bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Model of Ischemically Induced Ventricular Fibrillation for Comparison of Fixed‐dose and Escalating‐dose Defibrillation Strategies
Authors: Niemann James T. , Rosborough John P. , Walker Robert G. 
Published: June 2004

Abstract Objectives: Fixed‐ and escalating‐dose defibrillation protocols are both in clinical use. Clinical observations suggest that the probability of successful defibrillation is not constant across a population of patients with ventricular fibrillation (VF). Common animal models of electrically induced VF do not represent a clinical VF etiology or reproduce clinical heterogeneity in defibrillation probability. The authors hypothesized that a model of ischemically induced VF would exhibit heterogeneous defibrillation shock strength requirements and that an escalating‐dose strategy would more effectively achieve prompt defibrillation. Methods:Forty‐six swine were randomized to fixed, lower‐energy (150 J) transthoracic shocks (group 1) or escalating, higher‐energy (200 J–300 J–360 J) shocks (group 2). VF was induced by balloon occlusion of a coronary artery. After 1 or 5 minutes of VF, countershocks with a biphasic waveform were administered. The primary endpoint was successful defibrillation (termination of VF for 5 seconds) with ≤3 shocks. Results: VF was induced with occlusion or after reperfusion in 35 animals. Only five of 17 group 1 animals (29%, 95% CI = 10 to 56) could be defibrillated with ≤3 shocks; 15 of 18 group 2 animals (83%, 95% CI = 59 to 96) were defibrillated with ≤3 shocks (p < 0.002 vs. group 1). Nine of the group 1 animals (75%) that could not be defibrillated with 150‐J shocks were rescued with ≤3 shocks ranging from 200 to 360 J. Conclusions: In this ischemic VF animal model, defibrillation shock strength requirements varied among individuals, and when defibrillation was difficult, an escalating‐dose strategy was more effective for prompt defibrillation than fixed, lower‐energy shocks.
Raising Our HEADSS: Adolescent Psychosocial Documentation in the Emergency Department
Authors: Van Amstel Leanne L. , Lafleur Daniel L. , Blake Kim 
Published: June 2004

Abstract Objectives: To determine the effectiveness of a chart stamp featuring the acronym “HEADSS” (Home, Education, Alcohol, Drugs, Smoking, Sex) at improving adolescent psychosocial documentation in the emergency department (ED) chart. Methods:The study sample consisted of ten emergency physicians. The ED charts of 306 adolescent patients (aged 13–18 years) completed by these physicians were surveyed. An analysis of ED chart psychosocial documentation was conducted that compared a six‐week control phase (with no chart stamp) with a four‐week intervention phase (with a chart stamp featuring the HEADSS acronym). Presenting complaints in the ED, psychosocial documentation in the ED, and information from past medical records were compared between the two groups. Results: The ED charts surveyed consisted of 153 charts from each phase. HEADSS documentation ranged from 8% to 12% in the intervention phase and 0% to 7% in the control phase. Emergency physicians were more likely to document the topics of education (p = 0.029), alcohol (p = 0.045), and smoking (p = 0.009) as well as whether the patient was interviewed alone (p = 0.0001) in the intervention phase charts. Documentation of a detailed psychosocial assessment (>4/6 HEADSS topics addressed; p = 0.003) was more likely during the intervention phase. Conclusions: The HEADSS stamp is useful in prompting psychosocial documentation in the ED chart. Further study is needed to determine whether routine use of the HEADSS stamp technique can improve the detection and management of adolescent psychosocial problems.
Clinical Variables Associated with Mortality in Out‐of‐hospital Patients with Hemodynamically Significant Bradycardia
Authors: Schwartz Brian , Vermeulen Marian J. , Idestrup Chris , Datta Partha 
Published: June 2004

Abstract Objectives: To estimate mortality rates and identify clinical variables associated with mortality among patients with hemodynamically unstable bradycardia in an urban emergency medical services (EMS) system. Methods:This was a retrospective study conducted in a large, urban EMS system. Adult non–cardiac arrest patients transported by advanced life support paramedics from March 1996 to February 1997 with a heart rate ≤60 beats/min and systolic blood pressure ≤90 mm Hg were included. Transcutaneous pacing was not available. Patients under age 18 years, pregnant, or presenting with vital signs absent were excluded from the study population. Multivariate analysis of the association of patient characteristics with 30‐day mortality was conducted by using a Cox proportional hazards model. Results: Of the 247 patients studied, 133 (53.9%) received a fluid bolus, 37 (15.0%) were treated with atropine, and 17 (6.9%) received dopamine. Fifty‐one (20.7%) died in the 19‐month follow‐up period (15.6 per 100 person‐years); 10.5% died on the same day, 15.8% within 30 days, and 17.8% within one year. Variables associated with 30‐day mortality included wide QRS complex (adjusted risk ratio [RR] 2.6 [95% confidence interval (95% CI) = 1.3 to 5.2]), use of heart rate‐lowering calcium channel blockers (adjusted RR 2.1 [95% CI = 1.0 to 4.7]), and paramedic assessment of lack of patient improvement over the course of the call (adjusted RR 0.2 [95% CI = 0.1 to 0.6]). Conclusions: Out‐of‐hospital patients with hemodynamically unstable bradycardia have a high mortality rate. A wide QRS complex and use of heart rate‐lowering calcium channel blockers were associated with 30‐day mortality.
Phase I Trial of the Proteasome Inhibitor Bortezomib in Patients With Advanced Solid Tumors With Observations in Androgen-Independent Prostate Cancer
Authors: Papandreou Christos N. , Daliani Danai D. , Nix Darrell , Yang Hong , Madden Timothy , Wang Xuemei , Pien Christine S. , Millikan Randall E. , Tu Shi-Ming , Pagliaro Lance , Kim Jeri , Adams Julian , Elliott Peter , Esseltine Dixie , Petrusich Alexandria , Dieringer Pauline , Perez Cherie , Logothetis Christopher J. 
Published: May 2004

Purpose To determine the dose-limiting toxicity and maximum-tolerated dose of the proteasome inhibitor bortezomib administered intravenously weekly for 4 every 5 weeks; to determine the bortezomib pharmacokinetics and pharmacodynamics using plasma levels and an assay for 20S proteasome inhibition (PI) in whole blood; to correlate toxicity with bortezomib dose and degree of 20S PI; and to conduct a preliminary determination of the antitumor activity of bortezomib in patients with androgen independent prostate cancer (AIPCa). Patients and Methods Fifty-three patients (48 with AIPCa) received 128 cycles of bortezomib in doses ranging from 0.13 to 2.0 mg/m2/dose, utilizing a careful escalation scheme with a continuous reassessment method. Pharmacokinetic and pharmacodynamic studies were performed in 24 patients (at 1.45 to 2.0 mg/m2). Results A dose-related 20S PI was seen, with dose-limiting toxicity at 2.0 mg/m2 (diarrhea, hypotension) occurring at an average 1-hour post-dose of ≥ 75% 20S PI. Other side effects were fatigue, hypertension, constipation, nausea, and vomiting. No relationship was seen between body-surface area and bortezomib clearance over the narrow dose range tested. There was evidence of biologic activity (decline in serum prostate-specific antigen and interleukin-6 levels) at ≥ 50% 20S PI. Two patients with AIPCa had prostate-specific antigen response and two patients had partial response in lymph nodes. Conclusion The maximum-tolerated dose and recommended phase II dose of bortezomib in this schedule is 1.6 mg/m2. Biologic activity (inhibition of nuclear factor-kappa B-related markers) and antitumor activity is seen in AIPCa at tolerated doses of bortezomib. This agent should be further explored with chemotherapy agents in advanced prostate cancer.
Phase III Trial of Doxorubicin Plus Cisplatin With or Without Paclitaxel Plus Filgrastim in Advanced Endometrial Carcinoma: A Gynecologic Oncology Group Study
Authors: Fleming Gini F. , Brunetto Virginia L. , Cella David , Look Katherine Y. , Reid Gary C. , Munkarah Adnan R. , Kline Richard , Burger Robert A. , Goodman Annekathryn , Burks R. Tucker 
Published: May 2004

Purpose To determine whether the addition of paclitaxel to doxorubicin plus cisplatin improves overall survival (OS) in women with advanced or recurrent endometrial carcinoma. Secondary comparisons included progression-free survival (PFS), response rate (RR), and toxicities. Patients and Methods Eligible, consenting patients received doxorubicin 60 mg/m2 and cisplatin 50 mg/m2 (AP), or doxorubicin 45 mg/m2 and cisplatin 50 mg/m2 (day 1), followed by paclitaxel 160 mg/m2 (day 2) with filgrastim support (TAP). The initial doxorubicin dose in the AP arm was reduced to 45 mg/m2 in patients with prior pelvic radiotherapy and those older than 65 years. Both regimens were repeated every 3 weeks to a maximum of seven cycles. Patients completed a neurotoxicity questionnaire before each cycle. Results Two hundred seventy-three women (10 ineligible) were registered. Objective response (57% v 34%; P < .01), PFS (median, 8.3 v 5.3 months; P < .01), and OS (median, 15.3 v 12.3 months; P = .037) were improved with TAP. Treatment was hematologically well tolerated, with only 2% of patients receiving AP, and 3% of patients receiving TAP experiencing neutropenic fever. Neurologic toxicity was worse for those receiving TAP, with 12% grade 3, and 27% grade 2 peripheral neuropathy, compared with 1% and 4%, respectively, in those receiving AP. Patient-reported neurotoxicity was significantly higher in the TAP arm following two cycles of therapy. Conclusion TAP significantly improves RR, PFS, and OS compared with AP. Evaluation of this regimen in the high-risk adjuvant setting is warranted, but close attention should be paid to the increased risk of peripheral neuropathy.
Four Decades of Continuing Innovation With Fluorouracil: Current and Future Approaches to Fluorouracil Chemoradiation Therapy
Authors: Rich Tyvin A. , Shepard Robert C. , Mosley Stephen T. 
Published: May 2004

PurposeChemoradiotherapy, the combination of external radiation therapy and concurrent chemotherapy, has been the basis for the oncologic management of many patients since its development in the 1960s. Fluorouracil (FU) chemoradiotherapy has demonstrated success in several organ sites with multiple dosing schedules that now guide the selection of oral analogs of FU to provide new chemoradiotherapy options.MethodsThis article reviews the metabolism and pharmacology of FU and the advantages of administration of FU by continuous infusion or bolus. The potential role and impact of the oral fluorouracil prodrugs UFT, S-1, BOF-A2, and capecitabine as replacements for intravenous administration are discussed. The results of recent chemoradiotherapy studies with FU from 2000 to 2003 are summarized in rectal, head and neck, esophageal, gastric, pancreatic, biliary, anal, and cervical cancers.ResultsChemoradiotherapy with FU has the potential to widen the therapeutic window by minimizing normal tissue toxicity while maintaining effective tumor toxicity. Overall, FU chemoradiotherapy maximizes local control and, for some tumor sites (such as head and neck, pancreatic, biliary, cervical, esophageal, and gastric cancers), improves survival rates. Moreover, FU chemoradiotherapy results in improved organ preservation with excellent functional outcome in several anatomic sites including head and neck cancer, anal, and rectal cancer, with improved sphincter preservation.ConclusionFU chemoradiotherapy continues to play an important role in the management of many cancer sites. During the last four decades, optimal dosing schedules have produced a therapeutic gain. The introduction of oral prodrug analogs will likely further improve the results of FU therapy in several organ systems, such as the rectum, head and neck, and esophagus.
Failure of Higher-Dose Paclitaxel to Improve Outcome in Patients With Metastatic Breast Cancer: Cancer and Leukemia Group B Trial 9342
Authors: Winer Eric P. , Berry Donald A. , Woolf Susan , Duggan David , Kornblith Alice , Harris Lyndsay N. , Michaelson Richard A. , Kirshner Jeffrey A. , Fleming Gini F. , Perry Michael C. , Graham Mark L. , Sharp Stewart A. , Keresztes Roger , Henderson I. Craig , Hudis Clifford , Muss Hyman , Norton Larry 
Published: May 2004

Purpose Cancer and Leukemia Group B Protocol 9342 was initiated to determine the optimal dose of paclitaxel administered as a 3-hour infusion every 3 weeks to women with metastatic breast cancer. Patients and Methods Four hundred seventy-four women with metastatic breast cancer who had received one or no prior chemotherapy regimens were randomly assigned to one of three paclitaxel dosing regimens—175 mg/m2, 210 mg/m2, or 250 mg/m2—each administered as a 3-hour infusion every 3 weeks. Women completed self-administered quality of life and symptom assessment questionnaires at baseline and after three cycles of treatment. Results No evidence of a significant dose-response relationship was demonstrated over the dose range assessed. Response rates were 23%, 26%, and 21% for the three regimens, respectively. A marginally significant association (P = .04) was seen between dose and time to progression; however, in a multivariate analysis, the difference was even less apparent. No statistically significant difference was seen in survival. Neurotoxicity and hematologic toxicity were more severe on the higher dose arms. There was no significant difference in quality of life on the three arms. Conclusion Higher doses of paclitaxel administered as a 3-hour infusion to women with metastatic breast cancer did not improve response rate, survival, or quality of life. There was a slight improvement in time to progression with higher dose therapy, which was offset by greater toxicity. When a 3-hour infusion of paclitaxel is administered every 3 weeks, 175 mg/m2 should be considered the optimal dose.
Ki-67 Staining Is a Strong Predictor of Distant Metastasis and Mortality for Men With Prostate Cancer Treated With Radiotherapy Plus Androgen Deprivation: Radiation Therapy Oncology Group Trial 92–02
Authors: Pollack A. , DeSilvio M. , Khor L.-Y. , Li R. , Al-Saleem T.I. , Hammond M.E. , Venkatesan V. , Lawton C.A. , Roach M. , Shipley W.U. , Hanks G.E. , Sandler H.M. 
Published: May 2004

Purpose The Ki-67 staining index (Ki67-SI) has been associated with prostate cancer patient outcome; however, few studies have involved radiotherapy (RT) -treated patients. The association of Ki67-SI to local failure (LF), biochemical failure (BF), distant metastasis (DM), cause-specific death (CSD) and overall death (OD) was determined in men randomly assigned to short term androgen deprivation (STAD) + RT or long-term androgen deprivation (LTAD) + RT. Patients and Methods There were 537 patients (35.5%) on Radiation Therapy Oncology Group (RTOG) 92-02 who had sufficient tissue for Ki67-SI analysis. Median follow-up was 96.3 months. Ki67-SI cut points of 3.5% and 7.1% were previously found to be related to patient outcome and were examined here in a Cox proportional hazards multivariate analysis (MVA). Ki67-SI was also tested as a continuous variable. Covariates were dichotomized in accordance with stratification and randomization criteria. Results Median Ki67-SI was 6.5% (range, 0% to 58.2%). There was no difference in the distribution of patients in the Ki-67 analysis cohort (n = 537) and the other patients in RTOG 92-02 (n = 977) by any of the covariates or end points tested. In MVAs, Ki67-SI (continuous) was associated with LF (P = .08), BF (P = .0445), DM (P < .0001), CSD (P < .0001), and OD (P = .0094). When categoric variables were used in MVAs, the 3.5% Ki67-SI cut point was not significant. The 7.1% cut point was related to BF (P = .09), DM (P = .0008), and CSD (P = .017). Ki67-SI was the most significant correlate of DM and CSD. A detailed analysis of the hazard rates for DM in all possible covariate combinations revealed subgroups of patients treated with STAD + RT that did not require LTAD. Conclusion Ki67-SI was the most significant determinant of DM and CSD and was also associated with OD. The Ki67-SI should be considered for the stratification of patients in future trials.
Signal Transducer and Activator of Transcription-5 Activation and Breast Cancer Prognosis
Authors: Nevalainen Marja T. , Xie Jianwu , Torhorst Joachim , Bubendorf Lukas , Haas Philippe , Kononen Juha , Sauter Guido , Rui Hallgeir 
Published: May 2004

Purpose Transcription factor signal transducer and activator of transcription-5 (Stat5) promotes breast epithelial cell differentiation. We retrospectively analyzed whether levels of active Stat5 in breast cancer were linked to clinical outcome. Materials and Methods Immunohistochemistry was used to detect active, tyrosine-phosphorylated Stat5 in paraffin-embedded breast cancer specimens from three archival tissue microarray materials A, B, and C. Material A included 19 healthy human breast tissues and a progression series of primary lymph node-negative, primary lymph node-positive, and metastatic breast cancer (n = 400). Materials B (n = 785) and C (n = 570) represented two independent arrays of unselected primary breast cancer specimens with clinical follow-up data. Results Material A demonstrated that Stat5 activation, but not Stat5 protein expression, was gradually lost during cancer progression, with detectable activation in 100% of healthy breast specimens compared with less than 20% of node-positive breast cancers and metastases. Stat5 activation in tumors of material B was associated with favorable prognosis. This observation was confirmed and extended in material C to include both breast cancer-specific survival and disease-free survival. Stat5 activation remained an independent prognostic marker after adjusting for patient age, tumor size, histological grade, estrogen receptor, progesterone receptor, and Her2/neu status by Cox multivariate analysis (hazard ratio, 2.0; P = .029). Stat5 activation was a particularly favorable marker in the lymph node-negative breast cancer subpopulation (hazard ratio, 7.5; P = .003). Conclusion In our study, active Stat5 distinguishes breast cancer patients with favorable prognosis, and may be a useful marker for selection of more individualized treatment, especially in localized disease. These findings require confirmation in a large prospective study.
LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation
Authors: Kabeya Yukiko , Mizushima Noboru , Yamamoto Akitsugu , Oshitani-Okamoto Satsuki , Ohsumi Yoshinori , Yoshimori Tamotsu 
Published: May 2004

Rat LC3, a homologue of yeast Atg8 (Aut7/Apg8), localizes to autophagosomal membranes after post-translational modifications. The C-terminal fragment of LC3 is cleaved immediately following synthesis to yield a cytosolic form called LC3-I. A subpopulation of LC3-I is further converted to an autophagosome-associating form, LC3-II.Because yeast Atg8 is conjugated with phosphatidylethanolamine (PE) by a ubiquitin-like system, it has been hypothesized that LC3 is modified in a similar manner. Here, we show that [14C]-ethanolamine was preferentially incorporated into LC3-II, suggesting that LC3-II is a PE-conjugated form. LC3-II can be a substrate of mammalian Atg4B, a homologue of yeast Atg8-PE deconjugase, supporting the idea that LC3-II is LC3-PE. Moreover, two other mammalian homologues of yeast Atg8, γ-aminobutyric-acid-type-A-receptor-associated protein (GABARAP) and Golgi-associated ATPase enhancer of 16 kDa (GATE16) also generate form II, which are recovered in membrane fractions. Generation of the form II correlates with autophagosome association of GABARAP and GATE16. These results suggest that all mammalian Atg8 homologues receive a common modification to associate with autophagosomal membrane as the form II.
Ab Initio Quantum Chemical and Molecular Dynamics Simulation Study of Lithium Iodide in Acetonitrile
Authors: Bakó Imre , Megyes Tünde , Radnai Tamás , Pálinkás Gábor , Probst Michael , Fawcett W. Ronald 
Published: May 2004

Abstract

Ab initio calculations for clusters containing Li+ and up to six acetonitrile molecules have been performed by using the B3LYP, MP2(FC) and MP2(Full) methods with the 6-311+G** basis set. The three computational methods give similar results for highly symmetric structures. In the case of MP2 calculation the inclusion of core electrons does not effect the values of the intermolecular distances and binding energy in the Li+-acetonitrile complex. The average ion–ligand distance increases with increasing number of acetonitrile molecules in the cluster. It has been shown that the energy required to incorporate an additional acetonitrile molecule in the Li-acetonitrile clusters containing 5 and 6 acetonitrile molecules is almost equal to the acetonitrile–acetonitrile interaction energy in the most stable acetonitrile dimer and therefore it is very difficult to predict whether the coordination sphere of Li+ contains four, five or six acetonitrile molecules. A molecular dynamics simulation has also been performed on LiI-acetonitrile system. The coordination number of the Li+ and I− have been found to be 5.97 and 14, respectively. The first solvation shell of Li+ has an octahedral geometry; the coordination sphere of the I− ion does not show any special arrangement.
Reliable Thermodynamic Properties of Electrolyte Solutions – A Survey of Existing Data Sources
Authors: Westhaus Ulrich , Sass Richard 
Published: May 2004

Abstract
Chemical engineers and physical chemists dealing either with model development or the design of chemical apparatus or processes containing electrolytes have a pressing need to access reliable thermodynamic property data of the systems they are dealing with. A survey of the existing, publicly available data collections focused on electrolytes is given.
Hydration of Molecular Anions with Oxygen Sites – a Monte Carlo Study
Authors: Krienke Hartmut , Schmeer Georg 
Published: May 2004

Abstract
Equilibrium properties of molecular model water (in pure phase and in electrolyte solutions) are calculated with the help of spatial pair correlation functions, starting from classical molecular pair interactions. Simulations were performed for a new simple water model derived from combined quantum-mechanical and statistical calculations in a SCF/SSOZ scheme.
Ion hydration of molecular anions with oxygen sites such as nitrate and perchlorate ions is of special interest when compared with hydration structures of spherical atomic anions like the halide ions. The water structure around the different solutes, and their influence on solution properties, is discussed.