAI-1 protein enrichment at the MEJ in obese mice and in response to tumor necrosis factor (TNF-α) with a vascular cell coculture. However, PAI-1 mRNA was also found at the MEJ and transfection with a PAI-1–GFP with TNF-α did not demonstrate trafficking of the protein to the MEJ. We therefore hypothesized the PAI-1 mRNA was being locally translated and identified serpine binding protein-1, which stabilizes PAI-1 mRNA, as being enriched in obese mice and after treatment with TNF-α, whereas Staufen, which degrades PAI-1 mRNA, was absent in obese mice and after TNF-α application. We identified nicotinamide phosphoribosyl transferase as a serpine binding protein-1 binding partner with a functional τ-like microtubule binding domain. Application of peptides against the microtubule binding domain significantly decreased the number of MEJs and the amount of PAI-1 at the MEJ.

Conclusion—

We conclude that PAI-1 can be locally translated at the MEJ as a result of a unique mRNA binding protein complex.
Incidence and Outcome of Surgical Procedures After Coronary Bare-Metal and Drug-Eluting Stent Implantation
Authors: Tokushige Akihiro , Shiomi Hiroki , Morimoto Takeshi , Furukawa Yutaka , Nakagawa Yoshihisa , Kadota Kazushige , Iwabuchi Masashi , Shizuta Satoshi , Tada Tomohisa , Tazaki Junichi , Kato Yoshihiro , Hayano Mamoru , Abe Mitsuru , Ehara Natsuhiko , Inada Tsukasa , Kaburagi Satoshi , Hamasaki Shuichi , Tei Chuwa , Nakashima Hitoshi , Ogawa Hisao , Tatami Ryozo , Suwa Satoru , Takizawa Akinori , Nohara Ryuji , Fujiwara Hisayoshi , Mitsudo Kazuaki , Nobuyoshi Masakiyo , Kita Toru , Kimura Takeshi
Published: March 2012

Background—

There still remain safety concerns on surgical procedures after coronary drug-eluting stents (DES) implantation, and optimal management of perioperative antiplatelet therapy (APT) has not been yet established.

Methods and Results—

During 3-year follow-up of 12 207 patients (DES=6802 patients and bare-metal stent [BMS] only=5405 patients) who underwent coronary stent implantation in the CREDO-Kyoto registry cohort-2, surgical procedures were performed in 2398 patients (DES=1295 patients and BMS=1103 patients). Surgical procedures (early surgery in particular) were more frequently performed in the BMS group than in the DES group (4.4% versus 1.9% at 42-day and 23% versus 21% at 3-year, log-rank
P
=0.0007). Cumulative incidences of death/myocardial infarction (MI)/stent thrombosis (ST) and bleeding at 30 days after surgery were low, without differences between BMS and DES (3.5% versus 2.9%,
P
=0.4 and 3.2% versus 2.1%,
P
=0.2, respectively). The adjusted risks of DES use relative to BMS use for death/MI/ST and bleeding were not significant (hazard ratio: 1.63, 95% confidence interval: 0.93 to 2.87,
P
=0.09 and hazard ratio: 0.6, 95% confidence interval: 0.34 to 1.06,
P
=0.08, respectively). The risks of perioperative single- and no-APT relative to dual-APT for both death/MI/ST and bleeding were not significant; single-APT as compared with dual-APT tended to be associated with lower risk for death/MI/ST (hazard ratio: 0.4, 95% confidence interval: 0.13 to 1.01,
P
=0.053).

Conclusions—

Surgical procedures were commonly performed after coronary stent implantation, and the risk of ischemic and bleeding complications in surgical procedures was low. In patients selected to receive DES or BMS, there were no differences in outcomes. Perioperative administration of dual-APT was not associated with lower risk for ischemic events.
Comparison of 5-Year Clinical Outcomes Between Sirolimus-Versus Paclitaxel-Eluting Stent
Authors: Park Kyungil , Park Kyung Woo , Rha Seung-Woon , Bae Jang-Ho , Hur Seung-Ho , Park Jong-Seon , Yoon Jung-Han , Jang Yangsoo , Jeong Myung-Ho , Kim Hyo-Soo
Published: March 2012

Background—

The paclitaxel-eluting stent (PES) and sirolimus-eluting stent (SES) are first-generation drug-eluting stents (DES) that have been the most widely used; however, it is unclear whether there are differences in the long-term safety and efficacy between the 2 stents. The long-term effectiveness of DES in unselected people with diabetes is also currently unclear. Moreover, the possibility of late catch-up is suggested in the DES population.

Methods and Results—

This study is an 8-center collaborative network analysis of all comers who received SES and PES. All patients who received SES and PES from February 2003 to October 2006 were enrolled. We analyzed 9315 patients (33.3% with diabetes) treated with SES or PES in the major 8 centers representing whole area of Korea. The primary end point was a major adverse cardiac event (MACE) composite of overall death, myocardial infarction, and target lesion revascularization. All analyses were performed using multivariable, adjusted models and propensity score-matching methods. Long-term MACE for 5 years were significantly lower in the SES than the PES group (13.3% versus 15.6%; hazard ratio, 0.82; 95% confidence interval, 0.71 to 0.96;
P
=0.01), which was mainly driven by the difference of MACE within the first year (hazard ratio, 0.73; 95% CI, 0.59 to 0.90;
P
=0.003), but the rate of MACE between 1 and 5 years in the landmark analysis was not different between the 2 stents (1.9 versus 2.0%/yr). In the subpopulation of people with diabetes, in contrast to the whole population, PES was comparable to SES in terms of any clinical outcome, both within the first year and from 1 to 5 years (MACE for 5 years, 20.3 versus 17.9%; MACE within the first year, 9.6 versus 8.2%; MACE 1 to 5 years, 2.9 versus 2.6%/yr).

Conclusions—

The PES was inferior to the SES in the clinical follow-up of more than 9000 patients' cohort for 5 years, which was mainly driven by the difference in the first year. In the subpopulation of people with diabetes that showed higher MACE than people without diabetes, however, PES was comparable to SES in any clinical outcome for 5 years. Although these 2 stents are not frequently used as before, the data would be useful to expect the long-term clinical course of the current DES.
Long-Term Effects of Incident Diabetes Mellitus on Cardiovascular Outcomes in People Treated for Hypertension
Authors: Barzilay Joshua I. , Davis Barry R. , Pressel Sara L. , Cutler Jeffrey A. , Einhorn Paula T. , Black Henry R. , Cushman William C. , Ford Charles E. , Margolis Karen L. , Moloo Jamaluddin , Oparil Suzanne , Piller Linda B. , Simmons Debra L. , Sweeney Mary Ellen , Whelton Paul K. , Wong Nathan D. , Wright Jackson T. ,   for the ALLHAT Collaborative Research Group
Published: March 2012

Background—

Thiazide-type diuretics are associated with an increased incidence of diabetes compared with other antihypertensive medications. In this study, we determined the long-term cardiovascular disease (CVD) consequences of incident diuretic-associated diabetes compared with the effects of incident diabetes associated with calcium channel blocker and angiotensin-converting enzyme inhibitor use.

Methods and Results—

A total of 22 418 participants from the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) with baseline diabetes, incident diabetes (7.5% with chlorthalidone, 5.6% with amlodipine, and 4.3% with lisinopril), or no diabetes at 2 years of in-trial follow-up were followed for a mean total of 6.9 years (2.9 years in-trial and 4 additional years posttrial) through the use of national databases. The primary outcome was CVD mortality (death from coronary heart disease [CHD], stroke, heart failure, or other CVD). Among other outcomes were all-cause mortality, non-CVD mortality, and CHD (nonfatal myocardial infarction or fatal CHD). Participants on chlorthalidone with incident diabetes versus no diabetes had consistently lower, nonsignificant risk for CVD mortality (hazard ratio [HR], 1.04; 95% CI, 0.74–1.47), all-cause mortality (HR, 1.04; 95% CI, 0.82–1.30), and non-CVD mortality (HR, 1.05; 95% CI, 0.77–1.42) than participants on amlodipine or lisinopril with incident diabetes (HR range, 1.22–1.53). Participants with incident diabetes had elevated CHD risk compared with those with no diabetes (HR, 1.46; 95% CI, 1.09–1.96), but those on chlorthalidone had significantly lower risk than those on lisinopril (HR, 1.18 versus 2.57;
P
=0.04 for interaction).

Conclusions—

The findings suggest that thiazide-related incident diabetes has less adverse long-term CVD impact than incident diabetes that develops while on other antihypertensive medications.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00000542.
Islet1
Derivatives in the Heart Are of Both Neural Crest and Second Heart Field Origin
Authors: Engleka Kurt A. , Manderfield Lauren J. , Brust Rachael D. , Li Li , Cohen Ashley , Dymecki Susan M. , Epstein Jonathan A.
Published: March 2012

Rationale:

Islet1
(
Isl1
) has been proposed as a marker of cardiac progenitor cells derived from the second heart field and is utilized to identify and purify cardiac progenitors from murine and human specimens for ex vivo expansion. The use of
Isl1
as a specific second heart field marker is dependent on its exclusion from other cardiac lineages such as neural crest.

Objective:

Determine whether
Isl1
is expressed by cardiac neural crest.

Methods and Results:

We used an intersectional fate-mapping system using the
RC
::FrePe allele, which reports dual Flpe and Cre recombination. Combining
Isl1

Cre

/+
, a SHF driver, and
Wnt1
::Flpe, a neural crest driver, with
Rc
::FrePe reveals that some
Isl1
derivatives in the cardiac outflow tract derive from
Wnt1
-expressing neural crest progenitors. In contrast, no overlap was observed between
Wnt1
-derived neural crest and an alternative second heart field driver,
Mef2c-AHF-Cre
.

Conclusions:

Isl1
is not restricted to second heart field progenitors in the developing heart but also labels cardiac neural crest. The intersection of
Isl1
and
Wnt1
lineages within the heart provides a caveat to using
Isl1
as an exclusive second heart field cardiac progenitor marker and suggests that some
Isl1
-expressing progenitor cells derived from embryos, embryonic stem cultures, or induced pluripotent stem cultures may be of neural crest lineage.
Neurointerventional Procedural Volume per Hospital in United States
Authors: Grigoryan Mikayel , Chaudhry Saqib A. , Hassan Ameer E. , Suri Fareed K. , Qureshi Adnan I.
Published: March 2012

Background and Purpose—

Availability of neurointerventional procedures is recommended as a necessary component of a comprehensive stroke center by various regulatory guidelines that also emphasize adequate procedural volumes. We studied the volumes of neurointerventional procedures performed in various hospitals across the United States with subsequent comparisons with rates of minimum procedural volumes recommended by various professional bodies or used in clinical trials to ensure adequate operator experience.

Methods—

We reviewed the Nationwide Inpatient Sample database in the United States for the years 2005 to 2008. Using International Classification of Disease—Clinical Modification, 9th revision, and Medicare severity diagnosis-related group codes, we identified among hospitals that admit stroke patients those that met the minimum criteria for overall and individual procedural volumes specified in various guidelines. We then compared the characteristics between the high-volume hospitals that performed at least 100 cervicocerebral angiograms and met ≥1 other procedural criterion (n=79) and low-volume hospitals (n=958).

Results—

Proportions of hospitals that met individual procedural volume criteria over the 4-year period according to procedure were: cervicocerebral angiography (7.0%–7.8%); endovascular acute ischemic stroke treatments (0.4%–2.6%); carotid angioplasty/stent placement (3.0%–5.3%); intracranial angioplasty/stent placement (0.3%–1.3%); and aneurysm embolization (1.3%–2.6%). There were significant trends for increasing numbers of all the endovascular procedures except intracranial angioplasty/stent placement over the course of 4 years. The high-volume hospitals were more likely to be urban teaching hospitals (70.9% versus 13.1%;
P
<0.001), had larger bed size (79.7% versus 26.9%;
P
<0.001), and had significantly higher rates of hemorrhagic stroke admissions and lower rates of transient ischemic attack admissions. Urban teaching location/status (OR, 8.92; CI, 4.3–18.2;
P
<0.001) and large bed size (OR, 4.40; CI, 2.0–9.5;
P
<0.001) remained as independent predictors of a high-volume hospital when adjusted for age, gender, risk factors, and stroke subtype.

Conclusions—

There are very few hospitals in the United States that meet all the neurointerventional procedural volume criteria for all endovascular procedures recommended to ensure adequate operator experience. Our results support the creation of specialized regional centers for ensuring adequate procedural volume within treating hospitals.
MODIS Cloud-Top Property Refinements for Collection 6
Authors: Baum Bryan A. , Menzel W. Paul , Frey Richard A. , Tobin David C. , Holz Robert E. , Ackerman Steve A. , Heidinger Andrew K. , Yang Ping
Published: March 2012

This paper summarizes the Collection-6 refinements in the Moderate Resolution Imaging Spectroradiometer (MODIS) operational cloud-top properties algorithm. The focus is on calibration improvements and on cloud macrophysical properties including cloud-top pressure–temperature–height and cloud thermodynamic phase. The cloud phase is based solely on infrared band measurements. In addition, new parameters will be provided in Collection 6, including cloud-top height and a flag for clouds near the tropopause. The cloud parameters are improved primarily through 1) improved knowledge of the spectral response functions for the MODIS 15-μm carbon dioxide bands gleaned from comparison of coincident MODIS and Atmospheric Infrared Sounder (AIRS) radiance measurements and 2) continual comparison of global MODIS and Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) instantaneous cloud products throughout the course of algorithm refinement. Whereas the cloud-top macrophysical parameters were provided through Collection 5 solely at 5-km spatial resolution, these parameters will be available additionally at 1-km spatial resolution in Collection 6.
An Investigation of the Short-Term Predictability of Precipitation Using High-Resolution Composite Radar Observations
Authors: Ruzanski Evan , Chandrasekar V.
Published: March 2012

The short-term predictability of precipitation patterns observed by meteorological radar is an important concept as it establishes a means to characterize precipitation and provides an upper limit on the extent of useful nowcasting. Predictability also varies on the basis of spatial and temporal scales of the observed meteorological phenomena. This paper describes an investigation of the short-term predictability of precipitation patterns containing microalpha (0.2–2 km) to mesobeta (20–200 km) scales using high-resolution (0.5 km–1 min–1 dBZ) composite radar reflectivity data, extending the analysis presented in previous work to smaller space and time scales. An experimental approach is used in which continuous and categorical lifetimes of radar reflectivity fields in Eulerian and Lagrangian space are used to quantify short-term predictability. The space–time scale dependency of short-term predictability is analyzed, and a practical upper limit on the extent of Lagrangian persistence-based nowcasting is estimated. Connections to the predictability of larger scales are made within the context of previous work. The results show that short-term predictability estimates in terms of lifetime are approximately 14–15 and 20–21 min in Eulerian and Lagrangian space, respectively, and suggest that a linear relationship exists between predictability and space–time structure from microalpha to macrobeta (2000–10 000 km) scales.