bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 10-year follow-up of the effect of continuous-combined hormone replacement therapy and its discontinuation on bone in postmenopausal women
Authors: Heikkinen Jorma , Vaheri Raija , Haapalahti Jouko , Timonen Ulla 
Published: May 2008

Objective To establish the effect on bone mineral density (BMD) of long-term (nine years) continuous-combined hormone replacement therapy (ccHRT) with estradiol valerate/medroxyprogesterone acetate (E2V/MPA) and follow-up one year after discontinuation of ccHRT. Study design A total of 279 women were treated with daily dosages of E2V + MPA: 1 mg + 2.5 mg (n = 69), 1 mg + 5 mg (n = 70) or 2 mg + 5 mg (n = 140) (Indivina®, Orion Pharma, Espoo, Finland) for 8.5 years; all subjects received the lowest dosage for the next six months. BMD was measured at baseline, between 6 and 12 months, annually until the end of study and at one-year postdiscontinuation of ccHRT. Main outcome measure Change in BMD during nine years of treatment with ccHRT and at one-year post-discontinuation of ccHRT. Results Progressive increase of vertebral BMD was observed with all dosage regimens throughout nine years, with corresponding reduction in the proportion of women fulfilling criteria for osteoporosis or osteopaenia. Femoral neck BMD reached a peak at about five to six years, whereas in the lumbar spine the BMD increase was sustained until the end of the study treatment. Mean BMD declined after cessation of ccHRT use but remained substantially above baseline levels. In a subset of women (n = 58) there was a rapid (≤4%) loss of vertebral BMD in the year after termination of ccHRT use. These women had lower than average BMD at baseline but no other factor was identified that distinguished them from the overall study population. Conclusions Low-dose ccHRT in postmenopausal women is associated with increases in lumbar spine BMD for at least nine years. These gains are not sustained after cessation of therapy but the rate of BMD loss varies between individuals.
Direct Determination of Lipoprotein Particle Sizes and Concentrations by Ion Mobility Analysis
Authors: Caulfield Michael P , Li Shuguang , Lee Gloria , Blanche Patricia J , Salameh Wael A , Benner W Henry , Reitz Richard E , Krauss Ronald M 
Published: May 2008

AbstractBackground: Current methods for measuring the concentrations of lipoprotein particles and their distributions in particle subpopulations are not standardized. We describe here and validate a new gas-phase differential electrophoretic macromolecular mobility-based method (ion mobility, or IM) for direct quantification of lipoprotein particles, from small, dense HDL to large, buoyant, very-low-density lipoprotein (VLDL).Methods: After an ultracentrifugation step to remove albumin, we determined the size and concentrations of lipoprotein particles in serum samples using IM. Scan time is 2 min and covers a particle range of 17.2–540.0 Å. After scanning, data are pooled by totaling the particle number across a predetermined size range that corresponds to particular lipoprotein subclasses. IM results were correlated with those of standard methods for cholesterol and apolipoprotein analysis.Results: Intra- and interassay coefficients of variation for LDL particle size were &lt;1.0%. The intra- and interassay variation for LDL and HDL particle subfraction measurements was &lt;20%. IM-measured non-HDL correlated well with apolipoprotein B (r = 0.92).Conclusions: The IM method provides accurate, reproducible, direct determination of size and concentration for a broad range of lipoprotein particles. Use of this methodology in studies of patients with cardiovascular disease and other pathologic states will permit testing of its clinical utility for risk assessment and management of these conditions.
Delayed Acclimatization of the Ventilatory Threshold in Healthy Trekkers
Authors: Myers Stephen D. , Biccard Bruce M. , Chan Colin , Imray Christopher H.E. , Wright Alexander D. , Pattinson Kyle T.S. 
Published: May 2008

Objective To test the hypothesis that acclimatization to high altitude results in an improvement of the ventilatory threshold (VT). Methods Eight lowlanders underwent cardiopulmonary exercise testing with a cycle ergometer to determine VT and peak oxygen uptake (Vo2peak) in Coventry, United Kingdom (altitude: 80 m), on arrival in Leh, India (altitude: 3500 m), and after 12 days of acclimatization that included a 5-day high altitude trek up to 4770 m. Results Vo2peak fell on arrival at 3500 m and remained depressed at 12 days. VT was depressed on arrival at high altitude and was further depressed at 12 days. VT as a proportion of the Vo2peak was decreased on arrival at high altitude, and after acclimatization, this relationship was further decreased. Conclusions Individuals who are sedentary or not participating in regular physical training appear to require a longer period of acclimatization than trained athletes. With the increasing numbers participating in high-altitude trekking and charity climbs of peaks, such as Mt. Kilimanjaro, this information has clinically significant practical implications for those leading or acting as medical advisors.
Characterization of a Novel Ubiquitin-Conjugating Enzyme That Regulates β1,4-Galactosyltransferase-1 in Embryonic Stem Cells
Authors: Wassler Michael J. , Shur Barry D. , Zhou Wenxia , Geng Yong-Jian 
Published: May 2008

Abstract
In this study we identified a novel galactosyltransferase 1-associating protein (GTAP) by cDNA cloning from a murine embryonic cDNA library using the two-hybrid yeast system. GTAP is expressed in early embryonic tissues, as well as in adult tissues with active cell turnover, and belongs to the class III ubiquitin-conjugating (E2) enzyme family. Its COOH-terminal domain contains a consensus sequence for ubiquitin binding shared by all the ubiquitin-conjugating enzymes, whereas its NH2-terminal domain appears critical for the binding and internalization of cell surface galactosyltransferase 1 (GalT1) in embryonic stem cells through a monensin- and MG132-dependent pathway. We have found that GTAP regulates GalT1-associated, laminin-dependent embryonic cell adhesion and the formation of embryoid bodies. Thus, GTAP functions as an evolutionarily conserved E2 enzyme, which may participate in intercellular adhesion and embryonic development.
Disclosure of potential conflicts of interest is found at the end of this article.
Fate-Mapping Evidence That Hepatic Stellate Cells Are Epithelial Progenitors in Adult Mouse Livers
Authors: Yang Liu , Jung Youngmi , Omenetti Alessia , Witek Rafal P. , Choi Steve , Vandongen Hendrika M. , Huang Jiawen , Alpini Gianfranco D. , Diehl Anna Mae 
Published: May 2008

Abstract
Liver injury activates quiescent hepatic stellate cells (Q-HSC) to proliferative myofibroblasts. Accumulation of myofibroblastic hepatic stellate cells (MF-HSC) sometimes causes cirrhosis and liver failure. However, MF-HSC also promote liver regeneration by producing growth factors for oval cells, bipotent progenitors of hepatocytes and cholangiocytes. Genes that are expressed by primary hepatic stellate cell (HSC) isolates overlap those expressed by oval cells, and hepatocytic and ductular cells emerge when HSC are cultured under certain conditions. We evaluated the hypothesis that HSC are a type of oval cell and, thus, capable of generating hepatocytes to regenerate injured livers. Because Q-HSC express glial fibrillary acidic protein (GFAP), we crossed mice in which GFAP promoter elements regulated Cre-recombinase with ROSA-loxP-stop-loxP-green fluorescent protein (GFP) mice to generate GFAP-Cre/GFP double-transgenic mice. These mice were fed methionine choline-deficient, ethionine-supplemented diets to activate and expand HSC and oval cell populations. GFP(+) progeny of GFAP-expressing precursors were characterized by immunohistochemistry. Basal expression of mesenchymal markers was negligible in GFAP(+)Q-HSC. When activated by liver injury or culture, HSC downregulated expression of GFAP but remained GFP(+); they became highly proliferative and began to coexpress markers of mesenchyme and oval cells. These transitional cells disappeared as GFP-expressing hepatocytes emerged, began to express albumin, and eventually repopulated large areas of the hepatic parenchyma. Ductular cells also expressed GFAP and GFP, but their proliferative activity did not increase in this model. These findings suggest that HSC are a type of oval cell that transitions through a mesenchymal phase before differentiating into hepatocytes during liver regeneration.
Disclosure of potential conflicts of interest is found at the end of this article.
Improved Efficiency and Pace of Generating Induced Pluripotent Stem Cells from Human Adult and Fetal Fibroblasts
Authors: Mali Prashant , Ye Zhaohui , Hommond Holly H. , Yu Xiaobing , Lin Jeff , Chen Guibin , Zou Jizhong , Cheng Linzhao 
Published: May 2008

Abstract
It was reported recently that human fibroblasts can be reprogrammed into a pluripotent state that resembles that of human embryonic stem (hES) cells. This was achieved by ectopic expression of four genes followed by culture on mouse embryonic fibroblast (MEF) feeders under a condition favoring hES cell growth. However, the efficiency of generating human induced pluripotent stem (iPS) cells is low, especially for postnatal human fibroblasts. We started supplementing with an additional gene or bioactive molecules to increase the efficiency of generating iPS cells from human adult as well as fetal fibroblasts. We report here that adding SV40 large T antigen (T) to either set of the four reprogramming genes previously used enhanced the efficiency by 23–70-fold from both human adult and fetal fibroblasts. Discernible hES-like colonies also emerged 1–2 weeks earlier if T was added. With the improved efficiency, we succeeded in replacing MEFs with immortalized human feeder cells that we previously established for optimal hES cell growth. We further characterized individually picked hES-like colonies after expansion (up to 24 passages). The majority of them expressed various undifferentiated hES markers. Some but not all the hES-like clones can be induced to differentiate into the derivatives of the three embryonic germ layers in both teratoma formation and embryoid body (EB) formation assays. These pluripotent clones also differentiated into trophoblasts after EB formation or bone morphogenetic protein 4 induction as classic hES cells. Using this improved approach, we also generated hES-like cells from homozygous fibroblasts containing the sickle cell anemia mutation Hemoglobin Sickle.
Disclosure of potential conflicts of interest is found at the end of this article.
Use of Intravenous Bisphosphonates in Older Women with Breast Cancer
Authors: Giordano Sharon H. , Fang Shenying , Duan Zhigang , Kuo Yong-Fang , Hortobagyi Gabriel N. , Goodwin James S. 
Published: May 2008

Abstract

Learning Objectives
After completing this course, the reader will be able to: Make optimal use of i.v. bisphosphonates in women with breast cancer.Uphold the current guidelines for the use of bisphosphonates among women with metastatic breast cancer.Assess the relationship between bisphosphonate use and patient age.
CME This article is available for continuing medical education credit at CME.TheOncologist.com

Introduction.
i.v. bisphosphonates reduce skeletal events in women with bone metastases from breast cancer, but little is known about the prevalence and duration of bisphosphonate use.

Methods.
Patients were identified from the Surveillance, Epidemiology, and End Results–Medicare database who were aged ≥65 years and were diagnosed with invasive breast cancer in 1995–2002. Healthcare Common Procedure Coding System codes were used to identify patients treated with pamidronate and zoledronic acid. Descriptive statistics were used to describe patterns of use. Multivariate analyses were performed to determine the predictors of bisphosphonate use.

Results.
In total, 55,864 women with breast cancer were included, with 307,467 person-years of follow-up. Overall, 1.26% of women with all stages of breast cancer received i.v. bisphosphonates. In 2004, 2% of all breast cancer patients and 32% of patients with distant stage disease received bisphosphonates. Approximately two thirds of patients treated with bisphosphonates received zoledronic acid and one third received pamidronate in 2004. Multivariate analyses showed that patients who were ≥75 years old were less likely to receive bisphosphonates (75–79 years versus 65–69 years: odds ratio [OR], 0.81; 95% confidence interval [CI], 0.70–0.93; 80+ years versus 65–69 years: OR, 0.49; 95% CI, 0.42–0.57). The use of bisphosphonates dramatically increased over time. The majority of living patients were continued on i.v. bisphosphonates once started (83% at 1 year, 64% at 3 years, 50% at 5 years), but the median survival time after initiation of i.v. bisphosphonates was only 21 months.

Conclusions.
i.v. bisphosphonates appear to be underused in patients with metastatic breast cancer, particularly among those patients &gt;75 years of age.
Integrated Analysis of Zoledronic Acid for Prevention of Aromatase Inhibitor–Associated Bone Loss in Postmenopausal Women with Early Breast Cancer Receiving Adjuvant Letrozole
Authors: Brufsky Adam , Bundred Nigel , Coleman Robert , Lambert-Falls Rosemary , Mena Raul , Hadji Peyman , Jin Lixian , Schenk Nora , Ericson Solveig , Perez Edith A. 
Published: May 2008

Abstract

Learning Objectives
After reading this article, the reader should be able to: Monitor for and treat to prevent bone loss in postmenopausal breast cancer patients receiving an aromatase inhibitor.Describe the methodology of the Z-FAST and ZO-FAST clinical trials.Discuss the effectiveness and tolerability of zoledronic acid when administrated to prevent bone loss associated with aromatase inhibitors.
CME This article is available for continuing medical education credit at CME.TheOncologist.com

Background.
The interim (12-month) results of two similarly designed, ongoing studies (the Zometa®-Femara® Adjuvant Synergy Trials [Z-FAST and ZO-FAST]) suggest that zoledronic acid (4 mg intravenously every 6 months) when initiated with adjuvant letrozole increases bone mineral density (BMD) of the lumbar spine (LS) in postmenopausal women with early-stage breast cancer compared with patients who receive zoledronic acid only when bone loss became clinically significant or a fragility fracture occurred.

Methods.
An integrated analysis was performed to maximize the value of the large pool of data from the two studies in answering clinically relevant questions. The primary objective was to compare the change in LS BMD at month 12. Secondary objectives included comparing (a) the change in total hip (TH) BMD, (b) changes in bone turnover marker concentrations, (c) time to disease recurrence, and (d) safety at month 12.

Findings.
The integrated analysis included 1,667 patients. At month 12, LS BMD was 5.2% higher in the upfront group than in the delayed group; TH BMD was 3.5% higher. N-telopeptide and bone-specific alkaline phosphatase concentrations decreased by 21.3% and 12.8% in the upfront group and increased by 21.7% and 24.9% in the delayed group, respectively (p &lt; .0001 for intergroup comparisons). Fewer patients receiving upfront zoledronic acid experienced disease recurrence than patients in the delayed group—seven patients (0.84%) versus 17 patients (1.9%) (p = .0401). Fracture rates were similar. No confirmed osteonecrosis of the jaw was reported.

Conclusions.
The results of this analysis strengthen the statistical validity of the preliminary results of the Z-FAST and ZO-FAST studies, showing that upfront zoledronic acid prevents aromatase inhibitor–associated bone loss more effectively than delayed-start zoledronic acid in postmenopausal women with early-stage breast cancer receiving letrozole. Additionally, disease recurrence appears to be lower with upfront zoledronic acid, but further follow-up is needed to confirm these interim results.
Health Economic Evaluation of Treating Anemia in Cancer Patients Receiving Chemotherapy: A Study in Belgian Hospitals
Authors: Spaepen Erik , Demarteau Nadia , Van Belle Simon , Annemans Lieven 
Published: May 2008

AbstractBackground.Erythropoiesis-stimulating agents (ESAs) are used in chemotherapy-induced anemia (CIA) with the goal of improving quality of life and preventing RBC transfusions. This retrospective database study compared the three currently available ESAs, epoetin alfa (EPO-A), epoetin beta (EPO-B), and darbepoetin alfa (DARB), regarding costs and outcomes.Methods.Data were obtained from a Belgian longitudinal database, including medical and financial data on cancer patients receiving chemotherapy and ESAs, submitted by 46 Belgian hospitals. Propensity score matching was applied to correct for selection bias. The main effectiveness parameter was defined as transfusion- and anemia-readmission-free survival (TA-free survival) at 3 months. Costs were analyzed taking the health care payer perspective.Results.Including 1,584 EPO-A, 380 EPO-B, and 429 DARB propensity-matched patients, TA-free survival rates were similar for the three groups (DARB, 84.37%; EPO-A, 84.60%; EPO-B, 84.94%). Overall inpatient costs were €16,949 ± €1,025, €19,472 ± €901, and €19,295 ± €1,048 for DARB, EPO-A, and EPO-B, respectively (DARB versus EPO-A, p &lt; .0001 and DARB versus EPO-B, p = .008). Anemia-associated costs were €3,051 ± €218 in the DARB group, compared with €3,995 ± €144 for EPO-A (p &lt; .0001) and €3,752 ± €229 for EPO-B (p = .0132).Conclusion.To our knowledge, this is the first real-life matched retrospective study comparing ESAs with regard to both costs and effects. For similar patient profiles, the patients in the DARB group consumed the smallest amounts of ESAs, with similar clinical outcomes. These data therefore suggest a greater efficiency of DARB in the treatment of CIA.
Current Management of Medullary Thyroid Cancer
Authors: Sippel Rebecca S. , Kunnimalaiyaan Muthusamy , Chen Herbert 
Published: May 2008

Abstract

Learning Objectives
After completing this course, the reader will be able to: Evaluate a patient with a new diagnosis of medullary thyroid cancer.Use genetic testing for the ret proto-oncogene and assess how the location of the mutation affects the risks for the patient.Select among the surgical treatment options for patients with medullary thyroid cancer, including the optimal surgical treatment for patients with palpable disease as well as those patients who are found to be genetic carriers.
CME This article is available for continuing medical education credit at CME.TheOncologist.com
Medullary thyroid cancer accounts for 5%–10% of all thyroid cancers. The majority of medullary thyroid cancers are sporadic, but 20% of cases are a result of a germline mutation in the ret proto-oncogene. Hereditary medullary thyroid cancer can be seen as part of the multiple endocrine neoplasia syndrome type 2A or 2B or as part of familial medullary thyroid cancer. This article discusses the current methods available for the diagnosis and evaluation of a patient with suspected medullary thyroid cancer. The management of medullary thyroid cancer is predominantly surgical excision, consisting of a total thyroidectomy and lymph node dissection. The extent and timing of surgical excision are discussed. Systemic therapeutic options are limited for medullary thyroid cancer, but several therapeutic targets show promise for the development of new therapies in the future.
The Forgotten Team Member: Meeting the Needs of Oncology Support Staff
Authors: Cashavelly Barbara J. , Donelan Karen , Binda Kathryn D. , Mailhot Johanna R. , Clair-Hayes Katherine A. , Maramaldi Peter 
Published: May 2008

Abstract

Learning Objectives
After completing this course, the reader will be able to: Assess the impact of oncology care on nonlicensed support staff.Identify four areas that challenge support staff caring for oncology patients.Evaluate the impact of burnout and job satisfaction on support staff caring for oncology patients.
CME This article is available for continuing medical education credit at CME.TheOncologist.com

Introduction.
The impact of working in an oncology setting has been widely researched for physicians, nurses, social workers, and chaplains. The experiences of nonlicensed support staff in an oncology setting have rarely been acknowledged or addressed. Few studies have addressed support or education initiatives for support staff caring for oncology patients. The intent of this study was to understand the work experiences of oncology support staff. Emotional impact, patient relationships, and team relationships were addressed. These data would help shape the development of an oncology support staff program.

Methods.
A qualitative and quantitative approach was used to explore the experiences of support staff. Seven focus groups and individual interviews were conducted addressing work life in a cancer center. The quantitative survey collected baseline data on job satisfaction, working relationships, patient relationships, burnout, and support programs.

Results.
Four predominant themes emerged from the focus groups. These included: relationships with patients and families, coping with death and dying, value and recognition, and balancing function with emotion. The quantitative survey reported the highest satisfaction with patient relationships and the lowest satisfaction with job recognition and supervisor support. High personal accomplishment scores declined with duration of employment. Educational grand rounds were a high interest.

Discussion.
This study provides insight into the impact of caring for oncology patients on support staff. Burnout and job satisfaction can be costly. Recognizing the challenges inherent in the oncology environment is essential to supporting a successful oncology practice for licensed and nonlicensed support staff.
EBV-Associated Lymphoproliferative Disorders: Classification and Treatment
Authors: Carbone Antonino , Gloghini Annunziata , Dotti Giampietro 
Published: May 2008

Abstract

Learning Objectives
After completing this course, the reader will be able to: Assess patients with EBV-associated lymphoproliferative disorders.Describe the pathogenesis of the lymphoproliferative disorders linked to EBV infection.Evaluate EBV cell–based immunotherapy for use in patients with EBV-associated lymphoproliferative disorders.
CME This article is available for continuing medical education credit at CME.TheOncologist.com
Since its discovery as the first human tumor virus, Epstein-Barr virus (EBV) has been implicated in the development of a wide range of B-cell lymphoproliferative disorders, including Burkitt's lymphoma, classic Hodgkin's lymphoma, and lymphomas arising in immunocompromised individuals (post-transplant and HIV-associated lymphoproliferative disorders). T-cell lymphoproliferative disorders that have been reported to be EBV associated include a subset of peripheral T-cell lymphomas, angioimmunoblastic T-cell lymphoma, extranodal nasal type natural killer/T-cell lymphoma, and other rare histotypes. EBV encodes a series of products interacting with or exhibiting homology to a wide variety of antiapoptotic molecules, cytokines, and signal transducers, hence promoting EBV infection, immortalization, and transformation. However, the exact mechanism by which EBV promotes oncogenesis is an area of active debate. The focus of this review is on the pathology, diagnosis, classification, and pathogenesis of EBV-associated lymphomas. Recent advances in EBV cell–based immunotherapy, which is beginning to show promise in the treatment of EBV-related disorders, are discussed.