bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase I Dose Escalation, Pharmacokinetic and Pharmacodynamic Study of Naptumomab Estafenatox Alone in Patients With Advanced Cancer and With Docetaxel in Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Borghaei Hossein , Alpaugh Katherine , Hedlund Gunnar , Forsberg Göran , Langer Corey , Rogatko Andre , Hawkins Robert , Dueland Svein , Lassen Ulrik , Cohen Roger B.
Published: July 2009

Purpose

Two phase I studies were conducted of ABR-217620 alone or in combination with docetaxel. This is a recombinant fusion protein consisting of a mutated variant of the superantigen staphylococcal enterotoxin E (SEA/E-120) linked to fragment antigen binding moiety of a monoclonal antibody recognizing the tumor-associated antigen 5T4.

Patients and Methods

Patients with non–small-cell lung cancer (NSCLC), pancreatic cancer (PC), and renal cell cancer (RCC) received 5 daily boluses of ABR-217620 (3-month cycles) in escalating doses to determine the maximum-tolerated dose (MTD; ABR-217620 dose escalation monotherapy [MONO] study). Doses were selected based on individual patient anti–SEA/E-120 titers pretreatment. Patients with NSCLC received 4 daily, escalating doses of ABR-217620 followed by docetaxel in 21-day cycles (ABR-217620 dose escalation combination with docetaxel [COMBO] study).

Results

Thirty-nine patients were enrolled in the MONO study and 13 were enrolled in the COMBO study. The monotherapy MTD was 26 μg/kg (NSCLC and PC) and 15 μg/kg (RCC). Dose-limiting toxicities (DLTs) in the MONO study were fever, hypotension, acute liver toxicity, and vascular leak syndrome. In the COMBO study, the MTD was 22 μg/kg (neutropenic sepsis). Adverse events included grade 1 to 2 fever, hypotension, nausea, and chills. Treatment caused a systemic increase of inflammatory cytokines and selective expansion of SEA/E-120 reactive T-cells. Tumor biopsies demonstrated T-cell infiltration after therapy. Fourteen patients (36%) had stable disease (SD) on day 56 of the MONO study. Two patients (15%) in the COMBO study had partial responses, one in a patient with progressive disease on prior docetaxel, and five patients (38%) had SD on day 56.

Conclusion

ABR-217620 was well tolerated with evidence of immunological activity and antitumor activity.
Phase I Study of the Humanized Anti-CD40 Monoclonal Antibody Dacetuzumab in Refractory or Recurrent Non-Hodgkin's Lymphoma
Authors: Advani Ranjana , Forero-Torres Andres , Furman Richard R. , Rosenblatt Joseph D. , Younes Anas , Ren Hong , Harrop Kate , Whiting Nancy , Drachman Jonathan G.
Published: July 2009

Purpose

To evaluate the safety, maximum-tolerated dose (MTD), pharmacokinetics, and antitumor activity of dacetuzumab in patients with refractory or recurrent B-cell non-Hodgkin's lymphoma (NHL).

Patients and Methods

In this open-label, dose-escalation phase I study, dacetuzumab was administered to six cohorts of adult patients. In the first cohort, patients received 2 mg/kg weekly for 4 weeks; in all other cohorts, an intrapatient dose-escalation schedule was used with increasing doses up to a maximum of 8 mg/kg. Patients with clinical benefit after one cycle of dacetuzumab were eligible for a second cycle.

Results

In the 50 patients who received dacetuzumab, no dose dependence of adverse events (AEs) was observed. The most common AEs in ≥ 20% of patients were fatigue, pyrexia, and headache; most were grade 1 or 2. Noninfectious inflammatory eye disorders occurred in 12% of patients. AEs grade ≥ 3 occurred in 30% of patients and included disease progression, anemia, pleural effusion, and thrombocytopenia. Most laboratory abnormalities were grade 1 or 2; transient elevated hepatic aminotransferases occurred in 52% of patients. Two patients experienced dose-limiting toxicity: grade 3 conjunctivitis and transient vision loss in cohort (1), and grade 3 ALT elevation in cohort IV. The MTD of dacetuzumab was not established at the dose levels tested. Six objective responses were reported (one complete response, five partial responses). Tumor size decreased in approximately one third of patients.

Conclusion

Dacetuzumab monotherapy was well tolerated in patients with NHL in doses up to 8 mg/kg/wk. Preliminary response data are encouraging and support additional studies of dacetuzumab in this patient population.
Phase II Presurgical Feasibility Study of Bevacizumab in Untreated Patients With Metastatic Renal Cell Carcinoma
Authors: Jonasch Eric , Wood Christopher G. , Matin Surena F. , Tu Shi-Ming , Pagliaro Lance C. , Corn Paul G. , Aparicio Ana , Tamboli Pheroze , Millikan Randall E. , Wang Xuemei , Araujo John C. , Arap Wadih , Tannir Nizar
Published: July 2009

Purpose

To assess safety and efficacy of presurgical bevacizumab in patients with metastatic renal cell carcinoma (mRCC), and to explore the hypothesis that pretreatment of patients with antiangiogenic therapy will select patients who benefit most from cytoreductive nephrectomy.

Patients and Methods

Patients with newly diagnosed, clear cell mRCC whose primary tumors were considered resectable were enrolled. In this single-arm, phase II trial, patients received bevacizumab plus erlotinib (first patients, n = 23) or bevacizumab alone (n = 27 patients) for 8 weeks followed by restaging. If patients demonstrated progressive disease and had declining performance statuses after 8 weeks, nephrectomy procedures were deferred. Postoperatively, patients continued on the study drug or drugs if disease stabilization or regression had occurred.

Results

Between March 2005 and March 2008, 52 patients were enrolled on study, and 50 were included in the analysis. By Memorial Sloan-Kettering Cancer Center criteria, 82% of patients had intermediate-risk, and 18% had poor-risk, features. Forty-two patients underwent nephrectomy. Median progression-free survival was 11.0 months (95% CI, 5.5 to 15.6 months). Median overall survival was 25.4 months (95% CI, 11.4 months to not estimable). Two perioperative deaths occurred; neither was attributable to study drug. Wound dehiscence resulted in treatment discontinuation for three patients and treatment delay for two others.

Conclusion

Presurgical treatment with bevacizumab therapy yields clinical outcomes comparable to post-surgical treatment with antiangiogenic therapy in patients with mRCC, but it may result in wound-healing delays. Prospective, randomized trials to test the use of presurgical therapy as a method to select appropriate patients for cytoreductive nephrectomy are warranted.
Erythroid-Stimulating Agents in Cancer Therapy: Potential Dangers and Biologic Mechanisms
Authors: Hadland Brandon K. , Longmore Gregory D.
Published: July 2009

Erythropoietin-stimulating agents (ESAs) were originally designed to replace endogenous erythropoietin in patients with anemia secondary to renal failure. Their use has subsequently been expanded to include patients with anemia of other causes, including cancer patients, in whom deficiency of erythropoietin, per se, is not the primary cause of anemia. Although early studies showed promise of ESA administration in reducing the need for transfusions and improving the quality of life in cancer patients, several large randomized clinical trials have recently shown a potential detrimental effect of ESA administration on tumor progression and survival in these patients. These studies have called into question the safety of ESAs as supportive therapy in patients being treated for oncologic conditions. However, numerous questions remain to be addressed regarding the design of these studies, the effect of various targeted hemoglobin levels, and the potential biologic mechanisms proposed to explain promotion of tumor progression and reduced survival.
Comparison of Commission on Cancer–Approved and –Nonapproved Hospitals in the United States: Implications for Studies That Use the National Cancer Data Base
Authors: Bilimoria Karl Y. , Bentrem David J. , Stewart Andrew K. , Winchester David P. , Ko Clifford Y.
Published: July 2009

Background

The Commission on Cancer (CoC) designates cancer programs on the basis of the ability to provide a wide range of oncologic services and specialists. All CoC-approved hospitals are required to report their cancer diagnoses to the National Cancer Data Base (NCDB), and the cancer diagnoses at these hospitals account for approximately 70% of all new cancers diagnosed in the United States annually. However, it is unknown how CoC-approved programs compare with non–CoC-approved hospitals.

Methods

By using the American Hospital Association Annual Survey Database (2006), CoC-approved and non–CoC-approved hospitals were compared with respect to structural characteristics (ie, accreditations, geography, and oncologic services provided).

Results

Of the 4,850 hospitals identified, 1,412 (29%) were CoC-approved hospitals, and 3,438 (71%) were not CoC-approved hospitals. The proportion of CoC-approved hospitals varied at the state level from 0% in Wyoming to 100% in Delaware. Compared with non–CoC-approved hospitals, CoC-approved programs were more frequently accredited by the Joint Commission, designated as a Comprehensive Cancer Center by the National Cancer Institute, and affiliated with a medical school or residency program (P < .001). CoC-approved hospitals were less likely to be critical access hospitals or located in rural areas (P < .001). CoC-approved hospitals had more total beds and performed more operations per year (P < .001). CoC-approved programs more frequently offered oncology-related services, including screening programs, chemotherapy and radiation therapy services, and hospice/palliative care (P < .001).

Conclusion

Compared with non–CoC-approved hospitals, CoC-approved hospitals were larger, were more frequently located in urban locations, and had more cancer-related services available to patients. Studies that use the NCDB should acknowledge this limitation when relevant.
D-Dimer and Prothrombin Fragment 1 + 2 Predict Venous Thromboembolism in Patients With Cancer: Results From the Vienna Cancer and Thrombosis Study
Authors: Ay Cihan , Vormittag Rainer , Dunkler Daniela , Simanek Ralph , Chiriac Alexandru-Laurentiu , Drach Johannes , Quehenberger Peter , Wagner Oswald , Zielinski Christoph , Pabinger Ingrid
Published: July 2009

Purpose

Venous thromboembolism (VTE) is a well-recognized complication of cancer. Laboratory parameters might be useful to assess the VTE risk in patients with cancer. The aim of this study was to investigate D-dimer and prothrombin fragment 1 + 2 (F 1 + 2), which reflect activation of blood coagulation and fibrinolysis, for prediction of cancer-associated VTE.

Patients and Methods

In a prospective, observational, cohort study of 821 patients with newly diagnosed cancer or progression of disease who did not recently receive chemotherapy, radiotherapy, or surgery were enrolled and followed for a median of 501 days (interquartile range, 255 to 731 days). The malignancies in these patients were as follows: breast (n = 132), lung (n = 119), stomach (n = 35), lower gastrointestinal tract (n = 106), pancreas (n = 46), kidney (n = 22), and prostate (n = 101) cancers; high-grade glioma (n = 102); malignant lymphoma (n = 94); multiple myeloma (n = 17); and other tumor types (n = 47). The study end point was occurrence of objectively confirmed symptomatic or fatal VTE.

Results

VTE occurred in 62 patients (7.6%). The cutoff level for elevated D-dimer and elevated F 1 + 2 was set at the 75th percentile of the total study population. In multivariable analysis that included elevated D-dimer, elevated F 1 + 2, age, sex, surgery, chemotherapy, and radiotherapy, the hazard ratios (HRs) of VTE in patients with elevated D-dimer (HR, 1.8; 95% CI, 1.0 to 3.2; P = .048) and elevated F 1 + 2 (HR, 2.0; 95% CI, 1.2 to 3.6; P = .015) were statistically significantly increased. The cumulative probability of developing VTE after 6 months was highest in patients with both elevated D-dimer and elevated F 1 + 2 (15.2%) compared with patients with nonelevated D-dimer and nonelevated F 1 + 2 (5.0%; P < .001).

Conclusion

High D-dimer and F 1 + 2 levels independently predict occurrence of VTE in patients with cancer.
Phase II Study of Bevacizumab With Concurrent Capecitabine and Radiation Followed by Maintenance Gemcitabine and Bevacizumab for Locally Advanced Pancreatic Cancer: Radiation Therapy Oncology Group RTOG 0411
Authors: Crane Christopher H. , Winter Kathryn , Regine William F. , Safran Howard , Rich Tyvin A. , Curran Walter , Wolff Robert A. , Willett Christopher G.
Published: July 2009

Purpose

The primary objective of this study was to assess the 1-year survival of patients with locally advanced, unresectable pancreatic cancer treated with the combination of bevacizumab, capecitabine, and radiation. Secondary end points were toxicity, progression-free survival (PFS), and response rate (RR).

Patients and Methods

Patients with locally advanced pancreatic cancer without duodenal invasion were treated with 50.4 Gy per 28 fractions to the gross tumor with concurrent capecitabine 825 mg/m2 orally twice daily on days of radiation and bevacizumab 5 mg/kg on days 1, 15, and 29 followed by maintenance gemcitabine 1 g/m2 weekly for 3 weeks and bevacizumab 5 mg/kg every 2 weeks, both in 4-week cycles until progression. Treatment plans were reviewed for quality assurance (QA).

Results

Between January 2005 and February 2006, 82 eligible patients were treated. The median and 1-year survival rates were 11.9 months (95% CI, 9.9 to 14.0 months) and 47% (95% CI, 36% to 57%). Median PFS was 8.6 months (95% CI, 6.9 to 10.5), and RR was 26%. Overall, 35.4% of patients had grade 3 or greater treatment-related gastrointestinal toxicity (22.0% during chemoradiotherapy, 13.4% during maintenance chemotherapy). Unacceptable radiotherapy protocol deviations (ie, inappropriately generous volume contoured) correlated with grade 3 or greater gastrointestinal toxicity during chemoradiotherapy (45% v 18%; adjusted odds ratio, 3.7; 95% CI, 0.98 to 14.1; P = .05).

Conclusion

The addition of bevacizumab to chemoradiotherapy followed by bevacizumab and gemcitabine resulted in a similar median survival to previous Radiation Therapy Oncology Group studies in patients with locally advanced pancreatic cancer. Prospective QA may help limit toxicity in future trials.
Unsteady modelling of cavitating flow with artificial viscosity
Authors: Nouri N M , Moghimi M , Mirsaeedi S M H
Published: July 2009

In this study, a simple model for two-dimensional (2D) cavitating flows with artificial viscosity is proposed. The governing equations are the unsteady incompressible viscous Navier—Stokes equations. The proposed method includes the combination of a source and a sink of vapour through a dissipation term. The comparison between the obtained numerical results for a 2D wedge and the numerical solutions and experimental data shows that the cavity characteristics are well simulated. It can be concluded that introducing an artificial viscosity term improves both the numerical stability and the convergence rate.
Evaluation of van der Waals forces between the carbon nanotube tip and gold surface under an electron microscope
Authors: Liu P , Nakajima M , Yang Z , Fukuda T , Arai F
Published: July 2009

Carbon nanotubes (CNTs) have been widely used as nanobuilding blocks to assemble nanostructures and nanodevices. Therefore, the interaction between a CNT and an environment is important. In the present study, the interaction forces, which consisted mainly of van der Waals forces, between a single multi-walled carbon nanotube tip and a gold surface were evaluated under a scanning electron microscope by means of nanorobotic manipulation. The influence of electron beam irradiation was also investigated. It was found that electron beam irradiation can increase the interaction forces by producing contamination at the contact area. The van der Waals forces were calculated theoretically and the theoretical values were close to the experimental values.
Optimal Commodity Trading with a Capacitated Storage Asset
Authors: Secomandi Nicola
Published: July 2009

This paper considers the so-called warehouse problem with both space and injection/withdrawal capacity limits. This is a foundational problem in the merchant management of assets for the storage of commodities, such as energy sources and natural resources. When the commodity spot price evolves according to an exogenous Markov process, this work shows that the optimal inventory-trading policy of a risk-neutral merchant is characterized by two stage and spot-price dependent basestock targets. Under some assumptions, these targets are monotone in the spot price and partition the available inventory and spot-price space in each stage into three regions, where it is, respectively, optimal to buy and inject, do nothing, and withdraw and sell. In some cases of practical importance, one can easily compute the optimal basestock targets. The structure of the optimal policy is nontrivial because in each stage the merchant's qualification of high (selling) and low (buying) commodity prices in general depends on the merchant's inventory availability. This is a consequence of the interplay between the capacity and space limits of the storage asset and brings to light the nontrivial nature of the interface between trading and operations. A computational analysis based on natural gas data shows that mismanaging this interface can yield significant value losses. Moreover, adapting the merchant's optimal trading policy to the spot-price stochastic evolution has substantial value. This value can be almost entirely generated by reacting to the unfolding of price uncertainty, that is, by sequentially reoptimizing a model that ignores this source of uncertainty.
Technical Specialized Knowledge and Secondary Shares in Initial Public Offerings
Authors: Junkunc Marc T. , Eckhardt Jonathan T.
Published: July 2009

This paper utilizes an understudied but often utilized aspect of initial public offerings (IPOs), secondary shares, to examine whether the knowledge conditions of firms give rise to agency problems that limit the ability of founders and venture capitalists to sell equity at IPO. In an analysis of 2,190 IPOs spanning from 1992 through 2002, we find that private owners are less likely to be observed selling their equity at IPO in ventures that are highly dependent on technical specialized knowledge as measured by the count of individuals with Ph.D.s in the top management team and board of directors. However, we find that this limit on the financial liquidity of founders and venture capitalists is alleviated when the venture's output has received greater market acceptance. Hence, the findings suggest that the financial liquidity of individuals involved in entrepreneurship is likely to be influenced by the knowledge conditions of their venture.
Longitudinal associations between adolescent alcohol use and parents' sources of knowledge
Authors: Stavrinides Panayiotis , Georgiou Stelios , Demetriou Andreas
Published: July 2009

The aim of this study was to test the direction of effect in the relationship between parents' sources of knowledge (parental monitoring and child disclosure) and adolescent alcohol use. The participants were 215 adolescents and their mothers, randomly selected from urban and rural areas in Cyprus. A 3‐month, two‐timepoint longitudinal design was used in which adolescents completed the alcohol use disorders identification test while mothers completed a parental knowledge questionnaire. The results of this study showed that parental monitoring did not predict subsequent adolescent alcohol use. However, child disclosure at Time 1 negatively predicted adolescent alcohol use at Time 2. Moreover, adolescents' alcohol dependence symptoms at Time 1 negatively predicted both sources of parental knowledge at Time 2.
Innovative moments and change pathways: A good outcome case of narrative therapy
Authors: Santos Anita , Gonçalves Miguel , Matos Marlene , Salvatore Sergio
Published: July 2009

Objectives. Our aim was to explore the development of innovative moments (i‐moments) in therapeutic conversation and to study how they match our heuristic model that accounts for the development of change, drawn from previous empirical research.

Design. In this therapeutic process research, we analysed a good outcome case of narrative therapy with a woman victim of intimate violence.

Methods. This case, composed of 12 sessions, was analysed with the Innovative Moments Coding System: Version 1. This coding system allowed the identification of five different types of innovations (i‐moments) that appeared during the therapeutic process: action, reflection, protest, re‐conceptualization, and performing change. For each session, an index of temporal salience was computed, as the percentage of the time in the session that client and therapist spent talking about each i‐moment. Our analysis procedures provided a quantitative and also a complementary qualitative approach.

Results. Data showed that the types of i‐moments emerged differently throughout the process. Early sessions were characterized mainly by action and reflection (low temporal salience), middle sessions were found to have mainly protest i‐moments (low or middle temporal salience), and final sessions were characterized by the combination of high salient re‐conceptualization and performing change i‐moments.

Conclusions. Findings suggested that narrative change seems to develop in a cyclical way, in which different types of i‐moments contribute to the development of a new self‐narrative in different phases.
Executive disorders and perceived socio‐emotional changes after traumatic brain injury
Authors: Rochat Lucien. , Ammann Jussara. , Mayer Eugène. , Annoni Jean‐Marie. , Van der Linden Martial.
Published: July 2009

Although socio‐emotional changes are very frequently encountered after traumatic brain injury (TBI), the psychological mechanisms underlying these disorders are still poorly understood. This study aimed to explore the relationships between dysexecutive syndrome (assessed with the Behavioural Assessment of the Dysexecutive Syndrome [BADS]) and socio‐emotional changes assessed by the Iowa scales of personality change (ISPC) in patients with TBI. The BADS was thus administered to 25 patients with TBI and to 25 healthy controls. Simultaneously, a close relative of each patient was given the ISPC in order to assess socio‐emotional changes. Results indicated that patients displayed significantly lower executive performances than controls and experimented significant socio‐emotional changes. The Modified Six Elements Test was the only subtask of the BADS to be significantly related to behavioural changes, and more specifically to externalizing disorders. It is concluded that executive functions, and especially multitasking, encompass processes whereby one can consciously control one's emotional reactions and behaviours.
The cohesive power of new management alternatives: principal components of the Irizar model
Authors: Ugarte Luxio , Agirre Amaia , Juaristi Eli
Published: July 2009

The aim of this article is to explore the interesting contributions made by Complexity Sciences to the world of business management. These ideas enable us to see business management as a complex adaptive system with emerging properties (emerging companies), far removed from the mechanical
view, which is now considered anachronistic and obsolete. The article examines the main ideas of complexity science, contrasting them with management practices based on linear thinking and suggests a different way of managing companies. This leads to a description of the philosophy underlying
the management model of Irizar S. Coop., because of the features it shares with those of emerging companies. Finally, using a data set compiled through survey results, the article concludes with an analysis of the key factors behind the management dynamics of the Irizar cooperative.
Mondragon: notes on history, scope and structure
Authors: Freundlich Fred , Grellier Herv , Altuna Rafael
Published: July 2009

This article provides an introduction to the Mondragon cooperative experience. By providing background information on the history, philosophical roots and current scope and structure of the cooperative group, it seeks to set the context for a series of other, more specific articles
to follow in this issue of the Journal.
Specific tax issues of the cooperatives in the Mondragon group
Authors: Aginagalde German
Published: July 2009

Mondragon cooperatives must navigate a complex sea of tax regulation given their character as cooperative enterprises and their location in the Basque Country. This article outlines the tax issues the cooperatives face under these circumstances, that is, given both their specific legal
structure and the special fiscal context of firms headquartered in the Autonomous Basque Community.
The Mondragon experience: serving as a source of inspiration for transfer issues
Authors: Larrasquet Jean Michel , Dupouy Aline
Published: July 2009

The main objective of this article is to identify the key factors associated with the sustainable success of the Mondragon Group (Mondragn Corporacin Cooperativa, MCC) and to investigate their transfer to other contexts. The first main section of this article focuses on the identification
of key best practices that can be considered for transfer. The second section investigates the main conditions for a successful and sustainable transfer and places a greater emphasis on effective collaboration, learning and ethics.
Challenges in Atomic Spectroscopy
Authors: McNally J. R.
Published: July 2009

Three areas of research and development in the field of atomic spectroscopy are discussed and attention called to some of the challenging problems that exist in these areas. In view of the scope of the work to be covered justice cannot be done to any one topic but it is hoped that some of the information may prove of value even if only from the standpoint of broadening one's perspective. The topics to be discussed are: 1. Isotope spectrum shifts and their application to isotopic assay, 2. Atomic energy levels and spectrum line information, and 3. Thermonuclear applications of spectroscopy.
Spectroscopy of Radioactive Materials
Authors: Conway John G.
Published: July 2009

Every element of the 102 that have been discovered has at least one radioactive isotope. Therefore, any discussion of the handling of radioactive materials that attempted to cover all elements would be as varied as the properties of all the elements. There are still seven elements, however, whose emission spectra have not been observed—francium, berkelium, californium, einsteinium, fermium, mendelevium, and the still unnamed element of atomic number 102. When one speaks of radioactive elements, one usually means the group of elements of atomic number greater than xenon including the rare earths, thorium, uranium, and the elements of atomic number greater than uranium. This paper deals more specifically with the actinide group, the elements beyond thorium.
Application of X-Ray Spectroscopy to Unsolved Problems in Geochemistry
Authors: Adler Isidore
Published: July 2009

X-ray spectroscopy already occupies a unique position as one of the most powerful of the nondestructive analytical tools. Great strides forward in instrumentation and technique have led to an increased range of application on a routine basis. Although greater sensitivities are constantly being reported, there is need for still further improvement, and these needs can clearly be demonstrated by reference to specific geochemical and mineralogical problems. Recent researches in the geochemistry of sulfide minerals have shown that the distribution of trace elements between coexisting phases provides important data on the pressures and temperatures of formation of the minerals and quantitative data on the approach to thermodynamic equilibrium between the minerals and the solutions depositing them. This has given rise to a need for nondestructive methods of trace analysis of elements in concentrations of a few parts per million on grains that may be as small as 5 μ in diameter. In petrological studies, problems of compositional zoning of minerals, diffusion across grain boundaries, composition of exsolution bodies, fine-grained intergrowths, and inclusions require very specialized X-ray instrumentation to supply point by point chemical analysis on a microscopic scale.
Special Problems in the Determination of Tetraethyllead in Gasoline by Flame Photometry
Authors: Buell Bruce E.
Published: July 2009

A rapid direct method for the flame photometric determination of tetraethyllead in gasoline is presented. Variations in gasoline composition are compensated by diluting the sample fivefold, considering matrix effects in the choice of a standard solution and in making instrument adjustments. A study of variations in lead emission caused by different gasoline components and pure organic liquids has been made. Variables due to the burner, mirror, and hydrogen flow are discussed. The pooled coefficient of variation using lead naphthenate as a standard is 1.06. The method is accurate within experimental errors. A new approach using lead nitrate in an acetone mixture is presented and appears to give good precision and accuracy.
A Technique for Preparing Solid Organic Samples for Infrared Analysis
Authors: Strait Louis A. , Hrenoff Michael K.
Published: July 2009

A procedure is presented for obtaining well-comminuted and uniformsize particles of nonbrittle samples for dispersion in KBr disks or for other applications for spectrum analysis. A range of nonbrittle materials including tobacco, biological samples, resins, paper, and other organic materials which present a difficult problem, particularly in infrared analysis, have been comminuted at liquid nitrogen temperatures, and their infrared spectra are presented and compared with those from other methods of preparation.
The Application of Some Spectrographic Techniques to the Analysis of Water-Formed Deposits
Authors: Anderson Charles H.
Published: July 2009

The principles of conventional light-emission spectroscopy, flame photometry, and X-ray fluorescence spectroscopy are reviewed briefly as they apply to the determination of elements present in a water-formed deposit. Each field is discussed from the point of view of its applications, its advantages, and its limitations. New developments in each field are also discussed.
The Role of MITF Phosphorylation Sites During Coat Color and Eye Development in Mice Analyzed by Bacterial Artificial Chromosome Transgene Rescue
Authors: Bauer Georg L , Praetorius Christian , Bergsteinsdóttir Kristín , Hallsson Jón H , Gísladóttir Bryndís K , Schepsky Alexander , Swing Deborah A , O'Sullivan T Norene , Arnheiter Heinz , Bismuth Keren , Debbache Julien , Fletcher Colin , Warming Søren , Copeland Neal G , Jenkins Nancy A , Steingrímsson Eiríkur
Published: July 2009

The microphthalmia-associated transcription factor (Mitf) has emerged as an important model for gene regulation in eukaryotic organisms. In vertebrates, it regulates the development of several cell types including melanocytes and has also been shown to play an important role in melanoma. In vitro, the activity of MITF is regulated by multiple signaling pathways, including the KITL/KIT/B-Raf pathway, which results in phosphorylation of MITF on serine residues 73 and 409. However, the precise role of signaling to MITF in vivo remains largely unknown. Here, we use a BAC transgene rescue approach to introduce specific mutations in MITF to study the importance of specific phospho-acceptor sites and protein domains. We show that mice that carry a BAC transgene where single-amino-acid substitutions have been made in the Mitf gene rescue the phenotype of the loss-of-function mutations in Mitf. This may indicate that signaling from KIT to MITF affects other phospho-acceptor sites in MITF or that alternative sites can be phosphorylated when Ser73 and Ser409 have been mutated. Our results have implications for understanding signaling to transcription factors. Furthermore, as MITF and signaling mechanisms have been shown to play an important role in melanomas, our findings may lead to novel insights into this resilient disease.
Signature of Diversifying Selection on Members of the Pentatricopeptide Repeat Protein Family in Arabidopsis lyrata
Authors: Foxe John Paul , Wright Stephen I
Published: July 2009

Pentatricopeptide repeat (PPR) proteins compose a family of nuclear-encoded transcriptional regulators of cytoplasmic genes. They have shown dramatic expansion in copy number in plants, and although the functional importance of many remains unclear, a subset has been repeatedly implicated as nuclear restorers for cytoplasmic male sterility. Here we investigate the molecular population genetics and molecular evolution of seven single-copy PPR genes in the outcrossing model plant Arabidopsis lyrata. In comparison with neutral reference loci, we find, on average, elevated levels of polymorphism and an excess of high-frequency variants at these PPR genes, suggesting that natural selection is maintaining polymorphism at some of these loci. This elevation in diversity persists when we control for divergence and generally decreases in the flanking regions, suggesting that these genes are themselves the targets of selection. Some of the PPR genes also demonstrate elevated population differentiation, which is consistent with spatially varying selection. In contrast, no comparable patterns are observed at these loci in A. thaliana, providing no evidence for the action of balancing selection in this selfing species. Taken together, these results suggest that a subset of PPR genes may be subject to balancing selection associated with ongoing cytonuclear coevolution in the outcrossing A. lyrata, which is possibly mediated either by intergenomic conflict or by compensatory evolution.
Development of Primer-Probe Energy Transfer real-time PCR for the detection and quantification of porcine circovirus type 2
Authors: Bálint Ádám , Tenk Miklós , Deim Zoltán , Rasmussen Thomas , Uttenthal Åse , Cságola Attila , Tuboly Tamás , Farsang Attila , Fossum Caroline , Timmusk Sirje , Berg Mikael , Belák Sándor
Published: July 2009

A real-time PCR assay, based on Primer-Probe Energy Transfer (PriProET), was developed to improve the detection and quantification of porcine circovirus type 2 (PVC2). PCV2 is recognised as the essential infectious agent in post-weaning multisystemic wasting syndrome (PMWS) and has been associated with other disease syndromes such as porcine dermatitis and nephropathy syndrome (PDNS) and porcine respiratory disease complex (PRDC). Since circoviruses commonly occur in the pig populations and there is a correlation between the severity of the disease and the viral load in the organs and blood, it is important not only to detect PCV2 but also to determine the quantitative aspects of viral load. The PriProET real-time PCR assay described in this study was tested on various virus strains and clinical forms of PMWS in order to investigate any correlation between the clinical signs and viral loads in different organs. The data obtained in this study correlate with those described earlier; namely, the viral load in 1 ml plasma and in 500 ng tissue DNA exceeds 107copies in the case of PMWS. The results indicate that the new assay provides a specific, sensitive and robust tool for the improved detection and quantification of PCV2.
Laser-assisted removal of a feline eosinophilic granuloma from the back of the tongue
Authors: Kovács Katalin , Jakab Csaba , Szász Attila
Published: July 2009

Recently, an increase in the occurrence of oral diseases in cats has been observed. Symptoms vary from case to case, but loss of appetite or fastidiousness can almost always be noted. Proliferative inflammatory eosinophilic granulomatosis is a common disease in cats, which may be localised to the skin, the mucocutaneous junctions or the oral cavity. The disease has three different manifestations: indolent cellular ulcer, eosinophilic plaque, and eosinophilic granuloma. The last mentioned form predominantly affects the medial surface of the thigh, the cheek, the tongue and the palate. Pain is not common, the lesion is nonpruritic if localised to the skin, but the nodular form in the oral cavity may make deglutition difficult. In this case, a 10.5-year-old cat was presented in poor condition due to feeding problems. Examination revealed a mass of unknown origin with macroscopically tumorous appearance, localised to the pharyngeal part of the tongue, which made swallowing and voluntary feeding difficult. The granuloma was removed by laser-assisted surgery. After adequate preparation, a LASER diode with 6–10 W output power was used, set to continuous constant-amplitude output (CW) running in a 0.6 mm optic fibre to the site of interest. The removed tissue was examined for pathomorphological features: haematoxylin and eosin, Giemsa, Azan and PAS stainings were performed to aid diagnosis. After surgery the cat recovered fast on steroids, and its condition and quality of life improved greatly. The traditional surgical technique was inapplicable due to the heavy vasculature and corresponding bleeding of the tongue.
Effects of neuropeptides and vasoactive substances on microcirculation of the callus after tibial osteotomy in rabbits
Authors: Vendégh Zsolt , Melly András , Tóth Balázs , Wolf Konrad , Farkas Tamás , Józan Jolán , Hamar János , Kádas István
Published: July 2009

Previous studies have demonstrated a dynamic ingrowth of vessels into the developing callus. In this study, maturation and development of the regulation of microcirculation were followed in the callus of rabbits. In the first series, the effects of vasoactive substances on blood flow velocity, perfusion pressure, duration of effects and peripheral vascular resistance of the bone marrow in the femur and tibia were compared. In the second series, the same parameters were measured in the femur and in the developing callus 10 and 15 days following gap osteotomy of the tibia. There were no significant differences between the microcirculatory reactions of the intact femur and tibia. Basal blood flow could be verified in the callus on the 10th postoperative day. No vascular reactions could be elicited. Basal blood flow velocity was higher on the 15th day, when compared to the measurements on the 10th day. The substances elicited statistically significant differences in flow velocity, resistance and 50% recovery time in the callus on the 15th day. Blood flow reactions of the ipsilateral femoral and tibial bone marrow are identical, thus the femur can serve as a reference site for blood flow measurements in the callus. Regulation and maturation of callus microcirculation develop rapidly between the 10th and 15th days.
Potential Interaction Between Pomegranate Juice and Warfarin
Authors: Komperda Kathy E.
Published: July 2009

To my knowledge, no published reports have described an interaction between pomegranate juice and warfarin. Investigators from previous animal and in vitro studies have reported a potential for pomegranate juice to inhibit metabolism involving the cytochrome P450 system, an effect that could translate into a clinical drug‐diet interaction with warfarin. This case report describes a 64‐year‐old Caucasian woman who was treated with warfarin for recurrent deep vein thrombosis. She had been receiving a relatively stable dosage of warfarin 4 mg/day for several months, with stable international normalized ratios (INRs). During that time, the patient was consuming pomegranate juice 2–3 times/week. She stopped drinking the juice, and her INRs became subtherapeutic. Her dosage of warfarin was increased to maintain therapeutic anticoagulation. No rechallenge with pomegranate juice was performed. Use of the Drug Interaction Probability Scale indicated a possible relationship between the patient's subtherapeutic INR and the pomegranate juice. Although this potential interaction needs to be explored further, clinicians should be aware of the interaction and thoroughly interview and closely monitor their patients who are receiving warfarin.
Assessment of an Alternative Meropenem Dosing Strategy Compared with Imipenem‐Cilastatin or Traditional Meropenem Dosing After Cefepime Failure or Intolerance in Adults with Neutropenic Fever
Authors: Arnold Heather M. , McKinnon Peggy S. , Augustin Kristan M. , Hladnik Lindsay M. , Casabar Ed , Reichley Richard M. , Dubberke Erik R. , Westervelt Peter , Ritchie David J.
Published: July 2009

Study Objective. To compare clinical outcomes of patients receiving an alternative dosage of meropenem with those of patients receiving imipenem‐cilastatin or the traditional dosage of meropenem after failure of or intolerance to cefepime for treatment of febrile neutropenia.

Design. Retrospective, single‐center cohort study.

Setting. 1250‐bed urban academic medical center.

Patients. One hundred twenty‐seven adults with neutropenic fever who received either imipenem‐cilastatin or meropenem; imipenem‐cilastatin was the preferred carbapenem until September 1, 2006, after which meropenem became the formulary carbapenem.

Measurements and Main Results. Of the 127 patients, 40 received imipenem‐cilastatin 500 mg every 6 hours between September 1, 2005, and August 31, 2006; 87 patients received meropenem between September 1, 2006, and August 31, 2007: 29 received a traditional dosage of meropenem 1 g every 8 hours, and 58 received an alternative dosage of meropenem 500 mg every 6 hours. Primary outcomes of time to defervescence (median 3 vs 2 vs 3 days), need for additional antibiotics (20% vs 17% vs 14%), and time to receipt of additional antibiotics (median 5 vs 2 vs 1 days) were not significantly different among the imipenem‐cilastatin, traditionally dosed meropenem, and alternatively dosed meropenem groups, respectively. In addition, significant differences in secondary outcomes, which were treatment duration (median 10 vs 8 vs 8 days), seizure rate (0% vs 0% vs 0%), in‐hospital mortality (5% vs 7% vs 7%), and 30‐day mortality (13% vs 7% vs 14%), were not identified among the three groups, respectively.

Conclusion. The alternative meropenem dosage of 500 mg every 6 hours yielded similar patient outcomes, including time to defervescence, need for additional antibiotics, duration of therapy, and mortality, when compared with the traditional meropenem dosage and imipenem‐cilastatin in adults with febrile neutropenia. In addition, no adverse effects on clinical outcomes were observed with the alternative dosage of meropenem.
Intramuscular Haloperidol versus Intramuscular Olanzapine for Treatment of Acute Agitation: A Cost‐Minimization Study
Authors: Freeman Darren J. , DiPaula Bethany A. , Love Raymond C.
Published: July 2009

Study Objectives. To investigate prescribing patterns for antipsychotic regimens based on intramuscular haloperidol or intramuscular olanzapine for treating acute agitation; to compare the costs of each drug regimen, which included adjunctive anxiolytics and/or anticholinergics; and to compare the effectiveness and safety of each drug regimen.

Design. Retrospective medical record review.

Setting. State psychiatric facility.

Patients. Twenty‐seven patients who received intramuscular haloperidol to treat 47 episodes of acute agitation and 26 patients who received intramuscular olanzapine to treat 38 episodes.

Measurements and Main Results. Data from patients receiving the antipsychotic regimens between August 2004 and March 2007 were reviewed. Mean ± SD doses were 6.4 ± 2.4 mg (range 2.5–10 mg) for haloperidol and 8.1 ± 2.3 mg (range 5–10 mg) for olanzapine. The mean ± SD cost of treating an episode of agitation with haloperidol was significantly lower at $4.06 ± 3.98 (range $1.74‐18.35) versus $27.84 ± 10.40 (range $21.58‐52.46) for olanzapine (p<0.0001). Significantly fewer patients who received haloperidol than patients who received olanzapine required additional pharmacotherapy to manage agitation (41% vs 69%, χ2=4.34, p=0.04). No significant differences were found between groups in the mean number of repeat doses of psychotropic drugs needed/episode (0.6 [range 0–5] for haloperidol vs 0.8 [range 0–3] for olanzapine, p=0.47), in the percentages of patients who required seclusion and/or restraints (59% for haloperidol vs 58% for olanzapine, χ2=0.01, p=0.91), or in time spent in seclusion and/or restraints (3.7 ± 7.1 for haloperidol vs 3.6 ± 6.5 hrs for olanzapine, p=0.92). No adverse events were documented with either drug.

Conclusion. For the treatment of acute episodes of agitation, regimens based on intramuscular haloperidol were significantly less expensive than and at least as effective as those based on intramuscular olanzapine.
Economic Burden of Venous Thromboembolism in Hospitalized Patients
Authors: Dobesh Paul P.
Published: July 2009

Venous thromboembolism, a condition that includes deep vein thrombosis and pulmonary embolism, is a significant medical problem that affects more than 1 million patients each year. In addition to the immense impact of venous thromboembolism on morbidity and mortality, the economic burden of the disease is considerable, costing the health care system in the United States more than $1.5 billion/year. The cost of managing an initial episode of deep vein thrombosis is estimated at $7712‐10,804, and for an initial pulmonary embolism event $9566‐16,644. Management of acute venous thromboembolism in patients with cancer costs more than $20,000. Although much of the costs of venous thromboembolism are associated with managing the acute event, there are also significant costs associated with its long‐term complications such as recurrent venous thromboembolism, post‐thrombotic syndrome, and pulmonary hypertension. Data from numerous robust clinical trials have demonstrated that with appropriate prophylaxis, many of these venous thromboembolism events can be prevented in both surgical and medical patients. Even though the strong evidence supporting venous thromboembolism prophylaxis spans several decades, a number of large American and global registries have documented very poor use of appropriate venous thromboprophylaxis. Because of increasing regulatory requirements, hospitals nationwide are developing necessary documentation of appropriate venous thromboembolism prophylaxis programs for both surgical and medical patients. Hospitals and clinicians must have a firm understanding of not only the clinical impact but also the economic impact of failing to use appropriate prophylaxis and of the cost‐effectiveness of different venous thromboprophylaxis methods.
Overcoming Drug Resistance in Patients with Metastatic Breast Cancer
Authors: Wong Serena T. , Goodin Susan
Published: July 2009

Metastatic breast cancer is generally considered to be incurable, with response rates and duration of response progressively declining with subsequent lines of treatment. Tumors are either intrinsically resistant to systemic therapy or acquire resistance at some point during multiple courses of therapy. Mechanisms of drug resistance are numerous and include accelerated drug efflux, drug activation and inactivation, alterations in drug target, processing of drug‐induced damage, and evasion of apoptosis. Targeted anticancer agents for the treatment of breast cancer, such as hormonal agents or the more recently approved epidermal growth factor receptor inhibitors, are also associated with intrinsic and acquired resistance. A variety of strategies have been devised to prevent or overcome resistance to systemic anticancer therapy, including drug combinations and sequential regimens. However, it appears that resistance to established cytotoxic and targeted agents is inevitable. Novel agents with reduced susceptibility to resistance may prevent or delay the emergence of resistance and improve survival in patients with common solid tumors, including metastatic breast cancer. We are hopeful that further elucidation of the cellular and molecular processes that allow tumor cells to develop resistance and the use of new agents to combat these mechanisms will improve outcomes for patients with metastatic breast cancer.