bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized Controlled Trial Comparing Oral Doxifluridine Plus Oral Cyclophosphamide With Doxifluridine Alone in Women With Node-Positive Breast Cancer After Primary Surgery
Authors: Tominaga Takeshi , Koyama Hiroki , Toge Tetsuya , Miura Shigeto , Sugimachi Keizo , Yamaguchi Susumu , Hirata Koichi , Monden Yasumasa , Nomura Yasuo , Toi Masakazu , Kimijima Izo , Noguchi Shinzaburo , Sonoo Hiroshi , Asaishi Kazuaki , Ikeda Tadashi , Morimoto Tadaoki , Ota Jun , Ohashi Yasuo , Abe Osahiko 
Published: March 2003

Purpose: We compared the therapeutic usefulness of doxifluridine (5′-DFUR) alone and a combination of 5′-DFUR plus cyclophosphamide (CPM), both of which are considered effective against advanced and recurrent breast cancer, to determine which treatment is more beneficial as postoperative adjuvant chemotherapy. Patients and Methods: A total of 1,131 women with node-positive primary breast cancer were randomly assigned after primary surgery to receive 5′-DFUR alone or 5′-DFUR plus CPM. All patients initially received 5′-DFUR in an oral dose of 1,200 mg/d for 4 weeks, starting 4 weeks after surgery. Chemotherapy was then not given for 2 weeks. Patients in the 5′-DFUR group subsequently received five 4-week cycles of treatment consisting of oral 5′-DFUR (1,200 mg/d) for the first 2 weeks and no chemotherapy for the next 2 weeks. Those assigned to the 5′-DFUR plus CPM group also received oral CPM 100 mg/d for the first 2 weeks and no chemotherapy for the next 2 weeks. Women 50 years or older concurrently received 20 mg/d of tamoxifen for 2 years in both groups. Results: Of the 1,088 eligible women, 546 were assigned to receive 5′-DFUR alone and 542 were assigned to receive 5′-DFUR plus CPM. Overall disease-free survival was significantly better in women who received 5′-DFUR plus CPM than in those who received 5′-DFUR alone (log-rank test, P = .021). Toxic effects occurred in 20.0% of patients (109 of 546) in the 5′-DFUR group and 32.3% of patients (175 of 542) in the 5′-DFUR plus CPM group (χ2 test, P < .001). Conclusion: Combination therapy with 5′-DFUR plus CPM is more effective in preventing recurrence than 5′-DFUR alone.
Effect of Number of Lymph Nodes Sampled on Outcome in Patients With Stage I Non–Small-Cell Lung Cancer
Authors: Gajra Ajeet , Newman Nancy , Gamble Gary P. , Kohman Leslie J. , Graziano Stephen L. 
Published: March 2003

Purpose: We postulate that surgical sampling and pathologic evaluation of lymph nodes of surgical specimens from patients with stage I non–small-cell lung cancer (NSCLC) can have an effect on the time to recurrence and survival of these patients. Patients and Methods: We analyzed data on 442 patients with stage I NSCLC who were treated with surgical resection and some form of lymph node sampling. Associations between total lymph nodes sampled and disease-free survival (DFS) and overall survival (OS) were investigated. The effect of total lymph node stations sampled and the surgical techniques (random lymph node sampling, systematic sampling [SS], or complete mediastinal lymph node dissection [MLND]) on DFS and OS was also studied. Complete MLND and SS were defined as dissection or sampling of levels 4, 7, and 10 for right-sided lesions and levels 5 or 6 and 7 for left-sided lesions. Results: Patients were divided into quartiles on the basis of total number of lymph nodes sampled. Improved DFS and OS were associated with greater number of lymph nodes sampled. SS and MLND were associated with improved survival compared with random lymph node sampling. The total number of lymph nodes sampled maintained strong significance in the multivariate analysis. Conclusion: These results indicate that examining a greater number of lymph nodes in patients with stage I NSCLC treated with resection increases the likelihood of proper staging and affects patient outcome. Such information is important not only for therapy and prognosis of individuals but also for identifying those who may benefit from adjuvant therapy.
General Quality of Life 2 Years Following Treatment for Prostate Cancer: What Influences Outcomes? Results From the Prostate Cancer Outcomes Study
Authors: Penson David F. , Feng Ziding , Kuniyuki Alan , McClerran Dale , Albertsen Peter C. , Deapen Dennis , Gilliland Frank , Hoffman Richard , Stephenson Robert A. , Potosky Arnold L. , Stanford Janet L. 
Published: March 2003

Purpose: The goal of this study was to determine the relationship between primary treatment, urinary dysfunction, sexual dysfunction, and general health-related quality of life (HRQOL) in prostate cancer. Methods: A sample of men with newly diagnosed prostate cancer between 1994 and 1995 was randomly selected from six population-based Surveillance, Epidemiology, and End Results registries. A baseline survey was completed by 2,306 men within 6 to 12 months of diagnosis, and these men also completed a follow-up HRQOL survey 2 years after diagnosis. Logistic regression models were used to determine whether primary treatment, urinary dysfunction, and sexual dysfunction were independently associated with general HRQOL outcomes approximately 2 years after diagnosis as measured by the Medical Outcomes Study 36-item Short Form Health Survey. The magnitude of this effect was estimated using least square means models. Results: After adjustment for potential confounders, primary treatment was not associated with 2-year general HRQOL outcomes in men with prostate cancer. Urinary function and bother were independently associated with worse general HRQOL in all domains. Sexual function and bother were also independently associated with worse general HRQOL, although the relationship was not as strong as in the urinary domains. Conclusion: Primary treatment is not associated with 2-year general HRQOL outcomes in prostate cancer. Although both sexual and urinary function and bother are associated with quality of life, men who are more bothered by their urination or impotence are more likely to report worse quality of life. This implies that future research should be directed toward finding ways to improve treatment-related outcomes or help patients better cope with their posttreatment urinary or sexual dysfunction.
Impact of Metaiodobenzylguanidine Scintigraphy on Assessing Response of High-Risk Neuroblastoma to Dose-Intensive Induction Chemotherapy
Authors: Kushner Brian H. , Yeh Samuel D.J. , Kramer Kim , Larson Steven M. , Cheung Nai-Kong V. 
Published: March 2003

Purpose: The International Neuroblastoma Response Criteria (INRC) recommend, but do not make mandatory, metaiodobenzylguanidine (MIBG) scans. We present the first report on the effect of MIBG scans on the classification of response to dose-intensive induction therapy. Patients and Methods: After dose-intensive induction and before consolidative therapy, 162 Memorial Sloan-Kettering Cancer Center (MSKCC) patients with high-risk neuroblastoma (NB) had MIBG scans (99 with 131I, 63 with 123I), computed tomography, 99mTc-bone scan, bone marrow (BM) tests, and urine catecholamine measurements. Induction included high-dose cyclophosphamide (140 mg/kg) plus other agents and high-dose cisplatin (200 mg/m2)/etoposide (600 mg/m2). Results: In 90 patients treated with dose-intensive therapy from diagnosis at MSKCC, the use of MIBG scintigraphy increased the incomplete response numbers from 14 (15.5%) to 20 (22%), giving a complete remission/very good partial remission (CR/VGPR) rate of 78%. In 72 patients treated before referral to MSKCC for intensified therapy, MIBG findings changed the response classification of one patient; the CR/VGPR rate was 43%. MIBG scans showed no BM disease in 15 of 38 patients with histologically evident NB in BM but did show uptake consistent with BM involvement in five patients who had no NB observed in BM tests. Conclusion: With the less effective therapy consequent to the intensification of induction only after initial exposure to standard-dose chemotherapy, MIBG scintigraphy merely confirms the findings of other staging modalities for detection of relatively widespread residual NB. However, when dose-intensive therapy is initiated at diagnosis, the reliable achievement of major disease responses makes extensive BM testing and MIBG scintigraphy prerequisites for accurate determination of disease status.
Clinical Outcome of Stage I/II Melanoma Patients After Selective Sentinel Lymph Node Dissection: Long-Term Follow-Up Results
Authors: Vuylsteke R.J.C.L.M. , van Leeuwen P.A.M. , Muller M.G. Statius , Gietema H.A. , Kragt D.R. , Meijer S. 
Published: March 2003

Purpose: Although sentinel lymph node (SLN) status is part of the new American Joint Committee on Cancer staging system, there is no final proof that the SLN procedure in melanoma patients influences outcome of disease. This study investigated the accuracy of the SLN procedure and clinical outcome in melanoma patients after at least 60 months of follow-up. Patients and Methods: Between 1993 and 1996, 209 patients with stage I/II cutaneous melanoma underwent selective SLN dissection by the triple technique. If the SLN contained metastatic disease, a completion lymphadenectomy was performed. Survival analyses were performed using the Kaplan-Meier approach. Factors associated with survival were analyzed using the Cox proportional hazards regression model. Results: The success rate was 99.5%. Median follow-up was 72 months. Forty patients (19%) had a positive SLN. The false-negative rate was 9%. Five-year overall survival was 87% for the entire group and 92% and 67% for SLN-negative and SLN-positive patients (P < .0001), respectively. All patients with a positive SLN and a Breslow thickness ≤ 1.00 mm survived, and SLN-positive patients with a Breslow thickness less than 2.00 mm tend to have a better prognosis compared with SLN-negative patients with a Breslow thickness greater than 2.00 mm. SLN status (P = .002), Breslow thickness (P = .002), and lymphatic invasion (P = .0009) were all found to be independent prognostic factors for overall survival. Conclusion: With a success rate of 99.5% and a false-negative rate of 9% after long-term follow-up, the triple-technique SLN procedure is a reliable and accurate method. Survival data seem promising, although a therapeutic effect is still questionable. As shown in this study, not all SLN-positive patients have a poor prognosis.
Preoperative Concurrent Chemoradiotherapy in Locally Advanced Rectal Cancer With High-Dose Radiation and Oxaliplatin-Containing Regimen: The Lyon R0–04 Phase II Trial
Authors: Gérard Jean-Pierre , Chapet Olivier , Nemoz Chantal , Romestaing Pascale , Mornex Françoise , Coquard Régis , Barbet Nicolas , Atlan Dan , Adeleine Patrice , Freyer Gilles 
Published: March 2003

Purpose: The combination of radiation, fluorouracil, and oxaliplatin in locally advanced rectal cancer has been shown to be feasible in a phase I trial. The purpose of this phase II trial was to assess tolerance and efficacy of this regimen in a preoperative setting. Patients and Methods: Between May 2000 and October 2001, 40 operable patients were entered onto the study. Radiotherapy was delivered with a three-field technique to a dose of 50 Gy over 5 weeks with a concomitant boost approach. Two cycles of chemotherapy were given synchronously on weeks 1 and 5, with oxaliplatin 130 mg/m2 on day 1 followed by 5-day continuous infusion of fluorouracil 350 mg/m2 and l-folinic acid 100 mg/m2. Surgery was planned 5 weeks later. Results: All patients completed treatment without modification except one who experienced grade 3/4 toxicity. Grade 3 toxicity was seen in seven patients. Surgery was performed in all patients after a mean interval time of 5 weeks. An objective clinical response was seen in 30 patients (75%). Sphincter-saving surgery was possible in 26 patients. No postoperative deaths occurred. In four patients (10%), a reoperation was necessary (anastomotic fistula, n = 2; pelvic abscess, n = 2). In six cases the operative specimen was sterilized (15%), and in 12 cases (30%), only few residual cells were detected. Conclusion: Such a combined preoperative chemoradiotherapy and oxaliplatin-containing regimen is well tolerated with no increase in surgical toxicity. The good response rate observed warrants its use in further clinical trials.
Regulatory Approvals of Pediatric Oncology Drugs: Previous Experience and New Initiatives
Authors: Hirschfeld Steven , Ho Peter T.C. , Smith Malcolm , Pazdur Richard 
Published: March 2003

Purpose: To review the Food and Drug Administration (FDA) experience with approvals of new drugs for pediatric oncology and to discuss new regulatory initiatives directed at pediatric oncology. Methods: A retrospective review of FDA archival documents and the published literature. Results: More than 100 drugs have been approved by the Division of Oncology Drug Products of the FDA for the treatment of malignancies. Only 15 have pediatric use information in their labeling, which is less than 50% of the drugs commonly used in the treatment of pediatric malignancies. In the past 20 years, there have been six submissions to the FDA for pediatric oncology indications. To illustrate principles of the approval process, each submission is discussed. Conclusion: Potential reasons for a lack of New Drug Application submissions for pediatric oncology include the small pediatric oncology market compared with the adult oncology market and perceived barriers to performing studies in children. Reasons for failure to approve pediatric indications include small numbers of patients, lack of appropriate controls, and failure to demonstrate patient benefit. Approval criteria include the use of controlled trials, prospective data collection, and disease-appropriate end points. Regulatory initiatives to promote pediatric therapeutic development and product labeling are discussed.
Differential Patterns of Fos Induction in the Hypothalamus of the Rat Following Central Injections of Galanin-Like Peptide and Galanin
Authors: Fraley Gregory S. , Shimada Issei , Baumgartner James W. , Clifton Donald K. , Steiner Robert A. 
Published: March 2003

AbstractGalanin and its newly discovered relative galanin-like peptide (GALP) are neuropeptides that are implicated in the neuroendocrine regulation of body weight and reproduction. GALP has been shown to bind in vitro to galanin receptor subtypes 1 and 2, but whether it has its own specific receptor(s) is unknown. We reasoned that if GALP acts through a receptor that is distinct from galanin receptors, then GALP should activate central pathways that are different from those activated by galanin. The purpose of this study was to determine whether galanin and GALP produce different patterns of neuronal activation within the hypothalamus. Quantitative analysis of Fos immunoreactivity showed that galanin induced a significantly greater number of Fos-positive nuclei in the paraventricular nucleus compared with GALP (P &lt; 0.001); however, compared with galanin, GALP induced significantly more Fos-positive cells in the horizontal limb of the diagonal band of Broca, caudal preoptic area, arcuate nucleus, and median eminence (P &lt; 0.05). These observations suggest that GALP and galanin act through different receptor-mediated pathways to exert their effects on the regulation of body weight and reproduction and identify target cells for GALP’s specific actions in the hypothalamus, including the preoptic area, paraventricular and arcuate nuclei, and the median eminence.
Involvement of MEKK1/ERK/P21Waf1/Cip1 signal transduction pathway in inhibition of IGF‐I‐mediated cell growth response by methylglyoxal
Authors: Du Jun , Cai Shaohui , Suzuki Haruhiko , Akhand Anwarul A. , Ma Xiuyang , Takagi Yoshikazu , Miyata. Toshio , Nakashima Izumi , Nagase Fumihiko 
Published: March 2003

AbstractThe abnormal accumulation of methylglyoxal (MG), a physiological glucose metabolite, is strongly related to the development of diabetic complications by affecting the metabolism and functions of organs and tissues. These disturbances could modify the cell response to hormones and growth factors, including insulin‐like growth factor‐1 (IGF‐I). In this study, we investigated the effect of MG on IGF‐I‐induced cell proliferation and the mechanism of the effect in two cell lines, a human embryonic kidney cell line (HEK293), and a mouse fibroblast cell line (NIH3T3). MG rendered these cells resistant to the mitogenic action of IGF‐I, and this was associated with stronger and prolonged activation of ERK and over‐expression of P21Waf1/Cip1. The synergistic effect of MG with IGF‐I in activation of ERK was completely abolished by PD98059 but not by a specific PI3K inhibitor, LY294002, or a specific PKC inhibitor, bisindolylmaleimide. Blocking of Raf‐1 activity by expression of a dominant negative form of Raf‐1 did not reduce the enhancing effect of MG on IGF‐I‐induced activation of ERK. However, transfection of a catalytically inactive form of MEKK1 resulted in inactivation of the MG‐induced activation of ERK and partial inhibition of the enhanced activation of ERK and over‐expression of p21Waf1/Cip1 induced by co‐stimulation of MG and IGF‐I. These results suggested that the alteration of intracellular milieu induced by MG through a MEKK1‐mediated and PI3K/PKC/Raf‐1‐independent pathway resulted in the modification of cell response to IGF‐I for p21Waf1/Cip1‐mediated growth arrest, which may be one of the crucial mechanisms for MG to promote the development of chronic clinical complications in diabetes. J. Cell. Biochem. 88: 1235–1246, 2003. © 2003 Wiley‐Liss, Inc.
The impact of organizational structure on time‐based manufacturing and plant performance
Authors: Nahm Abraham Y , Vonderembse Mark A , Koufteros Xenophon A 
Published: March 2003

AbstractThe innovation and organizational theory literatures argue that implementing radical innovation can be facilitated or hindered by the organization’s structural design. As firms attempt to cope with an external environment that is changing from industrial to post‐industrial, how do they implement change? This study develops a research framework that examines relationships among various structural dimensions (i.e. number of layers in the hierarchy, level of horizontal integration, locus of decision‐making, nature of formalization, and level of communication), time‐based manufacturing practices, and plant performance. Based on 224 responses from manufacturing firms, this study develops instruments to measure these organizational sub‐dimensions using part of this sample (N=104), and it tests the structural relationships with the remaining responses (N=120). Results indicate that the nature of formalization, the number of layers in the hierarchy, and the level of horizontal integration have significant, direct, and positive effects on the locus of decision‐making and level of communication. Locus of decision‐making and the level of communication, in turn, have significant, direct, and positive effects on time‐based manufacturing practices. Finally, time‐based manufacturing practices have a significant, direct, and positive impact on plant performance.
Adhesion of perichondrial cells to a polylactic acid scaffold
Authors: Giurea Alexander , Klein Travis J. , Chen Albert C. , Goomer Randal S. , Coutts Richard D. , Akeson Wayne H. , Amiel David , Sah Robert L. 
Published: March 2003

AbstractThe number of chondrogenic cells available locally is an important factor in the repair process for cartilage defects. Previous studies demonstrated that the number of transplanted rabbit perichondrial cells (PC) remaining in a cartilage defect in vivo, after being carried into the site in a polylactic acid (PLA) scaffold, declined markedly within two days. This study examined the ability of in vitro culture of PC/PLA constructs to enhance subsequent biomechanical stability of the cells and the matrix content in an in vitro screening assay. PC/PLA constructs were analyzed after 1 h, 1 and 2 weeks of culture. The biomechanical adherence of PC to the PLA scaffold was tested by subjecting the PC/PLA constructs to a range of flow velocities (0.25–25 mm/s), spanning the range estimated to occur under conditions of construct insertion in vivo. The adhesion of PC to the PLA carrier was increased significantly by 1 and 2 weeks of incubation, with 25 mm/s flow causing a 57% detachment of cells after 1 h of seeding, but only 7% and 16% after 1 and 2 weeks of culture, respectively (p > 0.001). This adherence was associated with marked deposition of glycosaminoglycan and collagen. These findings suggest that pre‐incubation of PC‐laden PLA scaffolds markedly enhances the stability of the indwelling cells. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Approaching Complex Cases With a Crisis Intervention Model and Teamwork: A Commentary
Authors: Scheyett Anna M. 
Published: March 2003

AbstractThis article is a response to the case of SA presented by O'Daniel and Wells. In this response I support the approach used with the patient, and discuss and expand on the applicability of a crisis intervention model to genetic counseling. In addition, I explore the issue of autonomy and informed decision making for patients who are in crisis. I also discuss the surface contradiction between the mandate for nondirectiveness and the need to provide direction during crisis intervention are discussed and reframe the issue as one of process versus content directiveness. I argue that during times of crisis, genetic counselors may need to direct process in order for patients to be able to make autonomous decisions.
Clinical, enzymatic, and molecular genetic characterization of a biochemical variant type of argininosuccinic aciduria: prenatal and postnatal diagnosis in five unrelated families
Authors: Kleijer W. J. , Garritsen V. H. , Linnebank M. , Mooyer P. , Huijmans J. G. M. , Mustonen A. , Simola K. O. J. , Arslan‐Kirchner M. , Battini R. , Briones P. , Cardo E. , Mandel H. , Tschiedel E. , Wanders R. J. A. , Koch H. G. 
Published: March 2003

AbstractA biochemical variant of argininosuccinate lyase deficiency, found in five individuals, is introduced. In comparison to classical patients, the variant cases of argininosuccinate lyase deficiency were characterized by residual enzyme activity as measured by the incorporation of [14C]citrulline into proteins. The five patients of different ethnic backgrounds presented with relatively mild clinical symptoms, variable age of onset, marked argininosuccinic aciduria and severe, but not complete, deficiency of argininosuccinate lyase. [14C]Citrulline incorporation into proteins, which is completely blocked in classical argininosuccinic aciduria, was only partially reduced in fibroblasts of these patients. Further investigation showed that previous standard conditions of the assay were not optimal. Higher concentrations of citrulline in the incubation medium strongly stimulated 14C incorporation in normal cells, but not in the patients; as a result, the relative incorporation level in the patients dropped to 6–28% compared to 18–75% of normal in the original procedure. Prenatal diagnosis was successfully performed in three of the families. Affected pregnancies were indicated by (partial) deficiency of [14C]citrulline incorporation in chorionic villi and/or increased levels of argininosuccinate in amniotic fluid. Analysis of the ASL gene in the five patients revealed a considerable allelic heterogeneity. Three novel mutations—R385C (2 patients), V178M and R379C—were detected in homozygous states, whereas one patient was compound heterozygous for the known mutations R193Q and Q286R. In conclusion, there are patients of different ethnic backgrounds who are characterized by residual activity of argininosuccinate lyase and who present with less severe clinical courses. In addition, we present an improved biochemical assay for accurate prenatal and postnatal diagnosis.
Cytochrome oxidase deficiency in Lowe syndrome
Authors: Cifelli P. M. , Hargreaves I. , Grünewald S. 
Published: March 2003

AbstractWe report on a patient with complex IV deficiency who in later clinical course was diagnosed as a Lowe syndrome. Mitochondrial abnormalities can be present in Lowe syndrome and might lead to misdiagnosis, additionally because clinical features can be overlapping.