bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.
The Pathophysiology of Disease in Patients with Paroxysmal Nocturnal Hemoglobinuria
Authors: Bessler Monica , Hiken Jeffrey 
Published: December 2008

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractRecent 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

AbstractIn 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

AbstractSurvival 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

Abstract
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

AbstractAcute 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

Abstract
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

Abstract
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

Abstract
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.