bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship Between Epidemiologic Risk Factors and Breast Cancer Recurrence
Authors: Brewster Abenaa M. , Do Kim-Anh , Thompson Patricia A. , Hahn Karin M. , Sahin Aysegul A. , Cao Yumei , Stewart Maureen M. , Murray James L. , Hortobagyi Gabriel N. , Bondy Melissa L. 
Published: September 2007

Purpose Early-stage breast cancers are biologically heterogeneous and vary in clinical behavior, supporting the role of factors other than tumor size and lymph node involvement as outcome determinants. We evaluated the effect of epidemiologic breast cancer risk factors on recurrence in women with early-stage disease. Patients and Methods Medical records from 2,327 women with early-stage breast cancer, treated at the M.D. Anderson Cancer Center between 1985 and 2000, were used to derive information on epidemiologic, clinical, and histological factors. Cox proportional hazards models were used to estimate the hazard ratios of 5-year risk of breast cancer recurrence adjusted for treatment and stage. Statistical tests were two-sided. Results None of the breast cancer risk factors were associated with recurrence, adjusting for tumor characteristics and treatment. A significant interaction between hormone replacement therapy (HRT) use and tumor hormone receptor status on risk of recurrence (P = .0003) was observed. Among ever-users of HRT, recurrence risk was two-fold lower for estrogen receptor (ER) –positive and progesterone receptor (PR) –positive tumors compared with ER- and PR-negative tumors; whereas, among never-users of HRT, there was no statistically significant association between recurrence risk and receptor status. Conclusion HRT users who develop receptor-positive early-stage disease have better outcomes than those who develop receptor-negative disease. Among never-users of HRT, the expected beneficial effect of ER- or PR-positive tumors on recurrence risk was absent. These data lend support to the notion that the biology of hormone receptor–positive disease in HRT users differs from that in nonusers.
Randomized Active-Controlled Phase II Study of Denosumab Efficacy and Safety in Patients With Breast Cancer-Related Bone Metastases
Authors: Lipton Allan , Steger Guenther G. , Figueroa Jazmin , Alvarado Cristina , Solal-Celigny Philippe , Body Jean-Jacques , de Boer Richard , Berardi Rossana , Gascon Pere , Tonkin Katia S. , Coleman Robert , Paterson Alexander H.G. , Peterson Mark C. , Fan Michelle , Kinsey Amy , Jun Susie 
Published: September 2007

Purpose Denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor-κB ligand, suppresses bone resorption. In this study, we evaluated the efficacy and safety of five dosing regimens of denosumab in patients with breast cancer-related bone metastases not previously treated with intravenous bisphosphonates (IV BPs). Patients and Methods Eligible women (n = 255) with breast cancer-related bone metastases were stratified by type of antineoplastic therapy received and randomly assigned to one of six cohorts (five denosumab cohorts [blinded to dose and frequency]; one open-label IV BP cohort). Denosumab was administered subcutaneously every 4 weeks (30, 120, or 180 mg) or every 12 weeks (60 or 180 mg). The primary end point was percentage of change in the bone turnover marker urine N-telopeptide corrected for urine creatinine (uNTx/Cr) from baseline to study week 13. The percentage of patients achieving more than 65% uNTx/Cr reduction, time to more than 65% uNTx/Cr reduction, patients experiencing one or more on-study skeletal-related events (SRE), and safety were also evaluated. Results At study week 13, the median percent reduction in uNTx/Cr was 71% for the pooled denosumab groups and 79% for the IV BP group. Overall, 74% of denosumab-treated patients (157 of 211) achieved a more than 65% reduction in uNTx/Cr compared with 63% of bisphosphonate-treated patients (27 of 43). On-study SREs were experienced by 9% of denosumab-treated patients (20 of 211) versus 16% of bisphosphonate-treated patients (seven of 43). No serious or fatal adverse events related to denosumab occurred. Conclusion Subcutaneous denosumab may be similar to IV BPs in suppressing bone turnover and reducing SRE risk. The safety profile was consistent with an advanced breast cancer population receiving systemic therapy.
Melphalan, Prednisone, and Lenalidomide Treatment for Newly Diagnosed Myeloma: A Report From the GIMEMA—Italian Multiple Myeloma Network
Authors: Palumbo Antonio , Falco Patrizia , Corradini Paolo , Falcone Antonietta , Di Raimondo Francesco , Giuliani Nicola , Crippa Claudia , Ciccone Giovannino , Omedè Paola , Ambrosini Maria Teresa , Gay Francesca , Bringhen Sara , Musto Pellegrino , Foà Robin , Knight Robert , Zeldis Jerome B. , Boccadoro Mario , Petrucci Maria Teresa 
Published: September 2007

Purpose Lenalidomide has shown significant antimyeloma activity in clinical studies. Oral melphalan, prednisone, and thalidomide have been regarded as the standard of care in elderly multiple myeloma patients. We assessed dosing, efficacy, and safety of melphalan, prednisone, and lenalidomide (MPR) in newly diagnosed elderly myeloma patients. Patients and Methods Oral melphalan was administered in doses ranging from 0.18 to 0.25 mg/kg on days 1 to 4, prednisone at a 2-mg/kg dose on days 1 to 4, and lenalidomide at doses ranging from 5 to 10 mg on days 1 to 21, every 28 days for nine cycles, followed by maintenance therapy with lenalidomide alone. Aspirin was given as a prophylaxis for thrombosis. Results Fifty-four patients were enrolled and evaluated after completing the assigned treatment schedule. The maximum tolerated dose was defined as 0.18 mg/kg melphalan and 10 mg lenalidomide. With these doses, 81% of patients achieved at least a partial response, 47.6% achieved a very good partial response, and 23.8% achieved a complete immunofixation-negative response. In all patients, 1-year event-free and overall survival rates were 92% and 100%, respectively. At the maximum tolerated dose, grade 3 adverse events included neutropenia (38.1%), thrombocytopenia (14.2%), febrile neutropenia (9.5%), vasculitis (9.5%), and thromboembolism (4.8%); grade 4 adverse events were neutropenia (14.2%) and thrombocytopenia (9.5%). Conclusion Oral MPR therapy is a promising first-line treatment for elderly myeloma patients. Hematologic adverse events were frequent but manageable. A low incidence of nonhematologic adverse events was noted. Aspirin appears to provide adequate antithrombosis prophylaxis.
Bone Mineral Density in Adults with the Metabolic Syndrome: Analysis in a Population-Based U.S. Sample
Authors: Kinjo Mitsuyo , Setoguchi Soko , Solomon Daniel H. 
Published: September 2007

Abstract
Background: The metabolic syndrome is associated with low-grade inflammation. It has been suggested that proinflammatory cytokines and low-grade systemic inflammation activate bone resorption and may lead to reduced bone mineral density (BMD), but no previous studies have evaluated the association between the metabolic syndrome and BMD. We examined this relationship in a representative U.S. population-based sample from the Third National Health and Nutrition Examination Survey (NHANES III, 1988–1994).
Methods: We identified adult subjects enrolled in NHANES III with the metabolic syndrome as defined by the criteria of the Adult Treatment Panel III. We conducted a cross-sectional analysis of femoral neck BMD (FN-BMD) for subjects with and without the metabolic syndrome. Analyses were adjusted for relevant covariates and stratified by quintile of body mass index.
Results: Among 8197 persons at least 20 yr old who underwent FN-BMD measurement, 1773 (22%) had the metabolic syndrome. After multivariable adjustment, FN-BMD was higher among subjects with the metabolic syndrome (0.86 g/cm2) than those without (0.80 g/cm2; P &lt; 0.0001). When stratified by body mass index, FN-BMD was similar between subjects with and without the metabolic syndrome. Adjusted FN-BMD increased with additional components of the metabolic syndrome (P &lt; 0.0001 for trend), and there was a significant positive association with abdominal obesity (P &lt; 0.0001). A subgroup of subjects with diabetes had higher FM-BMD than those without, independent of abdominal obesity.
Conclusions: In NHANES III, the metabolic syndrome was not associated with reduced FN-BMD.
An analytical model for the natural frequencies of a railway wheel and comparison with experimental results
Authors: Sakamoto H 
Published: September 2007

Vibration generated at the contact surface between rails and wheels have been considered the main cause of noise from railway vehicles. Such noises are classified into three types: rolling, impact, and squeal noises. The mechanisms by which each noise is generated have been well researched. The current study treats mainly lateral and vertical vibrations of railway wheels, and focuses on squeal noises that originate on curves. The current study includes calculations of the natural frequencies of wheels based on elasticity theory, laboratory tests to measure the natural frequencies of wheels, and field tests to measure the sounds and vibrations of railway wheels. Many researchers have calculated natural frequencies by the finite-element method, which can give the exact quantitative number when information such as the model and boundary conditions is correct. The author obtained frequencies by elasticity theory, because a qualitative understanding is thought necessary, regardless of the boundary condition. The results of the current study showed that the origin of the squeal noise on a curved track comes from the lateral vibration of the wheel; but it is shown that the dominant component of rolling noise on a straight track at around 800 Hz is not related to wheel vibration.
Analysis of the structural characteristics of an intermediate rail vehicle and their effect on vehicle crash performance
Authors: Xue X , Schmid F , Smith R A 
Published: September 2007

In the current paper, the authors present an analysis of the structural characteristics of an intermediate rail vehicle and their effects on crash performance of the vehicle. Theirs is a simulation based analysis involving four stages. First, the crashworthiness of the vehicle is assessed by simulating an impact of the vehicle with a rigid wall. Second, the structural characteristics of the vehicle are analysed based on the structural behaviour during this impact and then the structure is modified. Third, the modified vehicle is tested again in the same impact scenario with a rigid wall. Finally, the modified vehicle is subjected to a modelled head-on impact which mirrors the real-life impact interface between two intermediate vehicles in a train impact. The emphasis of the current study is on the structural characteristics of the intermediate vehicle and the differences compared to an impact of a leading vehicle. The study shows that, similar to a leading vehicle, bending, or jackknifing is a main form of failure in this conventionally designed intermediate vehicle. It has also been found that the location of the door openings creates a major difference in the behaviour of an intermediate vehicle. It causes instability of the vehicle in the door area and leads to high stresses at the joint of the end beam with the solebar and shear stresses at the joint of the inner pillar with the cantrail. Apart from this, the shapes of the vehicle ends and impact interfaces are also different and have an effect on the crash performance of the vehicles. The simulation results allow the identification of the structural characteristics and show the effectiveness of relevant modifications. The conclusions have general relevance for the crashworthiness of rail vehicle design.
Fingolimod: A Novel Immunosuppressant for Multiple Sclerosis
Authors: Brown Brandon A , Kantesaria Pranish P , McDevitt Lisa M 
Published: September 2007

Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of fingolimod, a novel immune modulator. Data Sources: Information was obtained through a MEDLINE search (1966–February 2007) and from published abstracts. Search terms included fingolimod, FTY720, FTY-720, and sphlngosine-1-phosphate receptor agonist. Study Selection and Data Extraction: All English-language studies and abstracts pertaining to fingolimod were considered for inclusion. Preference was given to human data. Data Synthesis: Fingolimod Is the first in a new class of immune modulators known as the sphingosine-1-phosphate receptor agonists. It is administered orally once dairy and causes a dose-related reduction in the number ot circulating lymphocytes by preventing their egress from secondary lymph organs, but it does not alter T-cell activation or proliferation. Bradycardia and lymphopenia are the most common adverse effects. Clinical trials have evaluated the efficacy of fingolimod in renal transplantation and multiple sclerosis (MS). Further research for renal transplantation will not take place, but Phase 3 studies in MS are underway, as Phase 2 study results are favorable. Conclusions: Due to its distinct mechanism of action and its oral administration, fingolimod may be a useful therapeutic option for patients with relapsing forms of MS. More data are needed to assess the safety and clinical utility of fingolimod.
LInezolid for the Treatment of Nocardia spp. Infections
Authors: Jodlowski Tomasz Z , Melnychuk Igor , Conry John 
Published: September 2007

Objective: To review the available evidence regarding the use of linezolid for the treatment of Nocardia spp. infections. Data Sources: Data were identified through a search of MEDLINE (1966-May 2007), American Search Premier (1975-May 2007), International Pharmaceutical Abstracts (1960-2007), Science Citation Index Expanded (1996-2007), and Cochrane Databases (publications archived until May 2007) using the terms linezolid and Nocardia. Study Selection and Data Extraction: Prospective and retrospective studies, case reports, case series, and in vitro studies were eligible for inclusion if they used linezolid for nocardiosis regardless of site of infection and outcome. Data Synthesis: We identified 11 published cases of linezolid use for Nocardia spp. infections. The predominant species isolated were N. asteroides (n=4; 36%) and N. farcinica (n= 3; 27%). Nocardiosis with central nervous system involvement (n= 7; 64%) or disseminated disease (n= 4; 36%) were most common. The main reason for discontinuation of previous antimicrobials was most often related to adverse effects (n= 5; 45%), followed by clinical failure (n = 3; 27%). Linezolid was associated with cure or improvement in all cases (n =11; 100%). However, the majority of patients developed serious complications that may have led to premature discontinuation of therapy with linezolid, including myelosuppression (n = 5; 45%) or possible/confirmed peripheral neuropathy (n = 2; 18%). Conclusions: The limited published data suggest that linezolid appears to be an effective alternative to trimethoprim/sulfamethoxazole for the treatment of nocardiosis. Unfortunately, the high cost and potentially serious long-term toxicities of linezolid appear to limit its use and relegate it to salvage therapy alone or in combination with other antimicrobials.
Frequency of Adverse Events Associated with Intravenous Immunoglobulin Therapy in Patients with Pemphigus or Pemphigoid
Authors: Gürcan Hakan M , Ahmed A Razzaque 
Published: September 2007

Background: Intravenous immunoglobulin (IVIG) therapy is widely used in immune-mediated diseases as an immunomodulatory agent and is considered to be a safe biologic agent. Objective: To determine the frequency of adverse events associated with IVIG therapy in patients with pemphigus and pemphigoid. Methods: We retrospectively reviewed data on patients treated with IVIG for pemphigus and pemphigoid over a 10 year period. Patients had pemphigus vulgaris, pemphigus foliaceus, mucous membrane pemphigoid, or bullous pemphigoid. IVIG was given according to a published protocol at a dose of 2 g/kg administered over 3–5 days at prescribed intervals. Patient records were reviewed for information on sex, age, duration of treatment, number of cycles given, number of days each patient received IVIG, weight of each patient, IVIG dose each patient received per infusion, and early or delayed adverse effects reported by patients or observed by healthcare providers. Results: We identified 9892 infusions given to 174 patients. Headaches were the most common adverse effects; they were observed during 886 (8.9%) infusions and involved 123 (70.6%) patients. The incidence of other minor adverse effects, including fatigue, nausea, vomiting, chills, urticaria, swollen glands, hoarseness, thoracic discomfort, and palpitations, was 0.57–3.4% per infusion and 0.04–1,3% per patient. Hoarseness of voice and swelling of cervical lymph nodes have not been previously reported. Acute renal failure occurred in one patient and was the only major adverse effect observed. None of the patients required hospitalization, and there were no deaths. Conclusions: Adverse events associated with IVIG therapy are usually mild and self-limiting. The incidence of serious adverse events is low. Identification of risk factors and close monitoring of high-risk patients throughout the therapy are likely to decrease the occurrence of rare serious and less likely fatal adverse effects.
Long-Term Continuation on Cardiovascular Drug Treatment in Patients with Coronary Heart Disease
Authors: Wald David S , Morton Geraint , Walker Kate , Losson Neil , Curzen Nick P 
Published: September 2007

Background: Combination therapy to reduce risk factors is effective in preventing recurrent cardiovascular disease events in patients with coronary heart disease (CHD), but medications need to be continued indefinitely to maximize the benefits. Objective: To evaluate the extent of long-term continuation with cardiovascular drug therapy and its expected impact on the prevention of CHD. Methods: We studied 242 patients with CHD who underwent percutaneous coronary intervention following an acute coronary syndrome over a 6 month period in 2004. We prospectively examined the extent to which specific drugs and drug combinations were continued over lime by reviewing medication use at the time of hospital discharge and after 2 years. The results were used to estimate the expected loss in preventive efficacy due to discontinuation of therapy. Results: The changes over a 2 year period in the proportions of patients taking each drug class were as follows: 15% reduction for aspirin (95% Cl, -21 to -9), 10% reduction for statins (95% Cl, -16 to 5), 19% reduction for angiotensin-converting enzyme inhibitors (95% Cl, -26 to -12), 12% reduction for β-blockers (95% Cl, -18 to -6), 0% increase for calcium-channel blockers (95% Cl, -5 to 6), 2% increase for thiazides (95% Cl, -2 to 6), and 12% increase for angiotensin-11 receptor blockers (95% Cl, 6 to 18). The combination of aspirin, statin, and at least 2 blood pressure lowering drugs was prescribed to 81% of patients, three-quarters of whom remained on this combination after 2 years. The overall expected preventive effect on CHD of the combined medication taken during hospitalization and after 2 years was 80% and 74%, respectively. Conclusions: In patients with CHD, long-term continuation of combination cardiovascular drug therapy is considerably greater than generally perceived.
Molecular, Topographic, and Functional Organization of the Cerebellar Nuclei: Analysis by Three-Dimensional Mapping of the Olivonuclear Projection and Aldolase C Labeling
Authors: Sugihara Izumi , Shinoda Yoshikazu 
Published: September 2007

The olivocerebellar climbing fiber projection pattern is closely correlated with the pattern of aldolase C expression in cerebellar Purkinje cells. Based on this expression pattern, the olivocerebellar projection can be classified into five “groups” of functional compartments. Each group originates from a subarea within the inferior olive that projects to multiple cortical stripes of Purkinje cells, all of which are either aldolase C positive or aldolase C negative. However, no equivalent compartmental organization has been demonstrated in the cerebellar nuclei (CN). Thus, in the CN of the rat, we systematically mapped the location of olivonuclear projections belonging to the five groups and determined their relationship to the expression of aldolase C in Purkinje cell axonal terminals.The CN were divided into caudoventral aldolase C-positive and rostrodorsal aldolase C-negative parts. The olivonuclear terminations from the five groups projected topographically to five separate compartments within the CN that partly crossed the traditional boundaries that define the fastigial, interposed, and dentate nuclei. Each compartment had mostly uniform cytoarchitecture and the same aldolase C expression (either positive or negative) that was found in the corresponding olivocortical projection. These results suggest a new view of the organization of the CN whereby the pattern of olivonuclear terminations links portions of different CN together. We propose that each compartment in the CN, along with its corresponding olivary subarea and cortical stripes, may be related to a different aspect of motor control.
A Genome-Wide Linkage Scan of Insulin Level–Derived Traits
Authors: Hsueh Wen-Chi , Silver Kristi D. , Pollin Toni I. , Bell Callum J. , O’Connell Jeffrey R. , Mitchell Braxton D. , Shuldiner Alan R. 
Published: September 2007

OBJECTIVE—Serum insulin levels are altered in insulin resistance and insulin deficiency, states that are associated with the development of type 2 diabetes. The goal of our study was to identify chromosomal regions that are likely to harbor genetic determinants of these traits.
RESEARCH DESIGN AND METHODS—We conducted a series of genetic analyses, including genome-wide and fine-mapping linkage studies, based on insulin levels measured during an oral glucose tolerance test (OGTT) in 552 nondiabetic participants in the Amish Family Diabetes Study. Indices of insulin secretion included the insulinogenic index and insulin at 30 min postglucose load (insulin 30), while indices of insulin resistance included homeostasis model assessment of insulin resistance (HOMA-IR) and fasting insulin. Insulin area under the curve, a measure of both insulin secretion and insulin resistance, was also examined.
RESULTS—All traits were modestly heritable, with heritability estimates ranging from 0.1 to 0.4 (all P &lt; 0.05). There was significant genetic correlation between fasting insulin and HOMA-IR (ρG &gt; 0.86, P &lt; 0.05), as well as insulin 30 and insulinogenic index (ρG = 0.81, P &lt; 0.0001), suggesting that common genes influence variation in these pairs of traits. Suggestive linkage signals in the genome scan were to insulin 30 on chromosome 15q23 (logarithm of odds [LOD] 2.53, P = 0.00032) and to insulinogenic index on chromosome 2p13 (LOD 2.51, P = 0.00034). Fine-mapping study further refined our signal for insulin 30 on chromosome 15 (LOD 2.38 at 68 cM).
CONCLUSIONS—These results suggest that there may be different genes influencing variation in OGTT measures of insulin secretion and insulin resistance.