bluuebunny/crossref_metadata_2025 huggingface dataset:
Vision system for on‐line characterization of paper slurry
Authors: Sari‐Sarraf Hamed , Goddard James S. , Abidi Besma R. , Hunt Martin A.
Published: November 2004

This paper presents a detailed description of a vision system that detects and localizes the nonuniformities that appear on the paper slurry (wood fiber and water mixture) at the wet end of a paper machine. Specifically, the system monitors the paper slurry as it exits the headbox and alerts the operators of any event (e.g., streaks) that disrupts the otherwise homogeneous background. These events affect crucial product properties such as formation. A poor formation results in thick and thin spots on the sheet and impacts its strength and printability. This paper describes the vision system in terms of its hardware modules, as well as the image processing algorithms that it utilizes to perform its function. The system acquires intensity and topographic information from the scene. It uses texture‐based features for the detection and facet‐based descriptors for the localization of the nonuniformities. In addition to being tested in a laboratory environment, a prototype of this system was constructed and deployed to a paper mill, where its performance was evaluated under realistic conditions. Installed on a fourdrinier paper machine, running at 480 m/min and producing linerboard material, the vision system monitored about a 1 m wide area and successfully detected and localized slurry streaks. Published 2001 John Wiley & Sons, Inc. Int J Imaging Syst Technol, 11, 231–242, 2000
Instrumental relationships: A potential relational model for inner‐city youth programs
Authors: Halpern Robert
Published: November 2004

In this article, a distinct type of adult–youth relationship found in some youth programs and characterized as instrumental is discussed. Such relationships focus primarily on joint work on a task or project, or in a discipline, with the adult having expertise and a strong identity in the substantive domain involved, rather than in youth work per se. It is hypothesized that, by virtue of their matter‐of‐fact quality, their substantive focus, and their particular interactional patterns, instrumental relationships offer potential for some reworking of adolescents' sense of self. © 2005 Wiley Periodicals, Inc. J Comm Psychol 33: 11–20, 2005.
On urban ground: Understanding African‐American intergenerational partnerships in urban communities
Authors: Ginwright Shawn A.
Published: November 2004

Fewer job opportunities, rising violence, and failing schools have all shaped the structure of opportunities for both youth and adults in urban communities. However, researchers understand very little about how these factors influence the capacity for adults in urban communities to form meaningful partnerships with youth. First, this article explores how urban environments shape youth–adult partnerships within African‐American communities. Second, the article promotes the idea that adult development is a necessary component of effective intergenerational partnerships in urban communities. Third, the article highlights innovative practices that focus on how to support the development of adults to more effectively partner with young people. © 2005 Wiley Periodicals, Inc. J Comm Psychol 33: 101–110, 2005.
Inhibition of vascular endothelial growth factor with a sequence-specific hypoxia response element antagonist
Authors: Olenyuk Bogdan Z. , Zhang Guo-Jun , Klco Jeffery M. , Nickols Nicholas G. , Kaelin William G. , Dervan Peter B.
Published: November 2004

Vascular endothelial growth factor (VEGF) and its receptors have been implicated as key factors in tumor angiogenesis that are up-regulated by hypoxia. We evaluated the effects of DNA-binding small molecules on hypoxia-inducible transcription of
VEGF
. A synthetic pyrrole-imidazole polyamide designed to bind the hypoxia response element (HRE) was found to disrupt hypoxia-inducible factor (HIF) binding to HRE. In cultured HeLa cells, this resulted in a reduction of VEGF mRNA and secreted protein levels. The observed effects were polyamide-specific and dose-dependent. Analysis of genome-wide effects of the HRE-specific polyamide revealed that a number of hypoxia-inducible genes were down-regulated. Pathway-based regulation of hypoxia-inducible gene expression with DNA-binding small molecules may represent a new approach for targeting angiogenesis.
Simulation of the activation of α‐chymotrypsin: Analysis of the pathway and role of the propeptide
Authors: Mátrai Janka , Verheyden Gert , Krüger Peter , Engelborghs Yves
Published: November 2004

α‐Chymotrypsin undergoes a reversible conformational change from an inactive chymotrypsinogen‐like structure at high pH to an active conformation at neutral pH. In order to gain insight into this process on a structural level, we applied molecular dynamics and targeted molecular dynamics simulations in aqueous environment on the activation and inactivation processes of three different types of chymotrypsin. These are the wild‐type bovine chymotrypsin containing the propeptide and the bovine and rat chymotrypsin lacking the propeptide. From these simulations, the importance of the propeptide and of the sequence differences between the rat and bovine variants from the viewpoint of activation could be evaluated and compared with previous fluorescence stopped flow results. The obtained results show the unambiguous influence of the propeptide on the explored conformational space, whereas the sequence differences between bovine and rat chymotrypsin play a minor role. The main features of activation are present in both the wild type and the variant lacking the propeptide, despite the fact that different parts of the conformational space were explored. The comparison of all trajectories shows that particular amino acid residues, such as 17, 18, 19, 187, 217, 218, and 223, undergo large dihedral transitions during the activation process, suggesting a role as hinge residues during the conformational change.
Comparative computational analysis of prion proteins reveals two fragments with unusual structural properties and a pattern of increase in hydrophobicity associated with disease‐promoting mutations
Authors: Kuznetsov Igor B. , Rackovsky Shalom
Published: November 2004

Prion diseases are a group of neurodegenerative disorders associated with conversion of a normal prion protein, PrPC, into a pathogenic conformation, PrPSc. The PrPSc is thought to promote the conversion of PrPC. The structure and stability of PrPC are well characterized, whereas little is known about the structure of PrPSc, what parts of PrPC undergo conformational transition, or how mutations facilitate this transition. We use a computational knowledge‐based approach to analyze the intrinsic structural propensities of the C‐terminal domain of PrP and gain insights into possible mechanisms of structural conversion. We compare the properties of PrP sequences to those of a PrP paralog, Doppel, and to the distributions of structural propensities observed in known protein structures from the Protein Data Bank. We show that the prion protein contains at least two sequence fragments with highly unusual intrinsic propensities, PrP(114–125) and helix B. No segments with unusual properties were found in Doppel protein, which is topologically identical to PrP but does not undergo structural rearrangements. Known disease‐promoting PrP mutations form a statistically significant cluster in the region comprising helices B and C. Due to their unusual properties, PrP(114–125) and the C terminus of helix B may be considered as primary candidates for sites involved in conformational transition from PrPC to PrPSc. The results of our study also show that most PrP mutations associated with neurodegenerative disorders increase local hydrophobicity. We suggest that the observed increase in hydrophobicity may facilitate PrP‐to‐PrP or/and PrP‐to‐cofactor interactions, and thus promote structural conversion.
Correspondence between anomalous m‐ and Δ Cp‐values in protein folding
Authors: Otzen Daniel E. , Oliveberg Mikael
Published: November 2004

Proteins folding according to a classical two‐state system characteristically show V‐shaped chevron plots. We have previously interpreted the symmetrically curved chevron plot of the protein U1A as denaturant‐dependent movements in the position of the transition state ensemble (TSE). S6, a structural analog of U1A, shows a classical V‐shaped chevron plot indicative of straightforward two‐state kinetics, but the mutant LA30 has a curved unfolding limb, which is most consistent with TSE mobility. The kinetic m‐values (derivatives of the rate constants with respect to denaturant concentration) in themselves depend on denaturant concentration. To obtain complementary information about putative mobile TSEs, we have carried out a thermodynamic analysis of the three proteins, based on data for refolding and unfolding over the range 10°C to 70°C. The data at all temperatures can be fitted to two‐state model systems. Importantly, for all three proteins the activation heat capacities are, within error, identical to the heat capacities measured in independent experiments under equilibrium conditions. Although the equilibrium heat capacities are essentially invariant with regard to denaturant concentration, the activation heat capacities, similar to the structurally equivalent kinetic m‐values, show marked denaturant dependence. Furthermore, the values of β‡ at different denaturant concentrations measured by m‐values and by heat capacity values are very similar. These observations are consistent with significant transition state movements within the framework of two‐state folding. The basis for TSE movement appears to be enthalpic rather than entropic, suggesting that the binding energy of denaturant–protein interactions is a major determinant of the response of energy landscape contours to changing environments.
CATERPILLER: A Novel Gene Family Important in Immunity, Cell Death, and Diseases
Authors: Ting Jenny P-Y. , Davis Beckley K.
Published: November 2004

▪ Abstract  The newly discovered CATERPILLER (CLR) gene family encodes proteins with a variable but limited number of N-terminal domains, followed by a nucleotide-binding domain (NBD) and leucine-rich repeats (LRR). The N-terminal domain consists of transactivation, CARD, Pyrin, or BIR domains, with a minority containing undefined domains. These proteins are remarkably similar in structure to the TIR-NBD-LRR and CC-NBD-LRR disease resistance (R) proteins that mediate immune responses in plants. The NBD-LRR architecture is conserved in plants and vertebrates, but only remnants are found in worms and flies. The CLRs regulate inflammatory and apoptotic responses, and some act as sensors that detect pathogen products. Several CLR genes have been genetically linked to susceptibility to immunologic disorders. We describe prominent family members, including CIITA, CARD4/NOD1, NOD2/CARD15, CIAS1, CARD7/NALP1, and NAIP, in more detail. We also discuss implied roles of these proteins in diversifying immune detection and in providing a check-and-balance during inflammation.
QUANTUM MODE-COUPLING THEORY: Formulation and Applications to Normal and Supercooled Quantum Liquids
Authors: Rabani Eran , Reichman David R.
Published: November 2004

▪ Abstract  We review our recent efforts to formulate and study a mode-coupling approach to real-time dynamic fluctuations in quantum liquids. Comparison is made between the theory and recent neutron scattering experiments performed on liquid ortho-deuterium and para-hydrogen. We discuss extensions of the theory to supercooled and glassy states where quantum fluctuations compete with thermal fluctuations. Experimental scenarios for quantum glassy liquids are briefly discussed.
Syk tyrosine kinase participates in β1-integrin signaling and inflammatory responses in airway epithelial cells
Authors: Ulanova Marina , Puttagunta Lakshmi , Marcet-Palacios Marcelo , Duszyk Marek , Steinhoff Ulrich , Duta Florentina , Kim Moo-Kyung , Indik Zena K. , Schreiber Alan D. , Befus A. Dean
Published: November 2004

The protein tyrosine kinase Syk is critically involved in immunoreceptor signaling in hematopoietic cells. Recent studies demonstrate Syk expression in nonhematopoietic cells, including fibroblasts, endothelial cells, hepatocytes, and breast epithelium. However, the role of Syk in these cells is uncertain. We hypothesized that Syk is expressed in respiratory epithelial cells (EC) and that it functions as a signaling molecule involved in inflammatory responses in the epithelium. With the use of immunohistochemistry, Western blot, PCR, and laser scanning confocal microscopy, Syk was detected in human, rat, and mouse bronchial epithelium in situ and in cultured human bronchial EC in primary cells and the cell lines HS-24 and BEAS-2B. Syk-dependent signaling pathways in EC were initiated by engagement of β1-integrin receptors. Stimulation of β1-integrin receptors by fibronectin or antibody cross-linking caused redistribution of Syk from a cytoplasmic to plasma membrane localization. In stimulated cells, Syk and β1-integrin colocalized. In addition, following β1-integrin receptor engagement, tyrosine phosphorylation of Syk was observed. Expression of the intercellular adhesion molecule-1 (ICAM-1) and production of IL-6, both important molecules in lung inflammation, was downregulated in EC treated with Syk small interfering RNA or Syk inhibitor piceatannol. We propose that Syk is involved in signaling pathways induced by integrin engagement in airway EC. Syk-mediated signaling regulates IL-6 and ICAM-1 expression and may be important in the pathophysiology of lung inflammation.
Orexin stimulates breathing via medullary and spinal pathways
Authors: Young John K. , Wu Mingfei , Manaye Kebreten F. , Kc Prabha , Allard Joanne S. , Mack Serdia O. , Haxhiu Musa A.
Published: November 2004

A central neuronal network that regulates respiration may include hypothalamic neurons that produce orexin, a peptide that influences sleep and arousal. In these experiments, we investigated 1) projections of orexin-containing neurons to the pre-Bötzinger region of the rostral ventrolateral medulla that regulates rhythmic breathing and to phrenic motoneurons that innervate the diaphragm; 2) the presence of orexin A receptors in the pre-Bötzinger region and in phrenic motoneurons; and 3) physiological effects of orexin administered into the pre-Bötzinger region and phrenic nuclei at the C3–C4 levels. We found orexin-containing fibers within the pre-Bötzinger complex. However, only 0.5% of orexin-containing neurons projected to the pre-Bötzinger region, whereas 2.9% of orexin-containing neurons innervated the phrenic nucleus. Neurons of the pre-Bötzinger region and phrenic nucleus stained for orexin receptors, and activation of orexin receptors by microperfusion of orexin in either site produced a dose-dependent, significant ( P < 0.05) increase in diaphragm electromyographic activity. These data indicate that orexin regulates respiratory activity and may have a role in the pathophysiology of sleep-related respiratory disorders.
The Janus Face of Religion: On the Religious Factor in "New Wars"
Authors: Schäfer Heinrich
Published: November 2004

Every religion can be a base for respect and for violence. This is how the Bosnian peace activist Cvijeta Novacovic puts it. The Janus face of religion becomes especially visible when religion and politics mingle closely. This is the case in many of the so called "new wars," as for example in Bosnia, Kashmir, Sri Lanka, and other places. The present article focuses on how religion works within conflictive environments to mobilize people and to re-structure their identities. First, we will examine the special dynamics of new wars in order to focus the problem. Then, religion will be framed as a specific strategy of identity politics. On this basis we can analyze some ways by which religious logics operate in conflictive settings — for violence or for respect. The Bosnian war will serve as an example in most parts of the article.
Ham-Wasserman Lecture
Authors: Higgs Douglas R.
Published: November 2004

Over the past fifty years, many advances in our understanding of the general principles controlling gene expression during hematopoiesis have come from studying the synthesis of hemoglobin. Discovering how the α and β globin genes are normally regulated and documenting the effects of inherited mutations which cause thalassemia have played a major role in establishing our current understanding of how genes are switched on or off in hematopoietic cells. Previously, nearly all mutations causing thalassemia have been found in or around the globin loci, but rare inherited and acquired trans-acting mutations are being found with increasing frequency. Such mutations have demonstrated new mechanisms underlying human genetic disease. Furthermore, they are revealing new pathways in the regulation of globin gene expression which, in turn, may eventually open up new avenues for improving the management of patients with common types of thalassemia.
Hodgkin’s Lymphoma: Evolving Concepts with Implications for Practice
Authors: Meyer Ralph M. , Ambinder Richard F. , Stroobants Sigrid
Published: November 2004

Hodgkin’s lymphoma is a unique neoplasm of B lymphocytes. Recent data provide new understandings of the pathogenesis and options for staging and therapy of the disease. Three specific topics are addressed in this chapter.

In Section I, Dr. Richard Ambinder reviews implications of the relationship of Epstein-Barr virus (EBV) and Hodgkin’s lymphoma. This relation includes varying geographic epidemiologic associations, including varying associations with the clinical syndrome of infectious mononucleosis. There are plausible mechanisms, including processes initiated by viral proteins, by which EBV might lead to tumorigenesis. These mechanisms include promotion of genetic instability and alteration of normal processes of apoptosis. In addition to an epidemiologic association and potential role in pathogenesis, viral antigens may pose theoretical targets for anti-cancer therapies, including vaccination.

In Section II, Dr. Sigrid Stroobants describes the potential role of positron emission tomographic (PET) scanning. By assessing differences in the metabolic activities of cancer cells, PET scanning may be superior to computerized tomographic scanning, which is limited to showing structural anatomical abnormalities. In patients with Hodgkin’s and non-Hodgkin’s lymphoma, PET scanning has been tested as an initial staging tool, to assess the rate of therapeutic response from a prognostic perspective, and to differentiate residual tumor from fibrotic masses in patients who have completed therapy. Particularly in assessing the nature of a residual mass seen with other post-therapeutic imaging modalities, PET scanning may provide unique information; very high negative predictive values have been reported. However, before this technology can be recommended for incorporation into standard management, properly conducted prospective trials are required to better evaluate the clinical utility of PET with respect to eventual patient outcomes.

In Section III, Dr. Ralph Meyer reviews current data regarding the management of patients with limited-stage Hodgkin’s lymphoma. Over the past decade, standard treatment has evolved to consist of combined-modality therapy that includes an abbreviated course of chemotherapy and involved-field radiation. As this therapy continues to include radiation therapy, patients will remain at risk of long-term toxicities that include the development of second cancers and cardiovascular events. These “late-effects” now account for more deaths than those attributed to progressive Hodgkin’s lymphoma. Comparative data testing the role of chemotherapy alone are now available and demonstrate that omission of radiation therapy results in small but statistically significant reduction in disease control, but no detectable differences in overall survival. Further follow-up will clarify whether chemotherapy alone is the preferred treatment option; at present patients should be informed of the trade-offs involved in choosing between this option and combined modality therapy.
Myelodysplastic Syndromes
Authors: List Alan F. , Vardiman James , Issa Jean-Pierre J. , DeWitte Theo M.
Published: November 2004

The development of new therapeutic strategies for myelodysplastic syndromes (MDS) has gained new momentum fueled by improved characterization of the disease’s natural history and biology and by the recent US Food and Drug Administration (FDA) approval of the first agent with an indication for MDS. By integrating morphologic and cytogenetic features with greater discriminatory power, the World Health Organization (WHO) has refined the classification of these stem cell malignancies and enhanced its prognostic utility. Recognition that the malignant phenotype, which characterizes MDS, may arise from mechanistically diverse biological processes has raised new awareness that treatment strategies must be tailored to the pathobiology of the disease. Therapeutics targeting chromatin structure, angiogenesis and the microenvironment that nurtures the MDS phenotype have demonstrated remarkable activity and offer an opportunity to alter the natural history of the disease. This chapter provides an overview of recent developments in the characterization of MDS from the microscope to the laboratory and the translation of these findings into promising therapeutics.

In Section I, Dr. James Vardiman reviews the cytogenetic abnormalities that characterize MDS, their clinical and pathologic significance, and the application of the WHO classification. In Section II, Dr. Alan List reviews treatment goals driven by prognostic variables and biological features of the disease that have led to promising small molecule, selective therapeutics. In Section III, Dr. Jean-Pierre Issa provides an overview of epigenetic events regulating gene expression, which may be exploited therapeutically by chromatin remodeling agents. In Section IV, Dr. Theo DeWitte discusses new developments in hematopoietic stem cell transplantation, including reduced-intensity and myeloablative approaches.
Thrombophilia and New Anticoagulant Drugs
Authors: Weitz Jeffrey I. , Middeldorp Saskia , Geerts William , Heit John A.
Published: November 2004

Venous thromboembolism, which includes deep vein thrombosis and pulmonary embolism, is the result of an imbalance among procoagulant, anticoagulant and profibrinolytic processes. This imbalance reflects a complex interplay between genetic and environmental or acquired risk factors. Genetic thrombophilic defects influence the risk of a first episode of thrombosis. How these defects influence the risk of recurrence in patients whose first episode of venous thromboembolism was unprovoked is less certain. Thus, when anticoagulants are stopped, patients with unprovoked venous thromboembolism have a risk of recurrence of at least 7% to 10% per year, even in the absence of an underlying thrombophilic defect. Consequently, there is a trend toward longer durations of anticoagulation therapy for these patients, which is problematic given the limitation of existing anticoagulants. This chapter provides an overview of the thrombophilic defects and how they influence the risk of venous thromboembolism. The chapter also details advances in anticoagulant therapy, focusing on new inhibitors of factor Xa and thrombin.

In Section I, Dr. Saskia Middeldorp describes the various thrombophilic defects and reviews their relative importance in the pathogenesis of a first episode of venous thromboembolism. She then discusses the influence of these defects on the risk of recurrent thrombotic events in patients with unprovoked venous thromboembolism and in those whose thrombosis occurred in association with a known risk factor, such as surgery.

In Section II, Dr. William Geerts reviews the pharmacology of new parenteral and oral factor Xa inhibitors and describes the results of the Phase II and III clinical trials with these agents. He then provides perspective on the potential advantages and drawbacks of these drugs for the prevention and treatment of venous thromboembolism.

In Section III, Dr. John Heit focuses on direct thrombin inhibitors. He discusses their mechanism of action and compares and contrasts their pharmacological profiles prior to describing the results of Phase II and III clinical trials. Dr. Heit then provides perspective on the potential advantages and limitations of these drugs relative to existing anticoagulants.
Transfusion Medicine
Authors: Goodnough Lawrence T. , Hewitt Patricia E. , Silliman Christopher C.
Published: November 2004

In the vein-to-vein flow of blood from donor to patient, the role of the transfusion medicine specialist has become increasingly centered at the bedside. Three clinically centered issues in blood safety and in blood conservation are presented in this chapter.

In Section I, Dr. Patricia Hewitt presents the epidemiologic and clinical evidence regarding new variant Creutzfeldt-Jakob disease (nvCJD) in the UK and its relevance to transfusion medicine. Lessons learned from the responses by the National Blood Service to this crisis are discussed, particularly in the context of recent evidence of a case of vCJD transmission by blood transfusion and a second case of apparent transmission of abnormal prion protein without development of clinical illness.

In Section II, Dr. Christopher Silliman and his colleagues summarize recent knowledge gained regarding transfusion-related acute lung injury (TRALI), which is now the leading cause of transfusion-related mortality. Two different etiologies have been proposed: a single antibody-medicated event, involving anti-HLA Class I and Class II, or anti-granulocyte antibodies; and a two-event model, which includes the clinical condition of the patient resulting in pulmonary endothelial activation and neutrophil sequestration. The second event is the transfusion of a biologic response modifier (lipids or antibodies) in the blood component that activates primed neutrophils. Prevention, clinical treatment, and proposed definition of TRALI are discussed.

In Section III, Dr. Lawrence Goodnough and colleagues present a transfusion medicine service approach to the utilization of recombinant factor VIIa (rFVIIa) in non-approved clinical settings. rFVIIa has a potential role as a hemostatic intervention in a variety of clinical settings, yet few clinical trials have been completed to date to guide indications for its use. The policies presented here are those in place at the authors’ medical center, and will undergo periodic review and revision as relevant new information and data are generated.
Immune-Mediated Hemolytic Anemia
Authors: Rosse Wendell F. , Hillmen Peter , Schreiber Alan D.
Published: November 2004

Hemolytic anemia due to immune function is one of the major causes of acquired hemolytic anemia. In recent years, as more is known about the immune system, these entities have become better understood and their treatment improved. In this section, we will discuss three areas in which this progress has been apparent.

In Section I, Dr. Peter Hillmen outlines the recent findings in the pathogenesis of paroxysmal nocturnal hemoglobinuria (PNH), relating the biochemical defect (the lack of glycosylphosphatidylinositol [GPI]-linked proteins on the cell surface) to the clinical manifestations, particularly hemolysis (and its effects) and thrombosis. He discusses the pathogenesis of the disorder in the face of marrow dysfunction insofar as it is known. His major emphasis is on innovative therapies that are designed to decrease the effectiveness of complement activation, since the lack of cellular modulation of this system is the primary cause of the pathology of the disease. He recounts his considerable experience with a humanized monoclonal antibody against C5, which has a remarkable effect in controlling the manifestations of the disease. Other means of controlling the action of complement include replacing the missing modulatory proteins on the cell surface; these studies are not as developed as the former agent.

In Section II, Dr. Alan Schreiber describes the biochemistry, genetics, and function of the Fcγ receptors and their role in the pathobiology of autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura due to IgG antibodies. He outlines the complex varieties of these molecules, showing how they vary in genetic origin and in function. These variations can be related to three-dimensional topography, which is known in some detail. Liganding IgG results in the transduction of a signal through the tyrosine-based activation motif and Syk signaling. The role of these receptors in the pathogenesis of hematological diseases due to IgG antibodies is outlined and the potential of therapy of these diseases by regulation of these receptors is discussed.

In Section III, Dr. Wendell Rosse discusses the forms of autoimmune hemolytic anemia characterized by antibodies that react preferentially in the cold–cold agglutinin disease and paroxysmal cold hemoglobinuria (PCH). The former is due to IgM antibodies with a common but particular structure that reacts primarily with carbohydrate or carbohydrate-containing antigens, an interaction that is diminished at body temperature. PCH is a less common but probably underdiagnosed illness due to an IgG antibody reacting with a carbohydrate antigen; improved techniques for the diagnosis of PCH are described. Therapy for the two disorders differs somewhat because of the differences in isotype of the antibody. Since the hemolysis in both is primarily due to complement activation, the potential role of its control, as by the monoclonal antibody described by Dr. Hillmen, is discussed.
Acute Myeloid Leukemia
Authors: Stone Richard M. , O'Donnell Margaret R. , Sekeres Mikkael A.
Published: November 2004

Advances in our understanding of the pathophysiology of acute myeloid leukemia (AML) have not yet led to major improvements in disease-free and overall survival of adults with this disease. Only about one-third of those between ages 18–60 who are diagnosed with AML can be cured; disease-free survival is rare and current therapy devastating in older adults. In this chapter, challenges in the management of the adult with AML are discussed, including ongoing questions concerning the optimal choice of induction and postremission therapy such as the rationale for and role of allogeneic and autologous stem cell transplantation in a variety of settings, the special considerations pertaining to the older patient, and the development of new, so-called targeted therapies.

In Section I, Dr. Richard Stone reviews state-of the-art therapy in AML in the era of change from a morphological to a genetically based classification system. Questions being addressed in ongoing randomized cooperative group trials include anthracycline dose during induction, the efficacy of drug-resistance modulators, and the utility of pro-apoptotic agents such as the anti-bcl-2 antisense oligonucloetide. Developmental therapeutics in AML include drug resistance modulation, anti-angiogenic strategies, immunotherapy, and signal transduction-active agents, particularly the farnesyl transferase inhibitors as well as those molecules that inhibit the FLT3 tyrosine kinase, activated via mutation in 30% of patients.

In Section II Dr. Margaret O’Donnell discusses the role of stem cell transplantation in AML. Several advances including expanded donor pools, the movement toward peripheral blood stem cell collection, newer immunosuppressive drugs and antifungals, and particularly the advent of nonmyeloablative transplant have made the allogeneic option more viable. The subset-specific role for high-dose chemotherapy with autologous stem cell support and/or for allogeneic transplant in AML patients in first remission is outlined. Although preconceived notions about the role of transplant abound, the clinical data supporting a risk-adapted approach are covered. Finally, guidance concerning the use of nonmyeloablative or reduced-intensity allogeneic transplantation is provided.

In Section III Dr. Mikkael Sekeres reviews the approach to the older patient with AML. Unique biological and therapeutic considerations make AML in this age group a vastly different disease than that in younger adults. The outcome data, including the role of specific anthracylines, hematopoietic growth factors, and drug-resistance modulators, are summarized. Communicating with older adults with AML and their families regarding selection of the optimal treatment strategy, often a stark choice between induction chemotherapy and palliative care, is covered.
Hereditary risk factors for the development of gastric cancer in younger patients
Authors: Yaghoobi Mohammad , Rakhshani Naser , Sadr Farhad , Bijarchi Raheleh , Joshaghani Yasamin , Mohammadkhani Ashraf , Attari Arezou , Akbari Mohammad Reza , Hormazdi Mahshid , Malekzadeh Reza
Published: November 2004

Background

It is believed that the development of gastric cancer (GC) before the age of 50 has a hereditary basis. Blood group A and history of gastric cancer in first-degree relatives have been shown to be risk factors for GC.

Methods

In this case-control study, we enrolled patients with GC who were diagnosed before the age of 50. Patients who were diagnosed as having GC were selected. A total of 534 cases were found; of these, 44 diagnosed before the age of 50 were included in the case group. For the control group, 22 males and 22 females were randomly selected from the remaining subjects, who had diagnoses of GC after the age of 50. All the surviving patients and family members of the dead patients were interviewed about the history of cancer in the family and the age at which other family members developed cancer. The blood group of each subject was also obtained.

Results

forty-four cases under 50 years old (mean age: 36.2 years) and forty-four controls (mean age: 67.1 years) were enrolled in the study. At the time of the study, 59.1% of the study group and 50% of the control group were alive (P value = NS). In the study group, 68.1%, 13.6%, 13.6% and 4.5% had blood groups O, A, B and AB, respectively. In the control group the corresponding figures were 27.7%, 63.6%, 6.8% and 4.5%. First or second-degree relatives with cancer, including gastric (the most frequent), breast, lung, gynecological and hematological malignancies, were noted in 54.5% of the cases and 11.4% of the controls (p < 0.01). Family histories of cancer were accepted as valid provided that they were based on valid medical documents.

Conclusions

It seems that the development of GC before the age of 50 is likely to be accompanied by familial susceptibility. Interestingly, our study showed a significant correlation between blood group O and the development of gastric cancer under the age of 50.
Multimodal pressure-flow method to assess dynamics of cerebral autoregulation in stroke and hypertension
Authors: Novak Vera , Yang Albert CC , Lepicovsky Lukas , Goldberger Ary L , Lipsitz Lewis A , Peng Chung-Kang
Published: November 2004

Background

This study evaluated the effects of stroke on regulation of cerebral blood flow in response to fluctuations in systemic blood pressure (BP). The autoregulatory dynamics are difficult to assess because of the nonstationarity and nonlinearity of the component signals.

Methods

We studied 15 normotensive, 20 hypertensive and 15 minor stroke subjects (48.0 ± 1.3 years). BP and blood flow velocities (BFV) from middle cerebral arteries (MCA) were measured during the Valsalva maneuver (VM) using transcranial Doppler ultrasound.

Results

A new technique, multimodal pressure-flow analysis (MMPF), was implemented to analyze these short, nonstationary signals. MMPF analysis decomposes complex BP and BFV signals into multiple empirical modes, representing their instantaneous frequency-amplitude modulation. The empirical mode corresponding to the VM BP profile was used to construct the continuous phase diagram and to identify the minimum and maximum values from the residual BP (BPR) and BFV (BFVR) signals. The BP-BFV phase shift was calculated as the difference between the phase corresponding to the BPR and BFVR minimum (maximum) values. BP-BFV phase shifts were significantly different between groups. In the normotensive group, the BFVR minimum and maximum preceded the BPR minimum and maximum, respectively, leading to large positive values of BP-BFV shifts.

Conclusion

In the stroke and hypertensive groups, the resulting BP-BFV phase shift was significantly smaller compared to the normotensive group. A standard autoregulation index did not differentiate the groups. The MMPF method enables evaluation of autoregulatory dynamics based on instantaneous BP-BFV phase analysis. Regulation of BP-BFV dynamics is altered with hypertension and after stroke, rendering blood flow dependent on blood pressure.
Hematological changes during short-term tidal flow extracorporeal life support
Authors: Griffith G W , Toomasian J M , Schreiner R J , Dusset C M , Cook K E , Osterholzer K R , Merz S I , Bartlett R H
Published: November 2004

Various methods exist in the clinical practice of long-term venovenous (VV) extracorporeal life support (ECLS). Among the clinical techniques used are single venous access with a dual-lumen catheter, and cannulation of the jugular and femoral veins. Tidal flow VV ECLS uses a single-lumen catheter to achieve both venous drainage and arterialized reinfusion through a series of tubing occluders that are automated by a pump. A single venous occluder tidal flow system with a 15 Fr single-lumen cannula (n- 6) and passive filling M pump was compared to a conventional 14 Fr dual-lumen cannula (n- 7) and roller pump for four hours of VV ECLS. The changes in platelet count and plasma-free hemoglobin (pHgb) were compared. The results showed a decline in platelet counts typical of ECLS in both groups that were not significantly different from each other. A small elevation in pHgb did not rise above normal clinical levels of 15 mg/dL in either group after four hours of ECLS. Some recirculation was observed and needs to be addressed in future studies. Single occluder tidal flow ECLS may be feasible and efficacious for long-term application once recirculation is resolved and the system evaluated for long-term support.
A perfusionist’s role in lung transplant preservation
Authors: Tierney Alyssa , Foster Robert , Ogella David
Published: November 2004

The major obstacles of organ transplantation are the shortage of available organs from donors and the limited time an organ remains viable. The scarcity of organs has increased the importance of effective preservation technology. The optimal lung preservation techniques are controversial and in a state of evolution. Recent areas of research include the ideal perfusate solution, the benefit of different pharmacological additives and the best techniques for organ preservation. Our technique for lung preservation has yielded highly successful results. The perfusionist delivers 4-5 L of modified Euro-Collins solution and 500 mg of prostaglandin E1 through a circuit. The designed circuit allows the perfusate to be delivered cold and at a pressure less than 40 mmHg via the use of a manually operated centrifugal pump. Results: In 2002, the operative mortality for all lung transplants was 2.7%. One-year and two-year survival for recipients was 79% and 68% respectively; the national average for one-year survival was around 77% with a 9% mortality. As organ transplant surgery continues to grow, effective organ preservation techniques and technology will expand as well.
Influence of pericardial suction blood retransfusion on memory function and release of protein S100B
Authors: Svenmarker S , Engström K G , Karlsson T , Jansson E , Lindholm R , Åberg T
Published: November 2004

Background: To study the influence of pericardial suction blood (PSB) on postoperative memory disturbances and release patterns of protein S100B during and after cardiopulmonary bypass (CPB).

Methods: Sixty male patients admitted for coronary artery bypass surgery were prospectively randomized to receive PSB either by using conventional cardiotomy suction retransfusion or after cell-saver processing.

Results: The concentration of S100B rose during the period of CPB from 0.065±0.004 to 0.24±0.001 mg/L (p<0.001). PSB contained 18.0±1.7 mg/L of S100B. Direct retransfusion from the cardiotomy reservoir made the systemic level increase to 1.42±0.19 mg/L compared to 0.25±0.02 mg/L using a cell-saver. Signs of postoperative memory dysfunction (> 1 SD) were discovered in one of three tests, but were unrelated to technique of retransfusion. No associations were found between serum concentrations of S100B and memory function.

Conclusion: In this study, retransfusion of PSB during cardiac surgery appeared not to cause memory disturbances. PSB contained high concentrations of protein S100B making its use as a marker of cerebral injury unsuitable.
Treatment of recurrent posterior dislocation of the shoulder in cerebral palsy by injection with botulinum toxin A into the M. subscapularis
Authors: de Boer K S , Rozing P M , Arendzen J H
Published: November 2004

Subjects: A 20-year-old woman, known to have cerebral palsy and a spastic hemiparesis, suffered from frequent (up to 20 times a day) and painful posterior dislocation of the affected shoulder.

Interventions: For the last two years we have treated her with injections with botulinum toxin A (100 U Botox®) in the M. subscapularis.

Results: Pain and dislocation rate have improved substantially.
Assessment of apraxia: inter-rater reliability of a new apraxia test, association between apraxia and other cognitive deficits and prevalence of apraxia in a rehabilitation setting
Authors: Zwinkels Angeliek , Geusgens Chantal , van de Sande Peter , van Heugten Caroline
Published: November 2004

Objective: To investigate the inter-rater reliability of a new apraxia test. Furthermore to examine the association of apraxia with other neuropsychological impairments and the prevalence of apraxia in a rehabilitation setting on the basis of the new test.

Design: Cross-sectional cohort study, involving 100 patients with a first stroke admitted to a rehabilitation centre in the Netherlands.

Measures: General patient characteristics and stroke-related aspects. Cognitive screening involving apraxia, visuospatial scanning, abstract thinking and reasoning, memory, attention, planning and aphasia.

Results: The indices for inter-rater agreement range from excellent to poor. Significant correlations are found between apraxia and visuospatial scanning, memory, attention, planning and aphasia. The patients with apraxia perform significantly worse than the patients without apraxia on memory, the time needed to complete the tests for scanning and attention, and aphasia. The prevalence of apraxia is 25.3% in the total group, 51.3% in the left hemisphere stroke patients and 6.0% in the right hemisphere stroke patients. Patients with and without apraxia do not differ significantly concerning age, gender and type of stroke.

Conclusion: The apraxia test has been shown to be a reliable instrument. Apraxia is often associated with aphasia, memory problems and mental slowness. This study shows that on the basis of the apraxia test, the prevalence of apraxia among patients in the rehabilitation centre is high, especially among patients with left hemisphere lesions.
Berg Balance Scale and Functional Reach: determining the best clinical tool for individuals post acute stroke
Authors: Smith Patricia S , Hembree Judith A , Thompson Mary E
Published: November 2004

Objective: To begin the process of determining the best clinical tool for measuring balance in individuals post stroke.

Design: Prospective with descriptive and relational analyses.

Setting: Rehabilitation centres and stroke support group meetings.

Subjects: Seventy-five subjects who had suffered a stroke were divided into four groups based on the Duncan classification for stroke severity.

Main outcome measures: The motor section of the Fugl-Meyer Assessment of Physical Performance was completed for each person to classify the motor deficit. Subjects performed Functional Reach twice with the nonparetic arm and the average was recorded. Subjects performed the Berg Balance Scale and the total score on the first attempt was recorded.

Results: As motor impairment increased, balance ability declined and both the Functional Reach and Berg Balance Scale proved sensitive to this decline. Spearman rank correlation coefficient was excellent among the entire sample (rs-0.78).

Conclusion: Subjects' performance on the Berg Balance Scale was closely associated with performance on the Functional Reach. Therefore, the clinician may elect to use the shorter Functional Reach as a measure of balance where efficient use of time is the primary goal.
A newly recognized syndrome involving limbs, pelvis, and genital organs or a variant of Al‐Awadi/Raas‐Rothschild syndrome?
Authors: Kantaputra Piranit N. , Tanpaiboon Pranoot
Published: November 2004

We report on a 3‐year‐old Thai boy with limb, pelvic, and genital malformations. The combination of findings found in this patient is similar to that of Al‐Awadi/Raas‐Rothchild syndrome (AARRS) or limb/pelvis hypoplasia/aplasia syndrome. The upper limbs are more severely affected than the lower ones. Unlike that of AARRS, the radial ray is more severely affected than the ulnar ray. The presence of humeroulnar synostosis and humero‐ulnar‐radial synostosis and the absence of a radius distinguishes it from AARRS. The similarities and dissimilarities between the features in the present patient and other limb‐pelvic hypoplasia/aplasia syndromes are discussed. The findings in this group of patients appear to demonstrate limb‐pelvis‐genital organ developmental field defects. © 2004 Wiley‐Liss, Inc.
Four themes in youth work practice
Authors: Krueger Mark
Published: November 2004

With the purpose of contributing to the research and discussion about youth work as a contextual, interpersonal process of human interaction, it is suggested that youth work is like a modern dance that works best when youth workers are present, in sync with youth development rhythms for trusting and growing and making meaning in an atmosphere that supports their interactions. The article includes a brief definition of youth work, a method of reflective practice, and descriptions of the four themes—presence, rhythmic interaction, meaning making, and atmosphere. © 2005 Wiley Periodicals, Inc. J Comm Psychol 33: 21–29, 2005.
A comparison of youth‐driven and adult‐driven youth programs: Balancing inputs from youth and adults
Authors: Larson Reed , Walker Kathrin , Pearce Nickki
Published: November 2004

This article examines the unfolding of experiences in youth programs that differed in the degree of youth and adult influence over program activities. In‐depth qualitative data were obtained over a three‐ to four‐month cycle of activities in two “youth‐driven” and two “adult‐driven” programs for high‐school–aged youth. All had been identified as high quality, and in all of the programs, the adults were sensitive and respectful to the youth. Rather than finding that one approach was categorically better than the other, our analyses suggested that each provided distinct developmental experiences, and that each presented somewhat different day‐to‐day challenges to the adults. In the youth‐driven programs, the youth experienced a high degree of ownership and empowerment, and they reported development of leadership and planning skills. In the adult‐driven programs, the adults crafted student‐centered learning experiences that facilitated youth's development of specific talents. Across both approaches, youth also gained self‐confidence and benefited from the adults' experience in other ways. The article highlights balancing techniques that adults in both programs used for keeping youth's work in the program on track while keeping youth invested. © 2005 Wiley Periodicals, Inc. J Comm Psychol 33: 57–74, 2005.