bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I Clinical and Pharmacokinetic Study of the Novel Raf Kinase and Vascular Endothelial Growth Factor Receptor Inhibitor BAY 43-9006 in Patients With Advanced Refractory Solid Tumors
Authors: Strumberg Dirk , Richly Heike , Hilger Ralf A. , Schleucher Norbert , Korfee Sonke , Tewes Mitra , Faghih Markus , Brendel Erich , Voliotis Dimitris , Haase Claus G. , Schwartz Brian , Awada Ahmad , Voigtmann Rudolf , Scheulen Max E. , Seeber Siegfried 
Published: December 2004

Purpose BAY 43-9006 is a novel dual-action Raf kinase and vascular endothelial growth factor receptor inhibitor that inhibits tumor cell proliferation and angiogenesis. This study established the safety and pharmacokinetics of BAY 43-9006 in 69 patients with advanced refractory solid tumors. Patients and Methods BAY 43-9006 (50 to 800 mg) was administered once or twice daily on a varying weekly schedule. Pharmacokinetic sampling was performed in all patients; preliminary tumor response was also assessed. The effect of BAY 43-9006 on phorbol myristate acetate–stimulated ERK phosphorylation in peripheral blood lymphocytes was studied using flow cytometry. Results Mild to moderate diarrhea was the most common (55%) treatment-related adverse event. The maximum-tolerated dose was 400 mg bid continuous. Dose-limiting toxicities were grade 3 diarrhea and fatigue at 800 mg bid, and grade 3 skin toxicity at 600 mg bid. BAY 43-9006 pharmacokinetics were highly variable for single and multiple dosing, and toxicity did not appear to be dose dependent. Significant decreases of phorbol myristate acetate–stimulated ERK phosphorylation (P < .01) were identified at doses ≥ 200 mg bid continuous. Forty-five patients were assessable for efficacy; one patient had a partial response (hepatocellular carcinoma at 400 mg bid continuous), 25 patients had stable disease, with eight lasting > 6 months and five for >12 months. Eighteen patients had progressive disease, and tumor response could not be evaluated in one patient. Conclusion Oral BAY 43-9006 was well tolerated and appeared to provide some clinical benefits. Based on the results of this study, BAY 43-9006 at 400 mg bid continuous is recommended for ongoing and future studies.
Phase I Study of Sequential Vaccinations With Fowlpox-CEA(6D)-TRICOM Alone and Sequentially With Vaccinia-CEA(6D)-TRICOM, With and Without Granulocyte-Macrophage Colony-Stimulating Factor, in Patients With Carcinoembryonic Antigen–Expressing Carcinomas
Authors: Marshall John L. , Gulley James L. , Arlen Philip M. , Beetham Patricia K. , Tsang Kwong-Yok , Slack Rebecca , Hodge James W. , Doren Sandra , Grosenbach Douglas W. , Hwang Jimmy , Fox Evelyn , Odogwu Lauretta , Park Susie , Panicali Dennis , Schlom Jeffrey 
Published: December 2004

PurposeOur previous clinical experience with vaccinia and replication-defective avipox recombinant carcinoembryonic antigen (CEA) vaccines has demonstrated safety and clinical activity with a correlation between CEA-specific immune response and survival. Preclinical evidence demonstrated that the addition of the transgenes for three T-cell costimulatory molecules (B7-1, ICAM-1, LFA-3, designated TRICOM) results in a significant improvement in antigen-specific T-cell responses and antitumor activity. We describe here the first trial in humans of the CEA-TRICOM vaccines (also including an enhancer agonist epitope within the CEA gene).Patients and MethodsFifty-eight patients with advanced CEA-expressing cancers were accrued to eight cohorts that involved vaccinations with the following: replication-defective fowlpox recombinant (rF)-CEA(6D)-TRICOM; primary vaccination with recombinant vaccinia (rV)-CEA(6D)-TRICOM plus rF-CEA(6D)-TRICOM booster vaccinations; and rV-CEA(6D)-TRICOM and then rF-CEA(6D)-TRICOM, plus granulocyte-macrophage colony-stimulating factor (GM-CSF) with vaccines, or with divided doses of vaccine with GM-CSF. Vaccines were administered every 28 days for six doses and then once every 3 months. Reverting to treatments every 28 days was allowed if patients progressed on the 3-month schedule.ResultsIn this phase I study, no significant toxicity was observed. Twenty-three patients (40%) had stable disease for at least 4 months, with 14 of these patients having prolonged stable disease (> 6 months). Eleven patients had decreasing or stable serum CEA, and one patient had a pathologic complete response. Enhanced CEA-specific T-cell responses were observed in the majority of patients tested.ConclusionWe demonstrated that the CEA-TRICOM vaccines are safe and can generate significant CEA-specific immune responses, and they seem to have clinical benefit in some patients with advanced cancer.
A Novel Route to Octahedral In2O3 Particles Exhibiting Near Band Emission
Authors: Zhang Wu , Huang Zhen , Li Ting , Tang Qun , Ma Dekun , Qian Yitai 
Published: December 2004

Abstract
A novel solvothermal route combined with calcination was successfully established to synthesize octahedral In2O3 particles, which exhibit near band emission. Interesting shape transformation from amorphous sphere to well-shaped octahedron was found.
Acute Inhalant-Induced Neurotoxicity with Delayed Recovery
Authors: Finch Christopher K , Lobo Bob L 
Published: December 2004

OBJECTIVE: To report a case of neurotoxicity and subsequent hospitalization due to abuse of an ethyl chloride inhalant. CASE SUMMARY: A 41-year-old African American male presented to the emergency department due to mental status changes and an inability to walk. After the blood alcohol and urine drug screen returned negative, a family member revealed that the patient frequently abused an inhalant containing the volatile solvent ethyl chloride. DISCUSSION: Inhalant abuse is common and is facilitated by the widespread availability of volatile solvents that have legitimate commercial or household uses. Most inhalants are central nervous system depressants and are highly lipophilic. Maximum Impact, which contains ethyl chloride, is sold in stores and is readily available over the Internet. While the product has a legitimate use as a VCR head cleaner, it is often illicitly marketed over the Internet as a means of getting a “rush” or “high” and for enhancing sexual pleasure. Neurologic symptoms have been reported after deliberate inhalational exposure to ethyl chloride, and 2 deaths have been associated with its use. An objective causality assessment using the Naranjo probability scale revealed a probable adverse drug event. CONCLUSIONS: Inhalants should be included in the differential diagnosis of patients presenting with acute mental status changes and neurologic impairment that resolve over less than one week.
Immunosuppressant Drug Monitoring: Is the Laboratory Meeting Clinical Expectations?
Authors: Morris Raymond G 
Published: December 2004

OBJECTIVE: To review the literature relating to immunosuppressant drug measurement as performed in therapeutic drug monitoring laboratories associated with transplantation centers and consider whether the assay methods widely used for patient dosage management achieve acceptable quality criteria in the context of other sources of variability with these drugs. DATA SOURCES: Articles used were accessed primarily through MEDLINE, as well as references cited in related publications. Searches were restricted to organ transplantation in humans. STUDY SELECTION AND DATA EXTRACTION: Emphasis was placed on the literature relating to the quality of immunosuppressant drug assays, their limitations, and evidence of clinical benefit in dosage individualization. DATA SYNTHESIS: There is a dilemma evident between the quality of the analytical services offered by some diagnostic immunoassay manufacturers and the ability of a significant number of clinical laboratories globally to select only appropriate assay methods. CONCLUSIONS: In many cases, clinical laboratories fail to meet the reasonable clinical expectations required for interpretation of immunosuppressant drug assay results as an adjunct to optimal dosage individualization and patient care.
Eplerenone: A Selective Aldosterone Receptor Antagonist for Patients with Heart Failure
Authors: Barnes Brian J , Howard Patricia A 
Published: December 2004

OBJECTIVE: To evaluate the pharmacology, pharmacokinetics, safety, and clinical use of eplerenone in heart failure (HF). DATA SOURCES: English-language MEDLINE searches were performed from 1966 to May 2004. Key words included eplerenone, aldosterone receptor antagonist, heart failure, myocardial infarction, left-ventricular dysfunction, and cost-effectiveness. Additional references were identified from bibliographies of selected articles. STUDY SELECTION AND DATA EXTRACTION: Human trials evaluating the efficacy, safety, and cost-effectiveness of aldosterone receptor antagonists in HF were evaluated. DATA SYNTHESIS: Eplerenone is the first selective aldosterone receptor antagonist. The drug is indicated to improve the survival of stable patients with left-ventricular systolic dysfunction (ejection fraction <40%) and clinical evidence of HF following acute myocardial infarction. Efficacy and safety in this population have been demonstrated in a large, randomized clinical trial. Eplerenone is associated with severe and sometimes life-threatening hyperkalemia. Patients with reduced renal function and diabetes, as well as those on other drugs that increase potassium levels, are at highest risk. Eplerenone is metabolized by the cytochrome P450 system and may interact with drugs that interfere with this system. A major advantage of eplerenone over the nonselective aldosterone receptor antagonist spironolactone is lack of binding to progesterone and androgen receptors, which is associated with drug-induced gynecomastia, breast pain, and impotence. CONCLUSIONS: The addition of eplerenone to traditional HF therapy has been shown to reduce morbidity and mortality in patients who develop left-ventricular dysfunction after acute myocardial infarction. Eplerenone's selectivity reduces sex hormone—related adverse effects. Despite these benefits, the overall cost-effectiveness has yet to be determined.
Oxaliplatin-Associated Neuropathy: A Review
Authors: Cersosimo Robert J 
Published: December 2004

OBJECTIVE: To review the incidence, mechanism, signs, symptoms, and management of oxaliplatin-induced neurotoxicity. DATA SOURCES: English-language publications from the MEDLINE database (1995–August 2004), published articles, and meeting abstracts were reviewed. STUDY SELECTION AND DATA EXTRACTION: Relevant data were extracted from published reports and abstracts on studies and case reports of humans with cancer who received oxaliplatin chemotherapy and in vitro studies of oxaliplatin neurotoxicity. DATA SYNTHESIS: Neurotoxicity is a common adverse effect of oxaliplatin that usually presents as peripheral neuropathy. There are 2 forms of oxaliplatin-induced neurotoxicity: acute and chronic. The acute form occurs in >90% of patients and may begin during the infusion or within hours of completion, is usually self-limited, and may be exacerbated by exposure to cold. Chronic neuropathy is cumulative and is most commonly seen in patients who have received total doses ≥540 mg/m2. Although it is a sensory neuropathy, the intensity can increase to the point that it impairs physical functions, such as holding objects and writing. Preventive measures include administration of calcium and magnesium solutions, gabapentin, carbamazepine, amifostine, and glutathione. Treatment measures include calcium and magnesium solutions, gabapentin, and α-lipoic acid. CONCLUSIONS: Peripheral neuropathy is seen in the majority of patients who receive oxaliplatin. The acute form is usually transient and self-limited; however, the chronic form can be dose-limiting. Calcium and magnesium solutions are an effective and convenient means of treating and reducing the severity of neuropathic symptoms. Additional studies, including controlled trials, are needed to determine the best way to prevent and treat this complication.
Intensive Lipid-Lowering Therapy in Patients with Coronary Heart Disease
Authors: Lauderdale Stacy A , Sheehan Amy Heck 
Published: December 2004

OBJECTIVE: To describe current data evaluating the use of intensive lipid-lowering therapy in patients with coronary heart disease. DATA SOURCES: A literature search using MEDLINE (1966–September 2004) was conducted using the search terms lipoproteins, low-density lipoprotein cholesterol (LDL-C), hydroxymethylglutaryl-coenzyme A reductase inhibitors, coronary arteriosclerosis, and coronary disease to identify published trials comparing the effects of intensive and conventional lipid-lowering therapy. DATA SYNTHESIS: Intensive lipid-lowering therapy reduces LDL-C levels significantly more than conventional treatment and appears to reduce cardiovascular morbidity and mortality in patients who have recently experienced acute coronary syndrome (ACS). However, evidence suggesting clinical benefits in patients with stable coronary heart disease is currently lacking. CONCLUSIONS: Although data are limited, patients with ACS may benefit from intensive lipid-lowering therapy. Several studies are underway to determine the appropriate role of intensive lipid-lowering therapy.
Palonosetron HCl Compatibility and Stability with Doxorubicin HCl and Epirubicin HCl During Simulated Y-Site Administration
Authors: Trissel Lawrence A , Zhang Yanping 
Published: December 2004

BACKGROUND: Palonosetron HCl is a selective 5-HT3 receptor antagonist used for the prevention of chemotherapy-induced nausea and vomiting. Palonosetron HCl may be administered with other drugs by Y-site administration, including doxorubicin HCI and epirubicin HCI. Consequently, stability and compatability information are needed to verify the acceptability of such Y-site administration. OBJECTIVE: To evaluate the physical and chemical stability of undiluted palonosetron HCl 50 μg/mL with doxorubicin HCl 1 mg/mL and epirubicin HCl 0.5 mg/mL during simulated Y-site administration. METHODS: Triplicate samples of palonosetron HCl with each of the anthracycline chemotherapy drugs were tested. Samples were stored and evaluated for up to 4 hours at room temperature near 23°C. Physical stability was assessed using turbidimetric and particulate measurement, as well as visual inspection. Chemical stability was assessed by HPLC. RESULTS: All of the admixtures were clear and red—orange when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low initially and remained low throughout the study. The drug concentration was unchanged in any of the samples throughout the study. CONCLUSIONS: Palonosetron HCl is physically and chemically stable with doxorubicin HCl and epirubicin HCl during simulated Y-site administration of these drugs over 4 hours at ambient room temperature.
Molecular Distinction of Circulating Pregnancy-Associated Plasma Protein A in Myocardial Infarction and Pregnancy
Authors: Qin Qiu-Ping , Kokkala Saara , Lund Juha , Tamm Natalia , Voipio-Pulkki Liisa-Maria , Pettersson Kim 
Published: December 2004

AbstractBackground: In the blood of pregnant women, pregnancy-associated plasma protein A (PAPP-A) is present as a covalent complex with the proform of eosinophil major basic protein (proMBP). Recently, increased serum concentrations of PAPP-A have been found in acute coronary syndromes (ACS). The aim of this study was to investigate whether the circulating PAPP-A in ACS is the same as that in pregnancy.Methods: We developed two time-resolved immunofluorometric assays based on a relative epitope map constructed by the use of 17 monoclonal antibodies. One assay, which measured total PAPP-A, used two PAPP-A subunit-specific antibodies. The other assay, which measured PAPP-A/proMBP complex, used one proMBP subunit-specific antibody and one PAPP-A subunit-specific antibody. Serum samples from four patients with myocardial infarction (MI), three pregnant women in their first trimester, and one in her third trimester were fractionated by gel filtration on a Superose™ 6 precision column. The two assays were used to analyze fractions obtained by gel filtration as well as serum samples serially collected from four other MI patients.Results: Pregnancy-related PAPP-A was eluted as a single peak with a molecular mass of ∼700 kDa, whereas ACS-related PAPP-A was also eluted as a single peak but with a molecular mass of ∼530 kDa. Pregnancy-related PAPP-A was detected equally by the two assays, whereas increased ACS-related PAPP-A was detected only by the assay for total PAPP-A.Conclusions: Our results provide the first evidence that circulating ACS-related PAPP-A is different from circulating pregnancy-related PAPP-A in that it is not complexed with proMBP. These findings provide a solid foundation for the design of immunoassays to accurately measure atherosclerosis-associated plasma protein A in the circulation.
Evaluation of heat-treated wood swelling by differential scanning calorimetry in relation to chemical composition
Authors: Repellin Vincent , Guyonnet René 
Published: December 2004

AbstractRetification is a heat treatment that decreases the swelling of wood and increases its resistance to fungal attack. In this study, differential scanning calorimetry (DSC) was applied in order to determine the fibre saturation point (FSP) of natural and retified wood. FSP values were used to determine the total swelling of natural and heat-treated wood. The DSC method was compared to the volumetric shrinkage approach. The influence of heat treatment temperature and duration on the swelling of wood was investigated. Relationships between chemical changes and the reduction of swelling were analysed thoroughly.The equivalence of the DSC method and the volumetric shrinkage method is shown. FSP in association with anhydrous density is a good indicator for the evaluation of the overall swelling of heat-treated wood. Reduction of wood swelling with increasing temperature and duration of thermal treatment is often attributed to hemicellulose destruction. This study shows that the reduction of beech wood swelling cannot only be attributed to the disappearance of adsorption sites that goes with hemicellulose destruction. It is suggested that other phenomena such as structural modifications and chemical changes of lignin also play an important role.
Enhanced wet tensile paper properties via dielectric-barrier discharge
Authors: Vander Wielen Lorraine C. , Page Derek H. , Ragauskas Arthur J. 
Published: December 2004

Abstract
Dielectric-barrier discharge treatment was used to modify fully bleached softwood kraft and unbleached softwood thermomechanical pulp handsheets. The effect of dielectric-barrier discharge treatment on the physical strength properties and dimensional stability of handsheets were analyzed. Increased dielectric-barrier discharge treatment power resulted in significant increases in the wet tensile index of handsheets. Increases in the surface acid content of pulp fibers do not appear to contribute to changes in paper properties, nor do changes to relative bonded area within handsheets. Enhanced wet strength via dielectric-barrier discharge treatment corresponds to increased dimensional stability. This appears to be due to fiber cross-linking in the case of bleached kraft pulp, since the wet-strain decreases as wet tensile and wet Young's modulus increase. In the case of unbleached thermomechanical pulp, the wet-strain shows no decrease, yet the wet Young's modulus increases as the wet tensile index increases.
Survival of bacteria on wood and plastic particles: Dependence on wood species and environmental conditions
Authors: Milling Annett , Kehr Rolf , Wulf Alfred , Smalla Kornelia 
Published: December 2004

AbstractThe survival of two hygienically relevant bacteria,Escherichia colipIE639 andEnterococcus faecium, was followed on wooden sawdust of seven different European woods (pine, spruce, larch, beech, maple, poplar, and oak) versus polyethylene chips by using cultivation-dependent and molecular-based methods in parallel. The survival of the bacteria on wood was dependent on various factors such as the wood species, the type of the inoculated bacterium, the ambient temperature, and humidity. The bacterial titre decreased fastest on pine followed by oak compared to the other woods and plastic. Cultivation-independent analysis employing DNA extraction, Southern blot hybridisation, and PCR-based detection of marker genes of the test bacteria confirmed this result. The decline in bacterial numbers correlated with the decrease of bacterial DNA in the samples. Amounts of DNA ofE. coliandE. faeciumrecovered from pine and oak-wood sawdust were generally lower compared to the other woods and plastic.The presented study shows that pine and oak exhibit substantially better hygienic performance than plastic and indicates an antibacterial effect caused by a combination of the hygroscopic properties of wood and the effect of wood extractives.
Stone Tools, Style, and Social Identity: an Evolutionary Perspective on the Archaeological Record
Authors: Barton C. Michael 
Published: December 2004

Because of their prevalence in the archaeological record, chipped stone assemblages have long been used for the identification of social entities and the tracing of cultural relationships through space and time. To do this, archaeologists have focused primarily on variations in lithic morphology. Although the forms of stone artifacts are determined by a combination their utilitarian function, 'style', and the physical constraints of knapping different cryptocrystalline rocks, there is widespread belief that style provides the best information about social group membership. Style, however, is not a unified concept, including both passive variability resulting from stochastic processes and actively encoded social information, constrained by selection and manipulated by the makers and users of artifacts.A neo‐Darwinian framework is used to evaluate differing concepts of style and their applicability to the lithic archaeological record. Identifying prehistoric social entities and tracing cultural relationships is loosely analogous, methodologically and theoretically, to identifying taxa and tracing ancestor/descendant relationships in biology. Lithic technology is also examined from the point of view of neo‐Darwinian evolutionary theory to identity sources of morphological variability most likely to mark group social identity, and suggest methodologies best able to identify and differentiate prehistoric social groups.
John Eisner and Roger Cardinal, eds. The Cultures of Collecting; and Werner Muensterberger. Collecting, An Unruly Passion: Psychological Perspectives.
Authors: Price Sally 
Published: December 2004

The Cultures of Collecting. Edited by JOHN ELSNER and ROGER CARDINAL. Cambridge, Mass.: Harvard University Press, 1994. vii. 312 pp. Halftones, references, select bibliography, index. $39.95 (cloth), $18.95 (paper).Collecting, An Unruly Passion: Psychological Perspectives, WERNER MUENSTERBERGER. Princeton: Princeton University Press, 1994. xi. 295 pp. 12 b/w illus., notes, bibliography, index. $24.95 (cloth).
Art of Island Southeast Asia: The Fred and Rita Richman Collection in the Metropolitan Museum of Art./Island Ancestors: Oceanic Art from the Masco Collection
Authors: D'Alleva Anne 
Published: December 2004

Art of Island Southeast Asia: The Fred and Rita Richman Collection in the Metropolitan Museum of Art. Florina H. Capistrano‐Baker, with an introduction by Paul Michael Tayler. New York: The Metropolitan Museum of Art, 1994. 156 pp. 261 illus., with 16 in color, map, checklist of the collection, glossary, references. $39.95 (cloth); $29.95 (paper).Island Ancestors: Oceanic Art from the Masco Collection, Allen Wardwell. Seattle: University Washington Press, in association with The Detroit Institute of Arts, 1994. xiii. 282 pp. 153 illus., with 149 in color, maps, bibliography, index. $60.00 (cloth).