bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autoimmunity in a Phase I Trial of a Fully Human Anti-Cytotoxic T-Lymphocyte Antigen-4 Monoclonal Antibody With Multiple Melanoma Peptides and Montanide ISA 51 for Patients With Resected Stages III and IV Melanoma
Authors: Sanderson Kristin , Scotland Ronald , Lee Peter , Liu Dongxin , Groshen Susan , Snively Jolie , Sian Shirley , Nichol Geoffrey , Davis Thomas , Keler Tibor , Yellin Michael , Weber Jeffrey 
Published: December 2004

PurposeNineteen patients with high-risk resected stage III and IV melanoma were immunized with three tumor antigen epitope peptides from gp100, MART-1, and tyrosinase emulsified with adjuvant Montanide ISA 51 and received a fully human anti-cytotoxic T-lymphocyte antigen-4 (anti–CTLA-4) monoclonal antibody MDX-010. Each of three cohorts received escalating doses of antibody with vaccine primarily to evaluate the toxicities and maximum-tolerated dose (MTD) of MDX-010 with vaccine. MDX-010 pharmacokinetics and immune responses were secondary end points.Patients and MethodsPeptide immunizations with MDX-010 were administered every 4 weeks for 6 months and then every 12 weeks for 6 months. A leukapheresis to obtain peripheral-blood mononuclear cells for immune analyses was performed before treatment and after the sixth vaccination. Patients were observed until relapse.ResultsGrade 3 gastrointestinal (GI) toxicity (diarrhea or abdominal pain) was observed in three patients in the highest dose cohort and one in the middle dose cohort who seemed to be autoimmune. That defined the MTD with vaccine on this schedule at 1 mg/kg. Of eight patients with evidence of autoimmunity, three have experienced disease relapse. Of 11 patients without autoimmune symptoms, nine have experienced disease relapse. Significant immune responses were measured by tetramer and enzyme-linked immunospot assays against gp100 and MART-1.ConclusionDose-related autoimmune adverse events, predominantly skin and GI toxicities, were reversible. Patients mounted an antigen-specific immune response to a peptide vaccine when combined with a human anti–CTLA-4 antibody.
Phase II Study of Proteasome Inhibitor Bortezomib in Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma
Authors: Goy Andre , Younes Anas , McLaughlin Peter , Pro Barbara , Romaguera Jorge E. , Hagemeister Frederick , Fayad Luis , Dang Nam H. , Samaniego Felipe , Wang Michael , Broglio Kristine , Samuels Barry , Gilles Frederic , Sarris Andreas H. , Hart Susan , Trehu Elizabeth , Schenkein David , Cabanillas Fernando , Rodriguez Alma M. 
Published: December 2004

Purpose Evaluate efficacy and toxicity of bortezomib in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. Patients and Methods Patients were stratified, based on preclinical data, into arm A (mantle-cell lymphoma) or arm B (other B-cell lymphomas) without limitation in number of prior therapies. Bortezomib was administered as an intravenous push (1.5 mg/m2) on days 1, 4, 8, and 11 every 21 days for a maximum of six cycles. Results Sixty patients with a median number of prior therapies of 3.5 (range, one to 12 therapies) were enrolled; 33 patients were in arm A and 27 were in arm B, including 12 diffuse large B-cell lymphomas, five follicular lymphomas (FL), three transformed FLs, four small lymphocytic lymphomas (SLL), two Waldenström's macroglobulinemias (WM), and one marginal zone lymphoma. In arm A, 12 of 29 assessable patients responded (six complete responses [CR] and six partial responses [PR]) for an overall response rate (ORR) of 41% (95% CI, 24% to 61%), and a median time to progression not reached yet, with a median follow-up of 9.3 months (range, 1.7 to 24 months). In arm B, four of 21 assessable patients responded (one SLL patient had a CR, one FL patient had a CR unconfirmed, one diffuse large B-cell lymphoma patient had a PR, and one WM patient had a PR) for an ORR of 19% (95% CI, 5% to 42%). Grade 3 toxicity included thrombocytopenia (47%), gastrointestinal (20%), fatigue (13%), neutropenia (10%), and peripheral neuropathy (5%). Grade 4 toxicity occurred in nine patients (15%), and three deaths from progression of disease occurred within 30 days of withdrawal from study. Conclusion Bortezomib showed promising activity in relapsed mantle-cell lymphoma and encouraging results in other B-cell lymphomas. Future studies will explore bortezomib in combination with other cytotoxic or biologic agents.
Efficacy and Safety of Tositumomab and Iodine-131 Tositumomab (Bexxar) in B-Cell Lymphoma, Progressive After Rituximab
Authors: Horning Sandra J. , Younes Anas , Jain Vinay , Kroll Stewart , Lucas Jennifer , Podoloff Donald , Goris Michael 
Published: December 2004

PurposeTo determine overall response (OR) and complete response (CR) rates, response duration, progression-free (PFS) and overall survival and safety with the tositumomab and iodine-131 tositumomab (131I tositumomab) therapeutic regimen in patients with indolent, follicular large-cell, or transformed B-cell lymphoma, progressive after rituximab.Patients and MethodsFrom July 1998 to November 1999, 40 patients (24 rituximab nonresponders: 11 with response < 6 months, and five with response ≥ 6 months) received a therapeutic dose (0.65 to 0.75 Gy per platelet count) of131I tositumomab based on total-body dosimetry in this prospective phase II study. The median number of prior treatments was four; 59% of patients were chemotherapy-resistant.ResultsConfirmed OR (65%) and CR (38%) rates were not significantly associated with prior rituximab response. With a median follow-up of 3.3 years, the median PFS was 10.4 months, 24.5 months for responders, and not reached for CR patients. Among follicular grade 1 or 2 patients with tumors ≤ 7 cm (n = 21), the OR and CR rates were 86% and 57%. Estimated 3-year PFS in this subgroup was 48%, compared with 11% for all others (P = .002). Transient grade 3 to 4 marrow toxicity was seen in 50% of patients. Two patients, one of whom received two subsequent chemotherapy regimens, developed secondary myelodysplasia.Conclusion131I tositumomab is effective in CD20-positive lymphoma progressive after rituximab, with a 65% OR rate and median PFS of 24.5 months for responders. Patients with follicular grade 1 or 2 histology and tumors ≤ 7 cm achieved very high OR and CR rates, with 48% PFS at 3 years.
Undertreatment of Urinary Incontinence in General Practice
Authors: Beest Fernie JA Penning-van , Sturkenboom Miriam CJM , Bemelmans Bart LH , Herings Ron MC 
Published: December 2004

BACKGROUND: In the urinary incontinence guidelines that are issued by the Dutch College of General Practitioners, treatment guidelines are related to the type of incontinence. It is unknown whether treatment of urinary incontinence in general practice complies with these guidelines. OBJECTIVE: To describe treatment patterns and costs of urinary incontinence. METHODS: The source population for this retrospective cohort study included all women aged ≥40 years in the Integrated Primary Care Information general practice research database. Women were included in the final study cohort if they were newly identified as being urinary incontinent during the study period (1998–2000) and had at least one year of follow-up after the first diagnosis/treatment. The type of incontinence, treatment course, and costs of incontinence were assessed during the first year after the subjects' identification. RESULTS: The final study cohort comprised 1663 women (mean age 68.5 y). Overall, 71% of newly identified women with urinary incontinence did not receive active treatment within one year after identification. In 13%, the first treatment was bladder training or pelvic floor exercises, and 11% started treatment with a bladder relaxant drug. First treatment was related to the type of incontinence; however, in <50% of the women, the type of incontinence was reported or could be assessed. Absorbent products were used by 66% of the women; 87% of them received no active treatment. The mean direct costs of urinary incontinence over the first year amounted to ¢392 per woman, of which ¢200 (51%) for absorbent products. CONCLUSIONS: Less than one-third of the women with newly identified urinary incontinence were actively treated for their incontinence. Although treatment patterns were in line with guidelines, the high rate of undertreatment points to the need for better patient and physician education.
Effect of Lepirudin on the International Normalized Ratio
Authors: Stephens Jennifer L , Koerber John M , Mattson Joan C , Smythe Maureen A 
Published: December 2004

BACKGROUND: Many patients receiving direct thrombin inhibitor (DTI) therapy require transition to warfarin. This transition may be complicated by DTI-induced elevations in the international normalized ratio (INR). While the effect of argatroban on the INR has been characterized, data assessing the effect of lepirudin on the INR are limited. OBJECTIVE: To evaluate the effect of lepirudin on the INR. METHODS: Patients receiving lepirudin therapy between January 2000 and May 2001 were identified using the pharmacy database, and a retrospective chart review was conducted. Patients were included for analysis if they had paired activated partial thromboplastin time (aPTT) and INR data while receiving lepirudin monotherapy. RESULTS: Fifty-three paired aPTT and INR data points from 8 patients receiving lepirudin monotherapy were collected. The Organon MDA 180 instrument was used for aPTT and prothrombin time (PT) determination. Organon MDA Platelin L reagent was used for the aPTT and Organon Simplastin L reagent was used for the PT. The international sensitivity index (ISI) of the Simplastin L thromboplastin was 2.0. The mean ± SD lepirudin dose was 0.05 ± 0.04 mg/kg/h. Linear regression was used to identify the INRs that correspond to a therapeutic aPTT value of 45–75 seconds (1.5–2.5 times mean laboratory normal of 30 sec). The correlation between aPTT and INR was 0.77. An aPTT of 45–75 seconds with lepirudin correlated to an INR of 1.6–3.2. CONCLUSIONS: Based on laboratory results, when using a thromboplastin with an ISI of 2, lepirudin appears to elevate the INR in the absence of warfarin.
Fetal Toxic Effects of Angiotensin II Receptor Antagonists: Case Report and Follow-Up after Birth
Authors: Bos-Thompson Marie-Andrée , Hillaire-Buys Dominique , Muller Françoise , Dechaud Hervé , Mazurier Evelyne , Boulot Pierre , Morin Denis 
Published: December 2004

OBJECTIVE: To report a child born with renal impairment following severe anhydramnios due to maternal exposure to an angiotensin II receptor type 1 (AT1) antagonist, valsartan, and hydrochlorothiazide during the first 28 weeks of pregnancy. CASE SUMMARY: A hypertensive woman treated with valsartan 80 mg/day, hydrochlorothiazide 12.5 mg/day, prazosin 10 mg/day, lysine acetylsalicylate 100 mg/day, and levothyroxine 250 μg/day became pregnant. At 28 weeks' gestational age, severe anhydramnios associated with high β2-microglobulin levels in the fetal blood cord was observed. Upon discontinuation of valsartan, fetal renal prognosis improved. In this case, using the Naranjo probability scale, the renal insufficiency of the child was probably related to valsartan. At the age of 2.5 years, the child presented with only mild chronic renal insufficiency. Growth parameters were within the normal range, and there was no evidence of developmental delay. DISCUSSION: Exposure to AT1 antagonists during the second part of pregnancy can lead to abnormalities similar to those observed after exposure to angiotensin-converting enzyme inhibitors, that is, reduced fetal kidney perfusion that may result in oligoamnios and neonatal renal insufficiency. Fourteen previous reports of maternal exposure to AT1 antagonists during this period have been published. In 6 cases, fetal or neonatal death occurred; in 2 cases, pregnancy was terminated because of complete anhydramnios or fetal abnormalities; in 1 case, renal insufficiency persisted at 8 months of age; in 2 cases, kidney function was fairly normal at birth; and in 4 cases, including the one described here, neonatal renal failure improved in the first year of life. CONCLUSIONS: AT1 antagonists should be avoided throughout pregnancy. If these agents are prescribed accidentally to a pregnant woman, monitoring of amniotic fluid volume and β2-microglobulin fetal blood levels after discontinuation of the AT1 antagonist can provide critical data for advising parents on pregnancy and fetal outcome.
Evaluation of Serum Protein Profiling by Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry for the Detection of Prostate Cancer: I. Assessment of Platform Reproducibility
Authors: Semmes O John , Feng Ziding , Adam Bao-Ling , Banez Lionel L , Bigbee William L , Campos David , Cazares Lisa H , Chan Daniel W , Grizzle William E , Izbicka Elzbieta , Kagan Jacob , Malik Gunjan , McLerran Dale , Moul Judd W , Partin Alan , Prasanna Premkala , Rosenzweig Jason , Sokoll Lori J , Srivastava Shiv , Srivastava Sudhir , Thompson Ian , Welsh Manda J , White Nicole , Winget Marcy , Yasui Yutaka , Zhang Zhen , Zhu Liu 
Published: December 2004

Abstract
Background: Protein expression profiling for differences indicative of early cancer has promise for improving diagnostics. This report describes the first stage of a National Cancer Institute/Early Detection Research Network-sponsored multiinstitutional evaluation and validation of this approach for detection of prostate cancer.
Methods: Two sequential experimental phases were conducted to establish interlaboratory calibration and standardization of the surface-enhanced laser desorption (SELDI) instrumental and assay platform output. We first established whether the output from multiple calibrated Protein Biosystem II SELDI-ionization time-of-flight mass spectrometry (TOF-MS) instruments demonstrated acceptable interlaboratory reproducibility. This was determined by measuring mass accuracy, resolution, signal-to-noise ratio, and normalized intensity of three m/z “peaks” present in a standard pooled serum sample. We next evaluated the ability of the calibrated and standardized instrumentation to accurately differentiate between selected cases of prostate cancer and control by use of an algorithm developed from data derived from a single site 2 years earlier.
Results: When the described standard operating procedures were established at all laboratory sites, the across-laboratory measurements revealed a CV for mass accuracy of 0.1%, signal-to-noise ratio of ∼40%, and normalized intensity of 15–36% for the three pooled serum peaks. This was comparable to the intralaboratory measurements of the same peaks. The instrument systems were then challenged with sera from a selected group of 14 cases and 14 controls. The classification agreement between each site and the established decision algorithm were examined by use of both raw peak intensity boosting and ranked peak intensity boosting. All six sites achieved perfect blinded classification for all samples when boosted alignment of raw intensities was used. Four of six sites achieved perfect blinded classification with ranked intensities, with one site passing the criteria of 26 of 28 correct and one site failing with 19 of 28 correct.
Conclusions: These results demonstrate that “between-laboratory” reproducibility of SELDI-TOF-MS serum profiling approaches that of “within-laboratory” reproducibility as determined by measuring discrete m/z peaks over time and across laboratories.
On some physical properties of six aspen clones
Authors: Avramidis Stavros , Mansfield Shawn D. 
Published: December 2004

Abstract
Basic physical properties including density, permeability, water sorption characteristics and diffusion coefficients in desorption were measured with specimens taken from for six aspen clone trees harvested in northeastern British Columbia. Results showed that there are significant differences among the clones in their specific permeability and somewhat in the heat of wetting, but very little was found among density, diffusion coefficients and desorption isotherms. These results indicate that the porous structure could be variable among clones whereas the sorption site distribution and availability might not.
On the Mall: Presenting Maroon Tradition‐Bearers at the 1992 Festival of American Folklife/Enigma Variations
Authors: Handler Richard 
Published: December 2004

On the Mall: Presenting Maroon Tradition‐Bearers at the 1992 Festival of American Folklife. Richard and Sally Price. Bloomington: Folklore Institute, Indiana University, Special Publications, No. 4, 1994. xi. 123 pp.; 16 illus., notes, bibliography. $25.00 (cloth), $12.00 (paper).Enigma Variations, Richard and Sally Price. Cambridge, MA: Harvard University Press, 1995. 164 pp.; 155 illustrations, notes. $18.95 (cloth).
The Architectural Uncanny/ The Surreptitious Speech/ The Cinematic Grtot / Ethnographic Film Aesthetics & Narrative Traditions / Deer Camp / Magic Eyes / Partial Recall / Waucoma Twilight
Authors: Rabinow Paul , Bohm Arnd , De Brigard Emilie , Heider Karl , Ruby Jay 
Published: December 2004

The Architectural Uncanny. 1992. By Anthony Vidler. Cambridge: Mit PressThe Surreptitious Speech: Presence Africaine and The Politics of Otherness, 1947—1987. Ed. V. Y. Mudimbe. Chicago and London: The university of Chicago Press, 1992.The Cinematic Griot: the Ethnography of Jean Rouch. 1992. By Paul Stoller. xvii. 247 pp. Chicago: Chicago University Press. Emilie De Brigard Anthropological film research instituteEthnographic Film Aesthetics and Narrative Traditions: Proceedings From Nafa 2. 1992. Peter I. Crawford and Jan K. Simonsen (editors). Aarhus (Denmark): intervention press.Deer camp: Last Light in the Northeast Kingdom. 1993‐ Photographs and text by John M. Miller. 130 pp, 60 duotone illustrations Mit press, co–published with The Vermont Folklife Center.Magic Eyes: Scenes from an Andean Girlhood. 1992. By Wendy Ewald. From stories told by Alicia and Maria Vasquez. Photographs by wendy Ewald and children of Raquira. Colombia. 180 pp. With Illustrations. Seattle: bay press.Partial Recall 1993. Ed. Lucy Lippard. With essays by S. Benally. J. Durham. R. Green. J. Harjo. G. Mcmaster. J. Rickard. R. Sakiestewa. D. Seals. P. C. Smith. J. Quick–To–See Smith. G. Tremblay. and G. Vizenor. 199 pp. New York the New Press.Waucoma Twilight: Generations op the farm. 1992. By Dona Schwartz. 220 176 pp. With b/w halftones. Washington, D.c.: Smithsonian Instttution press.
Quality-of-Life Considerations in Patients with Advanced Lung Cancer: Effect of Topotecan on Symptom Palliation and Quality of Life
Authors: Gralla Richard J. 
Published: December 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Explain the rationale for evaluating quality of life as a treatment end point. Describe the multidisciplinary dimensions incorporated into validated quality-of-life questionnaires. Discuss the impacts on quality of life and symptoms (patient reported outcomes [PROs]) resulting from the use of topotecan given either i.v. or orally.
Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com
Key goals in the treatment of lung cancer are to improve both survival and quality of life (QOL). While formal techniques are frequently used to evaluate survival and response, such rigor is used less often in assessing the impact of treatment on quality of life. Many patients with lung cancer are elderly and have complex medical histories and a myriad of comorbidities. In these patients, with limited survival expectations, symptom palliation, quality of life, and convenience of therapy are especially important end points. Indeed, clinical trials are now incorporating symptom scores and QOL outcomes in their designs (now combined as “patient reported outcomes” or PROs). Moreover, symptom palliation correlates well with QOL and survival duration, providing further rationale for therapy selection based on these parameters. The potential palliative and QOL benefits of chemotherapy have been investigated for several agents in lung cancer trials. Of these, topotecan (Hycamtin®; GlaxoSmithKline; Philadelphia, PA) is the best characterized in relapsed small cell lung cancer (SCLC). In a phase III trial of topotecan versus cyclophosphamide, doxorubicin (Adriamycin®; Bedford Laboratories; Bedford, OH), and vincristine (Oncovin®; Eli Lilly and Company; Indianapolis, IN) (CAV) in patients with recurrent SCLC, topotecan was associated with statistically significant (p &lt; 0.05) improvements in general symptoms (e.g., fatigue and interference with daily activity) and disease-specific symptoms (e.g., dyspnea and hoarseness). Moreover, the introduction of oral therapies, such as oral topotecan, may increase the convenience of therapy by reducing the time needed for therapy and the need for frequent venipuncture. This review summarizes the role of chemotherapy in symptom palliation, with an emphasis on the impact of topotecan therapy on symptom parameters in patients with relapsed SCLC and the emerging role of oral therapy in this setting.
Topotecan in the Treatment of Recurrent Small Cell Lung Cancer: An Update
Authors: Ardizzoni Andrea 
Published: December 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Discuss the results of clinical trials of topotecan both as a single agent and in combination therapy in patients with recurrent SCLC. Describe differences in the incidences of hematologic toxicities between recurrent SCLC patients treated with lower-dose topotecan and those treated with the standard dose. Discuss the efficacy and safety of oral topotecan versus the i.v. formulation in recurrent SCLC patients.
Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com
Small cell lung cancer (SCLC) is an aggressive malignancy with a high propensity for early regional and distant metastasis. Response rates to first-line chemotherapy are typically high, but short lived. The outlook for patients with recurrent SCLC is poor. A variety of single- and multi-agent chemotherapy regimens have met with limited success in patients with recurrent SCLC, and survival is generally measured in weeks. Until recently, further chemotherapy was not widely considered appropriate for patients with relapsed SCLC. The choice of chemotherapy at relapse is dependent on many factors, including type of and response to first-line therapy, the treatment-free interval, and the patient's performance status. Intravenous topotecan (Hycamtin®; GlaxoSmithKline; Philadelphia, PA) has provided oncologists and patients in many countries with an effective and tolerable therapeutic option for recurrent SCLC. The clinical profile of topotecan was established in several phase II studies and confirmed in a randomized, phase III trial versus cyclophosphamide, doxorubicin (Adriamycin®; Bedford Laboratories; Bedford, OH), and vincristine (Oncovin®; Eli Lilly and Company; Indianapolis, IN)—CAV. In those studies, topotecan exhibited antitumor activity in both chemosensitive and refractory disease. Further, topotecan therapy is associated with significant symptom palliation in this patient population. Because the toxicity profile of topotecan is predictable, generally manageable, and noncumulative, the agent also has potential utility in patients with a poor prognosis and/or a poor performance status. Alternative dosing regimens (lower dose, weekly) and the introduction of an oral formulation may expand the use of topotecan as a single agent and in combination therapy in the second- and first-line treatment of this disease.