bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolving Approaches to Primary Treatment of Hodgkin Lymphoma
Authors: Connors Joseph M. 
Published: November 2005

AbstractTwo challenges confront the clinician treating Hodgkin lymphoma today: achieving a high level of effectiveness while minimizing toxicity. At least 80% of patients can be cured with currently available chemotherapy regimens, augmented in selected patients with the addition of involved field radiation or intensified chemotherapy assisted by granulocyte growth factors or stem cell transplantation. Major late toxicity including infertility, premature menopause, cardiovascular disease and second neoplasms can be avoided in most patients if the treatment program is chosen carefully.The extent of disease (stage) and, for advanced stage lymphoma, the presence of well-characterized prognostic factors can be established with readily available clinical, laboratory and imaging techniques. Results from carefully designed and analyzed clinical trials have identified optimal treatment approaches for patients with limited and advanced stage disease. Those with limited stage Hodgkin lymphoma should be treated with brief chemotherapy, only augmented with involved field irradiation if an early complete remission is not achieved. Most patients with advanced stage lymphoma can be cured with an extended course of ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine). The small minority under the age of 60 years with an International Prognostic Factors Project score of 5 or greater should be considered for intensified chemotherapy. Patients known to have bulky tumor(s) (> 10 cm) at diagnosis may require adjuvant irradiation at the conclusion of chemotherapy, but its utility has not been unequivocally established and radiation should be avoided in those who achieve a complete remission, where it is known to be ineffective.With careful selection of treatment program most patients found to have Hodgkin lymphoma today can be offered a high probability of cure and a low likelihood of major late toxicity. However, without detailed attention to the extent of lymphoma and other prognostic factors, there is as much danger of over-treatment as under-treatment. Only by thoughtfully adjusting the treatment program to the extent of disease and response to treatment can the clinician determine the optimal approach, maximizing likelihood of cure and minimizing late toxicity.
MGUS and Smoldering Multiple Myeloma: Update on Pathogenesis, Natural History, and Management
Authors: Rajkumar S. Vincent 
Published: November 2005

AbstractMonoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic, pre-malignant disorders characterized by monoclonal plasma cell proliferation in the bone marrow and absence of end-organ damage. Recent advances in the pathogenesis, natural history, and prognosis of MGUS and SMM are reviewed. A new risk stratification system to determine the prognosis of MGUS using the size and type of M protein, and the serum free light chain assay is discussed.
Early Genetic Events Provide the Basis for a Clinical Classification of Multiple Myeloma
Authors: Kuehl W. Michael , Bergsagel P. Leif 
Published: November 2005

Abstract
Multiple myeloma is a tumor of somatically mutated, isotype-switched plasma cells that accumulate in the bone marrow leading to bone destruction and bone marrow failure. The germinal center processes of somatic hypermutation and switch recombination are implicated in the development of recurrent immunoglobulin gene translocations in 40% of patients. These affect five loci: 11q13, 6p21, 4p16, 16q23 and 20q11, leading to dysregulation of CCND1, CCND2, FGFR3/MMSET, c-MAF and MAFB respectively. The remaining 60% of patients can be divided into four groups based on their expression of CCND1 and CCND2. The largest group (40%) ectopically express CCND1 bi-allelically and have hyperdiploidy with multiple trisomies of chromosomes 3, 5, 7, 9, 11, 15, 19 and 21. The translocation and cyclin D (TC) groups identify patients with different genetics, biology, clinical features, prognosis and response to therapy.
An Update of the Management of Multiple Myeloma: The Changing Landscape
Authors: Reece Donna E. 
Published: November 2005

AbstractThe management of multiple myeloma is rapidly changing. Cytogenetic, molecular and proteomic techniques have led to a better understanding of the pathophysiology of this heterogeneous malignancy. Novel agents designed to interrupt myeloma growth and survival pathways have entered into clinical usage with unprecedented speed, while new prognostic systems based on clinical and biologic features, such as cytogenetic abnormalities, have been developed. A plethora of clinical trials have been initiated utilizing novel agents, alone or in conjunction with established modalities such as conventional cytotoxic agents and stem cell transplantation. These newer treatments have increased the antitumor response rates in this disease and have provided options for patients whose disease has become resistant to conventional therapy. A major challenge is to define the optimal use of these new agents and combinations in order to significantly impact the natural history of myeloma.
Diagnosis and Management of Mild Bleeding Disorders
Authors: Hayward Catherine P. M. 
Published: November 2005

AbstractMild bleeding disorders are a common reason for a referral to a hematologist and these conditions can be challenging to evaluate. Recent research has highlighted that some bleeding symptoms are quite common in the general population and that there is clinical variability in symptom expression among individuals with defined bleeding problems. Moreover, bleeding risks for many bleeding disorders are unknown. This article reviews symptoms and problems that can be considered suspicious of a mild form of bleeding disorder and the diagnostic investigations useful to evaluate these problems. A stepwise approach is presented for the diagnostic evaluation, to allow detection of common and rare coagulation and fibrinolytic defects, and adequate assessments of potential von Willebrand factor and platelet problems. Some common problems in the diagnosis and management of mild bleeding problems are reviewed, including the common failure to establish a diagnosis with testing. An approach is proposed for translation of knowledge to patients who are challenged by mild bleeding problems.
Sexuality and Fertility after Cancer
Authors: Schover Leslie R. 
Published: November 2005

Abstract
As more people achieve long-term survival after cancer, sexual dysfunction and infertility have increasingly been recognized as negative consequences that impact quality of life. Sexual dysfunction is a frequent long-term side effect of cancer treatment, but damage to different underlying physiological systems is salient in men versus women. Men frequently have erectile dysfunction (ED) related to damage to the autonomic nervous system and/or reduced circulation of blood to the penis. Hormonal impairment of sexual function is less common. Women, in contrast, are able to overcome damage to autonomic nerves if genital tissues remain structurally intact and estrogenized. Female sexual dysfunction is frequently associated with sudden premature ovarian failure or direct effects of radiation fibrosis or scar tissue causing pain with sexual activity. The lack of validated interventions for sexual rehabilitation after cancer is a major problem, as is finding cost-effective ways of providing services. Concerns about fertility are also a major source of distress to people treated for cancer during childhood or young adulthood, yet many young survivors do not recall any discussion about future childbearing potential with their oncology team. Since fertility preservation is becoming more practical for both men and women, producing patient and professional educational materials and developing professional practice guidelines should be high priorities for oncology societies.
Familial and Acquired Hemophagocytic Lymphohistiocytosis
Authors: Janka Gritta , zur Stadt Udo 
Published: November 2005

AbstractHemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by uncontrolled hyperinflammation on the basis of various inherited or acquired immune deficiencies. Cardinal symptoms are prolonged fever, hepatosplenomegaly and cytopenias. Central nervous system (CNS) symptoms are common. Biochemical markers include elevated triglyceride and ferritin, high levels of the α chain of the soluble interleukin-2 receptor and low fibrinogen. Impaired function of natural killer (NK) cells and cytotoxic T-cells (CTL) is a characteristic of all forms of HLH.Genetic HLH occurs in familial forms (FHLH), in which HLH is the primary and only manifestation, and in association with the immune deficiencies Chédiak-Higashi syndrome (CHS), Griscelli syndrome (GS) and X-linked lymphoproliferative syndrome (XLP), in which secondary HLH occurs sporadically. Most patients with acquired HLH have no known underlying immune deficiency. Both acquired and genetic forms are triggered by infections, mostly viruses, or other stimuli. HLH also occurs as a complication of rheumatic diseases (macrophage activation syndrome) and of malignancies. The recent discovery of several genetic defects causing FHLH as well as the identification of the genes responsible for CHS, GS and XLP have underscored the role of granule (perforin/granzymes)-mediated cytotoxicity in both the killing of infected cells and the termination of the immune response. The immediate aim of therapy is suppression of the increased inflammatory response by immunosuppressive/immunomodulatory agents and cytotoxic drugs. Genetic cases can only be cured with stem cell transplantation. Awareness of the clinical symptoms and of diagnostic criteria for HLH is crucial to starting life-saving therapy in time.
IL-2 administration increases CD4+CD25hi Foxp3+ regulatory T cells in cancer patients
Authors: Ahmadzadeh Mojgan , Rosenberg Steven A. 
Published: November 2005

AbstractInterleukin-2 (IL-2) is historically known as a T-cell growth factor. Accumulating evidence from knockout mice suggests that IL-2 is crucial for the homeostasis and function of CD4+CD25+ regulatory T cells in vivo. However, the impact of administered IL-2 in an immune intact host has not been studied in rodents or humans. Here, we studied the impact of IL-2 administration on the frequency and function of human CD4+CD25hi T cells in immune intact patients with melanoma or renal cancer. We found that the frequency of CD4+CD25hi T cells was significantly increased after IL-2 treatment, and these cells expressed phenotypic markers associated with regulatory T cells. In addition, both transcript and protein levels of Foxp3, a transcription factor exclusively expressed on regulatory T cells, were consistently increased in CD4 T cells following IL-2 treatment. Functional analysis of the increased number of CD4+CD25hi T cells revealed that this population exhibited potent suppressive activity in vitro. Collectively, our results demonstrate that administration of high-dose IL-2 increased the frequency of circulating CD4+CD25hi Foxp3+ regulatory T cells. Our findings suggest that selective inhibition of IL-2-mediated enhancement of regulatory T cells may improve the therapeutic effectiveness of IL-2 administration. (Blood. 2006;107:2409-2414)
B-lymphocyte stimulator (BLyS) stimulates immunoglobulin production and malignant B-cell growth in Waldenström macroglobulinemia
Authors: Elsawa Sherine F. , Novak Anne J. , Grote Deanna M. , Ziesmer Steven C. , Witzig Thomas E. , Kyle Robert A. , Dillon Stacey R. , Harder Brandon , Gross Jane A. , Ansell Stephen M. 
Published: November 2005

AbstractWaldenström macroglobulinemia (WM) is a serious and frequently fatal B-cell malignancy associated with an elevated monoclonal IgM protein in the serum. Many of the mechanisms leading to this disease are not yet known. B-lymphocyte stimulator (BLyS) is a TNF family member that is critical for maintenance of normal B-cell development and homeostasis. BLyS is overexpressed in a variety of B-cell malignancies and has been shown to inhibit apoptosis in malignant B cells. It also regulates immunoglobulin secretion by normal B cells. To determine the relevance of BLyS in WM, we examined the role of BLyS in WM patient samples. Malignant B cells were found to bind soluble BLyS and variably express the receptors BAFF-R, TACI, and BCMA. We also found expression of BLyS in bone marrow specimens by immunohistochemistry and elevated serum BLyS levels in patients with WM. BLyS, alone or in combination with cytokines that induce immunoglobulin production, was found to increase IgM secretion by malignant B cells. Furthermore, BLyS was found to increase the viability and proliferation of malignant B cells from WM patients. Due to the role of BLyS in WM, strategies to inhibit BLyS may potentially have therapeutic efficacy in these patients.
Genome-wide identification of the regulatory targets of a transcription factor using biochemical characterization and computational genomic analysis
Authors: Jolly Emmitt R , Chin Chen-Shan , Herskowitz Ira , Li Hao 
Published: November 2005

Abstract
Background
A major challenge in computational genomics is the development of methodologies that allow accurate genome-wide prediction of the regulatory targets of a transcription factor. We present a method for target identification that combines experimental characterization of binding requirements with computational genomic analysis.

Results
Our method identified potential target genes of the transcription factor Ndt80, a key transcriptional regulator involved in yeast sporulation, using the combined information of binding affinity, positional distribution, and conservation of the binding sites across multiple species. We have also developed a mathematical approach to compute the false positive rate and the total number of targets in the genome based on the multiple selection criteria.

Conclusion
We have shown that combining biochemical characterization and computational genomic analysis leads to accurate identification of the genome-wide targets of a transcription factor. The method can be extended to other transcription factors and can complement other genomic approaches to transcriptional regulation.
How and why community hospital clinicians document a positive screen for intimate partner violence: a cross-sectional study
Authors: Gerber Megan R , Leiter Karen S , Hermann Richard C , Bor David H 
Published: November 2005

Abstract

Background
This two-part study examines primary care clinicians' chart documentation and attitudes when confronted by a positive waiting room screen for intimate partner violence (IPV).

Methods
Patients at community hospital-affiliated health centers completed a screening questionnaire in waiting rooms that primary care providers (PCPs) were subsequently given at the time of the visit. We first reviewed the medical records of patients who screened positive for IPV, evaluating the presence and quality of documentation. Next we administered a survey to PCPs that measured their knowledge, attitudes and practice regarding IPV.

Results
Seventy-two percent of charts contained some documentation of IPV, however only 10% contained both a referral and safety plan. PCPs were more likely to refer patients (p < .05) who screened positively for mood or anxiety disorders, disclosed that they feared for their safety or were economically disadvantaged. Those that feared for their safety or endorsed mood or anxiety disorders were more likely to have notation of a safety plan in their records. When surveyed, 81.6% of clinicians strongly agreed that it is their role to inquire about IPV, but only 68% expressed confidence in their ability to manage it. In contrast, 93% expressed confidence in managing depression. Sixty-seven percent identified time constraints as a barrier to care. Predictors of PCP confidence in treating patients who have experienced IPV (p < .05) included hours of recent training and clinical experience with IPV.

Conclusion
Mandatory waiting room screening for IPV does not result in high levels of referral or safety planning by PCPs. Despite the implementation of a screening process, clinicians lack confidence and time to address IPV in their patient populations suggesting that alternative methods of training and supporting PCPs need to be developed.
Smoking, oxidative stress and inflammation: Impact on resting energy expenditure in diabetic nephropathy
Authors: Agarwal Rajiv 
Published: November 2005

Abstract

Background
Inflammation is associated with increased resting energy expenditure (REE) in patients with chronic kidney disease. Oxidative stress, on the other hand, appears not to increase REE. Smoking is a common mechanism for generating oxidative stress and inflammation. Whether smokers have increased REE and if so, whether it is accounted for by the pro-oxidant and inflammatory state is not known.

Methods
A case control study of 11 smokers and 24 non-smokers with overt diabetic nephropathy was performed to evaluate the chronic effect of smoking on REE. REE (indirect calorimetry), glomerular filtration rate (iothalamate clearance), markers of oxidative stress (urinary and plasma malondialdehyde (MDA), and protein carbonyls) and inflammation (C-reactive protein, tumor necrosis factor-alpha, interleukin-6) were measured on two occasions four months apart.

Results
Biomarkers of inflammation (C-reactive protein) and oxidative stress (urinary and plasma MDA) were increased in smokers. REE was increased in smokers, 24.3 kcal/kg/day compared to 21 kcal/kg/day (p = 0.009) in non-smokers. After adjusting for age, GFR, MDA, C-reactive protein, and hemoglobin A1C the difference in REE between the two groups persisted (adjusted difference 3.51 kcal/kg/d, 95% confidence interval 0.59 – 6.45, p = 0.020).

Conclusion
Patients with overt diabetic nephropathy who smoke have a higher REE, oxidative and inflammatory state. Elevated REE is not attributable to heightened oxidative stress and inflammatory state. Smoking is an independent risk factor for elevated REE in patients with diabetic nephropathy and provides an additional mechanism by which it may lead to poor outcomes.
Teratoma occupying the left hemithorax
Authors: Zisis Charalambos , Rontogianni Dimitra , Stratakos Grigorios , Voutetakis Konstantinos , Skevis Konstantinos , Argiriou Mihalis , Bellenis Ion 
Published: November 2005

Abstract

Background
Teratomas are manifested with a great variety of clinical and radiological features, while sometimes they simply represent incidental findings.

Case presentation
A rare case of benign teratoma of the dermoid cyst type, in an adult 40-year-old female patient, is reported. The patient had presented recurrent pulmonary infections for the previous 2 months, persistent cough, and progressively aggravating dyspnea. A chest X-ray showed total atelectasis of the left lung, and the thoracic CT-scan revealed a huge mass, containing multiple elements of heterogeneous density, probably originating from the mediastinum, occupying the whole left hemithorax. The mass compressed the vital structures of the mediastinum, great vessels and airways, and a chest MRI was performed to accurately detect the anatomical relations. The patient underwent left thoracotomy and the tumor was totally resected. The size of the tumor was extremely large although no invasion to the vessels or to the airway had occurred. Adherence to the adjacent left pulmonary artery and left main bronchus was present, but without erosion or fistulization. The postoperative course was uneventful, while the histological examination confirmed a teratoma.

Conclusion
A teratoma is a non-homogeneous pathological entity, clinically, radiologically or histologically. It is predominantly diagnosed between the second and fourth decade and the incidence is equal for both sexes. Symptoms are absent in one half of the patients. The case reported is noteworthy as the tumor appeared with total atelectasis of the left lung, and symptoms started 2 months prior to diagnosis. Total removal of the tumor is adequate treatment for this type of teratoma and the prognosis is excellent.
Intermittent pneumatic compression for prevention of pulmonary thromboembolism after gynecologic surgery
Authors: Suzuki Nao , Kataoka Fumio , Higashiguchi Atsushi , Hirao Takeshi , Ezawa Sachiko , Nomura Hiroyuki , Tomita Akiyo , Susumu Nobuyuki , Aoki Daisuke 
Published: November 2005

Abstract

Background
To investigate the incidence of pulmonary embolism and risk factors for this condition after obstetric and gynecologic surgery, as well as the efficacy of intermittent pneumatic compression.

Methods
A total of 6,218 patients operated at Keio University Hospital excluding obstetric or infertility-related surgery and uterine cervical conization were evaluated retrospectively to determine the preventive effect of intermittent pneumatic compression on postoperative pulmonary embolism.

Results
Pulmonary embolism occurred in 42 patients (0.68%). Multivariate analysis showed that malignancy, blood transfusion, and a body mass index ≥25 kg/m2 or ≥28 kg/m2 were independent risk factors for postoperative pulmonary embolism. A significantly lower incidence of pulmonary embolism occurred in patients receiving pneumatic compression postoperatively versus those without it. Among gynecologic malignancies, endometrial cancer was a significant risk factor for pulmonary embolism.

Conclusion
Preventive measures, including intermittent pneumatic compression, should be taken to avoid postoperative pulmonary thromboembolism in the gynecology field.
Activation of nuclear factor kappa B (NF-κB) by connective tissue growth factor (CCN2) is involved in sustaining the survival of primary rat hepatic stellate cells
Authors: Gao Runping , Brigstock David R 
Published: November 2005

Abstract

Background/Aims
Connective tissue growth factor (CCN2) is a matricellular protein that plays a role in hepatic stellate cell (HSC)-mediated fibrogenesis. The aim of this study was to investigate the regulation by CCN2 of cell survival pathways in primary HSC.

Methods
Primary HSC were obtained by in situ enzymatic perfusion of rat liver. NF-κB activation was assessed by immunoblotting for IκBα phosphorylation and degradation and by NF-κB p50 or p65 nuclear accumulation. NF-κB DNA-binding activity was determined by gel mobility shift assay while NF-κB response gene expression was evaluated using a luciferase reporter. Cell viability was assessed by Trypan blue staining or ATP luminescent assay while apoptosis was evaluated by caspase-3 activity.

Results
CCN2 induced IκBα phosphorylation and degradation as well as nuclear accumulation of NF-κB. Activated NF-κB comprised three dimers, p65/p65, p65/p50 and p50/p50, that individually bound to DNA-binding sites and subsequently triggered transcriptional activity. This was confirmed by showing that CCN2 promoted activity of a NF-κB luciferase reporter. CCN2 promoted survival of serum-starved HSC and protected the cells from death induced by blocking the NF-κB signaling pathway using Bay-11-7082, a specific inhibitor of IκBα phosphorylation.

Conclusion
CCN2 contributes to the survival of primary HSC through the NF-κB pathway.