bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose Escalation Study on Oxaliplatin and Capecitabine (Xeloda) in Patients with Advanced Solid Tumors
Authors: Kakolyris S. , Souglakos J. , Kouroussis C. , Androulakis N. , Samonis G. , Vardakis N. , Amarantidis K. , Agelaki S. , Mavroudis D. , Xenidis N. , Georgoulias V. 
Published: June 2004

<i>Objectives:</i> Capecitabine (CAP) and oxaliplatin (OX) have shown interesting activity in a wide range of solid tumors. A phase I study was conducted in order to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of their combination in patients with refractory solid tumors. <i>Patients and Methods:</i> Thirty-three pretreated patients with histologically confirmed inoperable neoplasms were enrolled. The patients’ median age was 64 years, 21 were males, and 27 had a WHO performance status of 0–1. OX was administered on days 1 and 8, as a 3-hour intravenous infusion, at escalated doses ranging from 50 to 70 mg/m<sup>2</sup>. CAP was administered orally for 14 consecutive days, at escalated doses ranging from 1,200 to 2,100 mg/m<sup>2</sup>/day. Treatment was repeated every 3 weeks. <i>Results: </i>At the dose of 2,100 mg/m<sup>2</sup> (Xeloda) and 70 mg/m<sup>2</sup> (OX), all 3 enrolled patients presented DLT (grade 3 diarrhea, grade 3 asthenia and grade 3 neurotoxicity, respectively), and, thus, the recommended MTD for future phase II studies are 2,000 mg/m<sup>2</sup> for CAP and 70 mg/m<sup>2 </sup>for OX. A total of 145 treatment cycles were administered. Toxicity was very mild. Grade 2/3 neutropenia was observed in 4 (3%) treatment cycles. The main nonhematologic toxicities were grade 2/3 nausea/vomiting (7 cycles; 5%), grade 2/3 neurotoxicity (10 cycles; 7%), grade 2/3 asthenia (8 cycles; 5.5%) and grade 2/3 diarrhea (6 cycles; 4%). There was no treatment-related death. One (4%) complete remission, 2 (8%) partial remissions, and 9 (36%) cases of stable disease were observed among 25 evaluable patients. <i>Conclusions:</i> The results demonstrate that CAP and OX can be safely combined at clinically relevant doses and that this regimen merits further evaluation.
17β-Estradiol Promotes Striatal Medium Size Spiny Neuronal Maturation in vitro
Authors: Stroppolo Antonella , Tian Chai , Guinea Barbara , Olm Vicki , Sheffield Roxanne , Sommer John , Ehrlich Michelle E. 
Published: June 2004

Gender differences exist in the development of the nigrostriatal dopamine system, and in the incidence and course of pediatric and adult neuropsychiatric diseases in which this system is implicated. The medium size spiny neuron (MSN) is the major output neuron of the caudate nucleus. It receives a large dopaminergic input from the substantia nigra, and 96% of the MSNs express DARPP-32, a dopamine and cyclic AMP-regulated phosphoprotein and key mediator of dopamine function. There are few examples, however, of direct effects of sex hormones, including 17β-estradiol (E<sub>2</sub>), on the MSN. We report that in vitro, E<sub>2</sub> (10–50 n<i>M</i>) promotes MSN phenotypic maturation, as determined by increased soma size, neurite length, and DARPP-32 protein levels. Treatment with the ‘anti-estrogen’ ICI 182,780 or the partial-agonist tamoxifen also increases DARPP-32 levels, but when added to E<sub>2</sub>, ICI 182,780 only prevents the increase in DARPP-32 levels and increase in soma size and neurite length. Surprisingly, maturation effects are more robust in cells derived exclusively from female embryos. Western blot analysis of protein lysates and immunocytochemistry of cultured MSNs reveals the presence of the estrogen receptor β (ERβ). These data suggest that ERβ may mediate the differentiating effect of E<sub>2</sub> on embryonic MSNs, and provide new avenues of investigation for the role of sex hormones in the development of the striatum and in diseases affecting the basal ganglia.
Nitric Oxide Levels in Preterm and Term Infants and in Premature Infants with Bacteremia
Authors: Marom D. , Yuhas Y. , Sirota L. , Livni G. , Ashkenazi S. 
Published: June 2004

<i>Objective:</i> To determine the serum nitric oxide levels in healthy neonates and in infants with bacteremia. <i>Methods:</i> We performed a prospective study in a tertiary neonatal intensive care unit. The serum nitric oxide levels were measured in all infants at birth (basal) and in the infected neonates also on the first 2 days of bacteremia. <i>Results:</i> Thirty-three neonates (10 term, 23 preterm) were included. Eleven preterm infants (mean gestational age 27 weeks) had bacteremia. The main blood culture isolates included coagulase-negative staphylococci (n = 4), <i>Klebsiella pneumonia</i>e (n = 3), and <i>Escherichia coli</i> (n = 3). The serum nitric oxide levels increased during infection in 10 infants (p < 0.008). The mean nitric oxide level before infection was 44 µ<i>M</i> and during infection 96 µ<i>M</i> (p = 0.008). In the healthy babies, the mean nitric oxide level was 26 µ<i>M</i> in those with a gestational age <27 weeks, 44 µ<i>M</i> in those born between 28 and 36 weeks of gestation, and 63 µ<i>M</i> in term infants. <i>Conclusions:</i> Bacteremic preterm infants produce significantly higher amounts of nitric oxide. The basal nitric oxide levels at birth may be correlated with gestational age.
Prevalence of Congenital Hypothyroidism in Isfahan, Iran: Results of a Survey on 20,000 Neonates
Authors: Hashemipour Mahin , Amini Massoud , Iranpour Ramin , Sadri Gholam Hossein , Javaheri Narges , Haghighi Sassan , Hovsepian Silva , Javadi Abbas Ali , Nematbakhsh Mahdi , Sattari Goshtasb 
Published: June 2004

<i>Aims:</i> To evaluate the prevalence of congenital hypothyroidism (CH) in a screening program performed for the first time in Isfahan, Iran. <i>Methods:</i> From May 2002 to December 2002, T<sub>4</sub> and TSH serum concentrations of 20,000 3- to 7-day-old newborns, born in all 17 hospitals of the city, were measured by radioimmunoassay and immunoradiometric assay, respectively. The newborns with abnormal screening results (TSH >20 mIU/l, T<sub>4</sub> <6.5 µg/dl and based on the weight) were re-examined. <i>Results:</i> Of 531 recalled subjects (recall rate 2.6%), 54 were confirmed to be hypothyroid, showing a prevalence of 1:370 for CH. <i>Conclusion:</i> Considering the high frequency of CH, the necessity of implementing a routine screening program in the healthcare system of Isfahan Province is emphasized.
The Privatization of Protection: Extortion and The State in the Circassian Mamluk Period
Authors: Meloy John 
Published: June 2004

AbstractThis article examines privatized forms of protection (himāyah ), and especially extortion, during the Circassian Mamluk period as reported in contemporary chronicles and a tract calling for administrative reform. Protection rackets were characterized by a symbiotic relationship between "protectors" and state officials. The article concludes with a discussion of the implications of extortion for our understanding of the effective power of the Mamluk Sultanate during its last century of rule. Cet article examine les formes privées de protection pratiquées durant le règne des Mamelouks circassiens, en particulier l'extorsion. Ces pratiques sont rapportées par les chroniques de l'époque et par un manifeste appelant à des réformes administratives. Cette forme de "racket" se caractérisait par la relation symbiotique liant les "protecteurs" aux fonctionnaires. En conclusion, cette étude nous amène à nous interroger sur la manière dont ces pratiques d'extorsion permettent de mieux cerner le pouvoir réel au sein du sultanat mamelouk pendant le dernier siècle de son existence.
Economic Boundaries? Late Antiquity and Early Islam
Authors: Morony Michael 
Published: June 2004

AbstractThe Mediterranean economy was retracting from the mid-sixth century while the Sasanian economy was expanding. Six trends are identified during Late Antiquity that extended into the Islamic period: (1) the development and spread of large estates with tenant labor, (2) the monetization of the economy, (3) the development and spread of irrigated agriculture, (4) the revival of mining, (5) the emergence of merchant diasporas, and (6) the domination of Indian Ocean commerce by Persian shipping. It is argued that these trends were strongest in Sasanian territory where the economic system identified as "Islamic" originated. À partir du milieu du sixième siècle l'économie méditerranéenne connaissait une régression alors que celle de l'Empire sasanide était en plein essor. Durant l'époque de l'Antiquité tardive et au cours de la période islamique, six tendances peuvent être relevées: 1) le développement et la diffusion des grands domaines avec fermiers à bail; (2) la monétarisation de l'économie; (3) l'extension de l'agriculture irriguée; (4) la revivi fication du secteur minier; (5) l'émergence des diasporas commerciales; et (6) la domination commerciale de la marine perse dans l'Océan indien. Selon notre analyse, ces tendances étaient plus fortement ressenties en territoire sasanide où le système économique dit "islamique" connut le jour.
Local and International Trade and Traders in The Straits of Melaka Region: 600-1500
Authors: Hall Kenneth 
Published: June 2004

AbstractThis article notes that the recent mainstream scholarship on the pre-1500 Indian Ocean trade by non-Southeast Asia specialists has limited itself to Middle Eastern, South Asian, and Chinese evidence—and that these scholars' exclusion of Southeast Asian documentation has led to erroneous statements and conclusions. Based on selected examples of the omitted Southeast Asia evidence, this study highlights the changes taking place in the maritime trade network from the eleventh through the fifteenth centuries, and the increasing complexity of the Asian trade system. It demonstrates that scholars need to reconsider their characterizations of Asian trade "centers" ("emporia"), and that by the fifteenth century an Asia trade "center" is a convenient and commonly agreed upon marketplace that is networked with and shared by merchant sojourners who are based in other significant regional "centers." It also contends that assertions that there was a late fourteenth- through fifteenth-century Asian trade decline are incorrect, and that Asian commerce was robust when the Portuguese appeared on the scene at the beginning of the sixteenth century—and seized Melaka in their failed attempt to dominate the Asia maritime trade network. Cet article relève que le courant principal récent de la recherche sur le commerce dans l'Océan indien avant le XVe siècle par des non-spécialistes du Sud-Est asiatique a concentré ses études sur l'Asie moyenne orientale, méridionale et la Chine; en ignorant la documentation provenant de l'Asie du Sud-Est, ces chercheurs ont été conduits à avancer des conclusions erronées. Fondée sur des exemples choisis dans cette dernière région, cette étude met en évidence les changements intervenus dans le réseau du commerce maritime entre le XIe et XVe siècles et la complexité accrue du système commercial asiatique. Elle souligne également que les chercheurs doivent reconsidérer les caractéristiques qu'ils accordent aux "centres" ("emporia") de commerce asiatique et qu'au XVe siècle un "centre" est une place commerciale pratique intégrée dans un réseau partagé par des négociants installés dans d'autres "centres" notoires de la région. Elle s'élève en fin contre les affirmations avançant que le commerce était en déclin à la fin du XIVe et au XVe siècle; au contraire, il était encore fl orissant quand les Portugais apparaissent dans la région au début du XVIe siècle et s'emparent de Malacca dans leur tentative avortée de dominer le commerce maritime asiatique.
Assimilation and Revolt in the Territory of Isauria, From the 1st Century BC to the 6th Century AD
Authors: Lenski Noel 
Published: June 2004

AbstractThis article investigates shifts in the scale and organization of violence in the region of Isauria during the period of Roman rule. In contrast with the fundamental paper of B. Shaw in JESHO, volume 33 (1990), which argues that Isaurian violence was a constant in all periods of history, this study attempts to show that major Isaurian uprisings were brought under control from the mid-first century to the mid-third century AD. In these centuries the Isaurians became increasingly sedentarized, adopted Hellenistic social and political structures, and cooperated with the Roman state actively, particularly as soldiers. Only after the midthird century did Isauria again turn against Rome, this time with increased strength built on the economic and social development it had experienced under Roman rule.
The Turkish Officers of Samarra: Revenue and the Exercise of Authority
Authors: Gordon Matthew 
Published: June 2004

AbstractThe present article concerns the access to revenue on the part of the Turkish officers of Abbāsid Samarra. It is argued that the revenue in question explains their considerable influence. It is also argued that among the arrangements made for the Turkish officers were specific forms of land tenure which represented a decisive step toward the system of the new style iqtā so widely used after the third/ninth century in the Islamic Near East.
Targeted deletion of T-cell clones using alpha-emitting suicide MHC tetramers
Authors: Yuan Rui Rong , Wong Phillip , McDevitt Michael R. , Doubrovina Ekaterina , Leiner Ingrid , Bornmann William , O'Reilly Richard , Pamer Eric G. , Scheinberg David A. 
Published: June 2004

AbstractImmunosuppressive agents in current use are nonspecific. The capacity to delete specific CD8 T-cell clones of unique specificity could prove to be a powerful tool for dissecting the precise role of CD8+ T cells in human disease and could form the basis for a safe, highly selective therapy of autoimmune disorders. Major histocompatibility complex (MHC) tetramers (multimeric complexes capable of binding to specific CD8 T-cell clones) were conjugated to 225Ac (an alpha-emitting atomic nanogenerator, capable of single-hit killing from the cell surface) to create an agent for CD8 T-cell clonal deletion. The “suicide” tetramers specifically bound to, killed, and reduced the function of their cognate CD8 T cells (either human anti–Epstein-Barr virus (EBV) or mouse anti-Listeria in 2 model systems) while leaving the nonspecific control CD8 T-cell populations unharmed. Such an approach may allow a pathway to selective ablation of pathogenic T-cell clones ex vivo or in vivo without disturbing general immune function.
Bicalutamide Monotherapy Versus Leuprolide Monotherapy for Prostate Cancer: Effects on Bone Mineral Density and Body Composition
Authors: Smith Matthew R. , Goode Melissa , Zietman Anthony L. , McGovern Francis J. , Lee Hang , Finkelstein Joel S. 
Published: June 2004

Purpose Gonadotropin-releasing hormone agonists decrease bone mineral density, lean mass, and muscle size and increase fat mass in men with prostate cancer. Less is known about the effects of bicalutamide monotherapy on bone mineral density and body composition. Patients and Methods In a 12-month, open-label study, we randomly assigned 52 men with prostate cancer and no bone metastases to receive either leuprolide or bicalutamide (150 mg by mouth daily). Bone mineral density and body composition were measured by dual energy x-ray absorptiometry and quantitative computed tomography. Results Mean (± standard error) bone mineral density of the posterior-anterior lumbar spine decreased by 2.5% ± 0.5% in the leuprolide group and increased by 2.5 ± 0.5 in the bicalutamide group from baseline to 12 months (P < .001). Mean changes in bone mineral density of the total body, total hip, femoral neck, and trabecular bone of the lumbar spine also differed significantly between groups (P ≤ .003 for each comparison). Fat mass increased by 11.1% ± 1.3% in the leuprolide group and by 6.4% ± 1.1% in the bicalutamide group (P = .01). Changes in lean mass, muscle size, and muscle strength were similar between the groups. Breast tenderness and enlargement were more common in the bicalutamide group than in the leuprolide group. Fatigue, loss of sexual interest, and vasomotor flushing were less common in the bicalutamide group than in the leuprolide group. Conclusion In men with prostate cancer, bicalutamide monotherapy increases bone mineral density, lessens fat accumulation, and has fewer bothersome side effects than treatment with a gonadotropin-releasing hormone agonist.
Randomized, Controlled Trial Investigating Short-Term Health-Related Quality of Life With Doxorubicin and Paclitaxel Versus Doxorubicin and Cyclophosphamide As First-Line Chemotherapy in Patients With Metastatic Breast Cancer: European Organization for Research and Treatment of Cancer Breast Cancer Group, Investigational Drug Branch for Breast Cancer and the New Drug Development Group Study
Authors: Bottomley Andrew , Biganzoli Laura , Cufer Tanja , Coleman Robert E. , Coens Corneel , Efficace Fabio , Calvert Hilary Allan , Gamucci Teresa , Twelves Chris , Fargeot Pierre , Piccart Martine 
Published: June 2004

Purpose To compare health-related quality of life (HRQOL) in patients with metastatic breast cancer receiving the combination of doxorubicin and paclitaxel (AT) or doxorubicin and cyclophosphamide (AC) as first-line chemotherapy treatment. Patients and Methods Eligible patients (n = 275) with anthracycline-naive measurable metastatic breast cancer were randomly assigned to AT (doxorubicin 60 mg/m2 as an intravenous bolus plus paclitaxel 175 mg/m2 as a 3-hour infusion) or AC (doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2) every 3 weeks for a maximum of six cycles. Dose escalation of paclitaxel (200 mg/m2) and cyclophosphamide (750 mg/m2) was planned at cycle 2 to reach equivalent myelosuppression in the two groups. HRQOL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and the EORTC Breast Module at baseline and the start of cycles 2, 4, and 6, and 3 months after the last cycle. Results Seventy-nine percent of the patients (n = 219) completed a baseline measure. However, there were no statistically significant differences in HRQOL between the two treatment groups. In both groups, selected aspects of HRQOL were impaired over time, with increased fatigue, although some clinically significant improvements in emotional functioning were seen, as well as a reduction in pain over time. Overall, global quality of life was maintained in both treatment groups. Conclusion This information is important when advising women patients of the expected HRQOL consequences of treatment regimens and should help clinicians and their patients make informed treatment decisions.
Concurrent and Adjuvant Chemotherapy for Nasopharyngeal Carcinoma: A Factorial Study
Authors: Kwong Dora L.W. , Sham Jonathan S.T. , Au Gordon K.H. , Chua Daniel T.T. , Kwong Philip W.K. , Cheng Ashley C.K. , Wu P.M. , Law Martin W.M. , Kwok Carol C.H. , Yau C.C. , Wan K.Y. , Chan Raymond T.T. , Choy Damon D.K. 
Published: June 2004

Purpose To study the efficacy of concurrent chemoradiotherapy (CRT) and adjuvant chemotherapy (AC) for nasopharyngeal carcinoma (NPC). Patients and Methods Patients with Ho's stage T3 or N2/N3 NPC or neck node ≥ 4 cm were eligible. Patients were randomly assigned to have radiotherapy (RT) or CRT with uracil and tegafur and to have AC or no AC after RT/CRT. AC comprised alternating cisplatin, fluorouracil, vincristine, bleomycin, and methotrexate for six cycles. There were four treatment groups: A, RT; B, CRT; C, RT and AC; D, CRT and AC. For CRT versus RT, groups B and D were compared with groups A and C. For AC versus no AC, groups C and D were compared with groups A and B. Results Three-year failure-free survival (FFS) and overall survival (OS) for CRT versus RT were 69.3% versus 57.8% and 86.5% versus 76.8%, respectively (P = .14 and .06; n = 110 v 109). Distant metastases rate (DMR) was significantly reduced with CRT (14.8% v 29.4%; P = .026). Locoregional failure rates (LRFR) were similar (20% v 27.6%; P = .39). Three-year FFS and OS for AC versus no AC were 62.5% versus 65% and 80.4% versus 83.1%, respectively (P = .83 and .69; n = 111 v 108). DMR and LRFR were not reduced with AC (P = .34 and .15, respectively). Cox model showed CRT to be a favorable prognostic factor for OS (hazard ratio, 0.42; P = .009). Conclusion An improvement in OS with CRT was observed but did not achieve statistical significance. The improvement seemed to be associated with a significant reduction in DMR. AC did not improve outcome.
Prophylactic Urokinase in the Management of Long-Term Venous Access Devices in Children: A Children's Oncology Group Study
Authors: Dillon Peter W. , Jones Gary R. , Bagnall-Reeb Holly A. , Buckley Jonathon D. , Wiener Eugene S. , Haase Gerald M. 
Published: June 2004

Purpose Infection and thrombosis are serious complications of long-term vascular access devices in children undergoing chemotherapy. Since routine fibrinolytic therapy may decrease these complications, the purpose of this study was to compare the efficacy of an every-2-week administration of urokinase with standard heparin flushes in reducing the incidence of device-related infections and occlusions. Materials and Methods This study was a prospective, randomized phase III multicenter trial conducted by the Children's Cancer Group, in which patients with implantable ports or tunneled catheters received either urokinase or heparin every 2 weeks for 12 months. Study end points were time to first occlusion or time to first device-related infection. Results Five hundred seventy-seven patients from 29 institutions were enrolled, of whom 51% had external catheters and 49% had ports. Urokinase administration resulted in fewer occlusive events than heparin (23% v 31%; P = .02), a longer time to first occlusive event (log-rank analysis, P = .006), and a 1.6-fold difference in the rate of occlusive events (Poisson regression, P = .003). Similar results were noted when comparing ports and tunneled catheters. The urokinase group also had a 1.4-fold difference in the rate of infection (Poisson regression, P = .05) and longer time to first infection (log-rank, P = .07), but the difference was significant only in tunneled catheters. Conclusion Urokinase administration every 2 weeks significantly affects the rate of occlusive events in ports and tunneled catheters and of infectious events in external catheters compared with heparin administration.
Coamplification of DDX1 Correlates With an Improved Survival Probability in Children With MYCN-Amplified Human Neuroblastoma
Authors: Weber Axel , Imisch Patricia , Bergmann Eckhard , Christiansen Holger 
Published: June 2004

Purpose Amplification of the MYCN oncogene at chromosome 2p24-25 identifies an aggressive subtype of human neuroblastoma with a poor clinical outcome. Differences in amplicon structure and coamplification of genes telomeric and centromeric to the MYCN oncogene have previously been described. A relevant role of gene coamplification for neuroblastoma pathogenesis remains elusive. Patients and Methods We analyzed 98 primary neuroblastoma tumors with MYCN amplification for coamplification of seven additional genes at chromosome 2p24-25 (DDX1, NAG, NSE1, LPIN1, EST- AA581763 , SMC6, and SDC1). Two semiquantitative multiplex polymerase chain reactions were used to obtain the amplification status of the target genes in relation to a reference gene on chromosome 2q (Inhibin-beta-b). Furthermore, mRNA expression pattern of coamplified genes in a subset of tumors was analyzed. Results Our results show that the frequency of gene coamplification on 2p24-25 in neuroblastoma is correlated directly to the physical distance to MYCN. Coamplification is correlated to an upregulated gene expression for DDX1 and NAG. Coamplification of the DDX1 gene within 400kb telomeric to MYCN identifies a subgroup of advanced stage neuroblastoma tumors with a more favorable outcome (P = .027, log-rank test). A high expression level of DDX1 is associated with a trend towards a better survival probability (P = .058, log-rank test). Conclusion Our results indicate that DDX1 coamplification correlates with a better prognosis and improved patient survival in MYCN-amplified neurobastoma.