bluuebunny/crossref_metadata_2025 huggingface dataset:
The Association of Transient Ischemic Attack Symptoms With Memory Impairment Among Elderly Participants of the Third US National Health and Nutrition Examination Survey
Authors: Takahashi Paul Y. , Dyrbye Liselotte N. , Thomas Kris G. , Quirindongo Cedeno Onelis , North Frederick , Stroebel Robert J. , DeJesus Ramona S. , Targonski Paul V.
Published: December 2008

Background and Purpose: Stroke is a well-known risk factor for vascular dementia. However, the association of transient ischemic attacks with cognitive impairment is less well-established.

Methods: Records from Third National Health and Nutrition Examination Survey were abstracted for demographic and medical information for participants with an age !60 years who reported being free of stroke. Five self-reported symptoms (weakness, numbness, loss of vision, inability to speak, and severe dizziness) were used as surrogates representing transient ischemic attacks. Information on conventional risk factors for vascular dementia was also obtained. Multivariable logistic regression was used to examine risk factors for memory impairment. Results: 4617 participants were included with a sample-weighted prevalence of memory impairment of 6.6% (1417 participants). The final multivariable analysis revealed a significant association between transient weakness and memory impairment (odds ratio 1.52, 95% CI 1.11-2.07). The other 4 transient ischemic attacks symptoms were not significantly associated with memory impairment in the final model. Systolic blood pressure >140 was most strongly associated with prevalent memory impairment (odds ratio, 9.78, 95% CI 1.49-64.3). Other associated risk factors included non-white race, male gender, age, education ≤12 years, and history of any alcohol use.

Conclusion: Among transient ischemic attacks symptoms, self-reported weakness in the face, arm, or leg was significantly associated with memory impairment. This study indicates that transient ischemic attacks symptoms are, even in the absence of stroke, associated with memory impairment. Aggressive risk factor modification in patients with TIA symptoms may be warranted to prevent potential future memory loss.
Lupus-associated pancreatitis complicated by pancreatic pseudocyst and central nervous system vasculitis
Authors: Myung DS , Kim TJ , Lee SJ , Park SC , Kim JS , Kim JC , Yoon W , Lee SS , Park YW
Published: December 2008

Pancreatitis is an uncommon manifestation of systemic lupus erythematosus (SLE), but this can occasionally cause major complications. We report in this article, a case of 33-year-old female patient who developed lupus-associated pancreatitis that was subsequently complicated by pancreatic pseudocyst and central nervous system (CNS) vasculitis. Abdominal computed tomography (CT) showed an oedematous swelling of the pancreas and a pseudocyst measuring 4 × 3 cm2. Brain magnetic resonance imaging (MRI) showed multiple high–signal intensity lesions in both cerebral hemispheres. The pseudocyst did not completely resolve with high-dose steroid therapy, and it was later complicated by infection and rupture. After a surgical drainage for the complicated pseudocyst, her clinical symptoms and signs were markedly improved. This case shows the importance of performing early drainage rather than conservative treatment for a pancreatic pseudocyst in a patient with lupus-associated pancreatitis.
Antiribosomal-P protein antibodies in a patient with systemic lupus erythematosus and non-Hodgkin’s lymphoma: more than coincidental finding?
Authors: Miljic P , Bonaci-Nikolic B , Colovic N , Terzic T , Colovic M
Published: December 2008

Patients with systemic lupus erythematosus (SLE) are at an increased risk of lymphomas, but mechanisms underlying this association are obscure. Recently, it has been shown that antiribosomal-P protein (anti-P) antibodies cross-react with phospholipids and enhance the production of cytokines which may influence lymphomagenesis. We report a 46-year-old woman who suffered high grade diffuse large B-cell non-Hodgkin’s lymphoma (DLBCL) 28 months after the diagnosis of SLE. Development of lymphoma was associated with occurrence of serum monoclonal IgM, and pronounced prolongation of phospholipid-dependent clotting tests. Anti-P IgG antibodies were highly positive both on HEp-2 cells and in ELISA test. Anticardiolipin, anti-β2 glycoprotein I, and antiprothrombin IgM antibodies have also been found in high concentrations. Complete remission of DLBCL and SLE, with normalisation of clotting tests, and disappearance of M component was achieved with administration of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. The progression of SLE to DLBCL associated with presence of anti-P antibodies has not been previously reported. This association may not be coincidental, but further investigations are required to confirm this hypothesis.
Anti–double stranded DNA and lupus syndrome induced by interferon-β therapy in a patient with multiple sclerosis
Authors: Bonaci-Nikolic B , Jeremic I , Andrejevic S , Sefik-Bukilica M , Stojsavljevic N , Drulovic J
Published: December 2008

We present a 43-year-old woman with relapsing–remitting multiple sclerosis (MS) who developed lupus syndrome after 32 months of IFN-β-1a therapy. She presented with malaise, myalgia, arthralgia and fever. Laboratory tests showed high erythrocyte sedimentation rate, anaemia and lymphopenia. Antibodies to double stranded DNA (dsDNA) of IgG, IgM and IgA classes were detected on Critidia luciliae. Additionally, high levels of anti-nucleosomal antibodies, low levels of anti-histone and anti-Ro/SSA antibodies were also found. Diagnosis of drug-induced SLE was established. Treatment with IFN-β was discontinued and oral prednisone was started. Twelve weeks after cessation of IFN-β therapy, the patient’s symptoms completely resolved and autoantibodies disappeared. To the best of our knowledge, this is the first report of a patient with MS in whom treatment with IFN-β induced lupus syndrome and antibodies to dsDNA and nucleosome.
Renal expression of galectin-3 in systemic lupus erythematosus patients with nephritis
Authors: Kang EH , Moon KC , Lee EY , Lee YJ , Lee EB , Ahn C , Song YW
Published: December 2008

The aim of the study is to characterize the expression pattern of galectin-3 (Gal-3) in renal tissues of patients with systemic lupus erythematosus (SLE) nephritis and to determine whether tissue and serum Gal-3 are associated with SLE nephritis. Gal-3 expressions were examined with immunohistochemistry in renal biopsy specimens of 88 patients with SLE nephritis and in five normal specimens. Activity and chronicity indexes and glomerular Gal-3 expressions were analysed in each specimen. Serum Gal-3 levels were measured using enzyme-linked immunosorbent assays in 20 patients with SLE, including 11 with nephritis, and in 50 healthy controls. Glomerular Gal-3 expression was observed in 81.8% (72/88) of patients with SLE nephritis but not in 5 controls. Gal-3 staining was attributed mainly to its cellular expression rather than its deposition, and Gal-3 expression levels were correlated with histologic activity indexes, anti-dsDNA titers, and complement 3 and 4 levels. Serum Gal-3 levels were higher in patients with SLE, particularly in those with nephritis, than in healthy controls, and correlated with anti-dsDNA titers. In conclusion, glomerular Gal-3 expression in renal tissue and serum Gal-3 levels were elevated in patients with SLE nephritis versus healthy controls; moreover, they reflected disease activity. These findings suggest that Gal-3 might contribute to the inflammatory process in SLE.
Association of interleukin-18 promoter polymorphisms with WHO pathological classes and serum IL-18 levels in Chinese patients with lupus nephritis
Authors: Chen DY , Hsieh CW , Chen KS , Chen YM , Lin FJ , Lan JL
Published: December 2008

Accumulating evidence indicates that interleukin (IL)-18 has a central role in the pathogenesis of lupus nephritis (LN). Although two recent studies showed that IL-18 promoter gene polymorphisms might be associated with systemic lupus erythematosus (SLE), to our knowledge, there have not been any reports concerning their association with LN. The aim of our study was to investigate the association of IL-18 promoter polymorphisms with World Health Organization pathological classes and identify their functional correlations. Sequence-specific primer polymerase chain reaction and the restriction fragment length polymorphism method were used to analyse the genotypes of IL-18 promoter polymorphism at the position −607 in 101 unrelated patients with LN, 64 non-renal patients with SLE and 174 ethnically matched healthy controls. Serum IL-18 levels were determined using enzyme-linked immunosorbent assay during the active phase. Immunohistochemical analysis was performed for IL-18 expression on renal biopsies from 72 patients with LN. Our results showed that patients with non-renal SLE had significantly higher frequencies of SNP−607/AA when compared to patients with LN (37.5% vs 18.8%, P < 0.05). LN patients with the AA genotype had significantly lower levels of serum IL-18 than those with the CA or CC genotype ( P < 0.01) and also had lower levels of glomerular IL-18 expression than those with the CC genotype ( P < 0.05). Significantly, higher frequencies of the SNP−607/AA genotype were observed in LN patients with WHO class III than in those with class IV (34.6% vs 15.6%, P < 0.05). The SNP−607/AA genotype was not observed in patients with LN who progressed to end-stage renal failure that required haemodialysis or renal transplantation. In conclusion, the SNP−607/AA genotype that had lower IL-18 levels might be a genetically protective factor against renal involvement in Chinese patients with SLE and against development of severe nephritis in patients with LN.
Honeybee royal jelly inhibits autoimmunity in SLE-prone NZB × NZW F1 mice
Authors: Mannoor MK , Shimabukuro I , Tsukamotoa M , Watanabe H , Yamaguchi K , Sato Y
Published: December 2008

Royal jelly (RJ) is a gelatinous secretion from young nurse worker bees ( Apis mellifera), which serves as the sole food for the queen bee. Because of its pleiotropic functions for queen bees, RJ has also been used as a dietary supplement with various health benefits for humans. Because RJ is being indicated to have immunomodulatory potential for humans, we undertook the study to determine whether the oral administration of RJ could alter the development of systemic autoimmunity in New Zealand Black (NZB) × New Zealand White (NZW) F1 mice that genetically exhibit many manifestations similar to human systemic lupus erythematosus (SLE). We herein reported that mice administered with RJ showed a significant delay in the onset of the disease, as manifested by decreased proteinuria and a prolongation of lifespan. In addition, RJ administration after the onset of the disease significantly improved the renal symptoms, leading to an extended lifespan. RJ administration to mice caused a significant decrease in the serum level of IL-10, and in the autoantibodies against ssDNA, dsDNA and erythrocytes, as well as a reduction in the number of splenic autoreactive B cells. In conclusion, our data suggest that the use of RJ may be beneficial in the prevention of the early onset of SLE and in the control of the active progression of the manifestations of SLE.
Women Reading Texts on Marriage
Authors: Siddiqua Chaudhry Ayesha , Muers Rachel , Rashkover Randi
Published: December 2008

We present readings, by Jewish, Christian and Muslim women scholars, of `difficult' texts from three scriptural traditions, viz. Ephesians 5.21-33, Sura' 4.32-35 and Genesis 30.1-26. All three texts concern marriage and point in different ways to the erasure of women's significance or agency, and we ask what happens when women read such texts as scripture. Our readings were developed in conversation with one another, following the developing practice of `Scriptural Reasoning', and they suggest ways in which the texts and their feminist readers can `correct' and challenge each other. We propose that feminist biblical hermeneutics and inter-traditional scriptural reasoning can be mutually informative, with both practices seeking to take embodied difference seriously and to allow unresolved critical questions to arise in reading.
“Pretty Prudent” or Rhetorically Responsive?
Authors: Cooper Drury A. , Marvin Overby L. , Ang Adrian , Yitan Li
Published: December 2008

In the United States, public support can play a crucial role in the decisions to initiate and terminate military action. Some scholars argue that the public holds “prudent” opinions regarding the use of the military—supporting efforts to stop aggression but not to engage in nation building. We argue that what seems like a “prudent” opinion may be driven more by the White House’s rhetoric. Experimental tests show that the rhetorical complexity has a more powerful impact on the respondent’s support for military action than the actual policy goal, although this result is substantially tempered by political awareness.
High-Throughput Biochemical Kinase Selectivity Assays: Panel Development and Screening Applications
Authors: Card Amy , Caldwell Chris , Min Hyunsuk , Lokchander Bina , Hualin Xi  , Sciabola Simone , Kamath Ajith V. , Clugston Susan L. , Tschantz William R. , Leyu Wang  , Moshinsky Deborah J.
Published: December 2008

Kinases represent attractive targets for drug discovery. Eight small-molecule kinase inhibitors are currently marketed in the area of oncology, and numerous others are in clinical trials. Characterization of the selectivity profiles of these compounds is important to target appropriate patient populations and to reduce the potential of toxicity due to off-target effects. The authors describe the development, validation, and utilization of a biochemical kinase assay panel for the selectivity profiling of inhibitors. The panel was developed as 29 radiometric Flashplate™ assays, and then an initial 13 were transitioned to a nonradiometric Caliper mobility shift assay format. Generation of high-quality data from the panel is detailed along with a comparison of the assay formats. Both assay technologies were found to be suitable for panel screening, but mobility shift assays yielded higher data quality. The selectivity data generated here should be useful in computational modeling and help facilitate, in conjunction with sequence and structural information, the rational design of inhibitors with well-defined selectivity profiles. ( Journal of Biomolecular Screening 2009:31-42)
Work and the Struggle for Recognition
Authors: Smith Nicholas H.
Published: December 2008

This article examines a neglected but crucial feature of Honneth's critical theory: its use of a concept of recognition to articulate the norms that are apposite for the contemporary world of work. The article shows that from his first writings on the structure of critical social theory in the early 1980s to the recent exchange with Nancy Fraser on recognition and redistribution, the problem of grounding a substantive critique of work under capitalism has been central to Honneth's enterprise. This answers the routine objection that the recognition paradigm fails to take into account economic or material realities. At the same time, Honneth's approach to the critique of work has undergone significant shifts, and it is yet to be fully developed. The article traces these changes in direction, and it proposes an expressivist conception of work that builds upon the `normative content' of the concept of work described by Honneth in his 1980 essay `Work and Instrumental Action'.
The Pathophysiology of Disease in Patients with Paroxysmal Nocturnal Hemoglobinuria
Authors: Bessler Monica , Hiken Jeffrey
Published: December 2008

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia caused by the expansion of a hematopoietic progenitor cell that has acquired a mutation in the X-linked PIGA gene. PNH occurs on the background of bone marrow failure. Bone marrow failure and the presence of the abnormal cells account for the clinical phenotype of patients with PNH including hemolysis, cytopenia, and thrombophilia. PIGA is essential for the synthesis of glycosyl phosphatidylinositol (GPI) anchor molecules. PNH blood cells are therefore deficient in all proteins that use such an anchor molecule for attachment to the cell membrane. Two of these proteins regulate complement activation on the cell surface. Their deficiency therefore explains the exquisite sensitivity of PNH red blood cells to complement-mediated lysis. Complement-mediated lysis of red blood cells is intravascular, and intravascular hemolysis contributes significantly to the morbidity and mortality in patients with this condition. PNH is an outstanding example of how an increased understanding of pathophysiology may directly improve the diagnosis, care, and treatment of disease.
Novel Small Molecule Therapeutics for Sickle Cell Disease: Nitric Oxide, Carbon Monoxide, Nitrite, and Apolipoprotein A-I
Authors: Kato Gregory J.
Published: December 2008

A hemolysis-linked subphenotype of sickle cell disease (SCD), characterized by pulmonary hypertension, stroke, priapism and leg ulcers, is associated with decreased nitric oxide bioavailability and vasculopathy. Vasculopathy appears to have a multifactorial etiology, including mechanisms primarily that involve deficient nitric oxide (NO) signaling, but also involving altered function of NO synthase related to substrate availability and cooperating factors such as apolipoproteins. Improved understanding of the vascular pathophysiology of SCD has led to new vascular targets for translational research in SCD. This growing vascular therapeutics field in SCD is complementary to the ongoing efforts to reduce the morbidity of vaso-occlusive pain crisis. This presentation will review the current biology and translational clinical development of novel small molecules targeting sickle cell vasculopathy. Strategies targeting the hemeoxygenase-carbon monoxide pathway, the arginine-NO synthase-cGMP-phosphodiesterase 5 pathway, the nitrate-nitrite-NO pathway, and the apolipoprotein A-I pathways will be reviewed. In this context, current clinical trials of inhaled NO, CO, nitrite, sildenafil and apoA-I mimetics will be discussed.
Viral-Associated Immune Thrombocytopenic Purpura
Authors: Liebman Howard A.
Published: December 2008

Chronic immune thrombocytopenic purpura (CITP) is a diagnosis of exclusion that occurs either de novo or secondary to other underlying disorders. Chronic infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are now well-characterized causes of CITP. Between 6% and 15% of patients infected with HIV may develop thrombocytopenia. Patients with CITP with risk factors for HIV infection should be screened for the virus. Treatment of HIV-related CITP should be directed toward antiviral therapy with highly active antiretroviral therapy (HAART) regimens. Hepatitis C viral infection can also be associated with chronic thrombocytopenia, even in the absence of overt liver disease. While HCV-related thrombocytopenia is typically less severe than primary CITP, affected patients are at greater risk of major bleeding. Sustained suppression of HCV virus with interferon-ribavirin therapy can improve platelet counts. Screening for HCV infection should be considered in patients with ITP with risk factors for infection, from regions with high rates of infection or in patients with unexplained mild elevations of liver enzymes.
Evidence-Based Guidelines—An Introduction
Authors: Lim Wendy , Arnold Donald M. , Bachanova Veronika , Haspel Richard L. , Rosovsky Rachel P. , Shustov Andrei R. , Crowther Mark A.
Published: December 2008

Recommendations in the form of clinical practice guidelines are increasingly common. Clinical guidelines are systematically developed statements designed to help administrators, practitioners and patients make decisions about appropriate health care for specific circumstances. In North America, guidelines developed by professional societies, government panels and cooperative groups are frequently used to measure quality, to allocate resources and to determine how health care dollars are spent. For clinicians, guidelines provide a summary of the relevant medical literature and offer assistance in deciding which diagnostic tests to order, which treatments to use for specific conditions, when to discharge patients from the hospital, and many other aspects of clinical practice.
Management of Excessive Anticoagulant Effect Due to Vitamin K Antagonists
Authors: Dentali Francesco , Crowther Mark A.
Published: December 2008

Unexpectedly elevated INR values are commonly encountered in clinical practice. In the absence of bleeding, such values may be treated with either simple warfarin withdrawal or the administration of low doses of oral vitamin K. Oral vitamin K will more rapidly return the INR to the therapeutic reference interval; however, its impact on bleeding is unknown. If the INR is in excess of 10, most experts would recommend the administration of vitamin K and, in the case of active bleeding, additional administration of coagulation factors either in the form of fresh frozen plasma (FFP) or prothrombin complex concentrates (PCC). Coagulation factor replacement is required given the need to urgently correct the INR; however, vitamin K should not be forgotten since it is required to antagonize the effect of warfarin, preventing “rebound” anticoagulation after transfused coagulation factors are consumed. This paper will review the evidence supporting various treatment modalities and will provide suggestions for treatment. Future advances in this area will likely focus on evaluations of the relative merits of FFP and PCCs.
Investigative Tools for Diagnosis and Management
Authors: Munshi Nikhil C.
Published: December 2008

Recent advances in genomics and proteomics have advanced our understanding of myeloma pathogenesis, recognized novel mediators of disease process, and identified new therapeutic targets. These developments have provided newer diagnostic tools for myeloma, improved monitoring of the disease status and allowed for molecular classification of the disease. The recent advances in investigative techniques that have helped refine the diagnostic work up in myeloma includes use of serum free light chains, especially in oligosecretory myeloma, patients with renal disease and with amyloidosis; use of MRI and PET scan in diagnosis and managing bone disease; and use of cytogenetics and fluorescent in situ hybridization (FISH) technique to determine prognosis. Newer risk stratification protocols have included international staging systems as well as FISH-detected chromosomal changes, specifically t(4;14), t(14;16), and del 17p. These improved predictive risk stratification models are guiding treatment algorithms. As the novel therapies are able to attain complete responses in a significant number of patients, the response categories are also being redefined. Immunophenotypic identification of clonal plasma cells, inclusion of free light chain response and molecular markers of disease now allow us to define stringent complete responses. Recent studies show the increasing importance of attaining complete remission to extended overall survival. The ongoing oncogenomic studies including high-throughput expression profiling, high-density single nucleotide polymorphism (SNP)–arrays and array based comparative hybridization (aCGH) have been utilized to not only understand myeloma pathobiology, but for gene discovery, identification of biomarkers, and delineation of patient subgroups to incorporate them into therapeutic strategies and to eventually provide optimal individualized therapy.
Induction Therapy in Multiple Myeloma
Authors: Harousseau Jean-Luc
Published: December 2008

In most hematologic malignancies the role of induction treatment is to achieve complete remission (CR). In multiple myeloma this has been possible only with the introduction of high-dose therapy plus autologous stem-cell transplantation (ASCT). In the context of ASCT there is a statistical relationship between CR or very good partial remission (VGPR) achievement and progression-free survival or overall survival. High-dose therapy consists of 3 to 6 courses of a dexamethasone alone or combined with vincristine-adriamycin (VAD) to reduce the tumor burden and the plasma cell infiltration followed by 1 or 2 courses of high-dose melphalan plus ASCT. This treatment induces 20% to 40% CR and 40% to 55% CR/VGPR. The introduction of novel agents in the induction treatment is changing this scenario. The combinations of dexamethasone with thalidomide, bortezomib or lenalidomide increase the CR/VGPR rates compared to dexamethasone or VAD. Triple combinations are currently being evaluated, but preliminary results with not more than 3 or 4 cycles show post-ASCT CR/VGPR rates of 60% to 75%

In elderly patients who are not candidates for ASCT, combinations of melphalan-prednisone with a novel agent (thalidomide, bortezomib or lenalidomide) yield CR/VGPR rates that are quite comparable to those achieved in younger patients with ASCT. Prolonged treatment with the combination of lenalidomide plus dexamethasone can be administered safely and appears to induce very high (up to 70%) CR/VGPR rates as well.
Treatment of Acute Lymphoblastic Leukemia in Children and Adolescents: Peaks and Pitfalls
Authors: Seibel Nita L.
Published: December 2008

Survival of children with acute lymphoblastic leukemia (ALL) is often described as the success story for oncology. The improvements in the treatment of ALL represent the work of cooperative groups at their best. Fifty years ago a pediatric oncologist would have never considered using the term “cure” in a discussion with a family whose child was diagnosed with ALL. Today the term is not only used in the initial discussion but referred to frequently thereafter. However, as we all know, cure is not assured and is not obtained without sequelae. This review will focus on the improvements in treatment for newly diagnosed ALL in children and adolescents according to risk group and some of the challenges that remain despite the improved outcome.
Does High-Dose Therapy and Autologous Hematopoietic Stem Cell Transplantation Have a Role in the Primary Treatment of Peripheral T-Cell Lymphomas?
Authors: Shustov Andrei R. , Savage Kerry J.
Published: December 2008

A 58-year-old woman presents with a recent diagnosis of peripheral T-cell lymphoma, unspecified. She has read through Google® that the “best treatment” for this disorder is stem cell transplantation—she asks you if you recommend this treatment?
Curative Strategies in Acute Promyelocytic Leukemia
Authors: Tallman Martin S. , Altman Jessica K.
Published: December 2008

Acute promyelocytic leukemia (APL) was initially described as a distinct clinical entity in 1957, one year before the first meeting of the American Society of Hematology. With routine administration of all-trans retinoic acid (ATRA) combined with chemotherapy in the early 1990s and arsenic trioxide (ATO) in the late 1990s, cure can now be expected in the majority of both newly diagnosed and relapsed patients. ATRA with anthracycline-based chemotherapy for induction and consolidation followed by ATRA plus low-dose chemotherapy maintenance is currently the standard of care for newly diagnosed patients. Early institution of ATRA before the diagnosis is confirmed by genetics and aggressive blood product support are important to reduce induction mortality, which remains approximately 10% among patients entered on clinical trials, but is certainly higher when all patients are considered. The relapse rate among high-risk patients is approximately 20%, and new strategies include administration of intensified anthracyclines, intermediate- or high-dose ara-C in either induction or consolidation, or ATO as early consolidation. Central nervous system (CNS) prophylaxis for such patients and those with relapsed disease may be important to prevent the development of extramedullary disease. New therapeutic strategies have focused on minimizing chemotherapy and administering ATRA plus ATO as initial therapy. Recent studies suggest that patients who are molecularly negative after intensive consolidation may not benefit from maintenance therapy. Most exciting is the combination of ATRA and ATO, given with minimal chemotherapy only for leukocytosis, which is a very effective new strategy for patients who are unable to tolerate anthracyclines or older adults and soon may replace conventional therapy for many patients. Patients with relapsed disease do well with ATO followed by autologous hematopoietic stem cell transplantation
Molecular Genetic Pathways as Therapeutic Targets in Acute Myeloid Leukemia
Authors: Haferlach Torsten
Published: December 2008

The heterogeneity of acute myeloid leukemia (AML) results from a complex network of cytogenetic aberrations and molecular mutations. These genetic markers are the basis for the categorization of cases within distinct subgroups and are highly relevant for the prediction of prognosis and for therapeutic decisions in AML. Clinical variances within distinct genetically defined subgroups could in part be linked to the interaction of diverse mutation classes, and the subdivision of normal karyotype AML on the basis of recurrent molecular mutations gains increasing relevance for therapeutic decisions. In parallel to these important insights in the complexity of the genetic networks in AML, a variety of diverse new compounds is being investigated in preclinical and clinical studies. These approaches aim to develop targeted treatment concepts that are based on interference with molecular genetic or epigenetic mechanisms. This review provides an overview on the most relevant genetic markers, which serve as basis for targeted therapy approaches now or might represent options for such approaches in the future, and summarizes recent results of targeted therapy studies.
Disease-Specific Complications of Chronic Lymphocytic Leukemia
Authors: Dearden Claire
Published: December 2008

The majority of disease-specific complications in chronic lymphocytic leukemia (CLL), notably infection and autoimmunity, relate to the underlying alterations in immune function. Both cellular and humoral immunity are impaired with qualitative and quantitative defects in B cells, T cells, NK cells, neutrophils and the monocyte/macrophage lineage. Virtually all patients have reduced immunoglobulin levels, even in early stages, and this is associated with an increased frequency and severity of infection. Although prophylactic intravenous immunoglobulin may be of clinical benefit in selected patients, it does not reduce mortality and is certainly not cost-effective. Autoimmune complications occur in up to a quarter of CLL patients and predominantly target blood cells. Autoimmune hemolytic anemia (AHA) is the most common manifestation; immune thrombocytopenia, pure red cell aplasia and autoimmune neutropenia are less common, while non-hematological autoimmunity is rare. The UK CLL4 trial is the largest prospective trial in CLL to examine the significance of both a positive direct antiglobulin test (DAT) and AHA. The study confirmed the usefulness of the DAT in predicting the development of AHA or not, demonstrated that AHA occurred more frequently in patients receiving treatment with chlorambucil or fludarabine alone compared with the combination of fludarabine and cyclophosphamide, and showed that a positive DAT and the development of AHA were poor prognostic markers. Management of CLL-associated autoimmunity rests on good supportive care and the use of immunosuppressive therapies such as steroids and cyclosporine. Splenectomy remains useful, and monoclonal antibodies (rituximab and alemtuzumab) have given promising results.
Patient and Family Requests for Hastened Death
Authors: Abrahm Janet L.
Published: December 2008

Patient and family requests for hastened death, upsetting as they are to the treating team, are usually a way for patients and their families to express their need for an increase in the intensity of communication, improved symptom control, or acknowledgment of an existential or spiritual crisis. Rarely do they represent the need for patients to control the time, place, and manner of their death. Using a hypothetical case study, this paper reviews the unspoken concerns underlying these requests; characteristics of patients who request a hastened death, and when and why they make the request; the Oregon Death with Dignity Act and its implementation since its passage in 1997; the effect these requests have on clinicians, their common reactions, and suggestions for self-care after such requests; techniques for responding to the requests and keeping the dialogue open with the patient and family; and the legal and ethical options available to clinicians outside of Oregon.
Palliative Care and Psychosocial Contributions in the ICU
Authors: Loscalzo Matthew J.
Published: December 2008

Psychosocial domains and palliative care medicine are the connective tissue of our fragmented health care system. The psychosocial domains of palliative care are central to creating new partnerships with physicians, patients, and their caregivers in emotionally charged medical environments, especially Intensive Care Units. Managing the psychological, social, emotional, spiritual, practical and existential reactions of patients and their loved ones supports effective action and problem-solving. Practical aspects to establishing realistic goals of care among the health care team and other specialists, communicating effectively with patients and families in crisis, using the diverse and ambiguous emotional responses of patients, families, faculty and staff therapeutically, and helping to create meaning in the experience is essential to whole-patient and family care centered. The family conference is an excellent vehicle to create an environment of honest and open communication focused on mobilizing the resources of the patient, family and health care team toward a mutually agreed upon plan of action resulting in clearly defined goals of care.
The Role of JAK2 Mutations in RARS and Other MDS
Authors: Hellström-Lindberg Eva , Cazzola Mario
Published: December 2008

Acquired sideroblastic anemia with unilineage dysplasia (WHO RARS) is a clonal stem cell disorder characterized by erythroid dysplasia, mitochondrial accumulation of mitochondrial ferritin, defective erythroid maturation and anemia. A fraction of these patients also show elevated platelet counts; since 2001 this has been defined as RARS with marked thrombocytosis (RARS-T). It has recently been described that around half of RARS-T patients, along with a small subset of other MDS and mixed myelodysplastic/ myeloproliferative disorders, carry the JAK2 mutation, and that MPL mutations are found in single patients. Clinically, RARS-T patients show features of both RARS, essential thrombocythmia (ET) and to some extent also myelofibrosis. However, the degree of anemia and overall survival is more similar to RARS than myeloproliferative disorders. The occurrence of JAK2 mutations and features of ET in RARS is too frequent to be the result of chance only, and it is possible that this link may provide a key to an increased understanding of the genetic abnormalities causing ring sideroblast formation.
Association between fatty acid compositions and genotypes of FABP4 and LXR-alpha in Japanese Black cattle
Authors: Hoashi Shogo , Hinenoya Tomoko , Tanaka Atsuko , Ohsaki Hideki , Sasazaki Shinji , Taniguchi Masaaki , Oyama Kenji , Mukai Fumio , Mannen Hideyuki
Published: December 2008

Background

Fatty acid composition has become an important trait in the beef industry in terms of beef flavor and decreasing the circulating concentration of LDL cholesterol. In this study, we examined the association between polymorphisms of six genes, adipocytes-type fatty acid binding protein (FABP4), liver X receptor α (LXRα), cytochrome b
5 (Cyt b
5), long-chain acyl-CoA synthetase (ACSL) 1, ACSL4 and diacylglycerol acyltransferase 2 (DGAT2) and fatty acid composition.

Results

Sequence comparisons revealed 14 single nucleotide polymorphisms in six genes. Four of them, I74V and V110M in FABP4 and G51E and V133I in LXRα, were nonsynonymous substitutions. The associations between the genotypes and fatty acid compositions were analyzed by using 234 Japanese Black cattle. The genotypes of FABP4 I74V and LXRα V133I were significantly associated with palmitoleic acids (C16:1, P = 0.0086) and linoleic acid (C18:2, P = 0.0121) content in intramuscular fat, respectively.

Conclusion

Our findings suggest that the two polymorphisms of FABP4 I74V and LXRα V133I might be genetic factors in part associated with palmitoleic acid (FABP4 I74V) and linoleic acid (LXRα V133I) composition in intramuscular fat of Japanese Black cattle, respectively. Especially, FABP4 I74V had highly significant effect (P < 0.01) on C16:1 proportion, indicating that the I/I homozygote exhibited 0.5% higher percentage than V/V homozygote.
Persimmon bezoar successfully treated by oral intake of Coca-Cola: a case report
Authors: Hayashi Kazuki , Ohara Hirotaka , Naitoh Itaru , Okumura Fumihiro , Andoh Tomoaki , Itoh Takafumi , Nakazawa Takahiro , Joh Takashi
Published: December 2008

Background

An 82-year-old male presented with a chief complaint of upper abdominal pain. Subsequently, a bezoar and a gastric ulcer were detected by upper gastrointestinal endoscopy.

Case presentation

The bezoar was dark green in color and extremely hard, having a major axis of 7 cm. After hospitalization, 500–1000 ml/day of Coca-Cola was orally administered continuously for 3 weeks.

Conclusion

Thereafter, the bezoar decreased in size to a major axis of 4 cm and showed a softening trend. Therefore, lithotripsy was thereafter carried out under endoscopy using forceps.
Land and Power: Theory and Evidence from Chile
Authors: Baland Jean-Marie , Robinson James A
Published: December 2008

Many employment relationships concede rents to workers. Depending on the political institutions, the presence of such rents allows employers to use the threat of withdrawing them to control their workers' political behavior, such as their votes in the absence of secret ballot. We examine the effects of the introduction of the secret ballot in Chile in 1958 on voting behavior. Before the reforms, localities with more pervasive patron-client relationships tended to exhibit a much stronger support for the right-wing parties, traditionally associated with the landed oligarchy. After the reform, however, this difference across localities completely disappeared. (JEL D72, N46, O13, O15, O17)
Does Job Corps Work? Impact Findings from the National Job Corps Study
Authors: Schochet Peter Z , Burghardt John , McConnell Sheena
Published: December 2008

This paper presents findings from an experimental evaluation of Job Corps, the nation's largest training program for disadvantaged youths. The study uses survey data collected over four years and tax data over nine years on a nationwide sample of 15,400 treatments and controls. The Job Corps model has promise; program participation increases educational attainment, reduces criminal activity, and increases earnings for several postprogram years. Based on tax data, however, the earnings gains were not sustained except for the oldest participants. Nonetheless, Job Corps is the only federal training program that has been shown to increase earnings for this population. (JEL I28, I38, J13, J24)
Consumption Inequality and Partial Insurance
Authors: Blundell Richard , Pistaferri Luigi , Preston Ian
Published: December 2008

This paper examines the link between income and consumption inequality. We create panel data on consumption for the Panel Study of Income Dynamics using an imputation procedure based on food demand estimates from the Consumer Expenditure Survey. We document a disjuncture between income and consumption inequality over the 1980s and show that it can be explained by changes in the persistence of income shocks. We find some partial insurance of permanent shocks, especially for the college educated and those near retirement. We find full insurance of transitory shocks except among poor households. Taxes, transfers, and family labor supply play an important role in insuring permanent shocks. (JEL D12, D31, D91, E21)
Liquidity and Insurance for the Unemployed
Authors: Shimer Robert , Werning Iván
Published: December 2008

We study unemployment insurance for workers who sequentially sample job opportunities. We focus on the optimal timing of benefits and the desirability of allowing borrowing and saving. When workers have constant absolute risk aversion, a simple policy is optimal: a constant benefit during unemployment, a constant tax during employment, and free access to a riskless asset. With constant relative risk aversion, optimal policy involves nearly constant benefits; more elaborate policies offer minuscule welfare gains. We highlight two distinct policy roles: ensuring workers have sufficient liquidity to smooth their consumption; and providing unemployment subsidies to insure against uncertain spell duration. (JEL J65)
Trading Tasks: A Simple Theory of Offshoring
Authors: Grossman Gene M , Rossi-Hansberg Esteban
Published: December 2008

We propose a theory of the global production process that focuses on tradeable tasks, and use it to study how falling costs of offshoring affect factor prices in the source country. We identify a productivity effect of task trade that benefits the factor whose tasks are more easily moved offshore. In the light of this effect, reductions in the cost of trading tasks can generate shared gains for all domestic factors, in contrast to the distributional conflict that typically results from reductions in the cost of trading goods. (JEL F11, F16)
Optimal Tariffs and Market Power: The Evidence
Authors: Broda Christian , Limão Nuno , Weinstein David E
Published: December 2008

We find that prior to World Trade Organization membership, countries set import tariffs 9 percentage points higher on inelastically supplied imports relative to those supplied elastically. The magnitude of this effect is similar to the size of average tariffs in these countries, and market power explains more of the tariff variation than a commonly used political economy variable. Moreover, US trade restrictions not covered by the WTO are significantly higher on goods where the United States has more market power. We find strong evidence that these importers have market power and use it in setting noncooperative trade policy. (JEL F12, F13)
Contextual Inference in Markets: On the Informational Content of Product Lines
Authors: Kamenica Emir
Published: December 2008

Context can influence decisions. This malleability of choice is usually invoked as evidence that people do not maximize stable preference orderings. In a market equilibrium, however, context conveys payoff-relevant information to consumers. Consequently, these consumers rationally violate naïve formulations of standard choice theoretic principles. I identify informational asymmetries under which apparently anomalous behaviors, namely the compromise effect and choice overload, arise as market equilibria. Firms respond to consumers' contextual inference; in case of the compromise effect, a firm may introduce premium loss leaders (expensive goods of overly high quality that increase the demand for other goods). (JEL D11, D83, M31)
Conversations among Competitors
Authors: Stein Jeremy C
Published: December 2008

I develop a model of bilateral conversations in which players honestly exchange ideas with their competitors. The key to incentive compatibility is complementarity in the information structure: a player can generate a new insight only if he has access to his counterpart's previous thoughts on a topic. I then examine a social network in which A has a conversation with B, then B has a conversation with C, and so on. Relatively underdeveloped ideas can travel long distances over the network. More valuable ideas, by contrast, tend to remain localized among small groups of agents. (JEL D83)
Impaired Working Memory Duration But Normal Learning Abilities Found in Mice That Are Conditionally Deficient in the Close Homolog of L1
Authors: Kolata Stefan , Wu Junfang , Light Kenneth , Schachner Melitta , Matzel Louis D.
Published: December 2008

In addition to its role in axon growth and neuronal migration, the close homolog of L1 (CHL1), a member of the L1 family of cell adhesion molecules, is involved in synaptic plasticity. To date, little has been done to disassociate the role of CHL1 during adulthood from its role during development. To address this issue, mice conditionally deficient in CHL1 (lacking CHL1 only after the third postnatal week) were tested relative to littermate controls as adults in five learning tasks and several tests of working memory (including duration and selective attention). CHL1-deficient mice showed no impairments in the learning tasks compared with wild-type controls. CHL1 deletion had no effect on selective attention despite its widespread impairment of working memory duration. These results suggest a role for CHL1 in the adult-brain in the short-term maintenance of information.
Dopamine D1Receptor Modulates Hippocampal Representation Plasticity to Spatial Novelty
Authors: Tran Anh Hai , Uwano Teruko , Kimura Tatsuo , Hori Etsuro , Katsuki Motoya , Nishijo Hisao , Ono Taketoshi
Published: December 2008

The human hippocampus is critical for learning and memory. In rodents, hippocampal pyramidal neurons fire in a location-specific manner, forming relational representations of environmental cues. The importance of glutamatergic systems in learning and in hippocampal neural synaptic plasticity has been shown. However, the role of dopaminergic systems in the response of hippocampal neural plasticity to novel and familiar spatial stimuli remains unclear. To clarify this important issue, we recorded hippocampal neurons from dopamine D1receptor knock-out (D1R-KO) mice and their wild-type (WT) littermates under the manipulation of distinct spatial cues in a familiar and a novel environment. Here we report that in WT mice, the majority of place cells quickly responded to the manipulations of distal and proximal cues in both familiar and novel environments. In contrast, the influence of distal cues on spatial firing in D1R-KO mice was abolished. In the D1R-KO mice, the influence of proximal cues was facilitated in a familiar environment, and in a novel environment most of the place cells were less likely to respond to changes of spatial cues. Our results demonstrate that hippocampal neurons in mice can rapidly and flexibly encode information about space from both distal and proximal cues to cipher a novel environment. This ability is necessary for many types of learning, and lacking D1R can radically alter this learning-related neural activity. We propose that D1R is crucially implicated in encoding spatial information in novel environments, and influences the plasticity of hippocampal representations, which is important in spatial learning and memory.